{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T17:34:00Z","timestamp":1792949640472,"version":"4.5.0"},"reference-count":92,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Natural Science Research Project of Bengbu Medical University","award":["2024byzd129"],"award-info":[{"award-number":["2024byzd129"]}]},{"name":"Health Research Project of Bengbu City","award":["BBWK2024C205"],"award-info":[{"award-number":["BBWK2024C205"]}]},{"name":"Medical Innovation Foundation from Spinal Deformity Clinical Medicine and Research Center of Anhui Province","award":["AHJZJX-GG2023-004"],"award-info":[{"award-number":["AHJZJX-GG2023-004"]}]},{"name":"Natural Science Research Project of Anhui Educational Committee","award":["2024AH051233"],"award-info":[{"award-number":["2024AH051233"]}]},{"name":"Natural Science Research Project of Anhui Educational Committee","award":["2025AHGXZK31546"],"award-info":[{"award-number":["2025AHGXZK31546"]}]},{"name":"Science Research Project of Anhui Health Commission","award":["AHWJ2023A30070"],"award-info":[{"award-number":["AHWJ2023A30070"]}]},{"name":"Clinical and Translational Research Project of Anhui Province","award":["202527c10020116"],"award-info":[{"award-number":["202527c10020116"]}]},{"name":"The \u201cChallenge and Response\u201d Scientific Research Project of Bengbu Medical College","award":["2025byjbgs036"],"award-info":[{"award-number":["2025byjbgs036"]}],"id":[{"id":"https:\/\/ror.org\/01f8qvj05","id-type":"ROR","asserted-by":"crossref"}]},{"name":"The Excellent Scientific Research and Innovation team in Colleges and Universities of Anhui Province","award":["2024AH010020"],"award-info":[{"award-number":["2024AH010020"]}]},{"name":"Graduate Student Scientific Research Innovation Program","award":["(Byycx24089)"],"award-info":[{"award-number":["(Byycx24089)"]}]},{"name":"Bengbu City Youth Project","award":["BB25C060"],"award-info":[{"award-number":["BB25C060"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Investigative Medicine"],"abstract":"<jats:p>\n                    Molecular hydrogen (H\n                    <jats:sub>2<\/jats:sub>\n                    ) has attracted increasing interest as a potential therapeutic agent because of its redox-modulating and anti-inflammatory properties. This review summarizes current evidence regarding its biological mechanisms, multisystem effects, and emerging delivery strategies. Experimental studies suggest that H\n                    <jats:sub>2<\/jats:sub>\n                    may attenuate oxidative injury and inflammatory signaling through both direct interactions with highly reactive species and indirect modulation of pathways involving nuclear factor erythroid 2\u2013related factor 2 (Nrf2), nuclear factor-\u03baB (NF-\u03baB), NLRP3, mitochondrial function, and immune regulation. Protective effects have been reported across cardiovascular, neurological, respiratory, digestive, renal, musculoskeletal, and metabolic disease models. However, the available evidence remains predominantly preclinical, whereas human studies are comparatively limited and heterogeneous. The optimal route of administration, dose, treatment duration, pharmacokinetic profile, and long-term safety and efficacy also remain insufficiently defined. Emerging delivery platforms may improve local retention and controlled release but remain largely experimental. Overall, molecular hydrogen represents a promising adjunctive therapeutic strategy, although further mechanistic validation and well-designed clinical studies are required before routine clinical application.\n                  <\/jats:p>","DOI":"10.1177\/10815589261497358","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:34:26Z","timestamp":1791434066000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular hydrogen in biomedicine: A comprehensive review of mechanisms, multi-system therapeutic effects, and emerging delivery strategies"],"prefix":"10.1177","author":[{"given":"Qiaoyu","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Orthopaedics, The First Affiliated Hospital of Bengbu Medical University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, The First Affiliated Hospital of Bengbu Medical University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yawei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, The First Affiliated Hospital of Bengbu Medical University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijie","family":"An","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, The First Affiliated Hospital of Bengbu Medical University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianzong","family":"Hang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, The