Database Query Results : Hydrogen Gas, ,

H2, Hydrogen Gas: Click to Expand ⟱
Features:
Hydrogen Gas, Powerful Antioxidant

1.Antioxidant and Nrf2/ARE Pathway: activate Nrf2, which induces antioxidant enzymes.
2.NF-κB Pathway: reported to inhibit NF-κB activation, thereby reducing inflammatory cytokine production
3.Mitochondrial Apoptosis Pathway
4.MAPK (Mitogen-Activated Protein Kinases) Pathway
5.PI3K/Akt/mTOR Pathway
6.Inflammatory Cytokine Signaling: Reducing cytokines (such as IL-6, TNF-α)
7.p53 Pathway
8.Autophagy Pathways: might regulate autophagy, (dual roles in cancer)

Example unit sometimes used in studies
Example Canadian Supplier

Hydrogen gas can be generated in small amount by hydrogenase of certain members of the human gastrointestinal tract microbiota from unabsorbed carbohydrates in the intestine through degradation and metabolism, which then is partially diffused into blood flow and released and detected in exhaled breath, indicating its potential to serve as a biomarker.

Many studies have shown that H2 therapy can reduce oxidative stress. This, however, contradicts radiation therapy and chemotherapy, in which ROS are required to induce apoptosis and combat cancer. Yet many studies show chemoprotective and radioprotective and some even show chemosentizing
Nevertheless there are some papers claiming ROS ↑ for cancer cells

Hydrogen Gas in Water is also used.
- the amount of H2 dissolved in solutions is limited: up to 0.8 mM (1.6 mg/L) H2 can be dissolved in water under atmospheric pressure at room temperature
Scientific Papers found: Click to Expand⟱
3777- H2,    Molecular Hydrogen: an Emerging Therapeutic Medical Gas for Brain Disorders
- Review, AD, NA - Review, Stroke, NA - Review, Park, NA
*neuroP↑, imary mechanism underlying hydrogen's neuroprotection.

3762- H2,    Effects of Molecular Hydrogen Assessed by an Animal Model and a Randomized Clinical Study on Mild Cognitive Impairment
- in-vivo, AD, NA
*ROS↓, In mice, drinking H2-water decreased oxidative stress markers and suppressed the decline of memory impairment and neurodegeneration.
*memory↑,
*neuroP↑, Hydrogen-water Suppressed Neurodegeneration
*cognitive↑, carriers of the apolipoprotein E4 (APOE4) geno-type in the H2-group were improved significantly on total ADAS-cog score and word recall task score (one of the sub-scores in the ADAS-cog score).
*OS↑, Hydrogen-water Extended the Average Lifespan of Mice( of DAL101 mice)

3763- H2,    Long-Term Inhalation of Hydrogen Gas for Patients with Advanced Alzheimer's Disease: A Case Report Showing Improvement in Fecal Incontinence
- Case Report, AD, NA
*cognitive↑, went to the bathroom by herself for adequate excretion. She remained to be able to go to the bathroom for her bowel movements in time, afterwards.
*neuroP↑, MRI of the brain to generate DTI images with an anisotropic (FA) value of 0.2 (FA = 0.2) showed improved integrity of the hippocampal neurons along with these clinical improvements

3764- H2,    Therapeutic Effects of Hydrogen Gas Inhalation on Trimethyltin-Induced Neurotoxicity and Cognitive Impairment in the C57BL/6 Mice Model
- in-vivo, AD, NA
*memory↑, However, after H2 treatment, memory deficits were ameliorated.
*Aβ↓, H2 treatment also decreased AD-related biomarkers, such as Apo-E, Aβ-40, p-tau, and Bax and OS markers such as ROS, NO, Ca2+, and MDA in both serum and brain.
*p‑tau↓,
*BAX↓,
*ROS↓,
*NO↓,
*Ca+2↓,
*MDA↓,
*Catalase↓, In contrast, catalase and GPx activities were significantly increased in the TMT-only group and decreased after H2 gas treatment in serum and brain
*GPx↓,
*TNF-α↓, (G-CSF), interleukin (IL)-6, and tumor necrosis factor alpha (TNF-α) were found to be significantly decreased after H2 treatment in both serum and brain lysates
*Bcl-2↑, In contrast, Bcl-2 and vascular endothelial growth factor (VEGF) expression levels were found to be enhanced after H2 treatment.
*VEGF↑,
*Inflam↓, 2% H2 gas inhalation in TMT-treated mice exhibits memory enhancing activity and decreases the AD, OS, and inflammatory-related markers.
*cognitive↑,

3765- H2,    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
- Study, AD, NA
*antiOx↑, 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.
*Inflam↓,
*cognitive↑, The mean individual ADAS-cog change showed significant improvement after 6 months of H2 treatment (−4.1) vs. untreated patients (+2.6).
*BBB↑, H2 has the ability to cross the blood-brain barrier (BBB)

3766- H2,    The role of hydrogen in Alzheimer′s disease
- Review, AD, NA
*antiOx↑, hydrogen has shown great anti-oxidative stress and anti-inflammatory effect in many cerebral disease models
*Inflam↓,
*AMPK↑, hydrogen-rich water can stimulate AMPK-Sirt1-FoxO3a pathway which could play a role in anti-oxidative stress,
*SIRT1↑,
*FOXO↑,
*mtDam↓, diminishing mitochondrial damage and acting as a neuroprotective agent, and neutralize ROS induced by Aβ
*neuroP↑,
*ROS↓,
*p38↓, hydrogen water could suppress the activation of phospho-p38 and JNK
*cognitive↑, Currently, Hou et al.50 reported that hydrogen-rich water could improve cognition function in female transgenic AD mice by reducing the decline in brain estrogen levels
*BDNF↑, reducing the decline in brain estrogen levels, estrogen receptor (ER) β, and the expression of brain-derived neuro-trophic factor (BDNF)
*memory↑, Li et al.71 found that hydrogen-rich saline could reduce learning and memory impairments and neural inflammation which were induced by Aβ in rats
*lipid-P↓, Moreover, hydrogen-rich saline suppressed lipid peroxidation products, inflammatory factor like interleukin-6 and TNF-α, and the activation of astrocytes
*IL6↓,
*TNF-α↓,
*JNK↓, protective effect of hydrogen-rich saline may be due to inhibition of the activation of JNK and NF-κB
*NF-kB↓,
*NLRP3↓, Hydrogen-rich water inhibit NLRP3, and weaken the oestrogen-ERβ-BDNF signalling pathway.

3767- H2,    The role of hydrogen therapy in Alzheimer's disease management: Insights into mechanisms, administration routes, and future challenges
- Review, AD, NA
*Inflam↓, Hydrogen therapy AD: inflammation, energy regulation, prevents neuronal damage.
*neuroP↑,
*toxicity↓, Hydrogen therapy's low side effects make it a complement to AD treatment. Even at high concentrations, hydrogen gas is still non-toxic, and has been widely used in the diving field.
*antiOx↑, hydrogen’s role as a natural antioxidant,
*ROS↓, Hydrogen has been shown to mitigate the amount of ROS released from mitochondria, thereby reducing mitochondrial DNA peroxidation and inhibiting the expression of NOD-like receptor thermal protein domain associated protein 3 (NLRP3), caspase-1, and I
*NLRP3↓,
*IL1β↓,
*mtDam↓, curtail mitochondrial damage, thereby bolstering ATP synthesis and fortifying the electron transport chain within mitochondria
*ATP↑,
*AMPK↑, activating AMPK and amplifying the downstream antioxidant response of forkhead box O3a (FOXO3
*FOXO3↑,
*SOD1↑, It elevates the levels of intracellular antioxidant enzymes, notably superoxide dismutase 1 (SOD1) and catalase (CAT), thereby serving as a neuroprotective agent that diminishes the risk and progression of AD
*Catalase↑,
*NRF2↑, Hydrogen slows AD progression by activating the cellular endogenous antioxidant system Nrf2;
*NO↓, Reduced inflammatory markers such as ROS, Nitric oxide (NO) and Malondialdehyde (MDA)
*MDA↓,
*lipid-P↓, drinking HRW significantly reduced lipid peroxidation in the brain of SAMP8 mice.
*memory↑, HRW inhibited the decline of learning and memory impairment
*ER(estro)↓, Decreased hormone levels, estrogen receptor (ER) β, and BDNF expression improve cognitive function in female transgenic AD mice.
*BDNF↑, upsurge in BDNF levels, which further ameliorated the cognitive impairments observed in mice affected by sepsis.
*cognitive↑,
*APP↓, The expression of APP, BACE1, and SAPPβ was proficiently suppressed, thereby curtailing the overproduction of Aβ in Alzheimer's
*BACE↓,
*Aβ↓,
*BP∅, inhaling hydrogen gas has no effect on blood pressure and other blood parameters (such as pH, body temperature, etc.),
*BBB↑, efficiently crossing the blood-brain barrier to perform their functions.

