ABSTRACT
While drug therapy plays a crucial role in cancer treatment, many anticancer drugs, particularly cytotoxic and molecular-targeted drugs, cause severe side effects, which often limit the dosage of these drugs. Efforts have been made to alleviate these side effects by developing derivatives, analogues, and liposome formulations of existing anticancer drugs and by combining anticancer drugs with substances that reduce side effects. However, these approaches have not been sufficiently effective in reducing side effects. Molecular hydrogen (H2) has shown promise in this regard. It directly reduces reactive oxygen species, which have very strong oxidative capacity, and indirectly exerts antioxidant, anti-inflammatory, and anti-apoptotic effects by regulating gene expression. Its clinical application in various diseases has been expanded worldwide. Although H2 has been reported to reduce the side effects of anticancer drugs in animal studies and clinical trials, the underlying molecular mechanisms remain unclear. Our comprehensive literature review revealed that H2 protects against tissue injuries induced by cisplatin, oxaliplatin, doxorubicin, bleomycin, and gefitinib. The underlying mechanisms involve reductions in oxidative stress and inflammation. H2 itself exhibits anticancer activity. Therefore, the combination of H2 and anticancer drugs has the potential to reduce the side effects of anticancer drugs and enhance their anticancer activities. This is an exciting prospect for future cancer treatments.
ABSTRACT
The Michael J. Fox Foundation has been funding research on Parkinson's disease for 35 years, but has yet to find a cure. This is due to a problem with the philosophy behind the development of modern medical treatments. In this paper, we will introduce "smart medicine" with a substance that can solve all the problems of central nervous system drugs. The substance is the smallest diatomic molecule, the hydrogen molecule. Due to their size, hydrogen molecules can easily penetrate the cell membrane and enter the brain. In the midbrain of Parkinson's disease patients, hydroxyl radicals generated by the Fenton reaction cause a chain reaction of oxidation of dopamine, but hydrogen entering the midbrain can convert the hydroxyl radicals into water molecules and inhibit the oxidation of dopamine. In this paper, we focus on the etiology of neurological diseases, especially Parkinson's disease, and present a case in which hydrogen inhalation improves the symptoms of Parkinson's disease, such as body bending and hand tremor. And we confidently state that if Michael J. Fox encountered "smart medicine" that could be realized with molecular hydrogen, he would not be a "lucky man" but a "super-lucky man."
Subject(s)
Hydrogen , Parkinson Disease , Parkinson Disease/therapy , Parkinson Disease/drug therapy , Humans , Hydrogen/chemistry , Hydrogen/administration & dosage , Administration, Inhalation , Brain/metabolism , MaleABSTRACT
Fluorescent dyes are commonly used as conservative groundwater tracers to track the migration of water. Over- or underestimation of important parameters such as the water flow rate can occur if the concentration of a dye is changed by unexpected reactions. Because such errors may seriously affect the results of experiments, the reactions and processes that change fluorescent dye concentrations need to be understood. In this study, we focused on the widely used fluorescent dye uranine (UR) and aimed to identify microbes contributing to decreases in UR concentrations in groundwater. First, we identified the conditions (water temperature, pH, and salinity) under which significant decreases in UR concentrations occurred to show that the decrease in UR concentrations were caused by the effects of microbes in the groundwater. Next, we obtained information about the metabolism of organic matter by potential contributing microbes. These results were used to narrow down possible microbes that could decrease the UR concentration. Analysis of the microbial community in groundwater using 16S rRNA gene sequencing was then used to further identify contributing microbes. Finally, a verification experiment was conducted using a strain of one of the identified microbes (Parapontixanthobacter aurantiacus). Our results showed that conservation of the concentration of fluorescent dye solutions prepared with on-site groundwater was affected by several microbes with different metabolic characteristics, including P. aurantiacus. When fluorescent dye solutions prepared with on-site groundwater are used in field investigations or tracer tests, the pros and cons of using fluorescent dyes should be carefully evaluated because of the potential effects of microbes in the groundwater.