First Affiliated Hospital of Bengbu Medical University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, The First Affiliated Hospital of Bengbu Medical University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, The First Affiliated Hospital of Bengbu Medical University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, The First Affiliated Hospital of Bengbu Medical University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Basic Teaching of General Practice, The Second Affiliated Hospital of Bengbu Medical University (The Second Clinical College of Bengbu Medical University), China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongqiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Geriatric Hospital of Nanjing Medical University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8359-6935","authenticated-orcid":false,"given":"Kun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, The First Affiliated Hospital of Bengbu Medical University, China"},{"name":"Institute of Digital and Intelligent Healthcare, Bengbu Medical University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"crossref","unstructured":"Fukuda K Asoh S Ishikawa M et al. Inhalation of hydrogen gas suppresses hepatic injury caused by ischemia\/reperfusion through reducing oxidative stress. Biochem Biophys Res Commun 2007; 361(3): 670\u2013674. https:\/\/doi.org\/10.1016\/j.bbrc.2007.07.088","DOI":"10.1016\/j.bbrc.2007.07.088"},{"key":"e_1_3_3_3_2","doi-asserted-by":"crossref","unstructured":"Ohta S. Recent progress toward hydrogen medicine: potential of molecular hydrogen for preventive and therapeutic applications. Curr Pharm Des 2011; 17(22): 2241\u20132252. https:\/\/doi.org\/10.2174\/138161211797052664","DOI":"10.2174\/138161211797052664"},{"key":"e_1_3_3_4_2","doi-asserted-by":"crossref","unstructured":"Satoh Y. The potential of hydrogen for improving mental disorders. Curr Pharm Des 2021; 27(5): 695\u2013702. https:\/\/doi.org\/10.2174\/1381612826666201113095938","DOI":"10.2174\/1381612826666201113095938"},{"key":"e_1_3_3_5_2","doi-asserted-by":"crossref","unstructured":"Hirano SI Ichikawa Y Sato B et al. Potential therapeutic applications of hydrogen in chronic inflammatory diseases: possible inhibiting role on mitochondrial stress. Int J Mol Sci 2021; 22(5): 1\u201312. https:\/\/doi.org\/10.3390\/ijms22052549","DOI":"10.3390\/ijms22052549"},{"key":"e_1_3_3_6_2","doi-asserted-by":"crossref","unstructured":"Chen JB Kong XF Qian W et al. Two weeks of hydrogen inhalation can significantly reverse adaptive and innate immune system senescence patients with advanced non-small cell lung cancer: a self-controlled study. Med Gas Res 2020; 10(4): 149\u2013154. https:\/\/doi.org\/10.4103\/2045-9912.304221","DOI":"10.4103\/2045-9912.304221"},{"key":"e_1_3_3_7_2","doi-asserted-by":"crossref","unstructured":"Zhang Y Ren X Zhang L et al. Hydrogen gas inhalation ameliorates LPS-induced BPD by inhibiting inflammation via regulating the TLR4-NF\u03baB-IL6\/NLRP3 signaling pathway in the placenta. Eur J Med Res 2024; 29(1): 285. https:\/\/doi.org\/10.1186\/s40001-024-01874-9","DOI":"10.1186\/s40001-024-01874-9"},{"key":"e_1_3_3_8_2","doi-asserted-by":"crossref","unstructured":"Tian Y Zhang Y Wang Y et al. Hydrogen a novel therapeutic molecule regulates oxidative stress inflammation and apoptosis. Front Physiol 2021; 12: 789507. https:\/\/doi.org\/10.3389\/fphys.2021.789507","DOI":"10.3389\/fphys.2021.789507"},{"key":"e_1_3_3_9_2","doi-asserted-by":"crossref","unstructured":"Zhang Y Zhang J Fu Z. Molecular hydrogen is a potential protective agent in the management of acute lung injury. Mol Med 2022; 28(1): 27. https:\/\/doi.org\/10.1186\/s10020-022-00455-y","DOI":"10.1186\/s10020-022-00455-y"},{"key":"e_1_3_3_10_2","doi-asserted-by":"crossref","unstructured":"Ohta S. Molecular hydrogen as a preventive and therapeutic medical gas: initiation development and potential of hydrogen medicine. Pharmacol Ther 2014; 144(1): 1\u201311. https:\/\/doi.org\/10.1016\/j.pharmthera.2014.04.006","DOI":"10.1016\/j.pharmthera.2014.04.006"},{"key":"e_1_3_3_11_2","doi-asserted-by":"crossref","unstructured":"Page MJ McKenzie JE Bossuyt PM et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. J Clin Epidemiol 2021; 134: 178\u2013189. https:\/\/doi.org\/10.1016\/j.jclinepi.2021.03.001","DOI":"10.1016\/j.jclinepi.2021.02.003"},{"key":"e_1_3_3_12_2","doi-asserted-by":"crossref","unstructured":"Page MJ McKenzie JE Bossuyt PM et al. Updating guidance for reporting systematic reviews: development of the PRISMA 2020 statement. J Clin Epidemiol 2021; 134: 