3768- H2,    Effects of Hydrogen Gas Inhalation on Community-Dwelling Adults of Various Ages: A Single-Arm, Open-Label, Prospective Clinical Trial
- Trial, AD, NA
*ROS↓, Investigation of oxidative stress markers such as reactive oxygen species and nitric oxide showed that their levels decreased post-treatment.
*NO↓,
*BACE↓, BACE-1), amyloid beta (Aβ), r (BDNF), (VEGF-A), T-tau, monocyte chemotactic protein-1 (MCP-1), and inflammatory cytokines (interleukin-6), showed that their cognitive condition significantly improved after treatment, in most cases.
*BDNF↑, see figure 5
*VEGF↑,
*p‑tau↓, t-tau and p-tau levels reduced dramatically in different ages within 4 weeks of treatment;
*MCP1↓, MCP-1 (p < 0.001) (Figure 7A), IL-6 (p < 0.05) (Figure 7B), and VEGF-A (Figure 7C) levels significantly decreased
*IL6↓,
*cognitive↑, H2 gas inhalation may be a good candidate for improving AD with cognitive dysfunction
*toxicity∅, H2 gas inhalation treatment did not cause any adverse effects, indicating that it was safe.

3770- H2,    Role of Molecular Hydrogen in Ageing and Ageing-Related Diseases
- Review, AD, NA - Review, Park, NA
*antiOx↑, antioxidative properties as it directly neutralizes hydroxyl radicals and reduces peroxynitrite level
*NRF2↑, activates Nrf2 and HO-1, which regulate many antioxidant enzymes and proteasomes.
*HO-1↑,
*Inflam↓, hydrogen may prevent inflammation
*neuroP↑, prevention and treatment of various ageing-related diseases, such as neurodegenerative disorders, cardiovascular disease, pulmonary disease, diabetes, and cancer.
*cardioP↑,
*other↓, It also prevented ischemia-reperfusion (I/R) injury and stroke in a rat model
*ROS↓, H2 has been shown to exert its beneficial effects in various pathological conditions that involve free radicals and oxidative stress
*NADPH↓, figure 2, H2 Inhibits NADPH Oxidase Activity
*Catalase↑,
*GPx1↑,
*NO↓, H2 Indirectly Reduces Nitric Oxide (NO) Production
*mt-ROS↓, H2 Decreases Mitochondrial ROS
*SIRT3↑, In the kidneys, H2 suppressed the downregulated Sirt3 expression, which is the most abundant member of the sirtuin family, by reducing oxidative stress reactions
*SIRT1↑, In the liver, H2 elevated HO-1 to induce Sirt1 expression
*TLR4↓, H2 inhibits TLR4, which involves hyperglycemia in type 2 diabetes mellitus
*mTOR↓, For example, H2 inhibits mTOR, activates autophagy, and alleviates cognitive impairment resulting from sepsis
*cognitive↑,
*Sepsis↓,
*PTEN↓, It inhibits the activation of the PTEN/AKT/mTOR pathway and alleviates peritoneal fibrosis
*Akt↓,
*NLRP3↓, It also facilitates autophagy-mediated NLRP3 inflammasome inactivation and alleviates mitochondrial dysfunction and organ damage
*AntiAg↑, antiageing mechanism of H2 and the influence on ageing hallmarks are summarized in Figure 3.
*IL6↓, significantly suppressed inflammatory cytokines (IL-6, TNF-α, and IL-1β), MDA, and 8-OHdG, and improved memory dysfunction
*TNF-α↓,
*IL1β↓,
*MDA↓,
*memory↑,
*FOXO3↑, HRW can also upregulate Sirt1-Forkhead box protein O3a (FOXO3a
TumCG↓, H2 inhibits lung cancer progression
*LDL↓, Decreases oxidized LDL; improves HDL function

3771- H2,    Molecular Hydrogen Neuroprotection in Post-Ischemic Neurodegeneration in the Form of Alzheimer’s Disease Proteinopathy: Underlying Mechanisms and Potential for Clinical Implementation—Fantasy or Reality?
- Review, AD, NA - Review, Stroke, NA
*cognitive↑, hydrogen improves cognitive and neurological deficits and prevents or delays the onset of neurodegenerative changes in the brain.
AntiCan↑, Chinese National Health and Medical Commission in 2020 recommended the use of inhaled hydrogen in addition to oxygen therapy for anti-cancer, anti-inflammatory and anti-oxidant treatments
*Inflam↓,
*antiOx↑,
*ROS↓, Hydrogen has been suggested as a new complementary therapy against stroke, which, e.g., reduces oxidative stress,
*neuroP↑, Molecular Hydrogen Neuroprotection in Post-Ischemic Brain Injury
*SOD↑, molecular hydrogen significantly increases SOD and GSH-Px activity, reduces malondialdehyde levels and infarct volume, relieves cerebral edema, improves neurological outcomes and alleviates cognitive deficits
*GPx↑,
*MDA↑,
*BBB↑, Molecular hydrogen has been shown to protect the permeability of the blood-brain barrier after focal and global cerebral ischemia
*OS↑, It was documented that hydrogen therapy significantly improved the 7-day survival rate of mice after global brain ischemia, from 8.3 to 50%
*Ca+2↓, In addition, hydrogen lowered the increased levels of intracellular Ca2+ caused by glutamate toxicity
*APP↓, Taken together, these results indicate that treatment with hydrogen-rich water prevents proteolysis of the amyloid protein precursor towards amyloid
*p‑tau↓, hydrogen-rich water significantly inhibited the phosphorylation of the tau protein

3772- H2,    Therapeutic potential of hydrogen-rich water in zebrafish model of Alzheimer’s disease: targeting oxidative stress, inflammation, and the gut-brain axis
- in-vivo, AD, NA
*cognitive↑, HRW can significantly improve cognitive impairment and depression-like behavior in zebrafish AD model, reduce Aβ deposition
*Aβ↓, A critical finding of this study was the reduction of Aβ deposition in HRW-treated zebrafish,
*Inflam↓, reduce neuroinflammation, and reduce oxidative stress.
*ROS↓,
*GutMicro↑, HRW reduced the number of harmful bacteria linked to AD pathology by restoring the balance of microbiota in the gut.
*TNF-α↓, HRW significantly decreased pro-inflammatory cytokine levels (TNF-α, IL-6, IL-1β) and increased IL-10 levels in zebrafish brains, suggesting that HRW exerts a strong anti-inflammatory effect.
*IL6↓,
*IL1β↓,
*IL10↓,
*Catalase↑, increase in antioxidative enzymes such as CAT and GSH
*GSH↑,

3773- H2,    Role and mechanism of molecular hydrogen in the treatment of Parkinson’s diseases
- Review, Park, NA
*neuroP↑, potential neuroprotective effects, attributed to its selective antioxidant and anti-inflammatory properties.
*antiOx↑,
*Inflam↓,
*ROS↓, potential of molecular hydrogen to attenuate oxidative stress,
*NADPH↓, via the inhibition of NADPH oxidase activity
*NRF2↑, it also enhances the endogenous defense system by modulating the Nrf2/ARE pathway.
*BBB↑, easily penetrate the blood–brain barrier
*IL1β↓, H₂ significantly reduces the release of pro-inflammatory factors, including IL-1β, IL-6, TNF-α, NF-κB, and HMGB1,
*IL6↓,
*TNF-α↓,
*NF-kB↓,
*NLRP3↓, hydrogen can mitigate neuroinflammation by inhibiting the NLRP3 inflammasome pathway
*Sepsis↓, hydrogen intervention in sepsis models
*p‑mTOR↓, inhibits the phosphorylation level of mTOR (indicated by a decrease in the p-mTOR/mTOR ratio) while activating the AMPK s
*AMPK↑,
*SIRT1↑, hydrogen-rich water alleviates intestinal oxidative stress by upregulating the expression of SIRT1, Nrf2, and HO-1
*HO-1↑,