ABSTRACT
As diabetes rates surge globally, there is a corresponding rise in the number of patients suffering from diabetic kidney disease (DKD), a common complication of diabetes. DKD is a significant contributor to chronic kidney disease, often leading to end-stage renal failure. However, the effectiveness of current medical treatments for DKD leaves much to be desired. Molecular hydrogen (H2) is an antioxidant that selectively reduces hydroxyl radicals, a reactive oxygen species with a very potent oxidative capacity. Recent studies have demonstrated that H2 not only possesses antioxidant properties but also exhibits anti-inflammatory effects, regulates cell lethality, and modulates signal transduction. Consequently, it is now being utilized in clinical applications. Many factors contribute to the onset and progression of DKD, with mitochondrial dysfunction, oxidative stress, and inflammation being strongly implicated. Recent preclinical and clinical trials reported that substances with antioxidant properties may slow the progression of DKD. Hence, we undertook a comprehensive review of the literature focusing on animal models and human clinical trials where H2 demonstrated effectiveness against a variety of renal diseases. The collective evidence from this literature review, along with our previous findings, suggests that H2 may have therapeutic benefits for patients with DKD by enhancing mitochondrial function. To substantiate these findings, future large-scale clinical studies are needed.
ABSTRACT
Intestinal bacteria can be classified into "beneficial bacteria" and "harmful bacteria." However, it is difficult to explain the mechanisms that make "beneficial bacteria" truly beneficial to human health. This issue can be addressed by focusing on hydrogen-producing bacteria in the intestines. Although it is widely known that molecular hydrogen can react with hydroxyl radicals, generated in the mitochondria, to protect cells from oxidative stress, the beneficial effects of hydrogen are not fully pervasive because it is not generally thought to be metabolized in vivo. In recent years, it has become clear that there is a close relationship between the amount of hydrogen produced by intestinal bacteria and various diseases, and this report discusses this relationship.
Subject(s)
Hydrogen , Oxidative Stress , Humans , Hydrogen/pharmacology , Hydroxyl Radical , BacteriaABSTRACT
Despite the fact that we have reported on the dangers of the explosion of hydrogen gas inhalers, hydrogen gas inhalers with explosive hazards are, as a matter of fact, still being sold today. In this study, we investigated past reports of hydrogen gas inhaler explosion accidents to clarify the causes of these explosion incidents. As a result of this investigation, we found that the central cause was the leakage of hydrogen gas inside the hydrogen gas inhaler. Although it is said that the explosive concentration of hydrogen is between 10% and 75%, and that the gas does not explode above 75% due to the lack of oxygen, we confirmed through a series of ignition experiments that explosions can occur even in hydrogen gas inhalers that produce 100% hydrogen gas. Some manufacturers of such highly concentrated hydrogen gas inhalers claim that the high concentration and purity of hydrogen is safe and that there is no risk of explosion. We believe that manufacturing or selling such products that pose a risk of explosion or detonation is a violation of social justice. This paper presents ideas for selecting safe hydrogen gas inhalers based on a survey of past accident cases.
Subject(s)
Explosions , Hydrogen , Accidents , Nebulizers and Vaporizers , OxygenABSTRACT
Most of the drugs used in modern medical treatments are symptomatic treatments and are far from being a cure for the diseases. The adverse effects are unavoidable in the drugs in modern medical treatments. Molecular hydrogen (H2) has a remarkable therapeutic effect on various diseases, and many clinical studies have reported that H2 has no adverse effects. Therefore, H2 is a novel medical gas that is outside the concept of modern medical treatment. H2, unlike drugs, works on the root of many diseases by scavenging the two kinds of strong reactive oxygen species, hydroxyl radical (·OH) and peroxynitrite (ONOO-). Since the H2 alleviates the root of diseases and can treat many diseases at the same time, the medical application of H2 may be called "machine gun therapy." In this review, we demonstrated that the root of many diseases is based on ·OH-induced oxidative stress in the mitochondria, and at the same time, the root of chronic inflammation is also attributed to ·OH.
