Hyperbaric oxygen therapy

1. The review states that the principal mechanisms of hyperbaric oxygen are based on intracellular generation of reactive species of oxygen and nitrogen, which act through cell signal transduction cascades.

   Hyperbaric oxygen therapy → Reactive oxygen species source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

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   experimental_model

   Narrative review of therapeutic mechanisms and clinical trial evidence

   exposure

   Hyperbaric oxygen as used clinically, typically 2.0 to 2.5 atmospheres absolute

   limitations

   A narrative review, not a primary experiment. It is recorded as the framing source the reader was given; every mechanism it names is also recorded here from its own primary paper.

   nutrient_topic

   Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

   organism

   Human, with supporting animal work

   plain_language

   The therapy works by making the cell produce reactive molecules that carry signals, not simply by supplying more oxygen.

   primary_references

   [hbot-p21200283] Hyperbaric oxygen: its mechanisms and efficacy. (2011). https://pubmed.ncbi.nlm.nih.gov/21200283/ DOI: 10.1097/prs.0b013e3181fbe2bf

   tissue_or_cell_type

   Multiple tissues

   Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 62–73

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Narrative review of therapeutic mechanisms and clinical trial evidence · source_derived_draft · unverified_draft

   ### hbot-review-reactive-species-framing The review states that the principal mechanisms of hyperbaric oxygen are based on intracellular generation of reactive species of oxygen and nitrogen, which act through cell signal transduction cascades. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The therapy works by making the cell produce reactive molecules that carry signals, not simply by supplying more oxygen. organism: Human, with supporting animal work tissue_or_cell_type: Multiple tissues experimental_model: Narrative review of therapeutic mechanisms and clinical trial evidence limitations: A narrative review, not a primary experiment. It is recorded as the framing source the reader was given; every mechanism it names is also recorded here from its own primary paper. exposure: Hyperbaric oxygen as used clinically, typically 2.0 to 2.5 atmospheres absolute evidence_span: {"source_cache": "artifacts/hbot-research/21200283.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "541f2eb700a843e35093e589069b7839f1a3577c2de8cd1edb444698c1379380", "start_char": 0, "end_char": 1120, "text_sha256": "541f2eb700a843e35093e589069b7839f1a3577c2de8cd1edb444698c1379380"} [hbot-p21200283] Hyperbaric oxygen: its mechanisms and efficacy. (2011). https://pubmed.ncbi.nlm.nih.gov/21200283/ DOI: 10.1097/prs.0b013e3181fbe2bf

   Complete structured claim and evidence

2. The review reports that systematic reviews and randomised clinical trials support clinical use of hyperbaric oxygen for refractory diabetic wound healing and radiation injuries, while compromised flaps, grafts and ischaemia-reperfusion disorders are supported by animal studies and a small number of clinical trials.

   Hyperbaric oxygen therapy → Wound healing source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

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   experimental_model

   Narrative review of therapeutic mechanisms and clinical trial evidence

   exposure

   Hyperbaric oxygen as used clinically, typically 2.0 to 2.5 atmospheres absolute

   limitations

   A narrative review, not a primary experiment. It is recorded as the framing source the reader was given; every mechanism it names is also recorded here from its own primary paper.

   nutrient_topic

   Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

   organism

   Human, with supporting animal work

   plain_language

   The evidence is strongest for stubborn diabetic wounds and radiation damage, and thinner elsewhere.

   primary_references

   [hbot-p21200283] Hyperbaric oxygen: its mechanisms and efficacy. (2011). https://pubmed.ncbi.nlm.nih.gov/21200283/ DOI: 10.1097/prs.0b013e3181fbe2bf

   tissue_or_cell_type

   Multiple tissues

   Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 75–86

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Narrative review of therapeutic mechanisms and clinical trial evidence · source_derived_draft · unverified_draft

   ### hbot-review-efficacy-scope The review reports that systematic reviews and randomised clinical trials support clinical use of hyperbaric oxygen for refractory diabetic wound healing and radiation injuries, while compromised flaps, grafts and ischaemia-reperfusion disorders are supported by animal studies and a small number of clinical trials. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The evidence is strongest for stubborn diabetic wounds and radiation damage, and thinner elsewhere. organism: Human, with supporting animal work tissue_or_cell_type: Multiple tissues experimental_model: Narrative review of therapeutic mechanisms and clinical trial evidence limitations: A narrative review, not a primary experiment. It is recorded as the framing source the reader was given; every mechanism it names is also recorded here from its own primary paper. exposure: Hyperbaric oxygen as used clinically, typically 2.0 to 2.5 atmospheres absolute evidence_span: {"source_cache": "artifacts/hbot-research/21200283.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "541f2eb700a843e35093e589069b7839f1a3577c2de8cd1edb444698c1379380", "start_char": 0, "end_char": 1120, "text_sha256": "541f2eb700a843e35093e589069b7839f1a3577c2de8cd1edb444698c1379380"} [hbot-p21200283] Hyperbaric oxygen: its mechanisms and efficacy. (2011). https://pubmed.ncbi.nlm.nih.gov/21200283/ DOI: 10.1097/prs.0b013e3181fbe2bf

   Complete structured claim and evidence

3. The review argues that reactive species of oxygen and nitrogen play a major role in the cell signal transduction cascades through which hyperbaric oxygen mediates wound healing and ameliorates post-ischaemic and inflammatory injuries.

   Reactive oxygen species → Wound healing source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

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   experimental_model

   Narrative review of reactive species in hyperbaric oxygen mechanisms

   exposure

   Clinical hyperbaric oxygen protocols

   limitations

   A second narrative review by the same group. Recorded for its framing claim only; it is not primary evidence for any individual mechanism.

   nutrient_topic

   Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

   organism

   Human and animal

   plain_language

   The same reactive molecules that can damage tissue are the ones carrying the healing signal.

   primary_references

   [hbot-p18845776] Oxidative stress is fundamental to hyperbaric oxygen therapy. (2009). https://pubmed.ncbi.nlm.nih.gov/18845776/ DOI: 10.1152/japplphysiol.91004.2008

   tissue_or_cell_type

   Multiple tissues

   Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 88–99

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Narrative review of reactive species in hyperbaric oxygen mechanisms · source_derived_draft · unverified_draft

   ### hbot-review-oxidative-stress-central The review argues that reactive species of oxygen and nitrogen play a major role in the cell signal transduction cascades through which hyperbaric oxygen mediates wound healing and ameliorates post-ischaemic and inflammatory injuries. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The same reactive molecules that can damage tissue are the ones carrying the healing signal. organism: Human and animal tissue_or_cell_type: Multiple tissues experimental_model: Narrative review of reactive species in hyperbaric oxygen mechanisms limitations: A second narrative review by the same group. Recorded for its framing claim only; it is not primary evidence for any individual mechanism. exposure: Clinical hyperbaric oxygen protocols evidence_span: {"source_cache": "artifacts/hbot-research/18845776.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "eb24faa214730ea0aa0cdd25baa8a6ae6481e6b98bd174f0131c0d117b5d828c", "start_char": 0, "end_char": 600, "text_sha256": "eb24faa214730ea0aa0cdd25baa8a6ae6481e6b98bd174f0131c0d117b5d828c"} [hbot-p18845776] Oxidative stress is fundamental to hyperbaric oxygen therapy. (2009). https://pubmed.ncbi.nlm.nih.gov/18845776/ DOI: 10.1152/japplphysiol.91004.2008

   Complete structured claim and evidence

4. Transcutaneous oxygen tension measured on the dorsum of the foot rose significantly more in the treated group, by 14.0 mmHg versus 5.0 mmHg.

   Hyperbaric oxygen therapy → Transcutaneous oxygen tension on the foot source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/hbot-research/8941460.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2f2904fa77e07a14257977ef8ca30fc46ee5ada35e65be2cc6512161bd0b440e", "start_char": 0, "end_char": 1910, "text_sha256": "2f2904fa77e07a14257977ef8ca30fc46ee5ada35e65be2cc6512161bd0b440e"}

   experimental_model

   Randomised study of 70 people admitted with severe prevalently ischaemic diabetic foot ulcer

   exposure

   Systemic hyperbaric oxygen, mean 38.8 sessions, added to a full treatment protocol

   limitations

   A single-centre randomised study with amputation as the endpoint. Adjunctive to an aggressive protocol, so the effect is of the addition, not of hyperbaric oxygen alone.

   nutrient_topic

   Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

   organism

   Human

   plain_language

   The treatment measurably raised the oxygen reaching the skin of the foot.

   primary_references

   [hbot-p8941460] Adjunctive systemic hyperbaric oxygen therapy in treatment of severe prevalently ischemic diabetic foot ulcer. A randomized study. (1996). https://pubmed.ncbi.nlm.nih.gov/8941460/ DOI: 10.2337/diacare.19.12.1338

   tissue_or_cell_type

   Foot

   Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 101–112

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomised study of 70 people admitted with severe prevalently ischaemic diabetic foot ulcer · source_derived_draft · unverified_draft

   ### hbot-tcpo2-rise Transcutaneous oxygen tension measured on the dorsum of the foot rose significantly more in the treated group, by 14.0 mmHg versus 5.0 mmHg. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The treatment measurably raised the oxygen reaching the skin of the foot. organism: Human tissue_or_cell_type: Foot experimental_model: Randomised study of 70 people admitted with severe prevalently ischaemic diabetic foot ulcer limitations: A single-centre randomised study with amputation as the endpoint. Adjunctive to an aggressive protocol, so the effect is of the addition, not of hyperbaric oxygen alone. exposure: Systemic hyperbaric oxygen, mean 38.8 sessions, added to a full treatment protocol evidence_span: {"source_cache": "artifacts/hbot-research/8941460.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2f2904fa77e07a14257977ef8ca30fc46ee5ada35e65be2cc6512161bd0b440e", "start_char": 0, "end_char": 1910, "text_sha256": "2f2904fa77e07a14257977ef8ca30fc46ee5ada35e65be2cc6512161bd0b440e"} [hbot-p8941460] Adjunctive systemic hyperbaric oxygen therapy in treatment of severe prevalently ischemic diabetic foot ulcer. A randomized study. (1996). https://pubmed.ncbi.nlm.nih.gov/8941460/ DOI: 10.2337/diacare.19.12.1338

   Complete structured claim and evidence

5. Major amputation occurred in 3 of 35 treated subjects (8.6%) versus 11 of 33 untreated (33.3%), a relative risk of 0.26, with the protective role confirmed on multivariate analysis.

   Hyperbaric oxygen therapy → Major lower-limb amputation source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/hbot-research/8941460.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2f2904fa77e07a14257977ef8ca30fc46ee5ada35e65be2cc6512161bd0b440e", "start_char": 0, "end_char": 1910, "text_sha256": "2f2904fa77e07a14257977ef8ca30fc46ee5ada35e65be2cc6512161bd0b440e"}

   experimental_model

   Randomised study of 70 people admitted with severe prevalently ischaemic diabetic foot ulcer

   exposure

   Systemic hyperbaric oxygen, mean 38.8 sessions, added to a full treatment protocol

   limitations

   A single-centre randomised study with amputation as the endpoint. Adjunctive to an aggressive protocol, so the effect is of the addition, not of hyperbaric oxygen alone.

   nutrient_topic

   Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

   organism

   Human

   plain_language

   Fewer people in the treated group lost a limb in this trial.

   primary_references

   [hbot-p8941460] Adjunctive systemic hyperbaric oxygen therapy in treatment of severe prevalently ischemic diabetic foot ulcer. A randomized study. (1996). https://pubmed.ncbi.nlm.nih.gov/8941460/ DOI: 10.2337/diacare.19.12.1338

   tissue_or_cell_type

   Foot

   Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 114–125

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomised study of 70 people admitted with severe prevalently ischaemic diabetic foot ulcer · source_derived_draft · unverified_draft

   ### hbot-amputation-reduction Major amputation occurred in 3 of 35 treated subjects (8.6%) versus 11 of 33 untreated (33.3%), a relative risk of 0.26, with the protective role confirmed on multivariate analysis. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Fewer people in the treated group lost a limb in this trial. organism: Human tissue_or_cell_type: Foot experimental_model: Randomised study of 70 people admitted with severe prevalently ischaemic diabetic foot ulcer limitations: A single-centre randomised study with amputation as the endpoint. Adjunctive to an aggressive protocol, so the effect is of the addition, not of hyperbaric oxygen alone. exposure: Systemic hyperbaric oxygen, mean 38.8 sessions, added to a full treatment protocol evidence_span: {"source_cache": "artifacts/hbot-research/8941460.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2f2904fa77e07a14257977ef8ca30fc46ee5ada35e65be2cc6512161bd0b440e", "start_char": 0, "end_char": 1910, "text_sha256": "2f2904fa77e07a14257977ef8ca30fc46ee5ada35e65be2cc6512161bd0b440e"} [hbot-p8941460] Adjunctive systemic hyperbaric oxygen therapy in treatment of severe prevalently ischemic diabetic foot ulcer. A randomized study. (1996). https://pubmed.ncbi.nlm.nih.gov/8941460/ DOI: 10.2337/diacare.19.12.1338

   Complete structured claim and evidence

6. In propensity-score-adjusted models, individuals receiving hyperbaric oxygen were less likely to have their foot ulcer heal (hazard ratio 0.68) and more likely to have an amputation (2.37), and additional analyses including an instrumental variable did not change the result.

   Hyperbaric oxygen therapy → Diabetic foot ulcer healing source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/hbot-research/23423696.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2129b8a0c7356a65fbcedf4032e381f7dc22548282f894b785504f067fa6ced4", "start_char": 0, "end_char": 1491, "text_sha256": "2129b8a0c7356a65fbcedf4032e381f7dc22548282f894b785504f067fa6ced4"}

   experimental_model

   Longitudinal observational cohort of 6259 people in a wound care network, propensity-score adjusted

   exposure

   Hyperbaric oxygen as delivered under Medicare eligibility criteria

   limitations

   A large observational cohort, not a randomised trial. Propensity scores and an instrumental variable were used, but treatment selection by severity cannot be fully excluded; the direction of the result is opposite to the randomised study recorded alongside it.

   nutrient_topic

   Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

   organism

   Human

   plain_language

   In routine care, the treated group did worse, not better.

   primary_references

   [hbot-p23423696] Lack of effectiveness of hyperbaric oxygen therapy for the treatment of diabetic foot ulcer and the prevention of amputation: a cohort study. (2013). https://pubmed.ncbi.nlm.nih.gov/23423696/ DOI: 10.2337/dc12-2160

   tissue_or_cell_type

   Foot

   Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 127–138

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Longitudinal observational cohort of 6259 people in a wound care network, propensity-score adjusted · source_derived_draft · unverified_draft

   ### hbot-cohort-no-benefit In propensity-score-adjusted models, individuals receiving hyperbaric oxygen were less likely to have their foot ulcer heal (hazard ratio 0.68) and more likely to have an amputation (2.37), and additional analyses including an instrumental variable did not change the result. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: In routine care, the treated group did worse, not better. organism: Human tissue_or_cell_type: Foot experimental_model: Longitudinal observational cohort of 6259 people in a wound care network, propensity-score adjusted limitations: A large observational cohort, not a randomised trial. Propensity scores and an instrumental variable were used, but treatment selection by severity cannot be fully excluded; the direction of the result is opposite to the randomised study recorded alongside it. exposure: Hyperbaric oxygen as delivered under Medicare eligibility criteria evidence_span: {"source_cache": "artifacts/hbot-research/23423696.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2129b8a0c7356a65fbcedf4032e381f7dc22548282f894b785504f067fa6ced4", "start_char": 0, "end_char": 1491, "text_sha256": "2129b8a0c7356a65fbcedf4032e381f7dc22548282f894b785504f067fa6ced4"} [hbot-p23423696] Lack of effectiveness of hyperbaric oxygen therapy for the treatment of diabetic foot ulcer and the prevention of amputation: a cohort study. (2013). https://pubmed.ncbi.nlm.nih.gov/23423696/ DOI: 10.2337/dc12-2160

   Complete structured claim and evidence

7. Two seizures were documented in 80,679 patient-treatments, an incidence of 2.4 per 100,000 patient-treatments, both in a multiplace chamber at 2.4 ATA with oxygen by mask.

   Hyperbaric oxygen therapy → Central nervous system oxygen toxicity seizure source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/hbot-research/15559001.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5507526d06e294cc1dfe4ce0be912be957c850b3d7e8243c7fd947c5a10c2c82", "start_char": 0, "end_char": 1303, "text_sha256": "5507526d06e294cc1dfe4ce0be912be957c850b3d7e8243c7fd947c5a10c2c82"}

   experimental_model

   Retrospective review of 80,679 patient-treatments in two university hyperbaric departments

   exposure

   Routine hyperbaric oxygen protocols, including 2.4 ATA by mask with air breaks

   limitations

   A retrospective incidence count. It describes risk under appropriate exclusion criteria and treatment profiles, and does not estimate risk for an individual.

   nutrient_topic

   Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

   organism

   Human

   plain_language

   The feared brain side effect happened about twice in eighty thousand treatments.

   primary_references

   [hbot-p15559001] Seizure incidence in 80,000 patient treatments with hyperbaric oxygen. (2004). https://pubmed.ncbi.nlm.nih.gov/15559001/

   tissue_or_cell_type

   Central nervous system

   Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 140–151

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Retrospective review of 80,679 patient-treatments in two university hyperbaric departments · source_derived_draft · unverified_draft

   ### hbot-seizure-incidence Two seizures were documented in 80,679 patient-treatments, an incidence of 2.4 per 100,000 patient-treatments, both in a multiplace chamber at 2.4 ATA with oxygen by mask. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The feared brain side effect happened about twice in eighty thousand treatments. organism: Human tissue_or_cell_type: Central nervous system experimental_model: Retrospective review of 80,679 patient-treatments in two university hyperbaric departments limitations: A retrospective incidence count. It describes risk under appropriate exclusion criteria and treatment profiles, and does not estimate risk for an individual. exposure: Routine hyperbaric oxygen protocols, including 2.4 ATA by mask with air breaks evidence_span: {"source_cache": "artifacts/hbot-research/15559001.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5507526d06e294cc1dfe4ce0be912be957c850b3d7e8243c7fd947c5a10c2c82", "start_char": 0, "end_char": 1303, "text_sha256": "5507526d06e294cc1dfe4ce0be912be957c850b3d7e8243c7fd947c5a10c2c82"} [hbot-p15559001] Seizure incidence in 80,000 patient treatments with hyperbaric oxygen. (2004). https://pubmed.ncbi.nlm.nih.gov/15559001/

   Complete structured claim and evidence

8. After 30 minutes at 5 ATA, regional cerebral blood flow fell by 23 to 37% in substantia nigra, caudate putamen, hippocampus and parietal cortex.

   Hyperbaric oxygen therapy → Regional cerebral blood flow source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/hbot-research/11139368.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9823a7f177483257b812d7c8c8e8052c3f04d6a7aa052876369c7c64b55668f3", "start_char": 0, "end_char": 1672, "text_sha256": "9823a7f177483257b812d7c8c8e8052c3f04d6a7aa052876369c7c64b55668f3"}

   experimental_model

   Regional cerebral blood flow measurement in rats with nitric oxide metabolite and hydroxyl radical assays

   exposure

   Oxygen at 5 atmospheres absolute for 30 minutes, with L-NAME, a nitric oxide donor, or intravascular superoxide dismutase

   limitations

   Five atmospheres is well above therapeutic pressure and was chosen to study oxygen toxicity. The superoxide dismutase rescue is the key mechanistic step.

   nutrient_topic

   Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

   organism

   Rat

   plain_language

   Breathing oxygen under pressure narrows brain vessels rather than flooding them.

   primary_references

   [hbot-p11139368] Hyperbaric oxygen reduces cerebral blood flow by inactivating nitric oxide. (2000). https://pubmed.ncbi.nlm.nih.gov/11139368/ DOI: 10.1006/niox.2000.0313

   tissue_or_cell_type

   Brain

   Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 153–164

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Regional cerebral blood flow measurement in rats with nitric oxide metabolite and hydroxyl radical assays · source_derived_draft · unverified_draft

   ### hbot-cbf-reduction After 30 minutes at 5 ATA, regional cerebral blood flow fell by 23 to 37% in substantia nigra, caudate putamen, hippocampus and parietal cortex. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Breathing oxygen under pressure narrows brain vessels rather than flooding them. organism: Rat tissue_or_cell_type: Brain experimental_model: Regional cerebral blood flow measurement in rats with nitric oxide metabolite and hydroxyl radical assays limitations: Five atmospheres is well above therapeutic pressure and was chosen to study oxygen toxicity. The superoxide dismutase rescue is the key mechanistic step. exposure: Oxygen at 5 atmospheres absolute for 30 minutes, with L-NAME, a nitric oxide donor, or intravascular superoxide dismutase evidence_span: {"source_cache": "artifacts/hbot-research/11139368.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9823a7f177483257b812d7c8c8e8052c3f04d6a7aa052876369c7c64b55668f3", "start_char": 0, "end_char": 1672, "text_sha256": "9823a7f177483257b812d7c8c8e8052c3f04d6a7aa052876369c7c64b55668f3"} [hbot-p11139368] Hyperbaric oxygen reduces cerebral blood flow by inactivating nitric oxide. (2000). https://pubmed.ncbi.nlm.nih.gov/11139368/ DOI: 10.1006/niox.2000.0313

   Complete structured claim and evidence

9. Brain nitric oxide metabolite levels fell by 31% and correlated with the fall in blood flow, while estimated hydroxyl radical production rose by 56%, and the blood-flow decrease was completely abolished by intravascular superoxide dismutase.

   Superoxide radical anion → NO source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/hbot-research/11139368.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9823a7f177483257b812d7c8c8e8052c3f04d6a7aa052876369c7c64b55668f3", "start_char": 0, "end_char": 1672, "text_sha256": "9823a7f177483257b812d7c8c8e8052c3f04d6a7aa052876369c7c64b55668f3"}

   experimental_model

   Regional cerebral blood flow measurement in rats with nitric oxide metabolite and hydroxyl radical assays

   exposure

   Oxygen at 5 atmospheres absolute for 30 minutes, with L-NAME, a nitric oxide donor, or intravascular superoxide dismutase

   limitations

   Five atmospheres is well above therapeutic pressure and was chosen to study oxygen toxicity. The superoxide dismutase rescue is the key mechanistic step.

   nutrient_topic

   Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

   organism

   Rat

   plain_language

   Superoxide destroys the molecule that keeps vessels relaxed, and removing superoxide removes the effect.

   primary_references

   [hbot-p11139368] Hyperbaric oxygen reduces cerebral blood flow by inactivating nitric oxide. (2000). https://pubmed.ncbi.nlm.nih.gov/11139368/ DOI: 10.1006/niox.2000.0313

   tissue_or_cell_type

   Brain

   Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 166–177

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Regional cerebral blood flow measurement in rats with nitric oxide metabolite and hydroxyl radical assays · source_derived_draft · unverified_draft

   ### hbot-no-inactivation Brain nitric oxide metabolite levels fell by 31% and correlated with the fall in blood flow, while estimated hydroxyl radical production rose by 56%, and the blood-flow decrease was completely abolished by intravascular superoxide dismutase. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Superoxide destroys the molecule that keeps vessels relaxed, and removing superoxide removes the effect. organism: Rat tissue_or_cell_type: Brain experimental_model: Regional cerebral blood flow measurement in rats with nitric oxide metabolite and hydroxyl radical assays limitations: Five atmospheres is well above therapeutic pressure and was chosen to study oxygen toxicity. The superoxide dismutase rescue is the key mechanistic step. exposure: Oxygen at 5 atmospheres absolute for 30 minutes, with L-NAME, a nitric oxide donor, or intravascular superoxide dismutase evidence_span: {"source_cache": "artifacts/hbot-research/11139368.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9823a7f177483257b812d7c8c8e8052c3f04d6a7aa052876369c7c64b55668f3", "start_char": 0, "end_char": 1672, "text_sha256": "9823a7f177483257b812d7c8c8e8052c3f04d6a7aa052876369c7c64b55668f3"} [hbot-p11139368] Hyperbaric oxygen reduces cerebral blood flow by inactivating nitric oxide. (2000). https://pubmed.ncbi.nlm.nih.gov/11139368/ DOI: 10.1006/niox.2000.0313

   Complete structured claim and evidence

10. Administration of superoxide dismutase into the circulation before exposure completely abolished the decrease in regional cerebral blood flow at 5 ATA.

    Human copper-zinc superoxide dismutase / SOD1 → Regional cerebral blood flow source_derived_draftungraded
    Experimental context and source evidence

    availability_state

    machinery_impairment Imported condition classification; unverified.

    evidence_span

    {"source_cache": "artifacts/hbot-research/11139368.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9823a7f177483257b812d7c8c8e8052c3f04d6a7aa052876369c7c64b55668f3", "start_char": 0, "end_char": 1672, "text_sha256": "9823a7f177483257b812d7c8c8e8052c3f04d6a7aa052876369c7c64b55668f3"}

    experimental_model

    Regional cerebral blood flow measurement in rats with nitric oxide metabolite and hydroxyl radical assays

    exposure

    Oxygen at 5 atmospheres absolute for 30 minutes, with L-NAME, a nitric oxide donor, or intravascular superoxide dismutase

    limitations

    Five atmospheres is well above therapeutic pressure and was chosen to study oxygen toxicity. The superoxide dismutase rescue is the key mechanistic step.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Rat

    plain_language

    Giving the enzyme that clears superoxide kept the vessels open.

    primary_references

    [hbot-p11139368] Hyperbaric oxygen reduces cerebral blood flow by inactivating nitric oxide. (2000). https://pubmed.ncbi.nlm.nih.gov/11139368/ DOI: 10.1006/niox.2000.0313

    tissue_or_cell_type

    Brain

    trigger_kind

    machinery_impairment Imported condition classification; unverified.

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 179–190

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Regional cerebral blood flow measurement in rats with nitric oxide metabolite and hydroxyl radical assays · source_derived_draft · unverified_draft

    ### hbot-sod-rescue Administration of superoxide dismutase into the circulation before exposure completely abolished the decrease in regional cerebral blood flow at 5 ATA. Condition category: machinery_impairment nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Giving the enzyme that clears superoxide kept the vessels open. organism: Rat tissue_or_cell_type: Brain experimental_model: Regional cerebral blood flow measurement in rats with nitric oxide metabolite and hydroxyl radical assays limitations: Five atmospheres is well above therapeutic pressure and was chosen to study oxygen toxicity. The superoxide dismutase rescue is the key mechanistic step. exposure: Oxygen at 5 atmospheres absolute for 30 minutes, with L-NAME, a nitric oxide donor, or intravascular superoxide dismutase evidence_span: {"source_cache": "artifacts/hbot-research/11139368.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9823a7f177483257b812d7c8c8e8052c3f04d6a7aa052876369c7c64b55668f3", "start_char": 0, "end_char": 1672, "text_sha256": "9823a7f177483257b812d7c8c8e8052c3f04d6a7aa052876369c7c64b55668f3"} [hbot-p11139368] Hyperbaric oxygen reduces cerebral blood flow by inactivating nitric oxide. (2000). https://pubmed.ncbi.nlm.nih.gov/11139368/ DOI: 10.1006/niox.2000.0313

    Complete structured claim and evidence

11. Blood flow fell by 26 to 43% at 3 and 4 ATA, but at 5 ATA it fell over 30 minutes then gradually returned to pre-exposure levels, preceding the onset of electroencephalographic spiking.

    Hyperbaric oxygen therapy → Regional cerebral blood flow source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/10749833.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1470d09e77b6d6f6af3131a6f7db2cca647dde3655662a1c83f9d5d375f1c687", "start_char": 0, "end_char": 1283, "text_sha256": "1470d09e77b6d6f6af3131a6f7db2cca647dde3655662a1c83f9d5d375f1c687"}

    experimental_model

    Regional cerebral blood flow and electroencephalography in anaesthetised rats

    exposure

    Oxygen at 1, 3, 4 and 5 ATA with L-NAME, L-arginine, nitric oxide donors or MK-801

    limitations

    A time-course study at toxic pressures. It shows the nitric oxide effect reverses with exposure time, which a single time point would miss.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Rat

    plain_language

    The vessel response flips during a long exposure, and the flip comes just before the seizure activity.

    primary_references

    [hbot-p10749833] Nitric oxide and cerebral blood flow responses to hyperbaric oxygen. (2000). https://pubmed.ncbi.nlm.nih.gov/10749833/ DOI: 10.1152/jappl.2000.88.4.1381

    tissue_or_cell_type

    Brain

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 192–203

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Regional cerebral blood flow and electroencephalography in anaesthetised rats · source_derived_draft · unverified_draft

    ### hbot-cbf-time-course Blood flow fell by 26 to 43% at 3 and 4 ATA, but at 5 ATA it fell over 30 minutes then gradually returned to pre-exposure levels, preceding the onset of electroencephalographic spiking. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The vessel response flips during a long exposure, and the flip comes just before the seizure activity. organism: Rat tissue_or_cell_type: Brain experimental_model: Regional cerebral blood flow and electroencephalography in anaesthetised rats limitations: A time-course study at toxic pressures. It shows the nitric oxide effect reverses with exposure time, which a single time point would miss. exposure: Oxygen at 1, 3, 4 and 5 ATA with L-NAME, L-arginine, nitric oxide donors or MK-801 evidence_span: {"source_cache": "artifacts/hbot-research/10749833.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1470d09e77b6d6f6af3131a6f7db2cca647dde3655662a1c83f9d5d375f1c687", "start_char": 0, "end_char": 1283, "text_sha256": "1470d09e77b6d6f6af3131a6f7db2cca647dde3655662a1c83f9d5d375f1c687"} [hbot-p10749833] Nitric oxide and cerebral blood flow responses to hyperbaric oxygen. (2000). https://pubmed.ncbi.nlm.nih.gov/10749833/ DOI: 10.1152/jappl.2000.88.4.1381

    Complete structured claim and evidence

12. A relative lack of nitric oxide activity contributed to the early decrease in blood flow, but as exposure was prolonged nitric oxide production increased and augmented blood flow in anticipation of neuronal excitation.

