Guptamcintyre6290

Oxidative stress (OS) contributes to Osteoarthritis (OA) pathogenesis and its effects are worsened by the impairment of homeostatic mechanisms such as autophagy in OA chondrocytes. Rescue of an efficient autophagic flux could therefore reduce the bulk of damaged molecules, and at the same time improve cell function and viability. As a promising dietary or intra-articular supplement to rescue autophagy in OA chondrocytes, we tested spermidine (SPD), known to induce autophagy and to reduce OS in several other cellular models. Chondrocytes were obtained from OA cartilage and seeded at high-density to keep their differentiated phenotype. The damaging effects of OS and the chondroprotective activity of SPD were assessed by evaluating the extent of cell death, oxidative DNA damage and caspase 3 activation. The autophagy promoting activity of SPD was evaluated by assessing pivotal autophagic effectors, i.e. VTP50469 price Beclin-1 (BECN-1), microtubule-associated protein 1 light chain 3 II (LC3-II) and p62. BECN-1 protein expressithe protection afforded by SPD against OS is exerted through the rescue of the autophagic flux. Pancreatic β-cells are vulnerable to oxidative stress, which promotes β-cell failure in type 2 diabetes. System χc- is a sodium-independent, cystine/glutamate antiporter that mediates the exchange of extracellular l-cystine and intracellular l-glutamate. The import of l-cystine through this transporter is the rate-limiting step in the glutathione (GSH) biosynthesis pathway that plays a significant role in antioxidative defense. Previously, we reported that 2-deoxy-d-ribose (dRib) induces oxidative damage through GSH depletion in pancreatic β-cells. In the current study, we elucidated the mechanism underlying the oxidative stress-induced β-cell damage. We measured the intracellular l-[14C]cystine uptake, GSH content, reactive oxygen species (ROS) levels, cytotoxicity, and apoptosis in rat insulinoma cell line, RINm5F. Treatment of dRib decreased the intracellular l-[14C]cystine uptake and GSH content and increased the intracellular ROS levels, cytotoxicity, and apoptosis in a time- and dose-dependent manner. Conversely, 2-mercaptoethanol (2-ME), a cystine uptake enhancer, recovered the dRib-induced decrease in l-[14C]cystine uptake, GSH content, and cell viability in a Na+-independent manner. In the case of isolated islets, dRib dose-dependently decreased the intracellular l-[14C]cystine uptake and cell viability; however, dRib-induced cytotoxicity was completely recovered by adding N-acetyl cysteine (NAC). To confirm that system χc- mediates the oxidative stress-induced β-cell damage, we overexpressed xCT (the substrate-specific subunit of system χc-) using a lentiviral vector in RINm5F cells. Overexpression of xCT fully recovered the dRib-induced decrease in l-[14C]cystine uptake and GSH content and prevented the dRib-induced increase in ROS levels, cytotoxicity, and apoptosis. The overexpression of xCT showed a protective effect against dRib-induced oxidative damage in RINm5F cells. Our study showed that dRib depletes intracellular GSH content through inhibition of cystine transport via system χc- in β-cells. Resveratrol (RSV) is a natural polyphenol with anti-obesity effects. However, the mechanisms of anti-obesity remain unclear due to its low bioavailability. Recent evidence demonstrates that gut microbiota plays a key role in obesity. This spurred us to investigate whether the anti-obesity effects of RSV are related to modulations in the gut microbiota and metabolic functions. Here, RSV significantly improved metabolic phenotype in the high-fat diet (HFD)-fed mice. A multi-omics approach was used to systematically profile the microbial signatures at both the phylogenetic and functional levels using 16S rRNA gene sequencing and metagenome. At the phylogenetic level, RSV treatment significantly modulated the gut microbiota composition in HFD-fed mice, characterized with increased Blautia abundance and decreased Desulfovibrio and Lachnospiraceae_NK4A136_group abundance. At the functional level, RSV significantly decreased pathways linked to host metabolic disease and increased pathways involved in the generation of small metabolites. Besides, the fecal microbiota transplantation experiment showed anti-obesity and microbiota-modulating effects similar to those observed in the oral RSV-feeding experiment. Moreover, metabolomic analysis and antibiotic treatment verified that 4-hydroxyphenylacetic acid (4-HPA) and 3-hydroxyphenylpropionic acid (3-HPP) were the two gut metabolites of RSV, which contribute to improving lipid metabolism in vitro. We concluded that the RSV-mediated alteration of gut microbiota and related gut metabolites contributed to prevention of metabolic syndrome in HFD-fed mice. BACKGROUND AND OBJECTIVE Tissue blood oxygenation contains critical information for biomedical studies and healthcare. The primary approach to extract the absolute value of tissue blood oxygenation (e.g., oxygen saturation) is spatial-resolved algorithm for near-infrared diffuse optical spectroscopy with continues-wave (CW) light, which require acquisition of the optical signals from multiple pairs of sources and detectors (S-D). This study reports the first attempt for absolute oxygenation measurement with single S-D pair of optical signals. METHODS A novel algorithm, namely, phantom-validation modified Beer-Lambert law (PV-MBLL), was created to fully utilize the optical signals from single S-D pair. This algorithm is combined with two-step phantom measurement to extract the absolute value of tissue oxygenation in CW system. The proposed PV-MBLL algorithm was compared with the conventional spatial-resolved algorithm on both step-varied liquid phantom and human experiment of cuff occlusion on arms. The one-way ANOVA analysis was performed to investigate the difference between the two algorithms. RESULTS By using the PV-MBLL algorithm, the reconstructed tissue absorption coefficient is highly accurate (not larger than 5.35% in error) over a wide range (0.02-0.20 cm-1). By contrast, the spatial-resolved algorithm leads to much larger errors (up to 37.57% in error). Moreover, the responses of oxygen saturation to cuff occlusion differ significantly (p  less then  0.005) with the two algorithms. CONCLUSIONS The proposed PV-MBLL algorithm has promising potential for accurate acquisition of oxygenation information. Additionally, the single S-D pair greatly reduces the size of optical probe and instrument cost, thus it is highly appropriate for the tissues with small size and large curvature.