HIF-1 alpha

evidence_span

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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

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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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

evidence_span

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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

evidence_access

Primary full text

experimental_model

Human and mouse PDAC model program; human-cell HIF1A/CA9 manipulations.

limitations

CA9 is a mediator in the tested models, not a universal aspartate transporter.

nutrient_topic

L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate

plain_language

An oxygen-response program increased an alternative nutrient-acquisition route.

primary_references

Adaptive stimulation of macropinocytosis overcomes aspartate limitation in cancer cells under hypoxia. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35726024/ · DOI 10.1038/s42255-022-00583-z

L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 266–272

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human and mouse PDAC model program; human-cell HIF1A/CA9 manipulations. · source_derived_draft · unverified_draft

## l-aspartate-hypoxia-hif-ca9 An oxygen-response program increased an alternative nutrient-acquisition route. Genetic and pharmacological experiments linked hypoxia-enhanced macropinocytosis to HIF1A and its target CA9 in KRAS-mutant PDAC models. Model: Human and mouse PDAC model program; human-cell HIF1A/CA9 manipulations. Limitations: CA9 is a mediator in the tested models, not a universal aspartate transporter. Evidence access: Primary full text Adaptive stimulation of macropinocytosis overcomes aspartate limitation in cancer cells under hypoxia. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35726024/ · DOI 10.1038/s42255-022-00583-z

evidence_access

Primary full text

experimental_model

Human endothelial cultures; sodium-metasilicate-derived preparation.

limitations

Expression association does not establish direct activation or clinical angiogenesis.

nutrient_topic

Silica collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Silica and soluble silicon

plain_language

A distinct vascular regulator changed after exposure.

primary_references

Ionic silicon improves endothelial cells' survival under toxic oxidative stress by overexpressing angiogenic markers and antioxidant enzymes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30062712/ · DOI 10.1002/term.2744

Silica: soluble silicon, cellular transport and particle-specific mechanisms (2026-09-19) · lines 528–534

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human endothelial cultures; sodium-metasilicate-derived preparation. · source_derived_draft · unverified_draft

## silica-endothelial-marker-hif1a A distinct vascular regulator changed after exposure. The 0.5 mM silicon preparation increased HIF1A expression in HUVECs with or without the tested peroxide challenge. Model: Human endothelial cultures; sodium-metasilicate-derived preparation. Limitations: Expression association does not establish direct activation or clinical angiogenesis. Evidence access: Primary full text Ionic silicon improves endothelial cells' survival under toxic oxidative stress by overexpressing angiogenic markers and antioxidant enzymes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30062712/ · DOI 10.1002/term.2744

evidence_access

Primary abstract

experimental_model

Human endothelial cells; released silicon in the ppm range.

limitations

Accessed abstract does not establish direct inhibitor binding; HIF PHD2 differs from collagen prolyl hydroxylase.

nutrient_topic

Silica collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Silica and soluble silicon

plain_language

A biomaterial study implicated oxygen-sensing machinery.

primary_references

Promoting angiogenesis with mesoporous microcarriers through a synergistic action of delivered silicon ion and VEGF. · 2017 · https://pubmed.ncbi.nlm.nih.gov/27918936/ · DOI 10.1016/j.biomaterials.2016.11.053

Silica: soluble silicon, cellular transport and particle-specific mechanisms (2026-09-19) · lines 272–278

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human endothelial cells; released silicon in the ppm range. · source_derived_draft · unverified_draft

## silica-microcarrier-hif A biomaterial study implicated oxygen-sensing machinery. Silicon-releasing microcarriers increased HIF1A expression and stabilization, attributed to reduced PHD2 activity in HUVECs. Model: Human endothelial cells; released silicon in the ppm range. Limitations: Accessed abstract does not establish direct inhibitor binding; HIF PHD2 differs from collagen prolyl hydroxylase. Evidence access: Primary abstract Promoting angiogenesis with mesoporous microcarriers through a synergistic action of delivered silicon ion and VEGF. · 2017 · https://pubmed.ncbi.nlm.nih.gov/27918936/ · DOI 10.1016/j.biomaterials.2016.11.053

evidence_span

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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

evidence_access

Primary abstract

experimental_model

Human cell experiments with beta-oxidation inhibition.