    NO → Regional cerebral blood flow source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/10749833.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1470d09e77b6d6f6af3131a6f7db2cca647dde3655662a1c83f9d5d375f1c687", "start_char": 0, "end_char": 1283, "text_sha256": "1470d09e77b6d6f6af3131a6f7db2cca647dde3655662a1c83f9d5d375f1c687"}

    experimental_model

    Regional cerebral blood flow and electroencephalography in anaesthetised rats

    exposure

    Oxygen at 1, 3, 4 and 5 ATA with L-NAME, L-arginine, nitric oxide donors or MK-801

    limitations

    A time-course study at toxic pressures. It shows the nitric oxide effect reverses with exposure time, which a single time point would miss.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Rat

    plain_language

    Early on there is too little of this molecule, later too much.

    primary_references

    [hbot-p10749833] Nitric oxide and cerebral blood flow responses to hyperbaric oxygen. (2000). https://pubmed.ncbi.nlm.nih.gov/10749833/ DOI: 10.1152/jappl.2000.88.4.1381

    tissue_or_cell_type

    Brain

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 205–216

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Regional cerebral blood flow and electroencephalography in anaesthetised rats · source_derived_draft · unverified_draft

    ### hbot-no-production-rises-late A relative lack of nitric oxide activity contributed to the early decrease in blood flow, but as exposure was prolonged nitric oxide production increased and augmented blood flow in anticipation of neuronal excitation. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Early on there is too little of this molecule, later too much. organism: Rat tissue_or_cell_type: Brain experimental_model: Regional cerebral blood flow and electroencephalography in anaesthetised rats limitations: A time-course study at toxic pressures. It shows the nitric oxide effect reverses with exposure time, which a single time point would miss. exposure: Oxygen at 1, 3, 4 and 5 ATA with L-NAME, L-arginine, nitric oxide donors or MK-801 evidence_span: {"source_cache": "artifacts/hbot-research/10749833.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1470d09e77b6d6f6af3131a6f7db2cca647dde3655662a1c83f9d5d375f1c687", "start_char": 0, "end_char": 1283, "text_sha256": "1470d09e77b6d6f6af3131a6f7db2cca647dde3655662a1c83f9d5d375f1c687"} [hbot-p10749833] Nitric oxide and cerebral blood flow responses to hyperbaric oxygen. (2000). https://pubmed.ncbi.nlm.nih.gov/10749833/ DOI: 10.1152/jappl.2000.88.4.1381

    Complete structured claim and evidence

13. The NMDA receptor inhibitor MK-801 did not alter the cerebrovascular responses to oxygen at 5 ATA but prevented the electroencephalographic spikes.

    Hyperbaric oxygen therapy → Central nervous system oxygen toxicity seizure source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/10749833.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1470d09e77b6d6f6af3131a6f7db2cca647dde3655662a1c83f9d5d375f1c687", "start_char": 0, "end_char": 1283, "text_sha256": "1470d09e77b6d6f6af3131a6f7db2cca647dde3655662a1c83f9d5d375f1c687"}

    experimental_model

    Regional cerebral blood flow and electroencephalography in anaesthetised rats

    exposure

    Oxygen at 1, 3, 4 and 5 ATA with L-NAME, L-arginine, nitric oxide donors or MK-801

    limitations

    A time-course study at toxic pressures. It shows the nitric oxide effect reverses with exposure time, which a single time point would miss.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Rat

    plain_language

    The seizure and the blood-flow change are separate events with separate causes.

    primary_references

    [hbot-p10749833] Nitric oxide and cerebral blood flow responses to hyperbaric oxygen. (2000). https://pubmed.ncbi.nlm.nih.gov/10749833/ DOI: 10.1152/jappl.2000.88.4.1381

    tissue_or_cell_type

    Brain

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 218–229

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Regional cerebral blood flow and electroencephalography in anaesthetised rats · source_derived_draft · unverified_draft

    ### hbot-seizure-glutamate-independent-flow The NMDA receptor inhibitor MK-801 did not alter the cerebrovascular responses to oxygen at 5 ATA but prevented the electroencephalographic spikes. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The seizure and the blood-flow change are separate events with separate causes. organism: Rat tissue_or_cell_type: Brain experimental_model: Regional cerebral blood flow and electroencephalography in anaesthetised rats limitations: A time-course study at toxic pressures. It shows the nitric oxide effect reverses with exposure time, which a single time point would miss. exposure: Oxygen at 1, 3, 4 and 5 ATA with L-NAME, L-arginine, nitric oxide donors or MK-801 evidence_span: {"source_cache": "artifacts/hbot-research/10749833.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1470d09e77b6d6f6af3131a6f7db2cca647dde3655662a1c83f9d5d375f1c687", "start_char": 0, "end_char": 1283, "text_sha256": "1470d09e77b6d6f6af3131a6f7db2cca647dde3655662a1c83f9d5d375f1c687"} [hbot-p10749833] Nitric oxide and cerebral blood flow responses to hyperbaric oxygen. (2000). https://pubmed.ncbi.nlm.nih.gov/10749833/ DOI: 10.1152/jappl.2000.88.4.1381

    Complete structured claim and evidence

14. Repeated exposures led to significant accumulation of plasma reactive oxygen metabolites and malondialdehyde across fifteen sessions.

    Hyperbaric oxygen therapy → Plasma reactive oxygen metabolites source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/15003734.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5e4b6cef5c64b735c97ae362e7a90c76433e3f8fef2978d3b3b2a584016e506f", "start_char": 0, "end_char": 1432, "text_sha256": "5e4b6cef5c64b735c97ae362e7a90c76433e3f8fef2978d3b3b2a584016e506f"}

    experimental_model

    Twelve patients sampled at the first and fifteenth hyperbaric session

    exposure

    Fifteen hyperbaric oxygen treatments without antioxidant supplementation

    limitations

    A small human series without a control group. The fall in enzyme activity may reflect oxidative modification of the enzymes themselves, which the authors state was still under investigation.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human

    plain_language

    Repeated treatment leaves measurable marks of oxidation in the blood.

    primary_references

    [hbot-p15003734] Oxidative stress and antioxidant status in patients undergoing prolonged exposure to hyperbaric oxygen. (2004). https://pubmed.ncbi.nlm.nih.gov/15003734/ DOI: 10.1016/j.clinbiochem.2003.12.001

    tissue_or_cell_type

    Plasma and erythrocytes

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 231–242

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Twelve patients sampled at the first and fifteenth hyperbaric session · source_derived_draft · unverified_draft

    ### hbot-rom-accumulation Repeated exposures led to significant accumulation of plasma reactive oxygen metabolites and malondialdehyde across fifteen sessions. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Repeated treatment leaves measurable marks of oxidation in the blood. organism: Human tissue_or_cell_type: Plasma and erythrocytes experimental_model: Twelve patients sampled at the first and fifteenth hyperbaric session limitations: A small human series without a control group. The fall in enzyme activity may reflect oxidative modification of the enzymes themselves, which the authors state was still under investigation. exposure: Fifteen hyperbaric oxygen treatments without antioxidant supplementation evidence_span: {"source_cache": "artifacts/hbot-research/15003734.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5e4b6cef5c64b735c97ae362e7a90c76433e3f8fef2978d3b3b2a584016e506f", "start_char": 0, "end_char": 1432, "text_sha256": "5e4b6cef5c64b735c97ae362e7a90c76433e3f8fef2978d3b3b2a584016e506f"} [hbot-p15003734] Oxidative stress and antioxidant status in patients undergoing prolonged exposure to hyperbaric oxygen. (2004). https://pubmed.ncbi.nlm.nih.gov/15003734/ DOI: 10.1016/j.clinbiochem.2003.12.001

    Complete structured claim and evidence

15. After fifteen sessions, erythrocyte superoxide dismutase activity fell significantly compared with the first exposure.

    Hyperbaric oxygen therapy → Erythrocyte superoxide dismutase activity source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/15003734.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5e4b6cef5c64b735c97ae362e7a90c76433e3f8fef2978d3b3b2a584016e506f", "start_char": 0, "end_char": 1432, "text_sha256": "5e4b6cef5c64b735c97ae362e7a90c76433e3f8fef2978d3b3b2a584016e506f"}

    experimental_model

    Twelve patients sampled at the first and fifteenth hyperbaric session

    exposure

    Fifteen hyperbaric oxygen treatments without antioxidant supplementation

    limitations

    A small human series without a control group. The fall in enzyme activity may reflect oxidative modification of the enzymes themselves, which the authors state was still under investigation.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human

    plain_language

    The cell’s own defence enzymes measured lower, not higher, after repeated sessions.

    primary_references

    [hbot-p15003734] Oxidative stress and antioxidant status in patients undergoing prolonged exposure to hyperbaric oxygen. (2004). https://pubmed.ncbi.nlm.nih.gov/15003734/ DOI: 10.1016/j.clinbiochem.2003.12.001

    tissue_or_cell_type

    Plasma and erythrocytes

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 244–255

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Twelve patients sampled at the first and fifteenth hyperbaric session · source_derived_draft · unverified_draft

    ### hbot-antioxidant-sod After fifteen sessions, erythrocyte superoxide dismutase activity fell significantly compared with the first exposure. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The cell’s own defence enzymes measured lower, not higher, after repeated sessions. organism: Human tissue_or_cell_type: Plasma and erythrocytes experimental_model: Twelve patients sampled at the first and fifteenth hyperbaric session limitations: A small human series without a control group. The fall in enzyme activity may reflect oxidative modification of the enzymes themselves, which the authors state was still under investigation. exposure: Fifteen hyperbaric oxygen treatments without antioxidant supplementation evidence_span: {"source_cache": "artifacts/hbot-research/15003734.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5e4b6cef5c64b735c97ae362e7a90c76433e3f8fef2978d3b3b2a584016e506f", "start_char": 0, "end_char": 1432, "text_sha256": "5e4b6cef5c64b735c97ae362e7a90c76433e3f8fef2978d3b3b2a584016e506f"} [hbot-p15003734] Oxidative stress and antioxidant status in patients undergoing prolonged exposure to hyperbaric oxygen. (2004). https://pubmed.ncbi.nlm.nih.gov/15003734/ DOI: 10.1016/j.clinbiochem.2003.12.001

    Complete structured claim and evidence

16. After fifteen sessions, erythrocyte catalase activity fell significantly compared with the first exposure.

    Hyperbaric oxygen therapy → Erythrocyte catalase activity source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/15003734.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5e4b6cef5c64b735c97ae362e7a90c76433e3f8fef2978d3b3b2a584016e506f", "start_char": 0, "end_char": 1432, "text_sha256": "5e4b6cef5c64b735c97ae362e7a90c76433e3f8fef2978d3b3b2a584016e506f"}

    experimental_model

    Twelve patients sampled at the first and fifteenth hyperbaric session

    exposure

    Fifteen hyperbaric oxygen treatments without antioxidant supplementation

    limitations

    A small human series without a control group. The fall in enzyme activity may reflect oxidative modification of the enzymes themselves, which the authors state was still under investigation.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human

    plain_language

    The cell’s own defence enzymes measured lower, not higher, after repeated sessions.

    primary_references

    [hbot-p15003734] Oxidative stress and antioxidant status in patients undergoing prolonged exposure to hyperbaric oxygen. (2004). https://pubmed.ncbi.nlm.nih.gov/15003734/ DOI: 10.1016/j.clinbiochem.2003.12.001

    tissue_or_cell_type

    Plasma and erythrocytes

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 257–268

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Twelve patients sampled at the first and fifteenth hyperbaric session · source_derived_draft · unverified_draft

    ### hbot-antioxidant-catalase After fifteen sessions, erythrocyte catalase activity fell significantly compared with the first exposure. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The cell’s own defence enzymes measured lower, not higher, after repeated sessions. organism: Human tissue_or_cell_type: Plasma and erythrocytes experimental_model: Twelve patients sampled at the first and fifteenth hyperbaric session limitations: A small human series without a control group. The fall in enzyme activity may reflect oxidative modification of the enzymes themselves, which the authors state was still under investigation. exposure: Fifteen hyperbaric oxygen treatments without antioxidant supplementation evidence_span: {"source_cache": "artifacts/hbot-research/15003734.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5e4b6cef5c64b735c97ae362e7a90c76433e3f8fef2978d3b3b2a584016e506f", "start_char": 0, "end_char": 1432, "text_sha256": "5e4b6cef5c64b735c97ae362e7a90c76433e3f8fef2978d3b3b2a584016e506f"} [hbot-p15003734] Oxidative stress and antioxidant status in patients undergoing prolonged exposure to hyperbaric oxygen. (2004). https://pubmed.ncbi.nlm.nih.gov/15003734/ DOI: 10.1016/j.clinbiochem.2003.12.001

    Complete structured claim and evidence

17. Glutathione peroxidase activity remained almost unchanged, and no relevant differences were detected in reduced glutathione, alpha-tocopherol or retinol plasma levels.

    Hyperbaric oxygen therapy → Erythrocyte glutathione peroxidase activity source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/15003734.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5e4b6cef5c64b735c97ae362e7a90c76433e3f8fef2978d3b3b2a584016e506f", "start_char": 0, "end_char": 1432, "text_sha256": "5e4b6cef5c64b735c97ae362e7a90c76433e3f8fef2978d3b3b2a584016e506f"}

    experimental_model

    Twelve patients sampled at the first and fifteenth hyperbaric session

    exposure

    Fifteen hyperbaric oxygen treatments without antioxidant supplementation

    limitations

    A small human series without a control group. The fall in enzyme activity may reflect oxidative modification of the enzymes themselves, which the authors state was still under investigation.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human

    plain_language

    The selenium-dependent enzyme and the vitamin pools held steady while two other enzymes fell.

    primary_references

    [hbot-p15003734] Oxidative stress and antioxidant status in patients undergoing prolonged exposure to hyperbaric oxygen. (2004). https://pubmed.ncbi.nlm.nih.gov/15003734/ DOI: 10.1016/j.clinbiochem.2003.12.001

    tissue_or_cell_type

    Plasma and erythrocytes

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 270–281

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Twelve patients sampled at the first and fifteenth hyperbaric session · source_derived_draft · unverified_draft

    ### hbot-gpx-unchanged Glutathione peroxidase activity remained almost unchanged, and no relevant differences were detected in reduced glutathione, alpha-tocopherol or retinol plasma levels. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The selenium-dependent enzyme and the vitamin pools held steady while two other enzymes fell. organism: Human tissue_or_cell_type: Plasma and erythrocytes experimental_model: Twelve patients sampled at the first and fifteenth hyperbaric session limitations: A small human series without a control group. The fall in enzyme activity may reflect oxidative modification of the enzymes themselves, which the authors state was still under investigation. exposure: Fifteen hyperbaric oxygen treatments without antioxidant supplementation evidence_span: {"source_cache": "artifacts/hbot-research/15003734.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5e4b6cef5c64b735c97ae362e7a90c76433e3f8fef2978d3b3b2a584016e506f", "start_char": 0, "end_char": 1432, "text_sha256": "5e4b6cef5c64b735c97ae362e7a90c76433e3f8fef2978d3b3b2a584016e506f"} [hbot-p15003734] Oxidative stress and antioxidant status in patients undergoing prolonged exposure to hyperbaric oxygen. (2004). https://pubmed.ncbi.nlm.nih.gov/15003734/ DOI: 10.1016/j.clinbiochem.2003.12.001

    Complete structured claim and evidence

18. A single treatment caused clear and reproducible DNA damage in lymphocytes, found only after the first exposure and not after further treatments of the same individuals.

    Hyperbaric oxygen therapy → Oxidative DNA damage in circulating lymphocytes measured by the comet assay source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/11023535.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "19b770dff3d327e2dd6d49180686f9823624190ab5693c28b88adcfaf703f14d", "start_char": 0, "end_char": 1576, "text_sha256": "19b770dff3d327e2dd6d49180686f9823624190ab5693c28b88adcfaf703f14d"}

    experimental_model

    Comet assay in lymphocytes of volunteers before and after hyperbaric oxygen, with enzyme expression measurement

    exposure

    100% oxygen at 2.5 ATA for three 20-minute periods

    limitations

    A human exposure study with a within-subject design. The iron-sequestration explanation is the authors’ inference from the pattern of protection, not a direct measurement of free iron.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human

    plain_language

    The first session damages DNA; later sessions do not.

    primary_references

    [hbot-p11023535] Induction of heme oxygenase-1 and adaptive protection against the induction of DNA damage after hyperbaric oxygen treatment. (2000). https://pubmed.ncbi.nlm.nih.gov/11023535/ DOI: 10.1093/carcin/21.10.1795

    tissue_or_cell_type

    Circulating lymphocytes

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 283–294

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Comet assay in lymphocytes of volunteers before and after hyperbaric oxygen, with enzyme expression measurement · source_derived_draft · unverified_draft

    ### hbot-first-exposure-dna-damage A single treatment caused clear and reproducible DNA damage in lymphocytes, found only after the first exposure and not after further treatments of the same individuals. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The first session damages DNA; later sessions do not. organism: Human tissue_or_cell_type: Circulating lymphocytes experimental_model: Comet assay in lymphocytes of volunteers before and after hyperbaric oxygen, with enzyme expression measurement limitations: A human exposure study with a within-subject design. The iron-sequestration explanation is the authors’ inference from the pattern of protection, not a direct measurement of free iron. exposure: 100% oxygen at 2.5 ATA for three 20-minute periods evidence_span: {"source_cache": "artifacts/hbot-research/11023535.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "19b770dff3d327e2dd6d49180686f9823624190ab5693c28b88adcfaf703f14d", "start_char": 0, "end_char": 1576, "text_sha256": "19b770dff3d327e2dd6d49180686f9823624190ab5693c28b88adcfaf703f14d"} [hbot-p11023535] Induction of heme oxygenase-1 and adaptive protection against the induction of DNA damage after hyperbaric oxygen treatment. (2000). https://pubmed.ncbi.nlm.nih.gov/11023535/ DOI: 10.1093/carcin/21.10.1795

    Complete structured claim and evidence

19. Blood taken 24 hours after treatment was significantly protected against DNA damage induced by hydrogen peroxide in vitro, while protection against gamma-irradiation was not significant.

    Hyperbaric oxygen therapy → Adaptive protection against oxidative DNA damage source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/11023535.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "19b770dff3d327e2dd6d49180686f9823624190ab5693c28b88adcfaf703f14d", "start_char": 0, "end_char": 1576, "text_sha256": "19b770dff3d327e2dd6d49180686f9823624190ab5693c28b88adcfaf703f14d"}

    experimental_model

    Comet assay in lymphocytes of volunteers before and after hyperbaric oxygen, with enzyme expression measurement

    exposure

    100% oxygen at 2.5 ATA for three 20-minute periods

    limitations

    A human exposure study with a within-subject design. The iron-sequestration explanation is the authors’ inference from the pattern of protection, not a direct measurement of free iron.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human

    plain_language

    One exposure leaves the cells better able to survive the next oxidative hit.

    primary_references

    [hbot-p11023535] Induction of heme oxygenase-1 and adaptive protection against the induction of DNA damage after hyperbaric oxygen treatment. (2000). https://pubmed.ncbi.nlm.nih.gov/11023535/ DOI: 10.1093/carcin/21.10.1795

    tissue_or_cell_type

    Circulating lymphocytes

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 296–307

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Comet assay in lymphocytes of volunteers before and after hyperbaric oxygen, with enzyme expression measurement · source_derived_draft · unverified_draft

    ### hbot-adaptive-protection Blood taken 24 hours after treatment was significantly protected against DNA damage induced by hydrogen peroxide in vitro, while protection against gamma-irradiation was not significant. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: One exposure leaves the cells better able to survive the next oxidative hit. organism: Human tissue_or_cell_type: Circulating lymphocytes experimental_model: Comet assay in lymphocytes of volunteers before and after hyperbaric oxygen, with enzyme expression measurement limitations: A human exposure study with a within-subject design. The iron-sequestration explanation is the authors’ inference from the pattern of protection, not a direct measurement of free iron. exposure: 100% oxygen at 2.5 ATA for three 20-minute periods evidence_span: {"source_cache": "artifacts/hbot-research/11023535.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "19b770dff3d327e2dd6d49180686f9823624190ab5693c28b88adcfaf703f14d", "start_char": 0, "end_char": 1576, "text_sha256": "19b770dff3d327e2dd6d49180686f9823624190ab5693c28b88adcfaf703f14d"} [hbot-p11023535] Induction of heme oxygenase-1 and adaptive protection against the induction of DNA damage after hyperbaric oxygen treatment. (2000). https://pubmed.ncbi.nlm.nih.gov/11023535/ DOI: 10.1093/carcin/21.10.1795

    Complete structured claim and evidence

20. Heme oxygenase-1 levels were increased in lymphocytes 24 hours after treatment, while superoxide dismutase, catalase and the DNA repair enzymes apurinic endonuclease and DNA polymerase beta were not enhanced in expression.

    Hyperbaric oxygen therapy → Human heme oxygenase 1 / HMOX1 source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/11023535.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "19b770dff3d327e2dd6d49180686f9823624190ab5693c28b88adcfaf703f14d", "start_char": 0, "end_char": 1576, "text_sha256": "19b770dff3d327e2dd6d49180686f9823624190ab5693c28b88adcfaf703f14d"}

    experimental_model

    Comet assay in lymphocytes of volunteers before and after hyperbaric oxygen, with enzyme expression measurement

    exposure

    100% oxygen at 2.5 ATA for three 20-minute periods

    limitations

    A human exposure study with a within-subject design. The iron-sequestration explanation is the authors’ inference from the pattern of protection, not a direct measurement of free iron.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human

    plain_language

    Only one defence protein went up, and it is the one that handles heme iron.

    primary_references

    [hbot-p11023535] Induction of heme oxygenase-1 and adaptive protection against the induction of DNA damage after hyperbaric oxygen treatment. (2000). https://pubmed.ncbi.nlm.nih.gov/11023535/ DOI: 10.1093/carcin/21.10.1795

    tissue_or_cell_type

    Circulating lymphocytes

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 309–320

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Comet assay in lymphocytes of volunteers before and after hyperbaric oxygen, with enzyme expression measurement · source_derived_draft · unverified_draft

    ### hbot-ho1-induction Heme oxygenase-1 levels were increased in lymphocytes 24 hours after treatment, while superoxide dismutase, catalase and the DNA repair enzymes apurinic endonuclease and DNA polymerase beta were not enhanced in expression. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Only one defence protein went up, and it is the one that handles heme iron. organism: Human tissue_or_cell_type: Circulating lymphocytes experimental_model: Comet assay in lymphocytes of volunteers before and after hyperbaric oxygen, with enzyme expression measurement limitations: A human exposure study with a within-subject design. The iron-sequestration explanation is the authors’ inference from the pattern of protection, not a direct measurement of free iron. exposure: 100% oxygen at 2.5 ATA for three 20-minute periods evidence_span: {"source_cache": "artifacts/hbot-research/11023535.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "19b770dff3d327e2dd6d49180686f9823624190ab5693c28b88adcfaf703f14d", "start_char": 0, "end_char": 1576, "text_sha256": "19b770dff3d327e2dd6d49180686f9823624190ab5693c28b88adcfaf703f14d"} [hbot-p11023535] Induction of heme oxygenase-1 and adaptive protection against the induction of DNA damage after hyperbaric oxygen treatment. (2000). https://pubmed.ncbi.nlm.nih.gov/11023535/ DOI: 10.1093/carcin/21.10.1795

    Complete structured claim and evidence

21. The authors suggest that increased sequestration of iron as a consequence of induced heme oxygenase-1 might be involved in the adaptive protection, and that induction of DNA damage is not the trigger for it.

    Human heme oxygenase 1 / HMOX1 → Availability of free transition metals inside the cell source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/11023535.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "19b770dff3d327e2dd6d49180686f9823624190ab5693c28b88adcfaf703f14d", "start_char": 0, "end_char": 1576, "text_sha256": "19b770dff3d327e2dd6d49180686f9823624190ab5693c28b88adcfaf703f14d"}

    experimental_model

    Comet assay in lymphocytes of volunteers before and after hyperbaric oxygen, with enzyme expression measurement

    exposure

    100% oxygen at 2.5 ATA for three 20-minute periods

    limitations

    A human exposure study with a within-subject design. The iron-sequestration explanation is the authors’ inference from the pattern of protection, not a direct measurement of free iron.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human

    plain_language

    The proposed protection is locking away the iron that would otherwise turn peroxide into a more dangerous radical.

    primary_references

    [hbot-p11023535] Induction of heme oxygenase-1 and adaptive protection against the induction of DNA damage after hyperbaric oxygen treatment. (2000). https://pubmed.ncbi.nlm.nih.gov/11023535/ DOI: 10.1093/carcin/21.10.1795

    tissue_or_cell_type

    Circulating lymphocytes

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 322–333

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Comet assay in lymphocytes of volunteers before and after hyperbaric oxygen, with enzyme expression measurement · source_derived_draft · unverified_draft

    ### hbot-iron-sequestration-hypothesis The authors suggest that increased sequestration of iron as a consequence of induced heme oxygenase-1 might be involved in the adaptive protection, and that induction of DNA damage is not the trigger for it. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The proposed protection is locking away the iron that would otherwise turn peroxide into a more dangerous radical. organism: Human tissue_or_cell_type: Circulating lymphocytes experimental_model: Comet assay in lymphocytes of volunteers before and after hyperbaric oxygen, with enzyme expression measurement limitations: A human exposure study with a within-subject design. The iron-sequestration explanation is the authors’ inference from the pattern of protection, not a direct measurement of free iron. exposure: 100% oxygen at 2.5 ATA for three 20-minute periods evidence_span: {"source_cache": "artifacts/hbot-research/11023535.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "19b770dff3d327e2dd6d49180686f9823624190ab5693c28b88adcfaf703f14d", "start_char": 0, "end_char": 1576, "text_sha256": "19b770dff3d327e2dd6d49180686f9823624190ab5693c28b88adcfaf703f14d"} [hbot-p11023535] Induction of heme oxygenase-1 and adaptive protection against the induction of DNA damage after hyperbaric oxygen treatment. (2000). https://pubmed.ncbi.nlm.nih.gov/11023535/ DOI: 10.1093/carcin/21.10.1795

    Complete structured claim and evidence

22. Treatment with the specific heme oxygenase-1 inhibitor tin-mesoporphyrin IX led to complete abrogation of the hyperbaric-oxygen-induced adaptive protection in human lymphocytes, and the time course of induction paralleled the development of protection.

    Tin-mesoporphyrin IX, a heme oxygenase-1 inhibitor → Adaptive protection against oxidative DNA damage source_derived_draftungraded
    Experimental context and source evidence

    availability_state

    machinery_impairment Imported condition classification; unverified.

    evidence_span

    {"source_cache": "artifacts/hbot-research/11751428.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d8fb2631feb55cff2514149c0935ad25230bbdc520cc82dddaec2baa4ada40f3", "start_char": 0, "end_char": 1641, "text_sha256": "d8fb2631feb55cff2514149c0935ad25230bbdc520cc82dddaec2baa4ada40f3"}

    experimental_model

    Isolated human lymphocytes exposed in vitro with a specific heme oxygenase-1 inhibitor

    exposure

    Hyperbaric oxygen in vitro, 2 hours at 3 bar; tin-mesoporphyrin IX

    limitations

    An inhibitor experiment that establishes requirement in this cell system. The authors state the exact mechanism by which the enzyme protects remains to be elucidated.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human lymphocytes and V79 cells

    plain_language

    Block that one enzyme and the protection disappears.

    primary_references

    [hbot-p11751428] Involvement of heme oxygenase-1 (HO-1) in the adaptive protection of human lymphocytes after hyperbaric oxygen (HBO) treatment. (2001). https://pubmed.ncbi.nlm.nih.gov/11751428/ DOI: 10.1093/carcin/22.12.1979

    tissue_or_cell_type

    Isolated lymphocytes

    trigger_kind

    machinery_impairment Imported condition classification; unverified.

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 335–346

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isolated human lymphocytes exposed in vitro with a specific heme oxygenase-1 inhibitor · source_derived_draft · unverified_draft

    ### hbot-ho1-required Treatment with the specific heme oxygenase-1 inhibitor tin-mesoporphyrin IX led to complete abrogation of the hyperbaric-oxygen-induced adaptive protection in human lymphocytes, and the time course of induction paralleled the development of protection. Condition category: machinery_impairment nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Block that one enzyme and the protection disappears. organism: Human lymphocytes and V79 cells tissue_or_cell_type: Isolated lymphocytes experimental_model: Isolated human lymphocytes exposed in vitro with a specific heme oxygenase-1 inhibitor limitations: An inhibitor experiment that establishes requirement in this cell system. The authors state the exact mechanism by which the enzyme protects remains to be elucidated. exposure: Hyperbaric oxygen in vitro, 2 hours at 3 bar; tin-mesoporphyrin IX evidence_span: {"source_cache": "artifacts/hbot-research/11751428.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d8fb2631feb55cff2514149c0935ad25230bbdc520cc82dddaec2baa4ada40f3", "start_char": 0, "end_char": 1641, "text_sha256": "d8fb2631feb55cff2514149c0935ad25230bbdc520cc82dddaec2baa4ada40f3"} [hbot-p11751428] Involvement of heme oxygenase-1 (HO-1) in the adaptive protection of human lymphocytes after hyperbaric oxygen (HBO) treatment. (2001). https://pubmed.ncbi.nlm.nih.gov/11751428/ DOI: 10.1093/carcin/22.12.1979

    Complete structured claim and evidence

23. Heat shock protein 32 expression increased significantly and peaked 12 hours after exposure, while heat shock proteins 27, 70 and 90 showed only slight and non-significant increases.

