Translational Health Science and Technology Institute

About: Translational Health Science and Technology Institute is a government organization based out in Gurgaon, India. It is known for research contribution in the topics: Population & Virus. The organization has 467 authors who have published 861 publications receiving 15251 citations.

Emergence of Members of TRAF and DUB of Ubiquitin Proteasome System in the Regulation of Hypertrophic Cardiomyopathy

Abstract: The ubiquitin proteasome system (UPS) plays an imperative role in many critical cellular processes, frequently by mediating the selective degradation of misfolded and damaged proteins and also by playing a non-degradative role especially important as in many signaling pathways. Over the last three decades, accumulated evidence indicated that UPS proteins are primal modulators of cell cycle progression, DNA replication, and repair, transcription, immune responses, and apoptosis. Comparatively, latest studies have demonstrated a substantial complexity by the UPS regulation in the heart. In addition, various UPS proteins especially ubiquitin ligases and proteasome have been identified to play a significant role in the cardiac development and dynamic physiology of cardiac pathologies such as ischemia/reperfusion injury, hypertrophy, and heart failure. However, our understanding of the contribution of UPS dysfunction in the plausible development of cardiac pathophysiology and the complete list of UPS proteins regulating these afflictions is still in infancy. The recent emergence of the roles of TNF receptor-associated factor (TRAFs) and deubiquitinating enzymes (DUBs) superfamily in hypertrophic cardiomyopathy has enhanced our knowledge. In this review, we have mainly compiled the TRAF superfamily of E3 ligases and few DUBs proteins with other well-documented E3 ligases such as MDM2, MuRF-1, Atrogin-I, and TRIM 32 that are specific to myocardial hypertrophy. In this review, we also aim to highlight their expression profile following physiological and pathological stimulation leading to the onset of hypertrophic phenotype in the heart that can serve as biomarkers and the opportunity for the development of novel therapies.

Biodegradation of toxic dyes: a comparative study of enzyme action in a microbial system

Abstract: Dyes used in textile industries are a major source of pollution. A wide range of untreated waste is generated and evacuated as effluents into the environment. This waste contains inorganic and organic pollutants and accumulation of these elements may cause deteriorations of human health and harm to the environment. The textile industry utilizes 50% of dyes, of which azo dyes comprise the largest proportion. Azo dyes and various other synthetic dyes, due to their persistent natures, have been reported to be mutagenic in nature. Degradation of toxic dyes can be achieved by physical, chemical, and biological processes, but the use of microbes for biological treatment is safe, economical, and eco-friendly. Decolorization of dyes takes place either by adsorption on the microbial biomass or by enzymatic degradation, thus converting it into less toxic substances. Thus an efficient degradation of toxic synthetic dyes can be achieved by mixed action or consortia of both bacteria and fungi.

Genetic and virulence characterisation of Vibrio parahaemolyticus isolated from Indian coast.

Abstract: V. parahaemolyticus is autochthonous to the marine environment and causes seafood-borne gastroenteritis in humans. Generally, V. parahaemolyticus recovered from the environment and/or seafood is thought to be non-pathogenic and the relationship between environmental isolates and acute diarrhoeal disease is poorly understood. In this study, we explored the virulence potential of environmental V. parahaemolyticus isolated from water, plankton and assorted seafood samples collected from the Indian coast. Twenty-two V. parahaemolyticus isolates from seafood harboured virulence associated genes encoding the thermostable-direct haemolysin (TDH), TDH-related haemolysin (TRH), and Type 3 secretion systems (T3SS) and 95.5% of the toxigenic isolates had pandemic strain attributes (toxRS/new+). Nine serovars, with pandemic strain traits were newly identified and an O4:K36 tdh−trh+V. parahaemolyticus bearing pandemic marker gene was recognised for the first time. Results obtained by reverse transcription PCR showed trh, T3SS1 and T3SS2β to be functional in the seafood isolates. Moreover, the environmental strains were cytotoxic and could invade Caco-2 cells upon infection as well as induce changes to the tight junction protein, ZO-1 and the actin cytoskeleton. Our study provides evidence that environmental isolates of V. parahaemolyticus are potentially invasive and capable of eliciting pathogenic characteristics typical of clinical strains and present a potential health risk. We also demonstrate that virulence of this pathogen is highly complex and hence draws attention for the need to investigate more reliable virulence markers in order to distinguish the environmental and clinical isolates, which will be crucial for the pathogenomics and control of this pathogen.

