Multiple parallel hits, including genetic differences, insulin resistance and intestinal microbiota, account for the progression of non-alcoholic steatohepatitis (NASH). Multiple hits induce adipokine secretion, endoplasmic reticulum (ER) and oxidative stress at the cellular level that subsequently induce hepatic steatosis, inflammation and fibrosis, among which oxidative stress is considered a key contributor to progression from simple fatty liver to NASH. Although several clinical trials have shown that anti-oxidative therapy can effectively control hepatitis activities in the short term, the long-term effect remains obscure. Several trials of long-term anti-oxidant protocols aimed at treating cerebrovascular diseases or cancer development have failed to produce a benefit. This might be explained by the non-selective anti-oxidative properties of these drugs. Molecular hydrogen is an effective antioxidant that reduces only cytotoxic reactive oxygen species (ROS) and several diseases associated with oxidative stress are sensitive to hydrogen. The progress of NASH to hepatocellular carcinoma can be controlled using hydrogen-rich water. Thus, targeting mitochondrial oxidative stress might be a good candidate for NASH treatment. Long term clinical intervention is needed to control this complex lifestyle-related disease.

Background and study aims  Linked color imaging (LCI) and blue laser imaging (BLI) are novel image-enhanced endoscopy technologies with strong, unique color enhancement. We investigated the efficacy of LCI and BLI-bright compared to conventional white light imaging (WLI) by measuring the color difference between early gastric cancer lesions and the surrounding mucosa. Patients and methods  Images of early gastric cancer scheduled for endoscopic submucosal dissection were captured by LCI, BLI-bright, and WLI under the same conditions. Color values of the lesion and surrounding mucosa were defined as the average of the color value in each region of interest. Color differences between the lesion and surrounding mucosa (ΔE) were examined in each mode. The color value was assessed using the CIE L*a*b* color space (CIE: Commission Internationale d’Eclairage). Results  We collected images of 43 lesions from 42 patients. Average ΔE values with LCI, BLI-bright, and WLI were 11.02, 5.04, and 5.99, respectively. The ΔE was significantly higher with LCI than with WLI ( P  < 0.001). Limited to cases of small ΔE with WLI, the ΔE was approximately 3 times higher with LCI than with WLI (7.18 vs. 2.25). The ΔE with LCI was larger when the surrounding mucosa had severe intestinal metaplasia ( P  = 0.04). The average color value of a lesion and the surrounding mucosa differed. This value did not have a sufficient cut-off point between the lesion and surrounding mucosa to distinguish them, even with LCI. Conclusion  LCI had a larger ΔE than WLI. It may allow easy recognition and early detection of gastric cancer, even for inexperienced endoscopists.

Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease (NAFLD), in which most patients exhibit non-progressive, non-alcoholic fatty liver (NAFL) attributable to simple steatosis. Multiple hits, including genetic differences, fat accumulation, insulin resistance and intestinal microbiota changes, account for the progression of NASH. NAFLD is strongly associated with obesity, which induces adipokine secretion, endoplasmic reticulum (ER) and oxidative stress at the cellular level, which in turn induces hepatic steatosis, inflammation and fibrosis. Among these factors, gut microbiota are acknowledged as having an important role in initiating this multifactorial disease. Oxidative stress is considered to be a key contributor in the progression from NAFL to NASH. Macrophage infiltration is apparent in NAFL and NASH, while T-cell infiltration is apparent in NASH. Although several clinical trials have shown that antioxidative therapy with vitamin E can effectively control hepatitis pathology in the short term, the long-term effects remain obscure and have often proved to be ineffective in many other diseases. Several long-term antioxidant protocols have failed to reduce mortality. New treatment modalities that incorporate current understanding of NAFLD molecular pathogenesis must be considered.