103\u2013112. https:\/\/doi.org\/10.1016\/j.jclinepi.2021.02.003","DOI":"10.1016\/j.jclinepi.2021.02.003"},{"key":"e_1_3_3_13_2","doi-asserted-by":"crossref","unstructured":"Levitt MD. Production and excretion of hydrogen gas in man. N Engl J Med 1969; 281(3): 122\u2013127. https:\/\/doi.org\/10.1056\/nejm196907172810303","DOI":"10.1056\/NEJM196907172810303"},{"key":"e_1_3_3_14_2","doi-asserted-by":"crossref","unstructured":"Suzuki A Ito M Hamaguchi T et al. Quantification of hydrogen production by intestinal bacteria that are specifically dysregulated in Parkinson\u2019s disease. PLoS One 2018; 13(12): e0208313. https:\/\/doi.org\/10.1371\/journal.pone.0208313","DOI":"10.1371\/journal.pone.0208313"},{"key":"e_1_3_3_15_2","doi-asserted-by":"crossref","unstructured":"Tanaka Y Kiuchi M Higashimura Y et al. The effects of ingestion of hydrogen-dissolved alkaline electrolyzed water on stool consistency and gut microbiota: a double-blind randomized trial. Med Gas Res 2021; 11(4): 138\u2013144. https:\/\/doi.org\/10.4103\/2045-9912.318858","DOI":"10.4103\/2045-9912.318858"},{"key":"e_1_3_3_16_2","doi-asserted-by":"crossref","unstructured":"Ohta S. Molecular hydrogen is a novel antioxidant to efficiently reduce oxidative stress with potential for the improvement of mitochondrial diseases. Biochim Biophys Acta 2012; 1820(5): 586\u2013594. https:\/\/doi.org\/10.1016\/j.bbagen.2011.05.006","DOI":"10.1016\/j.bbagen.2011.05.006"},{"key":"e_1_3_3_17_2","doi-asserted-by":"crossref","unstructured":"Iketani M Ohsawa I. Molecular hydrogen as a neuroprotective agent. Curr Neuropharmacol 2017; 15(2): 324\u2013331. https:\/\/doi.org\/10.2174\/1570159x14666160607205417","DOI":"10.2174\/1570159X14666160607205417"},{"key":"e_1_3_3_18_2","doi-asserted-by":"crossref","unstructured":"Gentile MA. Inhaled medical gases: more to breathe than oxygen. Respir Care 2011; 56(9): 1341\u20131357; discussion 57\u201359. https:\/\/doi.org\/10.4187\/respcare.01442","DOI":"10.4187\/respcare.01442"},{"key":"e_1_3_3_19_2","doi-asserted-by":"crossref","unstructured":"Shi MM Chen YT Wang XD et al. The efficacy of hydrogen\/oxygen therapy favored the recovery of omicron SARS-CoV-2 variant infection: results of a multicenter randomized controlled trial. J Clin Biochem Nutr 2023; 73(3): 228\u2013233. https:\/\/doi.org\/10.3164\/jcbn.23-32","DOI":"10.3164\/jcbn.23-32"},{"key":"e_1_3_3_20_2","doi-asserted-by":"crossref","unstructured":"Li J Fang Z Xu S et al. The link between neutrophils NETs and NLRP3 inflammasomes: the dual effect of CD177 and its therapeutic potential in acute respiratory distress syndrome\/acute lung injury. Biomol Biomed 2024; 24(4): 798\u2013812. https:\/\/doi.org\/10.17305\/bb.2023.10101","DOI":"10.17305\/bb.2023.10101"},{"key":"e_1_3_3_21_2","doi-asserted-by":"crossref","unstructured":"Muramatsu Y Ito M Oshima T et al. Hydrogen-rich water ameliorates bronchopulmonary dysplasia (BPD) in newborn rats. Pediatr Pulmonol 2016; 51(9): 928\u2013935. https:\/\/doi.org\/10.1002\/ppul.23386","DOI":"10.1002\/ppul.23386"},{"key":"e_1_3_3_22_2","doi-asserted-by":"crossref","unstructured":"Park SA Joo NR Park JH et al. Role of the SIRT1\/p53 regulatory axis in oxidative stress-mediated granulosa cell apoptosis. Mol Med Rep 2021; 23(1): 20. https:\/\/doi.org\/10.3892\/mmr.2020.11658","DOI":"10.3892\/mmr.2020.11658"},{"key":"e_1_3_3_23_2","doi-asserted-by":"crossref","unstructured":"Zheng ZG Sun WZ Hu JY et al. Hydrogen\/oxygen therapy for the treatment of an acute exacerbation of chronic obstructive pulmonary disease: results of a multicenter randomized double-blind parallel-group controlled trial. Respir Res 2021; 22(1): 149. https:\/\/doi.org\/10.1186\/s12931-021-01740-w","DOI":"10.1186\/s12931-021-01740-w"},{"key":"e_1_3_3_24_2","doi-asserted-by":"crossref","unstructured":"Aokage T Seya M Hirayama T et al. The effects of inhaling hydrogen gas on macrophage polarization fibrosis and lung function in mice with bleomycin-induced lung injury. BMC Pulm Med 2021; 21(1): 339. https:\/\/doi.org\/10.1186\/s12890-021-01712-2","DOI":"10.1186\/s12890-021-01712-2"},{"key":"e_1_3_3_25_2","doi-asserted-by":"crossref","unstructured":"Li L Xu Z Ni H et al. Hydrogen-rich water alleviates asthma airway inflammation by modulating tryptophan metabolism and activating aryl hydrocarbon receptor via gut microbiota regulation. Free Radic Biol Med 2024; 224: 50\u201361. https:\/\/doi.org\/10.1016\/j.freeradbiomed.2024.08.009","DOI":"10.1016\/j.freeradbiomed.2024.08.009"},{"key":"e_1_3_3_26_2","doi-asserted-by":"crossref","unstructured":"Liu W Shan LP Dong XS et al. Combined early fluid resuscitation and hydrogen inhalation attenuates lung and intestine injury. World J Gastroenterol 2013; 19(4): 