3774- H2,    The role of hydrogen in Alzheimer’s disease
- Review, AD, NA
*Inflam↓, hydrogen inhalation exhibit anti-inflammatory and anti-oxidant effects in many studies.
*antiOx↑,
*NLRP3↓, decline of nucleotide-binding domain leucin-rich repeat and pyrin domain-containing protein 3 (NLRP3) was proved to inhibit memory impairment and Aβ deposition.4
*memory↑,
*Aβ↓,
*AMPK↑, hydrogen-rich water can stimulate AMPK-Sirt1-FoxO3a pathway
*SIRT1↑,
*FOXO3↑,
*p‑p38↓, hydrogen water could suppress the activation of phospho-p38 and JNK
*JNK↓,
*ROS↓, hydrogen can reduce neuronal apoptosis by inhibiting ROS-activated caspase signaling and protecting mitochondria.
*cognitive↑, Currently, Hou et al.50 reported that hydrogen-rich water could improve cognition function in female transgenic AD mice by reducing the decline in brain estrogen levels, estrogen receptor (ER) β
*ER(estro)↑,
*BDNF↑, and the expression of brain-derived neurotrophic factor (BDNF),

3775- H2,    Molecular hydrogen therapy for neurological diseases: a review of current evidence
- Review, AD, NA - Review, Stroke, NA
*Inflam↓, anti-inflammatory and antioxidative effects.
*antiOx↑,
*neuroP↑, demonstrate neuroprotective effects of hydrogen therapy in stroke, neurodegenerative diseases, neurotrauma, and global brain injury.
*cognitive↑, Oral hydrogen water intake ameliorated cognitive impairment in senescent accelerated mice.

3776- H2,    The role of hydrogen in Alzheimer's disease
- Review, AD, NA
*antiOx↑, hydrogen has shown great anti-oxidative stress and anti-inflammatory effect in many cerebral disease models.
*Inflam↓,
*NLRP3↓, hydrogen could inhibit the activation of NLRP3 inflammasome in AD brains
*AMPK↑, hydrogen-rich water can stimulate AMPK-Sirt1-FoxO3a
*SIRT1↑,
*FOXO3↑,
*ROS↓, hydrogen can reduce neuronal apoptosis by inhibiting ROS-activated caspase signaling
*BDNF↑, by reducing the decline in brain estrogen levels, estrogen receptor (ER) β, and the expression of brain-derived neurotrophic factor (BDNF),

3761- H2,    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
- Human, AD, NA
*cognitive↑, the mean individual ADAS-cog change showed significant improvement after 6 months of H2 treatment (−4.1) vs. untreated patients (+2.6).
*BBB↑, H2 has the ability to cross the blood-brain barrier (BBB) by gaseous diffusion without a specific drug delivery system
*ROS↓, An oxidized form of porphyrin catalyzes the reaction of H2 with hydroxyl radicals, the most oxidative free radicals, to reduce the oxidative stress.
*NRF2↑, secondary anti-oxidative function, H2 activates NF-E2-related factor 2 (Nrf2) [9], which reduces oxidative stress through the expression of a variety of anti-oxidant enzymes
*Inflam↓, H2 relieves inflammation by decreasing pro-inflammatory cytokines [38].
*NFAT↓, resulting in suppressing the nuclear factor of activated T cell (NFAT) transcription pathway to down-regulate pro-inflammatory cytokines
*FAO↓, H2 inhibits the free radical chain reaction, resulting in a decrease in fatty acid peroxidation and its end-products such as 4-hydroxyl-nonenal (4-HNE),
*4-HNE↓,
*PGC-1α↑, In turn, the decrease in 4-HNE promotes the expression of PGC-1α, followed by increasing FGF21,
*Ferroptosis↓, H2 has an anti-cell-death function by inhibiting ferroptosis through a decrease in peroxide [36], and by down- and up-regulating pro- and anti-death factors, respectively

3787- H2,    Hydrogen, a Novel Therapeutic Molecule, Regulates Oxidative Stress, Inflammation, and Apoptosis
- Review, AD, NA
*Inflam↓, anti-inflammatory and antioxidant activity
*antiOx↑,
*ROS↓, annihilating excess reactive oxygen species production and modulating nuclear transcription factor.
*other↝, H2 does not explode if it is <10% when mixed with air or O2
*NF-kB↓, H2-rich saline inhibited the activation of crucial inflammatory signaling pathway NF-κB and reduced serum IL-1β, IL-6, and TNF-α levels,
*IL2↓,
*IL6↓,
*TNF-α↓,
*HO-1↑, Studies have demonstrated that H2 administration increased the HO-1 expression
Apoptosis↑, Similarly, cell apoptosis and autophagy were significantly enhanced in A549 and H1975 lung cancer cell lines treated with different concentrations of H2 gas
TumAuto↑,
*Sepsis↓, sepsis-related organ injury models, H2 treatment significantly reduced the expression of caspase-1 in the damaged organ and the levels of IL-1β and IL-18 cytokines
*NLRP3↓, NLRP3, caspase-1, and the N-terminal of gasdermin D (GSDMD-N), were reduced after lung inflation with 3% H2,
Pyro↑, H2-rich water inhibited the proliferation of endometrial cancer cells by triggering the NLRP3 inflammasome/caspase-1 mediated classical pyroptosis pathway and activated the downstream proinflammatory cytokine IL-1β.

4234- H2,    Hydrogen gas alleviates sepsis-induced neuroinflammation and cognitive impairment through regulation of DNMT1 and DNMT3a-mediated BDNF promoter IV methylation in mice
- in-vivo, Sepsis, NA
*cognitive↑, 2% H2 protects against sepsis-induced cognitive impairment in septic mice.
*DNMT1↓, 2% H2 decreases DNMT1, DNMT3a but not DNMT3b levels in the hippocampus.
*DNMT3A↓,
*BDNF↑, 2% H2 enhances BDNF levels through hypomethylating the BDNF promoter IV.

4235- H2,    PPARα contributes to the therapeutic effect of hydrogen gas against sepsis-associated encephalopathy with the regulation to the CREB-BDNF signaling pathway and hippocampal neuron plasticity-related gene expression
- in-vivo, Sepsis, NA
*PPARα↑, H2 alleviates sepsis-induced brain injury in mice through the regulation of neurotrophins and hippocampal plasticity-related genes via PPARα by activating the CREB-BDNF signaling pathway.
*CREB↑,
*BDNF↑,
*OS↑, activation of PPARα in septic mice improved the survival rate and alleviated cognitive dysfunction.
*cognitive↑,

4236- H2,    Neuroprotective effects of hydrogen inhalation in an experimental rat intracerebral hemorrhage model
- in-vivo, Stroke, NA
*neuroP↑, H2 gas administration exerted a neuroprotective effect against early brain injury after ICH through anti-inflammatory, neuroprotective, anti-apoptotic, and antioxidative activity.
*Inflam↓,
*antiOx↑,
*BDNF↑, neuroprotective benefits of hydrogen inhalation might owe to down-regulation of caspase-3-related apoptotic signaling, and upregulation of BDNF expression related
*Casp3↓,

4237- H2,    Hydrogen-Rich Saline Protects Against Spinal Cord Injury in Rats
- in-vitro, NA, NA
*Apoptosis↓, administration of hydrogen-rich saline decreased the number of apoptotic cells, suppressed oxidative stress, and improved locomotor functions.
*ROS↓,
*motorD↑,
*BDNF↑, Hydrogen-rich saline increased the release of BDNF.

4306- H2,    Molecular Hydrogen as an Emerging Candidate for Preventing Alzheimer’s Disease
- Review, AD, NA
*ROS↓, As the result, drinking H2-water reduced oxidative stress in DAL101 mice, suppressed a decline in learning and memory impairment, and suppressed neurodegeneration
*memory↑,
*neuroP↑,
*OS↑, Moreover, H2-water extended the average lifespan of DAL mice [1].
*Inflam↓, Additionally, H2 reduced oxidative stress and inflammation in an amyloid-β-induced Alzheimer rat model [27].

