Hydrogen nanobubbles: A novel approach toward radio-sensitization agents

Background: Ocular melanoma is a rare kind of eye malignancy that threatens the patient’s eyesight. Radiotherapy and surgical removal are the most commonly used therapeutic modalities, and nanomedicine has lately entered this field. Brachytherapy using Ruthenium-106 (106 Ru) ophthalmic plaques has been used for decades to treat ocular melanoma, with the applicator placed on the patient’s eyes until the prescribed dose reaches the tumor apex. Purpose: To investigate the efficiency of hydrogen nanobubbles (H2 -NBs) employment during intraocular melanoma brachytherapy using a 106 Ru electron emitter plaque. Methods: The Monte Carlo (MC) simulation and experimental investigation using a 3D-designed phantom and thermoluminescence dosimetry (TLD) were employed. Various concentrations of H2 -NBs with a diameter of 100 nm were simulated inside tumor tissue. The results were presented as deposited energy and dose enhancement factor (DEF). An equivalent Resin phantom of the human eyeball was made using AutoCAD and 3D-Printer technologies. The glass-bead TLDs dosimeter were employed and placed inside the phantom. Results: Using a 1% concentration of H2 -NBs, a DEF of 93% and 98% were achieved at the tumor apex of 10 mm from the experimental setup and MC simulation, respectively. For simulated concentrations of 0.1%, 0.3%, 0.5%, 1%, and 4% H2 -NBs, a maximum dose enhancement of 154%, 174%, 188%, 200%, and 300% were achieved, respectively, and a dose reduction was seen at about 3 mm from the plaque surface. Conclusion: H2 -NBs can be used as an absorbed dose enhancer in 106 Ru eye brachytherapy because of their unique physical characteristics. Reducing plaque implantation time on the patient’s eye, reducing sclera absorbed dose, and decreasing the risk of patients’ healthy organs irradiation are reported as some of the potential benefits of using H2-NBs. Keywords: Ruthenium-106 ophthalmic plaque; brachytherapy; eye phantom; glass bead dosimeters; hydrogen nanobubbles.

Effects of Intestinal Bacterial Hydrogen Gas Production on Muscle Recovery following Intense Exercise in Adult Men: A Pilot Study

This study aimed to examine the effects of hydrogen gas (H2) produced by intestinal microbiota on participant conditioning to prevent intense exercise-induced damage. In this double-blind, randomized, crossover study, participants ingested H2-producing milk that induced intestinal bacterial H2 production or a placebo on the trial day, 4 h before performing an intense exercise at 75% maximal oxygen uptake for 60 min. Blood marker levels and respiratory variables were measured before, during, and after exercise. Visual analog scale scores of general and lower limb muscle soreness evaluated were 3.8- and 2.3-fold higher, respectively, on the morning after treatment than that before treatment during the placebo trial, but not during the test beverage consumption. Urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) concentrations and production rates significantly increased with placebo consumption; no changes were observed with test beverage consumption. After exercise, relative blood lactate levels with H2-producing milk consumption were lower than those with placebo consumption. A negative correlation was observed between the variation of 8-OHdG and the area under the curve (AUC) of breath H2 concentrations. Lipid oxidation AUC was 1.3-fold higher significantly with H2-producing milk than with placebo consumption. Conclusively, activating intestinal bacterial H2 production by consuming a specific beverage may be a new strategy for promoting recovery and conditioning in athletes frequently performing intense exercises.

Silicon nanoparticles for oral administration of molecular hydrogen

Medical use of hydrogen gas (H2) has been given increasing attention over the past 15 years with numerous clinical trials for a variety of indications. The biological activity of H2 includes antioxidant properties and thereby the ability to neutralize damaging reactive oxygen species (ROS). Administration of hydrogen as a medical gas is limited by the poor water solubility and by the flammability of H2 in air. Therefore, nanocarriers have been investigated for safer and more efficient administration of hydrogen. Silicon particles are suggested for oral administration with the ability to undergo a redox reaction with water to produce H2in vivo. The purpose of this work was to investigate the hydrogen generating abilities of silicon particles synthesized by centrifugal chemical vapor deposition (cCVD). High hydrogen generation rates up to 1310 ml/g at physiological pH 7.4 (82% yield) were observed. An in vitro model of oral administration showed that pretreatment in artificial gastric juice did not affect hydrogen generation. Thus, the cCVD silicon particles seem to be suitable for in vivo hydrogen generation. A surface carbon coating or addition of surfactants or albumin reduced hydrogen generation. The addition of egg white reduced hydrogen generation but did not block it.

