Systematic review on the treatment of pentoxifylline in patients with non-alcoholic fatty liver disease

<p>Abstract</p> <p>Background</p> <p>As an anti-TNF agent that targets inflammatory process directly, Pentoxifylline has been investigated for treatment of NASH in individual studies and pilot trials for years. We summarized the available information and generating hypotheses for future research.</p> <p>Data Sources</p> <p>Google, Cochrane, MEDLINE, and EMBASE and the <it>Chinese Biomedical </it>data bases for studies restricted to pentoxifylline treatment in humans with NAFLD in all languages until June 2010. Six studies (2 randomized, double-blind, placebo-controlled trials; 4 prospective cohort studies) extracted from 11604 references.</p> <p>Results</p> <p>Pentoxifylline-treated patients showed a significant decrease AST (n = 37, <it>P </it>= 0.01) and ALT (n = 50, <it>P </it>= 0.03), but no significant effect on IL-6 (n = 36, <it>P </it>= 0.33) and TNF-α (n = 68, <it>P </it>= 0.26) compared with Placebo or UDCA-controlled groups. Improvement in one or more histological variables was reported in two trails, only 1 study showed a reduction in of one or two points in fibrosis stage.</p> <p>Limitations</p> <p>The trails did not consistently report all of the outcomes of interest. Sample sizes (117 patients totally) were small and only 2 out of 6 studies had a randomized, controlled design.</p> <p>Conclusion</p> <p>Pentoxifylline reduce AST and ALT levels and may improve liver histological scores in patients with NALFD/NASH, but did not appear to affect cytokines. Large, prospective, and well-designed randomized, controlled studies are needed to address this issue. Novel therapeutic targets for activation of inflammatory signaling pathways by fat also merit investigation.</p

Effect of acetone extract of Rumex japonicas Houtt on hydrogen peroxide-induced apoptosis in rat myocardial cells

Purpose: To investigate the protective effect of the acetone extract of Rumex japonicas Houtt. (AER) on rat myocardial cells.Methods: R. japonicas was extracted with 75 % aqueous ethanol by reflux to afford total extract (TER). TER was suspended in water and then extracted with acetone to afford acetone fraction of R. japonicas (AER). High performance liquid chromatography (HPLC) combined with standard substances was carried out to analyze the major constituents of AER. Apoptosis in myocardial H9c2 cell line was induced by H2O2 (100 μmol/L). The cells were treated with AER (50, 100 and 200 μg/mL, and cell viability was evaluated by the 3-（4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, while oxidative stress level in H9c2 cells was evaluated by determining levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), creatinine kinase (CK), superoxide dismutase (SOD), and catalase (CAT). Furthermore, apoptotic proteins (caspase-3, Bax and Bcl-2) in H9c2 cells were analyzed by using western blot assay.Results: Results revealed that the main components of AER are aloe-emodin, rhein, emodin, chrysophanol and physcion. AER (50, 100 and 200 μg/mL) inhibited the cell viability reduction of the H9c2 cells induced by H2O2 (p &lt; 0.05, p &lt; 0.01, p &lt; 0.01, respectively). AER (50, 100 and 200 μg/mL) decreased LDH and CK contents of H9c2 cells (p &lt; 0.01). The levels of SOD (p&lt;0.01) and CAT (p &lt; 0.01) were increased by AER treatments (100 and 200 μg/mL); in addition, AER (50, 100 and 200 μg/mL) decreased MDA levels (p &lt; 0.01). Besides, the present results also revealed that AER could down-regulate caspase-3 and Bax, but up-regulated Bcl-2.Conclusion: AER alleviates apoptosis induced by H2O2 in myocardial H9c2 cells via inhibition of oxidative stress and mitochondria-mediated apoptosis. This finding suggests that AER can potentially be developed for the treatment of myocardial apoptosis.Keywords: Rumex japonicas Houtt., Myocardial cells, Apoptosis, H9c2 cell, Oxidative stres

