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391.
Gopalsamy Rajiv Gandhi Antony Stalin Kedike Balakrishna Savarimuthu Ignacimuthu Michael Gabriel Paulraj Rajagopal Vishal 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013
Background
The present study was aimed at isolating an antidiabetic molecule from a herbal source and assessing its mechanism of action.Methods
Embelin, isolated from Embelia ribes Burm. (Myrsinaceae) fruit, was evaluated for its potential to regulate insulin resistance, alter β-cell dysfunction and modulate key markers involved in insulin sensitivity and glucose transport using high-fat diet (HFD) fed-streptozotocin (STZ) (40 mg/kg)-induced type 2 diabetic rats. Molecular-dockings were performed to investigate the binding modes of embelin into PPARγ, PI3K, p-Akt and GLUT4 active sites.Results
Embelin (50 mg/kg b wt.) reduced body weight gain, blood glucose and plasma insulin in treated diabetic rats. It further modulated the altered lipid profiles and antioxidant enzymes with cytoprotective action on β-cell. Embelin significantly increased the PPARγ expression in epididymal adipose tissue compared to diabetic control group; it also inhibited adipogenic activity; it mildly activated PPARγ levels in the liver and skeletal muscle. It also regulated insulin mediated glucose uptake in epididymal adipose tissue through translocation and activation of GLUT4 in PI3K/p-Akt signaling cascade. Embelin bound to PPARγ; it disclosed stable binding affinities to the active sites of PI3K, p-Akt and GLUT4.Conclusions
These findings show that embelin could improve adipose tissue insulin sensitivity without increasing weight gain, enhance glycemic control, protect β-cell from damage and maintain glucose homeostasis in adipose tissue.General significance
Embelin can be used in the prevention and treatment of type 2 diabetes mellitus caused due to obesity. 相似文献392.
Fatemeh Parastesh Karthikeyan Rajagopal Anitha Karthikeyan Ahmed Alsaedi Tasawar Hayat Viet-Thanh Pham 《Cognitive neurodynamics》2018,12(6):607-614
The last two decades have seen many literatures on the mathematical and computational analysis of neuronal activities resulting in many mathematical models to describe neuron. Many of those models have described the membrane potential of a neuron in terms of the leakage current and the synaptic inputs. Only recently researchers have proposed a new neuron model based on the electromagnetic induction theorem, which considers inner magnetic fluctuation and external electromagnetic radiation as a significant missing part that can participate in neural activity. While the flux coupling of the membrane is considered equivalent to a memductance function of a memristor, standard memductance model of \(\alpha + 3\beta \phi^{2}\) has been used in the literatures, but in this paper we propose a new memductance function based on discontinuous flux coupling. Various dynamical properties of the neuron model with discontinuous flux coupling are studied and interestingly the proposed model shows hyperchaotic behavior which was not identified in the literatures. Furthermore, we consider a ring network of the proposed model and investigate whether the chimera state can emerge. The chimera state relates to the state with simultaneously coherence and incoherence in oscillatory networks and has received much attention in recent years. 相似文献
393.
394.
Kumar Rajagopal S Manickam P Periyasamy V Namasivayam N 《The Journal of nutritional biochemistry》2003,14(8):452-458
This study was undertaken to investigate the effect of Cassia auriculata leaf extract on tissue lipid peroxidation and antioxidant status in experimental hepatotoxicity. Administering ethanol to rats for 60 days resulted in significantly elevated levels of serum total bilirubin, aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) as compared with those of the experimental control rats. Significantly elevated levels of tissue thiobarbituric acid reactive substances (TBARS), hydroperoxides and lowered activities of superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) were also observed on alcohol treatment as compared with those of experimental control rats. Concentration of serum non-enzymic antioxidants such as vitamin E and vitamin C were also significantly lowered on alcohol supplementation. Treatment with Cassia auriculata leaf extract at a dose of 250 mg kg(-1) body weight and 500 mg kg(-1) body weight to rats administered alcohol, lowered the levels of TBARS and hydroperoxides and elevated the activities of SOD and CAT and the levels of reduced GSH in the liver, brain, kidney and intestine significantly compared to unsupplemented alcohol treated rats. Cassia auriculata leaf extract treatment restored the serum vitamin E, and vitamin C levels also to near those of the experimental control animals. Our data indicate that supplementation with Cassia auriculata leaf extract can offer protection against free radical mediated oxidative stress in experimental hepatotoxicity. In addition, histopathological studies of the liver and brain confirmed the beneficial role of Cassia auriculata leaf extract. 相似文献
395.
396.