    Hyperbaric oxygen therapy → Heat shock protein 32 / heme oxygenase-1 in the rat spinal-neuron study source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/24465817.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e79c9e686d7b5cab274a5bf6e25c188c42e44646fef7f478c53a12831de8e70f", "start_char": 0, "end_char": 1501, "text_sha256": "e79c9e686d7b5cab274a5bf6e25c188c42e44646fef7f478c53a12831de8e70f"}

    experimental_model

    Primary rat spinal neurons after hyperbaric oxygen preconditioning with heat shock protein inhibitors

    exposure

    A single hyperbaric oxygen exposure before hydrogen peroxide or oxygen-glucose deprivation

    limitations

    A preconditioning experiment in cultured neurons. Heat shock protein 32 is heme oxygenase-1 under another name, which is why the inhibitor used is a porphyrin.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Rat

    plain_language

    One heat shock protein responded strongly and the others barely moved.

    primary_references

    [hbot-p24465817] Hyperbaric oxygen preconditioning induces tolerance against oxidative injury and oxygen-glucose deprivation by up-regulating heat shock protein 32 in rat spinal neurons. (2014). https://pubmed.ncbi.nlm.nih.gov/24465817/ DOI: 10.1371/journal.pone.0085967

    tissue_or_cell_type

    Primary spinal neurons

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 348–359

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary rat spinal neurons after hyperbaric oxygen preconditioning with heat shock protein inhibitors · source_derived_draft · unverified_draft

    ### hbot-hsp32-induction Heat shock protein 32 expression increased significantly and peaked 12 hours after exposure, while heat shock proteins 27, 70 and 90 showed only slight and non-significant increases. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: One heat shock protein responded strongly and the others barely moved. organism: Rat tissue_or_cell_type: Primary spinal neurons experimental_model: Primary rat spinal neurons after hyperbaric oxygen preconditioning with heat shock protein inhibitors limitations: A preconditioning experiment in cultured neurons. Heat shock protein 32 is heme oxygenase-1 under another name, which is why the inhibitor used is a porphyrin. exposure: A single hyperbaric oxygen exposure before hydrogen peroxide or oxygen-glucose deprivation evidence_span: {"source_cache": "artifacts/hbot-research/24465817.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e79c9e686d7b5cab274a5bf6e25c188c42e44646fef7f478c53a12831de8e70f", "start_char": 0, "end_char": 1501, "text_sha256": "e79c9e686d7b5cab274a5bf6e25c188c42e44646fef7f478c53a12831de8e70f"} [hbot-p24465817] Hyperbaric oxygen preconditioning induces tolerance against oxidative injury and oxygen-glucose deprivation by up-regulating heat shock protein 32 in rat spinal neurons. (2014). https://pubmed.ncbi.nlm.nih.gov/24465817/ DOI: 10.1371/journal.pone.0085967

    Complete structured claim and evidence

24. Preconditioning significantly increased cell viability and decreased lactate dehydrogenase release in cultures treated with hydrogen peroxide or oxygen-glucose deprivation.

    Hyperbaric oxygen therapy → Primary rat spinal-neuron viability after oxidative or oxygen-glucose-deprivation injury source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/24465817.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e79c9e686d7b5cab274a5bf6e25c188c42e44646fef7f478c53a12831de8e70f", "start_char": 0, "end_char": 1501, "text_sha256": "e79c9e686d7b5cab274a5bf6e25c188c42e44646fef7f478c53a12831de8e70f"}

    experimental_model

    Primary rat spinal neurons after hyperbaric oxygen preconditioning with heat shock protein inhibitors

    exposure

    A single hyperbaric oxygen exposure before hydrogen peroxide or oxygen-glucose deprivation

    limitations

    A preconditioning experiment in cultured neurons. Heat shock protein 32 is heme oxygenase-1 under another name, which is why the inhibitor used is a porphyrin.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Rat

    plain_language

    Neurons preconditioned this way survived a later injury better.

    primary_references

    [hbot-p24465817] Hyperbaric oxygen preconditioning induces tolerance against oxidative injury and oxygen-glucose deprivation by up-regulating heat shock protein 32 in rat spinal neurons. (2014). https://pubmed.ncbi.nlm.nih.gov/24465817/ DOI: 10.1371/journal.pone.0085967

    tissue_or_cell_type

    Primary spinal neurons

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 361–372

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary rat spinal neurons after hyperbaric oxygen preconditioning with heat shock protein inhibitors · source_derived_draft · unverified_draft

    ### hbot-hsp32-protection Preconditioning significantly increased cell viability and decreased lactate dehydrogenase release in cultures treated with hydrogen peroxide or oxygen-glucose deprivation. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Neurons preconditioned this way survived a later injury better. organism: Rat tissue_or_cell_type: Primary spinal neurons experimental_model: Primary rat spinal neurons after hyperbaric oxygen preconditioning with heat shock protein inhibitors limitations: A preconditioning experiment in cultured neurons. Heat shock protein 32 is heme oxygenase-1 under another name, which is why the inhibitor used is a porphyrin. exposure: A single hyperbaric oxygen exposure before hydrogen peroxide or oxygen-glucose deprivation evidence_span: {"source_cache": "artifacts/hbot-research/24465817.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e79c9e686d7b5cab274a5bf6e25c188c42e44646fef7f478c53a12831de8e70f", "start_char": 0, "end_char": 1501, "text_sha256": "e79c9e686d7b5cab274a5bf6e25c188c42e44646fef7f478c53a12831de8e70f"} [hbot-p24465817] Hyperbaric oxygen preconditioning induces tolerance against oxidative injury and oxygen-glucose deprivation by up-regulating heat shock protein 32 in rat spinal neurons. (2014). https://pubmed.ncbi.nlm.nih.gov/24465817/ DOI: 10.1371/journal.pone.0085967

    Complete structured claim and evidence

25. Pretreatment with zinc protoporphyrin IX, a specific inhibitor of heat shock protein 32, significantly blocked the protective effects of preconditioning.

    Zinc protoporphyrin IX, a heme oxygenase inhibitor → Primary rat spinal-neuron viability after oxidative or oxygen-glucose-deprivation injury source_derived_draftungraded
    Experimental context and source evidence

    availability_state

    machinery_impairment Imported condition classification; unverified.

    evidence_span

    {"source_cache": "artifacts/hbot-research/24465817.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e79c9e686d7b5cab274a5bf6e25c188c42e44646fef7f478c53a12831de8e70f", "start_char": 0, "end_char": 1501, "text_sha256": "e79c9e686d7b5cab274a5bf6e25c188c42e44646fef7f478c53a12831de8e70f"}

    experimental_model

    Primary rat spinal neurons after hyperbaric oxygen preconditioning with heat shock protein inhibitors

    exposure

    A single hyperbaric oxygen exposure before hydrogen peroxide or oxygen-glucose deprivation

    limitations

    A preconditioning experiment in cultured neurons. Heat shock protein 32 is heme oxygenase-1 under another name, which is why the inhibitor used is a porphyrin.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Rat

    plain_language

    Blocking that protein removed the protection.

    primary_references

    [hbot-p24465817] Hyperbaric oxygen preconditioning induces tolerance against oxidative injury and oxygen-glucose deprivation by up-regulating heat shock protein 32 in rat spinal neurons. (2014). https://pubmed.ncbi.nlm.nih.gov/24465817/ DOI: 10.1371/journal.pone.0085967

    tissue_or_cell_type

    Primary spinal neurons

    trigger_kind

    machinery_impairment Imported condition classification; unverified.

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 374–385

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary rat spinal neurons after hyperbaric oxygen preconditioning with heat shock protein inhibitors · source_derived_draft · unverified_draft

    ### hbot-hsp32-required Pretreatment with zinc protoporphyrin IX, a specific inhibitor of heat shock protein 32, significantly blocked the protective effects of preconditioning. Condition category: machinery_impairment nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Blocking that protein removed the protection. organism: Rat tissue_or_cell_type: Primary spinal neurons experimental_model: Primary rat spinal neurons after hyperbaric oxygen preconditioning with heat shock protein inhibitors limitations: A preconditioning experiment in cultured neurons. Heat shock protein 32 is heme oxygenase-1 under another name, which is why the inhibitor used is a porphyrin. exposure: A single hyperbaric oxygen exposure before hydrogen peroxide or oxygen-glucose deprivation evidence_span: {"source_cache": "artifacts/hbot-research/24465817.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e79c9e686d7b5cab274a5bf6e25c188c42e44646fef7f478c53a12831de8e70f", "start_char": 0, "end_char": 1501, "text_sha256": "e79c9e686d7b5cab274a5bf6e25c188c42e44646fef7f478c53a12831de8e70f"} [hbot-p24465817] Hyperbaric oxygen preconditioning induces tolerance against oxidative injury and oxygen-glucose deprivation by up-regulating heat shock protein 32 in rat spinal neurons. (2014). https://pubmed.ncbi.nlm.nih.gov/24465817/ DOI: 10.1371/journal.pone.0085967

    Complete structured claim and evidence

26. Thioredoxin reductase activity fell by 51% after the 3-hour oxygen exposure, while cellular glutathione and the activities of several other antioxidant enzymes, including glyceraldehyde-3-phosphate dehydrogenase, showed no immediate effect.

    Hyperbaric oxygen therapy → Thioredoxin reductase catalytic activity source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/15642322.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e3bc035a17e4e19dd92d4fadb1a79f8e3801619dac24fb91dcf985728afaf995", "start_char": 0, "end_char": 2646, "text_sha256": "e3bc035a17e4e19dd92d4fadb1a79f8e3801619dac24fb91dcf985728afaf995"}

    experimental_model

    Cultured human lens epithelial cells exposed to extreme hyperbaric oxygen with enzyme assays and real-time PCR

    exposure

    99% oxygen at 50 atmospheres for 3 hours, then normal culture for up to 11 days

    limitations

    Fifty atmospheres is an extreme experimental exposure far above therapy, chosen to probe which defences matter. The selenoenzyme result is the informative part; the pressure is not clinically relevant.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human cells

    plain_language

    Of all the defences measured, the selenium enzyme was the one that was knocked down.

    primary_references

    [hbot-p15642322] Thioredoxin reductase may be essential for the normal growth of hyperbaric oxygen-treated human lens epithelial cells. (2004). https://pubmed.ncbi.nlm.nih.gov/15642322/ DOI: 10.1016/j.exer.2004.07.001

    tissue_or_cell_type

    Lens epithelium

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 387–398

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cultured human lens epithelial cells exposed to extreme hyperbaric oxygen with enzyme assays and real-time PCR · source_derived_draft · unverified_draft

    ### hbot-trxr-activity-loss Thioredoxin reductase activity fell by 51% after the 3-hour oxygen exposure, while cellular glutathione and the activities of several other antioxidant enzymes, including glyceraldehyde-3-phosphate dehydrogenase, showed no immediate effect. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Of all the defences measured, the selenium enzyme was the one that was knocked down. organism: Human cells tissue_or_cell_type: Lens epithelium experimental_model: Cultured human lens epithelial cells exposed to extreme hyperbaric oxygen with enzyme assays and real-time PCR limitations: Fifty atmospheres is an extreme experimental exposure far above therapy, chosen to probe which defences matter. The selenoenzyme result is the informative part; the pressure is not clinically relevant. exposure: 99% oxygen at 50 atmospheres for 3 hours, then normal culture for up to 11 days evidence_span: {"source_cache": "artifacts/hbot-research/15642322.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e3bc035a17e4e19dd92d4fadb1a79f8e3801619dac24fb91dcf985728afaf995", "start_char": 0, "end_char": 2646, "text_sha256": "e3bc035a17e4e19dd92d4fadb1a79f8e3801619dac24fb91dcf985728afaf995"} [hbot-p15642322] Thioredoxin reductase may be essential for the normal growth of hyperbaric oxygen-treated human lens epithelial cells. (2004). https://pubmed.ncbi.nlm.nih.gov/15642322/ DOI: 10.1016/j.exer.2004.07.001

    Complete structured claim and evidence

27. Recovery of thioredoxin reductase activity over four days paralleled the return of the cells to a normal rate of growth, and the authors conclude that full activity of TrxR1, required for production of deoxyribonucleotides for DNA synthesis, is essential for normal growth of oxygen-challenged cells.

    Thioredoxin reductase catalytic activity → Human lens epithelial cell growth source_derived_draftungraded
    Experimental context and source evidence

    availability_state

    machinery_impairment Imported condition classification; unverified.

    evidence_span

    {"source_cache": "artifacts/hbot-research/15642322.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e3bc035a17e4e19dd92d4fadb1a79f8e3801619dac24fb91dcf985728afaf995", "start_char": 0, "end_char": 2646, "text_sha256": "e3bc035a17e4e19dd92d4fadb1a79f8e3801619dac24fb91dcf985728afaf995"}

    experimental_model

    Cultured human lens epithelial cells exposed to extreme hyperbaric oxygen with enzyme assays and real-time PCR

    exposure

    99% oxygen at 50 atmospheres for 3 hours, then normal culture for up to 11 days

    limitations

    Fifty atmospheres is an extreme experimental exposure far above therapy, chosen to probe which defences matter. The selenoenzyme result is the informative part; the pressure is not clinically relevant.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human cells

    plain_language

    The cells could not start dividing again until that enzyme came back.

    primary_references

    [hbot-p15642322] Thioredoxin reductase may be essential for the normal growth of hyperbaric oxygen-treated human lens epithelial cells. (2004). https://pubmed.ncbi.nlm.nih.gov/15642322/ DOI: 10.1016/j.exer.2004.07.001

    tissue_or_cell_type

    Lens epithelium

    trigger_kind

    machinery_impairment Imported condition classification; unverified.

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 400–411

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cultured human lens epithelial cells exposed to extreme hyperbaric oxygen with enzyme assays and real-time PCR · source_derived_draft · unverified_draft

    ### hbot-trxr-growth-requirement Recovery of thioredoxin reductase activity over four days paralleled the return of the cells to a normal rate of growth, and the authors conclude that full activity of TrxR1, required for production of deoxyribonucleotides for DNA synthesis, is essential for normal growth of oxygen-challenged cells. Condition category: machinery_impairment nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The cells could not start dividing again until that enzyme came back. organism: Human cells tissue_or_cell_type: Lens epithelium experimental_model: Cultured human lens epithelial cells exposed to extreme hyperbaric oxygen with enzyme assays and real-time PCR limitations: Fifty atmospheres is an extreme experimental exposure far above therapy, chosen to probe which defences matter. The selenoenzyme result is the informative part; the pressure is not clinically relevant. exposure: 99% oxygen at 50 atmospheres for 3 hours, then normal culture for up to 11 days evidence_span: {"source_cache": "artifacts/hbot-research/15642322.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e3bc035a17e4e19dd92d4fadb1a79f8e3801619dac24fb91dcf985728afaf995", "start_char": 0, "end_char": 2646, "text_sha256": "e3bc035a17e4e19dd92d4fadb1a79f8e3801619dac24fb91dcf985728afaf995"} [hbot-p15642322] Thioredoxin reductase may be essential for the normal growth of hyperbaric oxygen-treated human lens epithelial cells. (2004). https://pubmed.ncbi.nlm.nih.gov/15642322/ DOI: 10.1016/j.exer.2004.07.001

    Complete structured claim and evidence

28. Cell death appeared to be caused by loss of ATP, with a 31% decrease immediately after exposure despite a 46% increase in lactate production, and damage occurred primarily in the mitochondria rather than the cytoplasm.

    Hyperbaric oxygen therapy → ATP source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/15642322.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e3bc035a17e4e19dd92d4fadb1a79f8e3801619dac24fb91dcf985728afaf995", "start_char": 0, "end_char": 2646, "text_sha256": "e3bc035a17e4e19dd92d4fadb1a79f8e3801619dac24fb91dcf985728afaf995"}

    experimental_model

    Cultured human lens epithelial cells exposed to extreme hyperbaric oxygen with enzyme assays and real-time PCR

    exposure

    99% oxygen at 50 atmospheres for 3 hours, then normal culture for up to 11 days

    limitations

    Fifty atmospheres is an extreme experimental exposure far above therapy, chosen to probe which defences matter. The selenoenzyme result is the informative part; the pressure is not clinically relevant.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human cells

    plain_language

    The damage landed on the mitochondria, and the cell could not make up the energy by fermenting.

    primary_references

    [hbot-p15642322] Thioredoxin reductase may be essential for the normal growth of hyperbaric oxygen-treated human lens epithelial cells. (2004). https://pubmed.ncbi.nlm.nih.gov/15642322/ DOI: 10.1016/j.exer.2004.07.001

    tissue_or_cell_type

    Lens epithelium

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 413–424

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cultured human lens epithelial cells exposed to extreme hyperbaric oxygen with enzyme assays and real-time PCR · source_derived_draft · unverified_draft

    ### hbot-mito-damage-and-atp Cell death appeared to be caused by loss of ATP, with a 31% decrease immediately after exposure despite a 46% increase in lactate production, and damage occurred primarily in the mitochondria rather than the cytoplasm. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The damage landed on the mitochondria, and the cell could not make up the energy by fermenting. organism: Human cells tissue_or_cell_type: Lens epithelium experimental_model: Cultured human lens epithelial cells exposed to extreme hyperbaric oxygen with enzyme assays and real-time PCR limitations: Fifty atmospheres is an extreme experimental exposure far above therapy, chosen to probe which defences matter. The selenoenzyme result is the informative part; the pressure is not clinically relevant. exposure: 99% oxygen at 50 atmospheres for 3 hours, then normal culture for up to 11 days evidence_span: {"source_cache": "artifacts/hbot-research/15642322.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e3bc035a17e4e19dd92d4fadb1a79f8e3801619dac24fb91dcf985728afaf995", "start_char": 0, "end_char": 2646, "text_sha256": "e3bc035a17e4e19dd92d4fadb1a79f8e3801619dac24fb91dcf985728afaf995"} [hbot-p15642322] Thioredoxin reductase may be essential for the normal growth of hyperbaric oxygen-treated human lens epithelial cells. (2004). https://pubmed.ncbi.nlm.nih.gov/15642322/ DOI: 10.1016/j.exer.2004.07.001

    Complete structured claim and evidence

29. Messenger RNA for heme oxygenase-1, manganese superoxide dismutase and cytoplasmic thioredoxin reductase 1 rose three- to six-fold nine hours after exposure, with heme oxygenase-1 rising a few hours before manganese superoxide dismutase, while catalase, copper-zinc superoxide dismutase, glutathione reductase, glutathione peroxidase and thioredoxin did not change.

    Hyperbaric oxygen therapy → TXNRD1 source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/15642322.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e3bc035a17e4e19dd92d4fadb1a79f8e3801619dac24fb91dcf985728afaf995", "start_char": 0, "end_char": 2646, "text_sha256": "e3bc035a17e4e19dd92d4fadb1a79f8e3801619dac24fb91dcf985728afaf995"}

    experimental_model

    Cultured human lens epithelial cells exposed to extreme hyperbaric oxygen with enzyme assays and real-time PCR

    exposure

    99% oxygen at 50 atmospheres for 3 hours, then normal culture for up to 11 days

    limitations

    Fifty atmospheres is an extreme experimental exposure far above therapy, chosen to probe which defences matter. The selenoenzyme result is the informative part; the pressure is not clinically relevant.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human cells

    plain_language

    The cell rebuilt exactly three proteins: the heme enzyme, the manganese enzyme and the selenium enzyme.

    primary_references

    [hbot-p15642322] Thioredoxin reductase may be essential for the normal growth of hyperbaric oxygen-treated human lens epithelial cells. (2004). https://pubmed.ncbi.nlm.nih.gov/15642322/ DOI: 10.1016/j.exer.2004.07.001

    tissue_or_cell_type

    Lens epithelium

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 426–437

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cultured human lens epithelial cells exposed to extreme hyperbaric oxygen with enzyme assays and real-time PCR · source_derived_draft · unverified_draft

    ### hbot-trxr-mrna-response Messenger RNA for heme oxygenase-1, manganese superoxide dismutase and cytoplasmic thioredoxin reductase 1 rose three- to six-fold nine hours after exposure, with heme oxygenase-1 rising a few hours before manganese superoxide dismutase, while catalase, copper-zinc superoxide dismutase, glutathione reductase, glutathione peroxidase and thioredoxin did not change. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The cell rebuilt exactly three proteins: the heme enzyme, the manganese enzyme and the selenium enzyme. organism: Human cells tissue_or_cell_type: Lens epithelium experimental_model: Cultured human lens epithelial cells exposed to extreme hyperbaric oxygen with enzyme assays and real-time PCR limitations: Fifty atmospheres is an extreme experimental exposure far above therapy, chosen to probe which defences matter. The selenoenzyme result is the informative part; the pressure is not clinically relevant. exposure: 99% oxygen at 50 atmospheres for 3 hours, then normal culture for up to 11 days evidence_span: {"source_cache": "artifacts/hbot-research/15642322.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e3bc035a17e4e19dd92d4fadb1a79f8e3801619dac24fb91dcf985728afaf995", "start_char": 0, "end_char": 2646, "text_sha256": "e3bc035a17e4e19dd92d4fadb1a79f8e3801619dac24fb91dcf985728afaf995"} [hbot-p15642322] Thioredoxin reductase may be essential for the normal growth of hyperbaric oxygen-treated human lens epithelial cells. (2004). https://pubmed.ncbi.nlm.nih.gov/15642322/ DOI: 10.1016/j.exer.2004.07.001

    Complete structured claim and evidence

30. The authors suggest that release of free iron from the degradation of heme by heme oxygenase-1 may have played a role in the later upregulation of the manganese dismutase.

    Human heme oxygenase 1 / HMOX1 → Human mitochondrial manganese superoxide dismutase / SOD2 source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/15642322.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e3bc035a17e4e19dd92d4fadb1a79f8e3801619dac24fb91dcf985728afaf995", "start_char": 0, "end_char": 2646, "text_sha256": "e3bc035a17e4e19dd92d4fadb1a79f8e3801619dac24fb91dcf985728afaf995"}

    experimental_model

    Cultured human lens epithelial cells exposed to extreme hyperbaric oxygen with enzyme assays and real-time PCR

    exposure

    99% oxygen at 50 atmospheres for 3 hours, then normal culture for up to 11 days

    limitations

    Fifty atmospheres is an extreme experimental exposure far above therapy, chosen to probe which defences matter. The selenoenzyme result is the informative part; the pressure is not clinically relevant.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human cells

    plain_language

    Iron freed from heme may be the signal that calls up the manganese enzyme.

    primary_references

    [hbot-p15642322] Thioredoxin reductase may be essential for the normal growth of hyperbaric oxygen-treated human lens epithelial cells. (2004). https://pubmed.ncbi.nlm.nih.gov/15642322/ DOI: 10.1016/j.exer.2004.07.001

    tissue_or_cell_type

    Lens epithelium

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 439–450

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cultured human lens epithelial cells exposed to extreme hyperbaric oxygen with enzyme assays and real-time PCR · source_derived_draft · unverified_draft

    ### hbot-ho1-iron-to-mnsod The authors suggest that release of free iron from the degradation of heme by heme oxygenase-1 may have played a role in the later upregulation of the manganese dismutase. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Iron freed from heme may be the signal that calls up the manganese enzyme. organism: Human cells tissue_or_cell_type: Lens epithelium experimental_model: Cultured human lens epithelial cells exposed to extreme hyperbaric oxygen with enzyme assays and real-time PCR limitations: Fifty atmospheres is an extreme experimental exposure far above therapy, chosen to probe which defences matter. The selenoenzyme result is the informative part; the pressure is not clinically relevant. exposure: 99% oxygen at 50 atmospheres for 3 hours, then normal culture for up to 11 days evidence_span: {"source_cache": "artifacts/hbot-research/15642322.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e3bc035a17e4e19dd92d4fadb1a79f8e3801619dac24fb91dcf985728afaf995", "start_char": 0, "end_char": 2646, "text_sha256": "e3bc035a17e4e19dd92d4fadb1a79f8e3801619dac24fb91dcf985728afaf995"} [hbot-p15642322] Thioredoxin reductase may be essential for the normal growth of hyperbaric oxygen-treated human lens epithelial cells. (2004). https://pubmed.ncbi.nlm.nih.gov/15642322/ DOI: 10.1016/j.exer.2004.07.001

    Complete structured claim and evidence

31. Mammalian thioredoxin reductase carries an essential selenocysteine in the conserved C-terminal sequence Gly-Cys-SeCys-Gly, forming a selenenylsulfide between Cys497 and SeCys498 that becomes a selenolthiol on reduction, alongside a separate Cys59-Cys64 disulfide identical to the glutathione reductase active site.

    Sec → TXNRD1 source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/10801974.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1627b8b48962b6d2b9bead351b64b71fb60b9681378b44f77a3fc288d35119e3", "start_char": 0, "end_char": 1719, "text_sha256": "1627b8b48962b6d2b9bead351b64b71fb60b9681378b44f77a3fc288d35119e3"}

    experimental_model

    Chemical modification, peptide sequencing, mass spectrometry and redox titration of mammalian thioredoxin reductase

    exposure

    Oxidised and NADPH-reduced enzyme states

    limitations

    Enzyme chemistry on purified protein. It establishes the selenium-containing active site; it is not a statement about selenium intake.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Rat and human enzyme

    plain_language

    The enzyme’s working end is built from a selenium amino acid paired with a cysteine.

    primary_references

    [hbot-p10801974] Structure and mechanism of mammalian thioredoxin reductase: the active site is a redox-active selenolthiol/selenenylsulfide formed from the conserved cysteine-selenocysteine sequence. (2000). https://pubmed.ncbi.nlm.nih.gov/10801974/ DOI: 10.1073/pnas.100114897

    tissue_or_cell_type

    Purified enzyme

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 452–463

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Chemical modification, peptide sequencing, mass spectrometry and redox titration of mammalian thioredoxin reductase · source_derived_draft · unverified_draft

    ### hbot-trxr-selenocysteine-site Mammalian thioredoxin reductase carries an essential selenocysteine in the conserved C-terminal sequence Gly-Cys-SeCys-Gly, forming a selenenylsulfide between Cys497 and SeCys498 that becomes a selenolthiol on reduction, alongside a separate Cys59-Cys64 disulfide identical to the glutathione reductase active site. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The enzyme’s working end is built from a selenium amino acid paired with a cysteine. organism: Rat and human enzyme tissue_or_cell_type: Purified enzyme experimental_model: Chemical modification, peptide sequencing, mass spectrometry and redox titration of mammalian thioredoxin reductase limitations: Enzyme chemistry on purified protein. It establishes the selenium-containing active site; it is not a statement about selenium intake. exposure: Oxidised and NADPH-reduced enzyme states evidence_span: {"source_cache": "artifacts/hbot-research/10801974.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1627b8b48962b6d2b9bead351b64b71fb60b9681378b44f77a3fc288d35119e3", "start_char": 0, "end_char": 1719, "text_sha256": "1627b8b48962b6d2b9bead351b64b71fb60b9681378b44f77a3fc288d35119e3"} [hbot-p10801974] Structure and mechanism of mammalian thioredoxin reductase: the active site is a redox-active selenolthiol/selenenylsulfide formed from the conserved cysteine-selenocysteine sequence. (2000). https://pubmed.ncbi.nlm.nih.gov/10801974/ DOI: 10.1073/pnas.100114897

    Complete structured claim and evidence

32. The SeCys498 to Cys enzyme retained catalytic activity in thioredoxin reduction with a 100-fold lower kcat and a 10-fold lower Km, and its pH optimum shifted from 7 to 9, strongly suggesting involvement of the low-pKa selenol in the mechanism.

    Recombinant rat thioredoxin reductase with SeCys498 replaced by cysteine → Thioredoxin reductase catalytic activity source_derived_draftungraded
    Experimental context and source evidence

    availability_state

    nutrient_deficiency Imported condition classification; unverified.

    evidence_span

    {"source_cache": "artifacts/hbot-research/10849437.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "13fe79ebefbddac9a76f4cae2e0f1aede8d648b6568adca72f0b0a550e66bc90", "start_char": 0, "end_char": 1374, "text_sha256": "13fe79ebefbddac9a76f4cae2e0f1aede8d648b6568adca72f0b0a550e66bc90"}

    experimental_model

    Recombinant rat thioredoxin reductase with selenocysteine mutations expressed in E. coli

    exposure

    SeCys498 replaced by cysteine or serine, and a truncated protein lacking the C-terminal SeCys-Gly dipeptide

    limitations

    The truncated construct is described by the authors as the form expected in selenium deficiency, which is what links this enzyme chemistry to nutrient supply. It remains a recombinant model, not a measurement in a selenium-deficient animal.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Rat enzyme in a bacterial expression host

    plain_language

    Swapping selenium for sulphur leaves an enzyme that barely works and only in the wrong conditions.

    primary_references

    [hbot-p10849437] Essential role of selenium in the catalytic activities of mammalian thioredoxin reductase revealed by characterization of recombinant enzymes with selenocysteine mutations. (2000). https://pubmed.ncbi.nlm.nih.gov/10849437/ DOI: 10.1074/jbc.m000690200

    tissue_or_cell_type

    Purified enzyme

    trigger_kind

    nutrient_deficiency Imported condition classification; unverified.

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 465–476

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant rat thioredoxin reductase with selenocysteine mutations expressed in E. coli · source_derived_draft · unverified_draft

    ### hbot-trxr-secys-mutant-activity The SeCys498 to Cys enzyme retained catalytic activity in thioredoxin reduction with a 100-fold lower kcat and a 10-fold lower Km, and its pH optimum shifted from 7 to 9, strongly suggesting involvement of the low-pKa selenol in the mechanism. Condition category: nutrient_deficiency nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Swapping selenium for sulphur leaves an enzyme that barely works and only in the wrong conditions. organism: Rat enzyme in a bacterial expression host tissue_or_cell_type: Purified enzyme experimental_model: Recombinant rat thioredoxin reductase with selenocysteine mutations expressed in E. coli limitations: The truncated construct is described by the authors as the form expected in selenium deficiency, which is what links this enzyme chemistry to nutrient supply. It remains a recombinant model, not a measurement in a selenium-deficient animal. exposure: SeCys498 replaced by cysteine or serine, and a truncated protein lacking the C-terminal SeCys-Gly dipeptide evidence_span: {"source_cache": "artifacts/hbot-research/10849437.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "13fe79ebefbddac9a76f4cae2e0f1aede8d648b6568adca72f0b0a550e66bc90", "start_char": 0, "end_char": 1374, "text_sha256": "13fe79ebefbddac9a76f4cae2e0f1aede8d648b6568adca72f0b0a550e66bc90"} [hbot-p10849437] Essential role of selenium in the catalytic activities of mammalian thioredoxin reductase revealed by characterization of recombinant enzymes with selenocysteine mutations. (2000). https://pubmed.ncbi.nlm.nih.gov/10849437/ DOI: 10.1074/jbc.m000690200

    Complete structured claim and evidence

33. Whereas hydrogen peroxide was a substrate for the wild-type enzyme, all mutant enzymes, including the truncated form expected in selenium deficiency, lacked hydroperoxidase activity, so selenium is required for the catalytic activities of thioredoxin reductase.

