Grape polyphenols attenuate inflammation and insulin resistance in human adipocytes and obese mice

Obesity is rapidly increasing worldwide among all age groups. Insulin resistance or type 2 diabetes is one of several debilitating health problems associated with obesity. An emerging feature of obesity and type 2 diabetes is their linkage with chronic, low-grade inflammation that begins in white adipose tissue (WAT) and eventually becomes systemic. One potential dietary strategy to reduce chronic inflammation is consumption of fruits and vegetables rich in polyphenols, including grape products, which possess anti-oxidant and anti-inflammatory properties. Notably, several clinical and animal studies have shown that supplementation with grape products like grape juice, grape powder or extracts, and red wine reduced oxidative damage and inflammation. However, the suppressive effects of grape powder on adipocyte-derived inflammation and insulin resistance remains uncertain. Additionally, the bioavailability of grape polyphenols and their ability to lower inflammation and insulin resistance in vitro and in a diet-induced obese animal model are unclear. Therefore, the specific aims of this research were to determine the extent to which 1) grape powder extract (GPE) and several of its polyphenols decrease tumor necrosis factor alpha (TNFa)-mediated inflammation and insulin resistance and their mechanisms of action in primary cultures of human adipocytes (Aim 1), and 2) grape powder polyphenols are absorbed and reduce markers of inflammation and insulin resistance in high fat-fed obese mice (Aim 2). In Aim 1, GPE and quercetin, an abundant polyphenol in GPE, attenuated TNFa-induced a) expression of inflammatory genes, b) activation of inflammatory mitogen-activated protein kinases (MAPKs) and transcription factors nuclear factor-kappa B (NF-kB) and activator protein-1 (AP-1), c) expression or abundance of two negative regulators of insulin sensitivity, and d) suppression of insulin-stimulated glucose uptake. Taken together, these data demonstrate that GPE and quercetin attenuate TNFa-mediated inflammation and insulin resistance in primary cultures of human adipocytes, possibly by suppressing the activation of inflammatory MAPKs and transcription factors that cause insulin resistance. In Aim 2, it was found that a) quercetin 3-O-glucoside was one of the most abundant polyphenols detected in the sera of mice gavaged with GPE, b) high fat-fed mice supplemented with quercetin-rich grape powder had improved glucose disposal rates acutely and reduced markers of inflammation in the sera and WAT chronically, and c) quercetin 3-O-glucoside reduced several markers of inflammation in primary cultures of human adipocytes. Collectively, these findings are expected to contribute critical insights for the development of dietary strategies using grape products for the control of obesity-related conditions including inflammation and insulin resistance or type 2 diabetes. However, clinical trials are needed to determine the extent to which these findings can be reproduced in humans

CAPIH: A Web interface for comparative analyses and visualization of host-HIV protein-protein interactions

<p>Abstract</p> <p>Background</p> <p>The Human Immunodeficiency Virus type one (HIV-1) is the major causing pathogen of the Acquired Immune Deficiency Syndrome (AIDS). A large number of HIV-1-related studies are based on three non-human model animals: chimpanzee, rhesus macaque, and mouse. However, the differences in host-HIV-1 interactions between human and these model organisms have remained unexplored.</p> <p>Description</p> <p>Here we present CAPIH (Comparative Analysis of Protein Interactions for HIV-1), the first web-based interface to provide comparative information between human and the three model organisms in the context of host-HIV-1 protein interactions. CAPIH identifies genetic changes that occur in HIV-1-interacting host proteins. In a total of 1,370 orthologous protein sets, CAPIH identifies ~86,000 amino acid substitutions, ~21,000 insertions/deletions, and ~33,000 potential post-translational modifications that occur only in one of the four compared species. CAPIH also provides an interactive interface to display the host-HIV-1 protein interaction networks, the presence/absence of orthologous proteins in the model organisms in the networks, the genetic changes that occur in the protein nodes, and the functional domains and potential protein interaction hot sites that may be affected by the genetic changes. The CAPIH interface is freely accessible at <url>http://bioinfo-dbb.nhri.org.tw/capih</url>.</p> <p>Conclusion</p> <p>CAPIH exemplifies that large divergences exist in disease-associated proteins between human and the model animals. Since all of the newly developed medications must be tested in model animals before entering clinical trials, it is advisable that comparative analyses be performed to ensure proper translations of animal-based studies. In the case of AIDS, the host-HIV-1 protein interactions apparently have differed to a great extent among the compared species. An integrated protein network comparison among the four species will probably shed new lights on AIDS studies.</p

Serum total antioxidant capacity reflects severity of illness in patients with severe sepsis

