Hydrogen-rich water protects against liver injury in nonalcoholic steatohepatitis through HO-1 enhancement via IL-10 and Sirt 1 signaling.

Nonalcoholic steatohepatitis (NASH) could progress to hepatic fibrosis in the absence of effective control. The purpose of our experiment was to investigate the protective effect of drinking water with a high concentration of hydrogen, namely, hydrogen-rich water (HRW), on mice with nonalcoholic fatty liver disease to elucidate the mechanism underlying the therapeutic action of molecular hydrogen. The choline-supplemented, l-amino acid-defined (CSAA) or the choline-deficient, l-amino acid-defined (CDAA) diet for 20 wk was used to induce NASH and fibrosis in the mice model and simultaneously treated with the high-concentration 7-ppm HRW for different periods (4 wk, 8 wk, and 20 wk). Primary hepatocytes were stimulated by palmitate to mimic liver lipid metabolism during fatty liver formation. Primary hepatocytes were cultured in a closed vessel filled with 21% O2 + 5% CO2 + 3.8% H2 and N2 as the base gas to verify the response of primary hepatocytes in a high concentration of hydrogen gas in vitro. Mice in the CSAA + HRW group had lower serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and milder histological damage. The inflammatory cytokines were expressed at lower levels in the HRW group than in the CSAA group. Importantly, HRW reversed hepatocyte fatty acid oxidation and lipogenesis as well as hepatic inflammation and fibrosis in preexisting hepatic fibrosis specimens. Molecular hydrogen inhibits the lipopolysaccharide-induced production of inflammation cytokines through increasing heme oxygenase-1 (HO-1) expression. Furthermore, HRW improved hepatic steatosis in the CSAA + HRW group. Sirtuin 1 (Sirt1) induction by molecular hydrogen via the HO-1/adenosine monophosphate activated protein kinase (AMPK)/peroxisome proliferator-activated receptor α (PPARα)/peroxisome proliferator-activated receptor γ (PPAR-γ) pathway suppresses palmitate-mediated abnormal fat metabolism. Orally administered HRW suppressed steatosis induced by CSAA and attenuated fibrosis induced by CDAA, possibly by reducing oxidative stress and the inflammation response.NEW & NOTEWORTHY The mRNA expression of inflammatory cytokines in the HRW group was lower than in the CSAA group. HRW reversed hepatocyte apoptosis as well as hepatic inflammation and fibrosis in NASH specimens. Molecular hydrogen inhibits LPS-induced inflammation via an HO-1/interleukin 10 (IL-10)-independent pathway. HRW improved hepatic steatosis in the CSAA + HRW group. Sirt1 induction by molecular hydrogen via the HO-1/AMPK/PPARα/PPARγ pathway suppresses palmitate-mediated abnormal fat metabolism.

In Vitro Validation of an Artefact Suppression Algorithm in X-Ray Phase-Contrast Computed Tomography.

X-ray phase-contrast tomography can significantly increase the contrast-resolution of conventional attenuation-contrast imaging, especially for soft-tissue structures that have very similar attenuation. Just as in attenuation-based tomography, phase contrast tomography requires a linear dependence of aggregate beam direction on the incremental direction alteration caused by individual voxels along the path of the X-ray beam. Dense objects such as calcifications in biological specimens violate this condition. There are extensive beam deflection artefacts in the vicinity of such structures because they result in large distortion of wave front due to the large difference of refractive index; for such large changes in beam direction, the transmittance of the silicon analyzer crystal saturates and is no longer linearly dependent on the angle of refraction. This paper describes a method by which these effects can be overcome and excellent soft-tissue contrast of phase tomography can be preserved in the vicinity of such artefact-producing structures.

Evaluation of the effect of methionine and glucosamine on adjuvant arthritis in rats.