Subject(s)
Hydrogen , Peroxynitrous Acid , Hydrogen/pharmacology , Hydrogen/therapeutic use , Hydroxyl Radical , Oxidative Stress , Peroxynitrous Acid/pharmacology , Reactive Oxygen SpeciesABSTRACT
Background: Hydrogen (H2) has been reported to be effective in reducing hearing loss due to several causes in animal studies. However, no study has examined the effectiveness of H2 in treating hearing loss in humans. Thus, we investigated whether H2 is effective for the treatment of idiopathic sudden sensorineural hearing loss (ISSNHL). Materials and methods: We conducted a double-blind randomized controlled trial at six hospitals between June 2019 and March 2022. The study protocol and trial registration have been published in the Japan Registry of Clinical Trials (jRCT, No. jRCTs06119004). We randomly assigned patients with ISSNHL to receive either H2 (H2 group) or air as a placebo (control group) through inhalation combined with the administration of systemic glucocorticoids and prostaglandin E1. The primary outcome was the hearing threshold and changes in hearing threshold 3 months after therapy. In contrast, the secondary outcomes included the proportion of patients with a good prognosis (complete recovery or marked improvement). Results: Sixty-five patients with ISSNHL (31 and 34 in the H2 and control groups, respectively) were included in this study. The hearing threshold 3 months after treatment was not significantly different between the groups; 39.0 decibels (dB) (95% confidence interval [CI]: 28.7-49.3) and 49.5 dB (95% CI: 40.3-58.7) in the H2 and control groups, respectively. In contrast, the changes in hearing threshold 3 months after treatment was 32.7 dB (95% CI: 24.2-41.3) and 24.2 dB (95% CI: 18.1-30.3) in the H2 and control groups, respectively. Consequently, the changes in hearing threshold were significantly better in the H2 group than in the control group (P = 0.048). However, no adverse effects due to the inhalation of H2 gas have been reported. Conclusion: This is the first study to investigate the efficacy of H2 for the treatment of ISSNHL in humans. The results suggest that H2 therapy may be effective for ISSNHL treatment. Clinical trial registration: [https://jrct.niph.go.jp/re/reports/detail/10442], identifier [jRCTs06119004].
ABSTRACT
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disorder that is characterized by fatigue that persists for more than 6 months, weakness, sleep disturbances, and cognitive dysfunction. There are multiple possible etiologies for ME/CFS, among which mitochondrial dysfunction plays a major role in abnormal energy metabolism. The potential of many substances for the treatment of ME/CFS has been examined; however, satisfactory outcomes have not yet been achieved. The development of new substances for curative, not symptomatic, treatments is desired. Molecular hydrogen (H2) ameliorates mitochondrial dysfunction by scavenging hydroxyl radicals, the most potent oxidant among reactive oxygen species. Animal experiments and clinical trials reported that H2 exerted ameliorative effects on acute and chronic fatigue. Therefore, we conducted a literature review on the mechanism by which H2 improves acute and chronic fatigue in animals and healthy people and showed that the attenuation of mitochondrial dysfunction by H2 may be involved in the ameliorative effects. Although further clinical trials are needed to determine the efficacy and mechanism of H2 gas in ME/CFS, our literature review suggested that H2 gas may be an effective medical gas for the treatment of ME/CFS.
ABSTRACT
Methanogens capable of accepting electrons from Fe0 cause severe corrosion in anoxic conditions. In previous studies, all iron-corrosive methanogenic isolates were obtained from marine environments. However, the presence of methanogens with corrosion ability using Fe0 as an electron donor and their contribution to corrosion in freshwater systems is unknown. Therefore, to understand the role of methanogens in corrosion under anoxic conditions in a freshwater environment, we investigated the corrosion activities of methanogens in samples collected from groundwater and rivers. We enriched microorganisms that can grow with CO2/NaHCO3 and Fe0 as the sole carbon source and electron donor, respectively, in ground freshwater. Methanobacterium sp. TO1, which induces iron corrosion, was isolated from freshwater. Electrochemical analysis revealed that strain TO1 can uptake electrons from the cathode at lower than -0.61 V vs SHE and has a redox-active component with electrochemical potential different from those of other previously reported methanogens with extracellular electron transfer ability. This study indicated the corrosion risk by methanogens capable of taking up electrons from Fe0 in anoxic freshwater environments and the necessity of understanding the corrosion mechanism to contribute to risk diagnosis.