    Thioredoxin reductase truncated of its C-terminal SeCys-Gly dipeptide, the form expected in selenium deficiency → Thioredoxin reductase hydroperoxidase activity toward hydrogen peroxide source_derived_draftungraded
    Experimental context and source evidence

    availability_state

    nutrient_deficiency Imported condition classification; unverified.

    evidence_span

    {"source_cache": "artifacts/hbot-research/10849437.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "13fe79ebefbddac9a76f4cae2e0f1aede8d648b6568adca72f0b0a550e66bc90", "start_char": 0, "end_char": 1374, "text_sha256": "13fe79ebefbddac9a76f4cae2e0f1aede8d648b6568adca72f0b0a550e66bc90"}

    experimental_model

    Recombinant rat thioredoxin reductase with selenocysteine mutations expressed in E. coli

    exposure

    SeCys498 replaced by cysteine or serine, and a truncated protein lacking the C-terminal SeCys-Gly dipeptide

    limitations

    The truncated construct is described by the authors as the form expected in selenium deficiency, which is what links this enzyme chemistry to nutrient supply. It remains a recombinant model, not a measurement in a selenium-deficient animal.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Rat enzyme in a bacterial expression host

    plain_language

    Without selenium the enzyme can no longer destroy peroxide at all.

    primary_references

    [hbot-p10849437] Essential role of selenium in the catalytic activities of mammalian thioredoxin reductase revealed by characterization of recombinant enzymes with selenocysteine mutations. (2000). https://pubmed.ncbi.nlm.nih.gov/10849437/ DOI: 10.1074/jbc.m000690200

    tissue_or_cell_type

    Purified enzyme

    trigger_kind

    nutrient_deficiency Imported condition classification; unverified.

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 478–489

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant rat thioredoxin reductase with selenocysteine mutations expressed in E. coli · source_derived_draft · unverified_draft

    ### hbot-trxr-truncated-no-activity Whereas hydrogen peroxide was a substrate for the wild-type enzyme, all mutant enzymes, including the truncated form expected in selenium deficiency, lacked hydroperoxidase activity, so selenium is required for the catalytic activities of thioredoxin reductase. Condition category: nutrient_deficiency nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Without selenium the enzyme can no longer destroy peroxide at all. organism: Rat enzyme in a bacterial expression host tissue_or_cell_type: Purified enzyme experimental_model: Recombinant rat thioredoxin reductase with selenocysteine mutations expressed in E. coli limitations: The truncated construct is described by the authors as the form expected in selenium deficiency, which is what links this enzyme chemistry to nutrient supply. It remains a recombinant model, not a measurement in a selenium-deficient animal. exposure: SeCys498 replaced by cysteine or serine, and a truncated protein lacking the C-terminal SeCys-Gly dipeptide evidence_span: {"source_cache": "artifacts/hbot-research/10849437.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "13fe79ebefbddac9a76f4cae2e0f1aede8d648b6568adca72f0b0a550e66bc90", "start_char": 0, "end_char": 1374, "text_sha256": "13fe79ebefbddac9a76f4cae2e0f1aede8d648b6568adca72f0b0a550e66bc90"} [hbot-p10849437] Essential role of selenium in the catalytic activities of mammalian thioredoxin reductase revealed by characterization of recombinant enzymes with selenocysteine mutations. (2000). https://pubmed.ncbi.nlm.nih.gov/10849437/ DOI: 10.1074/jbc.m000690200

    Complete structured claim and evidence

34. Copper, zinc superoxide dismutase catalyses the two-step dismutation of superoxide to molecular oxygen and hydrogen peroxide through alternate reduction and oxidation of the active-site copper, with a single complementary binding position for superoxide at the Cu(II) and the activity-important Arg141.

    Copper → Human copper-zinc superoxide dismutase / SOD1 source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/6316150.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dc20323f9774c6c743e01f8bdbeedbc42b0ddac982f1e17d53a9591b87bf5379", "start_char": 0, "end_char": 867, "text_sha256": "dc20323f9774c6c743e01f8bdbeedbc42b0ddac982f1e17d53a9591b87bf5379"}

    experimental_model

    Refinement of the 2 angstrom crystal structure of copper, zinc superoxide dismutase with molecular surface analysis

    exposure

    Structural and mechanistic analysis of the active site

    limitations

    Structural chemistry. It explains why the enzyme needs its metals; it is not a statement about dietary copper or zinc.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Bovine enzyme structure

    plain_language

    The copper atom itself is what takes and gives back the electron.

    primary_references

    [hbot-p6316150] Structure and mechanism of copper, zinc superoxide dismutase. (1983). https://pubmed.ncbi.nlm.nih.gov/6316150/ DOI: 10.1038/306284a0

    tissue_or_cell_type

    Purified enzyme

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 491–502

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Refinement of the 2 angstrom crystal structure of copper, zinc superoxide dismutase with molecular surface analysis · source_derived_draft · unverified_draft

    ### hbot-sod1-copper-mechanism Copper, zinc superoxide dismutase catalyses the two-step dismutation of superoxide to molecular oxygen and hydrogen peroxide through alternate reduction and oxidation of the active-site copper, with a single complementary binding position for superoxide at the Cu(II) and the activity-important Arg141. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The copper atom itself is what takes and gives back the electron. organism: Bovine enzyme structure tissue_or_cell_type: Purified enzyme experimental_model: Refinement of the 2 angstrom crystal structure of copper, zinc superoxide dismutase with molecular surface analysis limitations: Structural chemistry. It explains why the enzyme needs its metals; it is not a statement about dietary copper or zinc. exposure: Structural and mechanistic analysis of the active site evidence_span: {"source_cache": "artifacts/hbot-research/6316150.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dc20323f9774c6c743e01f8bdbeedbc42b0ddac982f1e17d53a9591b87bf5379", "start_char": 0, "end_char": 867, "text_sha256": "dc20323f9774c6c743e01f8bdbeedbc42b0ddac982f1e17d53a9591b87bf5379"} [hbot-p6316150] Structure and mechanism of copper, zinc superoxide dismutase. (1983). https://pubmed.ncbi.nlm.nih.gov/6316150/ DOI: 10.1038/306284a0

    Complete structured claim and evidence

35. The copper chaperone for superoxide dismutase is necessary for expression of an active copper-bound superoxide dismutase in vivo despite the enzyme’s 6 femtomolar dissociation constant for copper, and purified Cu(I)-CCS was sufficient to activate the apo-enzyme but necessary only when free copper was strictly limited.

    Human copper chaperone for SOD1 / CCS → Activation of superoxide dismutase 1 by copper insertion source_derived_draftungraded
    Experimental context and source evidence

    availability_state

    machinery_impairment Imported condition classification; unverified.

    evidence_span

    {"source_cache": "artifacts/hbot-research/10221913.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8f6658330988f9b33331f49c1599734e070075a33fa8f32a3a6025d9f0fbc0b8", "start_char": 0, "end_char": 1176, "text_sha256": "8f6658330988f9b33331f49c1599734e070075a33fa8f32a3a6025d9f0fbc0b8"}

    experimental_model

    Yeast genetics with purified copper chaperone and apo-enzyme reconstitution

    exposure

    CCS deletion, elevated copper, and abrogation of metallothioneins

    limitations

    A yeast system with purified protein reconstitution. The free-copper conclusion is drawn from this system and its metallothionein manipulations.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Saccharomyces cerevisiae and purified proteins

    plain_language

    Copper is handed over by a dedicated carrier, not picked up loose.

    primary_references

    [hbot-p10221913] Undetectable intracellular free copper: the requirement of a copper chaperone for superoxide dismutase. (1999). https://pubmed.ncbi.nlm.nih.gov/10221913/ DOI: 10.1126/science.284.5415.805

    tissue_or_cell_type

    Cytosol

    trigger_kind

    machinery_impairment Imported condition classification; unverified.

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 504–515

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Yeast genetics with purified copper chaperone and apo-enzyme reconstitution · source_derived_draft · unverified_draft

    ### hbot-ccs-required The copper chaperone for superoxide dismutase is necessary for expression of an active copper-bound superoxide dismutase in vivo despite the enzyme’s 6 femtomolar dissociation constant for copper, and purified Cu(I)-CCS was sufficient to activate the apo-enzyme but necessary only when free copper was strictly limited. Condition category: machinery_impairment nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Copper is handed over by a dedicated carrier, not picked up loose. organism: Saccharomyces cerevisiae and purified proteins tissue_or_cell_type: Cytosol experimental_model: Yeast genetics with purified copper chaperone and apo-enzyme reconstitution limitations: A yeast system with purified protein reconstitution. The free-copper conclusion is drawn from this system and its metallothionein manipulations. exposure: CCS deletion, elevated copper, and abrogation of metallothioneins evidence_span: {"source_cache": "artifacts/hbot-research/10221913.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8f6658330988f9b33331f49c1599734e070075a33fa8f32a3a6025d9f0fbc0b8", "start_char": 0, "end_char": 1176, "text_sha256": "8f6658330988f9b33331f49c1599734e070075a33fa8f32a3a6025d9f0fbc0b8"} [hbot-p10221913] Undetectable intracellular free copper: the requirement of a copper chaperone for superoxide dismutase. (1999). https://pubmed.ncbi.nlm.nih.gov/10221913/ DOI: 10.1126/science.284.5415.805

    Complete structured claim and evidence

36. The chaperone requirement was bypassed by elevated copper and by removing intracellular copper scavengers such as the metallothioneins, indicating that intracellular free copper is limited to less than one free copper ion per cell and that a pool of free copper is not used to activate metalloenzymes.

    Intracellular free copper ion concentration → Activation of superoxide dismutase 1 by copper insertion source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/10221913.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8f6658330988f9b33331f49c1599734e070075a33fa8f32a3a6025d9f0fbc0b8", "start_char": 0, "end_char": 1176, "text_sha256": "8f6658330988f9b33331f49c1599734e070075a33fa8f32a3a6025d9f0fbc0b8"}

    experimental_model

    Yeast genetics with purified copper chaperone and apo-enzyme reconstitution

    exposure

    CCS deletion, elevated copper, and abrogation of metallothioneins

    limitations

    A yeast system with purified protein reconstitution. The free-copper conclusion is drawn from this system and its metallothionein manipulations.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Saccharomyces cerevisiae and purified proteins

    plain_language

    There is effectively no loose copper in a cell; every atom is held by something.

    primary_references

    [hbot-p10221913] Undetectable intracellular free copper: the requirement of a copper chaperone for superoxide dismutase. (1999). https://pubmed.ncbi.nlm.nih.gov/10221913/ DOI: 10.1126/science.284.5415.805

    tissue_or_cell_type

    Cytosol

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 517–528

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Yeast genetics with purified copper chaperone and apo-enzyme reconstitution · source_derived_draft · unverified_draft

    ### hbot-free-copper-limit The chaperone requirement was bypassed by elevated copper and by removing intracellular copper scavengers such as the metallothioneins, indicating that intracellular free copper is limited to less than one free copper ion per cell and that a pool of free copper is not used to activate metalloenzymes. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: There is effectively no loose copper in a cell; every atom is held by something. organism: Saccharomyces cerevisiae and purified proteins tissue_or_cell_type: Cytosol experimental_model: Yeast genetics with purified copper chaperone and apo-enzyme reconstitution limitations: A yeast system with purified protein reconstitution. The free-copper conclusion is drawn from this system and its metallothionein manipulations. exposure: CCS deletion, elevated copper, and abrogation of metallothioneins evidence_span: {"source_cache": "artifacts/hbot-research/10221913.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8f6658330988f9b33331f49c1599734e070075a33fa8f32a3a6025d9f0fbc0b8", "start_char": 0, "end_char": 1176, "text_sha256": "8f6658330988f9b33331f49c1599734e070075a33fa8f32a3a6025d9f0fbc0b8"} [hbot-p10221913] Undetectable intracellular free copper: the requirement of a copper chaperone for superoxide dismutase. (1999). https://pubmed.ncbi.nlm.nih.gov/10221913/ DOI: 10.1126/science.284.5415.805

    Complete structured claim and evidence

37. CD34-positive cells in human peripheral blood doubled after a single 2.0 ATA exposure and rose eightfold over 20 treatments, without a significant increase in the overall white cell count.

    Hyperbaric oxygen therapy → Circulating CD34-positive stem and progenitor cells source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/16299259.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "76c0554557a30ac9a32f25b74b27edb5f8f8a57ee0c0660dfe5619b78732c730", "start_char": 0, "end_char": 1502, "text_sha256": "76c0554557a30ac9a32f25b74b27edb5f8f8a57ee0c0660dfe5619b78732c730"}

    experimental_model

    Human volunteers, mice, and endothelial nitric oxide synthase knockout mice

    exposure

    2.0 atmospheres absolute oxygen for 2 hours, single and over 20 treatments

    limitations

    The knockout and inhibitor arms carry the causal claim. Progenitor phenotype is defined by surface markers and colony formation, not by a demonstrated contribution to a healed vessel.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human and mouse

    plain_language

    The therapy calls stem cells out of the marrow into the blood.

    primary_references

    [hbot-p16299259] Stem cell mobilization by hyperbaric oxygen. (2006). https://pubmed.ncbi.nlm.nih.gov/16299259/ DOI: 10.1152/ajpheart.00888.2005

    tissue_or_cell_type

    Bone marrow and peripheral blood

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 530–541

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human volunteers, mice, and endothelial nitric oxide synthase knockout mice · source_derived_draft · unverified_draft

    ### hbot-cd34-mobilisation CD34-positive cells in human peripheral blood doubled after a single 2.0 ATA exposure and rose eightfold over 20 treatments, without a significant increase in the overall white cell count. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The therapy calls stem cells out of the marrow into the blood. organism: Human and mouse tissue_or_cell_type: Bone marrow and peripheral blood experimental_model: Human volunteers, mice, and endothelial nitric oxide synthase knockout mice limitations: The knockout and inhibitor arms carry the causal claim. Progenitor phenotype is defined by surface markers and colony formation, not by a demonstrated contribution to a healed vessel. exposure: 2.0 atmospheres absolute oxygen for 2 hours, single and over 20 treatments evidence_span: {"source_cache": "artifacts/hbot-research/16299259.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "76c0554557a30ac9a32f25b74b27edb5f8f8a57ee0c0660dfe5619b78732c730", "start_char": 0, "end_char": 1502, "text_sha256": "76c0554557a30ac9a32f25b74b27edb5f8f8a57ee0c0660dfe5619b78732c730"} [hbot-p16299259] Stem cell mobilization by hyperbaric oxygen. (2006). https://pubmed.ncbi.nlm.nih.gov/16299259/ DOI: 10.1152/ajpheart.00888.2005

    Complete structured claim and evidence

38. Colony-forming cells rose from 16 to 26 per 100,000 monocytes plated, entirely due to the CD34-positive subpopulation, and a high proportion of progeny cells expressed receptors for vascular endothelial growth factor-2 and for stromal-derived growth factor.

    Hyperbaric oxygen therapy → Colony-forming cells from circulating monocytes source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/16299259.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "76c0554557a30ac9a32f25b74b27edb5f8f8a57ee0c0660dfe5619b78732c730", "start_char": 0, "end_char": 1502, "text_sha256": "76c0554557a30ac9a32f25b74b27edb5f8f8a57ee0c0660dfe5619b78732c730"}

    experimental_model

    Human volunteers, mice, and endothelial nitric oxide synthase knockout mice

    exposure

    2.0 atmospheres absolute oxygen for 2 hours, single and over 20 treatments

    limitations

    The knockout and inhibitor arms carry the causal claim. Progenitor phenotype is defined by surface markers and colony formation, not by a demonstrated contribution to a healed vessel.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human and mouse

    plain_language

    The mobilised cells carry the receptors for the two signals that guide them to a wound.

    primary_references

    [hbot-p16299259] Stem cell mobilization by hyperbaric oxygen. (2006). https://pubmed.ncbi.nlm.nih.gov/16299259/ DOI: 10.1152/ajpheart.00888.2005

    tissue_or_cell_type

    Bone marrow and peripheral blood

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 543–554

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human volunteers, mice, and endothelial nitric oxide synthase knockout mice · source_derived_draft · unverified_draft

    ### hbot-cfc-increase Colony-forming cells rose from 16 to 26 per 100,000 monocytes plated, entirely due to the CD34-positive subpopulation, and a high proportion of progeny cells expressed receptors for vascular endothelial growth factor-2 and for stromal-derived growth factor. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The mobilised cells carry the receptors for the two signals that guide them to a wound. organism: Human and mouse tissue_or_cell_type: Bone marrow and peripheral blood experimental_model: Human volunteers, mice, and endothelial nitric oxide synthase knockout mice limitations: The knockout and inhibitor arms carry the causal claim. Progenitor phenotype is defined by surface markers and colony formation, not by a demonstrated contribution to a healed vessel. exposure: 2.0 atmospheres absolute oxygen for 2 hours, single and over 20 treatments evidence_span: {"source_cache": "artifacts/hbot-research/16299259.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "76c0554557a30ac9a32f25b74b27edb5f8f8a57ee0c0660dfe5619b78732c730", "start_char": 0, "end_char": 1502, "text_sha256": "76c0554557a30ac9a32f25b74b27edb5f8f8a57ee0c0660dfe5619b78732c730"} [hbot-p16299259] Stem cell mobilization by hyperbaric oxygen. (2006). https://pubmed.ncbi.nlm.nih.gov/16299259/ DOI: 10.1152/ajpheart.00888.2005

    Complete structured claim and evidence

39. Bone marrow nitric oxide concentration increased by 1,008 nM in association with exposure, and circulating stem cell factor rose by 50% in mice with a 3.4-fold rise in cells expressing stem cell antigen-1 and CD34.

    Hyperbaric oxygen therapy → Bone marrow nitric oxide concentration source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/16299259.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "76c0554557a30ac9a32f25b74b27edb5f8f8a57ee0c0660dfe5619b78732c730", "start_char": 0, "end_char": 1502, "text_sha256": "76c0554557a30ac9a32f25b74b27edb5f8f8a57ee0c0660dfe5619b78732c730"}

    experimental_model

    Human volunteers, mice, and endothelial nitric oxide synthase knockout mice

    exposure

    2.0 atmospheres absolute oxygen for 2 hours, single and over 20 treatments

    limitations

    The knockout and inhibitor arms carry the causal claim. Progenitor phenotype is defined by surface markers and colony formation, not by a demonstrated contribution to a healed vessel.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Mouse

    plain_language

    Nitric oxide rises inside the marrow itself, which is where the cells are released.

    primary_references

    [hbot-p16299259] Stem cell mobilization by hyperbaric oxygen. (2006). https://pubmed.ncbi.nlm.nih.gov/16299259/ DOI: 10.1152/ajpheart.00888.2005

    tissue_or_cell_type

    Bone marrow and peripheral blood

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 556–567

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human volunteers, mice, and endothelial nitric oxide synthase knockout mice · source_derived_draft · unverified_draft

    ### hbot-marrow-no-rise Bone marrow nitric oxide concentration increased by 1,008 nM in association with exposure, and circulating stem cell factor rose by 50% in mice with a 3.4-fold rise in cells expressing stem cell antigen-1 and CD34. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Nitric oxide rises inside the marrow itself, which is where the cells are released. organism: Mouse tissue_or_cell_type: Bone marrow and peripheral blood experimental_model: Human volunteers, mice, and endothelial nitric oxide synthase knockout mice limitations: The knockout and inhibitor arms carry the causal claim. Progenitor phenotype is defined by surface markers and colony formation, not by a demonstrated contribution to a healed vessel. exposure: 2.0 atmospheres absolute oxygen for 2 hours, single and over 20 treatments evidence_span: {"source_cache": "artifacts/hbot-research/16299259.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "76c0554557a30ac9a32f25b74b27edb5f8f8a57ee0c0660dfe5619b78732c730", "start_char": 0, "end_char": 1502, "text_sha256": "76c0554557a30ac9a32f25b74b27edb5f8f8a57ee0c0660dfe5619b78732c730"} [hbot-p16299259] Stem cell mobilization by hyperbaric oxygen. (2006). https://pubmed.ncbi.nlm.nih.gov/16299259/ DOI: 10.1152/ajpheart.00888.2005

    Complete structured claim and evidence

40. Stem cell mobilisation did not occur in knockout mice lacking genes for endothelial nitric oxide synthase, and pretreatment of wild-type mice with a nitric oxide synthase inhibitor prevented the elevation in stem cell factor and circulating stem cells.

    Experimental endothelial nitric oxide synthase knockout mouse genotype → Circulating CD34-positive stem and progenitor cells source_derived_draftungraded
    Experimental context and source evidence

    availability_state

    machinery_impairment Imported condition classification; unverified.

    evidence_span

    {"source_cache": "artifacts/hbot-research/16299259.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "76c0554557a30ac9a32f25b74b27edb5f8f8a57ee0c0660dfe5619b78732c730", "start_char": 0, "end_char": 1502, "text_sha256": "76c0554557a30ac9a32f25b74b27edb5f8f8a57ee0c0660dfe5619b78732c730"}

    experimental_model

    Human volunteers, mice, and endothelial nitric oxide synthase knockout mice

    exposure

    2.0 atmospheres absolute oxygen for 2 hours, single and over 20 treatments

    limitations

    The knockout and inhibitor arms carry the causal claim. Progenitor phenotype is defined by surface markers and colony formation, not by a demonstrated contribution to a healed vessel.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human and mouse

    plain_language

    Remove the enzyme that makes nitric oxide and the cells stay in the marrow.

    primary_references

    [hbot-p16299259] Stem cell mobilization by hyperbaric oxygen. (2006). https://pubmed.ncbi.nlm.nih.gov/16299259/ DOI: 10.1152/ajpheart.00888.2005

    tissue_or_cell_type

    Bone marrow and peripheral blood

    trigger_kind

    machinery_impairment Imported condition classification; unverified.

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 569–580

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human volunteers, mice, and endothelial nitric oxide synthase knockout mice · source_derived_draft · unverified_draft

    ### hbot-nos3-required Stem cell mobilisation did not occur in knockout mice lacking genes for endothelial nitric oxide synthase, and pretreatment of wild-type mice with a nitric oxide synthase inhibitor prevented the elevation in stem cell factor and circulating stem cells. Condition category: machinery_impairment nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Remove the enzyme that makes nitric oxide and the cells stay in the marrow. organism: Human and mouse tissue_or_cell_type: Bone marrow and peripheral blood experimental_model: Human volunteers, mice, and endothelial nitric oxide synthase knockout mice limitations: The knockout and inhibitor arms carry the causal claim. Progenitor phenotype is defined by surface markers and colony formation, not by a demonstrated contribution to a healed vessel. exposure: 2.0 atmospheres absolute oxygen for 2 hours, single and over 20 treatments evidence_span: {"source_cache": "artifacts/hbot-research/16299259.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "76c0554557a30ac9a32f25b74b27edb5f8f8a57ee0c0660dfe5619b78732c730", "start_char": 0, "end_char": 1502, "text_sha256": "76c0554557a30ac9a32f25b74b27edb5f8f8a57ee0c0660dfe5619b78732c730"} [hbot-p16299259] Stem cell mobilization by hyperbaric oxygen. (2006). https://pubmed.ncbi.nlm.nih.gov/16299259/ DOI: 10.1152/ajpheart.00888.2005

    Complete structured claim and evidence

41. Diabetic patients showed a more than twofold elevation in circulating stem cells after treatments, and the post-treatment CD34-positive population contained two- to threefold higher levels of hypoxia inducible factors 1, 2 and 3 and of thioredoxin-1.

    Hyperbaric oxygen therapy → Circulating CD34-positive stem and progenitor cells source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/21362081.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a830ae6900d884b73f4e5eac335263db6f9d981a0f95aa45ad3e266c44800e0b", "start_char": 0, "end_char": 1077, "text_sha256": "a830ae6900d884b73f4e5eac335263db6f9d981a0f95aa45ad3e266c44800e0b"}

    experimental_model

    Diabetic patients undergoing hyperbaric oxygen for refractory neuropathic ulcers, with wound margin biopsies

    exposure

    Clinical hyperbaric oxygen therapy courses for refractory lower-extremity ulcers

    limitations

    Human observational measurements within a treatment course, without a randomised comparison. Protein content is measured in the mobilised cells, not in healed tissue.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human

    plain_language

    The cells released carry more of the low-oxygen sensing proteins and more thioredoxin inside them.

    primary_references

    [hbot-p21362081] Vasculogenic stem cell mobilization and wound recruitment in diabetic patients: increased cell number and intracellular regulatory protein content associated with hyperbaric oxygen therapy. (2011). https://pubmed.ncbi.nlm.nih.gov/21362081/ DOI: 10.1111/j.1524-475x.2010.00660.x

    tissue_or_cell_type

    Peripheral blood, platelets and skin wound margins

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 582–593

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Diabetic patients undergoing hyperbaric oxygen for refractory neuropathic ulcers, with wound margin biopsies · source_derived_draft · unverified_draft

    ### hbot-diabetic-stem-mobilisation Diabetic patients showed a more than twofold elevation in circulating stem cells after treatments, and the post-treatment CD34-positive population contained two- to threefold higher levels of hypoxia inducible factors 1, 2 and 3 and of thioredoxin-1. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The cells released carry more of the low-oxygen sensing proteins and more thioredoxin inside them. organism: Human tissue_or_cell_type: Peripheral blood, platelets and skin wound margins experimental_model: Diabetic patients undergoing hyperbaric oxygen for refractory neuropathic ulcers, with wound margin biopsies limitations: Human observational measurements within a treatment course, without a randomised comparison. Protein content is measured in the mobilised cells, not in healed tissue. exposure: Clinical hyperbaric oxygen therapy courses for refractory lower-extremity ulcers evidence_span: {"source_cache": "artifacts/hbot-research/21362081.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a830ae6900d884b73f4e5eac335263db6f9d981a0f95aa45ad3e266c44800e0b", "start_char": 0, "end_char": 1077, "text_sha256": "a830ae6900d884b73f4e5eac335263db6f9d981a0f95aa45ad3e266c44800e0b"} [hbot-p21362081] Vasculogenic stem cell mobilization and wound recruitment in diabetic patients: increased cell number and intracellular regulatory protein content associated with hyperbaric oxygen therapy. (2011). https://pubmed.ncbi.nlm.nih.gov/21362081/ DOI: 10.1111/j.1524-475x.2010.00660.x

    Complete structured claim and evidence

42. Expression of CD133, CD34, hypoxia inducible factor-1 and thioredoxin-1 in wound margins increased with treatment, and was higher in 2-day-old abdominal wounds than in refractory lower-extremity wounds.

    Hyperbaric oxygen therapy → Wound healing source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/21362081.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a830ae6900d884b73f4e5eac335263db6f9d981a0f95aa45ad3e266c44800e0b", "start_char": 0, "end_char": 1077, "text_sha256": "a830ae6900d884b73f4e5eac335263db6f9d981a0f95aa45ad3e266c44800e0b"}

    experimental_model

    Diabetic patients undergoing hyperbaric oxygen for refractory neuropathic ulcers, with wound margin biopsies

    exposure

    Clinical hyperbaric oxygen therapy courses for refractory lower-extremity ulcers

    limitations

    Human observational measurements within a treatment course, without a randomised comparison. Protein content is measured in the mobilised cells, not in healed tissue.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human

    plain_language

    More of these cells and proteins turn up at the wound itself, and a fresh wound starts from a better position than a chronic one.

    primary_references

    [hbot-p21362081] Vasculogenic stem cell mobilization and wound recruitment in diabetic patients: increased cell number and intracellular regulatory protein content associated with hyperbaric oxygen therapy. (2011). https://pubmed.ncbi.nlm.nih.gov/21362081/ DOI: 10.1111/j.1524-475x.2010.00660.x

    tissue_or_cell_type

    Peripheral blood, platelets and skin wound margins

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 595–606

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Diabetic patients undergoing hyperbaric oxygen for refractory neuropathic ulcers, with wound margin biopsies · source_derived_draft · unverified_draft

    ### hbot-wound-recruitment Expression of CD133, CD34, hypoxia inducible factor-1 and thioredoxin-1 in wound margins increased with treatment, and was higher in 2-day-old abdominal wounds than in refractory lower-extremity wounds. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: More of these cells and proteins turn up at the wound itself, and a fresh wound starts from a better position than a chronic one. organism: Human tissue_or_cell_type: Peripheral blood, platelets and skin wound margins experimental_model: Diabetic patients undergoing hyperbaric oxygen for refractory neuropathic ulcers, with wound margin biopsies limitations: Human observational measurements within a treatment course, without a randomised comparison. Protein content is measured in the mobilised cells, not in healed tissue. exposure: Clinical hyperbaric oxygen therapy courses for refractory lower-extremity ulcers evidence_span: {"source_cache": "artifacts/hbot-research/21362081.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a830ae6900d884b73f4e5eac335263db6f9d981a0f95aa45ad3e266c44800e0b", "start_char": 0, "end_char": 1077, "text_sha256": "a830ae6900d884b73f4e5eac335263db6f9d981a0f95aa45ad3e266c44800e0b"} [hbot-p21362081] Vasculogenic stem cell mobilization and wound recruitment in diabetic patients: increased cell number and intracellular regulatory protein content associated with hyperbaric oxygen therapy. (2011). https://pubmed.ncbi.nlm.nih.gov/21362081/ DOI: 10.1111/j.1524-475x.2010.00660.x

    Complete structured claim and evidence

43. Nitric oxide synthase activity was acutely increased in patients’ platelets after treatment and remained elevated for at least 20 hours.