In the present study, we evaluated the effects of individual administration of methionine or glucosamine (GlcN) and compared with the combined administration of methionine and GlcN on the adjuvant arthritis model of rheumatoid arthritis in rats. Adjuvant arthritis was induced in female Lewis rats by injecting Freund's complete adjuvant (FCA) into the right hind paws, and methionine (200 mg/kg body weight/day) and/or GlcN (400 mg/kg/day) were orally administered for 21 days. The progression of the adjuvant arthritis was clinically evaluated for characteristic signs and symptoms by employing an arthritis score. The administration of methionine combined with GlcN suppressed the swelling of FCA-uninjected left hind paws and the arthritis score. Additionally, histopathological examination revealed that the combined administration of methionine and GlcN markedly suppressed synovial hyperplasia and the destruction of the cartilage surface and articular meniscus of the knee joints of FCA-injected right hind paws. Furthermore, combined methionine and GlcN administration suppressed the increase in the levels of nitric oxide, prostaglandin E(2) and hyaluronic acid in the plasma of rats with adjuvant arthritis. By contrast, individual administration of methionine or GlcN suppressed arthritis only slightly. These observations suggest that the combined administration of methionine and GlcN is more effective compared with individual administrations of methionine or GlcN in suppressing the progression of adjuvant arthritis (identified as swelling of joints and arthritis score), possibly by synergistically inhibiting synovial inflammation (identified as synovial hyperplasia and the destruction of the cartilage surface and articular meniscus) and the production of inflammatory mediators.

Effects of flavangenol, an extract of French maritime pine bark on collagen-induced arthritis in rats.

Flavangenol (FG), an extract of French maritime pine bark (Pinus maritime) mainly contains proanthocyanidin in oligomers. It has many physiological effects, including antioxidant and anti-atherosclerosis. In this study, we evaluated the effects of FG on rat collagen-induced arthritis, a model of human rheumatoid arthritis. The rats were fed with the diet of control, 0.3% FG, or 1% FG for 4 wk after the induction of arthritis. The FG diets, compared with the control diet, suppressed the increase in arthritic score and swelling of the paws in a dose-dependent manner. Histopathological examination revealed evidence that the 1% FG diet suppressed acute and chronic articular lesions in the rats. In addition, the FG diets (0.3% and 1%) suppressed the production of nitric oxide in the plasma of the rats. These results suggest that dietary FG has beneficial effects on collagen-induced arthritis in rats by inhibiting the acute and chronic inflammatory reactions.

Effects of a casein hydrolysate prepared from Aspergillus oryzae protease on adjuvant arthritis in rats.

We evaluated the effects of a casein hydrolysate (CH) prepared from Aspergillus oryzae protease on rat adjuvant arthritis, a model of human rheumatoid arthritis. CH was administered orally once a day to the animals for 22 d after the adjuvant injection. CH suppressed swelling in the adjuvant-uninjected hind paws, and a higher dose of CH suppressed the increase in arthritic score and swelling of the adjuvant-injected hind paws. A histopathological examination revealed evidence that the higher dose of CH suppressed the articular changes in the rats. In addition, CH suppressed the production of nitric oxide and prostaglandin E(2) in the plasma of the rats. These results suggest that CH had a suppressive effect on adjuvant arthritis by inhibiting the acute and chronic inflammatory reactions.

Isolation and characterization of Xanthobacter polyaromaticivorans sp. nov. 127W that degrades polycyclic and heterocyclic aromatic compounds under extremely low oxygen conditions.

Two bacterial strains, 127W and T102, were isolated from anoxic crude oil tank sludge as effective degraders of dibenzothiophene (DBT), a model sulfur containing heterocyclic aromatic compound in crude oil. Strain 127W was more tolerant to oxygen limitation than T102 and was capable of degrading two- and three-ring polycyclic and heterocyclic aromatic compounds under both aerobic and low oxygen conditions. Strain 127W degraded 0.082, 0.055, and 0.064 mM of DBT, naphthalene, and anthracene, respectively, in one week with dissolved oxygen < or =0.2ppm (0.006 mM). Degradation by 127W cell-free extracts for DBT was increased by addition of sodium hydrogencarbonate under this oxygen concentration. Phylogenetic analysis of the 16S rRNA gene sequence and physiological characteristics indicate that the strains 127W and T102 belong to new species of the genus Xanthobacter and Pseudomonas stutzeri, respectively. We propose X. polyaromaticivorans sp. nov. 127W.