limitations

Pharmacological inhibition has limitations; the complementary purified-PHD2 assay supports a separate mechanism.

nutrient_topic

Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate

plain_language

Fuel burning was not the only way it influenced HIF.

primary_references

Microbiota-derived butyrate is an endogenous HIF prolyl hydroxylase inhibitor. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34190032/ · DOI 10.1080/19490976.2021.1938380

Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 254–260

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human cell experiments with beta-oxidation inhibition. · source_derived_draft · unverified_draft

## butyrate-hif-without-oxidation Fuel burning was not the only way it influenced HIF. Butyrate still stabilized HIF in human epithelial-cell experiments when its beta-oxidation and associated oxygen consumption were inhibited. Model: Human cell experiments with beta-oxidation inhibition. Limitations: Pharmacological inhibition has limitations; the complementary purified-PHD2 assay supports a separate mechanism. Evidence access: Primary abstract Microbiota-derived butyrate is an endogenous HIF prolyl hydroxylase inhibitor. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34190032/ · DOI 10.1080/19490976.2021.1938380

evidence_access

Primary abstract

experimental_model

Human intestinal epithelial cultures, with separate mouse depletion/repletion experiments.

limitations

HIF stabilization has more than one possible route; this result does not exclude direct hydroxylase inhibition.

nutrient_topic

Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate

plain_language

Using the fuel changed local oxygen sensing.

primary_references

Crosstalk between Microbiota-Derived Short-Chain Fatty Acids and Intestinal Epithelial HIF Augments Tissue Barrier Function. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25865369/ · DOI 10.1016/j.chom.2015.03.005

Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 238–244

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human intestinal epithelial cultures, with separate mouse depletion/repletion experiments. · source_derived_draft · unverified_draft

## butyrate-oxygen-hif Using the fuel changed local oxygen sensing. Butyrate increased epithelial oxygen consumption and stabilized HIF in intestinal epithelial-cell experiments. Model: Human intestinal epithelial cultures, with separate mouse depletion/repletion experiments. Limitations: HIF stabilization has more than one possible route; this result does not exclude direct hydroxylase inhibition. Evidence access: Primary abstract Crosstalk between Microbiota-Derived Short-Chain Fatty Acids and Intestinal Epithelial HIF Augments Tissue Barrier Function. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25865369/ · DOI 10.1016/j.chom.2015.03.005

evidence_access

Primary full text, recombinant methods and enzyme kinetics

experimental_model

Human PHD2 residues 181–402; NMR and enzymatic assays.

limitations

Millimolar assay exposure is relevant to local gut questions, not evidence of inhibition throughout the body at normal blood levels.

nutrient_topic

Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate

plain_language

It also directly affected an enzyme that normally marks HIF for degradation.

primary_references

Microbiota-derived butyrate is an endogenous HIF prolyl hydroxylase inhibitor. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34190032/ · DOI 10.1080/19490976.2021.1938380

Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 246–252

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human PHD2 residues 181–402; NMR and enzymatic assays. · source_derived_draft · unverified_draft