    Hyperbaric oxygen therapy → Platelet nitric oxide synthase activity source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/21362081.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a830ae6900d884b73f4e5eac335263db6f9d981a0f95aa45ad3e266c44800e0b", "start_char": 0, "end_char": 1077, "text_sha256": "a830ae6900d884b73f4e5eac335263db6f9d981a0f95aa45ad3e266c44800e0b"}

    experimental_model

    Diabetic patients undergoing hyperbaric oxygen for refractory neuropathic ulcers, with wound margin biopsies

    exposure

    Clinical hyperbaric oxygen therapy courses for refractory lower-extremity ulcers

    limitations

    Human observational measurements within a treatment course, without a randomised comparison. Protein content is measured in the mobilised cells, not in healed tissue.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human

    plain_language

    The enzyme that releases the cells stays switched on well after the session ends.

    primary_references

    [hbot-p21362081] Vasculogenic stem cell mobilization and wound recruitment in diabetic patients: increased cell number and intracellular regulatory protein content associated with hyperbaric oxygen therapy. (2011). https://pubmed.ncbi.nlm.nih.gov/21362081/ DOI: 10.1111/j.1524-475x.2010.00660.x

    tissue_or_cell_type

    Peripheral blood, platelets and skin wound margins

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 608–619

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Diabetic patients undergoing hyperbaric oxygen for refractory neuropathic ulcers, with wound margin biopsies · source_derived_draft · unverified_draft

    ### hbot-platelet-nos Nitric oxide synthase activity was acutely increased in patients’ platelets after treatment and remained elevated for at least 20 hours. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The enzyme that releases the cells stays switched on well after the session ends. organism: Human tissue_or_cell_type: Peripheral blood, platelets and skin wound margins experimental_model: Diabetic patients undergoing hyperbaric oxygen for refractory neuropathic ulcers, with wound margin biopsies limitations: Human observational measurements within a treatment course, without a randomised comparison. Protein content is measured in the mobilised cells, not in healed tissue. exposure: Clinical hyperbaric oxygen therapy courses for refractory lower-extremity ulcers evidence_span: {"source_cache": "artifacts/hbot-research/21362081.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a830ae6900d884b73f4e5eac335263db6f9d981a0f95aa45ad3e266c44800e0b", "start_char": 0, "end_char": 1077, "text_sha256": "a830ae6900d884b73f4e5eac335263db6f9d981a0f95aa45ad3e266c44800e0b"} [hbot-p21362081] Vasculogenic stem cell mobilization and wound recruitment in diabetic patients: increased cell number and intracellular regulatory protein content associated with hyperbaric oxygen therapy. (2011). https://pubmed.ncbi.nlm.nih.gov/21362081/ DOI: 10.1111/j.1524-475x.2010.00660.x

    Complete structured claim and evidence

44. Hyperbaric oxygen activated HIF-1alpha at several levels, increasing both its stability, by a mechanism the authors call non-canonical, and its activity, shown by induction of target genes and by a hypoxia-responsive-element reporter assay.

    Hyperbaric oxygen therapy → HIF-1alpha protein stability source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/25532619.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bb139ca47291f581e4d45523657f9f244734ce42a3e44c5e460671e58946a3ac", "start_char": 0, "end_char": 1943, "text_sha256": "bb139ca47291f581e4d45523657f9f244734ce42a3e44c5e460671e58946a3ac"}

    experimental_model

    Human dermal fibroblasts, SKRC7 cells, HIF-1alpha knockout mouse embryonic fibroblasts, and db/db mice

    exposure

    Hyperbaric oxygen in vitro and in vivo, with adenoviral stable HIF-1alpha delivery

    limitations

    The knockout arm carries the causal claim. The authors describe the stabilisation as non-canonical, so the route from oxygen to HIF stability here is not the classical hydroxylase route.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human cells and mouse

    plain_language

    More oxygen, not less, switched on the machinery that normally reads low oxygen.

    primary_references

    [hbot-p25532619] Hyperbaric oxygen therapy activates hypoxia-inducible factor 1 (HIF-1), which contributes to improved wound healing in diabetic mice. (2015). https://pubmed.ncbi.nlm.nih.gov/25532619/ DOI: 10.1111/wrr.12253

    tissue_or_cell_type

    Dermal fibroblasts and diabetic wounds

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 621–632

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human dermal fibroblasts, SKRC7 cells, HIF-1alpha knockout mouse embryonic fibroblasts, and db/db mice · source_derived_draft · unverified_draft

    ### hbot-hif1-activation Hyperbaric oxygen activated HIF-1alpha at several levels, increasing both its stability, by a mechanism the authors call non-canonical, and its activity, shown by induction of target genes and by a hypoxia-responsive-element reporter assay. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: More oxygen, not less, switched on the machinery that normally reads low oxygen. organism: Human cells and mouse tissue_or_cell_type: Dermal fibroblasts and diabetic wounds experimental_model: Human dermal fibroblasts, SKRC7 cells, HIF-1alpha knockout mouse embryonic fibroblasts, and db/db mice limitations: The knockout arm carries the causal claim. The authors describe the stabilisation as non-canonical, so the route from oxygen to HIF stability here is not the classical hydroxylase route. exposure: Hyperbaric oxygen in vitro and in vivo, with adenoviral stable HIF-1alpha delivery evidence_span: {"source_cache": "artifacts/hbot-research/25532619.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bb139ca47291f581e4d45523657f9f244734ce42a3e44c5e460671e58946a3ac", "start_char": 0, "end_char": 1943, "text_sha256": "bb139ca47291f581e4d45523657f9f244734ce42a3e44c5e460671e58946a3ac"} [hbot-p25532619] Hyperbaric oxygen therapy activates hypoxia-inducible factor 1 (HIF-1), which contributes to improved wound healing in diabetic mice. (2015). https://pubmed.ncbi.nlm.nih.gov/25532619/ DOI: 10.1111/wrr.12253

    Complete structured claim and evidence

45. Induction of fibroblast proliferation by hyperbaric oxygen disappeared when HIF-1alpha was knocked down.

    HIF-1 alpha → Human fibroblast proliferation source_derived_draftungraded
    Experimental context and source evidence

    availability_state

    machinery_impairment Imported condition classification; unverified.

    evidence_span

    {"source_cache": "artifacts/hbot-research/25532619.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bb139ca47291f581e4d45523657f9f244734ce42a3e44c5e460671e58946a3ac", "start_char": 0, "end_char": 1943, "text_sha256": "bb139ca47291f581e4d45523657f9f244734ce42a3e44c5e460671e58946a3ac"}

    experimental_model

    Human dermal fibroblasts, SKRC7 cells, HIF-1alpha knockout mouse embryonic fibroblasts, and db/db mice

    exposure

    Hyperbaric oxygen in vitro and in vivo, with adenoviral stable HIF-1alpha delivery

    limitations

    The knockout arm carries the causal claim. The authors describe the stabilisation as non-canonical, so the route from oxygen to HIF stability here is not the classical hydroxylase route.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human cells and mouse

    plain_language

    Take the sensor away and the cells stop responding to the treatment.

    primary_references

    [hbot-p25532619] Hyperbaric oxygen therapy activates hypoxia-inducible factor 1 (HIF-1), which contributes to improved wound healing in diabetic mice. (2015). https://pubmed.ncbi.nlm.nih.gov/25532619/ DOI: 10.1111/wrr.12253

    tissue_or_cell_type

    Dermal fibroblasts and diabetic wounds

    trigger_kind

    machinery_impairment Imported condition classification; unverified.

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 634–645

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human dermal fibroblasts, SKRC7 cells, HIF-1alpha knockout mouse embryonic fibroblasts, and db/db mice · source_derived_draft · unverified_draft

    ### hbot-hif1-required-proliferation Induction of fibroblast proliferation by hyperbaric oxygen disappeared when HIF-1alpha was knocked down. Condition category: machinery_impairment nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Take the sensor away and the cells stop responding to the treatment. organism: Human cells and mouse tissue_or_cell_type: Dermal fibroblasts and diabetic wounds experimental_model: Human dermal fibroblasts, SKRC7 cells, HIF-1alpha knockout mouse embryonic fibroblasts, and db/db mice limitations: The knockout arm carries the causal claim. The authors describe the stabilisation as non-canonical, so the route from oxygen to HIF stability here is not the classical hydroxylase route. exposure: Hyperbaric oxygen in vitro and in vivo, with adenoviral stable HIF-1alpha delivery evidence_span: {"source_cache": "artifacts/hbot-research/25532619.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bb139ca47291f581e4d45523657f9f244734ce42a3e44c5e460671e58946a3ac", "start_char": 0, "end_char": 1943, "text_sha256": "bb139ca47291f581e4d45523657f9f244734ce42a3e44c5e460671e58946a3ac"} [hbot-p25532619] Hyperbaric oxygen therapy activates hypoxia-inducible factor 1 (HIF-1), which contributes to improved wound healing in diabetic mice. (2015). https://pubmed.ncbi.nlm.nih.gov/25532619/ DOI: 10.1111/wrr.12253

    Complete structured claim and evidence

46. Local transfer of stable HIF-1alpha-expressing adenovirus into experimental wounds in db/db mice had an additive effect on the improvements produced by hyperbaric oxygen.

    HIF-1 alpha → Wound healing source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/25532619.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bb139ca47291f581e4d45523657f9f244734ce42a3e44c5e460671e58946a3ac", "start_char": 0, "end_char": 1943, "text_sha256": "bb139ca47291f581e4d45523657f9f244734ce42a3e44c5e460671e58946a3ac"}

    experimental_model

    Human dermal fibroblasts, SKRC7 cells, HIF-1alpha knockout mouse embryonic fibroblasts, and db/db mice

    exposure

    Hyperbaric oxygen in vitro and in vivo, with adenoviral stable HIF-1alpha delivery

    limitations

    The knockout arm carries the causal claim. The authors describe the stabilisation as non-canonical, so the route from oxygen to HIF stability here is not the classical hydroxylase route.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Mouse

    plain_language

    Adding more of the sensor on top of the treatment helped further.

    primary_references

    [hbot-p25532619] Hyperbaric oxygen therapy activates hypoxia-inducible factor 1 (HIF-1), which contributes to improved wound healing in diabetic mice. (2015). https://pubmed.ncbi.nlm.nih.gov/25532619/ DOI: 10.1111/wrr.12253

    tissue_or_cell_type

    Dermal fibroblasts and diabetic wounds

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 647–658

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human dermal fibroblasts, SKRC7 cells, HIF-1alpha knockout mouse embryonic fibroblasts, and db/db mice · source_derived_draft · unverified_draft

    ### hbot-hif-additive Local transfer of stable HIF-1alpha-expressing adenovirus into experimental wounds in db/db mice had an additive effect on the improvements produced by hyperbaric oxygen. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Adding more of the sensor on top of the treatment helped further. organism: Mouse tissue_or_cell_type: Dermal fibroblasts and diabetic wounds experimental_model: Human dermal fibroblasts, SKRC7 cells, HIF-1alpha knockout mouse embryonic fibroblasts, and db/db mice limitations: The knockout arm carries the causal claim. The authors describe the stabilisation as non-canonical, so the route from oxygen to HIF stability here is not the classical hydroxylase route. exposure: Hyperbaric oxygen in vitro and in vivo, with adenoviral stable HIF-1alpha delivery evidence_span: {"source_cache": "artifacts/hbot-research/25532619.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bb139ca47291f581e4d45523657f9f244734ce42a3e44c5e460671e58946a3ac", "start_char": 0, "end_char": 1943, "text_sha256": "bb139ca47291f581e4d45523657f9f244734ce42a3e44c5e460671e58946a3ac"} [hbot-p25532619] Hyperbaric oxygen therapy activates hypoxia-inducible factor 1 (HIF-1), which contributes to improved wound healing in diabetic mice. (2015). https://pubmed.ncbi.nlm.nih.gov/25532619/ DOI: 10.1111/wrr.12253

    Complete structured claim and evidence

47. Treatment promoted expression of HIF-1alpha, NF-kappaB, VEGFA, SDF-1, VEGFR2 and CXCR4, with SDF-1 and VEGFA rising in human skin fibroblasts and CXCR4 and VEGFR2 rising in endothelial cells.

    Hyperbaric oxygen therapy → Stromal cell-derived factor 1 / SDF-1alpha / CXCL12 source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/32791151.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "106ed876131af9161051c4c178d88af4afd707a20e56a91447d35aa9ed290188", "start_char": 0, "end_char": 1662, "text_sha256": "106ed876131af9161051c4c178d88af4afd707a20e56a91447d35aa9ed290188"}

    experimental_model

    Diabetic foot mouse model with human skin fibroblasts and human umbilical vein endothelial cells

    exposure

    Hyperbaric oxygen with high glucose in vitro

    limitations

    Cell and mouse work with expression endpoints. Tube formation is an angiogenesis surrogate, not a vessel in a person.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Mouse and human cells

    plain_language

    The signal and its receptor go up on two different cell types at once, which is what lets them find each other.

    primary_references

    [hbot-p32791151] Hyperbaric oxygen potentiates diabetic wound healing by promoting fibroblast cell proliferation and endothelial cell angiogenesis. (2020). https://pubmed.ncbi.nlm.nih.gov/32791151/ DOI: 10.1016/j.lfs.2020.118246

    tissue_or_cell_type

    Skin wound, fibroblasts and endothelium

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 660–671

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Diabetic foot mouse model with human skin fibroblasts and human umbilical vein endothelial cells · source_derived_draft · unverified_draft

    ### hbot-hif-vegf-sdf-axis Treatment promoted expression of HIF-1alpha, NF-kappaB, VEGFA, SDF-1, VEGFR2 and CXCR4, with SDF-1 and VEGFA rising in human skin fibroblasts and CXCR4 and VEGFR2 rising in endothelial cells. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The signal and its receptor go up on two different cell types at once, which is what lets them find each other. organism: Mouse and human cells tissue_or_cell_type: Skin wound, fibroblasts and endothelium experimental_model: Diabetic foot mouse model with human skin fibroblasts and human umbilical vein endothelial cells limitations: Cell and mouse work with expression endpoints. Tube formation is an angiogenesis surrogate, not a vessel in a person. exposure: Hyperbaric oxygen with high glucose in vitro evidence_span: {"source_cache": "artifacts/hbot-research/32791151.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "106ed876131af9161051c4c178d88af4afd707a20e56a91447d35aa9ed290188", "start_char": 0, "end_char": 1662, "text_sha256": "106ed876131af9161051c4c178d88af4afd707a20e56a91447d35aa9ed290188"} [hbot-p32791151] Hyperbaric oxygen potentiates diabetic wound healing by promoting fibroblast cell proliferation and endothelial cell angiogenesis. (2020). https://pubmed.ncbi.nlm.nih.gov/32791151/ DOI: 10.1016/j.lfs.2020.118246

    Complete structured claim and evidence

48. Hyperbaric oxygen stimulated proliferation, migration and tube formation in human umbilical vein endothelial cells, and proliferation, migration and reactive oxygen species production in human skin fibroblasts.

    Hyperbaric oxygen therapy → Endothelial tube formation source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/32791151.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "106ed876131af9161051c4c178d88af4afd707a20e56a91447d35aa9ed290188", "start_char": 0, "end_char": 1662, "text_sha256": "106ed876131af9161051c4c178d88af4afd707a20e56a91447d35aa9ed290188"}

    experimental_model

    Diabetic foot mouse model with human skin fibroblasts and human umbilical vein endothelial cells

    exposure

    Hyperbaric oxygen with high glucose in vitro

    limitations

    Cell and mouse work with expression endpoints. Tube formation is an angiogenesis surrogate, not a vessel in a person.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Mouse and human cells

    plain_language

    Endothelial cells organise into tubes and fibroblasts start moving and dividing.

    primary_references

    [hbot-p32791151] Hyperbaric oxygen potentiates diabetic wound healing by promoting fibroblast cell proliferation and endothelial cell angiogenesis. (2020). https://pubmed.ncbi.nlm.nih.gov/32791151/ DOI: 10.1016/j.lfs.2020.118246

    tissue_or_cell_type

    Skin wound, fibroblasts and endothelium

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 673–684

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Diabetic foot mouse model with human skin fibroblasts and human umbilical vein endothelial cells · source_derived_draft · unverified_draft

    ### hbot-endothelial-tube Hyperbaric oxygen stimulated proliferation, migration and tube formation in human umbilical vein endothelial cells, and proliferation, migration and reactive oxygen species production in human skin fibroblasts. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Endothelial cells organise into tubes and fibroblasts start moving and dividing. organism: Mouse and human cells tissue_or_cell_type: Skin wound, fibroblasts and endothelium experimental_model: Diabetic foot mouse model with human skin fibroblasts and human umbilical vein endothelial cells limitations: Cell and mouse work with expression endpoints. Tube formation is an angiogenesis surrogate, not a vessel in a person. exposure: Hyperbaric oxygen with high glucose in vitro evidence_span: {"source_cache": "artifacts/hbot-research/32791151.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "106ed876131af9161051c4c178d88af4afd707a20e56a91447d35aa9ed290188", "start_char": 0, "end_char": 1662, "text_sha256": "106ed876131af9161051c4c178d88af4afd707a20e56a91447d35aa9ed290188"} [hbot-p32791151] Hyperbaric oxygen potentiates diabetic wound healing by promoting fibroblast cell proliferation and endothelial cell angiogenesis. (2020). https://pubmed.ncbi.nlm.nih.gov/32791151/ DOI: 10.1016/j.lfs.2020.118246

    Complete structured claim and evidence

49. Treatment significantly increased nitrate, VEGF and basic fibroblast growth factor levels and stabilised HIF-1alpha within one day, promoting blood vessel formation at 3 to 7 days and muscle healing at 5 to 7 days after contusion.

    Hyperbaric oxygen therapy → Vascular endothelial growth factor A source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/32066777.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f8915aa50d5b22722e66d20eb0542c6bb03b76a3182d37215a53bc9238ac697d", "start_char": 0, "end_char": 1357, "text_sha256": "f8915aa50d5b22722e66d20eb0542c6bb03b76a3182d37215a53bc9238ac697d"}

    experimental_model

    Contused rat skeletal muscle with a reactive oxygen species scavenger and a nitric oxide synthase inhibitor

    exposure

    2.5 ATA 100% oxygen for 120 minutes daily for 5 consecutive days

    limitations

    Both inhibitors were given before treatment, which is what makes the requirement claim interpretable. The exposure is a therapy-like protocol, unlike the extreme-pressure studies recorded elsewhere here.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Rat

    plain_language

    Within a day the growth signals rise; within a week there are new vessels and repaired muscle.

    primary_references

    [hbot-p32066777] VEGF and bFGF induction by nitric oxide is associated with hyperbaric oxygen-induced angiogenesis and muscle regeneration. (2020). https://pubmed.ncbi.nlm.nih.gov/32066777/ DOI: 10.1038/s41598-020-59615-x

    tissue_or_cell_type

    Skeletal muscle

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 686–697

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Contused rat skeletal muscle with a reactive oxygen species scavenger and a nitric oxide synthase inhibitor · source_derived_draft · unverified_draft

    ### hbot-no-vegf-bfgf Treatment significantly increased nitrate, VEGF and basic fibroblast growth factor levels and stabilised HIF-1alpha within one day, promoting blood vessel formation at 3 to 7 days and muscle healing at 5 to 7 days after contusion. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Within a day the growth signals rise; within a week there are new vessels and repaired muscle. organism: Rat tissue_or_cell_type: Skeletal muscle experimental_model: Contused rat skeletal muscle with a reactive oxygen species scavenger and a nitric oxide synthase inhibitor limitations: Both inhibitors were given before treatment, which is what makes the requirement claim interpretable. The exposure is a therapy-like protocol, unlike the extreme-pressure studies recorded elsewhere here. exposure: 2.5 ATA 100% oxygen for 120 minutes daily for 5 consecutive days evidence_span: {"source_cache": "artifacts/hbot-research/32066777.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f8915aa50d5b22722e66d20eb0542c6bb03b76a3182d37215a53bc9238ac697d", "start_char": 0, "end_char": 1357, "text_sha256": "f8915aa50d5b22722e66d20eb0542c6bb03b76a3182d37215a53bc9238ac697d"} [hbot-p32066777] VEGF and bFGF induction by nitric oxide is associated with hyperbaric oxygen-induced angiogenesis and muscle regeneration. (2020). https://pubmed.ncbi.nlm.nih.gov/32066777/ DOI: 10.1038/s41598-020-59615-x

    Complete structured claim and evidence

50. Administration of either N-acetylcysteine or L-NAME before treatment suppressed angiogenesis and muscle regeneration even after hyperbaric oxygen.

    N-Acetyl-L-cysteine → Skeletal muscle regeneration after contusion source_derived_draftungraded
    Experimental context and source evidence

    availability_state

    machinery_impairment Imported condition classification; unverified.

    evidence_span

    {"source_cache": "artifacts/hbot-research/32066777.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f8915aa50d5b22722e66d20eb0542c6bb03b76a3182d37215a53bc9238ac697d", "start_char": 0, "end_char": 1357, "text_sha256": "f8915aa50d5b22722e66d20eb0542c6bb03b76a3182d37215a53bc9238ac697d"}

    experimental_model

    Contused rat skeletal muscle with a reactive oxygen species scavenger and a nitric oxide synthase inhibitor

    exposure

    2.5 ATA 100% oxygen for 120 minutes daily for 5 consecutive days

    limitations

    Both inhibitors were given before treatment, which is what makes the requirement claim interpretable. The exposure is a therapy-like protocol, unlike the extreme-pressure studies recorded elsewhere here.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Rat

    plain_language

    Mopping up the reactive species, or blocking nitric oxide production, cancels the benefit.

    primary_references

    [hbot-p32066777] VEGF and bFGF induction by nitric oxide is associated with hyperbaric oxygen-induced angiogenesis and muscle regeneration. (2020). https://pubmed.ncbi.nlm.nih.gov/32066777/ DOI: 10.1038/s41598-020-59615-x

    tissue_or_cell_type

    Skeletal muscle

    trigger_kind

    machinery_impairment Imported condition classification; unverified.

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 699–710

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Contused rat skeletal muscle with a reactive oxygen species scavenger and a nitric oxide synthase inhibitor · source_derived_draft · unverified_draft

    ### hbot-nac-lname-block Administration of either N-acetylcysteine or L-NAME before treatment suppressed angiogenesis and muscle regeneration even after hyperbaric oxygen. Condition category: machinery_impairment nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Mopping up the reactive species, or blocking nitric oxide production, cancels the benefit. organism: Rat tissue_or_cell_type: Skeletal muscle experimental_model: Contused rat skeletal muscle with a reactive oxygen species scavenger and a nitric oxide synthase inhibitor limitations: Both inhibitors were given before treatment, which is what makes the requirement claim interpretable. The exposure is a therapy-like protocol, unlike the extreme-pressure studies recorded elsewhere here. exposure: 2.5 ATA 100% oxygen for 120 minutes daily for 5 consecutive days evidence_span: {"source_cache": "artifacts/hbot-research/32066777.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f8915aa50d5b22722e66d20eb0542c6bb03b76a3182d37215a53bc9238ac697d", "start_char": 0, "end_char": 1357, "text_sha256": "f8915aa50d5b22722e66d20eb0542c6bb03b76a3182d37215a53bc9238ac697d"} [hbot-p32066777] VEGF and bFGF induction by nitric oxide is associated with hyperbaric oxygen-induced angiogenesis and muscle regeneration. (2020). https://pubmed.ncbi.nlm.nih.gov/32066777/ DOI: 10.1038/s41598-020-59615-x

    Complete structured claim and evidence

51. Induction of ICAM-1 required simultaneous hypoxia and hypoglycaemia, and hyperbaric oxygen reduced its expression to control levels.

    Hyperbaric oxygen therapy → Intercellular adhesion molecule 1 / ICAM-1 source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/10666024.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9bb8781cab37af1af9f292e4611c19f273de986e86be681a357058d2cfb87ad8", "start_char": 0, "end_char": 1182, "text_sha256": "9bb8781cab37af1af9f292e4611c19f273de986e86be681a357058d2cfb87ad8"}

    experimental_model

    Human umbilical vein and bovine aortic endothelial cells in an in vitro ischaemia-reperfusion model

    exposure

    Hyperbaric oxygen after combined hypoxia and hypoglycaemia; L-NAME

    limitations

    An in vitro model requiring both hypoxia and hypoglycaemia to induce the adhesion molecule. The nitric oxide synthase inhibitor arm supports the proposed route.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human and bovine cells

    plain_language

    The treatment switched off the docking molecule that inflamed vessels put out.

    primary_references

    [hbot-p10666024] Hyperbaric oxygen downregulates ICAM-1 expression induced by hypoxia and hypoglycemia: the role of NOS. (2000). https://pubmed.ncbi.nlm.nih.gov/10666024/ DOI: 10.1152/ajpcell.2000.278.2.c292

    tissue_or_cell_type

    Vascular endothelium

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 712–723

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human umbilical vein and bovine aortic endothelial cells in an in vitro ischaemia-reperfusion model · source_derived_draft · unverified_draft

    ### hbot-icam1-downregulation Induction of ICAM-1 required simultaneous hypoxia and hypoglycaemia, and hyperbaric oxygen reduced its expression to control levels. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The treatment switched off the docking molecule that inflamed vessels put out. organism: Human and bovine cells tissue_or_cell_type: Vascular endothelium experimental_model: Human umbilical vein and bovine aortic endothelial cells in an in vitro ischaemia-reperfusion model limitations: An in vitro model requiring both hypoxia and hypoglycaemia to induce the adhesion molecule. The nitric oxide synthase inhibitor arm supports the proposed route. exposure: Hyperbaric oxygen after combined hypoxia and hypoglycaemia; L-NAME evidence_span: {"source_cache": "artifacts/hbot-research/10666024.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9bb8781cab37af1af9f292e4611c19f273de986e86be681a357058d2cfb87ad8", "start_char": 0, "end_char": 1182, "text_sha256": "9bb8781cab37af1af9f292e4611c19f273de986e86be681a357058d2cfb87ad8"} [hbot-p10666024] Hyperbaric oxygen downregulates ICAM-1 expression induced by hypoxia and hypoglycemia: the role of NOS. (2000). https://pubmed.ncbi.nlm.nih.gov/10666024/ DOI: 10.1152/ajpcell.2000.278.2.c292

    Complete structured claim and evidence

52. Neutrophil adhesion to endothelial cells increased 3.4-fold after hypoxia and hypoglycaemia and was reduced to control levels by hyperbaric oxygen.

    Hyperbaric oxygen therapy → Persistent neutrophil adherence to endothelium source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/10666024.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9bb8781cab37af1af9f292e4611c19f273de986e86be681a357058d2cfb87ad8", "start_char": 0, "end_char": 1182, "text_sha256": "9bb8781cab37af1af9f292e4611c19f273de986e86be681a357058d2cfb87ad8"}

    experimental_model

    Human umbilical vein and bovine aortic endothelial cells in an in vitro ischaemia-reperfusion model

    exposure

    Hyperbaric oxygen after combined hypoxia and hypoglycaemia; L-NAME

    limitations

    An in vitro model requiring both hypoxia and hypoglycaemia to induce the adhesion molecule. The nitric oxide synthase inhibitor arm supports the proposed route.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human and bovine cells

    plain_language

    With the docking molecule gone, the white cells no longer stick.

    primary_references

    [hbot-p10666024] Hyperbaric oxygen downregulates ICAM-1 expression induced by hypoxia and hypoglycemia: the role of NOS. (2000). https://pubmed.ncbi.nlm.nih.gov/10666024/ DOI: 10.1152/ajpcell.2000.278.2.c292

    tissue_or_cell_type

    Vascular endothelium

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 725–736

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human umbilical vein and bovine aortic endothelial cells in an in vitro ischaemia-reperfusion model · source_derived_draft · unverified_draft

    ### hbot-pmn-adhesion-drop Neutrophil adhesion to endothelial cells increased 3.4-fold after hypoxia and hypoglycaemia and was reduced to control levels by hyperbaric oxygen. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: With the docking molecule gone, the white cells no longer stick. organism: Human and bovine cells tissue_or_cell_type: Vascular endothelium experimental_model: Human umbilical vein and bovine aortic endothelial cells in an in vitro ischaemia-reperfusion model limitations: An in vitro model requiring both hypoxia and hypoglycaemia to induce the adhesion molecule. The nitric oxide synthase inhibitor arm supports the proposed route. exposure: Hyperbaric oxygen after combined hypoxia and hypoglycaemia; L-NAME evidence_span: {"source_cache": "artifacts/hbot-research/10666024.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9bb8781cab37af1af9f292e4611c19f273de986e86be681a357058d2cfb87ad8", "start_char": 0, "end_char": 1182, "text_sha256": "9bb8781cab37af1af9f292e4611c19f273de986e86be681a357058d2cfb87ad8"} [hbot-p10666024] Hyperbaric oxygen downregulates ICAM-1 expression induced by hypoxia and hypoglycemia: the role of NOS. (2000). https://pubmed.ncbi.nlm.nih.gov/10666024/ DOI: 10.1152/ajpcell.2000.278.2.c292

    Complete structured claim and evidence

53. Exposure induced endothelial nitric oxide synthase synthesis, and the inhibitor L-NAME attenuated the inhibition of ICAM-1 expression.

    Human endothelial nitric oxide synthase / eNOS / NOS3 → Intercellular adhesion molecule 1 / ICAM-1 source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/10666024.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9bb8781cab37af1af9f292e4611c19f273de986e86be681a357058d2cfb87ad8", "start_char": 0, "end_char": 1182, "text_sha256": "9bb8781cab37af1af9f292e4611c19f273de986e86be681a357058d2cfb87ad8"}

    experimental_model

    Human umbilical vein and bovine aortic endothelial cells in an in vitro ischaemia-reperfusion model

    exposure

    Hyperbaric oxygen after combined hypoxia and hypoglycaemia; L-NAME

    limitations

    An in vitro model requiring both hypoxia and hypoglycaemia to induce the adhesion molecule. The nitric oxide synthase inhibitor arm supports the proposed route.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human and bovine cells

    plain_language

    The effect runs through the nitric oxide enzyme the vessel wall makes.

    primary_references

    [hbot-p10666024] Hyperbaric oxygen downregulates ICAM-1 expression induced by hypoxia and hypoglycemia: the role of NOS. (2000). https://pubmed.ncbi.nlm.nih.gov/10666024/ DOI: 10.1152/ajpcell.2000.278.2.c292

    tissue_or_cell_type

    Vascular endothelium

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 738–749

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human umbilical vein and bovine aortic endothelial cells in an in vitro ischaemia-reperfusion model · source_derived_draft · unverified_draft

    ### hbot-enos-mediates-icam Exposure induced endothelial nitric oxide synthase synthesis, and the inhibitor L-NAME attenuated the inhibition of ICAM-1 expression. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The effect runs through the nitric oxide enzyme the vessel wall makes. organism: Human and bovine cells tissue_or_cell_type: Vascular endothelium experimental_model: Human umbilical vein and bovine aortic endothelial cells in an in vitro ischaemia-reperfusion model limitations: An in vitro model requiring both hypoxia and hypoglycaemia to induce the adhesion molecule. The nitric oxide synthase inhibitor arm supports the proposed route. exposure: Hyperbaric oxygen after combined hypoxia and hypoglycaemia; L-NAME evidence_span: {"source_cache": "artifacts/hbot-research/10666024.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9bb8781cab37af1af9f292e4611c19f273de986e86be681a357058d2cfb87ad8", "start_char": 0, "end_char": 1182, "text_sha256": "9bb8781cab37af1af9f292e4611c19f273de986e86be681a357058d2cfb87ad8"} [hbot-p10666024] Hyperbaric oxygen downregulates ICAM-1 expression induced by hypoxia and hypoglycemia: the role of NOS. (2000). https://pubmed.ncbi.nlm.nih.gov/10666024/ DOI: 10.1152/ajpcell.2000.278.2.c292

    Complete structured claim and evidence

54. Hyperbaric oxygen did not inhibit the initial interaction of leukocytes with brain microvasculature, but persistent adherence, which is due to beta-2 integrins, did not occur; in vitro the leukocytes showed absent beta-2 integrin function while surface expression, elastase release and superoxide production on stimulation remained normal.