Oxidative stress is a strong contributor to the progression from simple fatty liver to nonalcoholic steatohepatitis (NASH). Molecular hydrogen is an effective antioxidant that reduces cytotoxic reactive oxygen species. In this study, we investigated the effects of hydrogen-rich water and the drug pioglitazone on the progression of NASH in mouse models. A methionine-choline-deficient (MCD) diet mouse model was prepared. Mice were divided into three experimental groups and fed for 8 weeks as follows: (1) MCD diet 1 control water (CW group); (2) MCD diet 1 hydrogen-rich water (HW group); and (3) MCD diet mixed with pioglitazone (PGZ group). Plasma alanine aminotransferase levels, hepatic expression of tumor necrosis factor-a, interleukin-6, fatty acid synthesis-related genes, oxidative stress biomarker 8-hydroxydeoxyguanosine (8-OHdG), and apoptosis marker terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nickend labeling (TUNEL)-positive cells in the liver were decreased in the HW and PGZ groups. The HW group showed a smaller decrease in hepatic cholesterol; however, stronger antioxidative effects in serum and lower peroxisome proliferator-activated receptor-a expression in the liver were seen in comparison with the PGZ group. We then investigated the effects of hydrogen in the prevention of hepatocarcinogenesis in STAM mice, known as the NASH-related hepatocarcinogenesis model. Eight-week-old male STAM mice were divided into three experimental groups as follows: (1) control water (CW-STAM); (2) hydrogen-rich water (HW-STAM); and (3) pioglitazone (PGZ-STAM). After 8 weeks, hepatic tumors were evaluated. The number of tumors was significantly lower in the HW-STAM and PGZ-STAM groups than in the CW-STAM group. The maximum tumor size was smaller in the HW-STAM group than in the other groups. Conclusion: Consumption of hydrogen-rich water may be an effective treatment for NASH by reducing hepatic oxidative stress, apoptosis, inflammation, and hepatocarcinogenesis. (HEPATOLOGY 2012;56:912-921)

We study the Schwinger pair production in confining theories. The production rate in an external electric field E is numerically evaluated by using the holographic description. There exist two kinds of critical values of the electric field: (i) E ¼ E c , above which there is no potential barrier and particles are freely generated, and (ii) E ¼ E s , below which the confining string tension dominates the electric field and the pair production does not occur. We argue the universal exponents associated with the critical behaviors.

The interaction between Λ c and a nucleon (N) is investigated by employing the HAL QCD method in the (2+1)-flavor lattice QCD on a (2.9 fm) 3 volume at m π ≃ 410, 570, 700MeV. We study the central potential in 1 S 0 channel as well as central and tensor potentials in 3 S 1 − 3 D 1 channel, and find that the tensor potential for Λ c N is negligibly weak and central potentials in both 1 S 0 and 3 S 1 − 3 D 1 channels are almost identical with each other except at short distances. Phase shifts and scattering lengths calculated with these potentials show that the interaction of Λ c N system is attractive and has a similar strength in 1 S 0 and 3 S 1 channels at low energies (i.e. the kinetic energy less than about 40 MeV). While the attractions are not strong enough to form two-body bound states, our results lead to a possibility to form Λ c hypernuclei for sufficiently large atomic numbers (A). To demonstrate this, we derive a single-folding potential for Λ c hypernuclei from the Λ c -nucleon potential obtained in lattice QCD, and find that Λ c hypernuclei can exist for A ≥ 12 with the binding energies of a few MeV. We also estimate the Coulomb effect for the Λ c hypernuclei.

We study classical chaotic motions in the Berenstein-Maldacena-Nastase (BMN) matrix model. For this purpose, it is convenient to focus upon a reduced system composed of two-coupled anharmonic oscillators by supposing an ansatz. We examine three ansätze: 1) two pulsating fuzzy spheres, 2) a single Coulomb-type potential, and 3) integrable fuzzy spheres. For the first two cases, we show the existence of chaos by computing Poincaré sections and a Lyapunov spectrum. The third case leads to an integrable system. As a result, the BMN matrix model is not integrable in the sense of Liouville, though there may be some integrable subsectors.

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