Corrigendum: CitE Enzymes Are Essential for Mycobacterium tuberculosis to Establish Infection in Macrophages and Guinea Pigs.

Abstract: Bacterial citrate lyase activity has been demonstrated in various eukaryotes, bacteria and archaea, underscoring their importance in energy metabolism of the cell. While the bacterial citrate lyase comprises of three different subunits, M. tuberculosis genome lacks CitD and CitF subunits of citrate lyase complex but encodes for 2 homologs of CitE subunits, Rv2498c and Rv3075c. Using temperature sensitive mycobacteriophages, we were able to generate both single and double citE mutant strains of M. tuberculosis. The survival experiments revealed increased susceptibility of the double mutant strain to oxidative stress in comparison to the parental strain. Also, simultaneous deletion of both citE1 and citE2 in M. tuberculosis genome also resulted in impairment of intracellular replication in macrophages. The double mutant strain displayed reduced growth in lungs and spleens of guinea pigs. This is the first study demonstrating that M. tuberculosis critically requires CitE subunits of citrate lyase for pathogenesis. Taken together, these findings position these enzymes as potential targets for development of anti-tubercular small molecules.

Allylmethylsulfide, a Sulfur Compound Derived from Garlic, Attenuates Isoproterenol-Induced Cardiac Hypertrophy in Rats.

Abstract: Allylmethylsulfide (AMS) is a novel sulfur metabolite found in the garlic-fed serum of humans and animals. In the present study, we have observed that AMS is safe on chronic administration and has a potential antihypertrophic effect. Chronic administration of AMS for 30 days did not cause any significant differences in the body weight, electrocardiogram, food intake, serum biochemical parameters, and histopathology of vital organs. Single-dose pharmacokinetics of AMS suggests that AMS is rapidly metabolized into Allylmethylsulfoxide (AMSO) and Allylmethylsulfone (AMSO2). To evaluate the efficacy of AMS, cardiac hypertrophy was induced by subcutaneous implantation of ALZET® osmotic minipump containing isoproterenol (~5 mg/kg/day), cotreated with AMS (25 and 50 mg/kg/day) and enalapril (10 mg/kg/day) for 2 weeks. AMS and enalapril significantly reduced cardiac hypertrophy as studied by the heart weight to body weight ratio and mRNA expression of fetal genes (ANP and β-MHC). We have observed that TBARS, a parameter of lipid peroxidation, was reduced and the antioxidant enzymes (glutathione, catalase, and superoxide dismutase) were improved in the AMS and enalapril-cotreated hypertrophic hearts. The extracellular matrix (ECM) components such as matrix metalloproteinases (MMP2 and MMP9) were significantly upregulated in the diseased hearts; however, with the AMS and enalapril, it was preserved. Similarly, caspases 3, 7, and 9 were upregulated in hypertrophic hearts, and with the AMS and enalapril treatment, they were reduced. Further to corroborate this finding with in vitro data, we have checked the nuclear expression of caspase 3/7 in the H9c2 cells treated with isoproterenol and observed that AMS cotreatment reduced it significantly. Histopathological investigation of myocardium suggests AMS and enalapril treatment reduced fibrosis in hypertrophied hearts. Based on our experimental results, we conclude that AMS, an active metabolite of garlic, could reduce isoproterenol-induced cardiac hypertrophy by reducing oxidative stress, apoptosis, and stabilizing ECM components.