    Hyperbaric oxygen therapy → Neutrophil beta-2 integrin adhesive function source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/8248932.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "54ab057eb31320490d893896d8ab5b0c856a8b59489424b14b81409f01a78f7f", "start_char": 0, "end_char": 1870, "text_sha256": "54ab057eb31320490d893896d8ab5b0c856a8b59489424b14b81409f01a78f7f"}

    experimental_model

    Rats poisoned with carbon monoxide, with leukocyte function assays

    exposure

    3 atmospheres absolute for 45 minutes, given 24 hours before or up to 45 minutes after poisoning; 3 ATA pressure without oxygen as a control

    limitations

    The pressure-only control separates oxygen from pressure. The integrin defect is functional: surface expression was normal, which is the informative detail.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Rat

    plain_language

    The white cells still arrive and still work, but they cannot lock on and stay.

    primary_references

    [hbot-p8248932] Functional inhibition of leukocyte B2 integrins by hyperbaric oxygen in carbon monoxide-mediated brain injury in rats. (1993). https://pubmed.ncbi.nlm.nih.gov/8248932/ DOI: 10.1006/taap.1993.1243

    tissue_or_cell_type

    Brain microvasculature and polymorphonuclear leukocytes

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 751–762

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rats poisoned with carbon monoxide, with leukocyte function assays · source_derived_draft · unverified_draft

    ### hbot-b2-integrin-inhibition Hyperbaric oxygen did not inhibit the initial interaction of leukocytes with brain microvasculature, but persistent adherence, which is due to beta-2 integrins, did not occur; in vitro the leukocytes showed absent beta-2 integrin function while surface expression, elastase release and superoxide production on stimulation remained normal. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The white cells still arrive and still work, but they cannot lock on and stay. organism: Rat tissue_or_cell_type: Brain microvasculature and polymorphonuclear leukocytes experimental_model: Rats poisoned with carbon monoxide, with leukocyte function assays limitations: The pressure-only control separates oxygen from pressure. The integrin defect is functional: surface expression was normal, which is the informative detail. exposure: 3 atmospheres absolute for 45 minutes, given 24 hours before or up to 45 minutes after poisoning; 3 ATA pressure without oxygen as a control evidence_span: {"source_cache": "artifacts/hbot-research/8248932.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "54ab057eb31320490d893896d8ab5b0c856a8b59489424b14b81409f01a78f7f", "start_char": 0, "end_char": 1870, "text_sha256": "54ab057eb31320490d893896d8ab5b0c856a8b59489424b14b81409f01a78f7f"} [hbot-p8248932] Functional inhibition of leukocyte B2 integrins by hyperbaric oxygen in carbon monoxide-mediated brain injury in rats. (1993). https://pubmed.ncbi.nlm.nih.gov/8248932/ DOI: 10.1006/taap.1993.1243

    Complete structured claim and evidence

55. Exposure inhibited carbon monoxide-mediated brain lipid peroxidation by preventing the conversion of xanthine dehydrogenase to oxidase, a conversion known to be due to the action of leukocytes.

    Hyperbaric oxygen therapy → Conversion of xanthine dehydrogenase to xanthine oxidase source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/8248932.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "54ab057eb31320490d893896d8ab5b0c856a8b59489424b14b81409f01a78f7f", "start_char": 0, "end_char": 1870, "text_sha256": "54ab057eb31320490d893896d8ab5b0c856a8b59489424b14b81409f01a78f7f"}

    experimental_model

    Rats poisoned with carbon monoxide, with leukocyte function assays

    exposure

    3 atmospheres absolute for 45 minutes, given 24 hours before or up to 45 minutes after poisoning; 3 ATA pressure without oxygen as a control

    limitations

    The pressure-only control separates oxygen from pressure. The integrin defect is functional: surface expression was normal, which is the informative detail.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Rat

    plain_language

    Stopping the white cells sticking stops the enzyme switch that generates the damage.

    primary_references

    [hbot-p8248932] Functional inhibition of leukocyte B2 integrins by hyperbaric oxygen in carbon monoxide-mediated brain injury in rats. (1993). https://pubmed.ncbi.nlm.nih.gov/8248932/ DOI: 10.1006/taap.1993.1243

    tissue_or_cell_type

    Brain microvasculature and polymorphonuclear leukocytes

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 764–775

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rats poisoned with carbon monoxide, with leukocyte function assays · source_derived_draft · unverified_draft

    ### hbot-xanthine-oxidase-prevention Exposure inhibited carbon monoxide-mediated brain lipid peroxidation by preventing the conversion of xanthine dehydrogenase to oxidase, a conversion known to be due to the action of leukocytes. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Stopping the white cells sticking stops the enzyme switch that generates the damage. organism: Rat tissue_or_cell_type: Brain microvasculature and polymorphonuclear leukocytes experimental_model: Rats poisoned with carbon monoxide, with leukocyte function assays limitations: The pressure-only control separates oxygen from pressure. The integrin defect is functional: surface expression was normal, which is the informative detail. exposure: 3 atmospheres absolute for 45 minutes, given 24 hours before or up to 45 minutes after poisoning; 3 ATA pressure without oxygen as a control evidence_span: {"source_cache": "artifacts/hbot-research/8248932.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "54ab057eb31320490d893896d8ab5b0c856a8b59489424b14b81409f01a78f7f", "start_char": 0, "end_char": 1870, "text_sha256": "54ab057eb31320490d893896d8ab5b0c856a8b59489424b14b81409f01a78f7f"} [hbot-p8248932] Functional inhibition of leukocyte B2 integrins by hyperbaric oxygen in carbon monoxide-mediated brain injury in rats. (1993). https://pubmed.ncbi.nlm.nih.gov/8248932/ DOI: 10.1006/taap.1993.1243

    Complete structured claim and evidence

56. Exposing rats to 3 ATA pressure with 0.21 ATA oxygen after poisoning had no significant effects, and 1 ATA oxygen did not significantly inhibit xanthine oxidase formation or lipid peroxidation.

    Raised chamber pressure without raised oxygen fraction → Brain lipid peroxidation after carbon monoxide poisoning source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/8248932.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "54ab057eb31320490d893896d8ab5b0c856a8b59489424b14b81409f01a78f7f", "start_char": 0, "end_char": 1870, "text_sha256": "54ab057eb31320490d893896d8ab5b0c856a8b59489424b14b81409f01a78f7f"}

    experimental_model

    Rats poisoned with carbon monoxide, with leukocyte function assays

    exposure

    3 atmospheres absolute for 45 minutes, given 24 hours before or up to 45 minutes after poisoning; 3 ATA pressure without oxygen as a control

    limitations

    The pressure-only control separates oxygen from pressure. The integrin defect is functional: surface expression was normal, which is the informative detail.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Rat

    plain_language

    Pressure by itself did nothing; it is the oxygen at pressure that matters.

    primary_references

    [hbot-p8248932] Functional inhibition of leukocyte B2 integrins by hyperbaric oxygen in carbon monoxide-mediated brain injury in rats. (1993). https://pubmed.ncbi.nlm.nih.gov/8248932/ DOI: 10.1006/taap.1993.1243

    tissue_or_cell_type

    Brain microvasculature and polymorphonuclear leukocytes

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 777–788

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rats poisoned with carbon monoxide, with leukocyte function assays · source_derived_draft · unverified_draft

    ### hbot-pressure-alone-ineffective Exposing rats to 3 ATA pressure with 0.21 ATA oxygen after poisoning had no significant effects, and 1 ATA oxygen did not significantly inhibit xanthine oxidase formation or lipid peroxidation. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Pressure by itself did nothing; it is the oxygen at pressure that matters. organism: Rat tissue_or_cell_type: Brain microvasculature and polymorphonuclear leukocytes experimental_model: Rats poisoned with carbon monoxide, with leukocyte function assays limitations: The pressure-only control separates oxygen from pressure. The integrin defect is functional: surface expression was normal, which is the informative detail. exposure: 3 atmospheres absolute for 45 minutes, given 24 hours before or up to 45 minutes after poisoning; 3 ATA pressure without oxygen as a control evidence_span: {"source_cache": "artifacts/hbot-research/8248932.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "54ab057eb31320490d893896d8ab5b0c856a8b59489424b14b81409f01a78f7f", "start_char": 0, "end_char": 1870, "text_sha256": "54ab057eb31320490d893896d8ab5b0c856a8b59489424b14b81409f01a78f7f"} [hbot-p8248932] Functional inhibition of leukocyte B2 integrins by hyperbaric oxygen in carbon monoxide-mediated brain injury in rats. (1993). https://pubmed.ncbi.nlm.nih.gov/8248932/ DOI: 10.1006/taap.1993.1243

    Complete structured claim and evidence

57. Beta-2 integrin function could be restored by incubating the cells with 8-bromo-cyclic GMP, and phorbol ester stimulated adherence in both control and exposed cells.

    8-bromo-cyclic GMP → Neutrophil beta-2 integrin adhesive function source_derived_draftungraded
    Experimental context and source evidence

    availability_state

    machinery_impairment Imported condition classification; unverified.

    evidence_span

    {"source_cache": "artifacts/hbot-research/8248932.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "54ab057eb31320490d893896d8ab5b0c856a8b59489424b14b81409f01a78f7f", "start_char": 0, "end_char": 1870, "text_sha256": "54ab057eb31320490d893896d8ab5b0c856a8b59489424b14b81409f01a78f7f"}

    experimental_model

    Rats poisoned with carbon monoxide, with leukocyte function assays

    exposure

    3 atmospheres absolute for 45 minutes, given 24 hours before or up to 45 minutes after poisoning; 3 ATA pressure without oxygen as a control

    limitations

    The pressure-only control separates oxygen from pressure. The integrin defect is functional: surface expression was normal, which is the informative detail.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Rat

    plain_language

    The block sits on a specific signalling step, because supplying that signal reverses it.

    primary_references

    [hbot-p8248932] Functional inhibition of leukocyte B2 integrins by hyperbaric oxygen in carbon monoxide-mediated brain injury in rats. (1993). https://pubmed.ncbi.nlm.nih.gov/8248932/ DOI: 10.1006/taap.1993.1243

    tissue_or_cell_type

    Brain microvasculature and polymorphonuclear leukocytes

    trigger_kind

    machinery_impairment Imported condition classification; unverified.

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 790–801

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rats poisoned with carbon monoxide, with leukocyte function assays · source_derived_draft · unverified_draft

    ### hbot-cgmp-restores-integrin Beta-2 integrin function could be restored by incubating the cells with 8-bromo-cyclic GMP, and phorbol ester stimulated adherence in both control and exposed cells. Condition category: machinery_impairment nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The block sits on a specific signalling step, because supplying that signal reverses it. organism: Rat tissue_or_cell_type: Brain microvasculature and polymorphonuclear leukocytes experimental_model: Rats poisoned with carbon monoxide, with leukocyte function assays limitations: The pressure-only control separates oxygen from pressure. The integrin defect is functional: surface expression was normal, which is the informative detail. exposure: 3 atmospheres absolute for 45 minutes, given 24 hours before or up to 45 minutes after poisoning; 3 ATA pressure without oxygen as a control evidence_span: {"source_cache": "artifacts/hbot-research/8248932.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "54ab057eb31320490d893896d8ab5b0c856a8b59489424b14b81409f01a78f7f", "start_char": 0, "end_char": 1870, "text_sha256": "54ab057eb31320490d893896d8ab5b0c856a8b59489424b14b81409f01a78f7f"} [hbot-p8248932] Functional inhibition of leukocyte B2 integrins by hyperbaric oxygen in carbon monoxide-mediated brain injury in rats. (1993). https://pubmed.ncbi.nlm.nih.gov/8248932/ DOI: 10.1006/taap.1993.1243

    Complete structured claim and evidence

58. A one-hour exposure at oxygen pressures between 106 and 300 kPa increased proliferation of both normal and diabetic fibroblasts, with a dose-dependent peak at 250 kPa for normal and 200 kPa for diabetic cells, and the effects were not due to hydrostatic pressure per se.

    Hyperbaric oxygen therapy → Human fibroblast proliferation source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/16984424.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "59b39998f7e669db88fb2c3e69315ddfd6a1c52c82ab06997527991ac456d65a", "start_char": 0, "end_char": 1236, "text_sha256": "59b39998f7e669db88fb2c3e69315ddfd6a1c52c82ab06997527991ac456d65a"}

    experimental_model

    Human fibroblasts from normal skin and from chronic diabetic foot ulcers

    exposure

    One hour of hyperbaric oxygen at 106 to 300 kPa, with a hydrostatic pressure control

    limitations

    A dose-response in culture with a pressure control. The authors note the effects may not be due to oxygen availability alone.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human cells

    plain_language

    There is a best pressure, and going higher does not help more.

    primary_references

    [hbot-p16984424] Dose-dependent hyperbaric oxygen stimulation of human fibroblast proliferation. (1997). https://pubmed.ncbi.nlm.nih.gov/16984424/ DOI: 10.1046/j.1524-475x.1997.50206.x

    tissue_or_cell_type

    Dermal fibroblasts

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 803–814

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human fibroblasts from normal skin and from chronic diabetic foot ulcers · source_derived_draft · unverified_draft

    ### hbot-fibroblast-dose-response A one-hour exposure at oxygen pressures between 106 and 300 kPa increased proliferation of both normal and diabetic fibroblasts, with a dose-dependent peak at 250 kPa for normal and 200 kPa for diabetic cells, and the effects were not due to hydrostatic pressure per se. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: There is a best pressure, and going higher does not help more. organism: Human cells tissue_or_cell_type: Dermal fibroblasts experimental_model: Human fibroblasts from normal skin and from chronic diabetic foot ulcers limitations: A dose-response in culture with a pressure control. The authors note the effects may not be due to oxygen availability alone. exposure: One hour of hyperbaric oxygen at 106 to 300 kPa, with a hydrostatic pressure control evidence_span: {"source_cache": "artifacts/hbot-research/16984424.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "59b39998f7e669db88fb2c3e69315ddfd6a1c52c82ab06997527991ac456d65a", "start_char": 0, "end_char": 1236, "text_sha256": "59b39998f7e669db88fb2c3e69315ddfd6a1c52c82ab06997527991ac456d65a"} [hbot-p16984424] Dose-dependent hyperbaric oxygen stimulation of human fibroblast proliferation. (1997). https://pubmed.ncbi.nlm.nih.gov/16984424/ DOI: 10.1046/j.1524-475x.1997.50206.x

    Complete structured claim and evidence

59. Tissue levels of Nrf2 and its downstream targets were significantly increased in patients receiving hyperbaric oxygen compared with standard therapy alone.

    Hyperbaric oxygen therapy → Human Nrf2 / NFE2L2 source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/31035003.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e0b19a857412f1a255ecc82052eb403389bcf5596a562828c04558e1d4354efc", "start_char": 0, "end_char": 1966, "text_sha256": "e0b19a857412f1a255ecc82052eb403389bcf5596a562828c04558e1d4354efc"}

    experimental_model

    Randomised comparison of 32 patients receiving standard wound care with or without hyperbaric oxygen, with ulcer tissue biopsies

    exposure

    Hyperbaric oxygen with standard wound care for 20 days

    limitations

    A small randomised human study with tissue-level molecular endpoints. Correlations between Nrf2 and growth factors are associations within treated tissue.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human

    plain_language

    The master switch for antioxidant defence is measurably higher in the treated wound.

    primary_references

    [hbot-p31035003] Tissue-specific role of Nrf2 in the treatment of diabetic foot ulcers during hyperbaric oxygen therapy. (2019). https://pubmed.ncbi.nlm.nih.gov/31035003/ DOI: 10.1016/j.freeradbiomed.2019.04.031

    tissue_or_cell_type

    Diabetic foot ulcer tissue

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 816–827

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomised comparison of 32 patients receiving standard wound care with or without hyperbaric oxygen, with ulcer tissue biopsies · source_derived_draft · unverified_draft

    ### hbot-nrf2-induction Tissue levels of Nrf2 and its downstream targets were significantly increased in patients receiving hyperbaric oxygen compared with standard therapy alone. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The master switch for antioxidant defence is measurably higher in the treated wound. organism: Human tissue_or_cell_type: Diabetic foot ulcer tissue experimental_model: Randomised comparison of 32 patients receiving standard wound care with or without hyperbaric oxygen, with ulcer tissue biopsies limitations: A small randomised human study with tissue-level molecular endpoints. Correlations between Nrf2 and growth factors are associations within treated tissue. exposure: Hyperbaric oxygen with standard wound care for 20 days evidence_span: {"source_cache": "artifacts/hbot-research/31035003.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e0b19a857412f1a255ecc82052eb403389bcf5596a562828c04558e1d4354efc", "start_char": 0, "end_char": 1966, "text_sha256": "e0b19a857412f1a255ecc82052eb403389bcf5596a562828c04558e1d4354efc"} [hbot-p31035003] Tissue-specific role of Nrf2 in the treatment of diabetic foot ulcers during hyperbaric oxygen therapy. (2019). https://pubmed.ncbi.nlm.nih.gov/31035003/ DOI: 10.1016/j.freeradbiomed.2019.04.031

    Complete structured claim and evidence

60. Treatment increased tissue levels of the angiogenesis markers EGF, VEGF, PDGF, FGF-2 and CXCL10, and Nrf2 correlated positively with EGF, VEGF and PDGF.

    Hyperbaric oxygen therapy → Angiogenesis / new blood vessel formation source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/31035003.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e0b19a857412f1a255ecc82052eb403389bcf5596a562828c04558e1d4354efc", "start_char": 0, "end_char": 1966, "text_sha256": "e0b19a857412f1a255ecc82052eb403389bcf5596a562828c04558e1d4354efc"}

    experimental_model

    Randomised comparison of 32 patients receiving standard wound care with or without hyperbaric oxygen, with ulcer tissue biopsies

    exposure

    Hyperbaric oxygen with standard wound care for 20 days

    limitations

    A small randomised human study with tissue-level molecular endpoints. Correlations between Nrf2 and growth factors are associations within treated tissue.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human

    plain_language

    Five different growth signals rose together in the treated wound.

    primary_references

    [hbot-p31035003] Tissue-specific role of Nrf2 in the treatment of diabetic foot ulcers during hyperbaric oxygen therapy. (2019). https://pubmed.ncbi.nlm.nih.gov/31035003/ DOI: 10.1016/j.freeradbiomed.2019.04.031

    tissue_or_cell_type

    Diabetic foot ulcer tissue

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 829–840

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomised comparison of 32 patients receiving standard wound care with or without hyperbaric oxygen, with ulcer tissue biopsies · source_derived_draft · unverified_draft

    ### hbot-angiogenic-markers Treatment increased tissue levels of the angiogenesis markers EGF, VEGF, PDGF, FGF-2 and CXCL10, and Nrf2 correlated positively with EGF, VEGF and PDGF. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Five different growth signals rose together in the treated wound. organism: Human tissue_or_cell_type: Diabetic foot ulcer tissue experimental_model: Randomised comparison of 32 patients receiving standard wound care with or without hyperbaric oxygen, with ulcer tissue biopsies limitations: A small randomised human study with tissue-level molecular endpoints. Correlations between Nrf2 and growth factors are associations within treated tissue. exposure: Hyperbaric oxygen with standard wound care for 20 days evidence_span: {"source_cache": "artifacts/hbot-research/31035003.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e0b19a857412f1a255ecc82052eb403389bcf5596a562828c04558e1d4354efc", "start_char": 0, "end_char": 1966, "text_sha256": "e0b19a857412f1a255ecc82052eb403389bcf5596a562828c04558e1d4354efc"} [hbot-p31035003] Tissue-specific role of Nrf2 in the treatment of diabetic foot ulcers during hyperbaric oxygen therapy. (2019). https://pubmed.ncbi.nlm.nih.gov/31035003/ DOI: 10.1016/j.freeradbiomed.2019.04.031

    Complete structured claim and evidence

61. Expression of endothelial nitric oxide synthase and nitrite concentrations were significantly increased in treated subjects, and treatment sensitised macrophages to release FGF-2 and EGF while increasing the neutrophil attractant CXCL-8 and thereby the release of CCL2.

    Hyperbaric oxygen therapy → Nitrite concentration in wound tissue source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/31035003.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e0b19a857412f1a255ecc82052eb403389bcf5596a562828c04558e1d4354efc", "start_char": 0, "end_char": 1966, "text_sha256": "e0b19a857412f1a255ecc82052eb403389bcf5596a562828c04558e1d4354efc"}

    experimental_model

    Randomised comparison of 32 patients receiving standard wound care with or without hyperbaric oxygen, with ulcer tissue biopsies

    exposure

    Hyperbaric oxygen with standard wound care for 20 days

    limitations

    A small randomised human study with tissue-level molecular endpoints. Correlations between Nrf2 and growth factors are associations within treated tissue.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human

    plain_language

    The same nitric oxide enzyme appears again, this time in the wound, with the immune cells joining in.

    primary_references

    [hbot-p31035003] Tissue-specific role of Nrf2 in the treatment of diabetic foot ulcers during hyperbaric oxygen therapy. (2019). https://pubmed.ncbi.nlm.nih.gov/31035003/ DOI: 10.1016/j.freeradbiomed.2019.04.031

    tissue_or_cell_type

    Diabetic foot ulcer tissue

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 842–853

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomised comparison of 32 patients receiving standard wound care with or without hyperbaric oxygen, with ulcer tissue biopsies · source_derived_draft · unverified_draft

    ### hbot-enos-nitrite-wound Expression of endothelial nitric oxide synthase and nitrite concentrations were significantly increased in treated subjects, and treatment sensitised macrophages to release FGF-2 and EGF while increasing the neutrophil attractant CXCL-8 and thereby the release of CCL2. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The same nitric oxide enzyme appears again, this time in the wound, with the immune cells joining in. organism: Human tissue_or_cell_type: Diabetic foot ulcer tissue experimental_model: Randomised comparison of 32 patients receiving standard wound care with or without hyperbaric oxygen, with ulcer tissue biopsies limitations: A small randomised human study with tissue-level molecular endpoints. Correlations between Nrf2 and growth factors are associations within treated tissue. exposure: Hyperbaric oxygen with standard wound care for 20 days evidence_span: {"source_cache": "artifacts/hbot-research/31035003.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e0b19a857412f1a255ecc82052eb403389bcf5596a562828c04558e1d4354efc", "start_char": 0, "end_char": 1966, "text_sha256": "e0b19a857412f1a255ecc82052eb403389bcf5596a562828c04558e1d4354efc"} [hbot-p31035003] Tissue-specific role of Nrf2 in the treatment of diabetic foot ulcers during hyperbaric oxygen therapy. (2019). https://pubmed.ncbi.nlm.nih.gov/31035003/ DOI: 10.1016/j.freeradbiomed.2019.04.031

    Complete structured claim and evidence

62. Prolyl 4-hydroxylase catalyses formation of 4-hydroxyproline in collagens by hydroxylating proline residues in X-Pro-Gly sequences, and the reaction requires Fe2+, 2-oxoglutarate, O2 and ascorbate, involving oxidative decarboxylation of 2-oxoglutarate.

    Molecular oxygen → 4-Hydroxyproline source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/2537773.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3fdda2e4cf4392ec7a88b137274cee8f321255473992a2d8df781df12cad6cfe", "start_char": 0, "end_char": 2024, "text_sha256": "3fdda2e4cf4392ec7a88b137274cee8f321255473992a2d8df781df12cad6cfe"}

    experimental_model

    Review of prolyl 4-hydroxylase enzymology and subunit structure

    exposure

    Hydroxylation of proline in X-Pro-Gly sequences

    limitations

    An authoritative enzymology review rather than a single experiment. It is the source for the cosubstrate list, which is the point at which oxygen, iron and vitamin C meet in collagen synthesis.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Mammalian enzyme

    plain_language

    Making collagen needs oxygen, iron, vitamin C and a Krebs-cycle acid, all four at once.

    primary_references

    [hbot-p2537773] Protein hydroxylation: prolyl 4-hydroxylase, an enzyme with four cosubstrates and a multifunctional subunit. (1989). https://pubmed.ncbi.nlm.nih.gov/2537773/ DOI: 10.1096/fasebj.3.5.2537773

    tissue_or_cell_type

    Endoplasmic reticulum

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 855–866

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Review of prolyl 4-hydroxylase enzymology and subunit structure · source_derived_draft · unverified_draft

    ### hbot-p4h-cosubstrates Prolyl 4-hydroxylase catalyses formation of 4-hydroxyproline in collagens by hydroxylating proline residues in X-Pro-Gly sequences, and the reaction requires Fe2+, 2-oxoglutarate, O2 and ascorbate, involving oxidative decarboxylation of 2-oxoglutarate. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Making collagen needs oxygen, iron, vitamin C and a Krebs-cycle acid, all four at once. organism: Mammalian enzyme tissue_or_cell_type: Endoplasmic reticulum experimental_model: Review of prolyl 4-hydroxylase enzymology and subunit structure limitations: An authoritative enzymology review rather than a single experiment. It is the source for the cosubstrate list, which is the point at which oxygen, iron and vitamin C meet in collagen synthesis. exposure: Hydroxylation of proline in X-Pro-Gly sequences evidence_span: {"source_cache": "artifacts/hbot-research/2537773.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3fdda2e4cf4392ec7a88b137274cee8f321255473992a2d8df781df12cad6cfe", "start_char": 0, "end_char": 2024, "text_sha256": "3fdda2e4cf4392ec7a88b137274cee8f321255473992a2d8df781df12cad6cfe"} [hbot-p2537773] Protein hydroxylation: prolyl 4-hydroxylase, an enzyme with four cosubstrates and a multifunctional subunit. (1989). https://pubmed.ncbi.nlm.nih.gov/2537773/ DOI: 10.1096/fasebj.3.5.2537773

    Complete structured claim and evidence

63. Ascorbate is not consumed during most catalytic cycles, but the enzyme also decarboxylates 2-oxoglutarate without subsequent hydroxylation, and ascorbate is required as a specific alternative oxygen acceptor in those uncoupled cycles.

    L-Ascorbate → Collagen prolyl 4-hydroxylase, the alpha2beta2 tetramer source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/2537773.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3fdda2e4cf4392ec7a88b137274cee8f321255473992a2d8df781df12cad6cfe", "start_char": 0, "end_char": 2024, "text_sha256": "3fdda2e4cf4392ec7a88b137274cee8f321255473992a2d8df781df12cad6cfe"}

    experimental_model

    Review of prolyl 4-hydroxylase enzymology and subunit structure

    exposure

    Hydroxylation of proline in X-Pro-Gly sequences

    limitations

    An authoritative enzymology review rather than a single experiment. It is the source for the cosubstrate list, which is the point at which oxygen, iron and vitamin C meet in collagen synthesis.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Mammalian enzyme

    plain_language

    Vitamin C is not used up every turn; it is the reserve that resets the enzyme when a cycle misfires.

    primary_references

    [hbot-p2537773] Protein hydroxylation: prolyl 4-hydroxylase, an enzyme with four cosubstrates and a multifunctional subunit. (1989). https://pubmed.ncbi.nlm.nih.gov/2537773/ DOI: 10.1096/fasebj.3.5.2537773

    tissue_or_cell_type

    Endoplasmic reticulum

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 868–879

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Review of prolyl 4-hydroxylase enzymology and subunit structure · source_derived_draft · unverified_draft

    ### hbot-ascorbate-uncoupled-cycles Ascorbate is not consumed during most catalytic cycles, but the enzyme also decarboxylates 2-oxoglutarate without subsequent hydroxylation, and ascorbate is required as a specific alternative oxygen acceptor in those uncoupled cycles. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Vitamin C is not used up every turn; it is the reserve that resets the enzyme when a cycle misfires. organism: Mammalian enzyme tissue_or_cell_type: Endoplasmic reticulum experimental_model: Review of prolyl 4-hydroxylase enzymology and subunit structure limitations: An authoritative enzymology review rather than a single experiment. It is the source for the cosubstrate list, which is the point at which oxygen, iron and vitamin C meet in collagen synthesis. exposure: Hydroxylation of proline in X-Pro-Gly sequences evidence_span: {"source_cache": "artifacts/hbot-research/2537773.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3fdda2e4cf4392ec7a88b137274cee8f321255473992a2d8df781df12cad6cfe", "start_char": 0, "end_char": 2024, "text_sha256": "3fdda2e4cf4392ec7a88b137274cee8f321255473992a2d8df781df12cad6cfe"} [hbot-p2537773] Protein hydroxylation: prolyl 4-hydroxylase, an enzyme with four cosubstrates and a multifunctional subunit. (1989). https://pubmed.ncbi.nlm.nih.gov/2537773/ DOI: 10.1096/fasebj.3.5.2537773

    Complete structured claim and evidence

64. The active enzyme is an alpha2beta2 tetramer whose beta subunit is identical to protein disulfide isomerase and a major cellular thyroid-hormone-binding protein, and whose C-terminal Lys-Asp-Glu-Leu sequence retains the enzyme in the endoplasmic reticulum.

