Molecular Hydrogen Therapy: Mechanisms, Delivery Methods, Preventive, and Therapeutic Application

Jiayi Jin , Lijun Yue , Maoru Du , Feng Geng , Xue Gao , Yuming Zhou , Qianqian Lu , Xiaohong Pan

MedComm ›› 2025, Vol. 6 ›› Issue (5) : e70194

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MedComm ›› 2025, Vol. 6 ›› Issue (5) : e70194 DOI: 10.1002/mco2.70194
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Molecular Hydrogen Therapy: Mechanisms, Delivery Methods, Preventive, and Therapeutic Application

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Abstract

Molecular hydrogen (H2), recognized as the smallest gas molecule, is capable of permeating cellular membranes and diffusing throughout the body. Due to its high bioavailability, H2 is considered a therapeutic gas for the treatment of various diseases. The therapeutic efficacy of hydrogen is contingent upon factors such as the administration method, duration of contact with diseased tissue, and concentration at targeted sites. H2 can be administered exogenously and is also produced endogenously within the intestinal tract. A comprehensive understanding of its delivery mechanisms and modes of action is crucial for advancing hydrogen medicine. This review highlights H₂’s mechanisms of action, summarizes its administration methods, and explores advancements in treating intestinal diseases (e.g., inflammatory bowel disease, intestinal ischemia–reperfusion, colorectal cancer). Additionally, its applications in managing other diseases are discussed. Finally, the challenges associated with its clinical application and potential solutions are explored. We propose that current delivery challenges faced by H2 can be effectively addressed through the use of nanoplatforms; furthermore, interactions between hydrogen and gut microbiota may provide insights into its mechanisms for treating intestinal diseases. Future research should explore the synergistic effects of H2 in conjunction with conventional therapies and develop personalized treatment plans to achieve precision medicine.

Keywords

delivery methods / intestinal diseases / molecular hydrogen (H2) / mechanisms of action / nanoplatforms

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Jiayi Jin, Lijun Yue, Maoru Du, Feng Geng, Xue Gao, Yuming Zhou, Qianqian Lu, Xiaohong Pan. Molecular Hydrogen Therapy: Mechanisms, Delivery Methods, Preventive, and Therapeutic Application. MedComm, 2025, 6(5): e70194 DOI:10.1002/mco2.70194

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References

[1]

T. Kawamura, K. Higashida, and I. Muraoka, “Application of Molecular Hydrogen as a Novel Antioxidant in Sports Science,” Oxidative Medicine and Cellular Longevity 2020 (2020): 2328768.

[2]

M. Dole, F. R. Wilson, and W. P. Fife, “Hyperbaric Hydrogen Therapy: A Possible Treatment for Cancer,” Science 190, no. 4210 (1975): 152-154.

[3]

I. Ohsawa, M. Ishikawa, K. Takahashi, et al., “Hydrogen Acts as a Therapeutic Antioxidant by Selectively Reducing Cytotoxic Oxygen Radicals,” Nature Medicine 13, no. 6 (2007): 688-694.

[4]

J. Li, C. Wang, J. H. Zhang, J. M. Cai, Y. P. Cao, and X. J. Sun, “Hydrogen-rich Saline Improves Memory Function in a Rat Model of Amyloid-beta-induced Alzheimer's Disease by Reduction of Oxidative Stress,” Brain Research 1328 (2010): 152-161.

[5]

K. Ohno, M. Ito, M. Ichihara, and M. Ito, “Molecular Hydrogen as an Emerging Therapeutic Medical Gas for Neurodegenerative and Other Diseases,” Oxidative Medicine and Cellular Longevity 2012 (2012): 353152.

[6]

N.-R. Bao, T. Yuan, and J.-N. Zhao, “Hydrogen Applications: Advances in the Field of Medical Therapy,” Medical Gas Research 13, no. 3 (2023): 99-107.

[7]

W. Boling, D. Ramanathan, L. Huang, and T. Wilson, “Molecular Hydrogen Therapy for Neurological Diseases: A Review of Current Evidence,” Medical Gas Research 13, no. 3 (2023): 94-98.

[8]

K. Saengsin, R. Sittiwangkul, S. C. Chattipakorn, and N. Chattipakorn, “Hydrogen Therapy as a Potential Therapeutic Intervention in Heart Disease: From the Past Evidence to Future Application,” Cellular and Molecular Life Sciences 80, no. 6 (2023): 174.

[9]

Y. Yang, P. Y. Liu, W. Bao, S. J. Chen, F. S. Wu, and P. Y. Zhu, “Hydrogen Inhibits Endometrial Cancer Growth via a ROS/NLRP3/Caspase-1/GSDMD-mediated Pyroptotic Pathway,” BMC Cancer 20, no. 1 (2020): 28.

[10]

B. Zhu, H. Cui, and W. Xu, “Hydrogen Inhibits the Proliferation and Migration of Gastric Cancer Cells by Modulating lncRNA MALAT1/miR-124-3p/EZH2 Axis,” Cancer Cell International 21, no. 1 (2021): 70.

[11]

L. Qian, J. Liu, W. Ma, Y. Liu, X. Wang, and D. Liu, “Hydrogen-Rich Water Ameliorates Murine Chronic Graft-versus-Host Disease Through Antioxidation,” Oxidative Medicine and Cellular Longevity 2021 (2021): 1165928.

[12]

Y. Zheng and D. Zhu, “Molecular Hydrogen Therapy Ameliorates Organ Damage Induced by Sepsis,” Oxidative Medicine and Cellular Longevity 2016 (2016): 5806057.

[13]

L. Qian, Z. Wu, J. Cen, S. Pasca, and C. Tomuleasa, “Medical Application of Hydrogen in Hematological Diseases,” Oxidative Medicine and Cellular Longevity 2019 (2019): 3917393.

[14]

F. Yang, R. Yue, X. Luo, R. Liu, and X. Huang, “Hydrogen: A Potential New Adjuvant Therapy for COVID-19 Patients,” Frontiers in Pharmacology 11 (2020): 543718.

[15]

W. Chen, D. Ni, Z. T. Rosenkrans, T. Cao, and W. Cai, “Smart H(2)S-Triggered/Therapeutic System (SHTS)-Based Nanomedicine,” Advanced Science (Weinh) 6, no. 22 (2019): 1901724.

[16]

G. Zhou, E. Goshi, and Q. He, “Micro/Nanomaterials-Augmented Hydrogen Therapy,” Advanced Healthcare Materials 8, no. 16 (2019): e1900463.

[17]

Y. Yang, Y. Zhu, and X. Xi, “Anti-inflammatory and Antitumor Action of Hydrogen via Reactive Oxygen Species,” Oncology Letters 16, no. 3 (2018): 2771-2776.

[18]

T. Itoh, Y. Fujita, M. Ito, et al., “Molecular Hydrogen Suppresses FcepsilonRI-mediated Signal Transduction and Prevents Degranulation of Mast Cells,” Biochemical and Biophysical Research Communications 389, no. 4 (2009): 651-656.

[19]

N. Matei, R. Camara, and J. H. Zhang, “Emerging Mechanisms and Novel Applications of Hydrogen Gas Therapy,” Medical Gas Research 8, no. 3 (2018): 98-102.

[20]

C. Zhang, Y. Xing, X. Wu, et al., “Inhalation of Hydrogen Gas Protects Against Mitomycin-induced Pulmonary Veno-occlusive Disease,” Respiratory Research 25, no. 1 (2024): 281.

[21]

H. Li, H. Sun, S. Li, et al., “Hydrogen Alleviates Hypoxic-ischaemic Brain Damage in Neonatal Rats by Inhibiting Injury of Brain Pericytes,” Journal of Cellular and Molecular Medicine 28, no. 13 (2024): e18505.

[22]

W. Yan, Q. He, P. Long, T. Chen, L. Zhang, and H. Wang, “Effect of Molecular Hydrogen, a Novelly-established Antioxidant, on the Retinal Degeneration of Hereditary Retinitis Pigmentosa: An in-vivo Study,” Frontiers in Pharmacology 14 (2024): 1294315.

[23]

N. Miwa, Y. Tanaka, and Y. Saitoh, “Electrolytically Generated Hydrogen Warm Water Cleanses the Keratin-plug-clogged Hair-pores and Promotes the Capillary Blood-streams, More Markedly Than Normal Warm Water Does,” Medical Gas Research 8, no. 1 (2018): 12-18.

[24]

S. Roy and S. Dhaneshwar, “Role of Prebiotics, Probiotics, and Synbiotics in Management of Inflammatory Bowel Disease: Current Perspectives,” World Journal of Gastroenterology 29 (2023): 2078-2100.

[25]

B. Zhou, Y. Yuan, S. Zhang, et al., “Intestinal Flora and Disease Mutually Shape the Regional Immune System in the Intestinal Tract,” Frontiers in Immunology 11 (2020): 575.

[26]

A. Perez-Lopez, J. Behnsen, S. P. Nuccio, and M. Raffatellu, “Mucosal Immunity to Pathogenic Intestinal Bacteria,” Nature Reviews Immunology 16, no. 3 (2016): 135-148.

[27]

A. Bruneau, M. T. Baylatry, A. C. Joly, and H. Sokol, “Gut Microbiota: What Impact on Colorectal Carcinogenesis and Treatment?,” Bulletin Du Cancer 105 (2018): 70-80.

[28]

Y. Ichikawa, H. Yamamoto, S.-I. Hirano, B. Sato, Y. Takefuji, and F. Satoh, “The Overlooked Benefits of Hydrogen-producing Bacteria,” Medical Gas Research 13, no. 3 (2023): 108-111.

[29]

F. Xie, Y. Song, Y. Yi, et al., “Therapeutic Potential of Molecular Hydrogen in Metabolic Diseases From Bench to Bedside,” Pharmaceuticals 16, no. 4 (2023): 541.

[30]

Y. Chen, J. Zhou, and L. Wang, “Role and Mechanism of Gut Microbiota in Human Disease,” Frontiers in Cellular and Infection Microbiology 11 (2021): 625913.

[31]

H. Si, Q. Yang, H. Hu, C. Ding, H. Wang, and X. Lin, “Colorectal Cancer Occurrence and Treatment Based on Changes in Intestinal Flora,” Seminars in Cancer Biology 70 (2021): 3-10.

[32]

C. D. S. Leite, G. A. Bonafé, J. Carvalho Santos, C. A. R. Martinez, M. M. Ortega, and M. L. Ribeiro, “The Anti-Inflammatory Properties of Licorice (Glycyrrhiza glabra)-Derived Compounds in Intestinal Disorders,” International Journal of Molecular Sciences 23 (2023): 4121.