ABSTRACT
Si, featuring ultra-large theoretical specific capacity, is a very promising alternative to graphite for Li-ion batteries (LIBs). However, Si suffers from intrinsic low electrical conductivity and structural instability upon lithiation, thereby severely deteriorating its electrochemical performance. To address these issues, B-doping into Si, N-doped carbon coating layer, and carbon nanotube conductive network are combined in this work. The obtained Si/C hybrid anode material can be "grown" onto the Cu foil without using any binder and delivers large specific capacity (2328â¯mAhâ¯g-1 at 0.2â¯Aâ¯g-1), great rate capability (1296.8â¯mAhâ¯g-1 at 4â¯Aâ¯g-1), and good cyclability (76.7% capacity retention over 500 cycles). Besides, a cellulose separator derived from cotton is found to be superior to traditional polypropylene separator. By using cellulose as both the separator host and the mechanical skeleton of two electrodes, a flexible all-in-one paper-like LIB is assembled via a facile layer-by-layer filtration method. In this all-in-one LIB, all the components are integrated together with robust interfaces. This LIB is able to offer commercial-level areal capacity of 3.47â¯mAhâ¯cm-2 (corresponding to 12.73â¯mWhâ¯cm-2 and 318.3â¯mWhâ¯cm-3) and good cycling stability even under bending. This study offers a new route for optimizing Si-based anode materials and constructing flexible energy storage devices with a large areal capacity.
ABSTRACT
The silicon-based anode has been regarded as the most competitive anode candidate for next-generation lithium-ion batteries based on its high theoretical specific capacity. However, the severe volume expansion of the anode leads to undesirable cycling performance, hindering its further application in full cells. In this work, a preactivation method is carried out in a LiNi0.5Co0.2Mn0.3O2â¥Si-graphite battery with an in situ gel electrolyte composed of carbonate solvents, lithium hexafluorophosphate (LiPF6), ß-cyanoethyl ether of poly(vinyl alcohol) (PVA-CN), and additive lithium difluoro(oxalato)borate (LiDFOB). After the charge-discharge test at ambient temperature (300 cycles), the capacity retention of the battery with the in situ gel electrolyte (75.4%) is impressively promoted compared with that with a base liquid electrolyte (45.7%). The in situ gelation and the strong solid electrolyte interphase (SEI) film effectively suppress the volume expansion of the anode, and the detected cathode transition metal elements on cycled anodes sharply decline. At an elevated temperature (55 °C), the cycle stability and Coulombic efficiency of the battery are also effectively improved. Meanwhile, the battery owns good rate capability and low-temperature performances similar to that with the liquid electrolyte. These results would provide a feasible solution for applying in situ gel electrolytes in wide temperature range batteries with Si-based anodes in practical applications.
ABSTRACT
Metal selenides have attracted increasing attention recently as anodes for sodium-ion batteries (SIBs) because of their large capacities, high electric conductivity, as well as environmental benignity. However, the application of metal selenides is hindered by the huge volume variation, which causes electrode structure devastation and the consequent degrading cycling stability and rate capability. To overcome the aforementioned obstacles, herein, SnSe2 /FeSe2 nanocubes capsulated in nitrogen-doped carbon (SFS@NC) are fabricated via a facile co-precipitation method, followed by poly-dopamine wrapping and one-step selenization/carbonization procedure. The most remarkable feature of SFS@NC is the ultra-stability under high current density while delivering a large capacity. The synergistic effect of dual selenide components and core-shell architecture mitigates the volume effect, alleviates the agglomeration of nanoparticles, and further improves the electric conductivity. The as-prepared SFS@NC nanocubes present a high capacity of 408.1 mAh g-1 after 1200 cycles at 6 A g-1 , corresponding to an 85.3% retention, and can achieve a capacity of 345.0 mAh g-1 at an extremely high current density of 20 A g-1 . The outstanding performance of SFS@NC may provide a hint to future material structure design strategy, and promote further developments and applications of SIBs.