4307- H2,    Hydrogen Gas Attenuates Toxic Metabolites and Oxidative Stress-Mediated Signaling to Inhibit Neurodegeneration and Enhance Memory in Alzheimer’s Disease Models
- in-vivo, AD, NA
*cognitive↑, H2 treatment significantly prevented cognitive deficits, oxidative stress, the accumulation of toxic metabolites, and the increase in inflammatory markers in 5xFAD mice.
*Inflam↓,
*ROS↓, H2 therapy has been shown to attenuate OS via selective reduction in ROS. 1.2-fold decrease in ROS levels
*neuroP↑, thereby reducing neurodegeneration and memory loss in AD.
*memory↑,
*BBB↑, making it easy for H2 to penetrate cell membranes and cross the blood–brain barrier
*BDNF↑, H2 therapy has been shown to modulate brain-derived neurotrophic factor and estrogen receptor β,
*TNF-α↓, We observed a significant reduction in TNF-α mRNA levels
*Catalase↑, 1.4-fold increase in catalase activity
*IL6↓, H2 treatment markedly suppressed TNF-α and IL-6 mRNA expression by 1.6-fold
*Aβ↓, observed that Aβ plaque accumulation in GFAP decreased by 2.8-fold in the cortex
*GABA↓, GABA levels were markedly lower
*Dose↝, Approximately 1–4% of H2 is deemed safe [ 36 ], and 3% of inhaled H2 has been reported to improve cognitive and diffusion tensor imaging scores in patients with AD

4308- H2,    A biomimetic upconversion nanoreactors for near-infrared driven H2 release to inhibit tauopathy in Alzheimer's disease therapy
- in-vivo, AD, NA
*BioAv↝, However, conventional administration methods of H2 face significant challenges in controlling H2 release on demand and fail to achieve effective accumulation at lesion sites.
*ROS↓, As an antioxidant, hydrogen gas (H2) has the potential to mitigate AD by scavenging highly harmful ROS such as •OH.
*p‑tau↓, nanoreactors release H2 in situ to scavenge local excess ROS and attenuate tau hyperphosphorylation in the AD mice model.
*Dose↝, Currently, H2 administration can be achieved through three common routes, which include inhalation of H2, oral intake of H2-rich water, and injection of H2-dissolved saline
*cognitive↑, Moreover, such a local H2 generation in the cortex and hippocampus rescued the neuronal density and improved cognitive function by suppressing p-tau pathology in mice of AD models.

4343- H2,    Inhibitory effects of hydrogen on in vitro platelet activation and in vivo prevention of thrombosis formation
- vitro+vivo, NA, NA
*antiOx↑, H2 has antithrombotic effects, which may be due to its antioxidant property and subsequent inhibition of platelet activation via NO/cGMP/PKG/ERK pathway.
*AntiAg↑,
*NO↑,
*ERK↑,

4344- H2,    Hydrogen May Inhibit Collagen-Induced Platelet Aggregation: An ex vivo and in vivo Study
- in-vivo, NA, NA - ex-vivo, NA, NA
*AntiAg↑, Collagen-induced platelet aggregation was significantly decreased in H 2 gas and HS group rats (p= 0.042, 0.018, respectively)

4345- H2,    The Benefit of Hydrogen Gas as an Adjunctive Therapy for Chronic Obstructive Pulmonary Disease
- Human, NA, NA
*Inflam↓, anti-inflammatory and antioxidant effects of hydrogen gas are attributed to its ability to target reactive oxygen species (ROS) and inhibit NLRP3 inflammasome activation in macrophages
*antiOx↑,
*ROS↓,
*NLRP3↑,
*NF-kB↓, inhibiting the activation of the transcription factor NF-κB
*SOD↑, hydrogen gas regulates the expression of antioxidant enzymes like superoxide dismutase (SOD) and catalase, providing protection against oxidative stress-induced damage
*Catalase↑,
*AntiAg↑, Additionally, Qian et al. found that hydrogen-rich saline may inhibit collagen-induced platelet aggregation in healthy volunteers’ blood samples.

4346- H2,    Medical Application of Hydrogen in Hematological Diseases
- Review, NA, NA
*AntiAg↑, hydrogen-rich saline may inhibit collagen-induced platelet aggregation in healthy volunteers' blood samples.
*TNF-α↓, hydrogen may improve the body weight, number of peripheral blood cells, and the bone marrow microenvironment by decreasing the levels of TNF-α, IFN-γ, and IL-6.
*IL6↓,
*IFN-γ↓,
*NF-kB↓, decreased activation of NF-κB

4347- H2,    Hydrogen may inhibit collagen-induced platelet aggregation: an ex vivo and in vivo study
- ex-vivo, NA, NA
*AntiAg↑, Collagen-induced platelet aggregation was significantly decreased in H2 gas and HS group rats (p=0.042, 0.018, respectively),

2517- H2,    Molecular Hydrogen Enhances Proliferation of Cancer Cells That Exhibit Potent Mitochondrial Unfolded Protein Response
- in-vitro, Var, A549 - in-vitro, NA, HCT116 - in-vitro, NA, HeLa - in-vitro, NA, HepG2 - in-vitro, NA, HT1080 - in-vitro, NA, PC3 - in-vitro, NA, SH-SY5Y
TumCP↓, the proliferation of four cell lines (A549, HeLa, HT1080, and PC3 cells) was increased 1.16–1.27-fold by 5% hydrogen gas, and 1.30–1.41-fold by 10% hydrogen
other↝, responders have higher mitochondrial mass, higher mitochondrial superoxide, higher mitochondrial membrane potential, and higher mitochondrial spare respiratory capacity than the non-responders.
eff↝, Effects of Hydrogen on Cell Proliferation Are Independent of Concentrations of Cellular Reactive Oxygen Species (ROS)
mt-UPR↑, hydrogen induces mtUPR as evidenced by upregulation of mtUPR-related molecules (ATF5, p-eIf2α, and HSP60) in the responders

2504- H2,    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
- Trial, Lung, NA
CD8+↑, As previously reported, hydrogen gas improves the prognosis of patients with cancer by restoring exhausted CD8+ T cells into active CD8+ T cells
OS↑, Median survival time (MST) for the HGN-treated patients was 28 months, a length that is approximately 3-fold longer than that for NO-treated patients (MST 9 months)
eff↝, (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
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.
PDT+↓,
PGC-1α↑, As hydrogen gas is reported to activate PGC1-α (14), it is also one of the mitochondrial activation mediators.
Dose↝, Patients were continuously treated with nivolumab (1 mg/kg) every 2 weeks. Patients also inhaled hydrogen gas 3 h daily at their home through a cannula or mask that they rented or purchased and connected to a Hycellvator ET 100
*toxicity∅, Recently, hydrogen gas inhalation was used in patients with post-cardiac arrest syndrome, and adverse events were not observed

2505- H2,    Hydrogen gas restores exhausted CD8+ T cells in patients with advanced colorectal cancer to improve prognosis
- Trial, CRC, NA
PGC-1α↑, hydrogen gas was recently reported to activate PGC‑1α,
Dose↝, hydrogen gas for 3 h/day at their own homes and received chemotherapy
CD8+↑, Notably, hydrogen gas decreased the abundance of exhausted terminal PD‑1+ CD8+ T cells, increased that of active terminal PD‑1‑ CD8+ T cells, and improved PFS and OS times,
OS↑,

2506- H2,    Molecular hydrogen suppresses activated Wnt/β-catenin signaling
- in-vivo, Arthritis, NA
*Wnt↓, H2 suppresses activated Wnt/β-catenin signaling by promoting phosphorylation and degradation οf β-catenin.
*β-catenin/ZEB1↓,
*Dose↝, Oral intake of H2 water tended to ameliorate cartilage degradation in a surgery-induced rat osteoarthritis model through attenuating β-catenin accumulation.

