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1
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Todorović N, Kuzmanovic J, Javorac D, Ostojic SM. Role of molecular hydrogen in obesity treatment: modulation of GLP-1, irisin, and PGC-1α for improved metabolism. Med Gas Res 2025; 15:442-443. [PMID: 40251025 PMCID: PMC12054667 DOI: 10.4103/mgr.medgasres-d-24-00146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Revised: 01/03/2025] [Accepted: 01/17/2025] [Indexed: 04/20/2025] Open
Affiliation(s)
- Nikola Todorović
- Applied Bioenergetics Lab, Faculty of Sport and PE, University of Novi Sad, Novi Sad, Serbia
| | - Jovan Kuzmanovic
- Applied Bioenergetics Lab, Faculty of Sport and PE, University of Novi Sad, Novi Sad, Serbia
| | - Dejan Javorac
- Applied Bioenergetics Lab, Faculty of Sport and PE, University of Novi Sad, Novi Sad, Serbia
| | - Sergej M. Ostojic
- Applied Bioenergetics Lab, Faculty of Sport and PE, University of Novi Sad, Novi Sad, Serbia
- Department of Nutrition and Public Health, University of Agder, Kristiansand, Norway
- Faculty of Health Sciences, University of Pécs, Pécs, Hungary
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2
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Lu H, Chen W, Ying Y, Gu D, Li R, Li X, Cheng J, Sun X, Zhang Y, Liu W, Shen H. Dietary addition of magnesium hydride nanoparticles: a breakthrough in combating high-fat diet-induced chronic kidney disease. Med Gas Res 2025; 15:374-382. [PMID: 40251018 PMCID: PMC12054669 DOI: 10.4103/mgr.medgasres-d-24-00090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Revised: 10/28/2024] [Accepted: 11/28/2024] [Indexed: 04/20/2025] Open
Abstract
A substantial body of evidence indicates a positive correlation between dyslipidemia and an elevated risk of chronic kidney disease, with renal interstitial fibrosis frequently serving as a common pathway in the advanced stages of chronic kidney disease progression. Hydrogen has anti-inflammatory and antioxidant properties, and magnesium hydride nanoparticle is a material with high hydrogen storage capacity. Magnesium hydride -fortified feed is capable of releasing hydrogen gas steadily and continuously within the digestive tract. A 12-week high-fat diet significantly elevated the serum urea and creatinine levels in mice. In contrast, dietary addition of magnesium hydride demonstrated a notable protective effect against pathological conditions. Additionally, magnesium hydride -fortified feed was found to reduce renal fibrosis and thereby improve renal function. In support of these findings, an in vitro study utilizing human kidney cortical proximal tubule epithelial cells (HK-2 cells) exposed to palmitic acid under conditions mimicking a high-fat diet confirmed the renoprotective effects of magnesium hydride. Furthermore, the primary target phosphatase and tensin homologue deleted on chromosome 10 and the molecular mechanisms underlying the effects of magnesium hydride, specifically its ability to inhibit the transforming growth factor-beta -Smad family member 2 and 3 (Smad2/3) axis through downregulating the expression of phosphatase and tensin homologue deleted on chromosome 10, were elucidated. Additionally, overexpression of Hes family BHLH transcription factor 1 can negate the beneficial effects of magnesium hydride, suggesting that Hes family BHLH transcription factor 1 may serve as an upstream regulatory target in the context of the effects of magnesium hydride. In conclusion, this study demonstrated that magnesium hydride functions as a safe and effective hydrogen source capable of inhibiting the activation of the transforming growth factor-beta/Smad2/3 and protein kinase B/mechanistic target of rapamycin pathways by increasing the expression of phosphatase and tensin homologue deleted on chromosome 10. This mechanism counteracts the progression of high-fat diet-induced chronic renal damage.
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Affiliation(s)
- Hongtao Lu
- Department of Naval Medicine, Naval Medical University, Shanghai, China
| | - Wanqiu Chen
- Department of Naval Medicine, Naval Medical University, Shanghai, China
| | - Yajing Ying
- Department of Naval Medicine, Naval Medical University, Shanghai, China
| | - Deqian Gu
- No. 980 Hospital of Joint Logistics Support Force, Shijiazhuang, Hebei Province, China
| | - Rui Li
- Department of Naval Medicine, Naval Medical University, Shanghai, China
| | - Xiangtong Li
- Department of Naval Medicine, Naval Medical University, Shanghai, China
| | - Jin Cheng
- Internal Medicine III (Nephrology and Endocrinology), Naval Medical Center, Naval Medical University, Shanghai, China
| | - Xuejun Sun
- Department of Naval Medicine, Naval Medical University, Shanghai, China
- Department of Nephrology, Seventh People’s Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yinyin Zhang
- Department of Naval Medicine, Naval Medical University, Shanghai, China
| | - Wenrui Liu
- Center of Hydrogen Science, Shanghai Jiao Tong University, Shanghai, China
| | - Hui Shen
- Department of Naval Medicine, Naval Medical University, Shanghai, China
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3
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Grepl P, Botek M, Krejčí J, McKune A. Molecular hydrogen inhalation modulates resting metabolism in healthy females: findings from a randomized, double-blind, placebo-controlled crossover study. Med Gas Res 2025; 15:367-373. [PMID: 39923133 PMCID: PMC12054672 DOI: 10.4103/mgr.medgasres-d-24-00085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Revised: 10/31/2024] [Accepted: 11/19/2024] [Indexed: 02/10/2025] Open
Abstract
Initially, molecular hydrogen was considered a physiologically inert and non-functional gas. However, experimental and clinical studies have shown that molecular hydrogen has anti-inflammatory, anti-apoptotic, and strong selective antioxidant effects. This study aimed to evaluate the effects of 60 minutes of molecular hydrogen inhalation on respiratory gas analysis parameters using a randomized, double-blind, placebo-controlled, crossover design. The study was conducted at Faculty of Physical Culture, Palacký University Olomouc from September 2022 to March 2023. Twenty, physically active female participants aged 22.1 ± 1.6 years who inhaled either molecular hydrogen or ambient air through a nasal cannula (300 mL/min) for 60 minutes while resting were included in this study. Metabolic response was measured using indirect calorimetry. Breath-by-breath data were averaged over four 15-minute intervals. Compared with placebo (ambient air), molecular hydrogen inhalation significantly decreased respiratory exchange ratio and ventilation across all intervals. Furthermore, the change in respiratory exchange ratio was negatively correlated with body fat percentage from 30 minutes onwards. In conclusion, 60 minutes of resting molecular hydrogen inhalation significantly increased resting fat oxidation, as evidenced by decreased respiratory exchange ratio, particularly in individuals with higher body fat percentages.
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Affiliation(s)
- Pavel Grepl
- Department of Natural Sciences in Kinanthropology, Faculty of Physical Culture, Palacký University Olomouc, Olomouc, Czech Republic
| | - Michal Botek
- Department of Natural Sciences in Kinanthropology, Faculty of Physical Culture, Palacký University Olomouc, Olomouc, Czech Republic
| | - Jakub Krejčí
- Department of Natural Sciences in Kinanthropology, Faculty of Physical Culture, Palacký University Olomouc, Olomouc, Czech Republic
| | - Andrew McKune
- Faculty of Health, UC-Research Institute for Sport and Exercise, University of Canberra, Canberra, ACT, Australia
- Discipline of Biokinetics, Exercise and Leisure Sciences, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
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4
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Chen W, Zhang Y, Miao G, Ying Y, Ren Z, Sun X, Cai J, Shen H, Lu H. The augment effects of magnesium hydride on the lipid lowering effect of atorvastatin: an in vivo and in vitro investigation. Med Gas Res 2025; 15:148-155. [PMID: 39436189 PMCID: PMC11515074 DOI: 10.4103/mgr.medgasres-d-23-00047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Revised: 12/18/2023] [Accepted: 02/05/2024] [Indexed: 10/23/2024] Open
Abstract
There is strong evidence connecting increased serum lipid levels to cardiovascular disorders, including atherosclerosis. Statins is prescribed as the primary medication to decrease lipid levels. Recent research has demonstrated that hydrogen possesses anti-inflammatory and antioxidant properties by modulating the expression of peroxisome proliferator-activated receptor gamma coactivator-1α, ultimately leading to the preservation of lipid homeostasis. Magnesium hydride (MgH2) is a prolonged stable hydrogen storage medium, which can be utilized to investigate its synergistic lipid-lowering effect with statins and its detailed molecular mechanism, both in vivo and in vitro. To ascertain the safety and efficacy of MgH2, we executed a comprehensive research of its influence on both physiological and pathological metrics. We noted a substantial diminution in lipid levels when MgH2 was integrated with atorvastatin, as attested by oil red staining. Furthermore, we scrutinized the regulatory effect of MgH2 on cytochrome P450 3A, which is a metabolic enzyme of statins, and discovered that it could be reduced by the MgH2. Concluding from our results, we propose that MgH2 inhibits the expression of cytochrome P450 3A in the liver and exerts an auxiliary lipid-lowering effect by increasing the blood concentration of statins. By augmenting our comprehension of MgH2's role in ameliorating lipid metabolism, we aspire to develop more promising therapies in the future.
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Affiliation(s)
- Wanqiu Chen
- School of Public Health, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
| | - Yinyin Zhang
- Department of Naval Medicine, Naval Medical University, Shanghai, China
| | - Gen Miao
- Department of Naval Medicine, Naval Medical University, Shanghai, China
| | - Yajing Ying
- Department of Naval Medicine, Naval Medical University, Shanghai, China
| | - Zifu Ren
- Department of Naval Medicine, Naval Medical University, Shanghai, China
| | - Xuejun Sun
- Department of Naval Medicine, Naval Medical University, Shanghai, China
- Center of Hydrogen Science, Shanghai Jiao Tong University, Shanghai, China
| | - Jianming Cai
- School of Public Health, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
- Department of Naval Medicine, Naval Medical University, Shanghai, China
| | - Hui Shen
- Department of Naval Medicine, Naval Medical University, Shanghai, China
| | - Hongtao Lu
- Department of Naval Medicine, Naval Medical University, Shanghai, China
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Zheng CM, Hou YC, Liao MT, Tsai KW, Hu WC, Yeh CC, Lu KC. Potential role of molecular hydrogen therapy on oxidative stress and redox signaling in chronic kidney disease. Biomed Pharmacother 2024; 176:116802. [PMID: 38795643 DOI: 10.1016/j.biopha.2024.116802] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2024] [Revised: 05/20/2024] [Accepted: 05/20/2024] [Indexed: 05/28/2024] Open
Abstract
Oxidative stress plays a key role in chronic kidney disease (CKD) development and progression, inducing kidney cell damage, inflammation, and fibrosis. However, effective therapeutic interventions to slow down CKD advancement are currently lacking. The multifaceted pharmacological effects of molecular hydrogen (H2) have made it a promising therapeutic avenue. H2 is capable of capturing harmful •OH and ONOO- while maintaining the crucial reactive oxygen species (ROS) involved in cellular signaling. The NRF2-KEAP1 system, which manages cell redox balance, could be used to treat CKD. H2 activates this pathway, fortifying antioxidant defenses and scavenging ROS to counteract oxidative stress. H2 can improve NRF2 signaling by using the Wnt/β-catenin pathway and indirectly activate NRF2-KEAP1 in mitochondria. Additionally, H2 modulates NF-κB activity by regulating cellular redox status, inhibiting MAPK pathways, and maintaining Trx levels. Treatment with H2 also attenuates HIF signaling by neutralizing ROS while indirectly bolstering HIF-1α function. Furthermore, H2 affects FOXO factors and enhances the activity of antioxidant enzymes. Despite the encouraging results of bench studies, clinical trials are still limited and require further investigation. The focus of this review is on hydrogen's role in treating renal diseases, with a specific focus on oxidative stress and redox signaling regulation, and it discusses its potential clinical applications.
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Affiliation(s)
- Cai-Mei Zheng
- Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, School of Medicine, College of Medicine, Taipei Medical University, New Taipei City 11031, Taiwan; TMU Research Centre of Urology and Kidney, Taipei Medical University, New Taipei City 11031, Taiwan
| | - Yi-Chou Hou
- Division of Nephrology, Department of Internal Medicine, Cardinal-Tien Hospital, School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 24205, Taiwan
| | - Min-Tser Liao
- Department of Pediatrics, Taoyuan Armed Forces General Hospital, Taoyuan City, Taiwan; Department of Pediatrics, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Kuo-Wang Tsai
- Department of Medical Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan
| | - Wan-Chung Hu
- Department of Clinical Pathology, Taipei Tzu Chi Hospital, Buddhist Medical Tzu Chi Foundation, New Taipei City 23142, Taiwan
| | - Chien-Chih Yeh
- Division of colon and Rectal Surgery, Department of Surgery, Taoyuan Armed Forces General Hospital, Taoyuan 325, Taiwan; National Defense Medical Center, Tri-Service General Hospital, Taipei 114, Taiwan
| | - Kuo-Cheng Lu
- Division of Nephrology, Department of Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23142, Taiwan; Division of Nephrology, Department of Medicine, Fu Jen Catholic University Hospital, School of Medicine, Fu Jen Catholic University, New Taipei City 24352, Taiwan.