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Platinum (Pt) is the most effective bench-marked catalyst for producing renewable and clean hydrogen energy by electrochemical water splitting. There is demand for high HER catalytic activity to achieve efficient utilization and minimize the loading of Pt in catalysts. In this work, we significantly boost the HER mass activity of Pt nanoparticles in Ptx /Co to 8.3 times higher than that of commercial Pt/C by using Co/NC heterojunctions as a heterogeneous version of electron donors. The highly coupled interfaces between Co/NC and Pt metal enrich the electron density of Pt nanoparticles to facilitate the adsorption of H+ , the dissociation of Pt-H bonds and H2 release, giving the lowest HER overpotential of 6.9â mV vs. RHE at 10â mA cm-2 in acid among reported HER electrocatalysts. Given the easy scale-up synthesis due to the stabilization of ultrafine Pt nanoparticles by Co/NC solid ligands, Ptx /Co can even be a promising substitute for commercial Pt/C for practical applications.
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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.
Subject(s)
Antineoplastic Agents/pharmacology , Hydrogen/pharmacology , Neoplasms/genetics , Antineoplastic Agents/therapeutic use , Clinical Trials as Topic , Gene Expression Regulation, Neoplastic/drug effects , Humans , Hydrogen/therapeutic use , Neoplasms/drug therapy , Neoplasms/metabolism , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolismABSTRACT
Mibyou, or pre-symptomatic diseases, refers to state of health in which a disease is slowly developing within the body yet the symptoms are not apparent. Common examples of mibyou in modern medicine include inflammatory diseases that are caused by chronic inflammation. It is known that chronic inflammation is triggered by the uncontrolled release of proinflammatory cytokines by neutrophils and macrophages in the innate immune system. In a recent study, it was shown that molecular hydrogen (H2) has the ability to treat chronic inflammation by eliminating hydroxyl radicals (·OH), a mitochondrial reactive oxygen species (ROS). In doing so, H2 suppresses oxidative stress, which is implicated in several mechanisms at the root of chronic inflammation, including the activation of NLRP3 inflammasomes. This review explains these mechanisms by which H2 can suppress chronic inflammation and studies its applications as a protective agent against different inflammatory diseases in their pre-symptomatic state. While mibyou cannot be detected nor treated by modern medicine, H2 is able to suppress the pathogenesis of pre-symptomatic diseases, and thus exhibits prospects as a novel protective agent.
Subject(s)
Asymptomatic Diseases , Hydrogen/pharmacology , Protective Agents/pharmacology , Alzheimer Disease/prevention & control , Animals , Chronic Disease , Diabetes Mellitus, Type 2/prevention & control , Free Radical Scavengers/pharmacology , Hepatitis/prevention & control , Humans , Hypertension/prevention & control , Inflammation/prevention & control , Models, Biological , Neoplasms/prevention & control , Oxidative Stress , Parkinson Disease/prevention & control , Renal Insufficiency, Chronic/prevention & controlABSTRACT
Volume expansion hinders conversion-type transition-metal oxides (TMOs) as potential anode candidates for high-capacity lithium-ion batteries. While nanostructuring and nanosizing have been employed to improve the cycling stability of TMOs, we show here that both high initial Coulombic efficiency (ICE) and stable cycling reversibility are achieved in the layered compound Li0.9Nb0.9Mo1.1O6 (L0.9NMO) by inherent properties of the bulk crystal structure. In this model, MoO6 octahedra as active centers react with lithium ions and endow capacity, while a grid composed of NbO6 octahedra effectively suppresses the volume expansion, enhances the conductivity, and supports the structural skeleton from collapse. As a result, bulk L0.9NMO not only delivers a high discharge capacity of 1128 mA h g-1 at 100 mA g-1 with a considerable ICE of 87% but also exhibits long cycling stability and good rate performance (339 mA h g-1 after 500 cycles at 1 A g-1 with an average Coulombic efficiency approaching 100%). The self-confined structure provides a competitive strategy for stable conversion-type lithium storage.
