Glioblastoma multiforme (GBM) is the most common type of malignant intracranial tumor in adults. Tumor tissue hypoxia, high mitotic rate, and rapid tumor spread account for its poor prognosis. Hyperbaric oxygen therapy (HBOT) may improve the sensitivity of radio-chemotherapy by increasing oxygen tension within the hypoxic regions of the neoplastic tissue. This review summarizes the research of HBOT applications within the context of experimental and clinical GBM. Limited clinical trials and preclinical studies suggest that radiotherapy immediately after HBOT enhances the effects of radiotherapy in some aspects. HBOT also is able to strengthen the anti-tumor effect of chemotherapy when applied together. Overall, HBOT is well tolerated in the GBM patients and does not significantly increase toxicity. However, HBOT applied by itself as curative strategy against GBM is controversial in preclinical studies and has not been evaluated rigorously in GBM patients. In addition to HBOT favorably managing the therapeutic resistance of GBM, future research needs to focus on the multimodal or cocktail approaches to treatment, as well as molecular strategies targeting GBM stem cells.

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Increasing evidence indicates that molecular hydrogen-dissolved alkaline electrolyzed water (AEW) has various physiological activities such as antioxidative activity. Gut microbiota are deeply associated with our health through a symbiotic relationship. Recent reports have described that most gastrointestinal microbial species encode the genetic capacity to metabolize molecular hydrogen, meaning that molecular hydrogen might affect the gut microbial composition. Nevertheless, AEW effects on gut microbiota remain unknown. This study investigated AEW effects on the intestinal environment in mice, including microbial composition and short-chain fatty acid contents. After mice were administered AEW for 4 weeks, 16S rRNA gene sequencing analyses revealed their fecal microbiota profiles. Organic acid concentrations in cecal contents were measured using an HPLC system. Compared to the control group, AEW administration mice had significantly lower serum low-density lipoprotein cholesterol level and alanine aminotransferase activity. Organic acid concentrations of propionic, isobutyric, and isovaleric acids were higher in AEW-administered mice. Results of 16S rRNA gene sequencing analyses showed that the relative abundances of 20 taxa differed significantly in AEW-administered mice. Although the definitive role of gut microbes of AEW-administered mice remains unknown, our data demonstrate the possibility that AEW administration affects the gut microbial composition and that it has beneficial health effects in terms of cholesterol metabolism and liver protection.

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This study aimed to investigate the role of necroptosis in the neuroprotection of hydrogen in a mouse model of cerebral ischemia/reperfusion (I/R) injury. C57BL mice were randomly divided into sham group, I/R group, hydrogen/oxygen group (HO), nitrogen/oxygen group (NO). Middle cerebral artery occlusion (MCAO) for 1 hour followed by reperfusion was introduced to animals which were allowed to inhale 66.7% hydrogen/33.3% oxygen for 90 minutes since the beginning of reperfusion. Mice in NO group inhaled 66.7% nitrogen/33.3% oxygen. 24 hours after MCAO, brain infarction, brain water content and neurological function were evaluated. The protein expression of mixed lineage kinase domain like protein (MLKL) was detected at 3, 6, 12, 24 and 72 hours after reperfusion in HO group and the protein and mRNA expression of MLKL at 24 hours after MCAO in four groups. Hydrogen inhalation significantly reduced infarct volume, attenuated brain edema and improved neurobehavioral deficit in MCAO mice. The MLKL expression increased after MCAO and peaked at 6–24 hours after reperfusion. However, hydrogen inhalation had no significant effect on the MLKL expression at transcriptional and translational levels after MCAO. This study indicates high concentration hydrogen improves mouse neurological outcome after cerebral I/R injury independent of anti-necroptosis.