[33]

Y. Pu, X. Fan, Z. Zhang, et al., “Harnessing Polymer-derived Drug Delivery Systems for Combating Inflammatory Bowel Disease,” Journal of Controlled Release 354 (2023): 1-18.

[34]

Y. Xia, L. Zhang, D. K. W. Ocansey, Q. Tu, F. Mao, and X. Sheng, “Role of Glycolysis in Inflammatory Bowel Disease and Its Associated Colorectal Cancer,” Frontiers in Endocrinology (Lausanne) 10 (2023): 1242991.

[35]

A. Bardelčíková, J. Šoltys, and J. Mojžiš, “Oxidative Stress, Inflammation and Colorectal Cancer: An Overview,” Antioxidants (Basel) 12 (2023): 901.

[36]

A. S. Faye and J. F. Colombel, “Aging and IBD: A New Challenge for Clinicians and Researchers,” Inflammatory Bowel Diseases 28, no. 1 (2022): 126-132.

[37]

S. K. Murthy, “The 2023 Impact of Inflammatory Bowel Disease in Canada: Cancer and IBD,” Journal of the Canadian Association of Gastroenterology 6 (2023): S83-S96.

[38]

X. Jiang, Z. Jiang, M. Jiang, and Y. Sun, “Berberine as a Potential Agent for the Treatment of Colorectal Cancer,” Frontiers in Medicine (Lausanne) 28 (2022): 886996.

[39]

R. Medzhitov, “The Spectrum of Inflammatory Responses,” Science 374, no. 6571 (2021): 1070-1075.

[40]

G. S. Selders, A. E. Fetz, M. Z. Radic, and G. L. Bowlin, “An Overview of the Role of Neutrophils in Innate Immunity, Inflammation and Host-biomaterial Integration,” Regenerative Biomaterials 4, no. 1 (2017): 55-68.

[41]

M. F. Neurath, “Strategies for Targeting Cytokines in Inflammatory Bowel Disease,” Nature Reviews Immunology 24, no. 8 (2024): 559-576.

[42]

M. Schilperoort, D. Ngai, S. R. Sukka, K. Avrampou, H. Shi, and I. Tabas, “The Role of Efferocytosis-fueled Macrophage Metabolism in the Resolution of Inflammation,” Immunological Reviews 319, no. 1 (2023): 65-80.

[43]

B. M. Buchholz, D. J. Kaczorowski, R. Sugimoto, et al., “Hydrogen Inhalation Ameliorates Oxidative Stress in Transplantation Induced Intestinal Graft Injury,” American Journal of Transplantation 8, no. 10 (2008): 2015-2024.

[44]

J. Xue, M. Zhao, Y. Liu, et al., “Hydrogen Inhalation Ameliorates Hepatic Inflammation and Modulates Gut Microbiota in Rats With High-fat Diet-induced Non-alcoholic Fatty Liver Disease,” European Journal of Pharmacology 947 (2023): 175698.

[45]

W.-C. Yang, T.-T. Li, Q. Wan, et al., “Molecular Hydrogen Mediates Neurorestorative Effects after Stroke in Diabetic Rats: The TLR4/NF-κB Inflammatory Pathway,” Journal of Neuroimmune Pharmacology 18, no. 1-2 (2022): 90-99.

[46]

M. Diao, S. Zhang, L. Wu, et al., “Hydrogen Gas Inhalation Attenuates Seawater Instillation-Induced Acute Lung Injury via the Nrf2 Pathway in Rabbits,” Inflammation 39, no. 6 (2016): 2029-2039.

[47]

X. Zhuang, Y. Yu, Y. Jiang, et al., “Molecular Hydrogen Attenuates Sepsis-induced Neuroinflammation Through Regulation of Microglia Polarization Through an mTOR-autophagy-dependent Pathway,” International Immunopharmacology 81 (2020): 106287.

[48]

Y. Si, L. Liu, J. Cheng, et al., “Oral Hydrogen-Rich Water Alleviates Oxalate-Induced Kidney Injury by Suppressing Oxidative Stress, Inflammation, and Fibrosis,” Frontiers in Medicine 8 (2021): 713536.

[49]

J.-D. Ren, X.-B. Wu, R. Jiang, D.-P. Hao, and Y. Liu, “Molecular Hydrogen Inhibits Lipopolysaccharide-triggered NLRP3 Inflammasome Activation in Macrophages by Targeting the Mitochondrial Reactive Oxygen Species,” Biochimica Et Biophysica Acta (BBA)—Molecular Cell Research 1863, no. 1 (2016): 50-55.

[50]

A. Shao, H. Wu, Y. Hong, et al., “Hydrogen-Rich Saline Attenuated Subarachnoid Hemorrhage-Induced Early Brain Injury in Rats by Suppressing Inflammatory Response: Possible Involvement of NF-κB Pathway and NLRP3 Inflammasome,” Molecular Neurobiology 53, no. 5 (2015): 3462-3476.

[51]

N. Geng, X. Gao, X. Wang, et al., “Hydrogen Helps to Ameliorate Staphylococcus aureus-induced Mastitis in Mice,” International Immunopharmacology 109 (2022): 108940.

[52]

I.-S. You, S. Sharma, A. Fadriquela, et al., “Antioxidant Properties of Hydrogen Gas Attenuates Oxidative Stress in Airway Epithelial Cells,” Molecules (Basel, Switzerland) 26, no. 21 (2021): 6375.

[53]

P. An, X.-C. Zhao, M.-J. Liu, Y.-Q. You, and J.-Y. Li, “Gender-based Differences in Neuroprotective Effects of Hydrogen Gas Against Intracerebral Hemorrhage-induced Depression,” Neurochemistry International 153 (2022): 105276.

[54]

T. Hussain, B. Tan, Y. Yin, et al., “Oxidative Stress and Inflammation: What Polyphenols Can Do for Us?,” Oxidative Medicine and Cellular Longevity 2016, no. 1 (2016): 7432797.

[55]

H. Lu, W. Chen, W. Liu, et al., “Molecular Hydrogen Regulates PTEN-AKT-mTOR Signaling via ROS to Alleviate Peritoneal Dialysis-related Peritoneal Fibrosis,” The FASEB Journal 34, no. 3 (2020): 4134-4146.

[56]

S. Ohta, “Molecular Hydrogen as a Novel Antioxidant,” Hydrogen Sulfide in Redox Biology, Part B. (Methods in Enzymology, 2015): 289-317.

[57]

Y. Zhang, J. Chen, H. Wu, et al., “Hydrogen Regulates Mitochondrial Quality to Protect Glial Cells and Alleviates Sepsis-associated Encephalopathy by Nrf2/YY1 Complex Promoting HO-1 Expression,” International Immunopharmacology 118 (2023): 110009.

[58]

Y. Yu, J. Feng, N. Lian, et al., “Hydrogen Gas Alleviates Blood-brain Barrier Impairment and Cognitive Dysfunction of Septic Mice in an Nrf2-dependent Pathway,” International Immunopharmacology 85 (2020): 106585.

[59]

Y. Guo, J. Qin, R. Sun, et al., “Molecular Hydrogen Promotes Retinal Vascular Regeneration and Attenuates Neovascularization and Neuroglial Dysfunction in Oxygen-induced Retinopathy Mice,” Biological Research 57, no. 1 (2024): 43.

[60]

M. Tu, X. Fan, J. Shi, S. Jing, X. Xu, and Y. Wang, “2-Fluorofucose Attenuates Hydrogen Peroxide-Induced Oxidative Stress in HepG2 Cells via Nrf2/keap1 and NF-κB Signaling Pathways,” Life 12, no. 3 (2022): 406.

[61]

S. Li, M. Fujino, N. Ichimaru, et al., “Molecular Hydrogen Protects Against Ischemia-reperfusion Injury in a Mouse Fatty Liver Model via Regulating HO-1 and Sirt1 Expression,” Scientific Reports 8, no. 1 (2018): 14019.

[62]

H. Li, O. Chen, Z. Ye, et al., “Inhalation of High Concentrations of Hydrogen Ameliorates Liver Ischemia/Reperfusion Injury Through a(2A) Receptor Mediated PI3K-Akt Pathway,” Biochemical Pharmacology 130 (2017): 83-92.

[63]

Y. Zhang, Q. Sun, B. He, J. Xiao, Z. Wang, and X. Sun, “Anti-inflammatory Effect of Hydrogen-rich Saline in a Rat Model of Regional Myocardial Ischemia and Reperfusion,” International Journal of Cardiology 148, no. 1 (2011): 91-95.

[64]

L. Zhao, Y.-B. Wang, S.-R. Qin, et al., “Protective Effect of Hydrogen-rich Saline on Ischemia/Reperfusion Injury in Rat Skin Flap,” Journal of Zhejiang University SCIENCE B 14, no. 5 (2013): 382-391.

[65]

M. Hayashi, H. Obara, S. Matsuda, et al., “Protective Effects of Hydrogen Gas Inhalation for Hindlimb Ischaemia-Reperfusion Injury in a Mouse Model,” European Journal of Vascular and Endovascular Surgery 68, no. 1 (2024): 120-128.

[66]

H. Yang, J. Bai, C. Zhan, et al., “Hydrogen Attenuates Thyroid Hormone-Induced Cardiac Hypertrophy in Rats by Regulating Angiotensin II Type 1 Receptor and NADPH Oxidase 2 Mediated Oxidative Stress,” European Journal of Pharmacology 922 (2022): 174917.

[67]

K. Kohama, H. Yamashita, M. Aoyama-Ishikawa, et al., “Hydrogen Inhalation Protects Against Acute Lung Injury Induced by Hemorrhagic Shock and Resuscitation,” Surgery 158, no. 2 (2015): 399-407.

[68]

Y. Terasaki, T. Suzuki, K. Tonaki, et al., “Molecular Hydrogen Attenuates Gefitinib-induced Exacerbation of Naphthalene-evoked Acute Lung Injury Through a Reduction in Oxidative Stress and Inflammation,” Laboratory Investigation 99, no. 6 (2019): 793-806.

[69]

N. Ketelut-Carneiro and K. A. Fitzgerald, “Apoptosis, Pyroptosis, and Necroptosis—Oh My! the Many Ways a Cell Can Die,” Journal of Molecular Biology 434, no. 4 (2022): 167378.