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6
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Singh RB, Sumbalova Z, Fatima G, Mojto V, Fedacko J, Tarnava A, Pokotylo O, Gvozdjakova A, Ferenczyova K, Vlkovicova J, Kura B, Kalocayova B, Zenuch P, Slezak J. Effects of Molecular Hydrogen in the Pathophysiology and Management of Cardiovascular and Metabolic Diseases. Rev Cardiovasc Med 2024; 25:33. [PMID: 39077646 PMCID: PMC11262389 DOI: 10.31083/j.rcm2501033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 08/08/2023] [Accepted: 08/23/2023] [Indexed: 07/31/2024] Open
Abstract
Diet and lifestyle choices, notably the Western-type diet, are implicated in oxidative stress and inflammation, factors that elevate the risk of cardiovascular diseases (CVDs) and type 2 diabetes mellitus (T2DM). In contrast, the Mediterranean of diet, rich in antioxidants, appears to have protective effects against these risks. This article highlights the dual role of diet in generating molecular hydrogen ( H 2 ) in the gut, and H 2 's subsequent influence on the pathophysiology and prevention of CVD and T2DM. Dietary fiber, flavonoids, and probiotics contribute to the production of liters of H 2 in the gut, functioning as antioxidants to neutralize free radicals and dampen inflammation. In the last two decades, mounting evidence has demonstrated that both endogenously produced and exogenously administered H 2 , whether via inhalation or H 2 -rich water (HRW), have potent anti-inflammatory effects across a wide range of biochemical and pathophysiological processes. Recent studies indicate that H 2 can neutralize hydroxyl and nitrosyl radicals, acting as a cellular antioxidant, thereby reducing oxidative stress and inflammation-leading to a significant decline in CVDs and metabolic diseases. Clinical and experimental research support the therapeutic potential of H 2 interventions such as HRW in managing CVDs and metabolic diseases. However, larger studies are necessary to verify the role of H 2 therapy in the management of these chronic diseases.
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Affiliation(s)
- Ram B. Singh
- Halberg Hospital and Research Institute, 244001 Moradabad, India
| | - Zuzana Sumbalova
- Pharmacobiochemical Laboratory of 3rd Department of Internal Medicine, Faculty of Medicine, Comenius University in Bratislava, 811 08 Bratislava, Slovakia
| | - Ghizal Fatima
- Era Medical College, Era University, 226003 Lucknow, India
| | - Viliam Mojto
- 3rd Department of Internal Medicine, Faculty of Medicine, Comenius University in Bratislava, 833 05 Bratislava, Slovakia
| | - Jan Fedacko
- Department of Gerontology and Geriatric, PJ Safarik University, 040 86 Kosice, Slovakia
| | | | - Oleg Pokotylo
- Department of Food Biotechnology and Chemistry, Ternopil Ivan Puluj National Technical University, 46001 Ternopil, Ukraine
| | - Anna Gvozdjakova
- Pharmacobiochemical Laboratory of 3rd Department of Internal Medicine, Faculty of Medicine, Comenius University in Bratislava, 811 08 Bratislava, Slovakia
| | - Kristina Ferenczyova
- Center of Experimental Medicine, Institute for Heart Research, Slovak Academy of Sciences, 841 04 Bratislava, Slovakia
| | - Jana Vlkovicova
- Center of Experimental Medicine, Institute for Heart Research, Slovak Academy of Sciences, 841 04 Bratislava, Slovakia
| | - Branislav Kura
- Center of Experimental Medicine, Institute for Heart Research, Slovak Academy of Sciences, 841 04 Bratislava, Slovakia
| | - Barbora Kalocayova
- Center of Experimental Medicine, Institute for Heart Research, Slovak Academy of Sciences, 841 04 Bratislava, Slovakia
| | - Pavol Zenuch
- Department of Gerontology and Geriatric, PJ Safarik University, 040 86 Kosice, Slovakia
| | - Jan Slezak
- Center of Experimental Medicine, Institute for Heart Research, Slovak Academy of Sciences, 841 04 Bratislava, Slovakia
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7
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Johnsen HM, Hiorth M, Klaveness J. Molecular Hydrogen Therapy-A Review on Clinical Studies and Outcomes. Molecules 2023; 28:7785. [PMID: 38067515 PMCID: PMC10707987 DOI: 10.3390/molecules28237785] [Citation(s) in RCA: 31] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Revised: 11/21/2023] [Accepted: 11/23/2023] [Indexed: 12/18/2023] Open
Abstract
With its antioxidant properties, hydrogen gas (H2) has been evaluated in vitro, in animal studies and in human studies for a broad range of therapeutic indications. A simple search of "hydrogen gas" in various medical databases resulted in more than 2000 publications related to hydrogen gas as a potential new drug substance. A parallel search in clinical trial registers also generated many hits, reflecting the diversity in ongoing clinical trials involving hydrogen therapy. This review aims to assess and discuss the current findings about hydrogen therapy in the 81 identified clinical trials and 64 scientific publications on human studies. Positive indications have been found in major disease areas including cardiovascular diseases, cancer, respiratory diseases, central nervous system disorders, infections and many more. The available administration methods, which can pose challenges due to hydrogens' explosive hazards and low solubility, as well as possible future innovative technologies to mitigate these challenges, have been reviewed. Finally, an elaboration to discuss the findings is included with the aim of addressing the following questions: will hydrogen gas be a new drug substance in future clinical practice? If so, what might be the administration form and the clinical indications?
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Affiliation(s)
- Hennie Marie Johnsen
- Department of Pharmacy, University of Oslo, Sem Sælands Vei 3, 0371 Oslo, Norway
- Nacamed AS, Oslo Science Park, Guastadalléen 21, 0349 Oslo, Norway
| | - Marianne Hiorth
- Department of Pharmacy, University of Oslo, Sem Sælands Vei 3, 0371 Oslo, Norway
| | - Jo Klaveness
- Department of Pharmacy, University of Oslo, Sem Sælands Vei 3, 0371 Oslo, Norway
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Hu H, Zhu H, Yang H, Yao W, Zheng W. In vitro fermentation properties of magnesium hydride and related modulation effects on broiler cecal microbiome and metabolome. Front Microbiol 2023; 14:1175858. [PMID: 37621394 PMCID: PMC10445219 DOI: 10.3389/fmicb.2023.1175858] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Accepted: 07/24/2023] [Indexed: 08/26/2023] Open
Abstract
Magnesium hydride (MGH), a highly promising hydrogen-producing substance/additive for hydrogen production through its hydrolysis reaction, has the potential to enhance broiler production. However, before incorporating MGH as a hydrogen-producing additive in broiler feed, it is crucial to fully understand its impact on microbiota and metabolites. In vitro fermentation models provide a fast, reproducible, and direct assessment tool for microbiota metabolism and composition. This study aims to investigate the effects of MGH and coated-magnesium hydride (CMG) on fermentation characteristics, as well as the microbiota and metabolome in the culture of in vitro fermentation using cecal inocula from broilers. After 48 h of incubation, it was observed that the presence of MGH had a significant impact on various factors. Specifically, the content of N-NH3 decreased, while the total hydrogen gas and total SCFAs increased. Furthermore, the presence of MGH promoted the abundance of SCFA-producing bacteria such as Ruminococcus, Blautia, Coprobacillus, and Dysgonomonas. On the other hand, the presence of CMG led to an increase in the concentration of lactic acid, acetic acid, and valeric acid. Additionally, CMG affected the diversity of microbiota in the culture, resulting in an enrichment of the relative abundance of Firmicutes, as well as genera of Lactobacillus, Coprococcus, and Eubacterium. Conversely, the relative abundance of the phylum Proteobacteria and pathogenic bacteria Shigella decreased. Metabolome analysis revealed that MGH and CMG treatment caused significant changes in 21 co-regulated metabolites, primarily associated with lipid, amino acid, benzenoids, and organooxygen compounds. Importantly, joint correlation analysis revealed that MGH or CMG treatments had a direct impact on the microbiota, which in turn indirectly influenced metabolites in the culture. In summary, the results of this study suggested that both MGH and coated-MGH have similar yet distinct positive effects on the microbiota and metabolites of the broiler cecal in an in vitro fermentation model.
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Affiliation(s)
- Heng Hu
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu, China
| | - He Zhu
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu, China
| | - Haiyan Yang
- Center of Hydrogen Science, Shanghai Jiao Tong University, Shanghai, China
| | - Wen Yao
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu, China
- Key Lab of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing, Jiangsu, China
| | - Weijiang Zheng
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu, China
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Sumbalová Z, Kucharská J, Rausová Z, Gvozdjáková A, Szántová M, Kura B, Mojto V, Slezák J. The Effect of Adjuvant Therapy with Molecular Hydrogen on Endogenous Coenzyme Q 10 Levels and Platelet Mitochondrial Bioenergetics in Patients with Non-Alcoholic Fatty Liver Disease. Int J Mol Sci 2023; 24:12477. [PMID: 37569850 PMCID: PMC10419858 DOI: 10.3390/ijms241512477] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 07/30/2023] [Accepted: 08/03/2023] [Indexed: 08/13/2023] Open
Abstract
Molecular hydrogen (H2) has been recognized as a novel medical gas with antioxidant and anti-inflammatory effects. Non-alcoholic fatty liver disease (NAFLD) is a liver pathology with increased fat accumulation in liver tissue caused by factors other than alcohol consumption. Platelet mitochondrial function is considered to reflect systemic mitochondrial health. We studied the effect of adjuvant therapy with hydrogen-rich water (HRW) on coenzyme Q10 (CoQ10) content and platelet mitochondrial bioenergetics in patients with NAFLD. A total of 30 patients with NAFLD and 15 healthy volunteers were included in this clinical trial. A total of 17 patients (H2 group) drank water three × 330 mL/day with tablets producing HRW (>4 mg/L H2) for 8 weeks, and 13 patients (P group) drank water with placebo tablets producing CO2. The concentration of CoQ10-TOTAL was determined by the HPLC method, the parameter of oxidative stress, thiobarbituric acid reactive substances (TBARS), by the spectrophotometric method, and mitochondrial bioenergetics in platelets isolated from whole blood by high-resolution respirometry. The patients with NAFLD had lower concentrations of CoQ10-TOTAL in the blood, plasma, and platelets vs. the control group. Mitochondrial CI-linked LEAK respiration was higher, and CI-linked oxidative phosphorylation (OXPHOS) and CII-linked electron transfer (ET) capacities were lower vs. the control group. Plasma TBARS concentrations were higher in the H2 group. After 8 weeks of adjuvant therapy with HRW, the concentration of CoQ10 in platelets increased, plasma TBARS decreased, and the efficiency of OXPHOS improved, while in the P group, the changes were non-significant. Long-term supplementation with HRW could be a promising strategy for the acceleration of health recovery in patients with NAFLD. The application of H2 appears to be a new treatment strategy for targeted therapy of mitochondrial disorders. Additional and longer-term studies are needed to confirm and elucidate the exact mechanisms of the mitochondria-targeted effects of H2 therapy in patients with NAFLD.
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Affiliation(s)
- Zuzana Sumbalová
- Pharmacobiochemical Laboratory of 3rd Department of Internal Medicine, Faculty of Medicine, Comenius University in Bratislava, 811 08 Bratislava, Slovakia; (J.K.); (Z.R.); (A.G.)
| | - Jarmila Kucharská
- Pharmacobiochemical Laboratory of 3rd Department of Internal Medicine, Faculty of Medicine, Comenius University in Bratislava, 811 08 Bratislava, Slovakia; (J.K.); (Z.R.); (A.G.)
| | - Zuzana Rausová
- Pharmacobiochemical Laboratory of 3rd Department of Internal Medicine, Faculty of Medicine, Comenius University in Bratislava, 811 08 Bratislava, Slovakia; (J.K.); (Z.R.); (A.G.)
| | - Anna Gvozdjáková
- Pharmacobiochemical Laboratory of 3rd Department of Internal Medicine, Faculty of Medicine, Comenius University in Bratislava, 811 08 Bratislava, Slovakia; (J.K.); (Z.R.); (A.G.)
| | - Mária Szántová
- 3rd Department of Internal Medicine, Faculty of Medicine, Comenius University in Bratislava, 813 72 Bratislava, Slovakia; (M.S.); (V.M.)
| | - Branislav Kura
- Institute for Heart Research, Center of Experimental Medicine, Slovak Academy of Sciences, 841 04 Bratislava, Slovakia; (B.K.); (J.S.)
| | - Viliam Mojto
- 3rd Department of Internal Medicine, Faculty of Medicine, Comenius University in Bratislava, 813 72 Bratislava, Slovakia; (M.S.); (V.M.)
| | - Ján Slezák
- Institute for Heart Research, Center of Experimental Medicine, Slovak Academy of Sciences, 841 04 Bratislava, Slovakia; (B.K.); (J.S.)
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Xie F, Song Y, Yi Y, Jiang X, Ma S, Ma C, Li J, Zhanghuang Z, Liu M, Zhao P, Ma X. Therapeutic Potential of Molecular Hydrogen in Metabolic Diseases from Bench to Bedside. Pharmaceuticals (Basel) 2023; 16:ph16040541. [PMID: 37111299 PMCID: PMC10141176 DOI: 10.3390/ph16040541] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 03/26/2023] [Accepted: 03/29/2023] [Indexed: 04/29/2023] Open
Abstract
Oxidative stress and chronic inflammation have been implicated in the pathophysiology of metabolic diseases, including diabetes mellitus (DM), metabolic syndrome (MS), fatty liver (FL), atherosclerosis (AS), and obesity. Molecular hydrogen (H2) has long been considered a physiologically inert gas. In the last two decades, accumulating evidence from pre-clinical and clinical studies has indicated that H2 may act as an antioxidant to exert therapeutic and preventive effects on various disorders, including metabolic diseases. However, the mechanisms underlying the action of H2 remain unclear. The purpose of this review was to (1) provide an overview of the current research on the potential effects of H2 on metabolic diseases; (2) discuss the possible mechanisms underlying these effects, including the canonical anti-oxidative, anti-inflammatory, and anti-apoptotic effects, as well as suppression of ER stress, activation of autophagy, improvement of mitochondrial function, regulation of gut microbiota, and other possible mechanisms. The potential target molecules of H2 will also be discussed. With more high-quality clinical trials and in-depth mechanism research, it is believed that H2 will eventually be applied to clinical practice in the future, to benefit more patients with metabolic disease.
