• cancer therapy
• controlled release
• hydrogen therapy
• nanomedicine
• suppository

• Fluorouracil/pharmacology
• Fluorouracil/chemistry
• Fluorouracil/therapeutic use
• Hydrogen/chemistry
• Hydrogen/pharmacology
• Animals
• Colonic Neoplasms/drug therapy
• Colonic Neoplasms/pathology
• Colonic Neoplasms/metabolism
• Humans
• Suppositories/chemistry
• Mice
• Nanoparticles/chemistry
• Apoptosis/drug effects
• Cell Line, Tumor
• Mice, Inbred BALB C
• Delayed-Action Preparations/chemistry

• U23A20690 National Natural Science Foundation of China
• 82172078 National Natural Science Foundation of China
• RCJC20210706092010008 Shenzhen Science and Technology Program
• 2022YFB3804500 National Key Research and Development Program of China

• H(2) biology
• Hydrogen rich water (HRW)
• Interactions
• Postharvest senescence
• Regulator pathway

• Hydrogen/metabolism
• Food Preservation/methods
• Ethylenes/metabolism
• Horticulture
• Plant Development/drug effects

• biomedical applications
• gas delivery
• gas generating gas therapy
• therapeutic gases

• Humans
• Gases/chemistry
• Carbon Monoxide
• Nitric Oxide
• Animals
• Hydrogen Sulfide/chemistry
• Oxygen/chemistry
• Carbon Dioxide/chemistry
• Hydrogen/chemistry
• Drug Delivery Systems
• Neoplasms/therapy
• Neoplasms/drug therapy

• 38351 Fonds De La Recherche Scientifique - FNRS

• anticancer drug
• antitumor drug
• clinical application
• inflammation
• molecular hydrogen
• oxidative stress
• reactive oxygen species
• side effect
• tissue injury

• Cancer treatment
• Hydrogen
• Intestinal flora
• Oxidative stress
• Tumor immunity

• Humans
• Reactive Oxygen Species
• Hydrogen/pharmacology
• Hydrogen/therapeutic use
• Cell Proliferation
• Gastrointestinal Microbiome
• Immunomodulation
• Neoplasms/drug therapy
• Neoplasms/prevention & control

• anti-inflammatory
• cancer therapy
• hydrogen delivery
• metal hydride
• nanomedicine

• Antioxidants/pharmacology
• Antioxidants/therapeutic use
• Metals
• Hydrogen

• Hydrogen
• antioxidant
• cancer
• inflammation.
• oxidative stress
• therapeutic application

• Humans
• Hydrogen/pharmacology
• Hydrogen/therapeutic use
• Hydrogen/chemistry
• Neoplasms/drug therapy
• Neoplasms/pathology
• Animals
• Oxidative Stress/drug effects
• Antineoplastic Agents/pharmacology
• Antineoplastic Agents/therapeutic use
• Antioxidants/pharmacology
• Antioxidants/therapeutic use

• complex I
• hydrogenase
• mitochondria
• mitochondrial quality control
• molecular hydrogen (H2)

• hole-scavengers
• hydrogen therapy
• sonocatalysis
• sonosensitizers

• Humans
• Platinum/chemistry
• Cell Line, Tumor
• Nanoparticles/chemistry
• Oxygen/chemistry
• Glutathione
• Tumor Microenvironment
• Neoplasms/therapy
• Hydrogen Peroxide/chemistry

• BIRC3
• RNA sequencing
• XIAP
• hydrogen gas
• lung adenocarcinoma

Ageing is a physiological process of progressive decline in the organism function over time. It affects every organ in the body and is a significant risk for chronic diseases. Molecular hydrogen has therapeutic and preventive effects on various organs. It has antioxidative properties as it directly neutralizes hydroxyl radicals and reduces peroxynitrite level. It also activates Nrf2 and HO-1, which regulate many antioxidant enzymes and proteasomes. Through its antioxidative effect, hydrogen maintains genomic stability, mitigates cellular senescence, and takes part in histone modification, telomere maintenance, and proteostasis. In addition, hydrogen may prevent inflammation and regulate the nutrient-sensing mTOR system, autophagy, apoptosis, and mitochondria, which are all factors related to ageing. Hydrogen can also be used for prevention and treatment of various ageing-related diseases, such as neurodegenerative disorders, cardiovascular disease, pulmonary disease, diabetes, and cancer. This paper reviews the basic research and recent application of hydrogen in order to support hydrogen use in medicine for ageing prevention and ageing-related disease therapy.