2507- H2,    Hydrogen protects against chronic intermittent hypoxia induced renal dysfunction by promoting autophagy and alleviating apoptosis
- in-vivo, NA, NA
*RenoP↑, We demonstrated that rats who inhale hydrogen gas showed improved renal function, alleviated pathological damage, oxidative stress and apoptosis in CIH rats.
*ROS↓,
*Apoptosis↓,
*ER Stress↓, endoplasmic reticulum stress was decreased by H2 as the expressions of CHOP, caspase-12, and GRP78 were down-regulated
*CHOP↓,
*Casp12↓,
*GRP78/BiP↓,
*LC3‑Ⅱ/LC3‑Ⅰ↑, higher levels of LC3-II/I ratio and Beclin-1, with decreased expression of p62, were found after H2 administrated.
*Beclin-1↑,
*p62↓,
*mTOR↓, Inhibition of mTOR may be involved in the upregulation of autophagy by H2

2508- H2,    Molecular hydrogen is a promising therapeutic agent for pulmonary disease
- Review, Var, NA - Review, Sepsis, NA
*ROS↓, inhalation of 2% molecular hydrogen results in the selective scavenging of hydroxyl free radical (·OH) and peroxynitrite anion (ONOO-), significantly improving oxidative stress injury caused by cerebral ischemia/reperfusion (I/R)
eff↝, Molecular hydrogen can exert biological effects on almost all organs, including the brain, heart, lung, liver, and pancreas.
*Inflam↓, including roles in the regulation of oxidative stress and anti-inflammatory and anti-apoptotic effects
*NRF2↑, By stimulating nuclear factor erythroid 2-related factor 2 (Nrf2), which regulates the basal and induces expression of many antioxidant enzymes
*HO-1↑, hydrogen can increase the expression of heme oxygenase-1 (HO-1)
*SOD↑, increases the activity of the antioxidant enzymes SOD, CAT, and myeloperoxidase (MPO)
*Catalase↑,
*MPO↑,
*ASK1↓, Molecular hydrogen can block the apoptosis signal-regulating kinase 1 (ASK1) signaling pathway
*NADPH↓, thereby inhibiting nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and decreasing free radical production
*Sepsis↓, Emerging evidence suggests that hydrogen can prevent sepsis, providing a novel treatment strategy for sepsis-induced ALI.
*HMGB1↓, Hydrogen attenuates tissue injury and dysfunction by inhibiting HMGB-1.
ROS↑, it has been shown that hydrogen pretreatment enhances ROS and the expression of pyroptosis-related proteins, stimulates NLRP3 inflammasome/gasdermin D (GSDMD) activation, and inhibits endometrial cancer
NLRP3↑,
GSDMD↑,
chemoP↑, Hydrogen can alleviate the side effects of conventional anti-cancer therapies, such as chemotherapy and radiotherapy, and improve quality of life
eff↑, It significantly improves the physical status of patients, reduces fatigue, insomnia, anorexia, and pain, and decreases elevated tumor markers.

2509- H2,    Hydrogen inhibits endometrial cancer growth via a ROS/NLRP3/caspase-1/GSDMD-mediated pyroptotic pathway
- in-vitro, Endo, AN3CA - in-vivo, Endo, NA
selectivity↑, Hydrogen exerts a biphasic effect on cancer by promoting tumor cell death and protecting normal cells, which might initiate GSDMD pathway-mediated pyroptosis.
mt-ROS↑, We therefore concluded that molecular hydrogen activated ROS and mtROS generation in endometrial cancer cells.
ROS↑,
TumW↓,
GSDMD↑, ability of hydrogen to stimulate NLRP3 inflammasome/GSDMD activation in pyroptosis
Pyro↑,
Dose↝, Hydrogenated water was produced by H2 dissolved in water saturantly under 0.4 MPa pressure for 6 h with a concentration of 1.0 ppm produced by hydrogen water apparatus
eff↓, In contrast, NAC decreased ROS levels in hydrogen-treated endometrial cancer cells
TumVol↓, We demonstrated that drinking hydrogen-rich water reduced the volume of endometrial tumors in a xenograft mouse model.

2510- H2,    Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals
- in-vivo, Stroke, NA
*ROS↓, The inhalation of H(2) gas markedly suppressed brain injury by buffering the effects of oxidative stress.
*antiOx↑, Thus H(2) can be used as an effective antioxidant therapy; owing to its ability to rapidly diffuse across membranes, it can reach and react with cytotoxic ROS and thus protect against oxidative damage.

2511- H2,    Molecular hydrogen suppresses glioblastoma growth via inducing the glioma stem-like cell differentiation
- in-vivo, GBM, U87MG
TumCG↓, hydrogen inhalation could effectively suppress GBM tumor growth and prolong the survival of mice with GBM
OS↑,
CD133↓, 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.
Ki-67↓,
angioG↓,
Diff↑, pregulated GFAP expression, a marker of differentiation
TumCMig↓, Moreover, hydrogen treatment also suppressed the migration, invasion
TumCI↓,
Dose↝, AMS-H-3 hydrogen-oxygen nebulizer machine (Asclepius Meditec Inc., Shanghai, China), which produces 67% H2 and 33% O. inhaled the mixed air for 1 h two times per day
BBB↑, hydrogen gas can easily cross the BBB.
mt-ROS↑, Intriguingly, molecular hydrogen has also been reported to act as a mitohormetic effector by mildly inducing mitochondrial superoxide production [28]. Perhaps hydrogen-induced ROS promoted the differentiation and downregulation of stemness in GSCs.

2512- H2,    Hydrogen Attenuates Allergic Inflammation by Reversing Energy Metabolic Pathway Switch
- in-vivo, asthmatic, NA
selectivity↑, we treated mice with HRS for 7 days. HRS had no effects on OXPHOS and glycolytic activities in control mice
lactateProd↓, but prevented the elevation in lactate and reduction in ATP production in lungs of OVA-sensitized and challenged mice
ATP↑,
HK2↓, Consistently, HRS attenuated the increase in HK and PFK activities
PFK↓,
Hif1a↓, OVA sensitization and challenge increased HIF-1α nuclear translocation (stimulated HIF-1α activity), which was inhibited by HRS treatment
PGC-1α↑, By contrast, OVA sensitization and challenge downregulated PGC-1α protein expression, and HRS treatment reversed this downregulation
Glycolysis↓, H2 reverses energy metabolic switch by inhibiting glycolytic enzyme activities and by stimulating mitochondrial OXPHOS enzyme activities
OXPHOS↑,
Dose↝, HRS was prepared by dipping a plastic-shelled stick consisting of metallic magnesium (99.9% pure) and natural stones (Doctor SUISOSUI, Friendear Inc., Tokyo, Japan) into sterilized saline.

2513- H2,    Hydrogen therapy: from mechanism to cerebral diseases
- Review, Stroke, NA
*BBB?, blood-brain barrier, penetrability
*antiOx↑, therefore concluded that this selective antioxidant effect is the basis of H2 therapy for cerebral ischemia/reperfusion injury
*Inflam↓, H2 can decrease both the amount of inflammatory cytokines and immunocyte stimulation
*Apoptosis↓, Research showed that the apoptosis of neurons in newborn rats induced by hypoxia and ischemia is inhibited if inhaling H2,
*NF-kB↓, demonstrated the inhibition of NF-κB with the introduction of H2
*Dose↝, Furthermore, there are many methods for ingestion of H2, such as oral intake of H2 water, intravenous drip of H2 -rich saline, and inhalation of air containing 2–4% H2 gas

2514- H2,    Hydrogen: A Novel Option in Human Disease Treatment
- Review, NA, NA
*Inflam↓, Anti-Inflammatory Effect of H2
*IL1β↓, decrease the overexpression of early proinflammatory cytokines, such as interleukin- (IL-) 1β, IL-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF-α
*IL6↓,
*IL8↓,
*IL10↓,
*TNF-α↓,
*ROS↓, . H2 can also downregulate ROS directly or as a regulator of a gas-mediated signal.
*HO-1↓, H2 can enhance the expression of the heme oxygenase-1 (HO-1) antioxidant by activating nuclear factor erythroid 2-related factor 2 (Nrf-2), an upstream regulating molecule of HO-1
*NRF2↑,
*ER Stress↓, hydrogen inhalation significantly reduced the ER stress-related protein and alleviated tissue damage in myocardial I/R injury a
H2O2↑, H2-induced ROS production can also be observed in cancer cells.