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Affiliation(s)
- Fei Xie
- Faculty of Environment and Life, Beijing University of Technology, Beijing 100124, China
- Beijing Molecular Hydrogen Research Center, Beijing 100124, China
| | - Yifei Song
- Faculty of Environment and Life, Beijing University of Technology, Beijing 100124, China
- Beijing Molecular Hydrogen Research Center, Beijing 100124, China
| | - Yang Yi
- Faculty of Environment and Life, Beijing University of Technology, Beijing 100124, China
- Beijing Molecular Hydrogen Research Center, Beijing 100124, China
| | - Xue Jiang
- Faculty of Environment and Life, Beijing University of Technology, Beijing 100124, China
- Beijing Molecular Hydrogen Research Center, Beijing 100124, China
| | - Shiwen Ma
- Faculty of Environment and Life, Beijing University of Technology, Beijing 100124, China
- Beijing Molecular Hydrogen Research Center, Beijing 100124, China
| | - Chen Ma
- Faculty of Environment and Life, Beijing University of Technology, Beijing 100124, China
- Beijing Molecular Hydrogen Research Center, Beijing 100124, China
| | - Junyu Li
- Faculty of Environment and Life, Beijing University of Technology, Beijing 100124, China
- Beijing Molecular Hydrogen Research Center, Beijing 100124, China
| | - Ziyi Zhanghuang
- Faculty of Environment and Life, Beijing University of Technology, Beijing 100124, China
- Beijing Molecular Hydrogen Research Center, Beijing 100124, China
| | - Mengyu Liu
- Faculty of Environment and Life, Beijing University of Technology, Beijing 100124, China
- Beijing Molecular Hydrogen Research Center, Beijing 100124, China
| | - Pengxiang Zhao
- Faculty of Environment and Life, Beijing University of Technology, Beijing 100124, China
- Beijing Molecular Hydrogen Research Center, Beijing 100124, China
| | - Xuemei Ma
- Faculty of Environment and Life, Beijing University of Technology, Beijing 100124, China
- Beijing Molecular Hydrogen Research Center, Beijing 100124, China
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11
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Ono H, Nishijima Y, Ohta S. 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 (Basel) 2023; 16:ph16030434. [PMID: 36986533 PMCID: PMC10057981 DOI: 10.3390/ph16030434] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Revised: 03/03/2023] [Accepted: 03/06/2023] [Indexed: 03/18/2023] Open
Abstract
(1) Background: Alzheimer’s disease (AD) is a progressive and fatal neurodegenerative disorder. Hydrogen gas (H2) is a therapeutic medical gas with multiple functions such as anti-oxidant, anti-inflammation, anti-cell death, and the stimulation of energy metabolism. To develop a disease-modifying treatment for AD through multifactorial mechanisms, an open label pilot study on H2 treatment was conducted. (2) Methods: Eight patients with AD inhaled 3% H2 gas for one hour twice daily for 6 months and then followed for 1 year without inhaling H2 gas. The patients were clinically assessed using the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog). To objectively assess the neuron integrity, diffusion tensor imaging (DTI) with advanced magnetic resonance imaging (MRI) was applied to neuron bundles passing through the hippocampus. (3) Results: The mean individual ADAS-cog change showed significant improvement after 6 months of H2 treatment (−4.1) vs. untreated patients (+2.6). As assessed by DTI, H2 treatment significantly improved the integrity of neurons passing through the hippocampus vs. the initial stage. The improvement by ADAS-cog and DTI assessments were maintained during the follow-up after 6 months (significantly) or 1 year (non-significantly). (4) Conclusions: This study suggests that H2 treatment not only relieves temporary symptoms, but also has disease-modifying effects, despite its limitations.
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Affiliation(s)
- Hirohisa Ono
- Departments of Neurosurgery and Neurology, Nishijima Hospital, Ohoka, 2835-7, Numazu City 410-0022, Japan
- Correspondence: (H.O.); (S.O.); Tel.: +81-80-5658-5858 (H.O.); +81-90-9824-2970 (S.O.); Fax: +81-44-434-2336 (S.O.)
| | - Yoji Nishijima
- Departments of Neurosurgery and Neurology, Nishijima Hospital, Ohoka, 2835-7, Numazu City 410-0022, Japan
| | - Shigeo Ohta
- Department of Neurology Medicine, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
- Correspondence: (H.O.); (S.O.); Tel.: +81-80-5658-5858 (H.O.); +81-90-9824-2970 (S.O.); Fax: +81-44-434-2336 (S.O.)
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12
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Kamimura N, Wolf AM, Yokota T, Nito C, Takahashi H, Ohta S. Transgenic type2 diabetes mouse models for in vivo redox measurement of hepatic mitochondrial oxidative stress. Biochim Biophys Acta Gen Subj 2023; 1867:130302. [PMID: 36577487 DOI: 10.1016/j.bbagen.2022.130302] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Revised: 12/02/2022] [Accepted: 12/21/2022] [Indexed: 12/26/2022]
Abstract
BACKGROUND Oxidative stress is involved in the progression of diabetes and its associated complications. However, it is unclear whether increased oxidative stress plays a primary role in the onset of diabetes or is a secondary indicator caused by tissue damage. Previous methods of analyzing oxidative stress have involved measuring the changes in oxidative stress biomarkers. Our aim is to identify a novel approach to clarify whether oxidative stress plays a primary role in the onset of diabetes. METHODS We constructed transgenic type 2 diabetes mouse models expressing redox-sensitive green fluorescent proteins (roGFPs) that distinguished between mitochondria and whole cells. Pancreas, liver, skeletal muscle, and kidney redox states were measured in vivo. RESULTS Hepatic mitochondrial oxidation increased when the mice were 4 weeks old and continued to increase in an age-dependent manner. The increase in hepatic mitochondrial oxidation occurred simultaneously with weight gain and increased blood insulin levels before the blood glucose levels increased. Administering the oxidative stress inducer acetaminophen increased the vulnerability of the liver mitochondria to oxidative stress. CONCLUSIONS This study demonstrates that oxidative stress in liver mitochondria in mice begins at the onset of diabetes rather than after the disease has progressed. GENERAL SIGNIFICANCE RoGFP-expressing transgenic type 2 diabetes mouse models are effective and convenient tools for measuring hepatic mitochondrial redox statuses in vivo. These models may be used to assess mitochondria-targeting antioxidants and establish the role of oxidative stress in type 2 diabetes.
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Affiliation(s)
- Naomi Kamimura
- Department of Biochemistry and Cell Biology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan; Laboratory for Clinical Research, Collaborative Research Center, Nippon Medical School, Tokyo, Japan.
| | - Alexander M Wolf
- Department of Biochemistry and Cell Biology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Takashi Yokota
- Department of Biochemistry and Cell Biology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Chikako Nito
- Laboratory for Clinical Research, Collaborative Research Center, Nippon Medical School, Tokyo, Japan
| | - Hiroshi Takahashi
- Laboratory for Clinical Research, Collaborative Research Center, Nippon Medical School, Tokyo, Japan; Department of Ophthalmology, Nippon Medical School, Tokyo, Japan
| | - Shigeo Ohta
- Department of Biochemistry and Cell Biology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan; Department of Neurology Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
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13
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Todorovic N, Fernández-Landa J, Santibañez A, Kura B, Stajer V, Korovljev D, Ostojic SM. The Effects of Hydrogen-Rich Water on Blood Lipid Profiles in Clinical Populations: A Systematic Review and Meta-Analysis. Pharmaceuticals (Basel) 2023; 16:142. [PMID: 37259294 PMCID: PMC9967957 DOI: 10.3390/ph16020142] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Revised: 01/03/2023] [Accepted: 01/04/2023] [Indexed: 12/24/2023] Open
Abstract
Over the last two decades, a plethora of disease models and human studies have confirmed the beneficial effects of molecular hydrogen (H2), a simple biotherapeutic gas. Recent small-scale studies evaluating the effects of hydrogen-rich water (HRW) on various metabolic conditions pointed to advantageous effects of HRW in regulating blood lipid profiles. However, to the best of the authors' knowledge, no systematic review and/or meta-analysis (SRMA) were published considering HRW consumption and lipid/lipoprotein status. Therefore, the aim of this SRMA was to assess the effects of HRW consumption on blood lipid panel in clinical populations. The search strategy was designed using PRISMA guidelines, and the databases PubMed/Medline, Web of Science, and Scopus were explored from inception until 4 October 2022. A total of seven studies satisfied all the eligibility criteria and were included in SRMA. The results for the pooled meta-analysis showed a significant reduction in total cholesterol, low-density lipoprotein, and triglycerides after HRW intake (p = 0.01), with small to moderate effects (pooled SMD = -0.23 (from -0.40 to 0.05); pooled SMD = -0.22 (from -0.39 to 0.04); pooled SMD = -0.38 (from -0.59 to 0.18), respectively). Our findings indicate that drinking HRW can significantly improve lipid status in the clinical populations. Additional studies are warranted to further validate this connection.
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Affiliation(s)
- Nikola Todorovic
- Applied Bioenergetics Lab, Faculty of Sport and Physical Education, University of Novi Sad, 21000 Novi Sad, Serbia
| | - Julen Fernández-Landa
- Physical Education and Sports Department, Faculty of Education and Sport, University of the Basque Country (UPV/EHU), 01007 Vitoria, Spain
| | - Asier Santibañez
- Physical Education and Sports Department, Faculty of Education and Sport, University of the Basque Country (UPV/EHU), 01007 Vitoria, Spain
| | - Branislav Kura
- Centre of Experimental Medicine, Institute for Heart Research, Slovak Academy of Sciences, 841 04 Bratislava, Slovakia
| | - Valdemar Stajer
- Applied Bioenergetics Lab, Faculty of Sport and Physical Education, University of Novi Sad, 21000 Novi Sad, Serbia
| | - Darinka Korovljev
- Applied Bioenergetics Lab, Faculty of Sport and Physical Education, University of Novi Sad, 21000 Novi Sad, Serbia
| | - Sergej M. Ostojic
- Applied Bioenergetics Lab, Faculty of Sport and Physical Education, University of Novi Sad, 21000 Novi Sad, Serbia
- Department of Nutrition and Public Health, University of Agder, Universitetsveien 25, 4604 Kristiansand, Norway
- Faculty of Health Sciences, University of Pecs, 7601 Pecs, Hungary
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14
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Effects of Intestinal Bacterial Hydrogen Gas Production on Muscle Recovery following Intense Exercise in Adult Men: A Pilot Study. Nutrients 2022; 14:nu14224875. [PMID: 36432562 PMCID: PMC9693815 DOI: 10.3390/nu14224875] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2022] [Revised: 11/09/2022] [Accepted: 11/14/2022] [Indexed: 11/19/2022] Open
Abstract
This study aimed to examine the effects of hydrogen gas (H2) produced by intestinal microbiota on participant conditioning to prevent intense exercise-induced damage. In this double-blind, randomized, crossover study, participants ingested H2-producing milk that induced intestinal bacterial H2 production or a placebo on the trial day, 4 h before performing an intense exercise at 75% maximal oxygen uptake for 60 min. Blood marker levels and respiratory variables were measured before, during, and after exercise. Visual analog scale scores of general and lower limb muscle soreness evaluated were 3.8- and 2.3-fold higher, respectively, on the morning after treatment than that before treatment during the placebo trial, but not during the test beverage consumption. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations and production rates significantly increased with placebo consumption; no changes were observed with test beverage consumption. After exercise, relative blood lactate levels with H2-producing milk consumption were lower than those with placebo consumption. A negative correlation was observed between the variation of 8-OHdG and the area under the curve (AUC) of breath H2 concentrations. Lipid oxidation AUC was 1.3-fold higher significantly with H2-producing milk than with placebo consumption. Conclusively, activating intestinal bacterial H2 production by consuming a specific beverage may be a new strategy for promoting recovery and conditioning in athletes frequently performing intense exercises.
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15
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Lv X, Lu Y, Ding G, Li X, Xu X, Zhang A, Song G. Hydrogen Intake Relieves Alcohol Consumption and Hangover Symptoms in Healthy Adults: a Randomized and Placebo-Controlled Crossover Study. Am J Clin Nutr 2022; 116:1208-1218. [PMID: 36124653 DOI: 10.1093/ajcn/nqac261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 08/26/2022] [Accepted: 09/14/2022] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND Alcohol-induced hangover represents a significant, yet understudied, global hazard and a large socio-economic burden. OBJECTIVES The aim of this study was to investigate the effects of hydrogen (H2) on relieving drinking and hangover symptoms in 20 healthy volunteers. METHODS In this pilot, randomized, double-blinded, placebo-controlled, matched, crossover interventional trial, participants were matched into pairs and randomly assigned. Study group 1 inhaled placebo air for 1 hr, followed by drinking 100 ml of liquor (40% alcohol) within 10 min, and then pure water. Study group 2 inhaled a mixture of H2 and O2 gas for 1 hr, followed by drinking 100 ml of liquor within 10 min, and then H2 dissolved in water. On a second intervention day (crossover) ≥1 wk later, study-group subjects were switched to the opposite order. Breath alcohol concentration (BrAC), hangover severity, and cognitive scores were measured. RESULTS The BrACs within the H2 group were significantly lower than those within the placebo group after 30 min, 60 min, and 90 min (P < 0.05). The H2 group reported having fewer hangover symptoms compared with the placebo group (Placebo: 77% of symptoms absent, 19.7% of mild symptoms, 2.7% of moderate symptoms, 0.7% of severe symptoms; H2: 88.6% of symptoms absent, 10% of mild symptoms, 1.3% of moderate symptoms, 0% of severe symptoms; P < 0.001). H2 treatment improved cognitive testing scores (P < 0.05), including attention and executive functions. Furthermore, consumption of H2 was negatively (β = -13.016; 95% CI: -17.726, -8.305; P < 0.001) and female sex was positively (β = 22.611; 95% CI: 16.226, 28.997; P < 0.001) correlated with increased BrACs. Likewise, the consumption of H2 was negatively (OR: 0.035; 95% CI: 0.007, 0.168; P < 0.001) while female sex was positively (OR: 28.838; 95% CI: 5.961, 139.506; P < 0.001) correlated with the severity of hangover symptoms. CONCLUSIONS H2 decreases BrACs and relieves the symptoms of hangovers.This trial was registered at China Clinical Trial Registry as ChiCTR2200059988. URL of registration: http://www.chictr.org.cn/showproj.aspx?proj=58359.