## butyrate-phd2-inhibition It also directly affected an enzyme that normally marks HIF for degradation. Butyrate bound and inhibited a recombinant human PHD2 catalytic fragment; kinetic analysis gave a noncompetitive Ki of 5.3 ± 0.5 mM relative to 2-oxoglutarate. Model: Human PHD2 residues 181–402; NMR and enzymatic assays. Limitations: Millimolar assay exposure is relevant to local gut questions, not evidence of inhibition throughout the body at normal blood levels. Evidence access: Primary full text, recombinant methods and enzyme kinetics Microbiota-derived butyrate is an endogenous HIF prolyl hydroxylase inhibitor. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34190032/ · DOI 10.1080/19490976.2021.1938380

evidence_span

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experimental_model

Histone modification profiling and genome-wide transcriptome of trained human monocytes, with pathway inhibition and a myeloid conditional knockout

exposure

Beta-glucan training with inhibition of Akt, mTOR or HIF-1 alpha, and metformin as an AMPK activator

limitations

The metformin result is an experimental inhibition of an induced response, not a clinical interaction study.

nutrient_topic

Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. · Beta-glucan

organism

Human cells and mouse

plain_language

The rewiring costs energy: block the cell from burning glucose the fast way and the training does not take.

primary_references

[bg-p25258083] mTOR- and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity. (2014). https://pubmed.ncbi.nlm.nih.gov/25258083/ DOI: 10.1126/science.1250684

tissue_or_cell_type

Monocyte

Beta-glucan: a structural family rather than an agent, what decides whether a bound glucan actually signals, the complement route that a cereal and a yeast preparation share, and the unequal human evidence behind each (2026-09-22) · lines 437–448

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Histone modification profiling and genome-wide transcriptome of trained human monocytes, with pathway inhibition and a myeloid conditional knockout · source_derived_draft · unverified_draft

### bg-training-needs-aerobic-glycolysis Trained monocytes display high glucose consumption, high lactate production and a high ratio of NAD+ to NADH, reflecting a shift in metabolism with an increase in glycolysis dependent on the activation of mammalian target of rapamycin through a dectin-1-Akt-HIF-1 alpha pathway, inhibition of Akt, mTOR or HIF-1 alpha blocked monocyte induction of trained immunity whereas the AMP-activated protein kinase activator metformin inhibited the innate immune response to fungal infection, and mice with a myeloid cell-specific defect in HIF-1 alpha were unable to mount trained immunity against bacterial sepsis. Condition category: normal nutrient_topic: Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. plain_language: The rewiring costs energy: block the cell from burning glucose the fast way and the training does not take. organism: Human cells and mouse tissue_or_cell_type: Monocyte experimental_model: Histone modification profiling and genome-wide transcriptome of trained human monocytes, with pathway inhibition and a myeloid conditional knockout limitations: The metformin result is an experimental inhibition of an induced response, not a clinical interaction study. exposure: Beta-glucan training with inhibition of Akt, mTOR or HIF-1 alpha, and metformin as an AMPK activator evidence_span: {"source_cache": "artifacts/glucan-research/25258083.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "68c4cae9a0e4477a52864e63ecaf5ec977752b5d3246a9ba54aa22d160e41872", "start_char": 0, "end_char": 1225, "text_sha256": "68c4cae9a0e4477a52864e63ecaf5ec977752b5d3246a9ba54aa22d160e41872"} [bg-p25258083] mTOR- and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity. (2014). https://pubmed.ncbi.nlm.nih.gov/25258083/ DOI: 10.1126/science.1250684

evidence_access

Primary abstract

experimental_model

Human HUVECs; engineered local-release formulation.

limitations

Not evidence of oral silica/VEGF supplementation or a universal synergy.

nutrient_topic

Silica collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Silica and soluble silicon

plain_language

A tested growth-factor combination promoted vascular-cell behavior.

primary_references

Promoting angiogenesis with mesoporous microcarriers through a synergistic action of delivered silicon ion and VEGF. · 2017 · https://pubmed.ncbi.nlm.nih.gov/27918936/ · DOI 10.1016/j.biomaterials.2016.11.053

Silica: soluble silicon, cellular transport and particle-specific mechanisms (2026-09-19) · lines 280–286

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human HUVECs; engineered local-release formulation. · source_derived_draft · unverified_draft