2515- H2,    Recent Advances in Studies of Molecular Hydrogen against Sepsis
- Review, Sepsis, NA
*Sepsis↓, Molecular hydrogen exerts multiple biological effects involving anti-inflammation, anti-oxidation, anti-apoptosis, anti-shock, and autophagy regulation, which may attenuate the organ and barrier damage caused by sepsis.
*Inflam↓,
*antiOx↑,
*ROS↓, Studies have demonstrated that HRS reduces ROS production and attenuates mitochondrial dysfunction by inhibiting NADPH oxidase activity in rat cardiomyocytes
*NADPH↓,

2516- H2,    Hydrogen Gas in Cancer Treatment
- Review, Var, NA
*Half-Life↓, Except the thigh muscle required a longer time to saturate, the other organs need 5–10 min to reach Cmax (maximum hydrogen concentration).
*ROS↓, regulate several key players in cancer, including ROS, and certain antioxidant enzymes
*selectivity↑, hydrogen gas could selectively scavenge the most cytotoxic ROS, •OH, as tested in an acute rat model of cerebral ischemia and reperfusion
*SOD↑, the expression of superoxide dismutase (SOD) (48), heme oxyganase-1 (HO-1) (49), as well as nuclear factor erythroid 2-related factor 2 (Nrf2) (50), increased significantly, strengthening its potential in eliminating ROS.
*HO-1↑,
*NRF2↑,
*chemoP↑, reduce the adverse effects in cancer treatment while at the same time doesn't abrogate the cytotoxicity of other therapy, such as radiotherapy and chemotherapy
*radioP↑,
ROS↑, Interestingly, due the over-produced ROS in cancer cells (38), the administration of hydrogen gas may lower the ROS level at the beginning, but it provokes much more ROS production as a result of compensation effect, leading to the killing of cancer
*Inflam↓, By regulating inflammation, hydrogen gas can prevent tumor formation, progression, as well as reduce the side effects caused by chemotherapy/radiotherapy
eff↑, More importantly, hydrogen-rich water didn't impair the overall anti-tumor effects of gefitinib both in vitro and in vivo, while in contrast, it antagonized the weight loss induced by gefitinib and naphthalene, and enhanced the overall survival rate
*TNF-α↓, hydrogen-rich saline treatment exerted its protective effects via inhibiting the inflammatory TNF-α/IL-6 pathway, increasing the cleaved C8 expression and Bcl-2/Bax ratio, and attenuating cell apoptosis in both heart and liver tissue
*IL6↓,
*cl‑Casp8↑,
*Bax:Bcl2↓,
*Apoptosis↓,
*cardioP↑,
*hepatoP↑,
*RenoP↑, Hydrogen-rich water also showed renal protective effect against cisplatin-induced nephrotoxicity in rats.
*chemoP↑, nother study showed that both inhaling hydrogen gas (1% hydrogen in air) and drinking hydrogen-rich water (0.8 mM hydrogen in water) could reverse the mortality, and body-weight loss caused by cisplatin via its anti-oxidant property
eff↝, More importantly, hydrogen didn't impair the anti-tumor activity of cisplatin against cancer cell lines in vitro and in tumor-bearing mice
chemoP↑, hydrogen-rich water combinational treatment group exhibited no differences in liver function during the treatment, probably due to its antioxidant activity, indicating it a promising protective agent to alleviate the mFOLFOX6-related liver injury
radioP↑, consumption of hydrogen-rich water reduced the radiation-induced oxidative stress while at the same time didn't compromise anti-tumor effect of radiotherapy
eff↑, Hydrogen Gas Acts Synergistically With Thermal Therapy
TumCG↓, in vivo study showed that under hydrogen gas treatment, tumor growth was significantly inhibited, as well as the expression of Ki-67, VEGF and SMC3
Ki-67↓,
VEGF↓,
selectivity↑, H2-silica could concentration-dependently inhibit the cell viability of human esophageal squamous cell carcinoma (KYSE-70) cells, while it need higher dose to suppress normal human esophageal epithelial cells (HEEpiCs), indicating its selective profi

2503- H2,    Brain Metastases Completely Disappear in Non-Small Cell Lung Cancer Using Hydrogen Gas Inhalation: A Case Report
- Case Report, Lung, NA
TumVol↓, Hydrogen-gas monotherapy was started to control the tumor a month later. After 4 months, the size of multiple brain tumors was reduced significantly
OS↑, After 1 year, all brain tumors had disappeared, and there were no significant changes in metastases in the liver and lung.
Dose↝, The hydrogen oxygen nebulizer (AMS-H-03, Asclepius Meditec, Shanghai, China) generates 3 L/min hydrogen gas by hydrocephalus electrolysis. As measured by gas chromatography, the gas generated consisted of 67% hydrogen and 33% oxygen.
Dose↝, Using a special mask, the patient continued to inhale hydrogen for 3–6 hrs a day at rest, with no interruption even after the obvious relief of symptoms.
CEA↓, dropped from 29.44 to 12 ng/mL in 12 months (figure 3)
CA125↓, dropped from 150 to 60 u/mL (figure 3)
CYFRA21-1↓, dropped from 12 to 6 ng/mL (figure 3)
SIRT1↓, several scholars have demonstrated that hydrogen can suppress SIRT1 signaling in different model
COX2↓, hydrogen exerts neuroprotective effects by reducing cyclooxygenase-2 activity25 or activating expression of anti-apoptotic protein kinase B.
IL1β↓, Hydrogen inhalation can down-regulate the expression of various pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, tumor necrosis factor-α, intracellular adhesion molecule-1, high mobility group box-1, nuclear factor-kappa B, and prosta
IL6↓,
TNF-α↓,
HMGB1↓,
NF-kB↓,
EP2↓, and prostaglandin-E2

2518- H2,    Hydrogen Therapy Reverses Cancer-Associated Fibroblasts Phenotypes and Remodels Stromal Microenvironment to Stimulate Systematic Anti-Tumor Immunity
- in-vitro, BC, 4T1 - in-vitro, Nor, 3T3
TumCD↑, CaCO3 can not only directly kill tumor cells
CD4+↑, augment immune activities of CD4+ T cells
ROS↓, results indicated that hydrogen therapy by Mg-CaCO3 could decrease MMP and alleviate ROS within CAFs

2519- H2,    Hydrogen: an advanced and safest gas option for cancer treatment
- Review, Var, NA
antiOx↑, H2 has remarkable antioxidant and neuroprotective effects and other advantages
neuroP↓,
BBB↑, swift penetration ability to cross the blood–brain barrier
toxicity∅, H2 inhalation therapy has also been proposed in several countries as the safest mode of H2 administration
TumCP↓, A HeLa xenograft mouse model showed that H2 inhalation may increase the apoptosis rate, proliferation, and oxidative stress in HeLa cells
Apoptosis↓,
ROS↑,
Hif1a↓, H2 may affect tumor growth by regulating the expression of overexpressed subunits of transcription factors, such as hypoxia-inducible factor 1α and the nuclear factor-κB p65 subunit
NF-kB↓,
P53?, Hydrogen also increases the expression level of p53 tumor suppressor proteins.
OS↑, This study revealed that hydrogen gas inhalation 3 h/d can improve the prognosis and overall survival of stage IV colorectal carcinoma patients by decreasing the number of programmed cell death 1/CD8+ T cells
chemoP↑, H 2 anticancer therapy can minimize the debilitating side effects of conventional anticancer therapies by improving survival, quality of life, and blood parameters.

2520- H2,    The Impact of Molecular Hydrogen on Mitochondrial ROS and Apoptosis in Colorectal Cancer Cells
- in-vitro, CRC, NA
mt-ROS↓, hydrogen-rich medium, we found a significant mitochondrial ROS decrease (∼40%), especially in the aldolase B over-expressed CRC
ChemoSen↑, hydrogen can synergize the apoptotic response of chemotherapy (∼20% improvement).
other↝, However, the decreasing mtROS signal and increasing apoptosis seems to be controversial with our current understanding, and further study in more detail is required to explore the underlying mechanisms of mitochondrial function and related signaling