492\u2013502. https:\/\/doi.org\/10.3748\/wjg.v19.i4.492","DOI":"10.3748\/wjg.v19.i4.492"},{"key":"e_1_3_3_27_2","doi-asserted-by":"crossref","unstructured":"Liu Y Yang L Tao K et al. Protective effects of hydrogen enriched saline on liver ischemia reperfusion injury by reducing oxidative stress and HMGB1 release. BMC Gastroenterol 2014; 14: 12. https:\/\/doi.org\/10.1186\/1471-230x-14-12","DOI":"10.1186\/1471-230X-14-12"},{"key":"e_1_3_3_28_2","doi-asserted-by":"crossref","unstructured":"Li Y Li G Suo L et al. Recent advances in studies of molecular hydrogen in the treatment of pancreatitis. Life Sci 2021; 264: 118641. https:\/\/doi.org\/10.1016\/j.lfs.2020.118641","DOI":"10.1016\/j.lfs.2020.118641"},{"key":"e_1_3_3_29_2","doi-asserted-by":"crossref","unstructured":"Ge L Qi J Shao B et al. Microbial hydrogen economy alleviates colitis by reprogramming colonocyte metabolism and reinforcing intestinal barrier. Gut Microbes 2022; 14(1): 2013764. https:\/\/doi.org\/10.1080\/19490976.2021.2013764","DOI":"10.1080\/19490976.2021.2013764"},{"key":"e_1_3_3_30_2","doi-asserted-by":"crossref","unstructured":"Li SW Takahara T Que W et al. Hydrogen-rich water protects against liver injury in nonalcoholic steatohepatitis through HO-1 enhancement via IL-10 and Sirt 1 signaling. Am J Physiol Gastrointest Liver Physiol 2021; 320(4): G450\u2013G463. https:\/\/doi.org\/10.1152\/ajpgi.00158.2020","DOI":"10.1152\/ajpgi.00158.2020"},{"key":"e_1_3_3_31_2","doi-asserted-by":"crossref","unstructured":"Song L Zhang Y Zhu C et al. Hydrogen-rich water partially alleviate inflammation oxidative stress and intestinal flora dysbiosis in DSS-induced chronic ulcerative colitis mice. Adv Med Sci 2022; 67(1): 29\u201338. https:\/\/doi.org\/10.1016\/j.advms.2021.10.002","DOI":"10.1016\/j.advms.2021.10.002"},{"key":"e_1_3_3_32_2","doi-asserted-by":"crossref","unstructured":"Shen NY Bi JB Zhang JY et al. Hydrogen-rich water protects against in\ufb02ammatory bowel disease in mice by inhibiting endoplasmic reticulum stress and promoting heme oxygenase-1 expression. World J Gastroenterol 2017; 23(8): 1375\u20131386. https:\/\/doi.org\/10.3748\/wjg.v23.i8.1375","DOI":"10.3748\/wjg.v23.i8.1375"},{"key":"e_1_3_3_33_2","doi-asserted-by":"crossref","unstructured":"Peng J He Q Li S et al. Hydrogen-rich water mitigates LPS-induced chronic intestinal inflammatory response in rats via Nrf-2 and NF-\u03baB signaling pathways. Vet Sci 2022; 9(11): 621. https:\/\/doi.org\/10.3390\/vetsci9110621","DOI":"10.3390\/vetsci9110621"},{"key":"e_1_3_3_34_2","doi-asserted-by":"crossref","unstructured":"Wu F Su W Wang X et al. Hydrogen combined with needle-embedding therapy alleviates traumatic brain injury by inhibiting NLRP3 inflammasome activation via STING signaling pathway. Cytokine 2025; 190: 156931. https:\/\/doi.org\/10.1016\/j.cyto.2025.156931","DOI":"10.1016\/j.cyto.2025.156931"},{"key":"e_1_3_3_35_2","doi-asserted-by":"crossref","unstructured":"Yoritaka A Takanashi M Hirayama M et al. Pilot study of H2 therapy in Parkinson\u2019s disease: a randomized double-blind placebo-controlled trial. Mov Disord 2013; 28(6): 836\u2013839. https:\/\/doi.org\/10.1002\/mds.25375","DOI":"10.1002\/mds.25375"},{"key":"e_1_3_3_36_2","doi-asserted-by":"crossref","unstructured":"Sheinin M Mondal S Roy A et al. Suppression of experimental autoimmune encephalomyelitis in mice by \u03b2-hydroxy \u03b2-methylbutyrate a body-building supplement in humans. J Immunol 2023; 211(2): 187\u2013198. https:\/\/doi.org\/10.4049\/jimmunol.2200267","DOI":"10.4049\/jimmunol.2200267"},{"key":"e_1_3_3_37_2","doi-asserted-by":"crossref","unstructured":"Huang P Shen Z Liu J et al. Hydrogen sulfide inhibits high-salt diet-induced renal oxidative stress and kidney injury in Dahl rats. Oxid Med Cell Longev 2016; 2016: 2807490. https:\/\/doi.org\/10.1155\/2016\/2807490","DOI":"10.1155\/2016\/2807490"},{"key":"e_1_3_3_38_2","doi-asserted-by":"crossref","unstructured":"Xing Z Pan W Zhang J et al. Hydrogen rich water attenuates renal injury and fibrosis by regulation transforming growth factor-\u03b2 induced Sirt1. Biol Pharm Bull 2017; 40(5): 610\u2013615. https:\/\/doi.org\/10.1248\/bpb.b16-00832","DOI":"10.1248\/bpb.b16-00832"},{"key":"e_1_3_3_39_2","doi-asserted-by":"crossref","unstructured":"Da Ponte A Giovanelli N Nigris D et al. Effects of hydrogen rich water on prolonged intermittent exercise. J Sports Med Phys Fitness 2018; 58(5): 612\u2013621. https:\/\/doi.org\/10.23736\/s0022-4707.17.06883-9","DOI":"10.23736\/S0022-4707.17.06883-9"},{"key":"e_1_3_3_40_2","doi-asserted-by":"crossref","unstructured":"Nogueira JE Amorim MR Pinto AP et al. Molecular hydrogen downregulates acute exhaustive exercise-induced skeletal muscle