NIR-photocatalytic regulation of arthritic synovial microenvironment

Synovial microenvironment (SME) plays a vital role in the formation of synovial pannus and the induction of cartilage destruction in arthritis. In this work, a concept of the photocatalytic regulation of SME is proposed for arthritis treatment, and monodispersive hydrogen-doped titanium dioxide nanorods with a rutile single-crystal structure are developed by a full-solution method to achieve near infrared-photocatalytic generation of hydrogen molecules and simultaneous depletion of overexpressed lactic acid (LA) for realizing SME regulation in a collagen-induced mouse model of rheumatoid arthritis. Mechanistically, locally generated hydrogen molecules scavenge overexpressed reactive oxygen species to mediate the anti-inflammatory polarization of macrophages, while the simultaneous photocatalytic depletion of overexpressed LA inhibits the inflammatory/invasive phenotypes of synoviocytes and macrophages and ameliorates the abnormal proliferation of synoviocytes, thereby remarkably preventing the synovial pannus formation and cartilage destruction. The proposed catalysis-mediated SME regulation strategy will open a window to realize facile and efficient arthritis treatment.

Microbial hydrogen economy alleviates colitis by reprogramming colonocyte metabolism and reinforcing intestinal barrier

With the rapid development and high therapeutic efficiency and biosafety of gas-involving theranostics, hydrogen medicine has been particularly outstanding because hydrogen gas (H2), a microbial-derived gas, has potent anti-oxidative, anti-apoptotic, and anti-inflammatory activities in many disease models. Studies have suggested that H2-enriched saline/water alleviates colitis in murine models; however, the underlying mechanism remains poorly understood. Despite evidence demonstrating the importance of the microbial hydrogen economy, which reflects the balance between H2-producing (hydrogenogenic) and H2-utilizing (hydrogenotrophic) microbes in maintaining colonic mucosal ecosystems, minimal efforts have been exerted to manipulate relevant H2-microbe interactions for colonic health. Consistent with previous studies, we found that administration of hydrogen-rich saline (HS) ameliorated dextran sulfate sodium-induced acute colitis in a mouse model. Furthermore, we demonstrated that HS administration can increase the abundance of intestinal-specific short-chain fatty acid (SCFA)-producing bacteria and SCFA production, thereby activating the intracellular butyrate sensor peroxisome proliferator-activated receptor γ signaling and decreasing the epithelial expression of Nos2, consequently promoting the recovery of the colonic anaerobic environment. Our results also indicated that HS administration ameliorated disrupted intestinal barrier functions by modulating specific mucosa-associated mucolytic bacteria, leading to substantial inhibition of opportunistic pathogenic Escherichia coli expansion as well as a significant increase in the expression of interepithelial tight junction proteins and a decrease in intestinal barrier permeability in mice with colitis. Exogenous H2 reprograms colonocyte metabolism by regulating the H2-gut microbiota-SCFAs axis and strengthens the intestinal barrier by modulating specific mucosa-associated mucolytic bacteria, wherein improved microbial hydrogen economy alleviates colitis.

Colonic lactulose fermentation has no impact on glucagon-like peptide-1 and peptide-YY secretion in healthy young men

Context: The colon houses most of our gut microbiota, which ferments indigestible carbohydrates. The products of fermentation have been proposed to influence the secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) from the many endocrine cells in the colonic epithelium. However, little is known about the colonic contribution to fasting or postprandial plasma levels of L-cell products. Objective: To determine the impact of colonic lactulose fermentation on gut peptide secretion and to evaluate whether colonic endocrine secretion contributes to gut hormone concentrations measurable in the fasting state. Research design and methods: Ten healthy young men were studied on three occasions after an overnight fast. On two study days, lactulose (20 g) was given orally, and compared to water intake on a third study day. For one of the lactulose visits participants underwent a full colonic evacuation. Over a six-hour study protocol, lactulose fermentation was assessed by measuring exhaled hydrogen (H2), while gut peptide secretion, paracetamol and short chain fatty acid levels were measured in plasma. Results: Colonic evacuation markedly reduced hydrogen exhalation after lactulose intake (p=0.013). Our analysis suggests that the colon does not account for the measurable amounts of GLP-1 and PYY present in the circulation during fasting, and that fermentation and peptide secretion are not acutely related. Conclusion: Whether colonic luminal contents affect colonic L-cell secretion sufficiently to influence circulating concentrations requires further investigation. Colonic evacuation markedly reduced lactulose fermentation, but hormone releases were unchanged in the present study.