Molecular hydrogen ameliorates pathological states in a variety of human diseases, animal models, and cell models, but the effects of hydrogen on cancer have been rarely reported. In addition, the molecular mechanisms underlying the effects of hydrogen remain mostly unelucidated. We found that hydrogen enhances proliferation of four out of seven human cancer cell lines (the responders). The proliferation-promoting effects were not correlated with basal levels of cellular reactive oxygen species. Expression profiling of the seven cells showed that the responders have higher gene expression of mitochondrial electron transport chain (ETC) molecules than the non-responders. In addition, the responders have higher mitochondrial mass, higher mitochondrial superoxide, higher mitochondrial membrane potential, and higher mitochondrial spare respiratory capacity than the non-responders. In the responders, hydrogen provoked mitochondrial unfolded protein response (mtUPR). Suppression of cell proliferation by rotenone, an inhibitor of mitochondrial ETC complex I, was rescued by hydrogen in the responders. Hydrogen triggers mtUPR and induces cell proliferation in cancer cells that have high basal and spare mitochondrial ETC activities.

• cancer cell lines
• cellular proliferation
• mitochondrial electron transfer chain
• mitochondrial unfolded protein response
• molecular hydrogen

• Animals
• Cell Proliferation
• Hydrogen/metabolism
• Hydrogen/pharmacology
• Mitochondria/metabolism
• Neoplasms/drug therapy
• Neoplasms/metabolism
• Reactive Oxygen Species/metabolism
• Superoxides/metabolism
• Unfolded Protein Response

• 5-fluorouracil
• Antioxidants
• Colorectal cancer
• Inflammation
• Molecular hydrogen
• Oxidative stress

Hydrogen has been used to suppress tumor growth with considerable efficacy. Inhalation of hydrogen gas and oral ingestion of hydrogen-rich saline are two common systemic routes of hydrogen administration. We have developed a topical delivery method of hydrogen at targeted sites through the degradation of magnesium-based biomaterials. However, the underlying mechanism of hydrogen's role in cancer treatment remains ambiguous. Here, we investigate the mechanism of tumor cell apoptosis triggered by the hydrogen released from magnesium-based biomaterials. We find that the localized release of hydrogen increases the expression level of P53 tumor suppressor proteins, as demonstrated by the in vitro RNA sequencing and protein expression analysis. Then, the P53 proteins disrupt the membrane potential of mitochondria, activate autophagy, suppress the reactive oxygen species in cancer cells, and finally result in tumor suppression. The anti-tumor efficacy of magnesium-based biomaterials is further validated in vivo by inserting magnesium wire into the subcutaneous tumor in a mouse. We also discovered that the minimal hydrogen concentration from magnesium wires to trigger substantial tumor apoptosis is 91.2 μL/mm³ per day, which is much lower than that required for hydrogen inhalation. Taken together, these findings reveal the release of H₂ from magnesium-based biomaterial exerts its anti-tumoral activity by activating the P53-mediated lysosome-mitochondria apoptosis signaling pathway, which strengthens the therapeutic potential of this biomaterial as localized anti-tumor treatment.

•

The feasibility of using Mg implants is explored for localized delivery of hydrogen against colorectal tumors.

• Biodegradable magnesium
• Hydrogen
• P53
• Tumor apoptosis
• Underlying mechanism

Background: Cholangiofibrosis is a controversial intrahepatic cholangial lesion that precedes the development of cholangiocarcinoma. Here, we demonstrate that molecular hydrogen (H₂) can be used to effectively prevent cholangiofibrosis.