damage. Can J Physiol Pharmacol 2021; 99(8): 812\u2013820. https:\/\/doi.org\/10.1139\/cjpp-2020-0297","DOI":"10.1139\/cjpp-2020-0297"},{"key":"e_1_3_3_41_2","doi-asserted-by":"crossref","unstructured":"L\u00f6ffler J Sass FA Filter S et al. Compromised bone healing in aged rats is associated with impaired M2 macrophage function. Front Immunol 2019; 10: 2443. https:\/\/doi.org\/10.3389\/fimmu.2019.02443","DOI":"10.3389\/fimmu.2019.02443"},{"key":"e_1_3_3_42_2","doi-asserted-by":"crossref","unstructured":"Wang C Yan M Li Y et al. Hydrogen-oxygen mixture inhalation as an adjunctive treatment to home-based exercise in older patients with knee osteoarthritis: an open-label blinded-endpoint randomized controlled trial. Front Pharmacol 2025; 16: 1505922. https:\/\/doi.org\/10.3389\/fphar.2025.1505922","DOI":"10.3389\/fphar.2025.1505922"},{"key":"e_1_3_3_43_2","doi-asserted-by":"crossref","unstructured":"Guo JD Li L Shi YM et al. Hydrogen water consumption prevents osteopenia in ovariectomized rats. Br J Pharmacol 2013; 168(6): 1412\u20131420. https:\/\/doi.org\/10.1111\/bph.12036","DOI":"10.1111\/bph.12036"},{"key":"e_1_3_3_44_2","doi-asserted-by":"crossref","unstructured":"Meng J Yu P Tong J et al. Hydrogen treatment reduces tendon adhesion and inflammatory response. J Cell Biochem 2019; 120(2): 1610\u20131619. https:\/\/doi.org\/10.1002\/jcb.27441","DOI":"10.1002\/jcb.27441"},{"key":"e_1_3_3_45_2","doi-asserted-by":"crossref","unstructured":"Jiang Z Ainiwaer M Liu J et al. Hydrogen therapy: recent advances and emerging materials. Biomater Sci 2024; 12(16): 4136\u20134154. https:\/\/doi.org\/10.1039\/d4bm00446a","DOI":"10.1039\/D4BM00446A"},{"key":"e_1_3_3_46_2","doi-asserted-by":"crossref","unstructured":"Chen Y Wei Y Tang W. The role of hydrogen in the prevention and treatment of coronary atherosclerotic heart disease. Eur J Pharmacol 2024; 972: 176586. https:\/\/doi.org\/10.1016\/j.ejphar.2024.176586","DOI":"10.1016\/j.ejphar.2024.176586"},{"key":"e_1_3_3_47_2","doi-asserted-by":"crossref","unstructured":"Chen O Cao Z Li H et al. High-concentration hydrogen protects mouse heart against ischemia\/reperfusion injury through activation of thePI3K\/Akt1 pathway. Sci Rep 2017; 7(1): 14871. https:\/\/doi.org\/10.1038\/s41598-017-14072-x","DOI":"10.1038\/s41598-017-14072-x"},{"key":"e_1_3_3_48_2","unstructured":"Eslami M Esfandyari S Aghahosseini M et al. Astaxanthin protects human granulosa cells against oxidative stress through activation of NRF2\/ARE pathway and its downstream phase II enzymes. Cell J 2021; 23(3): 319\u2013328. https:\/\/doi.org\/10.22074\/cellj.2021.7222"},{"key":"e_1_3_3_49_2","doi-asserted-by":"crossref","unstructured":"Dhillon G Buddhavarapu V Grewal H et al. Hydrogen water: extra healthy or a hoax?\u2014A systematic review. Int J Mol Sci 2024; 25(2): 973. https:\/\/doi.org\/10.3390\/ijms25020973","DOI":"10.3390\/ijms25020973"},{"key":"e_1_3_3_50_2","doi-asserted-by":"crossref","unstructured":"Hu R Dai C Dong C et al. Living macrophage-delivered tetrapod PdH nanoenzyme for targeted atherosclerosis management by ROS scavenging hydrogen anti-inflammation and autophagy activation. ACS Nano 2022; 16(10): 15959\u201315976. https:\/\/doi.org\/10.1021\/acsnano.2c03422","DOI":"10.1021\/acsnano.2c03422"},{"key":"e_1_3_3_51_2","doi-asserted-by":"crossref","unstructured":"Noda M Liu J Long J. Neuroprotective and preventative effects of molecular hydrogen. Curr Pharm Des 2021; 27(5): 585\u2013591. https:\/\/doi.org\/10.2174\/1381612826666201019103020","DOI":"10.2174\/1381612826666201019103020"},{"key":"e_1_3_3_52_2","doi-asserted-by":"crossref","unstructured":"Chen X Zhao X Lan F et al. Hydrogen sulphide treatment increases insulin sensitivity and improves oxidant metabolism through the CaMKKbeta-AMPK pathway in PA-induced IR C2C12 cells. Sci Rep 2017; 7(1): 13248. https:\/\/doi.org\/10.1038\/s41598-017-13251-0","DOI":"10.1038\/s41598-017-13251-0"},{"key":"e_1_3_3_53_2","doi-asserted-by":"crossref","unstructured":"Zhou HX Han B Hou LM et al. Protective effects of hydrogen gas on experimental acute pancreatitis. PLoS One 2016; 11(4): e0154483. https:\/\/doi.org\/10.1371\/journal.pone.0154483","DOI":"10.1371\/journal.pone.0154483"},{"key":"e_1_3_3_54_2","doi-asserted-by":"crossref","unstructured":"Kajiyama S Hasegawa G Asano M et al. Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance. Nutr Res 2008; 28(3): 137\u2013143. https:\/\/doi.org\/10.1016\/j.nutres.2008.01.008","DOI":"10.1016\/j.nutres.2008.01.008"},{"key":"e_1_3_3_55_2","doi-asserted-by":"crossref","unstructured":"Kamimura N Ichimiya H Iuchi K et al. Molecular hydrogen stimulates the gene expression of transcriptional coactivator PGC-1\u03b1 to enhance fatty acid metabolism. NPJ Aging Mech Dis 2016; 2: 16008. https:\/\/doi.org\/10.1038\/npjamd.2016.8","DOI":"10.1038\/npjamd.2016.8"},{"key":"e_1_3_3_56_2","doi-asserted-by":"crossref","unstructured":"Zheng XF Sun XJ Xia ZF. Hydrogen resuscitation a new cytoprotective approach. Clin Exp Pharmacol Physiol 2011; 38(3): 155\u2013163. https:\/\/doi.org\/10.1111\/j.1440-1681.2011.05479.x","DOI":"10.1111\/j.1440-1681.2011.05479.x"},{"key":"e_1_3_3_57_2","doi-asserted-by":"crossref","unstructured":"Hanaoka T Kamimura N Yokota T et al. Molecular hydrogen protects chondrocytes from oxidative stress and indirectly alters gene expressions through reducing peroxynitrite derived from nitric oxide. Med Gas Res 2011; 1(1): 18. https:\/\/doi.org\/10.1186\/2045-9912-1-18","DOI":"10.1186\/2045-9912-1-18"},{"key":"e_1_3_3_58_2","doi-asserted-by":"crossref","unstructured":"Matei N Camara R Zhang JH. Emerging mechanisms and novel applications of hydrogen gas therapy. Med Gas Res 2018; 8(3): 98\u2013102. https:\/\/doi.org\/10.4103\/2045-9912.239959","DOI":"10.4103\/2045-9912.239959"},{"key":"e_1_3_3_59_2","doi-asserted-by":"crossref","unstructured":"Ge L Yang M Yang NN et al. Molecular hydrogen: a preventive and therapeutic medical gas for various diseases. Oncotarget 2017; 8(60): 102653\u2013102673. https:\/\/doi.org\/10.18632\/oncotarget.21130","DOI":"10.18632\/oncotarget.21130"},{"key":"e_1_3_3_60_2","doi-asserted-by":"crossref","unstructured":"Ohta S. Molecular hydrogen as a novel antioxidant: overview of the advantages of hydrogen for medical applications. Methods Enzymol 2015; 555: 289\u2013317. https:\/\/doi.org\/10.1016\/bs.mie.2014.11.038","DOI":"10.1016\/bs.mie.2014.11.038"},{"key":"e_1_3_3_61_2","doi-asserted-by":"crossref","unstructured":"Dumbuya JS Chen X Du J et al. Hydrogen-rich saline regulates NLRP3 inflammasome activation in sepsis-associated encephalopathy rat model. Int Immunopharmacol 2023; 123: 110758. https:\/\/doi.org\/10.1016\/j.intimp.2023.110758","DOI":"10.1016\/j.intimp.2023.110758"},{"key":"e_1_3_3_62_2","doi-asserted-by":"crossref","unstructured":"Baumer Y Pita MA Turner BS et al. Neighborhood socioeconomic deprivation and individual-level socioeconomic status are associated with dopamine-mediated changes to monocyte subset CCR2 expression via a cAMP-dependent pathway. Brain Behav Immun Health 2023; 30: 100640. https:\/\/doi.org\/10.1016\/j.bbih.2023.100640","DOI":"10.1016\/j.bbih.2023.100640"},{"key":"e_1_3_3_63_2","doi-asserted-by":"crossref","unstructured":"Ohsawa I Ishikawa M Takahashi K et al. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med 2007; 13(6): 688\u2013694. https:\/\/doi.org\/10.1038\/nm1577","DOI":"10.1038\/nm1577"},{"key":"e_1_3_3_64_2","doi-asserted-by":"crossref","unstructured":"Yu Y Yang Y Yang M et al. Hydrogen gas reduces HMGB1 release in lung tissues of septic mice in an Nrf2\/HO-1-dependent pathway. Int Immunopharmacol 2019; 69: 11\u201318. https:\/\/doi.org\/10.1016\/j.intimp.2019.01.022","DOI":"10.1016\/j.intimp.2019.01.022"},{"key":"e_1_3_3_65_2","doi-asserted-by":"crossref","unstructured":"Li S Fujino M Ichimaru N et al. Molecular hydrogen protects against ischemia-reperfusion injury in a mouse fatty liver model via regulating HO-1 and Sirt1 expression. Sci Rep 2018; 8(1): 14019. https:\/\/doi.org\/10.1038\/s41598-018-32411-4","DOI":"10.1038\/s41598-018-32411-4"},{"key":"e_1_3_3_66_2","doi-asserted-by":"crossref","unstructured":"Xu L Guo W Dai J et al. Hydrogen gas alleviates acute ethanol-induced hepatotoxicity in mice via modulating TLR4\/9 innate immune signaling and pyroptosis. Int Immunopharmacol 2024; 127: 111399. https:\/\/doi.org\/10.1016\/j.intimp.2023.111399","DOI":"10.1016\/j.intimp.2023.111399"},{"key":"e_1_3_3_67_2","doi-asserted-by":"crossref","unstructured":"Zhang CB Tang YC Xu XJ et al. Hydrogen gas inhalation protects against liver ischemia\/reperfusion injury by activating the NF-\u03baB signaling pathway. Exp Ther Med 2015; 9(6): 2114\u20132120. https:\/\/doi.org\/10.3892\/etm.2015.2385","DOI":"10.3892\/etm.2015.2385"},{"key":"e_1_3_3_68_2","doi-asserted-by":"crossref","unstructured":"Zou W Liu W Yang B et al. Quercetin protects against perfluorooctanoic acid-induced liver injury by attenuating oxidative stress and inflammatory response in mice. Int Immunopharmacol 2015; 28(1): 129\u2013135. https:\/\/doi.org\/10.1016\/j.intimp.2015.05.043","DOI":"10.1016\/j.intimp.2015.05.043"},{"key":"e_1_3_3_69_2","doi-asserted-by":"crossref","unstructured":"Du H Sheng M Wu L et al. Hydrogen-rich saline attenuates acute kidney injury after liver transplantation via activating p53-mediated autophagy. Transplantation 2016; 100(3): 