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Affiliation(s)
- Xiang Lv
- The Second Affiliated Hospital and School of Basic Medical Sciences of Shandong First Medical University & Shandong Academy of Medical Science, Taian 271000, China
| | - Yuanfeng Lu
- School of Nursing, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian 271016, China
| | - Guoyong Ding
- School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian 271016, China
| | - Xiao Li
- The Second Affiliated Hospital and School of Basic Medical Sciences of Shandong First Medical University & Shandong Academy of Medical Science, Taian 271000, China
| | - Xinxin Xu
- The Second Affiliated Hospital and School of Basic Medical Sciences of Shandong First Medical University & Shandong Academy of Medical Science, Taian 271000, China
| | - Aihua Zhang
- School of Nursing, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian 271016, China
| | - Guohua Song
- The Second Affiliated Hospital and School of Basic Medical Sciences of Shandong First Medical University & Shandong Academy of Medical Science, Taian 271000, China
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16
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Development and Validation of a Novel Circadian Rhythm-Related Signature to Predict the Prognosis of the Patients with Hepatocellular Carcinoma. BIOMED RESEARCH INTERNATIONAL 2022; 2022:4263261. [PMID: 35993051 PMCID: PMC9391189 DOI: 10.1155/2022/4263261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Revised: 07/06/2022] [Accepted: 07/18/2022] [Indexed: 12/24/2022]
Abstract
Hepatocellular carcinoma (HCC) is one of the most important causes of cancer-related deaths and remains a major public health challenge worldwide. Considering the extensive heterogeneity of HCC, more accurate prognostic models are imperative. The circadian genes regulate the daily oscillations of key biological processes, such as nutrient metabolism in the liver. Circadian rhythm disruption has recently been recognized as an independent risk factor for cancer. In this study, The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) were compared and 248 differentially expressed genes (DEGs) of the circadian rhythm were identified. HCC was classified into two subtypes based on these DEGs. The prognostic value of each circadian rhythm-associated gene (CRG) for survival was assessed by constructing a multigene signature from TCGA cohort. A 6-gene signature was created by applying the least absolute shrinkage and selection operator (LASSO) Cox regression method, and all patients in TCGA cohort were divided into high- and low-risk groups according to their risk scores. The survival rate of patients with HCC in the low-risk group was significantly higher than that in the high-risk group (p < 0.001). The patients with HCC in the Gene Expression Omnibus (GEO) cohort were also divided into two risk subgroups using the risk score of TCGA cohort, and the overall survival time (OS) was prolonged in the low-risk group (p = 0.012). Based on the clinical characteristics, the risk score was an independent predictor of OS in the patients with HCC. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that multiple metabolic pathways, cell cycle, etc., were enhanced in the high-risk group. Using the metabolic pathway single-sample gene set enrichment analysis (ssGSEA), it was found that the metabolic pathways in the high- and low-risk groups between TCGA and GEO cohorts were altered essentially in the same way. In conclusion, the circadian genes play an important role in HCC metabolic rearrangements and can be further used to predict the prognosis the patients with HCC.
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17
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Hancock JT. Editorial for Special Issue: “Production and Role of Molecular Hydrogen in Plants”. PLANTS 2022; 11:plants11152047. [PMID: 35956525 PMCID: PMC9370376 DOI: 10.3390/plants11152047] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 07/18/2022] [Accepted: 08/03/2022] [Indexed: 11/16/2022]
Abstract
Molecular hydrogen (H2) is an extremely small molecule, which is relatively insoluble in water and relatively inert [...]
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Affiliation(s)
- John T Hancock
- Department of Applied Sciences, University of the West of England, Bristol BS16 1QY, UK
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18
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Shi X, Zhu L, Wang S, Zhu W, Li Q, Wei J, Feng D, Liu M, Chen Y, Sun X, Lu H, Lv X. Magnesium Hydride Ameliorates Endotoxin-Induced Acute Respiratory Distress Syndrome by Inhibiting Inflammation, Oxidative Stress, and Cell Apoptosis. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:5918954. [PMID: 35528515 PMCID: PMC9072031 DOI: 10.1155/2022/5918954] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 03/16/2022] [Accepted: 04/01/2022] [Indexed: 11/17/2022]
Abstract
Acute respiratory distress syndrome (ARDS) causes uncontrolled pulmonary inflammation, resulting in high morbidity and mortality in severe cases. Given the antioxidative effect of molecular hydrogen, some recent studies suggest the potential use of molecular hydrogen as a biomedicine for the treatment of ARDS. In this study, we aimed to explore the protective effects of magnesium hydride (MgH2) on two types of ARDS models and its underlying mechanism in a lipopolysaccharide (LPS)-induced ARDS model of the A549 cell line. The results showed that LPS successfully induced oxidative stress, inflammatory reaction, apoptosis, and barrier breakdown in alveolar epithelial cells (AEC). MgH2 can exert an anti-inflammatory effect by down-regulating the expressions of inflammatory cytokines (IL-1β, IL-6, and TNF-α). In addition, MgH2 decreased oxidative stress by eliminating intracellular ROS, inhibited apoptosis by regulating the expressions of cytochrome c, Bax, and Bcl-2, and suppressed barrier breakdown by up-regulating the expression of ZO-1 and occludin. Mechanistically, the expressions of p-AKT, p-mTOR, p-P65, NLRP3, and cleaved-caspase-1 were decreased after MgH2 treatment, indicating that AKT/mTOR and NF-κB/NLRP3/IL-1β pathways participated in the protective effects of MgH2. Furthermore, the in vivo study also demonstrated that MgH2-treated mice had a better survival rate and weaker pathological damage. All these findings demonstrated that MgH2 could exert an ARDS-protective effect by regulating the AKT/mTOR and NF-κB/NLRP3/IL-1β pathways to suppress LPS-induced inflammatory reaction, oxidative stress injury, apoptosis, and barrier breakdown, which may provide a potential strategy for the prevention and treatment of ARDS.
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Affiliation(s)
- Xuan Shi
- Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Lina Zhu
- Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Sheng Wang
- Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Wanli Zhu
- Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Quanfu Li
- Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Juan Wei
- Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Di Feng
- Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Meiyun Liu
- Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Yuanli Chen
- Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Xuejun Sun
- Department of Naval Medicine, Naval Medical University, Shanghai, China
- Center of Hydrogen Science, Shanghai Jiao Tong University, Shanghai, China
| | - Hongtao Lu
- Department of Naval Medicine, Naval Medical University, Shanghai, China
| | - Xin Lv
- Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
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19
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He J, Cheng P, Wang J, Xu S, Zou J, Shen W. Magnesium hydride confers copper tolerance in alfalfa via regulating nitric oxide signaling. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2022; 231:113197. [PMID: 35032725 DOI: 10.1016/j.ecoenv.2022.113197] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 12/27/2021] [Accepted: 01/11/2022] [Indexed: 06/14/2023]
Abstract
Magnesium hydride (MgH2) as a solid-state hydrogen source might be potentially applied in industry and medicine. However, its biological function in plants has not yet been fully discovered. In this report, it was observed that MgH2 administration could relieve copper (Cu) toxicity in alfalfa that was confirmed by a reduction in root growth inhibition. By using old MgH2 as a negative control, it was concluded that above MgH2 function was primarily derived from the releasing of molecular hydrogen (H2), but not caused by either magnesium metabolites or pH alteration. Further results revealed that Cu-triggered nitric oxide (NO) production was intensified by MgH2. Subsequent pharmacological and biochemical experiments suggested that nitrate reductase might be mainly responsible for NO production during above processes. Cu accumulation in the root tissues was also obviously reduced in the presence of MgH2. Meanwhile, increased non-protein thiols (NPTs) content and the deposition of Cu in cell wall of seedling roots could be used to explain the mechanism underlying MgH2-alleviated Cu toxicity via NO signaling. Further, the plant redox balance was reestablished since the Cu stress-modulated antioxidant enzymes activities, reactive oxygen species (ROS) accumulation, and oxidative injury detected by in vivo histochemical and biochemical analyses, were differentially abolished by MgH2. The above responses could be blocked by the removal of endogenous NO after the addition of its scavenger. Taken together, these results clearly suggested that MgH2 control of plant tolerance against Cu toxicity might be mediated by NO signaling, which might open a new window for the application of solid-state hydrogen materials in agriculture.
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Affiliation(s)
- Junjie He
- College of Life Sciences, Laboratory Center of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China.
| | - Pengfei Cheng
- College of Life Sciences, Laboratory Center of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China.
| | - Jun Wang
- College of Life Sciences, Laboratory Center of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China.
| | - Sheng Xu
- Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China.
| | - Jianxin Zou
- Center of Hydrogen Science, Shanghai Jiao Tong University, Shanghai 200240, China.
| | - Wenbiao Shen
- College of Life Sciences, Laboratory Center of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China; Center of Hydrogen Science, Shanghai Jiao Tong University, Shanghai 200240, China.
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20
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Wang YQ, Liu YH, Wang S, Du HM, Shen WB. Hydrogen agronomy: research progress and prospects. J Zhejiang Univ Sci B 2021; 21:841-855. [PMID: 33150769 DOI: 10.1631/jzus.b2000386] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Agriculture is the foundation of social development. Under the pressure of population growth, natural disasters, environmental pollution, climate change, and food safety, the interdisciplinary "new agriculture" is becoming an important trend of modern agriculture. In fact, new agriculture is not only the foundation of great health and new energy sources, but is also the cornerstone of national food security, energy security, and biosafety. Hydrogen agronomy focuses mainly on the mechanism of hydrogen gas (H2) biology effects in agriculture, and provides a theoretical foundation for the practice of hydrogen agriculture, a component of the new agriculture. Previous research on the biological effects of H2 focused chiefly on medicine. The mechanism of selective antioxidant is the main theoretical basis of hydrogen medicine. Subsequent experiments have demonstrated that H2 can regulate the growth and development of plant crops, edible fungus, and livestock, and enhance the tolerance of these agriculturally important organisms against abiotic and biotic stresses. Even more importantly, H2 can regulate the growth and development of crops by changing the soil microbial community composition and structure. Use of H2 can also improve the nutritional value and postharvest quality of agricultural products. Researchers have also shown that the biological functions of molecular hydrogen are mediated by modulating reactive oxygen species (ROS), nitric oxide (NO), and carbon monoxide (CO) signaling cascades in plants and microbes. This review summarizes and clarifies the history of hydrogen agronomy and describes recent progress in the field. We also argue that emerging hydrogen agriculture will be an important direction in the new agriculture. Further, we discuss several scientific problems in hydrogen agronomy, and suggest that the future of hydrogen agronomy depends on contributions by multiple disciplines. Important future research directions of hydrogen agronomy include hydrogen agriculture in special environments, such as islands, reefs, aircraft, and outer space.
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Affiliation(s)
- Yue-Qiao Wang
- College of Life Sciences, Laboratory Center of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China
| | - Yu-Hao Liu
- College of Life Sciences, Laboratory Center of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China
| | - Shu Wang
- College of Life Sciences, Laboratory Center of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China
| | - Hong-Mei Du
- Center of Hydrogen Science, Shanghai Jiao Tong University, Shanghai 200240, China.,School of Design, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Wen-Biao Shen
- College of Life Sciences, Laboratory Center of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China.,Center of Hydrogen Science, Shanghai Jiao Tong University, Shanghai 200240, China
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21
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Molecular Hydrogen as a Novel Antitumor Agent: Possible Mechanisms Underlying Gene Expression. Int J Mol Sci 2021; 22:ijms22168724. [PMID: 34445428 PMCID: PMC8395776 DOI: 10.3390/ijms22168724] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Revised: 08/10/2021] [Accepted: 08/12/2021] [Indexed: 01/10/2023] Open
Abstract
While many antitumor drugs have yielded unsatisfactory therapeutic results, drugs are one of the most prevalent therapeutic measures for the treatment of cancer. The development of cancer largely results from mutations in nuclear DNA, as well as from those in mitochondrial DNA (mtDNA). Molecular hydrogen (H2), an inert molecule, can scavenge hydroxyl radicals (·OH), which are known to be the strongest oxidizing reactive oxygen species (ROS) in the body that causes these DNA mutations. It has been reported that H2 has no side effects, unlike conventional antitumor drugs, and that it is effective against many diseases caused by oxidative stress and chronic inflammation. Recently, there has been an increasing number of papers on the efficacy of H2 against cancer and its effects in mitigating the side effects of cancer treatment. In this review, we demonstrate the efficacy and safety of H2 as a novel antitumor agent and show that its mechanisms may not only involve the direct scavenging of ·OH, but also other indirect biological defense mechanisms via the regulation of gene expression.