## silica-microcarrier-vegf A tested growth-factor combination promoted vascular-cell behavior. Microcarriers releasing silicon and loaded VEGF increased endothelial migration and tubular networking. Model: Human HUVECs; engineered local-release formulation. Limitations: Not evidence of oral silica/VEGF supplementation or a universal synergy. Evidence access: Primary abstract Promoting angiogenesis with mesoporous microcarriers through a synergistic action of delivered silicon ion and VEGF. · 2017 · https://pubmed.ncbi.nlm.nih.gov/27918936/ · DOI 10.1016/j.biomaterials.2016.11.053

evidence_span

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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

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

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

evidence_span

{"source_cache": "artifacts/metformin-research/24843020.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "21403805272b0d702f0f60887d805b1e52b4ce87a9335fcde1d34cefda8b16ae", "start_char": 0, "end_char": 1142, "text_sha256": "21403805272b0d702f0f60887d805b1e52b4ce87a9335fcde1d34cefda8b16ae"}

experimental_model

Human cancer cells and mouse xenografts with the metformin-resistant yeast NDI1 as a genetic rescue

exposure

Metformin in the presence and absence of glucose; NDI1 overexpression

limitations

Cancer-cell concentrations are far above therapeutic plasma levels. The NDI1 rescue is strong evidence that the effects run through complex I in this model, not evidence of an antitumour indication.

nutrient_topic

Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin

organism

Human cells; mouse in vivo

plain_language

Slowing the chain also changed how the cell reads low oxygen.

primary_references

[metformin-p24843020] Metformin inhibits mitochondrial complex I of cancer cells to reduce tumorigenesis. (2014). https://pubmed.ncbi.nlm.nih.gov/24843020/ DOI: 10.7554/elife.02242

tissue_or_cell_type

Cancer cells and tumours

Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 424–435

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human cancer cells and mouse xenografts with the metformin-resistant yeast NDI1 as a genetic rescue · source_derived_draft · unverified_draft

### metformin-hif1-reduction Metformin reduced hypoxic activation of hypoxia-inducible factor 1 in these cells. Condition category: normal nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: Slowing the chain also changed how the cell reads low oxygen. organism: Human cells; mouse in vivo tissue_or_cell_type: Cancer cells and tumours experimental_model: Human cancer cells and mouse xenografts with the metformin-resistant yeast NDI1 as a genetic rescue limitations: Cancer-cell concentrations are far above therapeutic plasma levels. The NDI1 rescue is strong evidence that the effects run through complex I in this model, not evidence of an antitumour indication. exposure: Metformin in the presence and absence of glucose; NDI1 overexpression evidence_span: {"source_cache": "artifacts/metformin-research/24843020.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "21403805272b0d702f0f60887d805b1e52b4ce87a9335fcde1d34cefda8b16ae", "start_char": 0, "end_char": 1142, "text_sha256": "21403805272b0d702f0f60887d805b1e52b4ce87a9335fcde1d34cefda8b16ae"} [metformin-p24843020] Metformin inhibits mitochondrial complex I of cancer cells to reduce tumorigenesis. (2014). https://pubmed.ncbi.nlm.nih.gov/24843020/ DOI: 10.7554/elife.02242

evidence_span

{"source_cache": "artifacts/dihydrocapsaicin-research/32107104.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a00c09c7443e15a674b7e9c6451ddd60a161f69ff98e33c32bcce0039662f8b1", "start_char": 0, "end_char": 1350, "text_sha256": "a00c09c7443e15a674b7e9c6451ddd60a161f69ff98e33c32bcce0039662f8b1"}

experimental_model

Fourteen-day outcome study after middle cerebral artery occlusion in rats with BrdU labelling

exposure

Dihydrocapsaicin at 10 mg/kg body weight after 2 hours of occlusion

limitations

The dose here is roughly an order of magnitude above the hypothermia studies and no temperature is reported, so this may not be a hypothermic effect at all. Recorded with that stated.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Rat

plain_language

At a much larger dose it made new blood vessels grow into the damaged area over two weeks.

