Peroxisome proliferator-activated receptor gamma (PPARγ), a type II nuclear receptor present in adipose tissue, colon and macrophages. It reduces the hyperglycemia associated metabolic syndromes. Particularly, type II diabetes-related cardiovascular system risk in human beings. The fatty acid storage and glucose metabolism are regulated by PPARγ activation in human body. According to recent reports commercially available PPARγ activating drugs have been causing severe side effects. At the same time, natural products have been proved to be a promising area of drug discovery. Recently, many studies have been attempted to screen and identify a potential drug candidate to activate PPARγ. Hence, in this study we have selected some of the bio-active molecules from traditional medicinal plants. Molecular docking studies have been carried out against the target, PPARγ. We Results suggested that Punigluconin has a efficient docking score and it is found to have good binding affinities than other ligands. Hence, we concluded that Punigluconin is a better drug candidate for activation of PPARγ gene expression. Further studies are necessary to confirm their efficacy and possibly it can develop as a potential drug in future.
A graphene oxide mediated hybrid nano system for pH stimuli-responsive and in vitro drug delivery targeted for cancer was described in this study. Graphene oxide (GO) functionalized Chitosan (CS) mediated nanocarrier capped with xyloglucan (XG) was fabricated with and without Kappa carrageenan (κ-C) from red seaweed, Kappaphycus alverzii, as an active drug. FTIR, EDAX, XPS, XRD, SEM and HR-TEM studies were carried out for GO-CS-XG nanocarrier loaded with and without active drugs to understand the physicochemical properties. XPS (C1s, N1s and O1s) confirmed the fabrications of XG and functionalization of GO by CS via the binding energies at 284.2 eV, 399.4 eV and 531.3 eV, respectively. The amount of drug loaded in vitro was 0.422 mg/mL. The GO-CS-XG nanocarrier showed a cumulative drug release of 77 % at acidic pH 5.3. In contrast to physiological conditions, the release rate of κ-C from the GO-CS-XG nanocarrier was considerably higher in the acidic condition. Thus, a pH stimuli-responsive anticancer drug release was successfully achieved with the GO-CS-XG-κ-C nanocarrier system for the first time. The drug release mechanism was carried out using various kinetic models that showed a mixed release behavior depending on concentration and diffusion/swelling mechanism. The best-fitting model which supports our release mechanism are zero order, first order and Higuchi models. GO-CS-XG and κ-C loaded nanocarrier biocompatibility were determined by in vitro hemolysis and membrane stabilization studies. MCF-7 and U937 cancer cell lines were used to study the cytotoxicity of the nanocarrier by MTT assay, which indicates excellent cytocompatibility. These findings support the versatile use of a green renewable biocompatible GO-CS-XG nanocarrier as targeted drug delivery and potential anticancer agent for therapeutic purposes.
Effect of selenium and acidification in freshwater environment was assessed solitary but no reports are available on the impacts of both factors act together. In the present study, effects of combined simultaneous exposure to selenium (Se) and low pH were assessed in Mozambique tilapia, Oreochromis mossambicus. Responses were measured based on antioxidant defenses (enzymatic SOD, CAT, GPx and non-enzymatic GSH), biotransformation enzyme (GST), metallothionein levels (MT), oxidative damage (LPO, CP), Na+/K+-ATPase (NKA) activity in gills and liver tissues and neurotoxicity (acetylcholinesterase, AChE) response in brain tissue. Fish were exposed to combined treatment at different pH levels (7.5, control (optimum pH for tilapia growth); 5.5, low pH) and Se concentrations (0, 10, and 100 μg L-1). Toxicity levels of Se were not significantly different under control and low pH indicating that pH did not affect Se toxicity. Levels of GSH and MT were enhanced in Se-exposed fish at both pH. Combined effects of high Se concentration and low pH decreased SOD and CAT activities and increased those of GPx and GST. However, organisms were not able to prevent cellular damage (LPO and CP), indicating a condition of oxidative stress. Furthermore, inhibition of Na+/K+-ATPase activity was showed. Additionally, neurotoxicity effect was observed by inhibition of cholinesterase activity in organisms exposed to Se at both pH conditions. As a result, the combined stress of selenium and freshwater acidification has a slight impact on antioxidant defense mechanisms while significantly inhibiting cholinesterase and Na+/K + -ATPase activity in fish. The mechanisms of freshwater acidification mediating the toxic effects of trace non-metal element on freshwater fish need to investigate further.
In widespread species, the diverse ecological conditions in which the populations occur, and the presence of many potential geographical barriers through their range are expected to have created ample opportunities for the evolution of distinct, often cryptic lineages. In this work, we tested for species boundaries in one such widespread species, the king cobra, Ophiophagus hannah (Cantor, 1836), a largely tropical elapid snake distributed across the Oriental realm. Based on extensive geographical sampling across most of the range of the species, we initially tested for candidate species (CS) using Maximum-Likelihood analysis of mitochondrial genes. We then tested the resulting CS using both morphological data and sequences of three single-copy nuclear genes. We used snapclust to determine the optimal number of clusters in the nuclear dataset, and Bayesian Phylogenetics and Phylogeography (BPP) to test for likely species status. We used non-metric multidimensional scaling (nMDS) analysis for discerning morphological separation. We recovered four independently evolving, geographically separated lineages that we consider Confirmed Candidate Species: (1) Western Ghats lineage; (2) Indo-Chinese lineage (3) Indo-Malayan lineage; (4) Luzon Island lineage, in the Philippine Archipelago. We discuss patterns of lineage divergence, particularly in the context of low morphological divergence, and the conservation implications of recognizing several endemic king cobra lineages.