ABSTRACT
Although intensity-modulated radiation therapy (IMRT) has been developed as an alternative to conventional radiotherapy, reducing bone marrow damage is limited. Thus, a novel technology is needed to further mitigate IMRT-induced bone marrow damage. Molecular hydrogen (H2) was recently reported as a preventive and therapeutic antioxidant that selectively scavenges hydroxyl radical (·OH) and peroxynitrite (ONOO-). This observational study aimed to examine whether H2 gas treatment improves IMRT-induced bone marrow damage in cancer patients. The study was performed at Clinic C4 in Tokyo, Japan between May 2015 and November 2016. During this period, all enrolled patients received IMRT once per day for 1 to 4 weeks. After each time of IMRT, the patients of control group (n = 7, 3 men and 4 women, age range: 26-70 years) received mild hyperbaric oxygen therapy in health care chamber for 30 minutes, and the patients of H2 group (n = 16, 8 men and 8 women, age range: 35-82 years) received 5% H2 gas in health care chamber for 30 minutes once per day. Radiation-induced bone marrow damage was evaluated by hematological examination of peripheral blood obtained before and after IMRT, and the data were expressed by the ratio after to before treatment. The total number of radiation times and total exposure doses of radiation were similar between the control and H2 groups. IMRT with health care chamber therapy significantly reduced white blood cells and platelets, but not red blood cells, hemoglobin and hematocrit. In contrast, H2 gas treatment significantly alleviates the reducing effects of white blood cells and platelets (P = 0.0011 and P = 0.0275, respectively). Tumor responses to IMRT were similar between the two groups. The results obtained demonstrated that H2 gas inhalation therapy alleviated IMRT-induced bone marrow damage without compromising the anti-tumor effects of IMRT. The present study suggests that this novel approach of H2 gas inhalation therapy may be applicable to IMRT-induced bone marrow damage in cancer patients. The study protocol was approved by an Ethics Committee Review of Tokyo Clinic and Research Institute ICVS Incorporated (Tokyo, Japan) on February 1, 2019, and was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN ID: UMIN000035864) on February 20, 2019.
Subject(s)
Bone Marrow , Uterine Cervical Neoplasms , Adult , Aged , Aged, 80 and over , Female , Humans , Hydrogen , Male , Middle Aged , Radiotherapy Dosage , Radiotherapy Planning, Computer-AssistedABSTRACT
Although ionizing radiation (radiation) is commonly used for medical diagnosis and cancer treatment, radiation-induced damages cannot be avoided. Such damages can be classified into direct and indirect damages, caused by the direct absorption of radiation energy into DNA and by free radicals, such as hydroxyl radicals (â¢OH), generated in the process of water radiolysis. More specifically, radiation damage concerns not only direct damages to DNA, but also secondary damages to non-DNA targets, because low-dose radiation damage is mainly caused by these indirect effects. Molecular hydrogen (H2) has the potential to be a radioprotective agent because it can selectively scavenge â¢OH, a reactive oxygen species with strong oxidizing power. Animal experiments and clinical trials have reported that H2 exhibits a highly safe radioprotective effect. This paper reviews previously reported radioprotective effects of H2 and discusses the mechanisms of H2, not only as an antioxidant, but also in intracellular responses including anti-inflammation, anti-apoptosis, and the regulation of gene expression. In doing so, we demonstrate the prospects of H2 as a novel and clinically applicable radioprotective agent.