Methods: The safety and quality of life (QOL) of rats was firstly evaluated. H₂ was administered to rats subjected to thioacetamide (TAA)-induced cholangiofibrosis throughout the whole process. Then, rats were administrated with TAA for 3 months and then followed by H₂ intervention. Rat livers were harvested and assessed by light microscopy and convolutional neural network. RNA-seq was performed to analyze the genetic changes in these animal models.

Results: Continuous use of H₂-rich water was safe and improved QOL.The incidence and average number of cholangiofibrosis in the liver were higher in the TAA group (100%, 12.0 ± 10.07) than that in the H₂ group (57.1%, 2.86 ± 5.43). The AI algorithm revealed higher Alesion/Aliver in the TAA group (19.6% ± 9.01) than that in the H₂ group (7.54% ± 11.0). RNA-seq analysis revealed that H₂ results in a decline in glycolysis. Moreover, in the third experiment, the incidence of microscopic or suspicious tumors and the ratio of liver lesions was decreased after long-term use of H₂ (12.5%, 0.57% ± 0.45) compared with untreated group (100%, 0.98% ± 0.73). A number of intestinal microbiota was changed after H₂ usage, including clostridiaceae_1, ruminococcus, turicibacter, coriobacteriales, actinobacteria, and firmicutes_bacterium.

Conclusion: Hydrogen-rich water protects against liver injury and cholangiofibrosis and improved quality of life partially through regulating the composition of intestinal flora.

• H2
• artificial intelligence
• cancer prevention
• cholangiofibrosis
• quality of life

• Hydrogen gas (H2); Hydrogen agronomy; New agriculture

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.

• DNA mutation
• ROS
• antitumor agent
• antitumor effect
• clinical application
• gene expression
• molecular hydrogen
• oxidative stress
• reactive oxygen species

• X-ray
• hydrogen gas therapy
• long afterglow
• photocatalysis
• radiotherapy

• Dissolved hydrogen molecule
• human gastric adenocarcinoma cells
• nanomedicine
• platinum nanocolloid
• reactive oxygen species

• Hydrogen gas
• field trials
• hydrogen agriculture
• hydrogen biology
• low-carbon agriculture
• molecular mechanism

• advanced cancer
• clinical rehabilitation
• disease control rate
• hydrogen inhalation therapy
• life quality
• physical status
• real world survey
• tumor marker
• tumor stage

• Endometrial cancer
• GSDMD
• Hydrogen
• NLRP3
• Pyroptosis

• Ischemic stroke
• free radical scavenging
• nanoerythrocyte
• natural oxygen sponge effect

• Animals
• Brain Ischemia/drug therapy
• Brain Ischemia/metabolism
• Brain Ischemia/pathology
• Erythrocytes/metabolism
• Erythrocytes/pathology
• Free Radical Scavengers/chemistry
• Free Radical Scavengers/pharmacology
• Ischemic Stroke/drug therapy
• Ischemic Stroke/metabolism
• Ischemic Stroke/pathology
• Mice
• Nanostructures/chemistry
• Nanostructures/therapeutic use
• PC12 Cells
• RAW 264.7 Cells
• Rats
• Rats, Sprague-Dawley

• anti-apoptosis
• anti-inflammation
• antioxidant
• molecular hydrogen
• molecular mechanism

• Drug Delivery Systems
• Humans
• Hydrogen/therapeutic use
• Inflammation/therapy
• Nanostructures/therapeutic use
• Neoplasms/therapy

• Case report
• Hydrogen gas
• Metastatic gallbladder cancer

• antioxidation
• hydrogen therapy
• inflammation
• nanomaterials
• reactive oxygen species

Glioblastoma (GBM) is the most common type of primary malignant brain tumor. Molecular hydrogen has been considered a preventive and therapeutic medical gas in many diseases including cancer. In our study, we sought to assess the potential role of molecular hydrogen on GBM.