[70]

T.-T. Li, T. Sun, Y.-Z. Wang, Q. Wan, W.-Z. Li, and W.-C. Yang, “Molecular Hydrogen Alleviates Lung Injury After Traumatic Brain Injury: Pyroptosis and Apoptosis,” European Journal of Pharmacology 914 (2022): 174664.

[71]

H. Jiang, P. A. N. Yu, D.-H. Qian, et al., “Hydrogen-rich Medium Suppresses the Generation of Reactive Oxygen Species, Elevates the Bcl-2/Bax Ratio and Inhibits Advanced Glycation End Product-induced Apoptosis,” International Journal of Molecular Medicine 31, no. 6 (2013): 1381-1387.

[72]

X. Ji, W. Zheng, and W. Yao, “Protective Role of Hydrogen Gas on Oxidative Damage and Apoptosis in Intestinal Porcine Epithelial Cells (IPEC-J2) Induced by Deoxynivalenol: A Preliminary Study,” Toxins 12, no. 1 (2019): 5.

[73]

P. Guan, Z.-M. Sun, L.-F. Luo, et al., “Hydrogen Protects Against Chronic Intermittent Hypoxia Induced Renal Dysfunction by Promoting Autophagy and Alleviating Apoptosis,” Life Sciences 225 (2019): 46-54.

[74]

G. Zhang, S. Gao, X. Li, et al., “Pharmacological Postconditioning With Lactic Acid and Hydrogen Rich Saline Alleviates Myocardial Reperfusion Injury in Rats,” Scientific Reports 5, no. 1 (2015): 9858.

[75]

H. Liu, N. Hua, K. Xie, T. Zhao, and Y. Yu, “Hydrogen-rich Saline Reduces Cell Death Through Inhibition of DNA Oxidative Stress and Overactivation of Poly (ADP-ribose) Polymerase-1 in Retinal Ischemia-reperfusion Injury,” Molecular Medicine Reports 12, no. 2 (2015): 2495-2502.

[76]

D. Wang, L. Wang, Y. Zhang, Y. Zhao, and G. Chen, “Hydrogen Gas Inhibits Lung Cancer Progression Through Targeting SMC3,” Biomedicine & Pharmacotherapy 104 (2018): 788-797.

[77]

J. Meng, L. Liu, D. Wang, Z. Yan, and G. Chen, “Hydrogen Gas Represses the Progression of Lung Cancer via Down-regulating CD47,” Bioscience Reports 40, no. 4 (2020): BSR20192761.

[78]

Y. Jiang, G. Liu, L. Zhang, et al., “Therapeutic Efficacy of Hydrogen‑Rich Saline Alone and in Combination With PI3K Inhibitor in Non‑Small Cell Lung Cancer,” Molecular Medicine Reports 18, no. 2 (2018): 2182-2190.

[79]

J. Chu, J. Gao, J. Wang, et al., “Mechanism of Hydrogen on Cervical Cancer Suppressionsssss Revealed by High‑Throughput RNA Sequencing,” Oncology Reports 46, no. 1 (2021): 141.

[80]

Y. Liu, Y. Huang, C. Xu, et al., “Mitochondrial Dysfunction and Therapeutic Perspectives in Cardiovascular Diseases,” International Journal of Molecular Sciences 23, no. 24 (2022): 16053.

[81]

M. M. Klemmensen, S. H. Borrowman, C. Pearce, B. Pyles, and B. Chandra, “Mitochondrial Dysfunction in Neurodegenerative Disorders,” Neurotherapeutics 21, no. 1 (2024): e00292.

[82]

G. Paradies, “Oxidative Stress, Cardiolipin and Mitochondrial Dysfunction in Nonalcoholic Fatty Liver Disease,” World Journal of Gastroenterology 20, no. 39 (2014): 14205-14218.

[83]

J. S. Dumbuya, S. Li, L. Liang, Y. Chen, J. Du, and Q. Zeng, “Effects of Hydrogen-rich Saline in Neuroinflammation and Mitochondrial Dysfunction in Rat Model of Sepsis-associated Encephalopathy,” Journal of Translational Medicine 20, no. 1 (2022): 546.

[84]

Q. U. Liu, B.-S. Li, Y.-J. Song, et al., “Hydrogen-rich Saline Protects Against Mitochondrial Dysfunction and Apoptosis in Mice With Obstructive Jaundice,” Molecular Medicine Reports 13, no. 4 (2016): 3588-3596.

[85]

A. Dong, Y. Yu, Y. Wang, et al., “Protective Effects of Hydrogen Gas Against Sepsis-induced Acute Lung Injury via Regulation of Mitochondrial Function and Dynamics,” International Immunopharmacology 65 (2018): 366-372.

[86]

Y. Cui, S. Meng, N. Zhang, et al., “High-concentration Hydrogen Inhalation Mitigates Sepsis-associated Encephalopathy in Mice by Improving Mitochondrial Dynamics,” CNS Neuroscience & Therapeutics 30, no. 9 (2024): e70021.

[87]

C. J. Obara, J. Nixon-Abell, A. S. Moore, et al., “Motion of VAPB Molecules Reveals ER-mitochondria Contact Site Subdomains,” Nature 626, no. 7997 (2024): 169-176.

[88]

H.-G. Chen, H.-Z. Han, Y. Li, Y.-H. Yu, and K.-L. Xie, “Hydrogen Alleviated Organ Injury and Dysfunction in Sepsis: The Role of Cross-talk Between Autophagy and Endoplasmic Reticulum Stress: Experimental Research,” International Immunopharmacology 78 (2020): 106049.

[89]

Q. Sun, W. Han, H. Hu, et al., “Hydrogen Alleviates Hyperoxic Acute Lung Injury Related Endoplasmic Reticulum Stress in Rats Through Upregulation of SIRT1,” Free Radical Research 51, no. 6 (2017): 622-632.

[90]

N. Y. Shen, J. B. Bi, J. Y. Zhang, et al., “Hydrogen-rich Water Protects Against in fl Ammatory Bowel Disease in Mice by Inhibiting Endoplasmic Reticulum Stress and Promoting Heme Oxygenase-1 Expression,” World Journal of Gastroenterology 23, no. 8 (2017): 1375-1386.

[91]

C. Aoki, K. Imai, T. Mizutani, et al., “Molecular Hydrogen Has a Positive Impact on Pregnancy Maintenance Through Enhancement of Mitochondrial Function and Immunomodulatory Effects on T Cells,” Life Sciences 308 (2022): 120955.

[92]

K.-C. Xu, J.-B. Chen, X.-F. Kong, 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,” Medical Gas Research 10, no. 4 (2020): 149-154.

[93]

J.-B. Chen, X.-F. Kong, and F. Mu, “High-flow Hydrogen Inhalation Might Suppresses the Immune Function of Middle-aged Participants,” Medical Gas Research 11, no. 1 (2021): 12-17.

[94]

Q. Li, P. Yu, Q. Zeng, et al., “Neuroprotective Effect of Hydrogen-Rich Saline in Global Cerebral Ischemia/Reperfusion Rats: Up-Regulated Tregs and Down-Regulated miR-21, miR-210 and NF-kappaB Expression,” Neurochemical Research 41, no. 10 (2016): 2655-2665.

[95]

S. Zhao, Y. Yang, W. Liu, et al., “Protective Effect of Hydrogen-rich Saline Against Radiation-induced Immune Dysfunction,” Journal of Cellular and Molecular Medicine 18, no. 5 (2014): 938-946.

[96]

T. Ishibashi, M. Ichikawa, B. Sato, et al., “Improvement of Psoriasis-associated Arthritis and Skin Lesions by Treatment With Molecular Hydrogen: A Report of Three Cases,” Molecular Medicine Reports 12, no. 2 (2015): 2757-2764.

[97]

C. S. Huang, T. Kawamura, Y. Toyoda, and A. Nakao, “Recent Advances in Hydrogen Research as a Therapeutic Medical Gas,” Free Radical Research 44, no. 9 (2010): 971-982.

[98]

R. Pluta, S. Januszewski, and S. J. Czuczwar, “Molecular Hydrogen Neuroprotection in Post-Ischemic Neurodegeneration in the Form of Alzheimer's Disease Proteinopathy: Underlying Mechanisms and Potential for Clinical Implementation-Fantasy or Reality?,” International Journal of Molecular Sciences 23, no. 12 (2022): 6591.

[99]

T. Kawamura, C. S. Huang, N. Tochigi, et al., “Inhaled Hydrogen Gas Therapy for Prevention of Lung Transplant-induced Ischemia/Reperfusion Injury in Rats,” Transplantation 90, no. 12 (2010): 1344-1351.

[100]

M. Yang, Y. Dong, Q. He, et al., “Hydrogen: A Novel Option in Human Disease Treatment,” Oxidative Medicine and Cellular Longevity 2020 (2020): 1-17.

[101]

Y. Zeng, W. Guan, K. Wang, et al., “Effect of Hydrogen/Oxygen Therapy for Ordinary COVID-19 Patients: A Propensity-score Matched Case-control Study,” BMC Infectious Diseases 23, no. 1 (2023): 440.

[102]

S. M. Ostojic, “Inadequate Production of H(2) by Gut Microbiota and Parkinson Disease,” Trends in Endocrinology and Metabolism 29, no. 5 (2018): 286-288.

[103]

S. W. Li, T. Takahara, W. Que, et al., “Hydrogen-rich Water Protects Against Liver Injury in Nonalcoholic Steatohepatitis Through HO-1 Enhancement via IL-10 and Sirt 1 Signaling,” American Journal of Physiology Gastrointestinal and Liver Physiology 320, no. 4 (2021): G450-G463.

[104]

C. Hou, Y. Peng, C. Qin, F. Fan, J. Liu, and J. Long, “Hydrogen-rich Water Improves Cognitive Impairment Gender-dependently in APP/PS1 Mice Without Affecting Abeta Clearance,” Free Radical Research 52, no. 11-12 (2018): 1311-1322.

[105]

M. Botek, J. Krejci, A. J. McKune, B. Sladeckova, and N. Naumovski, “Hydrogen Rich Water Improved Ventilatory, Perceptual and Lactate Responses to Exercise,” International Journal of Sports Medicine 40, no. 14 (2019): 879-885.

[106]

M. Botek, J. Krejci, A. J. McKune, and B. Sladeckova, “Hydrogen-Rich Water Supplementation and up-Hill Running Performance: Effect of Athlete Performance Level,” International Journal of Sports Physiology and Performance (2020): 1-4.