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Hyperbaric oxygen therapy (HBOT) is a medical technique which delivers oxygen at ambient pressures to increase the amount of dissolved oxygen in the blood and oxygen distribution to tissues. There are several beneficial properties of HBOT concomitant with elevated oxygen distribution in tissue including anti-inflammation, angiogenesis through vascular endothelial growth factor proliferation, augmented fibroblast activity through fibroblast growth factor proliferation, tissue and wound repair, enhancement of lymphocyte and macrophage activity, increased male testosterone secretion, and bactericidal activity. Given its renown in treating conditions such as decompression sickness and carbon monoxide poisoning, HBOT is making gradual strides for use in genitourinary medicine due to its low risk and likeliness to achieve favorable results. Early success has been observed in the treatment of Fournier's gangrene, radiation cystitis, and interstitial cystitis via the elimination of clinical symptoms such as pain. Further indications that have exhibited positive outcomes despite HBOT's ambiguous mechanism of action include cyclophosphamide hemorrhagic cystitis, emphysematous cystitis, pelvic radiation disease, radiation-induced proctopathy, dystrophic calcification of the prostate, erectile dysfunction secondary to urethroplasty, priapism, abnormal renal morphology, blood testosterone, calcific uremic arteriolopathy, and hidradenitis suppurativa. For other indications, multicenter studies must be conducted to determine HBOT's true efficacy, mechanism of action, risks, and advantages over conventional treatments.

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Ventilator-associated-pneumonia (VAP) is characterized by morbidity, mortality, and prolonged length of stay in intensive care unit (ICU). The present study aimed to examine the effect of N-acetyl-cysteine (NAC) in preventing VAP in patients hospitalized in ICU. We performed a prospective, randomized, double-blind, placebo-controlled trial of 60 mechanically ventilated patients at high risk of developing VAP. NAC (600 mg/twice daily) and placebo (twice daily) were administered to NAC group (n = 30) and control group (n = 30), respectively, through the nasogastric tube in addition to routine care. The clinical response was considered as primary (incidence of VAP) and secondary outcomes. Twenty-two (36.6%) patients developed VAP. Patients treated with NAC were significantly less likely to develop clinically confirmed VAP compared with patients treated with placebo (26.6% vs. 46.6%; P = 0.032). Patients treated with NAC had significantly less ICU length of stay (14.36 ± 4.69 days vs. 17.81 ± 6.37 days, P = 0.028) and less hospital stay (19.23 ± 5.54 days vs. 24.61 ± 6.81 days; P = 0.03) than patients treated with placebo. Time to VAP was significantly longer in the NAC group (9.42 ± 1.9 days vs. 6.46 ± 2.53 days; P = 0.002). The incidence of complete recovery was significantly higher in the NAC group (56.6% vs. 30%; P = 0.006). No adverse events related to NAC were identified. NAC is safe and effective to prevent and delay VAP, and improve its complete recovery rate in a selected, high-risk ICU population.

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Biomedical properties of hydrogen water have been extensively investigated, but the effect of hydrogen on good healthy subjects remains unclear. This study was designed to explore the hygiene improvement by electrolytically generated hydrogen warm water (40°C) on capillary blood streams, skin moisture, and keratin plugs in skin pores in normal good healthy subjects with their informed consents. Fingertip-capillary blood stream was estimated after hand-immersing in hydrogen warm water by videography using a CCD-based microscope, and the blood flow levels increased to about 120% versus normal warm water, after 60 minutes of the hand-immersing termination. Skin moisture of subjects was assessed using an electro-conductivity-based skin moisture meter. Immediately after taking a bath filled with hydrogen warm water, the skin moisture increased by 5–10% as compared to before bathing, which was kept on for the 7-day test, but indistinct, because of lower solubility of hydrogen in “warm” water than in room-temperature water. Cleansing of keratin plugs in skin-pores was assessed by stereoscopic microscopy and scanning electron microscopy. After hydrogen warm water bathing, the numbers of cleansed keratin plugs also increased on cheek of subjects 2.30- to 4.47-fold as many as the control for normal warm water. And areas of cleansed keratin plugs in the cheeks increased about 1.3-fold as much as the control. More marked improvements were observed on cheeks than on nostrils. Hydrogen warm water may thoroughly cleanse even keratin-plugs of residual amounts that could not be cleansed by normal warm water, through its permeability into wide-ranged portions of hair-pores, and promote the fingertip blood streams more markedly than merely through warmness due to normal warm water.

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