Breath hydrogen produced by ingestion of commercial hydrogen water and milk

Objective: To compare how and to what extent ingestion of hydrogen water and milk increase breath hydrogen in adults. Methods: Five subjects without specific diseases, ingested distilled or hydrogen water and milk as a reference material that could increase breath hydrogen. Their end-alveolar breath hydrogen was measured. Results: Ingestion of hydrogen water rapidly increased breath hydrogen to the maximal level of approximately 40 ppm 10-15 min after ingestion and thereafter rapidly decreased to the baseline level, whereas ingestion of the same amount of distilled water did not change breath hydrogen (p < 0.001). Ingestion of hydrogen water increased both hydrogen peaks and the area under the curve (AUC) of breath hydrogen in a dose-dependent manner. Ingestion of milk showed a delayed and sustained increase of breath hydrogen in subjects with milk intolerance for up to 540 min. Ingestion of hydrogen water produced breath hydrogen at AUC levels of 2 to 9 ppm hour, whereas milk increased breath hydrogen to AUC levels of 164 ppm hour for 540 min after drinking. Conclusion: Hydrogen water caused a rapid increase in breath hydrogen in a dose-dependent manner; however, the rise in breath hydrogen was not sustained compared with milk.

Production and Excretion of Hydrogen Gas in Man

Technics employing intestinal infusions of gas were used to study H2 production in the human intestine. The volume of H2 in the bowel of 10 normal subjects varied from 0.06 to 29 ml. H2 production, which averaged 0.24 ml per minute in the fasting state, sharply increased after intestinal instillation of lactose to a mean peak rate of 1.6 ml per minute. Ingestion of food also increased H2 production by seven-fold to 30-fold. In the normal intestine, more than 99 per cent of H2 production was colonic, but small-bowel production was increased in a patient with excessive numbers of small-bowel bacteria. H2 production in man is primarily dependent upon the delivery of ingested, fermentable substrates to an abundant intestinal flora that normally is present only in the colon. A mean of 14 per cent of the total H2 production was excreted by the lungs, and rates of breath H2 excretion and H2 production correlated well (r = 0.94). Respiratory H2 excretion can therefore be used as an indicator of intestinal H2 production.

Production, metabolism, and excretion of hydrogen in the large intestine

Hydrogen is produced during fermentation in the large intestine and may be excreted in breath and flatus or further metabolized by the flora. However, there is little information about total H2 excretion from different substrates or the extent to which it is metabolized in the colon. We have therefore measured total H2 and methane excretion in 10 healthy subjects using a whole body calorimeter. Breath gases were measured simultaneously with total excretion in response to lactulose, pectin, and banana starch. Metabolic activities of the predominant H2 consuming anaerobes (methanogenic, sulfate reducing, and acetogenic bacteria) were measured in fecal samples. Total H2 excretion on a starch and fiber-free diet was 35 +/- 6.1 mL/24 h +/- SEM. H2 from 7.5 g, 15 g, and 22.5 g lactulose was 88.1 +/- 22.4 mL, 227.0 +/- 60.7 mL, and 321.8 +/- 79.2 mL. Four of the subjects also excreted CH4, which was 51.3 +/- 5.5 mL, 97.3 +/- 18.4 mL, and 157.5 +/- 36.3 mL for the respective lactulose doses. H2 excretion was less in methanogenic subjects (7.9 mL/g lactulose) than in nonmethanogenic (17.3 mL/g), but total H2 excreted as, hydrogen + methane, was 34.9 mL/g. H2 from pectin (20 g) was 14.1% +/- 3.2% and from starch (22.2 g) 38.6% +/- 9.2% of an equivalent lactulose dose. Sixty-five percent of total H2 and CH4 was expired in breath at total excretion rates up to 200 mL/24 h. Over this the proportion decreased to 25% with an overall average of 58%. Only subjects with CH4 excretion in vivo showed methanogenesis in feces, whereas nonmethanogenic subjects showed high sulfate-reducing activity in feces (58.7 +/- 5.6 nmol 35SO4 reduced.h-1.g-1 wet wt vs. 7.9 +/- 2.0 nmol.h-1.g-1 in methanogens). Acetogenesis rates were very low in both groups. It was concluded that H2 excretion varies with different substrates. The proportion of H2 that is exhaled in breath is higher than currently accepted and varies with total excretion rate. Substantial amounts of H2 are consumed by methanogenic and sulfate-reducing bacteria.

Hydrogen-related enhancement of in vivo antioxidant ability in the brain of rats fed coral calcium hydride

This study explored the effect of coral calcium hydride (CCH) on rat intrahippocampal antioxidant ability by measuring the PCAM nitroxide radical decay ratio when CCH was (a) co-perfused into the hippocampus and (b) fed orally to the rats for 4 weeks under a freely moving state. Estimation of the in vivo antioxidant effect was obtained by administration of the blood-brain barrier-permeable PCAM nitroxide radical and the measured PCAM radical decay ratio then correlated to the amount of antioxidant in the brain using electron spin resonance (ESR) spectroscopy combined with microdialysis. The half-life periods of PCAM in rats treated with CCH in both the co-perfusion and orally fed groups were significantly shorter compared to the control group. These results clarify the mechanism that CCH may exert antioxidant activity by significantly enhancing the basal endogenous antioxidant ability in the hippocampus through a synergistic effect with α-tocopherol and ascorbic acid.