2521- H2,    Oxyhydrogen Gas: A Promising Therapeutic Approach for Lung, Breast and Colorectal Cancer
- Review, CRC, NA - Review, Lung, NA - Review, BC, NA
Inflam↑, Oxyhydrogen gas, a mixture of 66% molecular hydrogen (H2) and 33% molecular oxygen (O2) has shown exceptional promise as a novel therapeutic agent due to its ability to modulate oxidative stress, inflammation, and apoptosis.
ROS↓, neutralises reactive oxygen and nitrogen species
ChemoSen↑, enhancing existing treatments and reducing harmful oxidative states in cancer cells. boosting the effectiveness of conventional therapies
p‑PI3K↓, inhibiting the PI3K/Akt phosphorylation cascade.
p‑Akt↓,
QoL↑, Similar results have been observed in breast cancer, where patients reported improved quality of life.
GutMicro↑, improves intestinal microflora dysbiosis.
chemoP↑, reduced oxidative stress and mitigated tissue damage, suggesting its potential as a cytoprotective agent in cancer patients undergoing radiation therapy or chemotherapy
radioP↑,
*NRF2↑, documented role in activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway.
*Catalase↑, consequently, hydrogen can enhance the expression of endogenous antioxidant enzymes, including catalase (CAT), glutathione peroxidase (GPx), haem oxygenase (e.g., HO-1), and superoxide dismutase (SOD) [45]
*GPx↑,
*HO-1↑,
*SOD↑,
*TNF-α↓, reducing the expression of proinflammatory mediators such as chemokines (e.g., CXCL15), cytokines (e.g., TNF-α), interleukins (e.g., IL-4, IL-6)
*IL4↓,
*IL6↓,
ChemoSen↑, further research demonstrates that oxyhydrogen gas enhanced the sensitivity of lung cancer cells to chemotherapy drugs, suggesting its potential as an adjuvant therapy
Appetite↑, inhaled oxyhydrogen gas over a minimum of 3 months. The results indicated substantial improvements in appetite, cognition, fatigue, pain, and sleeplessness
cognitive↑,
Pain↓,
Sleep↑,
other?, It is recommended that hydrogen should not exceed 4.6% in air or 4.1% by volume in pure oxygen gas (explosion risk)

2522- H2,    A Systematic Review of Molecular Hydrogen Therapy in Cancer Management
- Review, Var, NA
chemoP↑, H2 plays a promising therapeutic role as an independent therapy as well as an adjuvant in combination therapy, resulting in an overall improvement in survivability, quality of life, blood parameters, and tumour reduction.
OS↑,
QoL↑,
TumVol↑,
ROS↑, Hydrogen, the lightest element on the earth, is an effective antioxidant that has been shown to selectively reduce harmful reactive oxygen species (ROS) in tissues
AntiTum↑, Although H2 has demonstrated significant anti-tumoural effects, the underlying mechanisms have not yet been elucidated.
other↝, Many studies have shown that H2 therapy can reduce oxidative stress. This, however, contradicts radiation therapy and chemotherapy, in which ROS are required to induce apoptosis and combat cancer.

2523- H2,    Prospects of molecular hydrogen in cancer prevention and treatment
- Review, Var, NA
ROS↓, previous studies have shown that H2 can selectively scavenge highly toxic reactive oxygen species (ROS) and inhibit various ROS-dependent signaling pathways in cancer cells, thus inhibiting cancer cell proliferation and metastasis.
TumCP↓,
TumMeta↓,
AntiTum↑, Anti-tumor barrier: H2 produced by intestinal flora
GutMicro↑, hydrogen-rich water (HRW) supplementation significantly inhibited the expansion of opportunistic pathogenic E. coli and increased intestinal integrity in mice with colitis
Inflam↓, H2 maintains the integrity of the intestinal barrier, reduces intestinal inflammation and damage in rat
OS↑, inhalation of H2 for 3 h daily significantly prolonged progression-free survival and overall survival in stage IV colon and rectal patients
radioP↑, administration of inhaled H2 during radiotherapy treatment reduced the damage to the hematological and immune systems
selectivity↑, Through these studies, we believe that the ability of H2 to selectively scavenge highly toxic ROS may be the core and fundamental mechanism of its anti-tumor effects, so this paper mainly focuses on this point of discussion.
SOD↑, H2 inhibited ROS expression and increased SOD, IL-1β, IL-8, IL-13, and tumor necrosis factor-α (TNF-α) expression in lung tissue of cancer
IL1β↑,
IL8↑,
TNF-α↑,
neuroP↑, Ono et al. found that 3% H2 inhaled twice daily for 1 h significantly improved vital signs, stroke scale scores, physiotherapy index, and 2-week brain MRI in stroke patients compared with conventional treatment.

2524- H2,    Protective effect of hydrogen-rich water on liver function of colorectal cancer patients treated with mFOLFOX6 chemotherapy
- Trial, NA, NA
hepatoP↑, protective effect of hydrogen-rich water on the liver function of colorectal cancer (CRC) patients treated with mFOLFOX6 chemotherapy.
ALAT↓, The hydrogen-rich water group exhibited no significant differences in liver function before and after treatment, whereas the placebo group exhibited significantly elevated levels of ALT, AST and IBIL
AST↓,
Dose↝, Hydrogen-rich water was prepared by increasing the hydrogen pressure in the solution (7). First, the partial air pressure in the water was reduced using a 1406 type vacuum pump
Dose↝, started drinking hydrogen-rich water 1 day prior to chemotherapy until the end of the cycle, for a total of 4 days, with a daily intake of 1,000 ml in 4 doses (250 ml each). Hydrogen-rich water was consumed 0.5 h after a meal and before bedtime.

2525- H2,    Hydrogen-Rich Saline Attenuates Cardiac and Hepatic Injury in Doxorubicin Rat Model by Inhibiting Inflammation and Apoptosis
- in-vivo, NA, NA
OS↓, intraperitoneal injection of hydrogen-rich saline (H2 saline) ameliorated the mortality, cardiac dysfunction, and histopathological changes caused by DOX in rats
cardioP↑,
*AST↓, serum brain natriuretic peptide (BNP), aspartate transaminase (AST), alanine transaminase (ALT), albumin (ALB), tissue reactive oxygen species (ROS), and malondialdehyde (MDA) levels were also attenuated after H2 saline treatment.
ALAT↓,
*ROS↓,
*MDA↓,
*hepatoP↑, H2 saline treatment could inhibit cardiac and hepatic inflammation
*Inflam↓,
chemoP↑, protective effect of H2 saline on DOX-induced cardiotoxicity and hepatotoxicity in rats by inhibiting inflammation and apoptosis.

2526- H2,    Influence of hydrogen-occluding-silica on migration and apoptosis in human esophageal cells in vitro
- in-vitro, ESCC, KYSE-510
*ROS↓, many studies have shown that hydrogen gas or hydrogen water can reduce the levels of reactive oxygen species in the living body
selectivity↑, 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 (normal cells)
ROS↓, Intracellular levels of superoxide radical tended to decrease with increasing H2-silica concentrations.

2527- H2,    The healing effect of hydrogen-rich water on acute radiation-induced skin injury in rats
- in-vivo, Wounds, NA
*Dose↝, After skin wound formation, rats were individually administrated with distilled water, HRW (1.0 ppm) or HRW (2.0 ppm).
*SOD↑, SOD activity in the two HRW-treated groups was higher
*EGF↑, The EGF level was also significantly increased at the end of the 1st and 2nd weeks
*antiOx↑, HRW accelerates wound healing of radiation-induced skin lesions through anti-oxidative and anti-inflammatory effect
*Inflam↓,
*Dose↝, Compared with the HRW (1.0 ppm) group, the healing rate was higher and the healing time was reduced in the HRW (2.0 ppm)

2528- H2,    Local generation of hydrogen for enhanced photothermal therapy
- in-vitro, Var, NA
eff↑, release of bio-reductive hydrogen as well as generation of heat. This hydrogenothermal approach has presented a cancer-selective strategy for synergistic cancer treatment
ROS↓, PdH0.2 nanocrystals immediately caused remarkable decrease of the intracellular ROS level in both cancer and normal cell models in a concentration-dependent way
selectivity↑, Cancer cells were more sensitive to PdH0.2 nanocrystals than normal cells, possibly owing to the higher initial ROS level in cancer cells.
ROS↑, Owing to the relatively higher ROS level in cancer cells, the initial ROS loss in cancer cells was higher and the subsequent ROS rebound was also intenser/higher than that in normal cells.
other↝, The highly overexpressed ROS in cancer cells was hardly eliminated to the normal level, leading to the oxidative stress remarkably . see figure 3
ROS↑, The damage to the mitochondria of cancer cells was possibly attributed to the increase of intracellular ROS level (Fig. 3c).

2529- H2,    Guidelines for the selection of hydrogen gas inhalers based on hydrogen explosion accidents
- Analysis, Nor, NA
other↑, Most commercially available hydrogen gas inhalers emit hydrogen that is generated by the electrolysis of water directly through the inhalation port, which poses a risk of explosion
eff↝, Generated hydrogen should be diluted with air or another dilution gas in order to ensure that the concentration is below the lower explosive limit.
eff↝, Hydrogen gas inhalers of the direct dilution type do not allow an explosive concentration of hydrogen to accumulate or flow inside them, and thus ensure safety.
other↝, 1. inhaler must dilute hydrogen immediately at the source (using a fan)
other↝, 2. concentration of the H2 must be below 10% at this point
other↝, 3. inhaler must have an indicator for the hydrogen concentration in %
other↝, 4. must have a safetly device to stop production, when concentration is too high
other↝, 5. water used must be purified water!