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Jin Z, Sun Y, Yang T, Tan L, Lv P, Xu Q, Tao G, Qin S, Lu X, He Q. Nanocapsule-mediated sustained H 2 release in the gut ameliorates metabolic dysfunction-associated fatty liver disease. Biomaterials 2021; 276:121030. [PMID: 34298442 DOI: 10.1016/j.biomaterials.2021.121030] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Revised: 05/14/2021] [Accepted: 07/14/2021] [Indexed: 12/20/2022]
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) is estimated to affect a quarter of all population and represents a major health threat to all societies. Yet, currently no approved pharmacological treatment is available for MAFLD. H2-rich water has recently been reported to reduce hepatic lipid accumulation in MAFLD patients but its efficacy is limited due to low H2 dosage. Increasing H2 dose may enhance its therapeutic effects but remains technically challenging. In this study, we designed and synthesized a hydrogen nanocapsule by encapsulating ammonia borane into hollow mesoporous silica nanoparticles to achieve ultrahigh and sustained H2 release in the gut. We then investigated its efficacy in treating early-stage MAFLD and other metabolic dysfunctions such as obesity and diabetes. The hydrogen nanocapsule attenuated both diet-induced and genetic mutation induced early-stage MAFLD, obesity, and diabetes in mice, without any tissue toxicity. Mechanistically, we discovered that sustained and ultrahigh H2 supply by hydrogen nanocapsule increased, among other species, the abundance of Akkermansia muciniphila, highlighting reshaped gut microbiota as a potential mechanism of H2 in treating metabolic dysfunctions. Moreover, hepatic transcriptome showed a reprogramed liver metabolism profile with reduced lipid synthesis and increased fatty acid metabolism.
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Affiliation(s)
- Zhaokui Jin
- Guangdong Provincial Key Laboratory of Immunity and Diseases, Marshall Laboratory of Biomedical Engineering, Shenzhen University, Shenzhen, China; School of Biomedical Engineering, Health Science Center, Shenzhen University, No. 1066 Xueyuan Avenue, Shenzhen, 518060, Guangdong, China
| | - Yuan Sun
- Department of Physiology, Health Science Center, Shenzhen University, No. 1066 Xueyuan Avenue, Shenzhen, 518060, Guangdong, China; Department of Pharmacology, College of Pharmacy, Shenzhen Technology University, Shenzhen, China
| | - Tian Yang
- School of Biomedical Engineering, Health Science Center, Shenzhen University, No. 1066 Xueyuan Avenue, Shenzhen, 518060, Guangdong, China
| | - Lunbo Tan
- School of Biomedical Engineering, Health Science Center, Shenzhen University, No. 1066 Xueyuan Avenue, Shenzhen, 518060, Guangdong, China; Department of Physiology, Health Science Center, Shenzhen University, No. 1066 Xueyuan Avenue, Shenzhen, 518060, Guangdong, China
| | - Peixun Lv
- School of Biomedical Engineering, Health Science Center, Shenzhen University, No. 1066 Xueyuan Avenue, Shenzhen, 518060, Guangdong, China
| | - Qingqing Xu
- School of Biomedical Engineering, Health Science Center, Shenzhen University, No. 1066 Xueyuan Avenue, Shenzhen, 518060, Guangdong, China
| | - Geru Tao
- Institute of Atherosclerosis, Taishan Institute for Hydrogen Biological Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, 271000, Shandong, China
| | - Shucun Qin
- Institute of Atherosclerosis, Taishan Institute for Hydrogen Biological Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, 271000, Shandong, China
| | - Xifeng Lu
- Guangdong Provincial Key Laboratory of Immunity and Diseases, Marshall Laboratory of Biomedical Engineering, Shenzhen University, Shenzhen, China; Department of Physiology, Health Science Center, Shenzhen University, No. 1066 Xueyuan Avenue, Shenzhen, 518060, Guangdong, China.
| | - Qianjun He
- Guangdong Provincial Key Laboratory of Immunity and Diseases, Marshall Laboratory of Biomedical Engineering, Shenzhen University, Shenzhen, China; School of Biomedical Engineering, Health Science Center, Shenzhen University, No. 1066 Xueyuan Avenue, Shenzhen, 518060, Guangdong, China; Institute of Atherosclerosis, Taishan Institute for Hydrogen Biological Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, 271000, Shandong, China; Center of Hydrogen Science, Shanghai Jiao Tong University, Shanghai, 200240, China.
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Hydrogen gas as a central on-off functional switch of reversible metabolic arrest - New perspectives for biotechnological applications. J Biotechnol 2021; 335:9-18. [PMID: 34090950 DOI: 10.1016/j.jbiotec.2021.06.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2021] [Revised: 05/09/2021] [Accepted: 06/01/2021] [Indexed: 11/23/2022]
Abstract
Metabolism is the sum of all chemical reactions that sustain life. There is an ongoing effort to control metabolic rate, which correlates with the maximum lifespan potential and constitutes one of the oldest scientific questions. Herein, we report on the complete reversible arrest of cellular metabolism and cell growth in a series of organisms, from microalgae to yeast upon exposure to a 100 % hydrogen atmosphere. We also report a tolerance of the microalgae under these conditions against extreme stress conditions, like high salt concentrations. The addition of oxygen or air almost completely restores the metabolic rate and cell growth. Molecular dynamics simulations are employed to decipher this phenomenon at atomic scale. Various proteins, including photosynthetic and respiratory complexes (LHCII, cytochrome c5) are probed in the interaction with hydrogen. Exposure to hydrogen, as opposed to oxygen, decreases the fluctuations of protein residues indicating thermostability. According to the above mechanism, an absolute hydrogen atmosphere can preserve biological products (e.g. fruits) for a long time without consuming any energy. By combining biological, chemical and computational methods, in this research we provide the basis for future innovative studies and advances in the field of biotechnology.
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Saitoh Y, Yamaguchi Y, Okada Y. Protective effects of dissolved molecular hydrogen against hydrogen peroxide-, hydroperoxide-, and glyoxal-induced injuries to human skin keratinocytes. Mol Cell Biochem 2021; 476:3613-3622. [PMID: 34028646 DOI: 10.1007/s11010-021-04189-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Accepted: 05/18/2021] [Indexed: 12/13/2022]
Abstract
Molecular hydrogen (H2) is recognized as a gaseous antioxidant, and it is expected to ameliorate various disorders related to oxidative stress and inflammation. However, there are still many unclear points regarding its effectiveness in the skin. Therefore, the purpose of this study was to examine the protective effect of H2 against ultraviolet (UV) irradiation-related stress injury in human epidermal HaCaT cells. We investigated the effects of H2 against three types of UV-derived oxidative stress using human skin keratinocytes: hydrogen peroxide (H2O2)-induced oxidative stress, tert-butyl hydroperoxide (t-BuOOH)-induced lipid peroxidation stress, and glyoxal-induced carbonyl stress. Our results showed that H2 exerted cytoprotective effects against stress induced by H2O2, t-BuOOH, and glyoxal. Furthermore, our results also revealed that H2 suppressed H2O2-induced increases in intracellular peroxide and H2O2 levels, and suppressed the progression of lipid peroxidation. Taken together, our results demonstrate that H2 can exert protective effects against oxidative stress-, lipid peroxidation-, and carbonyl stress-induced cellular injuries in human keratinocytes, partly mediated via suppression of intracellular oxidative stress and peroxide generation. Therefore, H2 is expected to be utilized as an effective and attractive component in cosmetic formulations in the future.
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Affiliation(s)
- Yasukazu Saitoh
- Laboratory of Bioscience & Biotechnology for Cell Function Control, Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, 5562 Nanatsuka, Shobara, Hiroshima, 727-0023, Japan.
| | - Yuuki Yamaguchi
- Laboratory of Bioscience & Biotechnology for Cell Function Control, Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, 5562 Nanatsuka, Shobara, Hiroshima, 727-0023, Japan
| | - Yuhei Okada
- Laboratory of Bioscience & Biotechnology for Cell Function Control, Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, 5562 Nanatsuka, Shobara, Hiroshima, 727-0023, Japan
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Drinking Molecular Hydrogen Water Is Beneficial to Cardiovascular Function in Diet-Induced Obesity Mice. BIOLOGY 2021; 10:biology10050364. [PMID: 33922704 PMCID: PMC8146054 DOI: 10.3390/biology10050364] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 04/10/2021] [Accepted: 04/20/2021] [Indexed: 11/17/2022]
Abstract
Molecular hydrogen (MH) reportedly exerts therapeutic effects against inflammatory diseases as a suppressor of free radical chain reactions. Here, the cardiovascular protective effects of the intake of molecular hydrogen water (MHW) were investigated using high-fat diet-induced obesity (DIO) mice. MHW was prepared using supplier sticks and degassed water as control. MHW intake for 2 weeks did not improve blood sugar or body weight but decreased heart weight in DIO mice. Moreover, MHW intake improved cardiac hypertrophy, shortened the width of cardiomyocytes, dilated the capillaries and arterioles, activated myocardial eNOS-Ser-1177 phosphorylation, and restored left ventricular function in DIO mice. MHW intake promoted the histological conversion of hypertrophy to hyperplasia in white and brown adipose tissues (WAT and BAT) with the upregulation of thermogenic and cardiovascular protective genes in BAT (i.e., Ucp-1, Vegf-a, and eNos). Furthermore, the results of a colony formation assay of bone-marrow-derived endothelial progenitor cells (EPCs) indicated that MHW activated the expansion, differentiation, and mobilization of EPCs to maintain vascular homeostasis. These findings indicate that the intake of MHW exerts cardiovascular protective effects in DIO mice. Hence, drinking MHW is a potential prophylactic strategy against cardiovascular disorders in metabolic syndrome.
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Ohta S. Direct Targets and Subsequent Pathways for Molecular Hydrogen to Exert Multiple Functions: Focusing on Interventions in Radical Reactions. Curr Pharm Des 2021; 27:595-609. [PMID: 32767925 DOI: 10.2174/1381612826666200806101137] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2020] [Accepted: 05/27/2020] [Indexed: 01/10/2023]
Abstract
Molecular hydrogen (H2) was long regarded as non-functional in mammalian cells. We overturned the concept by demonstrating that H2 exhibits antioxidant effects and protects cells against oxidative stress. Subsequently, it has been revealed that H2 has multiple functions in addition to antioxidant effects, including antiinflammatory, anti-allergic functions, and as cell death and autophagy regulation. Additionally, H2 stimulates energy metabolism. As H2 does not readily react with most biomolecules without a catalyst, it is essential to identify the primary targets with which H2 reacts or interacts directly. As a first event, H2 may react directly with strong oxidants, such as hydroxyl radicals (•OH) in vivo. This review addresses the key issues related to this in vivo reaction. •OH may have a physiological role because it triggers a free radical chain reaction and may be involved in the regulation of Ca2+- or mitochondrial ATP-dependent K+-channeling. In the subsequent pathway, H2 suppressed a free radical chain reaction, leading to decreases in lipid peroxide and its end products. Derived from the peroxides, 4-hydroxy-2-nonenal functions as a mediator that up-regulates multiple functional PGC-1α. As the other direct target in vitro and in vivo, H2 intervenes in the free radical chain reaction to modify oxidized phospholipids, which may act as an antagonist of Ca2+-channels. The resulting suppression of Ca2+-signaling inactivates multiple functional NFAT and CREB transcription factors, which may explain H2 multi-functionality. This review also addresses the involvement of NFAT in the beneficial role of H2 in COVID-19, Alzheimer's disease and advanced cancer. We discuss some unsolved issues of H2 action on lipopolysaccharide signaling, MAPK and NF-κB pathways and the Nrf2 paradox. Finally, as a novel idea for the direct targeting of H2, this review introduces the possibility that H2 causes structural changes in proteins via hydrate water changes.
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Affiliation(s)
- Shigeo Ohta
- Department of Neurology Medicine, Juntendo University Graduate School of Medicine, Tokyo, 113-8421, Japan
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Chen J, Qian W, Mu F, Niu L, Du D, Xu K. The future of cryoablation: An abscopal effect. Cryobiology 2020; 97:1-4. [PMID: 32097610 DOI: 10.1016/j.cryobiol.2020.02.010] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Revised: 02/20/2020] [Accepted: 02/21/2020] [Indexed: 01/10/2023]
Abstract
Cryoablation has become a popular modality to treat a variety of malignant tumors in solid organs and soft tissues. In the future, the use of cryoablation should focus on its abscopal effect. The present review discusses the increased immune response triggered by cryoablation alone or by cryoablation combined with immunotherapies, which can improve the immune response and limit immunosuppression. First, cryoablative techniques should be improved to increase the area of necrosis and reduce the area of apoptosis. Second, cryoablation should be combined with immunotherapies, for example, cyclophosphamide, natural killer cells, granulocyte monocyte colony stimulating factor (GM-CSF), cytotoxic T lymphocyte-associated antigen (CTLA)-4, and programmed death receptor 1 (PD)-1 inhibitors. Cryoablation could also be combined with Hydrogen gas molecules, which were shown recently to stimulate peroxisome proliferator activated receptor gamma coactivator (PGC)-1α, thereby promoting mitochondrial function, which might rescue exhausted CD8+ T cells, leading to prolonged progression-free survival and overall survival of patients with advanced colorectal cancer.
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Affiliation(s)
- Jibing Chen
- Fuda Cancer Hospital, Jinan University, Guangzhou, China
| | - Wei Qian
- Fuda Cancer Hospital, Jinan University, Guangzhou, China
| | - Feng Mu
- Fuda Cancer Hospital, Jinan University, Guangzhou, China
| | - Lizhi Niu
- Fuda Cancer Hospital, Jinan University, Guangzhou, China
| | - Duanming Du
- Intervention Dept. of Shenzhen Second People's Hospital, Shenzhen, 518035, China.
| | - Kecheng Xu
- Fuda Cancer Hospital, Jinan University, Guangzhou, China.