563\u2013570. https:\/\/doi.org\/10.1097\/tp.0000000000001052","DOI":"10.1097\/TP.0000000000001052"},{"key":"e_1_3_3_70_2","doi-asserted-by":"crossref","unstructured":"Ichiakwa Y Sato B Hirano SI et al. Hypothesized mechanism of amelioration of colitis by Clostridium butyricum as a hydrogen-producing bacterium. Med Gas Res 2024; 14(3): 136\u2013139. https:\/\/doi.org\/10.4103\/2045-9912.390251","DOI":"10.4103\/2045-9912.390251"},{"key":"e_1_3_3_71_2","doi-asserted-by":"crossref","unstructured":"Russell G Nenov A Kisher H et al. Molecular hydrogen as medicine: an assessment of administration methods. Hydrogen 2021; 2(4): 444\u2013460. https:\/\/doi.org\/10.3390\/hydrogen2040025.","DOI":"10.3390\/hydrogen2040025"},{"key":"e_1_3_3_72_2","doi-asserted-by":"crossref","unstructured":"Tamura T Narumiya H Homma K et al. Combination of hydrogen inhalation and hypothermic temperature control after out-of-hospital cardiac arrest: a post hoc analysis of the efficacy of inhaled hydrogen on neurologic outcome following brain ischemia during postcardiac arrest care II trial. Crit Care Med 2024; 52(10): 1567\u20131576. https:\/\/doi.org\/10.1097\/ccm.0000000000006395","DOI":"10.1097\/CCM.0000000000006395"},{"key":"e_1_3_3_73_2","doi-asserted-by":"crossref","unstructured":"Huang L Applegate RL II Applegate PM et al. Inhalation of high-concentration hydrogen gas attenuates cognitive deficits in a rat model of asphyxia induced-cardiac arrest. Med Gas Res 2019; 9(3): 122\u2013126. https:\/\/doi.org\/10.4103\/2045-9912.266986","DOI":"10.4103\/2045-9912.266986"},{"key":"e_1_3_3_74_2","doi-asserted-by":"crossref","unstructured":"Tamura T Suzuki M Homma K et al. Efficacy of inhaled hydrogen on neurological outcome following brain ischaemia during post-cardiac arrest care (HYBRID II): a multi-centre randomised double-blind placebo-controlled trial. EClinicalMedicine 2023; 58: 101907. https:\/\/doi.org\/10.1016\/j.eclinm.2023.101907","DOI":"10.1016\/j.eclinm.2023.101907"},{"key":"e_1_3_3_75_2","doi-asserted-by":"crossref","unstructured":"Sano M Shirakawa K Katsumata Y et al. Low-flow nasal cannula hydrogen therapy. J Clin Med Res 2020; 12(10): 674\u2013680. https:\/\/doi.org\/10.14740\/jocmr4323","DOI":"10.14740\/jocmr4323"},{"key":"e_1_3_3_76_2","doi-asserted-by":"crossref","unstructured":"Kamimura N Nishimaki K Ohsawa I et al. Molecular hydrogen improves obesity and diabetes by inducing hepatic FGF21 and stimulating energy metabolism in db\/db mice. Obesity (Silver Spring) 2011; 19(7): 1396\u20131403. https:\/\/doi.org\/10.1038\/oby.2011.6","DOI":"10.1038\/oby.2011.6"},{"key":"e_1_3_3_77_2","doi-asserted-by":"crossref","unstructured":"Ishibashi T Sato B Rikitake M et al. Consumption of water containing a high concentration of molecular hydrogen reduces oxidative stress and disease activity in patients with rheumatoid arthritis: an open-label pilot study. Med Gas Res 2012; 2(1): 27. https:\/\/doi.org\/10.1186\/2045-9912-2-27","DOI":"10.1186\/2045-9912-2-27"},{"key":"e_1_3_3_78_2","doi-asserted-by":"crossref","unstructured":"Saitoh Y Harata Y Mizuhashi F et al. Biological safety of neutral-pH hydrogen-enriched electrolyzed water upon mutagenicity genotoxicity and subchronic oral toxicity. Toxicol Ind Health 2010; 26(4): 203\u2013216. https:\/\/doi.org\/10.1177\/0748233710362989","DOI":"10.1177\/0748233710362989"},{"key":"e_1_3_3_79_2","doi-asserted-by":"crossref","unstructured":"Radulescu DM Neacsu IA Grumezescu AM et al. New insights of scaffolds based on hydrogels in tissue engineering. Polymers (Basel) 2022; 14(4): 799. https:\/\/doi.org\/10.3390\/polym14040799","DOI":"10.3390\/polym14040799"},{"key":"e_1_3_3_80_2","doi-asserted-by":"crossref","unstructured":"Ma D Zhai S Wang Y et al. TiO2 photocatalysis for transfer hydrogenation. Molecules 2019; 24(2): 330. https:\/\/doi.org\/10.3390\/molecules24020330","DOI":"10.3390\/molecules24020330"},{"key":"e_1_3_3_81_2","doi-asserted-by":"crossref","unstructured":"Zhou H He Z Cao Y et al. An injectable magnesium-loaded hydrogel releases hydrogen to promote osteoporotic bone repair via ROS scavenging and immunomodulation. Theranostics 2024; 14(9): 3739\u20133759. https:\/\/doi.org\/10.7150\/thno.97412","DOI":"10.7150\/thno.97412"},{"key":"e_1_3_3_82_2","doi-asserted-by":"crossref","unstructured":"Holmes B Castro NJ Li J et al. Enhanced human bone marrow mesenchymal stem cell functions in novel 3D cartilage scaffolds with hydrogen treated multi-walled carbon nanotubes. Nanotechnology 2013; 24(36): 365102. https:\/\/doi.org\/10.1088\/0957-4484\/24\/36\/365102","DOI":"10.1088\/0957-4484\/24\/36\/365102"},{"key":"e_1_3_3_83_2","doi-asserted-by":"crossref","unstructured":"Eslahi N Abdorahim M Simchi A. Smart