The in vivo studies were performed using a rat orthotopic glioma model and a mouse subcutaneous xenograft model. Animals inhaled hydrogen gas (67%) 1 h two times per day. MR imaging studies were performed to determine the tumor volume. Immunohistochemistry (IHC), immunofluorescence staining, and flow cytometry analysis were conducted to determine the expression of surface markers. Sphere formation assay was performed to assess the cancer stem cell self-renewal capacity. Assays for cell migration, invasion, and colony formation were conducted.

The in vivo study showed that hydrogen inhalation could effectively suppress GBM tumor growth and prolong the survival of mice with GBM. IHC and immunofluorescence staining demonstrated that hydrogen treatment markedly downregulated the expression of markers involved in stemness (CD133, Nestin), proliferation (ki67), and angiogenesis (CD34) and also upregulated GFAP expression, a marker of differentiation. Similar results were obtained in the in vitro studies. The sphere-forming ability of glioma cells was also suppressed by hydrogen treatment. Moreover, hydrogen treatment also suppressed the migration, invasion, and colony-forming ability of glioma cells.

Together, these results indicated that molecular hydrogen may serve as a potential anti-tumor agent in the treatment of GBM.

• Cancer cell stemness
• Glioblastoma
• Glioma stem-like cell
• Molecular hydrogen

• MEG3
• Nrf2
• high-content hydrogen water
• miR-136
• non-alcoholic fatty liver disease

Hydrogen is the most abundant chemical element in the universe, and has been used as an inert gas for a long time. More recent studies have shown that molecular hydrogen as a kind of antioxidant, anti-inflammatory, anti-apoptosis, gene expression and signal modulation molecule, can be used for the treatment of many diseases. This review mainly focuses on the research progresses of hydrogen in various medical fields and the possible action mechanisms.

• action mechanisms
• antioxidant
• future direction
• gene expression
• hydrogen
• injection methods
• research progresses
• signal-transduction

In the last decade, many studies have shown that hydrogen gas or hydrogen water can reduce the levels of reactive oxygen species in the living body. Molecular hydrogen has antioxidant and antiapoptotic effects and a preventive effect on oxidative stress-induced cell death. In the present study, we investigated solidified hydrogen-occluding-silica (H₂-silica) that can release molecular hydrogen into cell culture medium because the use of hydrogen gas has strict handling limitations in hospital and medical facilities and laboratories, owing to its physicochemical characteristics. Human esophageal squamous cell carcinoma (KYSE-70) cells and normal human esophageal epithelial cells (HEEpiCs) were used to investigate the effects of H₂-silica on cell viability and proliferation. Cell migration was examined with wound healing and culture-insert migration assays. The intracellular levels of reactive oxygen species were evaluated with a nitroblue tetrazolium assay. To assess the apoptotic status of the cells, the Bax/Bcl-2 ratio and cleaved caspase-3 were analyzed by western blot. The results showed that KYSE-70 cells and HEEpiCs were generally inhibited by H₂-silica administration, and there was a significant proliferation-inhibitory effect in an H₂-silica concentration-dependent manner compared with the control group (P < 0.05) in KYSE-70. Apoptosis-inducing effect on KYSE-70 cells was observed in 10, 300, 600, and 1,200 ppm H₂-silica, and only 1,200 ppm H₂-silica caused a 2.4-fold increase in apoptosis in HEEpiCs compared with the control group as the index of Bax/Bcl-2. H₂ silica inhibited cell migration in KYSE-70 cells, and high concentrations had a cytotoxic effect on normal cells. These findings should provide insights into the mechanism of inhibition of H₂-silica on human cancer cells in vitro.