[107]

D. Javorac, V. Stajer, L. Ratgeber, et al., “Hydrotherapy With Hydrogen-rich Water Compared With RICE Protocol Following Acute Ankle Sprain in Professional Athletes: A Randomized Non-inferiority Pilot Trial,” Research in Sports Medicine 29, no. 6 (2021): 517-525.

[108]

X. Zhang, P. Yu, N. Hong, et al., “Effect and Mechanism of Hydrogen-rich Bath on Mice With Imiquimod-induced Psoriasis,” Experimental Dermatology 32, no. 10 (2023): 1674-1681.

[109]

N. Nakashima-Kamimura, T. Mori, I. Ohsawa, S. Asoh, and S. Ohta, “Molecular Hydrogen Alleviates Nephrotoxicity Induced by an Anti-cancer Drug Cisplatin Without Compromising Anti-tumor Activity in Mice,” Cancer Chemotheraphy and Pharmacology 64, no. 4 (2009): 753-761.

[110]

L. Xiao and N. Miwa, “Hydrogen-rich Water Achieves Cytoprotection From Oxidative Stress Injury in human Gingival Fibroblasts in Culture or 3D-tissue Equivalents, and Wound-healing Promotion, Together With ROS-scavenging and Relief From Glutathione Diminishment,” Human Cell 30, no. 2 (2017): 72-87.

[111]

T. W. LeBaron, R. Sharpe, and K. Ohno, “Electrolyzed-Reduced Water: Review I. Molecular Hydrogen Is the Exclusive Agent Responsible for the Therapeutic Effects,” International Journal of Molecular Sciences 23, no. 23 (2022): 14750.

[112]

T. Hamasaki, G. Harada, N. Nakamichi, et al., “Electrochemically Reduced Water Exerts Superior Reactive Oxygen Species Scavenging Activity in HT1080 Cells Than the Equivalent Level of Hydrogen-dissolved Water,” PLoS ONE 12, no. 2 (2017): e0171192.

[113]

Z. Fu, Z. Zhang, X. Wu, and J. Zhang, “Hydrogen-Rich Saline Inhibits Lipopolysaccharide-Induced Acute Lung Injury and Endothelial Dysfunction by Regulating Autophagy Through mTOR/TFEB Signaling Pathway,” BioMed Research International 2020 (2020): 9121894.

[114]

H. Wang, X. Huo, H. Chen, et al., “Hydrogen-Rich Saline Activated Autophagy via HIF-1alpha Pathways in Neuropathic Pain Model,” BioMed Research International 2018 (2018): 4670834.

[115]

T. T. Huo, Y. Zeng, X. N. Liu, et al., “Hydrogen-rich Saline Improves Survival and Neurological Outcome After Cardiac Arrest and Cardiopulmonary Resuscitation in Rats,” Anesthesia and Analgesia 119, no. 2 (2014): 368-380.

[116]

C. Liu, R. Kurokawa, M. Fujino, S. Hirano, B. Sato, and X.-K. Li, “Estimation of the Hydrogen Concentration in Rat Tissue Using an Airtight Tube Following the Administration of Hydrogen via Various Routes,” Scientific Reports 4, no. 1 (2014): 9629.

[117]

L. Liu, C. Yang, T. Qiu, et al., “Hydrogen Alleviates Acute Lung Injury Induced by Limb Ischaemia/Reperfusion in Mice,” Life Sciences 279 (2021): 119659.

[118]

F. Wang, G. Yu, S. Y. Liu, et al., “Hydrogen-rich Saline Protects Against Renal Ischemia/Reperfusion Injury in Rats,” Journal of Surgical Research 167, no. 2 (2011): e339-e344.

[119]

J. S. Dumbuya, X. Chen, J. Du, et al., “Hydrogen-rich Saline Regulates NLRP3 Inflammasome Activation in Sepsis-associated Encephalopathy Rat Model,” International Immunopharmacology 123 (2023): 110758.

[120]

L. Yang, Y. Guo, X. Fan, et al., “Amelioration of Coagulation Disorders and Inflammation by Hydrogen-Rich Solution Reduces Intestinal Ischemia/Reperfusion Injury in Rats Through NF-kappaB/NLRP3 Pathway,” Mediators of Inflammation 2020 (2020): 4359305.

[121]

M. Takahashi, T. F. Chen-Yoshikawa, M. Saito, et al., “Immersing Lungs in Hydrogen-rich Saline Attenuates Lung Ischaemia-reperfusion Injury,” European Journal of Cardio-Thoracic Surgery 51, no. 3 (2017): 442-448.

[122]

C. Wu, P. Zou, S. Feng, et al., “Molecular Hydrogen: An Emerging Therapeutic Medical Gas for Brain Disorders,” Molecular Neurobiology 60, no. 4 (2022): 1749-1765.

[123]

Y. Tian, Y. Zhang, Y. Wang, et al., “Hydrogen, a Novel Therapeutic Molecule, Regulates Oxidative Stress, Inflammation, and Apoptosis,” Frontiers in Physiology 12 (2021): 789507.

[124]

L. Wei, L. Ge, S. Qin, et al., “Hydrogen-rich Saline Protects Retina Against Glutamate-induced Excitotoxic Injury in guinea Pig,” Experimental Eye Research 94, no. 1 (2012): 117-127.

[125]

H. Oharazawa, T. Igarashi, T. Yokota, et al., “Protection of the Retina by Rapid Diffusion of Hydrogen: Administration of Hydrogen-loaded Eye Drops in Retinal Ischemia-reperfusion Injury,” Investigative Ophthalmology & Visual Science 51, no. 1 (2010): 487-492.

[126]

L. Jin, K. Fan, S. Tan, et al., “The Beneficial Effects of Hydrogen-Rich Saline Irrigation on Chronic Rhinitis: A Randomized, Double-Blind Clinical Trial,” Journal of Inflammation Research 15 (2022): 3983-3995.

[127]

J. Cai, Z. Kang, K. Liu, et al., “Neuroprotective Effects of Hydrogen Saline in Neonatal Hypoxia-ischemia Rat Model,” Brain Research 1256 (2009): 129-137.

[128]

M. Kajiya, K. Sato, M. J. Silva, et al., “Hydrogen From Intestinal Bacteria Is Protective for Concanavalin A-induced hepatitis,” Biochemical and Biophysical Research Communications 386, no. 2 (2009): 316-321.

[129]

N. Nishimura, H. Tanabe, E. Komori, Y. Sasaki, R. Inoue, and T. Yamamoto, “Transplantation of High Hydrogen-Producing Microbiota Leads to Generation of Large Amounts of Colonic Hydrogen in Recipient Rats Fed High Amylose Maize Starch,” Nutrients 10, no. 2 (2018): 144.

[130]

N. Nishimura, H. Tanabe, Y. Sasaki, et al., “Pectin and High-amylose Maize Starch Increase Caecal Hydrogen Production and Relieve Hepatic Ischaemia-reperfusion Injury in Rats,” British Journal of Nutrition 107, no. 4 (2012): 485-492.

[131]

D. F. Altomare, L. Bonfrate, M. Krawczyk, et al., “The Inulin Hydrogen Breath Test Predicts the Quality of Colonic Preparation,” Surgical Endoscopy 28, no. 5 (2014): 1579-1587.

[132]

J. Jahng, I. S. Jung, E. J. Choi, J. L. Conklin, and H. Park, “The Effects of Methane and Hydrogen Gases Produced by Enteric Bacteria on Ileal Motility and Colonic Transit Time,” Neurogastroenterology and Motility 24, no. 2 (2012): 185-190. e92.

[133]

A. Suzuki, M. Ito, T. Hamaguchi, et al., “Quantification of Hydrogen Production by Intestinal Bacteria That Are Specifically Dysregulated in Parkinson's Disease,” PLoS ONE 13, no. 12 (2018): e0208313.

[134]

A. Gasbarrini, G. R. Corazza, G. Gasbarrini, et al., “Methodology and Indications of H2-breath Testing in Gastrointestinal Diseases: The Rome Consensus Conference,” Alimentary Pharmacology & Therapeutics 2009; 29(Suppl 1): 1-49.

[135]

C. De Geyter, K. Van de Maele, B. Hauser, and Y. Vandenplas, “Hydrogen and Methane Breath Test in the Diagnosis of Lactose Intolerance,” Nutrients 13, no. 9 (2021): 3261.

[136]

P. Jirapinyo, T. T. Makuvire, W. Y. Dong, W. W. Chan, and C. C. Thompson, “Impact of Oral-Cecal Transit Time on the Interpretation of Lactulose Breath Tests after RYGB: A Personalized Approach to the Diagnosis of SIBO,” Obesity Surgery 29, no. 3 (2019): 771-775.

[137]

L. Li, X.-Y. Zhang, J.-S. Yu, et al., “Ability of Lactulose Breath Test Results to Accurately Identify Colorectal Polyps Through the Measurement of Small Intestine Bacterial Overgrowth,” World Journal of Gastrointestinal Surgery 15, no. 6 (2023): 1138-1148.

[138]

C. Li, Y. Cao, F. Kohei, et al., “Nano-bubble Hydrogen Water: An Effective Therapeutic Agent Against Inflammation Related Disease Caused by Viral Infection in Zebrafish Model,” Virologica Sinica 37, no. 2 (2022): 277-283.

[139]

S. Kato, D. Matsuoka, and N. Miwa, “Antioxidant Activities of Nano-bubble Hydrogen-dissolved Water Assessed by ESR and 2,2'-bipyridyl Methods,” Materials Science & Engineering C-Materials for Biological Applications 53 (2015): 7-10.

[140]

L. Xiao and N. Miwa, “Hydrogen Nano-Bubble Water Suppresses ROS Generation, Adipogenesis, and Interleukin-6 Secretion in Hydrogen-Peroxide- or PMA-Stimulated Adipocytes and Three-Dimensional Subcutaneous Adipose Equivalents,” Cells 10, no. 3 (2021): 626.

[141]

W. Zhang, L. Zeng, H. Yu, et al., “Injectable Spontaneous Hydrogen-releasing Hydrogel for Long-lasting Alleviation of Osteoarthritis,” Acta Biomaterialia 158 (2023): 163-177.

[142]

W. L. Wan, Y. J. Lin, P. C. Shih, et al., “An in Situ Depot for Continuous Evolution of Gaseous H2 Mediated by a Magnesium Passivation/Activation Cycle for Treating Osteoarthritis,” Angewandte Chemie (International ed in English) 57, no. 31 (2022): 9875-9879.