INTRODUCTION: We conducted the present study to evaluate the changes in serum total antioxidant capacity (TAC) in patients with severe sepsis and to investigate the association between serum TAC and clinical severity. METHOD: This was a prospective observational study involving a sample of patients who met established criteria for severe sepsis and were admitted to the emergency department of a university teaching hospital. Serum TAC was determined using the total radical-trapping antioxidant parameter method. The levels of TAC, uric acid, albumin, and bilirubin in sera were obtained in the emergency department and evaluated to determine whether there were any correlations between the major antioxidant biomarkers and clinical severity of sepsis. The Acute Physiology and Chronic Health Evaluation (APACHE) II score was used for clinical evaluation of the severity of sepsis. RESULTS: A total of 73 patients with sepsis, with a mean (± standard deviation) APACHE II score of 23.2 ± 8.2 and a mortality rate of 26.0%, were included. Seventy-six healthy individuals served as control individuals. Among the patients, serum TAC levels correlated significantly with APACHE II scores. Patients who died also had higher TAC than did those who survived. Serum uric acid levels correlated significantly with serum TAC and APACHE II scores in patients with severe sepsis. CONCLUSION: Elevated serum TAC level may reflect clinical severity of sepsis. In addition, serum uric acid levels appear to contribute importantly to the higher TAC levels observed in patients with severe sepsis

Patient-oriented simulation based on Monte Carlo algorithm by using MRI data

<p>Abstract</p> <p>Background</p> <p>Although Monte Carlo simulations of light propagation in full segmented three-dimensional MRI based anatomical models of the human head have been reported in many articles. To our knowledge, there is no patient-oriented simulation for individualized calibration with NIRS measurement. Thus, we offer an approach for brain modeling based on image segmentation process with <it>in vivo </it>MRI T1 three-dimensional image to investigate the individualized calibration for NIRS measurement with Monte Carlo simulation.</p> <p>Methods</p> <p>In this study, an individualized brain is modeled based on <it>in vivo </it>MRI 3D image as five layers structure. The behavior of photon migration was studied for this individualized brain detections based on three-dimensional time-resolved Monte Carlo algorithm. During the Monte Carlo iteration, all photon paths were traced with various source-detector separations for characterization of brain structure to provide helpful information for individualized design of NIRS system.</p> <p>Results</p> <p>Our results indicate that the patient-oriented simulation can provide significant characteristics on the optimal choice of source-detector separation within 3.3 cm of individualized design in this case. Significant distortions were observed around the cerebral cortex folding. The spatial sensitivity profile penetrated deeper to the brain in the case of expanded CSF. This finding suggests that the optical method may provide not only functional signal from brain activation but also structural information of brain atrophy with the expanded CSF layer. The proposed modeling method also provides multi-wavelength for NIRS simulation to approach the practical NIRS measurement.</p> <p>Conclusions</p> <p>In this study, the three-dimensional time-resolved brain modeling method approaches the realistic human brain that provides useful information for NIRS systematic design and calibration for individualized case with prior MRI data.</p

NBM-HD-1: A Novel Histone Deacetylase Inhibitor with Anticancer Activity

HDAC inhibitors (HDACis) have been developed as promising anticancer agents in recent years. In this study, we synthesized and characterized a novel HDACi, termed NBM-HD-1. This agent was derived from the semisynthesis of propolin G, isolated from Taiwanese green propolis (TGP), and was shown to be a potent suppressor of tumor cell growth in human breast cancer cells (MCF-7 and MDA-MB-231) and rat glioma cells (C6), with an IC50 ranging from 8.5 to 10.3 μM. Western blot demonstrated that levels of p21(Waf1/Cip1), gelsolin, Ac-histone 4, and Ac-tubulin markedly increased after treatment of cancer cells with NBM-HD-1. After NBM-HD-1 treatment for 1–4 h, p-PTEN and p-AKT levels were markedly decreased. Furthermore, we also found the anticancer activities of NBM-HD-1 in regulating cell cycle regulators. Treatment with NBM-HD-1, p21(Waf1/Cip1) gene expression had markedly increased while cyclin B1 and D1 gene expressions had markedly decreased. On the other hand, we found that NBM-HD-1 increased the expressions of tumor-suppressor gene p53 in a dose-dependent manner. Finally, we showed that NBM-HD-1 exhibited potent antitumor activity in a xenograft model. In conclusion, this study demonstrated that this compound, NBM-HD-1, is a novel and potent HDACi with anticancer activity in vitro and in vivo

Application of Flexible Micro Temperature Sensor in Oxidative Steam Reforming by a Methanol Micro Reformer

Advances in fuel cell applications reflect the ability of reformers to produce hydrogen. This work presents a flexible micro temperature sensor that is fabricated based on micro-electro-mechanical systems (MEMS) technology and integrated into a flat micro methanol reformer to observe the conditions inside that reformer. The micro temperature sensor has higher accuracy and sensitivity than a conventionally adopted thermocouple. Despite various micro temperature sensor applications, integrated micro reformers are still relatively new. This work proposes a novel method for integrating micro methanol reformers and micro temperature sensors, subsequently increasing the methanol conversion rate and the hydrogen production rate by varying the fuel supply rate and the water/methanol ratio. Importantly, the proposed micro temperature sensor adequately controls the interior temperature during oxidative steam reforming of methanol (OSRM), with the relevant parameters optimized as well