{"id":"1b4b49f1-846d-595f-889c-772cf0d1b9ef","stable_key":"488ea171-36b8-5ef6-b5d3-98563980fdbf:hbot-hif1-activation","predicate":"increases","statement":"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.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"58f3b716-d0ee-59b7-bf38-8747908a1015","mechanism_event_label":"More oxygen, not less, switched on the machinery that normally reads low oxygen.","subject":{"id":"581fa746-cb84-571b-87a0-4d461263f660","slug":"hyperbaric-oxygen","display_name":"Hyperbaric oxygen therapy","entity_type_key":"drug"},"object":{"id":"ac3b2cf2-17dd-586d-8622-c8866b70acf0","slug":"hif1a-protein-stability","display_name":"HIF-1alpha protein stability","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"58f3b716-d0ee-59b7-bf38-8747908a1015","stable_key":"488ea171-36b8-5ef6-b5d3-98563980fdbf:hbot-hif1-activation-event","event_type":"biochemical_relationship","label":"More oxygen, not less, switched on the machinery that normally reads low oxygen.","description":"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.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"b1207f94-96eb-5134-8055-cfd9881c106e","slug":"hif1-transcriptional-activity","display_name":"HIF-1 transcriptional activity","entity_type_key":"cellular_process"},"role":"downstream_process","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"581fa746-cb84-571b-87a0-4d461263f660","slug":"hyperbaric-oxygen","display_name":"Hyperbaric oxygen therapy","entity_type_key":"drug"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"ac3b2cf2-17dd-586d-8622-c8866b70acf0","slug":"hif1a-protein-stability","display_name":"HIF-1alpha protein stability","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"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\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human dermal fibroblasts, SKRC7 cells, HIF-1alpha knockout mouse embryonic fibroblasts, and db/db mice","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Hyperbaric oxygen in vitro and in vivo, with adenoviral stable HIF-1alpha delivery","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"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.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake.","comparator":null,"unit":null,"notes":"","entity":{"slug":"hyperbaric-oxygen","display_name":"Hyperbaric oxygen therapy","entity_type_key":"drug"}},{"dimension":"organism","value_text":"Human cells and mouse","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"More oxygen, not less, switched on the machinery that normally reads low oxygen.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[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","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Dermal fibroblasts and diabetic wounds","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"eaa1284a-52eb-50f7-bd9c-5cecd622b47c","evidence_kind":"source_excerpt","locator":"Lines 621-632","start_line":621,"end_line":632,"excerpt":"### hbot-hif1-activation\nHyperbaric 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.\nCondition category: normal\nnutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake.\nplain_language: More oxygen, not less, switched on the machinery that normally reads low oxygen.\norganism: Human cells and mouse\ntissue_or_cell_type: Dermal fibroblasts and diabetic wounds\nexperimental_model: Human dermal fibroblasts, SKRC7 cells, HIF-1alpha knockout mouse embryonic fibroblasts, and db/db mice\nlimitations: 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.\nexposure: Hyperbaric oxygen in vitro and in vivo, with adenoviral stable HIF-1alpha delivery\nevidence_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\"}\n[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","model_system":"Human dermal fibroblasts, SKRC7 cells, HIF-1alpha knockout mouse embryonic fibroblasts, and db/db mice","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study 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","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"dbf39b48-c95e-5291-b404-349ffbc4488f","stable_key":"import-488ea171-36b8-5ef6-b5d3-98563980fdbf","title":"Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"fb2443321804010d82c6b96ab61cc51b4b6628ddbb15751cb0e90b491606e79c","revision_id":"bb699ea5-b492-5728-b22c-48f0842a8ac9","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}