[143]

W. Wang, B. Xiao, Y. Qiu, et al., “pH-Responsive Delivery of H2 Through Ammonia Borane-Loaded Hollow Polydopamine for Intervertebral Disc Degeneration Therapy,” Oxidative Medicine and Cellular Longevity 2023 (2023): 1-16.

[144]

W. Xiao, K. He, C. Yu, et al., “Space Station-Like Composite Nanoparticles for Co-Delivery of Multiple Natural Compounds From Chinese Medicine and Hydrogen in Combating Sensorineural Hearing Loss,” Molecular Pharmaceutics 20, no. 8 (2023): 3987-4006.

[145]

H. Chen, Y. Guo, Z. Zhang, et al., “Symbiotic Algae-Bacteria Dressing for Producing Hydrogen to Accelerate Diabetic Wound Healing,” Nano Letters 22, no. 1 (2021): 229-237.

[146]

P. Wang, J. Wu, H. Yang, et al., “Intelligent Microneedle Patch With Prolonged Local Release of Hydrogen and Magnesium Ions for Diabetic Wound Healing,” Bioactive Materials 24 (2023): 463-476.

[147]

S. Bi, J. Qi, W. Zhang, and X. Jiang, “A Liquid Metal Dressing for Anti-inflammatory and Anti-infection Applications to Treat Diabetic Wounds,” Chemical Communications 59, no. 54 (2023): 8420-8423.

[148]

Q. Xu, S. Chen, L. Jiang, et al., “Sonocatalytic Hydrogen/Hole-combined Therapy for Anti-biofilm and Infected Diabetic Wound Healing,” National Science Review 10, no. 5 (2023): nwad063.

[149]

R. Hu, C. Dai, C. Dong, et al., “Living Macrophage-Delivered Tetrapod PdH Nanoenzyme for Targeted Atherosclerosis Management by ROS Scavenging, Hydrogen Anti-inflammation, and Autophagy Activation,” ACS Nano 16, no. 10 (2022): 15959-15976.

[150]

G. Tao, F. Liu, Z. Jin, et al., “A Strategy of Local Hydrogen Capture and Catalytic Hydrogenation for Enhanced Therapy of Chronic Liver Diseases,” Theranostics 13, no. 8 (2023): 2455-2470.

[151]

C. Nie, A. Rong, J. Wang, et al., “Controlled Release of Hydrogen-Carrying Perfluorocarbons for Ischemia Myocardium-Targeting 19F MRI-Guided Reperfusion Injury Therapy,” Advanced Science 10, no. 29 (2023): e2304178.

[152]

Z. Jin, Y. Sun, T. Yang, et al., “Nanocapsule-mediated Sustained H(2) Release in the Gut Ameliorates Metabolic Dysfunction-associated Fatty Liver Disease,” Biomaterials 276 (2021): 121030.

[153]

P. Zhao, Z. Jin, Q. Chen, et al., “Local Generation of Hydrogen for Enhanced Photothermal Therapy,” Nature Communications 9, no. 1 (2018): 4241.

[154]

N. Yang, F. Gong, B. Liu, et al., “Magnesium Galvanic Cells Produce Hydrogen and Modulate the Tumor Microenvironment to Inhibit Cancer Growth,” Nature Communications 13, no. 1 (2022): 2336.

[155]

Z. Kou, P. Zhao, Z. Wang, et al., “Acid-responsive H(2)-releasing Fe Nanoparticles for Safe and Effective Cancer Therapy,” Journal of Materials Chemistry B 7, no. 17 (2019): 2759-2765.

[156]

T. Yamada, K. Uchida, K. Onuma, et al., “Hydrogen Supplementation of Preservation Solution Improves Viability of Osteochondral Grafts,” Thescientificworldjournal [Electronic Resource] 2014 (2014): 109876.

[157]

M. Fan, Y. Wen, D. Ye, et al., “Acid-Responsive H2 -Releasing 2D MgB2 Nanosheet for Therapeutic Synergy and Side Effect Attenuation of Gastric Cancer Chemotherapy,” Adv Healthc Mater 8, no. 13 (2019): e1900157.

[158]

M. Kawamura, R. Imamura, Y. Kobayashi, et al., “Oral Administration of Si-Based Agent Attenuates Oxidative Stress and Ischemia-Reperfusion Injury in a Rat Model: A Novel Hydrogen Administration Method,” Frontiers in Medicine (Lausanne) 7 (2020): 95.

[159]

Q. Song, Y. Liu, X. Ding, et al., “A Drug co-delivery Platform Made of Magnesium-based Micromotors Enhances Combination Therapy for Hepatoma Carcinoma Cells,” Nanoscale 15, no. 38 (2023): 15573-15582.

[160]

H. Liu, X. Kang, P. Ren, et al., “Hydrogen Gas Ameliorates Acute Alcoholic Liver Injury via Anti-inflammatory and Antioxidant Effects and Regulation of Intestinal Microbiota,” International Immunopharmacology 120 (2023): 110252.

[161]

L. Zhao, Y. Wang, G. Zhang, T. Zhang, J. Lou, and J. Liu, “L-Arabinose Elicits Gut-Derived Hydrogen Production and Ameliorates Metabolic Syndrome in C57BL/6J Mice on High-Fat-Diet,” Nutrients 11, no. 12 (2019): 3054.

[162]

Q. Han, Y. Bai, C. Zhou, et al., “Effect of Molecular Hydrogen Treatment on Sepsis-Associated Encephalopathy in Mice Based on Gut Microbiota,” CNS Neuroscience & Therapeutics 29, no. 2 (2022): 633-645.

[163]

Y. A. Ghouri, V. Tahan, and B. Shen, “Secondary Causes of Inflammatory Bowel Diseases,” World Journal of Gastroenterology 26, no. 28 (2020): 3998-4017.

[164]

T. Huang, T. Okauchi, D. Hu, et al., “Pain Matrix Shift in the Rat Brain Following Persistent Colonic Inflammation Revealed by Voxel-based Statistical Analysis,” Molecular Pain 15 (2019): 744806919891327.

[165]

L. B. Grossberg, K. Papamichael, and A. S. Cheifetz, “Review Article: Emerging Drug Therapies in Inflammatory Bowel Disease,” Alimentary Pharmacology & Therapeutics 55, no. 7 (2022): 789-804.

[166]

I. Bjarnason and K. D. Rainsford, “NSAID-enteropathy and Intestinal Microbes,” Inflammopharmacology 29, no. 1 (2021): 1-4.

[167]

R. Ghosh, A. Alajbegovic, and A. V. Gomes, “NSAIDs and Cardiovascular Diseases: Role of Reactive Oxygen Species,” Oxidative Medicine and Cellular Longevity 2015 (2015): 536962.

[168]

Y. Akita, M. Higashiyama, C. Kurihara, et al., “Ameliorating Role of Hydrogen-Rich Water against NSAID-Induced Enteropathy via Reduction of ROS and Production of Short-Chain Fatty Acids,” Digestive Diseases and Sciences (2022): 1-11.

[169]

J. Peng, Q. He, S. Li, T. Liu, and J. Zhang, “Hydrogen-Rich Water Mitigates LPS-Induced Chronic Intestinal Inflammatory Response in Rats via Nrf-2 and NF-κB Signaling Pathways,” Veterinary Sciences 9, no. 11 (2022): 621.

[170]

D. Hu, T. Huang, M. Shigeta, et al., “Electrolyzed Hydrogen Water Alleviates Abdominal Pain Through Suppression of Colonic Tissue Inflammation in a Rat Model of Inflammatory Bowel Disease,” Nutrients 14, no. 21 (2022): 4451.

[171]

X. Qiu, K. Dong, J. Guan, and J. He, “Hydrogen Attenuates Radiation-induced Intestinal Damage by Reducing Oxidative Stress and Inflammatory Response,” International Immunopharmacology 84 (2020): 106517.

[172]

K.-D. Chen, K.-L. Wang, C. Chen, et al., “Hydrogen-rich Water Alleviates Constipation by Attenuating Oxidative Stress Through the sirtuin1/Nuclear Factor-erythroid-2-related Factor 2/Heme Oxygenase-1 Signaling Pathway,” World Journal of Gastroenterology 30, no. 20 (2024): 2709-2725.

[173]

S. T. Stengel, A. Fazio, S. Lipinski, et al., “Activating Transcription Factor 6 Mediates Inflammatory Signals in Intestinal Epithelial Cells Upon Endoplasmic Reticulum Stress,” Gastroenterology 159, no. 4 (2020): 1357-1374, e10.

[174]

M. Kajiya, M. J. Silva, K. Sato, K. Ouhara, and T. Kawai, “Hydrogen Mediates Suppression of Colon Inflammation Induced by Dextran Sodium Sulfate,” Biochemical and Biophysical Research Communications 386, no. 1 (2009): 11-15.

[175]

H. H. Arab, M. Y. Al-Shorbagy, and M. A. Saad, “Activation of Autophagy and Suppression of Apoptosis by Dapagliflozin Attenuates Experimental Inflammatory Bowel Disease in Rats: Targeting AMPK/mTOR, HMGB1/RAGE and Nrf2/HO-1 Pathways,” Chemico-Biological Interactions 335 (2021): 109368.

[176]

T. W. LeBaron, F. Asgharzadeh M. Khazei, B. Kura, A. Tarnava, and J. Slezak, “Molecular Hydrogen Is Comparable to Sulfasalazine as a Treatment for DSS-induced Colitis in Mice,” EXCLI Journal 20 (2021): 1106-1117.

[177]

H. Liu, D. Chen, X. Yang, et al., “Intestine-Targeted Controlled Hydrogen-Releasing MgH2 Microcapsules for Improving the Mitochondrial Metabolism of Inflammatory Bowel Disease,” Advanced Functional Materials 34, no. 33 (2024): 2316227.

[178]

Y. Wang, M. Wang, B. Xie, et al., “Effects of Molecular Hydrogen Intervention on the Gut Microbiome in Methamphetamine Abusers With Mental Disorder,” Brain Research Bulletin 193 (2023): 47-58.

[179]

K. Wei, F. Gong, J. Wu, et al., “Orally Administered Silicon Hydrogen Nanomaterials as Target Therapy to Treat Intestinal Diseases,” ACS Nano 17, no. 21 (2023): 21539-21552.

