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Randhawa, V.

Publications and source records attributed to Randhawa, V..

3 recordsLinked to original sources

Regional Differences in the Ghrelin-Growth Hormone Secretagogue Receptor Signalling System in Human Heart Disease

The hormone ghrelin and its receptor, the growth hormone secretagogue receptor (GHSR) are expressed in myocardium. GHSR binding activates signalling pathways coupled to cardiomyocyte survival and contractility. These properties have made the ghrelin-GHSR axis a candidate for a biomarker of cardiac function. The dynamics of ghrelin-GHSR are altered significantly in late stages of heart failure and cardiomyopathy, when left ventricular (LV) function is failing. We examined the relationship of GHSR with ghrelin in cardiac tissue from patients with valvular disease with no detectable changes in LV function. Biopsy samples from the LV and left atrium (LA) were obtained from 25 patients with valvular disease (of whom 13 also had coronary artery disease) and preserved LV ejection fraction, and compared control samples obtained via autopsy. Using quantitative confocal fluorescence microscopy, levels of GHSR were determined using a fluorescent peptide analog of ghrelin, Cy5-ghrelin(1-19); ghrelin, the heart failure marker natriuretic peptide type-b (BNP), and contractility marker sarcoplasmic reticulum ATPase pump (SERCA2a) were measured by immunofluorescence. A positive correlation between GHSR and ghrelin was apparent in only diseased tissue. Ghrelin and BNP significantly correlated in the LV and strongly co-localized to the same intracellular compartment in both diseased and control tissue. GHSR, ghrelin and BNP all strongly and significantly correlated with SERCA2a in the LV of diseased tissue only. Our results suggest that the dynamics of the myocardial ghrelin/GHSR axis is altered in cardiovascular disease in the absence of measurable changes in heart function, and may accompany a regional shift in endocrine programming.

molecular biology

Abundance and diversity of phages, microbial taxa and antibiotic resistance genes in the sediments of the river Ganges through metagenomic approach

In the present study, we have analyzed the metagenomic DNA from the pooled sediment sample of the river Ganges to explore the abundance and diversity of phages, microbial community and antibiotic resistance genes. Utilizing data from Illumina platform, 4174 ([~]0.0013%) reads were classified for the 285 different DNA viruses largely dominated by the group of 260 distinctive phages (3602 reads, [~]86.3%). Among all, Microcystis (782 hits), Haemophilus (403), Synechococcus (386), Pseudomonas (279), Enterococcus (232), Bacillus (196), Rhodococcus (166), Caulobacter (163), Salmonella (146), Enterobacteria (143), Mycobacterium (128), Propionibacterium (71), Erwinia (70), Ralstonia (56) phages shows the highest abundance and account for approximately 90% of the total identified phages. Additionally, we have also identified corresponding host pertaining to these phages. Mainly, Proteobacteria ([~]69.3%) dominates the microbial population structure. Primarily orders such as Caulobacterales ([~]28%), Burkholderiales ([~]13.9%), Actinomycetales ([~]13.7%), Pseudomonadales ([~]7.5%) signify the core section. Further, 21869 ([~]0.00695%) reads were classified in 20 ARG types (classes) and 240 ARGs (subtypes) among which 4 ARG types namely multidrug resistance (MDR) (12041 reads, [~]55%), bacitracin (3202 reads, [~]15%), macrolide-lincosamide-streptogramin (MLS) (1744 reads, [~]7.98%), and fosmidomycin (990 reads, [~]4.53%) has the highest abundance. Simultaneously, six resistance mechanisms were also recognized with the dominance of antibiotic efflux (72.8%, 15919 reads). The results unveil the distribution of (pro)-phages; microbial community and various ARGs in the Ganges river sediments. Further research on these identified phage(s) could be used in phage-based therapeutics against pathogenic bacteria.

genomics

The Growth Hormone Secretagogue Receptor, Ghrelin and Biochemical Signaling Molecules in Human Heart Failure

BackgroundCurrently, the early pre-clinical detection of left ventricular (LV) dysfunction is difficult as biomarkers are not specific for the cardiomyopathic process. The underlying molecular mechanisms leading to heart failure remain elusive, highlighting the need for identification of cardiac-specific markers. The growth hormone secretagogue receptor (GHSR) and its ligand ghrelin are present in cardiac tissue and are known to contribute to myocardial energetics. Here, we examined tissue ghrelin-GHSR levels as specific markers of cardiac dysfunction in patients who underwent cardiac transplantation.\n\nMethods and ResultsSamples of cardiac tissue were obtained from 10 cardiac transplant patients at the time of organ harvesting, and during serial post-transplant biopsies. Quantitative fluorescence microscopy using a novel fluorescent ghrelin analog was used to measure levels of GHSR, and immunofluorescence was used to measure levels of ghrelin, b-type natriuretic peptide (BNP) and tissue markers of cardiomyocyte contractility and growth. GHSR and ghrelin expression levels were highly variable in the explanted heart, less in the grafted heart biopsies. GHSR and ghrelin were strongly positively correlated, and both markers were negatively correlated with LV ejection fraction. Ghrelin had stronger positive correlations than BNP with the signaling markers for contractility and growth.\n\nConclusionsThese data suggest that GHSR-ghrelin have potential use as an integrated marker of cardiac dysfunction. Interestingly, tissue ghrelin appeared to be a more sensitive indicator than BNP to the biochemical processes that are characteristic of heart failure. This work allows for further use of ghrelin-GHSR to interrogate cardiac-specific biochemical mechanisms in pre-clinical stages of HF.\n\nPrecisThis study shows the relationships between GHSR, ghrelin, and signaling molecules with relation to heart function in human heart failure with tissue from diseased heart and healthy heart biopsies.

cell biology