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Hori A, Sobue S, Kurokawa R, Hirano SI, Ichihara M, Hotta N. Two-week continuous supplementation of hydrogenrich water increases peak oxygen uptake during an incremental cycling exercise test in healthy humans: a randomized, single-blinded, placebo-controlled study. Med Gas Res 2020; 10:163-169. [PMID: 33380582 PMCID: PMC8092150 DOI: 10.4103/2045-9912.304223] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Revised: 06/15/2020] [Accepted: 06/24/2020] [Indexed: 12/17/2022] Open
Abstract
The various beneficial effects of the intake of molecular hydrogen (H2) have been demonstrated in the field of sports science. Although supplementation of H2 has been reported to increase mitochondrial metabolism in animal studies, the effects of the administration of H2 on aerobic capacity during exercise in humans are still not clear. We investigated whether a single or 2-week continuous intake of H2-rich water (HW) enhanced the aerobic capacity during incremental exercise in healthy humans. In this randomized, single-blinded, placebo-controlled experimental study, the participants performed an incremental cycling exercise to measure peak oxygen uptake and peak load before and after a single (500 mL) or a 2-week supplementation (total 5 L) of HW. In the latter experiment, the participants drank the 500 mL of HW on all weekdays (i.e., 10 times). The single intake of HW did not significantly increase peak oxygen uptake and peak load, and did not significantly alter the responses in oxidative stress, antioxidant activity, and lactate levels. However, importantly, the 2-week continuous consumption of HW significantly augmented peak oxygen uptake and tended to increase the peak load without any significant changes in lactate levels, oxidative stress, and antioxidant responses. In conclusion, the continuous supplementation of HW potentially augments the aerobic capacity, implying that continuous supplementation of H2 might help improve aerobic exercise performance and physical health. This study protocol was approved by the Ethical Committee of Chubu University (approval No. 260086-2) on March 29, 2018.
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Affiliation(s)
- Amane Hori
- Graduate School of Life and Health Sciences, Chubu University, Kasugai, Japan
| | - Sayaka Sobue
- College of Life and Health Sciences, Chubu University, Kasugai, Japan
| | | | | | - Masatoshi Ichihara
- Graduate School of Life and Health Sciences, Chubu University, Kasugai, Japan
- College of Life and Health Sciences, Chubu University, Kasugai, Japan
| | - Norio Hotta
- Graduate School of Life and Health Sciences, Chubu University, Kasugai, Japan
- College of Life and Health Sciences, Chubu University, Kasugai, Japan
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30
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Akagi J, Baba H. Hydrogen gas activates coenzyme Q10 to restore exhausted CD8 + T cells, especially PD-1 +Tim3 +terminal CD8 + T cells, leading to better nivolumab outcomes in patients with lung cancer. Oncol Lett 2020; 20:258. [PMID: 32994821 DOI: 10.3892/ol.2020.12121] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Accepted: 06/23/2020] [Indexed: 12/18/2022] Open
Abstract
As previously reported, hydrogen gas improves the prognosis of patients with cancer by restoring exhausted CD8+ T cells into active CD8+ T cells, possibly by activating mitochondria. As mitochondrial activators exhibit synergistic effects with nivolumab, the current study investigated whether hydrogen gas also affects the clinical outcomes of nivolumab. A total of 42 of 56 patients with lung cancer treated with nivolumab received hydrogen gas. Exhausted markers (PD-1 and Tim-3) on cell populations in the CD8+ T cell differentiation pathway were analyzed using flow cytometry. The concentration of coenzyme Q10 (CoQ10) was measured as a marker of mitochondrial function. The 42 patients treated with hydrogen gas and nivolumab (HGN) indicated a significantly longer overall survival (OS) compared with those treated with nivolumab only (n=14). In multivariate analysis, PD-1+Tim-3+terminal CD8+ T cells (PDT+) were an independent poor prognostic factor in OS, and CoQ10 showed a tendency to be associated with improved OS. The change in the rate of PDT+ and CoQ10 after vs. before HGN (PDT+ ratio and CoQ10 ratio, respectively) revealed that patients with low PDT+ ratio (<0.81) and high CoQ10 ratio (>1.175) had significantly longer OS compared with those with high PDT+ ratio and low CoQ10 ratio. Furthermore, PDT+, with a significant reverse correlation with CoQ10, was significantly lower in patients with high CoQ10 and/or CoQ10 ratio than in those low CoQ10 and/or CoQ10. Hydrogen gas has been suggested to enhance the clinical efficacy of nivolumab by increasing CoQ10 (mitochondria) to reduce PDT+, with PDT+ and CoQ10 as reliable negative and positive biomarkers of nivolumab, respectively.
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Affiliation(s)
- Junji Akagi
- Department of Surgery, Tamana Regional Health Medical Center, Kumamoto 865-0005, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery Kumamoto University, Kumamoto 860-8556, Japan
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Ashrafizadeh M, Najafi M, Mohammadinejad R, Farkhondeh T, Samarghandian S. Flaming the fight against cancer cells: the role of microRNA-93. Cancer Cell Int 2020; 20:277. [PMID: 32612456 PMCID: PMC7325196 DOI: 10.1186/s12935-020-01349-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Accepted: 06/15/2020] [Indexed: 12/14/2022] Open
Abstract
There have been attempts to develop novel anti-tumor drugs in cancer therapy. Although satisfying results have been observed at a consequence of application of chemotherapeutic agents, the cancer cells are capable of making resistance into these agents. This has forced scientists into genetic manipulation as genetic alterations are responsible for generation of a high number of cancer cells. MicroRNAs (miRs) are endogenous, short non-coding RNAs that affect target genes at the post-transcriptional level. Increasing evidence reveals the potential role of miRs in regulation of biological processes including angiogenesis, metabolism, cell proliferation, cell division, and cell differentiation. Abnormal expression of miRs is associated with development of a number of pathologic events, particularly cancer. MiR-93 plays a significant role in both physiological and pathological mechanisms. At the present review, we show how this miR dually affects the proliferation and invasion of cancer cells. Besides, we elucidate the oncogenesis or oncosuppressor function of miR-93.
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Affiliation(s)
- Milad Ashrafizadeh
- Department of Basic Science, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran
| | - Masoud Najafi
- Radiology and Nuclear Medicine Department, School of Paramedical Sciences, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Reza Mohammadinejad
- Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
| | - Tahereh Farkhondeh
- Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Saeed Samarghandian
- Healthy Ageing Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran
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32
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Affiliation(s)
- Shigeo Ohta
- Department of Neurology Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
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LeBaron TW, Singh RB, Fatima G, Kartikey K, Sharma JP, Ostojic SM, Gvozdjakova A, Kura B, Noda M, Mojto V, Niaz MA, Slezak J. The Effects of 24-Week, High-Concentration Hydrogen-Rich Water on Body Composition, Blood Lipid Profiles and Inflammation Biomarkers in Men and Women with Metabolic Syndrome: A Randomized Controlled Trial. Diabetes Metab Syndr Obes 2020; 13:889-896. [PMID: 32273740 PMCID: PMC7102907 DOI: 10.2147/dmso.s240122] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Accepted: 03/03/2020] [Indexed: 12/14/2022] Open
Abstract
PURPOSE Metabolic syndrome is associated with several medical risk factors including dyslipidemia, hyperglycemia, and obesity, which has become a worldwide pandemic. The sequelae of this condition increase the risk of cardiovascular and neurological disease and increased mortality. Its pathophysiology is associated with redox dysregulation, excessive inflammation, and perturbation of cellular homeostasis. Molecular hydrogen (H2) may attenuate oxidative stress, improve cellular function, and reduce chronic inflammation. Pre-clinical and clinical studies have shown promising effects of H2-rich water (HRW) on specific features of metabolic syndrome, yet the effects of long-term, high-concentration HRW in this prevalent condition remain poorly addressed. METHODS We conducted a randomized, double-blinded, placebo-controlled trial in 60 subjects (30 men and 30 women) with metabolic syndrome. An initial observation period of one week was used to acquire baseline clinical data followed by randomization to either placebo or high-concentration HRW (> 5.5 millimoles of H2 per day) for 24 weeks. RESULTS Supplementation with high-concentration HRW significantly reduced blood cholesterol and glucose levels, attenuated serum hemoglobin A1c, and improved biomarkers of inflammation and redox homeostasis as compared to placebo (P < 0.05). Furthermore, H2 tended to promote a mild reduction in body mass index and waist-to-hip ratio. CONCLUSION Our results give further credence that high-concentration HRW might have promising effects as a therapeutic modality for attenuating risk factors of metabolic syndrome.
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Affiliation(s)
- Tyler W LeBaron
- Centre of Experimental Medicine, Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovak Republic
- Molecular Hydrogen Institute, Enoch, UT, USA
| | - Ram B Singh
- Hospital and Research Institute, Moradabad, India
| | | | | | | | - Sergej M Ostojic
- Applied Bioenergetics Lab, Faculty of Sport and PE, University of Novi Sad, Novi Sad, Serbia
- Faculty of Health Sciences, University of Pécs, Pécs, Hungary
| | - Anna Gvozdjakova
- Medical Faculty, Pharmacobiochemical Laboratory of 3rd Medical Department, Comenius University Bratislava, Bratislava, Slovakia
| | | | - Mami Noda
- Laboratory of Pathophysiology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan
| | - Viliam Mojto
- Third Internal Clinic, Faculty of Medicine, Comenius University, Bratislava, Slovakia
| | - Mohammad Arif Niaz
- Center of Nutrition Research, International College of Nutrition, Moradabad, India
| | - Jan Slezak
- Centre of Experimental Medicine, Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovak Republic
- Correspondence: Jan Slezak Centre of Experimental Medicine, Institute for Heart Research, Slovak Academy of Sciences, Dúbravská Cesta 9, Bratislava841 04, Slovak RepublicTel +421 903 620 181 Email
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Li L, Liu Y, Wang S, Zou J, Ding W, Shen W. Magnesium Hydride-Mediated Sustainable Hydrogen Supply Prolongs the Vase Life of Cut Carnation Flowers via Hydrogen Sulfide. FRONTIERS IN PLANT SCIENCE 2020; 11:595376. [PMID: 33362825 PMCID: PMC7755932 DOI: 10.3389/fpls.2020.595376] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Accepted: 10/13/2020] [Indexed: 05/08/2023]
Abstract
Magnesium hydride (MgH2) is a promising solid-state hydrogen source with high storage capacity (7.6 wt%). Although it is recently established that MgH2 has potential applications in medicine because it sustainably supplies hydrogen gas (H2), the biological functions of MgH2 in plants have not been observed yet. Also, the slow reaction kinetics restricts its practical applications. In this report, MgH2 (98% purity; 0.5-25 μm size) was firstly used as a hydrogen generation source for postharvest preservation of flowers. Compared with the direct hydrolysis of MgH2 in water, the efficiency of hydrogen production from MgH2 hydrolysis could be greatly improved when the citrate buffer solution is introduced. These results were further confirmed in the flower vase experiment by showing higher efficiency in increasing the production and the residence time of H2 in solution, compared with hydrogen-rich water. Mimicking the response of hydrogen-rich water and sodium hydrosulfide (a hydrogen sulfide donor), subsequent experiments discovered that MgH2-citrate buffer solution not only stimulated hydrogen sulfide (H2S) synthesis but also significantly prolonged the vase life of cut carnation flowers. Meanwhile, redox homeostasis was reestablished, and the increased transcripts of representative senescence-associated genes, including DcbGal and DcGST1, were partly abolished. By contrast, the discussed responses were obviously blocked by the inhibition of endogenous H2S with hypotaurine, an H2S scavenger. These results clearly revealed that MgH2-supplying H2 could prolong the vase life of cut carnation flowers via H2S signaling, and our results, therefore, open a new window for the possible application of hydrogen-releasing materials in agriculture.
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Affiliation(s)
- Longna Li
- Laboratory Center of Life Sciences, College of Life Sciences, Nanjing Agricultural University, Nanjing, China
| | - Yuhao Liu
- Laboratory Center of Life Sciences, College of Life Sciences, Nanjing Agricultural University, Nanjing, China
| | - Shu Wang
- Laboratory Center of Life Sciences, College of Life Sciences, Nanjing Agricultural University, Nanjing, China
| | - Jianxin Zou
- Center of Hydrogen Science, Shanghai Jiao Tong University, Shanghai, China
| | - Wenjiang Ding
- Center of Hydrogen Science, Shanghai Jiao Tong University, Shanghai, China
| | - Wenbiao Shen
- Laboratory Center of Life Sciences, College of Life Sciences, Nanjing Agricultural University, Nanjing, China
- Center of Hydrogen Science, Shanghai Jiao Tong University, Shanghai, China
- *Correspondence: Wenbiao Shen,
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Chen J, Mu F, Lu T, Ma Y, Du D, Xu K. A Gallbladder Carcinoma Patient With Pseudo-Progressive Remission After Hydrogen Inhalation. Onco Targets Ther 2019; 12:8645-8651. [PMID: 31695424 PMCID: PMC6804672 DOI: 10.2147/ott.s227217] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Accepted: 10/03/2019] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND Hydrogen therapy has been reported to convert exhausted programmed cell death receptor (PD-1)+CD8+ T cells to PD-1-CD8+ T cells, in advanced colorectal cancer patients, which is associated with significantly prolonged survival. CASE PRESENTATION A 72-year-old female patient presented with metastatic gallbladder cancer and underwent symptomatic treatment combined with hydrogen therapy. The tumors were initially enlarged and displayed increased tumor marker expression following hydrogen inhalation therapy, after which they continued to remit, similar to the pseudo-progression that occurs after anti-PD-1 treatment. During one month of hydrogen therapy, the patient's gallbladder and liver tumors continued to progress, and intestinal obstruction occurred. The intestinal obstruction was gradually relieved after symptomatic treatment, and the metastases in the abdominal cavity gradually decreased in size, anemia and hypoalbuminemia were corrected, and both the lymphocyte and tumor marker levels returned to normal. The patient was able to resume normal life two and a half months after hydrogen inhalation and survived over 10 months. CONCLUSION This is the first report of pseudo-progression followed by sustained remission after hydrogen inhalation. This phenomenon is similar to the pseudo-progression-remission pattern that occurs following PD-1 antibody treatment. These findings suggest that hydrogen may have an inhibitory effect on PD-1 expression.