[180]

S. Takahashi, K. Nakagawa, W. Nagata, A. Koizumi, and T. Ishizuka, “A Preliminary Therapeutic Study of the Effects of Molecular Hydrogen on Intestinal Dysbiosis and Small Intestinal Injury in High-fat Diet-loaded Senescence-accelerated Mice,” Nutrition (Burbank, Los Angeles County, Calif.) 122 (2024): 112372.

[181]

L. Song, Y. Zhang, C. Zhu, X. Ding, L. Yang, and H. Yan, “Hydrogen-rich Water Partially Alleviate Inflammation, Oxidative Stress and Intestinal Flora Dysbiosis in DSS-induced Chronic Ulcerative Colitis Mice,” Advances in Medical Sciences 67, no. 1 (2022): 29-38.

[182]

L. Ge, J. Qi, B. Shao, et al., “Microbial Hydrogen Economy Alleviates Colitis by Reprogramming Colonocyte Metabolism and Reinforcing Intestinal Barrier,” Gut Microbes 14, no. 1 (2022): 2013764.

[183]

Y. Q. Liu, Y. F. Liu, X. M. Ma, et al., “Hydrogen-rich Saline Attenuates Skin Ischemia/Reperfusion Induced Apoptosis via Regulating Bax/Bcl-2 Ratio and ASK-1/JNK Pathway,” Journal of Plastic, Reconstructive & Aesthetic Surgery 68, no. 7 (2015): e147-e156.

[184]

Z. Lu, Y. Lin, B. Peng, Z. Bao, K. Niu, and J. Gong, “Hydrogen-Rich Saline Ameliorates Hepatic Ischemia-Reperfusion Injury through Regulation of Endoplasmic Reticulum Stress and Apoptosis,” Digestive Diseases and Sciences 62, no. 12 (2017): 3479-3486.

[185]

C. B. Zhang, Y. C. Tang, X. J. Xu, S. X. Guo, and H. Z. Wang, “Hydrogen Gas Inhalation Protects Against Liver Ischemia/Reperfusion Injury by Activating the NF-kappaB Signaling Pathway,” Experimental and Therapeutic Medicine 9, no. 6 (2015): 2114-2120.

[186]

C. Nie, X. Ding, A. Rong, et al., “Hydrogen Gas Inhalation Alleviates Myocardial Ischemia-reperfusion Injury by the Inhibition of Oxidative Stress and NLRP3-mediated Pyroptosis in Rats,” Life Sciences 272 (2021): 119248.

[187]

X. Zhai, X. Chen, J. Shi, et al., “Lactulose Ameliorates Cerebral Ischemia-reperfusion Injury in Rats by Inducing Hydrogen by Activating Nrf2 Expression,” Free Radical Biology and Medicine 65 (2013): 731-741.

[188]

M. J. Wu, M. Chen, S. Sang, et al., “Protective Effects of Hydrogen Rich Water on the Intestinal Ischemia/Reperfusion Injury due to Intestinal Intussusception in a Rat Model,” Medical Gas Research 7, no. 2 (2017): 101-106.

[189]

Y. Shi, X. Zhang, Z. Wan, et al., “Mesenchymal Stem Cells Against Intestinal Ischemia-reperfusion Injury: A Systematic Review and Meta-analysis of Preclinical Studies,” Stem Cell Research & Therapy 13, no. 1 (2022): 216.

[190]

M. Levi and T. van der Poll, “Coagulation and Sepsis,” Thrombosis Research 149 (2017): 38-44.

[191]

S. Eryilmaz, Z. Turkyilmaz, R. Karabulut, et al., “The Effects of Hydrogen-rich Saline Solution on Intestinal Anastomosis Performed After Intestinal Ischemia Reperfusion Injury,” Journal of Pediatric Surgery 55, no. 8 (2020): 1574-1578.

[192]

T. Shigeta, S. Sakamoto, X.-K. Li, et al., “Luminal Injection of Hydrogen-Rich Solution Attenuates Intestinal Ischemia-Reperfusion Injury in Rats,” Transplantation 99, no. 3 (2015): 500-507.

[193]

B. Osterud, “Tissue Factor Expression in Blood Cells,” Thrombosis Research 125, no. Suppl 1 (2010): S31-S34.

[194]

K. Taniguchi and M. Karin, “NF-κB, Inflammation, Immunity and Cancer: Coming of Age,” Nature Reviews Immunology 18, no. 5 (2018): 309-324.

[195]

Y.-F. Mao, X.-F. Zheng, J.-M. Cai, et al., “Hydrogen-rich Saline Reduces Lung Injury Induced by Intestinal Ischemia/Reperfusion in Rats,” Biochemical and Biophysical Research Communications 381, no. 4 (2009): 602-605.

[196]

X. Zheng, Y. Mao, J. Cai, et al., “Hydrogen-rich Saline Protects Against Intestinal Ischemia/Reperfusion Injury in Rats,” Free Radical Research 43, no. 5 (2009): 478-484.

[197]

L. Zhang, Q. Wei, X. Liu, et al., “Exosomal microRNA-98-5p From Hypoxic Bone Marrow Mesenchymal Stem Cells Inhibits Myocardial Ischemia-reperfusion Injury by Reducing TLR4 and Activating the PI3K/Akt Signaling Pathway,” International Immunopharmacology 101, no. Pt B (2021): 107592.

[198]

S. Floyd, C. Favre, F. M. Lasorsa, et al., “The Insulin-Like Growth Factor-I-mTOR Signaling Pathway Induces the Mitochondrial Pyrimidine Nucleotide Carrier to Promote Cell Growth,” Molecular Biology of the Cell 18, no. 9 (2007): 3545-3555.

[199]

W. Yao, X. Lin, X. Han, et al., “MicroRNA Files in the Prevention of Intestinal Ischemia/Reperfusion Injury by Hydrogen Rich Saline,” Bioscience Reports 40, no. 1 (2020): BSR20191043.

[200]

R. L. Siegel, K. D. Miller, H. E. Fuchs, and A. Jemal, “Cancer Statistics, 2022,” CA: A Cancer Journal for Clinicians 72, no. 1 (2022): 7-33.

[201]

Y. Zheng, Y. Fu, P. P. Wang, and Z. Y. Ding, “Neoantigen: A Promising Target for the Immunotherapy of Colorectal Cancer,” Disease Markers 2022 (2022): 8270305.

[202]

C. Stefani and D. Miricescu, “Growth Factors, PI3K/AKT/mTOR and MAPK Signaling Pathways in Colorectal Cancer Pathogenesis: Where Are We Now?,” International Journal of Molecular Sciences 22, no. 19 (2021): 10260.

[203]

A. Kitamura, S. Kobayashi, T. Matsushita, H. Fujinawa, and K. Murase, “Experimental Verification of Protective Effect of Hydrogen-rich Water Against Cisplatin-induced Nephrotoxicity in Rats Using Dynamic Contrast-enhanced CT,” Bjr 83, no. 990 (2010): 509-514.

[204]

R. De Matteis, M. B. Flak, M. Gonzalez-Nunez, et al., “Aspirin Activates Resolution Pathways to Reprogram T Cell and Macrophage Responses in Colitis-associated Colorectal Cancer,” Science Advances 8, no. 5 (2022): eabl5420.

[205]

M. Kasamatsu, T. Arima, T. Ikebukuro, et al., “Prophylactic Instillation of Hydrogen-Rich Water Decreases Corneal Inflammation and Promotes Wound Healing by Activating Antioxidant Activity in a Rat Alkali Burn Model,” International Journal of Molecular Sciences 23, no. 17 (2022): 9774.

[206]

J. Akagi and H. Baba, “Hydrogen Gas Restores Exhausted CD8+ T Cells in Patients With Advanced Colorectal Cancer to Improve Prognosis,” Oncology Reports 41, no. 1 (2019): 301-311.

[207]

R. A. Igal, “Stearoyl CoA desaturase-1: New Insights Into a central Regulator of Cancer Metabolism,” Biochimica Et Biophysica Acta 1861, no. 12 Pt A (2016): 1865-1880.

[208]

E. Currie, A. Schulze, R. Zechner, and T. C. Walther, “Cellular Fatty Acid Metabolism and Cancer,” Cell Metabolism 18, no. 2 (2013): 153-161.

[209]

B. Peck, Z. T. Schug, Q. Zhang, et al., “Inhibition of Fatty Acid Desaturation Is Detrimental to Cancer Cell Survival in Metabolically Compromised Environments,” Cancer & Metabolism 4 (2016): 6.

[210]

A. M. Holder, A. M. Gonzalez-Angulo, H. Chen, et al., “High Stearoyl-CoA Desaturase 1 Expression Is Associated With Shorter Survival in Breast Cancer Patients,” Breast Cancer Research and Treatment 137, no. 1 (2013): 319-327.

[211]

J. Li, S. Condello, J. Thomes-Pepin, et al., “Lipid Desaturation Is a Metabolic Marker and Therapeutic Target of Ovarian Cancer Stem Cells,” Cell Stem Cell 20, no. 3 (2017): 303-314. e5.

[212]

S. Revathidevi and A. K. Munirajan, “Akt in Cancer: Mediator and More,” Seminars in Cancer Biology 59 (2019): 80-91.

[213]

X. Zhang, G. Tao, Y. Zhao, et al., “Molecular Hydrogen Inhibits Colorectal Cancer Growth via the AKT/SCD1 Signaling Pathway,” BioMed Research International 2022 (2022): 8024452.

[214]

F. Asgharzadeh, A. Tarnava, A. Mostafapour, M. Khazaei, and T. W. LeBaron, “Hydrogen-rich Water Exerts Anti-tumor Effects Comparable to 5-fluorouracil in a Colorectal Cancer Xenograft Model,” World Journal of Gastrointestinal Oncology 14, no. 1 (2022): 242-252.

[215]

T. Kawamura, N. Wakabayashi, N. Shigemura, et al., “Hydrogen Gas Reduces Hyperoxic Lung Injury via the Nrf2 Pathway in Vivo,” American Journal of Physiology. Lung Cellular and Molecular Physiology 304, no. 10 (2013): L646-L656.

[216]

M. Yang, Y. Yu, K. Xie, and Y. Yu, “Effects of Hydrogen on Lung Injury in Wild-type and Nrf2 Gene Knockout Mice: Relationship With Nrf2/HO-1/HMGB1 Pathway,” Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 31, no. 7 (2019): 862-866.

[217]

Y. Wang, Q. Han, L. Liu, et al., “Natural Hydrogen Gas and Engineered Microalgae Prevent Acute Lung Injury in sepsis,” Materials Today Bio 28 (2024): 101247.

