Release of GLP-1 and PYY in response to the activation of G protein-coupled bile acid receptor TGR5 is mediated by Epac/PLC-ε pathway and modulated by endogenous H2S

Activation of plasma membrane TGR5 receptors in enteroendocrine cells by bile acids is known to regulate gastrointestinal secretion and motility and glucose homeostasis. The endocrine functions of the gut are modulated by microenvironment of the distal gut predominantly by sulfur-containing bacteria of the microbiota that produce H2S. However, the mechanisms involved in the release of peptide hormones, GLP-1 and PYY in response to TGR5 activation by bile acids and the effect of H2S on bile acid-induced release of GLP-1 and PYY are unclear. In the present study, we have identified the signaling pathways activated by the bile acid receptor TGR5 to mediate GLP-1 and PYY release and the mechanism of inhibition of their release by H2S in enteroendocrine cells. The TGR5 ligand oleanolic acid (OA) stimulated Gs and cAMP formation, and caused GLP-1 and PYY release. OA-induced cAMP formation and peptide release were blocked by TGR5 siRNA. OA also caused an increase in PI hydrolysis and intracellular Ca2+. Increase in PI hydrolysis was abolished in cells transfected with PLC-ε siRNA. 8-pCPT-2’-O-Me-cAMP, a selective activator of Epac, stimulated PI hydrolysis, and GLP-1 and PYY release. L-Cysteine, which activates endogenous H2S producing enzymes cystathionine--lyase and cystathionine--synthase, and NaHS and GYY4137, which generate H2S, inhibited PI hydrolysis and GLP-1 and PYY release in response to OA or 8-pCPT-2’-O-Me-cAMP. Propargylglycine, an inhibitor of CSE, reversed the effect of L-cysteine on PI hydrolysis and GLP-1 and PYY release. We conclude: i) activation of Gs-coupled TGR5 receptors causes stimulation of PI hydrolysis, and release of GLP-1 and PYY via a PKA-independent, cAMP-dependent mechanism involving Epac/PLC-/Ca2+ pathway, and ii) H2S has potent inhibitory effects on GLP-1 and PYY release in response to TGR5 activation, and the mechanism involves inhibition of PLC-/Ca2+ pathway

Current trends and advances of Quorum sensing inhibitors and their biotechnological applications

255-280Serious setbacks were witnessed in shrimp farming, the food industry, and the ship industry during the past three decades primarily due to bacterial pathogens that coordinate by quorum sensing (QS). The influence of bacterial pathogens utilizing QS. The impact of QS cell communication on public health is extremely disastrous in terms of spread, spectrum, apart from their economic impact. The overuse of antibiotics has increased drastically to battle bacterial infections, including tons of antibiotics are distributed in the biosphere. Due to the indiscriminate use of antibiotics, multiple antibiotic-resistant strains have emerged, as the antibiotic resistance genes are being transferred to bacteria of terrestrial animals, humans, and pathogens. The increased public awareness of the negative drawbacks caused by over-exposure to antibiotics, also the emergence of multiple antibiotic resistant pathogenic stains led to the search for alternatives and unique solutions. One such unconventional, promising method is the interruption of bacterial cell to cell communication, which is currently termed QS inhibition. Now-a-days, QS inhibition is the potential objective for antimicrobial chemotherapy. This review summarizes the regulatory factors that attenuate the QS activities of deadly pathogens and discusses their distinctive characteristics. Improving awareness of the natural roles of regulatory elements might be useful in unveiling inhibitor applications to understand how QS is inhibited in pathogenic bacteria by different QS inhibitors

A Comprehensive Review on the Regulatory Action of TRP Channels: A Potential Therapeutic Target for Nociceptive Pain

The transient receptor potential (TRP) superfamily of ion channels in humans comprises voltage-gated, non-selective cation channels expressed both in excitable as well as non-excitable cells. Four TRP channel subunits associate to create functional homo- or heterotetramers that allow the influx of calcium, sodium, and/or potassium. These channels are highly abundant in the brain and kidney and are important mediators of diverse biological functions including thermosensation, vascular tone, flow sensing in the kidney and irritant stimuli sensing. Inherited or acquired dysfunction of TRP channels influences cellular functions and signaling pathways resulting in multifaceted disorders affecting skeletal, renal, cardiovascular, and nervous systems. Studies have demonstrated the involvement of these channels in the generation and transduction of pain. Based on the multifaceted role orchestrated by these TRP channels, modulation of the activity of these channels presents an important strategy to influence cellular function by regulating intracellular calcium levels as well as membrane excitability. Therefore, there has been a remarkable pharmaceutical inclination toward TRP channels as therapeutic interventions. Several candidate drugs influencing the activity of these channels are already in the clinical trials pipeline. The present review encompasses the current understanding of TRP channels and TRP modulators in pain and pain management