2530- H2,    Improvement of psoriasis-associated arthritis and skin lesions by treatment with molecular hydrogen: A report of three cases
- Case Report, PSA, NA
eff↑, psoriatic skin lesions almost disappeared at the end of the treatment.
Dose↝, Three methods were used to administer H2: Drop infusion of saline containing 1 ppm H2 (H2-saline), inhalation of 3% H2 gas, and drinking of water containing a high concentration (5-7-ppm) of H2 (high-H2 water).
eff↑, The patient then inhaled 3% H 2 gas for five days, after which PASI score as well as the pain VAS and itch VAS were decreased.
IL6↓, In particular, IL-6 was reduced by 92% (from 3.64 to 0.3 pg/ml)
eff↑, Patient #2: After a one week washout period, the patient inhaled H 2 gas foranother five days, after which all symptoms were improved. IL-6 showed the highest reduction (by 90% as compared with the baseline value).

3152- H2,  VitC,  Rad,    Hydrogen and Vitamin C Combination Therapy: A Novel Method of Radioprotection
- in-vitro, Nor, HUVECs - in-vivo, NA, NA
AntiTum↑, Hydrogen also has direct and indirect antitumor effects, which could be useful for the treatment of cancer patients. Hydrogen therapy improves overall survival, quality of life, blood parameters, and tumor reduction.
OS↑,
QoL↑,
TumVol↓,
radioP↑, In addition, hydrogen attenuates the risk of carcinogenesis induced by radiation.
Dose↑, Patients begin hydrogen inhalation 10 minutes prior to vitamin C injection. Patients are treated with high-dose vitamin C injection while inhaling simultaneous hydrogen
Dose↝, patients also performed the hydrogen and vitamin C combination therapy at home on their own as much as possible
eff↑, These results suggest that in normal cells, the combination of 1 mM vitamin C and hydrogen is the most effective radioprotective agent.

4126- Silicon,  H2,    Oral Administration of Si-Based Agent Attenuates Oxidative Stress and Ischemia-Reperfusion Injury in a Rat Model: A Novel Hydrogen Administration Method
- in-vivo, NA, NA
*creat↓, serum creatinine and urine protein were significantly decreased 72 h following IRI in rats that were administered nano-Si.
*ROS↓, oral nano-Si intake downregulated the biological processes related to oxidative stress, such as immune response, cytokine production, and extrinsic apoptotic signaling pathway.
*other↑, oral administration of nano-Si, which should be considered as a novel H2 administration method.
*MDA↓, Additionally, the serum malondialdehyde levels were significantly decreased in the IRI + nano-Si group compared
*other↑, new strategy to successfully generate large amounts of H2 molecules by crushing Si to nano-sized particles and allowing these nanoparticles to react with alkaline water.
*Inflam↓, H2 has been shown to exert anti-inflammatory and anti-apoptotic effects by suppressing oxidative stress


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 59

Results for Effect on Cancer/Diseased Cells:
p‑Akt↓,1,   ALAT↓,2,   angioG↓,1,   AntiCan↑,1,   antiOx↑,1,   AntiTum↑,3,   Apoptosis↓,1,   Apoptosis↑,1,   Appetite↑,1,   AST↓,1,   ATP↑,1,   BBB↑,2,   CA125↓,1,   cardioP↑,1,   CD133↓,1,   CD4+↑,1,   CD8+↑,2,   CEA↓,1,   chemoP↑,6,   ChemoSen↑,3,   cognitive↑,1,   CoQ10↑,1,   COX2↓,1,   CYFRA21-1↓,1,   Diff↑,1,   Dose↑,1,   Dose↝,11,   eff↓,1,   eff↑,8,   eff↝,6,   EP2↓,1,   Glycolysis↓,1,   GSDMD↑,2,   GutMicro↑,2,   H2O2↑,1,   hepatoP↑,1,   Hif1a↓,2,   HK2↓,1,   HMGB1↓,1,   IL1β↓,1,   IL1β↑,1,   IL6↓,2,   IL8↑,1,   Inflam↓,1,   Inflam↑,1,   Ki-67↓,2,   lactateProd↓,1,   neuroP↓,1,   neuroP↑,1,   NF-kB↓,2,   NLRP3↑,1,   OS↓,1,   OS↑,8,   other?,1,   other↑,1,   other↝,9,   OXPHOS↑,1,   P53?,1,   Pain↓,1,   PDT+↓,1,   PFK↓,1,   PGC-1α↑,3,   p‑PI3K↓,1,   Pyro↑,2,   QoL↑,3,   radioP↑,4,   ROS↓,5,   ROS↑,7,   mt-ROS↓,1,   mt-ROS↑,2,   selectivity↑,6,   SIRT1↓,1,   Sleep↑,1,   SOD↑,1,   TNF-α↓,1,   TNF-α↑,1,   toxicity∅,1,   TumAuto↑,1,   TumCD↑,1,   TumCG↓,3,   TumCI↓,1,   TumCMig↓,1,   TumCP↓,3,   TumMeta↓,1,   TumVol↓,3,   TumVol↑,1,   TumW↓,1,   mt-UPR↑,1,   VEGF↓,1,  
Total Targets: 89

Results for Effect on Normal Cells:
4-HNE↓,1,   Akt↓,1,   AMPK↑,5,   AntiAg↑,6,   antiOx↑,17,   Apoptosis↓,4,   APP↓,2,   ASK1↓,1,   AST↓,1,   ATP↑,1,   Aβ↓,5,   BACE↓,2,   BAX↓,1,   Bax:Bcl2↓,1,   BBB?,1,   BBB↑,6,   Bcl-2↑,1,   BDNF↑,10,   Beclin-1↑,1,   BioAv↝,1,   BP∅,1,   Ca+2↓,2,   cardioP↑,2,   Casp12↓,1,   Casp3↓,1,   cl‑Casp8↑,1,   Catalase↓,1,   Catalase↑,7,   chemoP↑,2,   CHOP↓,1,   cognitive↑,17,   creat↓,1,   CREB↑,1,   DNMT1↓,1,   DNMT3A↓,1,   Dose↝,6,   EGF↑,1,   ER Stress↓,2,   ER(estro)↓,1,   ER(estro)↑,1,   ERK↑,1,   FAO↓,1,   Ferroptosis↓,1,   FOXO↑,1,   FOXO3↑,4,   GABA↓,1,   GPx↓,1,   GPx↑,2,   GPx1↑,1,   GRP78/BiP↓,1,   GSH↑,1,   GutMicro↑,1,   Half-Life↓,1,   hepatoP↑,2,   HMGB1↓,1,   HO-1↓,1,   HO-1↑,6,   IFN-γ↓,1,   IL10↓,2,   IL1β↓,5,   IL2↓,1,   IL4↓,1,   IL6↓,11,   IL8↓,1,   Inflam↓,25,   JNK↓,2,   LC3‑Ⅱ/LC3‑Ⅰ↑,1,   LDL↓,1,   lipid-P↓,2,   MCP1↓,1,   MDA↓,5,   MDA↑,1,   memory↑,8,   motorD↑,1,   MPO↑,1,   mtDam↓,2,   mTOR↓,2,   p‑mTOR↓,1,   NADPH↓,4,   neuroP↑,12,   NF-kB↓,6,   NFAT↓,1,   NLRP3↓,7,   NLRP3↑,1,   NO↓,4,   NO↑,1,   NRF2↑,8,   OS↑,4,   other↓,1,   other↑,2,   other↝,1,   p38↓,1,   p‑p38↓,1,   p62↓,1,   PGC-1α↑,1,   PPARα↑,1,   PTEN↓,1,   radioP↑,1,   RenoP↑,2,   ROS↓,27,   mt-ROS↓,1,   selectivity↑,1,   Sepsis↓,5,   SIRT1↑,5,   SIRT3↑,1,   SOD↑,6,   SOD1↑,1,   p‑tau↓,4,   TLR4↓,1,   TNF-α↓,11,   toxicity↓,1,   toxicity∅,2,   VEGF↑,2,   Wnt↓,1,   β-catenin/ZEB1↓,1,  
Total Targets: 115

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:295  Target#:%  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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