[218]

Q. Li, M. Shi, Y. Ang, et al., “Hydrogen Ameliorates Endotoxin-induced Acute Lung Injury Through AMPK-mediated Bidirectional Regulation of Caspase3,” Molecular Immunology 168 (2024): 64-74.

[219]

H. Yin, Y. Feng, Y. Duan, S. Ma, Z. Guo, and Y. Wei, “Hydrogen Gas Alleviates Lipopolysaccharide-induced Acute Lung Injury and Inflammatory Response in Mice,” Journal of Inflammation (London) 19, no. 1 (2022): 16.

[220]

S. A. Christenson, B. M. Smith, M. Bafadhel, and N. Putcha, “Chronic Obstructive Pulmonary Disease,” Lancet 399, no. 10342 (2022): 2227-2242.

[221]

O. Editorial, “Erratum to the Effects of Hydrogen Treatment in a Cigarette Smoke Solution-induced Chronic Obstructive Pulmonary Disease-Like Changes in an Animal Model,” Journal of Thoracic Disease 15, no. 2 (2023): 942.

[222]

J. C. Su, Y. Zhang, C. Cheng, et al., “Hydrogen Regulates the M1/M2 Polarization of Alveolar Macrophages in a Rat Model of Chronic Obstructive Pulmonary Disease,” Experimental Lung Research 47, no. 7 (2021): 301-310.

[223]

M. Rekatsina, A. Paladini, A. Piroli, P. Zis, J. V. Pergolizzi, and G. Varrassi, “Pathophysiology and Therapeutic Perspectives of Oxidative Stress and Neurodegenerative Diseases: A Narrative Review,” Advances in Therapy 37, no. 1 (2020): 113-139.

[224]

L. Zhang, P. Zhao, C. Yue, et al., “Sustained Release of Bioactive Hydrogen by Pd Hydride Nanoparticles Overcomes Alzheimer's Disease,” Biomaterials 197 (2019): 393-404.

[225]

X.-B. Du, Y.-T. Lin, Q.-Q. Shi, et al., “Hydrogen-rich Water Ameliorates Neuropathological Impairments in a Mouse Model of Alzheimer's Disease Through Reducing Neuroinflammation and Modulating Intestinal Microbiota,” Neural Regeneration Research 17, no. 2 (2022): 409-417.

[226]

D. Lee and J. I. Choi, “Hydrogen-Rich Water Improves Cognitive Ability and Induces Antioxidative, Antiapoptotic, and Anti-Inflammatory Effects in an Acute Ischemia-Reperfusion Injury Mouse Model,” BioMed Research International 2021 (2021): 9956938.

[227]

X. Wang, L. Zhang, W. Zhao, and T. Liu, “The Protective Effects of Hydrogen on HO-1 Expression in the Brainafter Focal Cerebral Ischemia Reperfusion in Rats,” Turkish Journal of Medical Sciences 46, no. 5 (2016): 1534-1539.

[228]

Z. Peng, X. J. Li, Y. Zhou, et al., “Hydrogen Exerts Neuroprotective Effects After Subarachnoid Hemorrhage by Attenuating Neuronal Ferroptosis and Inhibiting Neuroinflammation,” Free Radical Biology and Medicine 215 (2024): 79-93.

[229]

L. Wang, Z. Yin, F. Wang, et al., “Hydrogen Exerts Neuroprotection by Activation of the miR-21/PI3K/AKT/GSK-3beta Pathway in an in Vitro Model of Traumatic Brain Injury,” Journal of Cellular and Molecular Medicine 24, no. 7 (2020): 4061-4071.

[230]

S. Coral-Perez, I. Martinez-Martel, M. Martinez-Serrat, et al., “Treatment With Hydrogen-Rich Water Improves the Nociceptive and Anxio-Depressive-Like Behaviors Associated With Chronic Inflammatory Pain in Mice,” Antioxidants (Basel) 11, no. 11 (2022): 2153.

[231]

N. Lian, M. Shen, K. Zhang, et al., “Drinking Hydrogen-Rich Water Alleviates Chemotherapy-Induced Neuropathic Pain through the Regulation of Gut Microbiota,” Journal of Pain Research 14 (2021): 681-691.

[232]

P. Guan, X. M. Lin, S. C. Yang, et al., “Hydrogen Gas Reduces Chronic Intermittent Hypoxia-induced Hypertension by Inhibiting Sympathetic Nerve Activity and Increasing Vasodilator Responses via the Antioxidation,” Journal of Cellular Biochemistry 120, no. 3 (2019): 3998-4008.

[233]

K. Sugai, T. Tamura, M. Sano, et al., “Daily Inhalation of Hydrogen Gas Has a Blood Pressure-lowering Effect in a Rat Model of Hypertension,” Scientific Reports 10, no. 1 (2020): 20173.

[234]

G. Song, H. Tian, J. Liu, H. Zhang, X. Sun, and S. Qin, “H2 inhibits TNF-alpha-induced Lectin-Like Oxidized LDL Receptor-1 Expression by Inhibiting Nuclear Factor kappaB Activation in Endothelial Cells,” Biotechnology Letters 33, no. 9 (2011): 1715-1722.

[235]

M. Xu, X. Zhang, B. Dong, W. Wang, and Z. Zhao, “Sustained Release of Hydrogen by PdH-Te Nanozyme for Anti-Inflammatory Therapy against Atherosclerosis,” Particle & Particle Systems Characterization 41, no. 4 (2023): 2300135.

[236]

A. T. Hernowo, S. Widyarti, and S. Aristyani, “Evaluating the Safety and Therapeutic Efficacy of Intravenous Hydrogen Nanobubble Infusions in a Hypercholesterolemic Rat Model,” Berkala Penelitian Hayati 30, no. 1 (2024): 40-47.

[237]

Z. Koksal, O. Kurtipek, M. Arslan, A. D. Dursun, Z. Yigman, and A. Ozer, “Protective Effects of Hydrogen Rich Saline Solution in Rats With Experimental Myocardial Ischemia Reperfusion Injury,” Heliyon 9, no. 12 (2023): e22973.

[238]

X. Li, L. Li, X. Liu, et al., “Attenuation of Cardiac Ischaemia-reperfusion Injury by Treatment With Hydrogen-rich Water,” Current Molecular Medicine 19, no. 4 (2019): 294-302.

[239]

L. Yao, H. Chen, Q. Wu, and K. Xie, “Hydrogen-rich Saline Alleviates Inflammation and Apoptosis in Myocardial I/R Injury via PINK-mediated Autophagy,” International Journal of Molecular Medicine 44, no. 3 (2019): 1048-1062.

[240]

X. Gong, X. Fan, X. Yin, et al., “Hydrogen Therapy After Resuscitation Improves Myocardial Injury Involving Inhibition of Autophagy in an Asphyxial Rat Model of Cardiac Arrest,” Experimental and Therapeutic Medicine 23, no. 6 (2022): 376.

[241]

C. Nie, R. Zou, S. Pan, et al., “Hydrogen Gas Inhalation Ameliorates Cardiac Remodelling and Fibrosis by Regulating NLRP3 Inflammasome in Myocardial Infarction Rats,” Journal of Cellular and Molecular Medicine 25, no. 18 (2021): 8997-9010.

[242]

X. Zhai, X. Chen, J. Lu, et al., “Hydrogen-rich Saline Improves Non‑Alcoholic Fatty Liver Disease by Alleviating Oxidative Stress and Activating Hepatic PPARalpha and PPARgamma,” Molecular Medicine Reports 15, no. 3 (2017): 1305-1312.

[243]

B. Liu, J. Xue, M. Zhang, et al., “Hydrogen Inhalation Alleviates Nonalcoholic Fatty Liver Disease in Metabolic Syndrome Rats,” Molecular Medicine Reports 22, no. 4 (2020): 2860-2868.

[244]

Q. Yang, G. Ji, R. Pan, Y. Zhao, and P. Yan, “Protective Effect of Hydrogen-rich Water on Liver Function of Colorectal Cancer Patients Treated With mFOLFOX6 Chemotherapy,” Molecular and Clinical Oncology 7, no. 5 (2017): 891-896.

[245]

Y. Gao, H. Yang, Y. Fan, L. Li, J. Fang, and W. Yang, “Hydrogen-Rich Saline Attenuates Cardiac and Hepatic Injury in Doxorubicin Rat Model by Inhibiting Inflammation and Apoptosis,” Mediators of Inflammation 2016 (2016): 1320365.

[246]

F. Li, T. Li, C.-R. Li, et al., “Potential Protective Role of Hydrogen Against Cisplatininduced Side Effects During Chemotherapy: A Mini-review of a Novel Hypothesis for Antagonism of Hydrogen,” Tropical Journal of Pharmaceutical Research 16, no. 11 (2018): 2773-2776.

[247]

B. Chen, D. Song, J. Ma, and W. Zhu, “Molecular Hydrogen Suppresses Renal Injury in Chronic Kidney Disease Rats,” Journal of Bioprocessing & Biotechniques 08, no. 04 (2018).

[248]

R. B. Singh, Z. Sumbalova, G. Fatima, et al., “Effects of Molecular Hydrogen in the Pathophysiology and Management of Cardiovascular and Metabolic Diseases,” Reviews in Cardiovascular Medicine 25, no. 1 (2024): 33.

[249]

J. L. Xue, B. Y. Liu, M. Zhao, et al., “Inhalation of 4% and 67% Hydrogen Ameliorates Oxidative Stress, Inflammation, Apoptosis, and Necroptosis in a Rat Model of Glycerol-induced Acute Kidney Injury,” Medical Gas Research 13, no. 2 (2023): 78-88.

[250]

J. Chen, H. Zhang, J. Hu, et al., “Hydrogen-Rich Saline Alleviates Kidney Fibrosis Following AKI and Retains Klotho Expression,” Frontiers in Pharmacology 8 (2017): 499.

[251]

J. Li, Z. Hong, H. Liu, et al., “Hydrogen-Rich Saline Promotes the Recovery of Renal Function After Ischemia/Reperfusion Injury in Rats via Anti-apoptosis and Anti-inflammation,” Frontiers in Pharmacology 7 (2016): 106.

[252]

Y. Zhang, G. Chen, Z. Yan, L. Wang, and D. Wang, “Hydrogen Gas Promotes Apoptosis of Lung Adenocarcinoma A549 Cells Through X-linked Inhibitor of Apoptosis and Baculoviral Inhibitor of Apoptosis Protein Repeat-Containing 3,” Journal of Cancer Research and Therapeutics 18, no. 5 (2022): 1380-1386.