Multifarious Beneficial Effect of Nonessential Amino Acid, Glycine: A Review

Glycine is most important and simple, nonessential amino acid in humans, animals, and many mammals. Generally, glycine is synthesized from choline, serine, hydroxyproline, and threonine through interorgan metabolism in which kidneys and liver are the primarily involved. Generally in common feeding conditions, glycine is not sufficiently synthesized in humans, animals, and birds. Glycine acts as precursor for several key metabolites of low molecular weight such as creatine, glutathione, haem, purines, and porphyrins. Glycine is very effective in improving the health and supports the growth and well-being of humans and animals. There are overwhelming reports supporting the role of supplementary glycine in prevention of many diseases and disorders including cancer. Dietary supplementation of proper dose of glycine is effectual in treating metabolic disorders in patients with cardiovascular diseases, several inflammatory diseases, obesity, cancers, and diabetes. Glycine also has the property to enhance the quality of sleep and neurological functions. In this review we will focus on the metabolism of glycine in humans and animals and the recent findings and advances about the beneficial effects and protection of glycine in different disease states

Feasibility and Safety of Peripheral Intravenous Administration of Vasopressor Agents in Resource-limited Settings

Vasopressors are conventionally administered through a central venous catheter (CVC) and not through a peripheral venous catheter (PVC) since the latter is believed to be associated with increased risk of extravasation. Placement of a CVC requires suitably trained personnel to be on hand, and in resource-limited settings, this requirement may delay placement. Because of this and in cases where suitably trained personnel are not immediately available, some clinicians may be prompted to utilise a PVC for infusing vasopressors. The objective of this study is to assess the feasibility and safety of vasopressors administered through a PVC

A study on the inhibition of oxidative stress, inflammation and apoptosis by Terminalia arjuna against acetaminophen-induced hepatotoxicity in wistar albino rats

The liver in the process of detoxifying chemicals is prone to injury due to overuse of therapeutic drugs like Acetaminophen and the liver cell death is largely inflammatory mediated. The present study aims to find out the effect of Terminalia arjuna (TA) bark against acetaminophen (APAP) induced liver cell death by testing the antioxidant levels, oxidative stress, and inflammation and apoptosis markers. In the present study, five groups (6 animals in each group) were considered for the experimental animal study. Control group, Acetaminophen (APAP) group, N-Acetylcysteine (NAC) group, Terminalia arjuna (TA) 250 mg/kg and Terminalia arjuna (TA) 500 mg/kg group. The antioxidant Glutathione (GSH), Lipid peroxidation (MDA), Interleukin 1β (IL-1β) levels, caspase-9 levels, and Protein kinase B (P-AKT) gene expression levels were assessed. The results indicated that pre-treated animals with Terminalia arjuna high dose bark had shown increased Glutathione (GSH) levels, thinned out malondialdehyde (MDA) levels, Inhibited IL-1β level, Caspase-9 levels and elevated gene expression level of P-AKT to regulate the cell signaling pathway. Hence, the study indicates that a high dose of TA 500 mg/kg ameliorated acetaminophen-induced hepatotoxicity

Biliary Cystadenomas: A Case for Complete Resection

Introduction and Objective. Biliary cystadenoma is a rare benign neoplasm of the liver with less than 200 cases being reported allover the world. We report a series of 13 cases highlighting the radiological findings and problems related to its management. Materials and Methods. Records of thirteen patients who underwent surgery for biliary cystadenomas, between March 2006 and October 2011, were reviewed retrospectively. Results. Majority of the patients were females (11 out of 13), with a median age of 46 (23–65) years. The most frequent symptom was abdominal pain (92%). Seven patients had presented with history of previous surgery for liver lesions. Five patients had presented with recurrence after partial resection for a suspected hydatid cyst and two after surgery for presumed simple liver cyst. Ten of the 13 patients had complete resection of the cyst with enucleation in 3 patients, 2 of whom in addition required T-tube drainage of the bile duct. There has been no recurrence during the follow-up period ranging from 3 months to 5 years. Conclusion. Biliary cystadenoma must be differentiated from other benign cysts. Hepatic resection or cyst enucleation is the recommended treatment option