primary_references

[dhc-p32107104] Dihydrocapsaicin-induced angiogenesis and improved functional recovery after cerebral ischemia and reperfusion in a rat model. (2020). https://pubmed.ncbi.nlm.nih.gov/32107104/ DOI: 10.1016/j.jphs.2020.02.001

tissue_or_cell_type

Brain vasculature

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 465–476

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Fourteen-day outcome study after middle cerebral artery occlusion in rats with BrdU labelling · source_derived_draft · unverified_draft

### dhc-angiogenesis-at-high-dose Dihydrocapsaicin at 10 mg/kg increased the expression of hypoxia inducible factor 1 alpha, vascular endothelial growth factor and matrix metalloprotease 9 at 3 and 14 days after ischaemia-reperfusion and of angiopoietin 1 and its receptor Tie-2 at 14 days, with angiogenesis confirmed by BrdU labelling co-localised with von Willebrand factor, alongside decreased neurological deficit scores and infarct volume and improved rotarod and pole test performance. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: At a much larger dose it made new blood vessels grow into the damaged area over two weeks. organism: Rat tissue_or_cell_type: Brain vasculature experimental_model: Fourteen-day outcome study after middle cerebral artery occlusion in rats with BrdU labelling limitations: The dose here is roughly an order of magnitude above the hypothermia studies and no temperature is reported, so this may not be a hypothermic effect at all. Recorded with that stated. exposure: Dihydrocapsaicin at 10 mg/kg body weight after 2 hours of occlusion evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/32107104.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a00c09c7443e15a674b7e9c6451ddd60a161f69ff98e33c32bcce0039662f8b1", "start_char": 0, "end_char": 1350, "text_sha256": "a00c09c7443e15a674b7e9c6451ddd60a161f69ff98e33c32bcce0039662f8b1"} [dhc-p32107104] Dihydrocapsaicin-induced angiogenesis and improved functional recovery after cerebral ischemia and reperfusion in a rat model. (2020). https://pubmed.ncbi.nlm.nih.gov/32107104/ DOI: 10.1016/j.jphs.2020.02.001

cross_nutrient

true

evidence_location

Primary abstract rate/extent and substrate comparisons

experimental_model

Purified enzyme with human HIF-1 alpha-derived peptide substrate

exposure

Ascorbate versus omission/alternative reducing agents; exact concentrations and enzyme constructs not recovered from primary abstract.

limitations

Peptide hydroxylation does not directly establish HIF degradation or transcription changes in intact cells; ankyrin probe is not physiological HIF.

nutrient_topic

Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C

organism

Human HIF-1 alpha substrate; purified recombinant hydroxylase

plain_language

Vitamin C also supported a different HIF enzyme that modifies an asparagine site.

primary_references

[c-reg-flashman] 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

Cell-free

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1131–1143

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified enzyme with human HIF-1 alpha-derived peptide substrate · source_derived_draft · unverified_draft

### c-reg-fih-ascorbate Ascorbate increased the initial rate and extent of FIH-catalyzed asparaginyl hydroxylation of human HIF-1 alpha peptide; the study separately tested a consensus ankyrin-repeat peptide. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin C also supported a different HIF enzyme that modifies an asparagine site. organism: Human HIF-1 alpha substrate; purified recombinant hydroxylase tissue_or_cell_type: Cell-free experimental_model: Purified enzyme with human HIF-1 alpha-derived peptide substrate limitations: Peptide hydroxylation does not directly establish HIF degradation or transcription changes in intact cells; ankyrin probe is not physiological HIF. exposure: Ascorbate versus omission/alternative reducing agents; exact concentrations and enzyme constructs not recovered from primary abstract. cross_nutrient: true evidence_location: Primary abstract rate/extent and substrate comparisons [c-reg-flashman] 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