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Affiliation(s)
- Jibing Chen
- Fuda Cancer Hospital of Jinan University, Guangzhou510665, People’s Republic of China
- Fuda Cancer Institute of Guangzhou City, Guangzhou510665, People’s Republic of China
| | - Feng Mu
- Fuda Cancer Hospital of Jinan University, Guangzhou510665, People’s Republic of China
| | - Tianyu Lu
- Fuda Cancer Hospital of Jinan University, Guangzhou510665, People’s Republic of China
| | - Yangyang Ma
- Fuda Cancer Hospital of Jinan University, Guangzhou510665, People’s Republic of China
| | - Duanming Du
- Intervention Department, The Second People’s Hospital of Shenzhen, Shenzhen518035, People’s Republic of China
| | - Kecheng Xu
- Fuda Cancer Hospital of Jinan University, Guangzhou510665, People’s Republic of China
- Fuda Cancer Institute of Guangzhou City, Guangzhou510665, People’s Republic of China
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Myalgic encephalomyelitis/chronic fatigue syndrome: From pathophysiological insights to novel therapeutic opportunities. Pharmacol Res 2019; 148:104450. [PMID: 31509764 DOI: 10.1016/j.phrs.2019.104450] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Revised: 08/26/2019] [Accepted: 09/06/2019] [Indexed: 12/12/2022]
Abstract
Myalgic encephalomyelitis (ME) or chronic fatigue syndrome (CFS) is a common and disabling condition with a paucity of effective and evidence-based therapies, reflecting a major unmet need. Cognitive behavioural therapy and graded exercise are of modest benefit for only some ME/CFS patients, and many sufferers report aggravation of symptoms of fatigue with exercise. The presence of a multiplicity of pathophysiological abnormalities in at least the subgroup of people with ME/CFS diagnosed with the current international consensus "Fukuda" criteria, points to numerous potential therapeutic targets. Such abnormalities include extensive data showing that at least a subgroup has a pro-inflammatory state, increased oxidative and nitrosative stress, disruption of gut mucosal barriers and mitochondrial dysfunction together with dysregulated bioenergetics. In this paper, these pathways are summarised, and data regarding promising therapeutic options that target these pathways are highlighted; they include coenzyme Q10, melatonin, curcumin, molecular hydrogen and N-acetylcysteine. These data are promising yet preliminary, suggesting hopeful avenues to address this major unmet burden of illness.
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Chen JB, Pan ZB, Du DM, Qian W, Ma YY, Mu F, Xu KC. Hydrogen gas therapy induced shrinkage of metastatic gallbladder cancer: A case report. World J Clin Cases 2019; 7:2065-2074. [PMID: 31423439 PMCID: PMC6695532 DOI: 10.12998/wjcc.v7.i15.2065] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2019] [Revised: 06/17/2019] [Accepted: 06/26/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND We present the case of a 72-year-old female patient with gallbladder cancer (GBC) who developed in situ recurrence and liver metastases 9 mo after irreversible electroporation ablation and oral tegafur (a fluoropyrimidine derivative) chemotherapy, which failed to control the progression of the disease. The patient further developed metastases in the lymph nodes around the head of the pancreas. The patient had severe anemia, requiring weekly blood transfusions. The gallbladder tumor invaded the descending part of the duodenum, causing intestinal leakage and hepatic colonic adhesion. CASE SUMMARY The patient refused other treatments and began daily hydrogen inhalation therapy. After 1 mo of treatment, the gallbladder and liver tumors continued to progress, and intestinal obstruction occurred. After continuous hydrogen therapy and symptomatic treatments including gastrointestinal decompression and intravenous nutrition support, the intestinal obstruction was gradually relieved. Three months after hydrogen therapy, the metastases in the abdominal cavity gradually reduced in size, her anemia and hypoalbuminemia were corrected, lymphocyte and tumor marker levels returned to normal, and the patient was able to resume normal life. CONCLUSION This is the first report of an efficacy and safety study about hydrogen therapy in patient with metastatic GBC and a critical general condition, who has remained stable for more than 4 months.
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Affiliation(s)
- Ji-Bing Chen
- Central Laboratory, Fuda Cancer Hospital of Jinan University, Guangzhou 510665, Guangdong Province, China
| | - Zhong-Bao Pan
- Central Laboratory, Fuda Cancer Hospital of Jinan University, Guangzhou 510665, Guangdong Province, China
| | - Duan-Ming Du
- Intervention Department of Shenzhen Second People’s Hospital, Shenzhen 518035, Guangdong Province, China
| | - Wei Qian
- Central Laboratory, Fuda Cancer Hospital of Jinan University, Guangzhou 510665, Guangdong Province, China
| | - Yang-Yang Ma
- Central Laboratory, Fuda Cancer Hospital of Jinan University, Guangzhou 510665, Guangdong Province, China
| | - Feng Mu
- Central Laboratory, Fuda Cancer Hospital of Jinan University, Guangzhou 510665, Guangdong Province, China
| | - Ke-Cheng Xu
- Central Laboratory, Fuda Cancer Hospital of Jinan University, Guangzhou 510665, Guangdong Province, China
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Kawashima M, Tsuno S, Matsumoto M, Tsubota K. Hydrogen-producing milk to prevent reduction in tear stability in persons using visual display terminals. Ocul Surf 2019; 17:714-721. [PMID: 31352083 DOI: 10.1016/j.jtos.2019.07.008] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2018] [Revised: 07/19/2019] [Accepted: 07/24/2019] [Indexed: 12/23/2022]
Abstract
PURPOSE To examine the effect of hydrogen (H2)-producing milk, which induces H2 production by intestinal microbiota, on the prevention of dry eye disease. METHODS A randomized, double-blind, placebo-controlled, parallel-group comparative study was conducted in humans. Of 118 candidates aged 20-60 years who were using visual display terminals daily, 54 subjects (mean age, 42.4 years) with mild-to-moderate dry eye symptoms, who were not dry eye patients based on the 2006 Japanese Diagnostic Criteria for Dry Eye, were included in the study. Subjects were assigned to the H2-producing milk group or the placebo group. They were instructed to ingest the assigned test beverage once per day for three consecutive weeks. Breath H2 concentration, fluorescein tear film breakup time (fTBUT), Schirmer's test, 8-OHdG concentration in tears, reported ocular symptoms using the dry eye-related QOL score questionnaire, and the visual analogue scale were assessed at weeks 0 and 3. RESULTS Change in fTBUT in the H2-producing milk group was significantly greater than that in the placebo group. A significant decline in fTBUT was observed in the placebo group (p = 0.04), but not the H2-producing group (p = 0.26). This phenomenon was strongly observed in females. We found a positive correlation between the change in fTBUT and net H2 production, and a negative correlation between the change in 8-OHdG concentration and net H2 production in young females. CONCLUSIONS H2-producing milk appeared to retard the decline in tear stability and may prevent short fTBUT-type dry eye by decreasing oxidative stress in the lacrimal functional unit.
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Affiliation(s)
- Motoko Kawashima
- Department of Ophthalmology, Keio University School of Medicine, Tokyo, 160-8582, Japan.
| | - Saki Tsuno
- Dairy Science and Technology Institute, Kyodo Milk Industry Co. Ltd., Hinode-machi, Nishitama-gun, Tokyo, 190-0182, Japan
| | - Mitsuharu Matsumoto
- Dairy Science and Technology Institute, Kyodo Milk Industry Co. Ltd., Hinode-machi, Nishitama-gun, Tokyo, 190-0182, Japan.
| | - Kazuo Tsubota
- Department of Ophthalmology, Keio University School of Medicine, Tokyo, 160-8582, Japan
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Mikami T, Tano K, Lee H, Lee H, Park J, Ohta F, LeBaron TW, Ohta S. Drinking hydrogen water enhances endurance and relieves psychometric fatigue: a randomized, double-blind, placebo-controlled study 1. Can J Physiol Pharmacol 2019; 97:857-862. [PMID: 31251888 DOI: 10.1139/cjpp-2019-0059] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Acute physical exercise increases reactive oxygen species in skeletal muscle, leading to tissue damage and fatigue. Molecular hydrogen (H2) acts as a therapeutic antioxidant directly or indirectly by inducing antioxidative enzymes. Here, we examined the effects of drinking H2 water (H2-infused water) on psychometric fatigue and endurance capacity in a randomized, double-blind, placebo-controlled fashion. In Experiment 1, all participants drank only placebo water in the first cycle ergometer exercise session, and for comparison they drank either H2 water or placebo water 30 min before exercise in the second examination. In these healthy non-trained participants (n = 99), psychometric fatigue judged by visual analogue scales was significantly decreased in the H2 group after mild exercise. When each group was divided into 2 subgroups, the subgroup with higher visual analogue scale values was more sensitive to the effect of H2. In Experiment 2, trained participants (n = 60) were subjected to moderate exercise by cycle ergometer in a similar way as in Experiment 1, but exercise was performed 10 min after drinking H2 water. Endurance and fatigue were significantly improved in the H2 group as judged by maximal oxygen consumption and Borg's scale, respectively. Taken together, drinking H2 water just before exercise exhibited anti-fatigue and endurance effects.
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Affiliation(s)
- Toshio Mikami
- Department of Health and Sports Science, Nippon Medical School, Musashino, Tokyo 180-0023, Japan
| | - Kohei Tano
- Fitness Club, Asahi Big S Mukogaoka, Kawasaki-city, Kanagawa pref. 214-0014, Japan
| | - Hosung Lee
- Department of Health and Sports Science, Nippon Medical School, Musashino, Tokyo 180-0023, Japan
| | - Hyowon Lee
- Department of Health and Sports Science, Nippon Medical School, Musashino, Tokyo 180-0023, Japan
| | - Jonghyuk Park
- Department of Health and Sports Science, Nippon Medical School, Musashino, Tokyo 180-0023, Japan
| | - Fumiaki Ohta
- Hydrogen Health Medical Laboratory, Co., Ltd., Arakawa-ku, Tokyo 116-0001, Japan
| | - Tyler W LeBaron
- Slovak Academy of Sciences, Centre of Experimental Medicine, Institute for Heart Research, Bratislava 84005, Slovak Republic.,Molecular Hydrogen Institute, Enoch, UT 84721, USA
| | - Shigeo Ohta
- Department of Neurology Medicine, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan
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LeBaron TW, Kura B, Kalocayova B, Tribulova N, Slezak J. A New Approach for the Prevention and Treatment of Cardiovascular Disorders. Molecular Hydrogen Significantly Reduces the Effects of Oxidative Stress. Molecules 2019; 24:E2076. [PMID: 31159153 PMCID: PMC6600250 DOI: 10.3390/molecules24112076] [Citation(s) in RCA: 83] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2019] [Revised: 05/20/2019] [Accepted: 05/24/2019] [Indexed: 12/12/2022] Open
Abstract
Cardiovascular diseases are the most common causes of morbidity and mortality worldwide. Redox dysregulation and a dyshomeostasis of inflammation arise from, and result in, cellular aberrations and pathological conditions, which lead to cardiovascular diseases. Despite years of intensive research, there is still no safe and effective method for their prevention and treatment. Recently, molecular hydrogen has been investigated in preclinical and clinical studies on various diseases associated with oxidative and inflammatory stress such as radiation-induced heart disease, ischemia-reperfusion injury, myocardial and brain infarction, storage of the heart, heart transplantation, etc. Hydrogen is primarily administered via inhalation, drinking hydrogen-rich water, or injection of hydrogen-rich saline. It favorably modulates signal transduction and gene expression resulting in suppression of proinflammatory cytokines, excess ROS production, and in the activation of the Nrf2 antioxidant transcription factor. Although H2 appears to be an important biological molecule with anti-oxidant, anti-inflammatory, and anti-apoptotic effects, the exact mechanisms of action remain elusive. There is no reported clinical toxicity; however, some data suggests that H2 has a mild hormetic-like effect, which likely mediate some of its benefits. The mechanistic data, coupled with the pre-clinical and clinical studies, suggest that H2 may be useful for ROS/inflammation-induced cardiotoxicity and other conditions.
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Affiliation(s)
- Tyler W LeBaron
- Centre of Experimental Medicine, Institute for Heart Research, Slovak Academy of Sciences, Bratislava 841 04, Slovak Republic.
- Molecular Hydrogen Institute, Enoch City, UT, 847 21, USA.
| | - Branislav Kura
- Centre of Experimental Medicine, Institute for Heart Research, Slovak Academy of Sciences, Bratislava 841 04, Slovak Republic.
| | - Barbora Kalocayova
- Centre of Experimental Medicine, Institute for Heart Research, Slovak Academy of Sciences, Bratislava 841 04, Slovak Republic.
| | - Narcis Tribulova
- Centre of Experimental Medicine, Institute for Heart Research, Slovak Academy of Sciences, Bratislava 841 04, Slovak Republic.
| | - Jan Slezak
- Centre of Experimental Medicine, Institute for Heart Research, Slovak Academy of Sciences, Bratislava 841 04, Slovak Republic.
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Klichko VI, Safonov VL, Safonov MY, Radyuk SN. Supplementation with hydrogen-producing composition confers beneficial effects on physiology and life span in Drosophila. Heliyon 2019; 5:e01679. [PMID: 31193183 PMCID: PMC6522691 DOI: 10.1016/j.heliyon.2019.e01679] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2018] [Revised: 04/08/2019] [Accepted: 05/03/2019] [Indexed: 12/11/2022] Open
Abstract
Recently, molecular hydrogen (H2) has become known as a new class of antioxidants and redox-modulating interventions. Effects of H2 have been documented for many acute and chronic pathological conditions. The present study was aimed at determining the effect of hydrogen on the physiology and longevity of Drosophila. The flies were given a patented food supplement consisting of a mixture of inert salts with metallic magnesium, which reacted with acidic aqueous solutions, thereby releasing hydrogen gas. The supplementation with hydrogen-rich food prolonged the life span of the wild-type strain. To gain insights into the effect of hydrogen, we used previously generated mutant under-expressing redox-regulating enzymes, peroxiredoxins, in mitochondria. The hydrogen-releasing material lessened the severe shortening of life span of the mutant. Hydrogen also delayed the development of intestinal dysfunction caused by under-expression of peroxiredoxins in the intestinal epithelium. Hydrogen also averted a significant decrease in the mobility of mutant flies that under-expressed peroxiredoxins globally or in specific tissues. Together, the results showed that the introduction of hydrogen to aging or short-lived flies could increase their survival, delay the development of the intestinal barrier dysfunction and significantly improve physical activity.