Ranjana Poddar Sathyanarayanan Rajagopal C. William Shuttleworth Surojit Paul 《The Journal of biological chemistry》2016,291(2):813-825
Excessive release of Zn2+ in the brain is implicated in the progression of acute brain injuries. Although several signaling cascades have been reported to be involved in Zn2+-induced neurotoxicity, a potential contribution of tyrosine phosphatases in this process has not been well explored. Here we show that exposure to high concentrations of Zn2+ led to a progressive increase in phosphorylation of the striatal-enriched phosphatase (STEP), a component of the excitotoxic-signaling pathway that plays a role in neuroprotection. Zn2+-mediated phosphorylation of STEP61 at multiple sites (hyperphosphorylation) was induced by the up-regulation of brain-derived neurotropic factor (BDNF), tropomyosin receptor kinase (Trk) signaling, and activation of cAMP-dependent PKA (protein kinase A). Mutational studies further show that differential phosphorylation of STEP61 at the PKA sites, Ser-160 and Ser-221 regulates the affinity of STEP61 toward its substrates. Consistent with these findings we also show that BDNF/Trk/PKA mediated signaling is required for Zn2+-induced phosphorylation of extracellular regulated kinase 2 (ERK2), a substrate of STEP that is involved in Zn2+-dependent neurotoxicity. The strong correlation between the temporal profile of STEP61 hyperphosphorylation and ERK2 phosphorylation indicates that loss of function of STEP61 through phosphorylation is necessary for maintaining sustained ERK2 phosphorylation. This interpretation is further supported by the findings that deletion of the STEP gene led to a rapid and sustained increase in ERK2 phosphorylation within minutes of exposure to Zn2+. The study provides further insight into the mechanisms of regulation of STEP61 and also offers a molecular basis for the Zn2+-induced sustained activation of ERK2. 相似文献
397.
Binhui Ren Zoulikha Azzegagh Ana?M. Jaramillo Yunxiang Zhu Ana Pardo-Saganta Rustam Bagirzadeh Jose?R. Flores Wei Han Yong-jun Tang Jing Tu Denise?M. Alanis Christopher?M. Evans Michele Guindani Paul?A. Roche Jayaraj Rajagopal Jichao Chen C.?William Davis Michael?J. Tuvim Burton?F. Dickey 《Bioscience reports》2015,35(3)
Airway mucin secretion is important pathophysiologically and as a model of polarized epithelial regulated exocytosis. We find the trafficking protein, SNAP23 (23-kDa paralogue of synaptosome-associated protein of 25 kDa), selectively expressed in secretory cells compared with ciliated and basal cells of airway epithelium by immunohistochemistry and FACS, suggesting that SNAP23 functions in regulated but not constitutive epithelial secretion. Heterozygous SNAP23 deletant mutant mice show spontaneous accumulation of intracellular mucin, indicating a defect in baseline secretion. However mucins are released from perfused tracheas of mutant and wild-type (WT) mice at the same rate, suggesting that increased intracellular stores balance reduced release efficiency to yield a fully compensated baseline steady state. In contrast, acute stimulated release of intracellular mucin from mutant mice is impaired whether measured by a static imaging assay 5 min after exposure to the secretagogue ATP or by kinetic analysis of mucins released from perfused tracheas during the first 10 min of ATP exposure. Together, these data indicate that increased intracellular stores cannot fully compensate for the defect in release efficiency during intense stimulation. The lungs of mutant mice develop normally and clear bacteria and instilled polystyrene beads comparable to WT mice, consistent with these functions depending on baseline secretion that is fully compensated. 相似文献
398.
Kristopher A. Standish Tristan M. Carland Glenn K. Lockwood Wayne Pfeiffer Mahidhar Tatineni C Chris Huang Sarah Lamberth Yauheniya Cherkas Carrie Brodmerkel Ed Jaeger Lance Smith Gunaretnam Rajagopal Mark E. Curran Nicholas J. Schork 《BMC bioinformatics》2015,16(1)
Motivation
Next-generation sequencing (NGS) technologies have become much more efficient, allowing whole human genomes to be sequenced faster and cheaper than ever before. However, processing the raw sequence reads associated with NGS technologies requires care and sophistication in order to draw compelling inferences about phenotypic consequences of variation in human genomes. It has been shown that different approaches to variant calling from NGS data can lead to different conclusions. Ensuring appropriate accuracy and quality in variant calling can come at a computational cost.Results
We describe our experience implementing and evaluating a group-based approach to calling variants on large numbers of whole human genomes. We explore the influence of many factors that may impact the accuracy and efficiency of group-based variant calling, including group size, the biogeographical backgrounds of the individuals who have been sequenced, and the computing environment used. We make efficient use of the Gordon supercomputer cluster at the San Diego Supercomputer Center by incorporating job-packing and parallelization considerations into our workflow while calling variants on 437 whole human genomes generated as part of large association study.Conclusions
We ultimately find that our workflow resulted in high-quality variant calls in a computationally efficient manner. We argue that studies like ours should motivate further investigations combining hardware-oriented advances in computing systems with algorithmic developments to tackle emerging ‘big data’ problems in biomedical research brought on by the expansion of NGS technologies.Electronic supplementary material
The online version of this article (doi:10.1186/s12859-015-0736-4) contains supplementary material, which is available to authorized users. 相似文献399.