    The prolyl 4-hydroxylase beta subunit, identical to protein disulfide isomerase → Collagen prolyl 4-hydroxylase, the alpha2beta2 tetramer source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/2537773.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3fdda2e4cf4392ec7a88b137274cee8f321255473992a2d8df781df12cad6cfe", "start_char": 0, "end_char": 2024, "text_sha256": "3fdda2e4cf4392ec7a88b137274cee8f321255473992a2d8df781df12cad6cfe"}

    experimental_model

    Review of prolyl 4-hydroxylase enzymology and subunit structure

    exposure

    Hydroxylation of proline in X-Pro-Gly sequences

    limitations

    An authoritative enzymology review rather than a single experiment. It is the source for the cosubstrate list, which is the point at which oxygen, iron and vitamin C meet in collagen synthesis.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Mammalian enzyme

    plain_language

    One half of this enzyme is a different enzyme doing a second job, and a four-letter tail keeps it where collagen is made.

    primary_references

    [hbot-p2537773] Protein hydroxylation: prolyl 4-hydroxylase, an enzyme with four cosubstrates and a multifunctional subunit. (1989). https://pubmed.ncbi.nlm.nih.gov/2537773/ DOI: 10.1096/fasebj.3.5.2537773

    tissue_or_cell_type

    Endoplasmic reticulum

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 881–892

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Review of prolyl 4-hydroxylase enzymology and subunit structure · source_derived_draft · unverified_draft

    ### hbot-p4h-structure The active enzyme is an alpha2beta2 tetramer whose beta subunit is identical to protein disulfide isomerase and a major cellular thyroid-hormone-binding protein, and whose C-terminal Lys-Asp-Glu-Leu sequence retains the enzyme in the endoplasmic reticulum. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: One half of this enzyme is a different enzyme doing a second job, and a four-letter tail keeps it where collagen is made. organism: Mammalian enzyme tissue_or_cell_type: Endoplasmic reticulum experimental_model: Review of prolyl 4-hydroxylase enzymology and subunit structure limitations: An authoritative enzymology review rather than a single experiment. It is the source for the cosubstrate list, which is the point at which oxygen, iron and vitamin C meet in collagen synthesis. exposure: Hydroxylation of proline in X-Pro-Gly sequences evidence_span: {"source_cache": "artifacts/hbot-research/2537773.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3fdda2e4cf4392ec7a88b137274cee8f321255473992a2d8df781df12cad6cfe", "start_char": 0, "end_char": 2024, "text_sha256": "3fdda2e4cf4392ec7a88b137274cee8f321255473992a2d8df781df12cad6cfe"} [hbot-p2537773] Protein hydroxylation: prolyl 4-hydroxylase, an enzyme with four cosubstrates and a multifunctional subunit. (1989). https://pubmed.ncbi.nlm.nih.gov/2537773/ DOI: 10.1096/fasebj.3.5.2537773

    Complete structured claim and evidence

65. A prolyl-4-hydroxylase, a functional homologue of human 2-oxoglutarate-dependent dioxygenases with essential roles in collagen biosynthesis and oxygen sensing, accumulated a C-H-cleaving high-spin Fe(IV)-oxo intermediate with a large substrate deuterium kinetic isotope effect on its decay.

    Ferrous iron / Fe(II) → The high-spin Fe(IV)-oxo reaction intermediate of a 2-oxoglutarate dioxygenase source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/17003127.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8c7def7926cf3f7a38d874fe22494fa3b72477ed41bdd2baee407cab4ea0d96d", "start_char": 0, "end_char": 1302, "text_sha256": "8c7def7926cf3f7a38d874fe22494fa3b72477ed41bdd2baee407cab4ea0d96d"}

    experimental_model

    Stopped-flow, optical absorption and Mossbauer spectroscopy of a prolyl-4-hydroxylase reaction

    exposure

    Catalysis with saturating substrates and deuterated substrate

    limitations

    Spectroscopy on a functional homologue, not the human enzyme. It identifies the chemical intermediate that does the work.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Bacterial enzyme homologous to the human enzymes

    plain_language

    The iron atom briefly becomes a highly reactive form that rips a hydrogen off the target carbon.

    primary_references

    [hbot-p17003127] Direct spectroscopic detection of a C-H-cleaving high-spin Fe(IV) complex in a prolyl-4-hydroxylase. (2006). https://pubmed.ncbi.nlm.nih.gov/17003127/ DOI: 10.1073/pnas.0604005103

    tissue_or_cell_type

    Purified enzyme

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 894–905

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Stopped-flow, optical absorption and Mossbauer spectroscopy of a prolyl-4-hydroxylase reaction · source_derived_draft · unverified_draft

    ### hbot-fe-iv-intermediate A prolyl-4-hydroxylase, a functional homologue of human 2-oxoglutarate-dependent dioxygenases with essential roles in collagen biosynthesis and oxygen sensing, accumulated a C-H-cleaving high-spin Fe(IV)-oxo intermediate with a large substrate deuterium kinetic isotope effect on its decay. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The iron atom briefly becomes a highly reactive form that rips a hydrogen off the target carbon. organism: Bacterial enzyme homologous to the human enzymes tissue_or_cell_type: Purified enzyme experimental_model: Stopped-flow, optical absorption and Mossbauer spectroscopy of a prolyl-4-hydroxylase reaction limitations: Spectroscopy on a functional homologue, not the human enzyme. It identifies the chemical intermediate that does the work. exposure: Catalysis with saturating substrates and deuterated substrate evidence_span: {"source_cache": "artifacts/hbot-research/17003127.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8c7def7926cf3f7a38d874fe22494fa3b72477ed41bdd2baee407cab4ea0d96d", "start_char": 0, "end_char": 1302, "text_sha256": "8c7def7926cf3f7a38d874fe22494fa3b72477ed41bdd2baee407cab4ea0d96d"} [hbot-p17003127] Direct spectroscopic detection of a C-H-cleaving high-spin Fe(IV) complex in a prolyl-4-hydroxylase. (2006). https://pubmed.ncbi.nlm.nih.gov/17003127/ DOI: 10.1073/pnas.0604005103

    Complete structured claim and evidence

66. Ascorbate is required for hydroxylation of proline residues in procollagen, hydroxyproline stabilises the collagen triple-helical structure, and consequently ascorbate stimulates procollagen secretion.

    L-Ascorbate → Procollagen secretion source_derived_draftungraded
    Experimental context and source evidence

    availability_state

    nutrient_deficiency Imported condition classification; unverified.

    evidence_span

    {"source_cache": "artifacts/hbot-research/1720597.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b769da8d030351b117b7a349262e9b52d54aab00ca3a2679900cb1372006bc31", "start_char": 0, "end_char": 1015, "text_sha256": "b769da8d030351b117b7a349262e9b52d54aab00ca3a2679900cb1372006bc31"}

    experimental_model

    Ascorbate-deficient guinea pigs, fasting controls, and cells cultured in scorbutic serum

    exposure

    Vitamin C deficiency, with fasting plus ascorbate supplementation as a comparison

    limitations

    The study separates a direct hydroxylation defect from a growth-factor-mediated one, so it argues against reading scurvy as pure under-hydroxylation.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Guinea pig and cultured cells

    plain_language

    Without vitamin C the collagen cannot be stiffened properly and does not leave the cell.

    primary_references

    [hbot-p1720597] Ascorbate requirement for hydroxylation and secretion of procollagen: relationship to inhibition of collagen synthesis in scurvy. (1991). https://pubmed.ncbi.nlm.nih.gov/1720597/ DOI: 10.1093/ajcn/54.6.1135s

    tissue_or_cell_type

    Connective tissue

    trigger_kind

    nutrient_deficiency Imported condition classification; unverified.

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 907–918

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ascorbate-deficient guinea pigs, fasting controls, and cells cultured in scorbutic serum · source_derived_draft · unverified_draft

    ### hbot-ascorbate-procollagen Ascorbate is required for hydroxylation of proline residues in procollagen, hydroxyproline stabilises the collagen triple-helical structure, and consequently ascorbate stimulates procollagen secretion. Condition category: nutrient_deficiency nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Without vitamin C the collagen cannot be stiffened properly and does not leave the cell. organism: Guinea pig and cultured cells tissue_or_cell_type: Connective tissue experimental_model: Ascorbate-deficient guinea pigs, fasting controls, and cells cultured in scorbutic serum limitations: The study separates a direct hydroxylation defect from a growth-factor-mediated one, so it argues against reading scurvy as pure under-hydroxylation. exposure: Vitamin C deficiency, with fasting plus ascorbate supplementation as a comparison evidence_span: {"source_cache": "artifacts/hbot-research/1720597.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b769da8d030351b117b7a349262e9b52d54aab00ca3a2679900cb1372006bc31", "start_char": 0, "end_char": 1015, "text_sha256": "b769da8d030351b117b7a349262e9b52d54aab00ca3a2679900cb1372006bc31"} [hbot-p1720597] Ascorbate requirement for hydroxylation and secretion of procollagen: relationship to inhibition of collagen synthesis in scurvy. (1991). https://pubmed.ncbi.nlm.nih.gov/1720597/ DOI: 10.1093/ajcn/54.6.1135s

    Complete structured claim and evidence

67. Collagen synthesis in ascorbate-deficient guinea pigs is decreased with only moderate effects on proline hydroxylation, proteoglycan synthesis which does not require ascorbate is also decreased, both correlate with weight loss, and the inhibition is reversed by IGF-I, the inhibitor appearing to be two IGF-binding proteins induced during deficiency and starvation.

    Experimental ascorbate deficiency in guinea pigs → Collagen synthesis source_derived_draftungraded
    Experimental context and source evidence

    availability_state

    nutrient_deficiency Imported condition classification; unverified.

    evidence_span

    {"source_cache": "artifacts/hbot-research/1720597.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b769da8d030351b117b7a349262e9b52d54aab00ca3a2679900cb1372006bc31", "start_char": 0, "end_char": 1015, "text_sha256": "b769da8d030351b117b7a349262e9b52d54aab00ca3a2679900cb1372006bc31"}

    experimental_model

    Ascorbate-deficient guinea pigs, fasting controls, and cells cultured in scorbutic serum

    exposure

    Vitamin C deficiency, with fasting plus ascorbate supplementation as a comparison

    limitations

    The study separates a direct hydroxylation defect from a growth-factor-mediated one, so it argues against reading scurvy as pure under-hydroxylation.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Guinea pig and cultured cells

    plain_language

    Scurvy lowers collagen by more than one route, and one of them is not about the hydroxylation step at all.

    primary_references

    [hbot-p1720597] Ascorbate requirement for hydroxylation and secretion of procollagen: relationship to inhibition of collagen synthesis in scurvy. (1991). https://pubmed.ncbi.nlm.nih.gov/1720597/ DOI: 10.1093/ajcn/54.6.1135s

    tissue_or_cell_type

    Connective tissue

    trigger_kind

    nutrient_deficiency Imported condition classification; unverified.

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 920–931

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ascorbate-deficient guinea pigs, fasting controls, and cells cultured in scorbutic serum · source_derived_draft · unverified_draft

    ### hbot-scurvy-beyond-hydroxylation Collagen synthesis in ascorbate-deficient guinea pigs is decreased with only moderate effects on proline hydroxylation, proteoglycan synthesis which does not require ascorbate is also decreased, both correlate with weight loss, and the inhibition is reversed by IGF-I, the inhibitor appearing to be two IGF-binding proteins induced during deficiency and starvation. Condition category: nutrient_deficiency nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Scurvy lowers collagen by more than one route, and one of them is not about the hydroxylation step at all. organism: Guinea pig and cultured cells tissue_or_cell_type: Connective tissue experimental_model: Ascorbate-deficient guinea pigs, fasting controls, and cells cultured in scorbutic serum limitations: The study separates a direct hydroxylation defect from a growth-factor-mediated one, so it argues against reading scurvy as pure under-hydroxylation. exposure: Vitamin C deficiency, with fasting plus ascorbate supplementation as a comparison evidence_span: {"source_cache": "artifacts/hbot-research/1720597.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b769da8d030351b117b7a349262e9b52d54aab00ca3a2679900cb1372006bc31", "start_char": 0, "end_char": 1015, "text_sha256": "b769da8d030351b117b7a349262e9b52d54aab00ca3a2679900cb1372006bc31"} [hbot-p1720597] Ascorbate requirement for hydroxylation and secretion of procollagen: relationship to inhibition of collagen synthesis in scurvy. (1991). https://pubmed.ncbi.nlm.nih.gov/1720597/ DOI: 10.1093/ajcn/54.6.1135s

    Complete structured claim and evidence

68. Silencing PHD2 alone was sufficient to stabilise and activate HIF-1alpha in normoxia in every human cell type investigated, while silencing PHD1 or PHD3 had no effect on HIF-1alpha stability, making PHD2 the critical oxygen sensor setting the low steady-state level of HIF-1alpha.

    EGLN1 / PHD2 → HIF-1 alpha source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/12912907.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "db0613321b1804356dbb60637bba0616eaaaeab041f63a095ecfcaeac3ec780e", "start_char": 0, "end_char": 1190, "text_sha256": "db0613321b1804356dbb60637bba0616eaaaeab041f63a095ecfcaeac3ec780e"}

    experimental_model

    Short interfering RNA silencing of each HIF prolyl-hydroxylase in human cells

    exposure

    PHD1, PHD2 and PHD3 silencing in normoxia and after brief hypoxia

    limitations

    A silencing study assigning distinct roles. It establishes which isoform sets the resting level, not the oxygen concentration at which each acts.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human cells

    plain_language

    One enzyme is the thermostat: it destroys the low-oxygen signal whenever oxygen is present.

    primary_references

    [hbot-p12912907] HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1alpha in normoxia. (2003). https://pubmed.ncbi.nlm.nih.gov/12912907/ DOI: 10.1093/emboj/cdg392

    tissue_or_cell_type

    Cytosol

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 933–944

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Short interfering RNA silencing of each HIF prolyl-hydroxylase in human cells · source_derived_draft · unverified_draft

    ### hbot-phd2-oxygen-sensor Silencing PHD2 alone was sufficient to stabilise and activate HIF-1alpha in normoxia in every human cell type investigated, while silencing PHD1 or PHD3 had no effect on HIF-1alpha stability, making PHD2 the critical oxygen sensor setting the low steady-state level of HIF-1alpha. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: One enzyme is the thermostat: it destroys the low-oxygen signal whenever oxygen is present. organism: Human cells tissue_or_cell_type: Cytosol experimental_model: Short interfering RNA silencing of each HIF prolyl-hydroxylase in human cells limitations: A silencing study assigning distinct roles. It establishes which isoform sets the resting level, not the oxygen concentration at which each acts. exposure: PHD1, PHD2 and PHD3 silencing in normoxia and after brief hypoxia evidence_span: {"source_cache": "artifacts/hbot-research/12912907.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "db0613321b1804356dbb60637bba0616eaaaeab041f63a095ecfcaeac3ec780e", "start_char": 0, "end_char": 1190, "text_sha256": "db0613321b1804356dbb60637bba0616eaaaeab041f63a095ecfcaeac3ec780e"} [hbot-p12912907] HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1alpha in normoxia. (2003). https://pubmed.ncbi.nlm.nih.gov/12912907/ DOI: 10.1093/emboj/cdg392

    Complete structured claim and evidence

69. PHD2 is itself upregulated by hypoxia, providing a HIF-1-dependent auto-regulatory mechanism driven by oxygen tension.

    HIF-1 alpha → EGLN1 / PHD2 source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/12912907.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "db0613321b1804356dbb60637bba0616eaaaeab041f63a095ecfcaeac3ec780e", "start_char": 0, "end_char": 1190, "text_sha256": "db0613321b1804356dbb60637bba0616eaaaeab041f63a095ecfcaeac3ec780e"}

    experimental_model

    Short interfering RNA silencing of each HIF prolyl-hydroxylase in human cells

    exposure

    PHD1, PHD2 and PHD3 silencing in normoxia and after brief hypoxia

    limitations

    A silencing study assigning distinct roles. It establishes which isoform sets the resting level, not the oxygen concentration at which each acts.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human cells

    plain_language

    The thermostat builds more of itself when oxygen is scarce, so the system resets when oxygen returns.

    primary_references

    [hbot-p12912907] HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1alpha in normoxia. (2003). https://pubmed.ncbi.nlm.nih.gov/12912907/ DOI: 10.1093/emboj/cdg392

    tissue_or_cell_type

    Cytosol

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 946–957

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Short interfering RNA silencing of each HIF prolyl-hydroxylase in human cells · source_derived_draft · unverified_draft

    ### hbot-phd2-autoregulation PHD2 is itself upregulated by hypoxia, providing a HIF-1-dependent auto-regulatory mechanism driven by oxygen tension. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The thermostat builds more of itself when oxygen is scarce, so the system resets when oxygen returns. organism: Human cells tissue_or_cell_type: Cytosol experimental_model: Short interfering RNA silencing of each HIF prolyl-hydroxylase in human cells limitations: A silencing study assigning distinct roles. It establishes which isoform sets the resting level, not the oxygen concentration at which each acts. exposure: PHD1, PHD2 and PHD3 silencing in normoxia and after brief hypoxia evidence_span: {"source_cache": "artifacts/hbot-research/12912907.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "db0613321b1804356dbb60637bba0616eaaaeab041f63a095ecfcaeac3ec780e", "start_char": 0, "end_char": 1190, "text_sha256": "db0613321b1804356dbb60637bba0616eaaaeab041f63a095ecfcaeac3ec780e"} [hbot-p12912907] HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1alpha in normoxia. (2003). https://pubmed.ncbi.nlm.nih.gov/12912907/ DOI: 10.1093/emboj/cdg392

    Complete structured claim and evidence

70. The initial rate and extent of PHD2-catalysed hydroxylation of two prolyl sites in human HIF-1alpha, and of FIH-catalysed asparaginyl hydroxylation, were increased in the presence of ascorbate; these are Fe(II) and 2-oxoglutarate-dependent oxygenases.

    L-Ascorbate → PHD2-catalysed prolyl hydroxylation of HIF-1alpha source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/20055761.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3b9ac610e9510ed4f2fd2ed696009ab95dadac196fff3a7fe1644f03ed29d1dd", "start_char": 0, "end_char": 1322, "text_sha256": "3b9ac610e9510ed4f2fd2ed696009ab95dadac196fff3a7fe1644f03ed29d1dd"}

    experimental_model

    Enzyme assays of PHD2 and FIH with ascorbate, ascorbate analogues and alternative reducing agents

    exposure

    Prolyl and asparaginyl hydroxylation with and without ascorbate, glutathione or dithiothreitol

    limitations

    Purified-enzyme kinetics. It identifies which part of the ascorbate molecule matters, and shows other reductants substitute only partially.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human enzymes

    plain_language

    Vitamin C makes the enzyme that destroys the low-oxygen signal work faster.

    primary_references

    [hbot-p20055761] Investigating the dependence of the hypoxia-inducible factor hydroxylases (factor inhibiting HIF and prolyl hydroxylase domain 2) on ascorbate and other reducing agents. (2010). https://pubmed.ncbi.nlm.nih.gov/20055761/ DOI: 10.1042/bj20091609

    tissue_or_cell_type

    Purified enzyme with HIF-1alpha peptides

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 959–970

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Enzyme assays of PHD2 and FIH with ascorbate, ascorbate analogues and alternative reducing agents · source_derived_draft · unverified_draft

    ### hbot-ascorbate-stimulates-phd The initial rate and extent of PHD2-catalysed hydroxylation of two prolyl sites in human HIF-1alpha, and of FIH-catalysed asparaginyl hydroxylation, were increased in the presence of ascorbate; these are Fe(II) and 2-oxoglutarate-dependent oxygenases. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Vitamin C makes the enzyme that destroys the low-oxygen signal work faster. organism: Human enzymes tissue_or_cell_type: Purified enzyme with HIF-1alpha peptides experimental_model: Enzyme assays of PHD2 and FIH with ascorbate, ascorbate analogues and alternative reducing agents limitations: Purified-enzyme kinetics. It identifies which part of the ascorbate molecule matters, and shows other reductants substitute only partially. exposure: Prolyl and asparaginyl hydroxylation with and without ascorbate, glutathione or dithiothreitol evidence_span: {"source_cache": "artifacts/hbot-research/20055761.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3b9ac610e9510ed4f2fd2ed696009ab95dadac196fff3a7fe1644f03ed29d1dd", "start_char": 0, "end_char": 1322, "text_sha256": "3b9ac610e9510ed4f2fd2ed696009ab95dadac196fff3a7fe1644f03ed29d1dd"} [hbot-p20055761] Investigating the dependence of the hypoxia-inducible factor hydroxylases (factor inhibiting HIF and prolyl hydroxylase domain 2) on ascorbate and other reducing agents. (2010). https://pubmed.ncbi.nlm.nih.gov/20055761/ DOI: 10.1042/bj20091609

    Complete structured claim and evidence

71. Replacing ascorbate with structural analogues showed that its side chain was not important for catalysis, whereas modifications to the ene-diol portion negated the ability to promote hydroxylation, and glutathione and dithiothreitol gave only partial, enzyme- and substrate-specific stimulation.

    The ene-diol group of ascorbate → PHD2-catalysed prolyl hydroxylation of HIF-1alpha source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/20055761.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3b9ac610e9510ed4f2fd2ed696009ab95dadac196fff3a7fe1644f03ed29d1dd", "start_char": 0, "end_char": 1322, "text_sha256": "3b9ac610e9510ed4f2fd2ed696009ab95dadac196fff3a7fe1644f03ed29d1dd"}

    experimental_model

    Enzyme assays of PHD2 and FIH with ascorbate, ascorbate analogues and alternative reducing agents

    exposure

    Prolyl and asparaginyl hydroxylation with and without ascorbate, glutathione or dithiothreitol

    limitations

    Purified-enzyme kinetics. It identifies which part of the ascorbate molecule matters, and shows other reductants substitute only partially.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human enzymes

    plain_language

    It is one specific chemical group on vitamin C that does the job, and other reducing agents only half substitute.

    primary_references

    [hbot-p20055761] Investigating the dependence of the hypoxia-inducible factor hydroxylases (factor inhibiting HIF and prolyl hydroxylase domain 2) on ascorbate and other reducing agents. (2010). https://pubmed.ncbi.nlm.nih.gov/20055761/ DOI: 10.1042/bj20091609

    tissue_or_cell_type

    Purified enzyme with HIF-1alpha peptides

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 972–983

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Enzyme assays of PHD2 and FIH with ascorbate, ascorbate analogues and alternative reducing agents · source_derived_draft · unverified_draft

    ### hbot-ascorbate-ene-diol Replacing ascorbate with structural analogues showed that its side chain was not important for catalysis, whereas modifications to the ene-diol portion negated the ability to promote hydroxylation, and glutathione and dithiothreitol gave only partial, enzyme- and substrate-specific stimulation. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: It is one specific chemical group on vitamin C that does the job, and other reducing agents only half substitute. organism: Human enzymes tissue_or_cell_type: Purified enzyme with HIF-1alpha peptides experimental_model: Enzyme assays of PHD2 and FIH with ascorbate, ascorbate analogues and alternative reducing agents limitations: Purified-enzyme kinetics. It identifies which part of the ascorbate molecule matters, and shows other reductants substitute only partially. exposure: Prolyl and asparaginyl hydroxylation with and without ascorbate, glutathione or dithiothreitol evidence_span: {"source_cache": "artifacts/hbot-research/20055761.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3b9ac610e9510ed4f2fd2ed696009ab95dadac196fff3a7fe1644f03ed29d1dd", "start_char": 0, "end_char": 1322, "text_sha256": "3b9ac610e9510ed4f2fd2ed696009ab95dadac196fff3a7fe1644f03ed29d1dd"} [hbot-p20055761] Investigating the dependence of the hypoxia-inducible factor hydroxylases (factor inhibiting HIF and prolyl hydroxylase domain 2) on ascorbate and other reducing agents. (2010). https://pubmed.ncbi.nlm.nih.gov/20055761/ DOI: 10.1042/bj20091609

    Complete structured claim and evidence

72. Ascorbate inhibited HIF-1 activity most dramatically under all mechanisms of iron competition, and HIF-1-dependent gene expression was prevented even under conditions that allowed HIF-1alpha protein stabilisation.

    L-Ascorbate → HIF-1 transcriptional activity source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/24495550.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "444b204ff84635f64eebf59c2db6afa112641b24f7b309fb2bcd6da04d4d0d0a", "start_char": 0, "end_char": 1497, "text_sha256": "444b204ff84635f64eebf59c2db6afa112641b24f7b309fb2bcd6da04d4d0d0a"}

    experimental_model

    Cells with defined intracellular ascorbate concentrations against several hydroxylase inhibitors

    exposure

    Intracellular ascorbate loading with CoCl2, NiCl2, desferrioxamine, dimethyloxalylglycine or hypoxia

    limitations

    Establishes an effect of intracellular ascorbate on the HIF response. The iron-competing inhibitors are the conditions where ascorbate mattered most.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human cells

    plain_language

    Vitamin C shuts down the low-oxygen gene programme even when the protein itself survives.

    primary_references

    [hbot-p24495550] Intracellular ascorbate enhances hypoxia-inducible factor (HIF)-hydroxylase activity and preferentially suppresses the HIF-1 transcriptional response. (2014). https://pubmed.ncbi.nlm.nih.gov/24495550/ DOI: 10.1016/j.freeradbiomed.2014.01.033

    tissue_or_cell_type

    Cytosol and nucleus

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 985–996

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cells with defined intracellular ascorbate concentrations against several hydroxylase inhibitors · source_derived_draft · unverified_draft

    ### hbot-ascorbate-suppresses-hif Ascorbate inhibited HIF-1 activity most dramatically under all mechanisms of iron competition, and HIF-1-dependent gene expression was prevented even under conditions that allowed HIF-1alpha protein stabilisation. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Vitamin C shuts down the low-oxygen gene programme even when the protein itself survives. organism: Human cells tissue_or_cell_type: Cytosol and nucleus experimental_model: Cells with defined intracellular ascorbate concentrations against several hydroxylase inhibitors limitations: Establishes an effect of intracellular ascorbate on the HIF response. The iron-competing inhibitors are the conditions where ascorbate mattered most. exposure: Intracellular ascorbate loading with CoCl2, NiCl2, desferrioxamine, dimethyloxalylglycine or hypoxia evidence_span: {"source_cache": "artifacts/hbot-research/24495550.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "444b204ff84635f64eebf59c2db6afa112641b24f7b309fb2bcd6da04d4d0d0a", "start_char": 0, "end_char": 1497, "text_sha256": "444b204ff84635f64eebf59c2db6afa112641b24f7b309fb2bcd6da04d4d0d0a"} [hbot-p24495550] Intracellular ascorbate enhances hypoxia-inducible factor (HIF)-hydroxylase activity and preferentially suppresses the HIF-1 transcriptional response. (2014). https://pubmed.ncbi.nlm.nih.gov/24495550/ DOI: 10.1016/j.freeradbiomed.2014.01.033

    Complete structured claim and evidence

73. The findings suggest that ascorbate acts primarily to stabilise and reduce the iron atom in the hydroxylase active site, and that the asparagine hydroxylase controlling HIF-1 transcriptional activity is particularly susceptible to fluctuations in intracellular ascorbate.

    L-Ascorbate → Ferrous iron / Fe(II) source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/24495550.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "444b204ff84635f64eebf59c2db6afa112641b24f7b309fb2bcd6da04d4d0d0a", "start_char": 0, "end_char": 1497, "text_sha256": "444b204ff84635f64eebf59c2db6afa112641b24f7b309fb2bcd6da04d4d0d0a"}

    experimental_model

    Cells with defined intracellular ascorbate concentrations against several hydroxylase inhibitors

    exposure

    Intracellular ascorbate loading with CoCl2, NiCl2, desferrioxamine, dimethyloxalylglycine or hypoxia

    limitations

    Establishes an effect of intracellular ascorbate on the HIF response. The iron-competing inhibitors are the conditions where ascorbate mattered most.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human cells

    plain_language

    Vitamin C’s job here is to keep the enzyme’s iron in the right state.

    primary_references

    [hbot-p24495550] Intracellular ascorbate enhances hypoxia-inducible factor (HIF)-hydroxylase activity and preferentially suppresses the HIF-1 transcriptional response. (2014). https://pubmed.ncbi.nlm.nih.gov/24495550/ DOI: 10.1016/j.freeradbiomed.2014.01.033

    tissue_or_cell_type

    Cytosol and nucleus

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 998–1009

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cells with defined intracellular ascorbate concentrations against several hydroxylase inhibitors · source_derived_draft · unverified_draft

    ### hbot-ascorbate-iron-site The findings suggest that ascorbate acts primarily to stabilise and reduce the iron atom in the hydroxylase active site, and that the asparagine hydroxylase controlling HIF-1 transcriptional activity is particularly susceptible to fluctuations in intracellular ascorbate. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Vitamin C’s job here is to keep the enzyme’s iron in the right state. organism: Human cells tissue_or_cell_type: Cytosol and nucleus experimental_model: Cells with defined intracellular ascorbate concentrations against several hydroxylase inhibitors limitations: Establishes an effect of intracellular ascorbate on the HIF response. The iron-competing inhibitors are the conditions where ascorbate mattered most. exposure: Intracellular ascorbate loading with CoCl2, NiCl2, desferrioxamine, dimethyloxalylglycine or hypoxia evidence_span: {"source_cache": "artifacts/hbot-research/24495550.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "444b204ff84635f64eebf59c2db6afa112641b24f7b309fb2bcd6da04d4d0d0a", "start_char": 0, "end_char": 1497, "text_sha256": "444b204ff84635f64eebf59c2db6afa112641b24f7b309fb2bcd6da04d4d0d0a"} [hbot-p24495550] Intracellular ascorbate enhances hypoxia-inducible factor (HIF)-hydroxylase activity and preferentially suppresses the HIF-1 transcriptional response. (2014). https://pubmed.ncbi.nlm.nih.gov/24495550/ DOI: 10.1016/j.freeradbiomed.2014.01.033

    Complete structured claim and evidence

74. Hyperbaric oxygen increased osteoblastic activity in irradiated distracted bone and shifted the osteogenic pattern towards that of non-irradiated bone, though not to the level of non-irradiated bone.