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42
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Kura B, Bagchi AK, Singal PK, Barancik M, LeBaron TW, Valachova K, Šoltés L, Slezák J. Molecular hydrogen: potential in mitigating oxidative-stress-induced radiation injury. Can J Physiol Pharmacol 2019; 97:287-292. [DOI: 10.1139/cjpp-2018-0604] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Uncontrolled production of oxygen and nitrogen radicals results in oxidative and nitrosative stresses that impair cellular functions and have been regarded as causative common denominators of many pathological processes. In this review, we report on the beneficial effects of molecular hydrogen in scavenging radicals in an artificial system of•OH formation. As a proof of principle, we also demonstrate that in rat hearts in vivo, administration of molecular hydrogen led to a significant increase in superoxide dismutase as well as pAKT, a cell survival signaling molecule. Irradiation of the rats caused a significant increase in lipid peroxidation, which was mitigated by pre-treatment of the animals with molecular hydrogen. The nuclear factor erythroid 2-related factor 2 is regarded as an important regulator of oxyradical homeostasis, as well as it supports the functional integrity of cells, particularly under conditions of oxidative stress. We suggest that the beneficial effects of molecular hydrogen may be through the activation of nuclear factor erythroid 2-related factor 2 pathway that promotes innate antioxidants and reduction of apoptosis, as well as inflammation.
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Affiliation(s)
- Branislav Kura
- Centre of Experimental Medicine, Institute for Heart Research, Slovak Academy of Sciences, 841 04 Bratislava, Slovak Republic
| | - Ashim K. Bagchi
- Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre, University of Manitoba, Winnipeg, MB R2H 2A6, Canada
| | - Pawan K. Singal
- Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre, University of Manitoba, Winnipeg, MB R2H 2A6, Canada
| | - Miroslav Barancik
- Centre of Experimental Medicine, Institute for Heart Research, Slovak Academy of Sciences, 841 04 Bratislava, Slovak Republic
| | - Tyler W. LeBaron
- Centre of Experimental Medicine, Institute for Heart Research, Slovak Academy of Sciences, 841 04 Bratislava, Slovak Republic
- Molecular Hydrogen Institute, Enoch, Utah 84721, USA
| | - Katarina Valachova
- Centre of Experimental Medicine, Institute of Experimental Pharmacology and Toxicology, 841 04 Bratislava, Slovak Republic
| | - Ladislav Šoltés
- Centre of Experimental Medicine, Institute of Experimental Pharmacology and Toxicology, 841 04 Bratislava, Slovak Republic
| | - Ján Slezák
- Centre of Experimental Medicine, Institute for Heart Research, Slovak Academy of Sciences, 841 04 Bratislava, Slovak Republic
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Cejka C, Kubinova S, Cejkova J. The preventive and therapeutic effects of molecular hydrogen in ocular diseases and injuries where oxidative stress is involved. Free Radic Res 2019; 53:237-247. [DOI: 10.1080/10715762.2019.1582770] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
- Cestmir Cejka
- Institute of Experimental Medicine, Czech Academy of Sciences, Prague, Czech Republic
| | - Sarka Kubinova
- Institute of Experimental Medicine, Czech Academy of Sciences, Prague, Czech Republic
| | - Jitka Cejkova
- Institute of Experimental Medicine, Czech Academy of Sciences, Prague, Czech Republic
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LeBaron TW, Larson AJ, Ohta S, Mikami T, Barlow J, Bulloch J, DeBeliso M. Acute Supplementation with Molecular Hydrogen Benefits Submaximal Exercise Indices. Randomized, Double-Blinded, Placebo-Controlled Crossover Pilot Study. J Lifestyle Med 2019; 9:36-43. [PMID: 30918832 PMCID: PMC6425901 DOI: 10.15280/jlm.2019.9.1.36] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Accepted: 12/22/2018] [Indexed: 12/31/2022] Open
Abstract
Background Clinical studies have reported hydrogen-rich water (HRW) to have therapeutic and ergogenic effects. The aim of this study was to determine the effect of acute supplementation with HRW on exercise performance as measured by VO2, respiratory exchange ratio (RER), heart rate (HR), and respiratory rate (RR). Methods Baseline levels of all exercise indices were determined in nineteen (4 female, 23.4 ± 9.1 yr; 15 male, 30.5 ± 6.8 yr) healthy subjects using a graded treadmill exercise test to exhaustion. Each subject was examined two additional times in a randomized double-blinded, placebo-controlled crossover fashion. Subjects received either HRW or placebo, which was consumed the day before and the day of the testing. HRW was delivered using the hydrogen-producing tablets, DrinkHRW (5 mg of H2). All data was analyzed with SPSS using pairwise comparisons with Bonferroni adjustment. Results HRW supplementation did not influence maximal or minimal indices of exercise performance (VO2, RER, HR and RR) (p < 0.05). However, HRW significantly decreased average exercising RR and HR (p < 0.05). HRW decreased exercising HR during minutes 1–9 of the graded exercise test (121 ± 26 bpm) compared to placebo (126 ± 26 bpm) and baseline (124 ± 27 bpm) (p < 0.001) without substantially influencing VO2. Conclusion Acute supplementation of DrinkHRW tablets may benefit submaximal aerobic exercise performance by lowering exercising HR. Further studies are needed to determine the influence and practical significance of HRW on varying exercise intensities as well as optimal dosing protocols and the effects of chronic use.
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Affiliation(s)
- Tyler W LeBaron
- Department of Kinesiology and Outdoor Recreation, Southern Utah University, UT, USA.,Molecular Hydrogen Institute, UT, USA.,Slovak Academy of Sciences, Centre of Experimental Medicine, Institute for Heart Research, Bratislava, Slovakia
| | - Abigail J Larson
- Department of Kinesiology and Outdoor Recreation, Southern Utah University, UT, USA
| | - Shigeo Ohta
- Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan
| | - Toshio Mikami
- Department of Sport Science, Nippon Medical School, Tokyo, Japan
| | - Jordon Barlow
- Department of Kinesiology and Outdoor Recreation, Southern Utah University, UT, USA
| | - Josh Bulloch
- Department of Kinesiology and Outdoor Recreation, Southern Utah University, UT, USA
| | - Mark DeBeliso
- Department of Kinesiology and Outdoor Recreation, Southern Utah University, UT, USA
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Nishiwaki H, Ito M, Negishi S, Sobue S, Ichihara M, Ohno K. Molecular hydrogen upregulates heat shock response and collagen biosynthesis, and downregulates cell cycles: meta-analyses of gene expression profiles. Free Radic Res 2018; 52:434-445. [PMID: 29424253 DOI: 10.1080/10715762.2018.1439166] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Molecular hydrogen exerts its effect on multiple pathologies, including oxidative stress, inflammation, and apoptosis. However, its molecular mechanisms have not been fully elucidated. In order to explore the effects of molecular hydrogen, we meta-analysed gene expression profiles modulated by molecular hydrogen. We performed microarray analysis of the mouse liver with or without drinking hydrogen water. We also integrated two previously reported microarray datasets of the rat liver into meta-analyses. We used two categories of meta-analysis methods: the cross-platform method and the conventional meta-analysis method (Fisher's method). For each method, hydrogen-modulated pathways were analysed by (i) the hypergeometric test (HGT) in the class of over-representation analysis (ORA), (ii) the gene set enrichment analysis (GSEA) in the class of functional class scoring (FCS), and (iii) the signalling pathway impact analysis (SPIA), pathway regulation score (PRS), and others in the class of pathway topology-based approach (PTA). Pathways in the collagen biosynthesis and the heat-shock response were up-regulated according to (a) HGT with the cross-platform method, (b) GSEA with the cross-platform method, and (c) PRS with the cross-platform method. Pathways in cell cycles were down-regulated according to (a) HGT with the cross-platform method, (b) GSEA with the cross-platform method, and (d) GSEA with the conventional meta-analysis method. Because the heat-shock response leads to up-regulation of collagen biosynthesis and a transient arrest of cell cycles, induction of the heat-shock response is likely to be a primary event induced by molecular hydrogen in the liver of wild-type rodents.
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Affiliation(s)
- Hiroshi Nishiwaki
- a Division of Neurogenetics , Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine , Nagoya , Japan
| | - Mikako Ito
- a Division of Neurogenetics , Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine , Nagoya , Japan
| | - Shuto Negishi
- a Division of Neurogenetics , Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine , Nagoya , Japan
| | - Sayaka Sobue
- b Department of Biomedical Sciences , College of Life and Health Sciences, Chubu University , Kasugai , Japan
| | - Masatoshi Ichihara
- b Department of Biomedical Sciences , College of Life and Health Sciences, Chubu University , Kasugai , Japan
| | - Kinji Ohno
- a Division of Neurogenetics , Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine , Nagoya , Japan
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Wang X, Liao Z, Bai Z, He Y, Duan J, Wei L. MiR-93-5p Promotes Cell Proliferation through Down-Regulating PPARGC1A in Hepatocellular Carcinoma Cells by Bioinformatics Analysis and Experimental Verification. Genes (Basel) 2018; 9:genes9010051. [PMID: 29361788 PMCID: PMC5793202 DOI: 10.3390/genes9010051] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2017] [Revised: 01/15/2018] [Accepted: 01/16/2018] [Indexed: 12/11/2022] Open
Abstract
Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A, formerly known as PGC-1a) is a transcriptional coactivator and metabolic regulator. Previous studies are mainly focused on the association between PPARGC1A and hepatoma. However, the regulatory mechanism remains unknown. A microRNA associated with cancer (oncomiR), miR-93-5p, has recently been found to play an essential role in tumorigenesis and progression of various carcinomas, including liver cancer. Therefore, this paper aims to explore the regulatory mechanism underlying these two proteins in hepatoma cells. Firstly, an integrative analysis was performed with miRNA–mRNA modules on microarray and The Cancer Genome Atlas (TCGA) data and obtained the core regulatory network and miR-93-5p/PPARGC1A pair. Then, a series of experiments were conducted in hepatoma cells with the results including miR-93-5p upregulated and promoted cell proliferation. Thirdly, the inverse correlation between miR-93-5p and PPARGC1A expression was validated. Finally, we inferred that miR-93-5p plays an essential role in inhibiting PPARGC1A expression by directly targeting the 3′-untranslated region (UTR) of its mRNA. In conclusion, these results suggested that miR-93-5p overexpression contributes to hepatoma development by inhibiting PPARGC1A. It is anticipated to be a promising therapeutic strategy for patients with liver cancer in the future.
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Affiliation(s)
- Xinrui Wang
- State Key Laboratory for Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
| | - Zhijun Liao
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China.
| | - Zhimin Bai
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China.
- Department of Clinical Laboratory, Jinjiang Municipal Hospital, Jinjiang 362200, China.
| | - Yan He
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China.
| | - Juan Duan
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China.
| | - Leyi Wei
- School of Computer Science and Technology, Tianjin University, Tianjin 300350, China.
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Protective Effect of Hydrogen Gas Inhalation on Muscular Damage Using a Mouse Hindlimb Ischemia-Reperfusion Injury Model. Plast Reconstr Surg 2017; 140:1195-1206. [DOI: 10.1097/prs.0000000000003878] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
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Lin CP, Chuang WC, Lu FJ, Chen CY. Anti-oxidant and anti-inflammatory effects of hydrogen-rich water alleviate ethanol-induced fatty liver in mice. World J Gastroenterol 2017; 23:4920-4934. [PMID: 28785146 PMCID: PMC5526762 DOI: 10.3748/wjg.v23.i27.4920] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2017] [Revised: 03/31/2017] [Accepted: 06/19/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the effects of hydrogen-rich water (HRW) treatment on prevention of ethanol (EtOH)-induced early fatty liver in mice.
METHODS In vitro reduction of hydrogen peroxide by HRW was determined with a chemiluminescence system. Female mice were randomly divided into five groups: control, EtOH, EtOH + silymarin, EtOH + HRW and EtOH + silymarin + HRW. Each group was fed a Lieber-DeCarli liquid diet containing EtOH or isocaloric maltose dextrin (control diet). Silymarin was used as a positive control to compare HRW efficacy against chronic EtOH-induced hepatotoxicity. HRW was freshly prepared and given at a dosage of 1.2 mL/mouse trice daily. Blood and liver tissue were collected after chronic-binge liquid-diet feeding for 12 wk.
RESULTS The in vitro study showed that HRW directly scavenged hydrogen peroxide. The in vivo study showed that HRW increased expression of acyl ghrelin, which was correlated with food intake. HRW treatment significantly reduced EtOH-induced increases in serum alanine aminotransferase, aspartate aminotransferase, triglycerol and total cholesterol levels, hepatic lipid accumulation and inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6. HRW attenuated malondialdehyde level, restored glutathione depletion and increased superoxide dismutase, glutathione peroxidase and catalase activities in the liver. Moreover, HRW reduced TNF-α and IL-6 levels but increased IL-10 and IL-22 levels.
CONCLUSION HRW protects against chronic EtOH-induced liver injury, possibly by inducing acyl ghrelin to suppress the pro-inflammatory cytokines TNF-α and IL-6 and induce IL-10 and IL-22, thus activating antioxidant enzymes against oxidative stress.
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