Low Bone Mineral Density in Chinese Adults with Nonalcoholic Fatty Liver Disease

Aim. To investigate bone metabolic characteristics in Chinese adults with nonalcoholic fatty liver disease (NAFLD). Methods. A total of 224 patients (99 males and 125 postmenopausal females) were recruited and divided into 4 groups: males without NAFLD, males with NAFLD, females without NAFLD, and females with NAFLD. Bone mineral density (BMD) was evaluated according to body mass index (BMI), waist circumference (WC), and serum biomarkers. β cell function was evaluated by HOMA2%B, HOMA2%S, and HOMA2IR. Results. Males in the NAFLD group had lower BMD of the right hip and the femoral neck (0.852±0.117 versus 0.930±0.123, P=0.002; 0.736±0.119 versus 0.812±0.132, P=0.004), and females had lower BMD of the right hip (0.725±0.141 versus 0.805±0.145, P=0.002) even after adjusted for weight, BMI, waist, HDL, and ALT. There was no significant difference in bone metabolic markers between patients with and without NAFLD. NAFLD was an important factor that affected the bone; moreover, the effect attenuated when HOMA2IR entered into the model (R2=0.160, β=−0.172, and P=0.008). Conclusions. NAFLD exerts a detrimental effect on BMD in both males and females. Insulin resistance may play an important role in this pathophysiological process

ATP Synthase β

HDL cholesterol is known to be inversely correlated with cardiovascular disease due to its diverse antiatherogenic functions. SR-BI mediates the selective uptake of HDL-C. SR-BI knockout diminishes but does not completely block the transport of HDL; other receptors may be involved. Ectopic ATP synthase β-chain in hepatocytes has been previously characterized as an apoA-I receptor, triggering HDL internalization. This study was undertaken to identify the overexpression of ectopic ATP synthase β-chain on DIL-HDL uptake in primary hepatocytes in vitro and on plasma HDL levels in SR-BI knockout mice. Human ATP synthase β-chain cDNA was delivered to the mouse liver by adenovirus and GFP adenovirus as control. The adenovirus-mediated overexpression of β-chain was identified at both mRNA and protein levels on mice liver and validated by its increasing of DiL-HDL uptake in primary hepatocytes. In response to hepatic overexpression of β-chain, plasma HDL-C levels and cholesterol were reduced in SR-BI knockout mice, compared with the control. The present data suggest that ATP synthase β-chain can serve as the endocytic receptor of HDL, and its overexpression can reduce plasma HDL-C

Device-Level Photonic Memories and Logic Applications Using Phase-Change Materials

This is the final version of the article. Available from Wiley via the DOI in this record.All data need to evaluate the conclusions in this Communication are present in this Communication and/or the Supporting Information. Additional data related to this Communication may be requested from the corresponding author (H.B.; [email protected] or Oxford Research Archive for Data (https://ora.ox.ac.uk).Inspired by the great success of fiber optics in ultrafast data transmission, photonic computing is being extensively studied as an alternative to replace or hybridize electronic computers, which are reaching speed and bandwidth limitations. Mimicking and implementing basic computing elements on photonic devices is a first and essential step toward all-optical computers. Here, an optical pulse-width modulation (PWM) switching of phase-change materials on an integrated waveguide is developed, which allows practical implementation of photonic memories and logic devices. It is established that PWM with low peak power is very effective for recrystallization of phase-change materials, in terms of both energy efficiency and process control. Using this understanding, multilevel photonic memories with complete random accessibility are then implemented. Finally, programmable optical logic devices are demonstrated conceptually and experimentally, with logic "OR" and "NAND" achieved on just a single integrated photonic phase-change cell. This study provides a practical and elegant technique to optically program photonic phase-change devices for computing applications.This research was supported via the Engineering and Physical Sciences Research Council Manufacturing Fellowships (EP/J018694/1), the Wearable and Flexible Technologies (WAFT) collaboration (EP/M015173/1), the Chalcogenide Advanced Manufacturing Partnership (EP/M015130/1), and the European Union's Horizon 2020 research and innovation program (780848, Fun‐COMP project)