    Hyperbaric oxygen therapy → Osteoblastic activity in distracted bone source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/15050074.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1fe4a8f81ae5308f452c7a4551e9de0f0426daf32cbcd153149ec6e6a7a61970", "start_char": 0, "end_char": 1615, "text_sha256": "1fe4a8f81ae5308f452c7a4551e9de0f0426daf32cbcd153149ec6e6a7a61970"}

    experimental_model

    Irradiated and non-irradiated rabbit mandibular distraction osteogenesis with fluoride autoradiography

    exposure

    2.5 ATA for 90 minutes daily, 18 sessions preoperatively, after 22.4 Gy irradiation

    limitations

    A pre-treatment protocol in irradiated bone. Osteoblastic activity was measured by fluoride uptake, an activity surrogate.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Rabbit

    plain_language

    Irradiated bone rebuilt more like healthy bone, without fully catching up.

    primary_references

    [hbot-p15050074] Osteoblastic activity and neoangiogenesis in distracted bone of irradiated rabbit mandible with or without hyperbaric oxygen treatment. (2004). https://pubmed.ncbi.nlm.nih.gov/15050074/ DOI: 10.1054/ijom.2003.0489

    tissue_or_cell_type

    Mandibular bone

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 1011–1022

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Irradiated and non-irradiated rabbit mandibular distraction osteogenesis with fluoride autoradiography · source_derived_draft · unverified_draft

    ### hbot-osteoblast-activity Hyperbaric oxygen increased osteoblastic activity in irradiated distracted bone and shifted the osteogenic pattern towards that of non-irradiated bone, though not to the level of non-irradiated bone. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Irradiated bone rebuilt more like healthy bone, without fully catching up. organism: Rabbit tissue_or_cell_type: Mandibular bone experimental_model: Irradiated and non-irradiated rabbit mandibular distraction osteogenesis with fluoride autoradiography limitations: A pre-treatment protocol in irradiated bone. Osteoblastic activity was measured by fluoride uptake, an activity surrogate. exposure: 2.5 ATA for 90 minutes daily, 18 sessions preoperatively, after 22.4 Gy irradiation evidence_span: {"source_cache": "artifacts/hbot-research/15050074.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1fe4a8f81ae5308f452c7a4551e9de0f0426daf32cbcd153149ec6e6a7a61970", "start_char": 0, "end_char": 1615, "text_sha256": "1fe4a8f81ae5308f452c7a4551e9de0f0426daf32cbcd153149ec6e6a7a61970"} [hbot-p15050074] Osteoblastic activity and neoangiogenesis in distracted bone of irradiated rabbit mandible with or without hyperbaric oxygen treatment. (2004). https://pubmed.ncbi.nlm.nih.gov/15050074/ DOI: 10.1054/ijom.2003.0489

    Complete structured claim and evidence

75. The angiogenic response was markedly increased by hyperbaric oxygen, with blood vessels more numerous in the central region than peripheral regions in irradiated animals given the treatment, a pattern absent in irradiated animals without it.

    Hyperbaric oxygen therapy → Neovascularisation of irradiated distracted bone source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/15050074.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1fe4a8f81ae5308f452c7a4551e9de0f0426daf32cbcd153149ec6e6a7a61970", "start_char": 0, "end_char": 1615, "text_sha256": "1fe4a8f81ae5308f452c7a4551e9de0f0426daf32cbcd153149ec6e6a7a61970"}

    experimental_model

    Irradiated and non-irradiated rabbit mandibular distraction osteogenesis with fluoride autoradiography

    exposure

    2.5 ATA for 90 minutes daily, 18 sessions preoperatively, after 22.4 Gy irradiation

    limitations

    A pre-treatment protocol in irradiated bone. Osteoblastic activity was measured by fluoride uptake, an activity surrogate.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Rabbit

    plain_language

    The new vessels came back in the pattern healthy bone shows.

    primary_references

    [hbot-p15050074] Osteoblastic activity and neoangiogenesis in distracted bone of irradiated rabbit mandible with or without hyperbaric oxygen treatment. (2004). https://pubmed.ncbi.nlm.nih.gov/15050074/ DOI: 10.1054/ijom.2003.0489

    tissue_or_cell_type

    Mandibular bone

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 1024–1035

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Irradiated and non-irradiated rabbit mandibular distraction osteogenesis with fluoride autoradiography · source_derived_draft · unverified_draft

    ### hbot-bone-neovascularisation The angiogenic response was markedly increased by hyperbaric oxygen, with blood vessels more numerous in the central region than peripheral regions in irradiated animals given the treatment, a pattern absent in irradiated animals without it. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The new vessels came back in the pattern healthy bone shows. organism: Rabbit tissue_or_cell_type: Mandibular bone experimental_model: Irradiated and non-irradiated rabbit mandibular distraction osteogenesis with fluoride autoradiography limitations: A pre-treatment protocol in irradiated bone. Osteoblastic activity was measured by fluoride uptake, an activity surrogate. exposure: 2.5 ATA for 90 minutes daily, 18 sessions preoperatively, after 22.4 Gy irradiation evidence_span: {"source_cache": "artifacts/hbot-research/15050074.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1fe4a8f81ae5308f452c7a4551e9de0f0426daf32cbcd153149ec6e6a7a61970", "start_char": 0, "end_char": 1615, "text_sha256": "1fe4a8f81ae5308f452c7a4551e9de0f0426daf32cbcd153149ec6e6a7a61970"} [hbot-p15050074] Osteoblastic activity and neoangiogenesis in distracted bone of irradiated rabbit mandible with or without hyperbaric oxygen treatment. (2004). https://pubmed.ncbi.nlm.nih.gov/15050074/ DOI: 10.1054/ijom.2003.0489

    Complete structured claim and evidence

76. A single 90-minute exposure increased the respiratory burst activity of neutrophil-like cells after exposure, and phagocytosis of Staphylococcus aureus was also increased.

    Hyperbaric oxygen therapy → Neutrophil respiratory burst activity source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/23770209.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1621131d902e359cb8c23a51c1d76596ddff036697818a1613e68b26095eed8a", "start_char": 0, "end_char": 1709, "text_sha256": "1621131d902e359cb8c23a51c1d76596ddff036697818a1613e68b26095eed8a"}

    experimental_model

    Differentiated HL-60 neutrophil-like cells across normoxia, hypoxia, hyperoxia, pressure alone and hyperbaric oxygen

    exposure

    97.9% oxygen at 2.4 ATA for 90 minutes, with hyperbaric normoxia as a pressure control

    limitations

    A cell-line model of the neutrophil with a pressure control. The authors report that both hyperoxia and pressure contributed, without a consistent pattern.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human cell line

    plain_language

    The cells that kill bacteria did so more strongly after a session.

    primary_references

    [hbot-p23770209] Effects of hyperbaric oxygen treatment on antimicrobial function and apoptosis of differentiated HL-60 (neutrophil-like) cells. (2013). https://pubmed.ncbi.nlm.nih.gov/23770209/ DOI: 10.1016/j.lfs.2013.06.003

    tissue_or_cell_type

    Neutrophil-like cells

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 1037–1048

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Differentiated HL-60 neutrophil-like cells across normoxia, hypoxia, hyperoxia, pressure alone and hyperbaric oxygen · source_derived_draft · unverified_draft

    ### hbot-respiratory-burst-increase A single 90-minute exposure increased the respiratory burst activity of neutrophil-like cells after exposure, and phagocytosis of Staphylococcus aureus was also increased. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The cells that kill bacteria did so more strongly after a session. organism: Human cell line tissue_or_cell_type: Neutrophil-like cells experimental_model: Differentiated HL-60 neutrophil-like cells across normoxia, hypoxia, hyperoxia, pressure alone and hyperbaric oxygen limitations: A cell-line model of the neutrophil with a pressure control. The authors report that both hyperoxia and pressure contributed, without a consistent pattern. exposure: 97.9% oxygen at 2.4 ATA for 90 minutes, with hyperbaric normoxia as a pressure control evidence_span: {"source_cache": "artifacts/hbot-research/23770209.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1621131d902e359cb8c23a51c1d76596ddff036697818a1613e68b26095eed8a", "start_char": 0, "end_char": 1709, "text_sha256": "1621131d902e359cb8c23a51c1d76596ddff036697818a1613e68b26095eed8a"} [hbot-p23770209] Effects of hyperbaric oxygen treatment on antimicrobial function and apoptosis of differentiated HL-60 (neutrophil-like) cells. (2013). https://pubmed.ncbi.nlm.nih.gov/23770209/ DOI: 10.1016/j.lfs.2013.06.003

    Complete structured claim and evidence

77. Pre-treatment had a pro-apoptotic effect, increasing caspase 3/7 activity and producing morphological changes associated with apoptosis, which the authors suggest may offset the potential detrimental effect of enhanced antimicrobial activity.

    Hyperbaric oxygen therapy → Neutrophil apoptosis source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/23770209.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1621131d902e359cb8c23a51c1d76596ddff036697818a1613e68b26095eed8a", "start_char": 0, "end_char": 1709, "text_sha256": "1621131d902e359cb8c23a51c1d76596ddff036697818a1613e68b26095eed8a"}

    experimental_model

    Differentiated HL-60 neutrophil-like cells across normoxia, hypoxia, hyperoxia, pressure alone and hyperbaric oxygen

    exposure

    97.9% oxygen at 2.4 ATA for 90 minutes, with hyperbaric normoxia as a pressure control

    limitations

    A cell-line model of the neutrophil with a pressure control. The authors report that both hyperoxia and pressure contributed, without a consistent pattern.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human cell line

    plain_language

    The same treatment also makes those cells die off on schedule, which is how inflammation ends.

    primary_references

    [hbot-p23770209] Effects of hyperbaric oxygen treatment on antimicrobial function and apoptosis of differentiated HL-60 (neutrophil-like) cells. (2013). https://pubmed.ncbi.nlm.nih.gov/23770209/ DOI: 10.1016/j.lfs.2013.06.003

    tissue_or_cell_type

    Neutrophil-like cells

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 1050–1061

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Differentiated HL-60 neutrophil-like cells across normoxia, hypoxia, hyperoxia, pressure alone and hyperbaric oxygen · source_derived_draft · unverified_draft

    ### hbot-neutrophil-apoptosis-increase Pre-treatment had a pro-apoptotic effect, increasing caspase 3/7 activity and producing morphological changes associated with apoptosis, which the authors suggest may offset the potential detrimental effect of enhanced antimicrobial activity. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The same treatment also makes those cells die off on schedule, which is how inflammation ends. organism: Human cell line tissue_or_cell_type: Neutrophil-like cells experimental_model: Differentiated HL-60 neutrophil-like cells across normoxia, hypoxia, hyperoxia, pressure alone and hyperbaric oxygen limitations: A cell-line model of the neutrophil with a pressure control. The authors report that both hyperoxia and pressure contributed, without a consistent pattern. exposure: 97.9% oxygen at 2.4 ATA for 90 minutes, with hyperbaric normoxia as a pressure control evidence_span: {"source_cache": "artifacts/hbot-research/23770209.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1621131d902e359cb8c23a51c1d76596ddff036697818a1613e68b26095eed8a", "start_char": 0, "end_char": 1709, "text_sha256": "1621131d902e359cb8c23a51c1d76596ddff036697818a1613e68b26095eed8a"} [hbot-p23770209] Effects of hyperbaric oxygen treatment on antimicrobial function and apoptosis of differentiated HL-60 (neutrophil-like) cells. (2013). https://pubmed.ncbi.nlm.nih.gov/23770209/ DOI: 10.1016/j.lfs.2013.06.003

    Complete structured claim and evidence

78. Cognitive sequelae at six weeks occurred in 25.0% of the hyperbaric group versus 46.1% of the normobaric group, an adjusted odds ratio of 0.45, and the difference persisted at 12 months.

    Hyperbaric oxygen therapy → Cognitive sequelae after acute carbon monoxide poisoning source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/12362006.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f1d5366f5eb1704ebe411ee13fba05068a310070c87ae65c8c75df678655dcca", "start_char": 0, "end_char": 1966, "text_sha256": "f1d5366f5eb1704ebe411ee13fba05068a310070c87ae65c8c75df678655dcca"}

    experimental_model

    Double-blind randomised trial of 152 patients with symptomatic acute carbon monoxide poisoning

    exposure

    Three hyperbaric oxygen sessions within 24 hours versus normobaric oxygen plus sham sessions

    limitations

    A randomised double-blind trial stopped early at a planned interim analysis, which tends to overstate effect size. Cerebellar dysfunction was imbalanced at baseline and was adjusted for.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human

    plain_language

    Fewer people had lasting thinking problems after the treatment.

    primary_references

    [hbot-p12362006] Hyperbaric oxygen for acute carbon monoxide poisoning. (2002). https://pubmed.ncbi.nlm.nih.gov/12362006/ DOI: 10.1056/nejmoa013121

    tissue_or_cell_type

    Brain

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 1063–1074

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind randomised trial of 152 patients with symptomatic acute carbon monoxide poisoning · source_derived_draft · unverified_draft

    ### hbot-co-cognitive-benefit Cognitive sequelae at six weeks occurred in 25.0% of the hyperbaric group versus 46.1% of the normobaric group, an adjusted odds ratio of 0.45, and the difference persisted at 12 months. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Fewer people had lasting thinking problems after the treatment. organism: Human tissue_or_cell_type: Brain experimental_model: Double-blind randomised trial of 152 patients with symptomatic acute carbon monoxide poisoning limitations: A randomised double-blind trial stopped early at a planned interim analysis, which tends to overstate effect size. Cerebellar dysfunction was imbalanced at baseline and was adjusted for. exposure: Three hyperbaric oxygen sessions within 24 hours versus normobaric oxygen plus sham sessions evidence_span: {"source_cache": "artifacts/hbot-research/12362006.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f1d5366f5eb1704ebe411ee13fba05068a310070c87ae65c8c75df678655dcca", "start_char": 0, "end_char": 1966, "text_sha256": "f1d5366f5eb1704ebe411ee13fba05068a310070c87ae65c8c75df678655dcca"} [hbot-p12362006] Hyperbaric oxygen for acute carbon monoxide poisoning. (2002). https://pubmed.ncbi.nlm.nih.gov/12362006/ DOI: 10.1056/nejmoa013121

    Complete structured claim and evidence

79. Carbon monoxide-mediated oxidative stress causes chemical alterations in myelin basic protein, which initiates an adaptive immunological response leading to a functional deficit, and poisoned rats do not improve in a radial maze.

    Carbon monoxide → Myelin basic protein source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/16325878.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6e0360f0f818602bdcf74234be1b33779b854e82daadfdd69e78ad24eaa5953f", "start_char": 0, "end_char": 1115, "text_sha256": "6e0360f0f818602bdcf74234be1b33779b854e82daadfdd69e78ad24eaa5953f"}

    experimental_model

    Rat model of carbon monoxide poisoning with myelin basic protein chemistry, immunology and maze testing

    exposure

    Hyperbaric oxygen given after carbon monoxide poisoning

    limitations

    An immunological mechanism in a rat model. The treatment prevented the functional deficit without eliminating all the chemical changes, which is the informative dissociation.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Rat

    plain_language

    The gas changes a brain protein enough that the immune system starts attacking it.

    primary_references

    [hbot-p16325878] Hyperbaric oxygen reduces delayed immune-mediated neuropathology in experimental carbon monoxide toxicity. (2006). https://pubmed.ncbi.nlm.nih.gov/16325878/ DOI: 10.1016/j.taap.2005.10.006

    tissue_or_cell_type

    Brain and immune system

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 1076–1087

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat model of carbon monoxide poisoning with myelin basic protein chemistry, immunology and maze testing · source_derived_draft · unverified_draft

    ### hbot-mbp-immune-mechanism Carbon monoxide-mediated oxidative stress causes chemical alterations in myelin basic protein, which initiates an adaptive immunological response leading to a functional deficit, and poisoned rats do not improve in a radial maze. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The gas changes a brain protein enough that the immune system starts attacking it. organism: Rat tissue_or_cell_type: Brain and immune system experimental_model: Rat model of carbon monoxide poisoning with myelin basic protein chemistry, immunology and maze testing limitations: An immunological mechanism in a rat model. The treatment prevented the functional deficit without eliminating all the chemical changes, which is the informative dissociation. exposure: Hyperbaric oxygen given after carbon monoxide poisoning evidence_span: {"source_cache": "artifacts/hbot-research/16325878.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6e0360f0f818602bdcf74234be1b33779b854e82daadfdd69e78ad24eaa5953f", "start_char": 0, "end_char": 1115, "text_sha256": "6e0360f0f818602bdcf74234be1b33779b854e82daadfdd69e78ad24eaa5953f"} [hbot-p16325878] Hyperbaric oxygen reduces delayed immune-mediated neuropathology in experimental carbon monoxide toxicity. (2006). https://pubmed.ncbi.nlm.nih.gov/16325878/ DOI: 10.1016/j.taap.2005.10.006

    Complete structured claim and evidence

80. Treatment prevented the functional deficit without eliminating all the chemical alterations in myelin basic protein: the protein was recognised normally by a battery of antibodies but retained an abnormal charge pattern, lymphocytes did not become activated, microglial activation was not apparent, and functional deficits did not occur.

    Hyperbaric oxygen therapy → Microglial activation source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/16325878.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6e0360f0f818602bdcf74234be1b33779b854e82daadfdd69e78ad24eaa5953f", "start_char": 0, "end_char": 1115, "text_sha256": "6e0360f0f818602bdcf74234be1b33779b854e82daadfdd69e78ad24eaa5953f"}

    experimental_model

    Rat model of carbon monoxide poisoning with myelin basic protein chemistry, immunology and maze testing

    exposure

    Hyperbaric oxygen given after carbon monoxide poisoning

    limitations

    An immunological mechanism in a rat model. The treatment prevented the functional deficit without eliminating all the chemical changes, which is the informative dissociation.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Rat

    plain_language

    The protein was still chemically altered, yet the immune attack and the disability did not follow.

    primary_references

    [hbot-p16325878] Hyperbaric oxygen reduces delayed immune-mediated neuropathology in experimental carbon monoxide toxicity. (2006). https://pubmed.ncbi.nlm.nih.gov/16325878/ DOI: 10.1016/j.taap.2005.10.006

    tissue_or_cell_type

    Brain and immune system

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 1089–1100

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat model of carbon monoxide poisoning with myelin basic protein chemistry, immunology and maze testing · source_derived_draft · unverified_draft

    ### hbot-hbo-prevents-immune-deficit Treatment prevented the functional deficit without eliminating all the chemical alterations in myelin basic protein: the protein was recognised normally by a battery of antibodies but retained an abnormal charge pattern, lymphocytes did not become activated, microglial activation was not apparent, and functional deficits did not occur. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The protein was still chemically altered, yet the immune attack and the disability did not follow. organism: Rat tissue_or_cell_type: Brain and immune system experimental_model: Rat model of carbon monoxide poisoning with myelin basic protein chemistry, immunology and maze testing limitations: An immunological mechanism in a rat model. The treatment prevented the functional deficit without eliminating all the chemical changes, which is the informative dissociation. exposure: Hyperbaric oxygen given after carbon monoxide poisoning evidence_span: {"source_cache": "artifacts/hbot-research/16325878.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6e0360f0f818602bdcf74234be1b33779b854e82daadfdd69e78ad24eaa5953f", "start_char": 0, "end_char": 1115, "text_sha256": "6e0360f0f818602bdcf74234be1b33779b854e82daadfdd69e78ad24eaa5953f"} [hbot-p16325878] Hyperbaric oxygen reduces delayed immune-mediated neuropathology in experimental carbon monoxide toxicity. (2006). https://pubmed.ncbi.nlm.nih.gov/16325878/ DOI: 10.1016/j.taap.2005.10.006

    Complete structured claim and evidence

81. Mean SOMA-LENT score improvement was nearly twice as large in the treated group (5.00 versus 2.61), with more responders per clinical assessment (88.9% versus 62.5%) and an absolute risk reduction of 32%, and the differences were abolished after crossover.

    Hyperbaric oxygen therapy → Refractory radiation proctitis severity by SOMA-LENT score source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/18342453.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e54a071083cc14d5dcb6461692588b064f94d560a91045313836b0dca18cfe85", "start_char": 0, "end_char": 1963, "text_sha256": "e54a071083cc14d5dcb6461692588b064f94d560a91045313836b0dca18cfe85"}

    experimental_model

    Randomised controlled double-blind crossover trial of 150 patients with refractory radiation proctitis

    exposure

    2.0 atmospheres absolute versus air at 1.1 atmospheres absolute, with crossover

    limitations

    A double-blind crossover trial with a sham arm and five-year follow-up. The crossover abolished the between-group difference, which is consistent with a real treatment effect.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human

    plain_language

    Most treated people improved, and the sham group improved too once they crossed over.

    primary_references

    [hbot-p18342453] Hyperbaric oxygen treatment of chronic refractory radiation proctitis: a randomized and controlled double-blind crossover trial with long-term follow-up. (2008). https://pubmed.ncbi.nlm.nih.gov/18342453/ DOI: 10.1016/j.ijrobp.2007.12.048

    tissue_or_cell_type

    Rectal mucosa

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 1102–1113

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomised controlled double-blind crossover trial of 150 patients with refractory radiation proctitis · source_derived_draft · unverified_draft

    ### hbot-radiation-proctitis-improvement Mean SOMA-LENT score improvement was nearly twice as large in the treated group (5.00 versus 2.61), with more responders per clinical assessment (88.9% versus 62.5%) and an absolute risk reduction of 32%, and the differences were abolished after crossover. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Most treated people improved, and the sham group improved too once they crossed over. organism: Human tissue_or_cell_type: Rectal mucosa experimental_model: Randomised controlled double-blind crossover trial of 150 patients with refractory radiation proctitis limitations: A double-blind crossover trial with a sham arm and five-year follow-up. The crossover abolished the between-group difference, which is consistent with a real treatment effect. exposure: 2.0 atmospheres absolute versus air at 1.1 atmospheres absolute, with crossover evidence_span: {"source_cache": "artifacts/hbot-research/18342453.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e54a071083cc14d5dcb6461692588b064f94d560a91045313836b0dca18cfe85", "start_char": 0, "end_char": 1963, "text_sha256": "e54a071083cc14d5dcb6461692588b064f94d560a91045313836b0dca18cfe85"} [hbot-p18342453] Hyperbaric oxygen treatment of chronic refractory radiation proctitis: a randomized and controlled double-blind crossover trial with long-term follow-up. (2008). https://pubmed.ncbi.nlm.nih.gov/18342453/ DOI: 10.1016/j.ijrobp.2007.12.048

    Complete structured claim and evidence

82. Telomere length of T helper, T cytotoxic, natural killer and B cells increased by over 20% after 60 sessions, with B cells rising 37.63% after the course.

    Hyperbaric oxygen therapy → Telomere length in peripheral blood mononuclear cells source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/33206062.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3ac16eb39be25c350e6a42fff6ee8cbf22159514a750bc3c7bafcbf734f03ecf", "start_char": 0, "end_char": 1622, "text_sha256": "3ac16eb39be25c350e6a42fff6ee8cbf22159514a750bc3c7bafcbf734f03ecf"}

    experimental_model

    Prospective trial of 35 healthy independently living adults aged 64 and over

    exposure

    Sixty daily hyperbaric oxygen exposures, sampled at baseline, 30 and 60 sessions and after the course

    limitations

    A single-arm prospective trial without a control group, in a normal ageing population. Telomere length and senescent-cell percentage are cell measurements, not health outcomes.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human

    plain_language

    A marker of cell ageing moved in the opposite direction to ageing.

    primary_references

    [hbot-p33206062] Hyperbaric oxygen therapy increases telomere length and decreases immunosenescence in isolated blood cells: a prospective trial. (2020). https://pubmed.ncbi.nlm.nih.gov/33206062/ DOI: 10.18632/aging.202188

    tissue_or_cell_type

    Peripheral blood mononuclear cells

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 1115–1126

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Prospective trial of 35 healthy independently living adults aged 64 and over · source_derived_draft · unverified_draft

    ### hbot-telomere-lengthening Telomere length of T helper, T cytotoxic, natural killer and B cells increased by over 20% after 60 sessions, with B cells rising 37.63% after the course. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: A marker of cell ageing moved in the opposite direction to ageing. organism: Human tissue_or_cell_type: Peripheral blood mononuclear cells experimental_model: Prospective trial of 35 healthy independently living adults aged 64 and over limitations: A single-arm prospective trial without a control group, in a normal ageing population. Telomere length and senescent-cell percentage are cell measurements, not health outcomes. exposure: Sixty daily hyperbaric oxygen exposures, sampled at baseline, 30 and 60 sessions and after the course evidence_span: {"source_cache": "artifacts/hbot-research/33206062.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3ac16eb39be25c350e6a42fff6ee8cbf22159514a750bc3c7bafcbf734f03ecf", "start_char": 0, "end_char": 1622, "text_sha256": "3ac16eb39be25c350e6a42fff6ee8cbf22159514a750bc3c7bafcbf734f03ecf"} [hbot-p33206062] Hyperbaric oxygen therapy increases telomere length and decreases immunosenescence in isolated blood cells: a prospective trial. (2020). https://pubmed.ncbi.nlm.nih.gov/33206062/ DOI: 10.18632/aging.202188

    Complete structured claim and evidence

83. Senescent T helper cells fell by 37.30% and senescent T cytotoxic cells by 10.96% after the course.

    Hyperbaric oxygen therapy → Senescent T helper and T cytotoxic cells source_derived_draftungraded
    Experimental context and source evidence

    evidence_span

    {"source_cache": "artifacts/hbot-research/33206062.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3ac16eb39be25c350e6a42fff6ee8cbf22159514a750bc3c7bafcbf734f03ecf", "start_char": 0, "end_char": 1622, "text_sha256": "3ac16eb39be25c350e6a42fff6ee8cbf22159514a750bc3c7bafcbf734f03ecf"}

    experimental_model

    Prospective trial of 35 healthy independently living adults aged 64 and over

    exposure

    Sixty daily hyperbaric oxygen exposures, sampled at baseline, 30 and 60 sessions and after the course

    limitations

    A single-arm prospective trial without a control group, in a normal ageing population. Telomere length and senescent-cell percentage are cell measurements, not health outcomes.

    nutrient_topic

    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

    organism

    Human

    plain_language

    Fewer worn-out immune cells were left in circulation.

    primary_references

    [hbot-p33206062] Hyperbaric oxygen therapy increases telomere length and decreases immunosenescence in isolated blood cells: a prospective trial. (2020). https://pubmed.ncbi.nlm.nih.gov/33206062/ DOI: 10.18632/aging.202188

    tissue_or_cell_type

    Peripheral blood mononuclear cells

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 1128–1139

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Prospective trial of 35 healthy independently living adults aged 64 and over · source_derived_draft · unverified_draft

    ### hbot-senescent-cell-clearance Senescent T helper cells fell by 37.30% and senescent T cytotoxic cells by 10.96% after the course. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Fewer worn-out immune cells were left in circulation. organism: Human tissue_or_cell_type: Peripheral blood mononuclear cells experimental_model: Prospective trial of 35 healthy independently living adults aged 64 and over limitations: A single-arm prospective trial without a control group, in a normal ageing population. Telomere length and senescent-cell percentage are cell measurements, not health outcomes. exposure: Sixty daily hyperbaric oxygen exposures, sampled at baseline, 30 and 60 sessions and after the course evidence_span: {"source_cache": "artifacts/hbot-research/33206062.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3ac16eb39be25c350e6a42fff6ee8cbf22159514a750bc3c7bafcbf734f03ecf", "start_char": 0, "end_char": 1622, "text_sha256": "3ac16eb39be25c350e6a42fff6ee8cbf22159514a750bc3c7bafcbf734f03ecf"} [hbot-p33206062] Hyperbaric oxygen therapy increases telomere length and decreases immunosenescence in isolated blood cells: a prospective trial. (2020). https://pubmed.ncbi.nlm.nih.gov/33206062/ DOI: 10.18632/aging.202188

    Complete structured claim and evidence

• Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source

• Does hyperbaric oxygen help a diabetic foot ulcer, or not?A randomised study of severe prevalently ischaemic ulcers found major amputation cut from 33% to 9%, while a propensity-adjusted cohort of 6259 people in routine wound care found treated people less likely to heal and more likely to lose a limb. The populations differ sharply: the trial selected severe ischaemic ulcers with an aggressive inpatient protocol, the cohort covered anyone meeting reimbursement criteria. Observational treatment selection by severity pushes in the direction the cohort found, and the trial is small and single-centre. Neither study measured the other population, and the reason for the difference is not established here.Read the recorded disagreement

• Whether the fall in erythrocyte superoxide dismutase and catalase activity across a course of hyperbaric oxygen reflects oxidative inactivation of the enzymes, consumption, or a regulatory decrease.The human series that measured the fall states this was still under investigation, and no record here distinguishes the three.
• Whether selenium, copper, zinc or manganese status changes the size of the adaptive response to hyperbaric oxygen.The enzyme chemistry establishes that these metals are required for the enzymes involved; no record here varies a nutrient and measures the hyperbaric response.
• Whether hyperbaric oxygen changes collagen hydroxylation in a wound by supplying the oxygen cosubstrate of prolyl 4-hydroxylase, as the shared cosubstrate would allow.The enzymology and the wound studies are separate records here. No study in this collection measured hydroxyproline or prolyl 4-hydroxylase activity during hyperbaric oxygen treatment.
• Whether raising oxygen accelerates PHD2-catalysed destruction of HIF-1alpha, given that oxygen is the enzyme’s cosubstrate, while hyperbaric oxygen is reported to stabilise HIF-1alpha by a non-canonical route.The two records point in opposite directions and were made in different systems. No record here measures PHD2 activity during hyperbaric oxygen exposure.
• Whether ascorbate status changes the HIF-1 response to hyperbaric oxygen, since ascorbate stimulates the hydroxylases that destroy HIF-1alpha.The ascorbate and hyperbaric records were produced independently; no record here varies vitamin C and measures the hyperbaric response.

Chapters are assembled from supplied drafts and curated literature summaries. Statements remain unverified against the primary studies, and the ledger is not medical advice.