• apoptosis-inducing effect
• car-cinogenic cells
• cell migration
• cytotoxic effect
• hydrogen-occluding-silica
• molecular hydrogen
• normal human culture cells
• reactive oxygen species

• Hydrogen
• caspase-3
• cognitive impairment
• isoflurane

• aqueous humor protein
• electroretinogram
• hydrogen
• hydrogen-rich saline
• inflammatory cells infiltration
• lipopolysaccharide
• slit lamp
• uveitis

Molecular hydrogen (H₂) is effective for many diseases. However, molecular bases of H₂ have not been fully elucidated. Cumulative evidence indicates that H₂ acts as a gaseous signal modulator. We found that H₂ suppresses activated Wnt/β-catenin signaling by promoting phosphorylation and degradation οf β-catenin. Either complete inhibition of GSK3 or mutations at CK1- and GSK3-phosphorylation sites of β-catenin abolished the suppressive effect of H₂. H₂ did not increase GSK3-mediated phosphorylation of glycogen synthase, indicating that H₂ has no direct effect on GSK3 itself. Knock-down of adenomatous polyposis coli (APC) or Axin1, which form the β-catenin degradation complex, minimized the suppressive effect of H₂ on β-catenin accumulation. Accordingly, the effect of H₂ requires CK1/GSK3-phosphorylation sites of β-catenin, as well as the β-catenin degradation complex comprised of CK1, GSK3, APC, and Axin1. We additionally found that H₂ reduces the activation of Wnt/β-catenin signaling in human osteoarthritis chondrocytes. Oral intake of H₂ water tended to ameliorate cartilage degradation in a surgery-induced rat osteoarthritis model through attenuating β-catenin accumulation. We first demonstrate that H₂ suppresses abnormally activated Wnt/β-catenin signaling, which accounts for the protective roles of H₂ in a fraction of diseases.

• GLUT4
• HFD
• HOMA-IR
• PEPCK
• STZ
• diabetes mellitus

• Animals
• Cinnamates/metabolism
• Cinnamates/pharmacology
• Depsides/metabolism
• Depsides/pharmacology
• Diabetes Mellitus, Experimental/drug therapy
• Diabetes Mellitus, Type 2/drug therapy
• Diet, High-Fat
• Glucose Transporter Type 4/chemistry
• Glucose Transporter Type 4/metabolism
• Hypoglycemic Agents/chemistry
• Hypoglycemic Agents/metabolism
• Insulin Resistance
• Muscle, Skeletal/chemistry
• Muscle, Skeletal/drug effects
• Phosphoenolpyruvate Carboxykinase (GTP)/chemistry
• Phosphoenolpyruvate Carboxykinase (GTP)/metabolism
• Rats
• Streptozocin/chemistry
• Streptozocin/pharmacology
• Rosmarinic Acid

Therapeutic effects of molecular hydrogen for a wide range of disease models and human diseases have been investigated since 2007. A total of 321 original articles have been published from 2007 to June 2015. Most studies have been conducted in Japan, China, and the USA. About three-quarters of the articles show the effects in mice and rats. The number of clinical trials is increasing every year. In most diseases, the effect of hydrogen has been reported with hydrogen water or hydrogen gas, which was followed by confirmation of the effect with hydrogen-rich saline. Hydrogen water is mostly given ad libitum. Hydrogen gas of less than 4 % is given by inhalation. The effects have been reported in essentially all organs covering 31 disease categories that can be subdivided into 166 disease models, human diseases, treatment-associated pathologies, and pathophysiological conditions of plants with a predominance of oxidative stress-mediated diseases and inflammatory diseases. Specific extinctions of hydroxyl radical and peroxynitrite were initially presented, but the radical-scavenging effect of hydrogen cannot be held solely accountable for its drastic effects. We and others have shown that the effects can be mediated by modulating activities and expressions of various molecules such as Lyn, ERK, p38, JNK, ASK1, Akt, GTP-Rac1, iNOS, Nox1, NF-κB p65, IκBα, STAT3, NFATc1, c-Fos, and ghrelin. Master regulator(s) that drive these modifications, however, remain to be elucidated and are currently being extensively investigated.

• Inflammatory diseases
• Ischemia-reperfusion injury
• Molecular hydrogen