[253]

Y. Saitoh, N. Kawasaki, N. Eguchi, and M. Ikeshima, “Combined Treatment With Dissolved Hydrogen Molecule and Platinum Nanocolloid Exerts Carcinostatic/Carcinocidal Effects by Increasing Hydrogen Peroxide Generation and Cell Death in the human Gastric Cancer Cell Line NUGC-4,” Free Radical Research 55, no. 3 (2021): 211-220.

[254]

K.-C. Xu, J.-B. Chen, X.-F. Kong, F. Mu, T.-Y. Lu, and Y.-Y. Lu, “Hydrogen Therapy Can be Used to Control Tumor Progression and Alleviate the Adverse Events of Medications in Patients With Advanced Non-small Cell Lung Cancer,” Medical Gas Research 10, no. 2 (2020): 75-80.

[255]

A. Tansel and D. J. Levinthal, “Understanding Our Tests: Hydrogen-Methane Breath Testing to Diagnose Small Intestinal Bacterial Overgrowth,” Clinical and Translational Gastroenterology 14, no. 4 (2023): e00567.

[256]

J. P. Algera, E. Colomier, C. Melchior, et al., “Associations Between Postprandial Symptoms, Hydrogen and Methane Production, and Transit Time in Irritable Bowel Syndrome,” Neurogastroenterology & Motility 35, no. 2 (2022): e14482.

[257]

N. Dharmawardana, T. Goddard, C. Woods, et al., “Breath Methane to Hydrogen Ratio as a Surrogate Marker of Intestinal Dysbiosis in Head and Neck Cancer,” Scientific Reports 10, no. 1 (2020): 15010.

[258]

M. Zhang, Y. Xu, J. Zhang, et al., “Application of Methane and Hydrogen-based Breath Test in the Study of Gestational Diabetes Mellitus and Intestinal Microbes,” Diabetes Research and Clinical Practice 176 (2021): 108818.

[259]

A. Mollar, M. P. Villanueva, E. NÚÑez, et al., “Hydrogen- and Methane-Based Breath Testing and Outcomes in Patients with Heart Failure,” Journal of Cardiac Failure 25, no. 5 (2019): 319-327.

[260]

L. Wang, Y.-M. Yu, Y.-Q. Zhang, J. Zhang, N. Lu, and N. Liu, “Hydrogen Breath Test to Detect Small Intestinal Bacterial Overgrowth: A Prevalence Case-control Study in Autism,” European Child & Adolescent Psychiatry 27, no. 2 (2017): 233-240.

[261]

B. Xie, Y. Wang, Y. Lu, et al., “A Novel Intervention of Molecular Hydrogen on the Unbalance of the Gut Microbiome in Opioid Addiction: Experimental and human Studies,” Biomedicine & Pharmacotherapy 178 (2024): 117273.

[262]

B. Liang, L. Shi, D. Du, et al., “Hydrogen-Rich Water Ameliorates Metabolic Disorder via Modifying Gut Microbiota in Impaired Fasting Glucose Patients: A Randomized Controlled Study,” Antioxidants 12, no. 6 (2023): 1245.

[263]

S. T. Wang, C. Bao, Y. He, et al., “Hydrogen Gas (XEN) Inhalation Ameliorates Airway Inflammation in Asthma and COPD Patients,” Qjm 113, no. 12 (2020): 870-875.

[264]

Y. Niu, Q. Nie, L. Dong, et al., “Hydrogen Attenuates Allergic Inflammation by Reversing Energy Metabolic Pathway Switch,” Scientific Reports 10, no. 1 (2020): 1962.

[265]

Z. G. Zheng, W. Z. Sun, J. Y. Hu, 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,” Respiratory Research 22, no. 1 (2021): 149.

[266]

Y. Tan, Y. Xie, G. Dong, et al., “The Effect of 14-Day Consumption of Hydrogen-Rich Water Alleviates Fatigue but Does Not Ameliorate Dyspnea in Long-COVID Patients: A Pilot, Single-Blind, and Randomized, Controlled Trial,” Nutrients 16, no. 10 (2024): 1529.

[267]

A. Yoritaka, Y. Kobayashi, T. Hayashi, S. Saiki, and N. Hattori, “Randomized Double-blind Placebo-controlled Trial of Hydrogen Inhalation for Parkinson's Disease: A Pilot Study,” Neurological Sciences 42, no. 11 (2021): 4767-4770.

[268]

H. Ono, Y. Nishijima, N. Adachi, et al., “Improved Brain MRI Indices in the Acute Brain Stem Infarct Sites Treated With Hydroxyl Radical Scavengers, Edaravone and Hydrogen, as Compared to Edaravone Alone. A Non-controlled Study,” Medical Gas Research 1, no. 1 (2011): 12.

[269]

K. Nagatani, H. Nawashiro, S. Takeuchi, et al., “Safety of Intravenous Administration of Hydrogen-enriched Fluid in Patients With Acute Cerebral Ischemia: Initial Clinical Studies,” Medical Gas Research 3, no. 1 (2013): 13.

[270]

S. Takeuchi, K. Mori, H. Arimoto, et al., “Effects of Intravenous Infusion of Hydrogen-rich Fluid Combined With Intra-cisternal Infusion of Magnesium Sulfate in Severe Aneurysmal Subarachnoid Hemorrhage: Study Protocol for a Randomized Controlled Trial,” BMC Neurology 14, no. 1 (2014): 176.

[271]

H. Ono, Y. Nishijima, S. Ohta, et al., “Hydrogen Gas Inhalation Treatment in Acute Cerebral Infarction: A Randomized Controlled Clinical Study on Safety and Neuroprotection,” Journal of Stroke and Cerebrovascular Diseases 26, no. 11 (2017): 2587-2594.

[272]

H. Ono, Y. Nishijima, and S. Ohta, “Therapeutic Inhalation of Hydrogen Gas for Alzheimer's Disease Patients and Subsequent Long-Term Follow-Up as a Disease-Modifying Treatment: An Open Label Pilot Study,” Pharmaceuticals 16, no. 3 (2023): 434.

[273]

T. Tamura, K. Hayashida, M. Sano, et al., “Feasibility and Safety of Hydrogen Gas Inhalation for Post-Cardiac Arrest Syndrome - First-in-Human Pilot Study,” Circulation Journal 80, no. 8 (2016): 1870-1873.

[274]

A. V. Deryugina, D. A. Danilova, Y. D. Brichkin, et al., “Molecular Hydrogen Exposure Improves Functional state of Red Blood Cells in the Early Postoperative Period,” Medical Gas Research 13, no. 2 (2023): 59-66.

[275]

G. Song, M. Li, H. Sang, et al., “Hydrogen-rich Water Decreases Serum LDL-cholesterol Levels and Improves HDL Function in Patients With Potential Metabolic Syndrome,” Journal of Lipid Research 54, no. 7 (2013): 1884-1893.

[276]

T. Tamura, H. Narumiya, K. Homma, and M. Suzuki, “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,” Critical Care Medicine 52, no. 10 (2024): 1567-1576.

[277]

S. Kajiyama, G. Hasegawa, M. Asano, et al., “Supplementation of Hydrogen-rich Water Improves Lipid and Glucose Metabolism in Patients With Type 2 Diabetes or Impaired Glucose Tolerance,” Nutrition Research 28, no. 3 (2008): 137-143.

[278]

M. Kubota, M. Kawashima, S. Inoue, et al., “Randomized, Crossover Clinical Efficacy Trial in Humans and Mice on Tear Secretion Promotion and Lacrimal Gland Protection by Molecular Hydrogen,” Scientific Reports 11, no. 1 (2021): 6434.

[279]

G. Tao, G. Zhang, W. Chen, et al., “A Randomized, Placebo-controlled Clinical Trial of Hydrogen/Oxygen Inhalation for Non-alcoholic Fatty Liver Disease,” Journal of Cellular and Molecular Medicine 26 (2022): 4113-4123.

[280]

R. Asada, Y. Saitoh, and N. Miwa, “Effects of Hydrogen-rich Water Bath on Visceral Fat and Skin Blotch, With Boiling-resistant Hydrogen Bubbles,” Medical Gas Research 9, no. 2 (2019): 68-73.

[281]

Q. Zhu, Y. Wu, Y. Li, et al., “Positive Effects of Hydrogen-water Bathing in Patients of Psoriasis and Parapsoriasis En Plaques,” Scientific Reports 8, no. 1 (2018): 8051.

[282]

Y. Tanaka, L. Xiao, and N. Miwa, “Hydrogen-rich Bath With Nano-sized Bubbles Improves Antioxidant Capacity Based on Oxygen Radical Absorbing and Inflammation Levels in human Serum,” Medical Gas Research 12, no. 3 (2022): 91-99.

[283]

K.-C. Lu, M.-C. Shen, R.-L. Wang, et al., “Using Oral Molecular Hydrogen Supplements to Combat Microinflammation in Humans: A Pilot Observational Study,” International Journal of Medical Sciences 21, no. 12 (2024): 2390-2401.

[284]

K.-C. Xu, J.-B. Chen, X.-F. Kong, et al., ““Real World Survey” of Hydrogen-controlled Cancer: A Follow-up Report of 82 Advanced Cancer Patients,” Medical Gas Research 9, no. 3 (2019): 115-121.

[285]

S.-I. Hirano, Y. Aoki, X.-K. Li, N. Ichimaru, S. Takahara, and Y. Takefuji, “Protective Effects of Hydrogen Gas Inhalation on Radiation-induced Bone Marrow Damage in Cancer Patients,” Medical Gas Research 11, no. 3 (2021): 104-109.

[286]

Y. Jiang, Y. Bian, N. Lian, et al., “iTRAQ-Based Quantitative Proteomic Analysis of Intestines in Murine Polymicrobial Sepsis With Hydrogen Gas Treatment,” Drug Design, Development and Therapy 14 (2020): 4885-4900.

[287]

M. Iketani, I. Sakane, Y. Fujita, M. Ito, and I. Ohsawa, “H2 -induced Transient Upregulation of Phospholipids With Suppression of Energy Metabolism,” Medical Gas Research 13, no. 3 (2023): 133-141.

[288]

L. Chen, Y. Chao, P. Cheng, N. Li, H. Zheng, and Y. Yang, “UPLC-QTOF/MS-Based Metabolomics Reveals the Protective Mechanism of Hydrogen on Mice with Ischemic Stroke,” Neurochem Res 44, no. 8 (2019): 1950-1963.

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