polymeric hydrogels for cartilage tissue engineering: a review on the chemistry and biological functions. Biomacromolecules 2016; 17(11): 3441\u20133463. https:\/\/doi.org\/10.1021\/acs.biomac.6b01235","DOI":"10.1021\/acs.biomac.6b01235"},{"key":"e_1_3_3_84_2","doi-asserted-by":"crossref","unstructured":"Bao J Zhao YF Wang XX et al. Azaphilone pigments from the marine-derived Penicillium sclerotium UJNMF 0503 and their neuroprotective potential against H(2)O(2)-induced cell apoptosis through modulating PI3K\/Akt pathway. Bioorg Chem 2024; 148: 107434. https:\/\/doi.org\/10.1016\/j.bioorg.2024.107434","DOI":"10.1016\/j.bioorg.2024.107434"},{"key":"e_1_3_3_85_2","doi-asserted-by":"crossref","unstructured":"Dong X Zhang H Duan P et al. An injectable and adaptable hydrogen sulfide delivery system for modulating neuroregenerative microenvironment. Sci Adv 2023; 9(51): eadi1078. https:\/\/doi.org\/10.1126\/sciadv.adi1078","DOI":"10.1126\/sciadv.adi1078"},{"key":"e_1_3_3_86_2","doi-asserted-by":"crossref","unstructured":"Zhang H Dong X Liu Y et al. An injectable and adaptable system for the sustained release of hydrogen sulfide for targeted diabetic wound therapy by improving the microenvironment of inflammation regulation and angiogenesis. Acta Biomater 2025; 196: 364\u2013379. https:\/\/doi.org\/10.1016\/j.actbio.2025.02.048","DOI":"10.1016\/j.actbio.2025.02.048"},{"key":"e_1_3_3_87_2","doi-asserted-by":"crossref","unstructured":"Kimura A Suehiro K Mukai A et al. Protective effects of hydrogen gas against spinal cord ischemia-reperfusion injury. J Thorac Cardiovasc Surg 2022; 164(6): e269\u2013e283. https:\/\/doi.org\/10.1016\/j.jtcvs.2021.04.077","DOI":"10.1016\/j.jtcvs.2021.04.077"},{"key":"e_1_3_3_88_2","doi-asserted-by":"crossref","unstructured":"Ishibashi T Sato B Shibata S et al. Therapeutic efficacy of infused molecular hydrogen in saline on rheumatoid arthritis: a randomized double-blind placebo-controlled pilot study. Int Immunopharmacol 2014; 21(2): 468\u2013473. https:\/\/doi.org\/10.1016\/j.intimp.2014.06.001","DOI":"10.1016\/j.intimp.2014.06.001"},{"key":"e_1_3_3_89_2","doi-asserted-by":"crossref","unstructured":"Zhao Z Ji H Zhao Y et al. Effectiveness and safety of hydrogen inhalation as an adjunct treatment in Chinese type 2 diabetes patients: a retrospective observational double-arm real-life clinical study. Front Endocrinol (Lausanne) 2022; 13: 1114221. https:\/\/doi.org\/10.3389\/fendo.2022.1114221","DOI":"10.3389\/fendo.2022.1114221"},{"key":"e_1_3_3_90_2","doi-asserted-by":"crossref","unstructured":"Maruyama T Ishikawa D Kurokawa R et al. Hydrogen gas inhalation improved intestinal microbiota in ulcerative colitis: a randomised double-blind placebo-controlled trial. Biomedicines 2025; 13(8): 1799. https:\/\/doi.org\/10.3390\/biomedicines13081799","DOI":"10.3390\/biomedicines13081799"},{"key":"e_1_3_3_91_2","doi-asserted-by":"crossref","unstructured":"Liu S Zha Z Chen S et al. Hydrogen-rich water alleviates chilling injury-induced lignification of kiwifruit by inhibiting peroxidase activity and improving antioxidant system. J Sci Food Agric 2023; 103(5): 2675\u20132680. https:\/\/doi.org\/10.1002\/jsfa.12272","DOI":"10.1002\/jsfa.12272"},{"key":"e_1_3_3_92_2","doi-asserted-by":"crossref","unstructured":"Ahmad A Baig AA Hussain M et al. Narrative on hydrogen therapy and its clinical applications: safety and efficacy. Curr Pharm Des 2022; 28(31): 2519\u20132537. https:\/\/doi.org\/10.2174\/1381612828666220728104200","DOI":"10.2174\/1381612828666220728104200"},{"key":"e_1_3_3_93_2","doi-asserted-by":"crossref","unstructured":"Kong X Lu T Lu YY et al. Effect of hydrogen inhalation therapy on hearing loss of patients with nasopharyngeal carcinoma after radiotherapy. Front Med (Lausanne) 2022; 9: 828370. https:\/\/doi.org\/10.3389\/fmed.2022.828370","DOI":"10.3389\/fmed.2022.828370"}],"container-title":["Journal of Investigative Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/10815589261497358","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/10815589261497358","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/10815589261497358","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T16:48:13Z","timestamp":1792946893000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/10815589261497358"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,7]]},"references-count":92,"alternative-id":["10.1177\/10815589261497358"],"URL":"https:\/\/doi.org\/10.1177\/10815589261497358","relation":{},"ISSN":["1081-5589","1708-8267"],"issn-type":[{"value":"1081-5589","type":"print"},{"value":"1708-8267","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,7]]},"article-number":"10815589261497358"}}