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

false

evidence_location

Figure 1B–C

experimental_model

HeLa adapted to serum-free Ham F-12; HIF immunoblot and luciferase reporter

exposure

0 versus 50 µM ascorbate; 0.2% versus 21% oxygen for 6-h protein assay, graded oxygen for 24-h reporter assay.

limitations

Cell-culture omission, not a controlled human dietary deficiency; residual adaptive reductant pathways were not eliminated.

nutrient_topic

Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C

organism

Homo sapiens

plain_language

Removing vitamin C from this adapted cancer-cell culture did not switch off its measured low-oxygen response.

primary_references

[c-reg-nytko] Vitamin C is dispensable for oxygen sensing in vivo. (2011). https://pubmed.ncbi.nlm.nih.gov/21346252/ DOI: 10.1182/blood-2010-09-307637

tissue_or_cell_type

Cervical carcinoma cells

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1173–1185

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · HeLa adapted to serum-free Ham F-12; HIF immunoblot and luciferase reporter · source_derived_draft · unverified_draft

### c-reg-hela-hypoxia-preserved HeLa cells maintained in serum-free, ascorbate-free defined medium retained hypoxic HIF-1 alpha stabilization and HIF-dependent reporter activation relative to cells supplied with 50 µM ascorbate. Condition category: nutrient_deficiency nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing vitamin C from this adapted cancer-cell culture did not switch off its measured low-oxygen response. organism: Homo sapiens tissue_or_cell_type: Cervical carcinoma cells experimental_model: HeLa adapted to serum-free Ham F-12; HIF immunoblot and luciferase reporter limitations: Cell-culture omission, not a controlled human dietary deficiency; residual adaptive reductant pathways were not eliminated. exposure: 0 versus 50 µM ascorbate; 0.2% versus 21% oxygen for 6-h protein assay, graded oxygen for 24-h reporter assay. cross_nutrient: false evidence_location: Figure 1B–C [c-reg-nytko] Vitamin C is dispensable for oxygen sensing in vivo. (2011). https://pubmed.ncbi.nlm.nih.gov/21346252/ DOI: 10.1182/blood-2010-09-307637

cross_nutrient

true

evidence_location

Primary abstract rate/extent and substrate comparisons

experimental_model

Purified enzyme with human HIF-1 alpha-derived peptide substrate

exposure

Ascorbate versus omission/alternative reducing agents; exact concentrations and enzyme constructs not recovered from primary abstract.

limitations

Peptide hydroxylation does not directly establish HIF degradation or transcription changes in intact cells; ankyrin probe is not physiological HIF.

nutrient_topic

Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C

organism

Human HIF-1 alpha substrate; purified recombinant hydroxylase

plain_language

Vitamin C increased the activity of an isolated oxygen-sensing proline hydroxylase.

primary_references

[c-reg-flashman] 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

Cell-free

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1117–1129

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified enzyme with human HIF-1 alpha-derived peptide substrate · source_derived_draft · unverified_draft

### c-reg-phd2-ascorbate Ascorbate increased the initial rate and extent of PHD2-catalyzed hydroxylation at both tested human HIF-1 alpha prolyl sites in purified-enzyme peptide experiments. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin C increased the activity of an isolated oxygen-sensing proline hydroxylase. organism: Human HIF-1 alpha substrate; purified recombinant hydroxylase tissue_or_cell_type: Cell-free experimental_model: Purified enzyme with human HIF-1 alpha-derived peptide substrate limitations: Peptide hydroxylation does not directly establish HIF degradation or transcription changes in intact cells; ankyrin probe is not physiological HIF. exposure: Ascorbate versus omission/alternative reducing agents; exact concentrations and enzyme constructs not recovered from primary abstract. cross_nutrient: true evidence_location: Primary abstract rate/extent and substrate comparisons [c-reg-flashman] 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