Biology subjects

Shalimar,

Publications and source records attributed to Shalimar,.

3 recordsLinked to original sources

bioRxiv2023

Conserved Cardiovascular Network: Bioinformatics Insights into Genes and Pathways for Establishing Caenorhabditis elegans as an Animal Model for Cardiovascular Diseases.

Cardiovascular disease (CVD) is a collective term for disorders of the heart and blood vessels. The molecular events and biochemical pathways associated with CVD are difficult to study in clinical settings on patients and in vitro conditions. Animal models play a pivotal and indispensable role in cardiovascular disease (CVD) research. Caenorhabditis elegans, a nematode species, has emerged as a prominent experimental organism widely utilised in various biomedical research fields. However, the specific number of CVD-related genes and pathways within the C. elegans genome remains undisclosed to date, limiting its in-depth utilisation for investigations. In the present study, we conducted a comprehensive analysis of genes and pathways related to CVD within the genomes of humans and C. elegans through a systematic bioinformatic approach. A total of 1113 genes in C. elegans orthologous to the most significant CVD-related genes in humans were identified, and the GO terms and pathways were compared to study the pathways that are conserved between the two species. In order to infer the functions of CVD-related orthologous genes in C. elegans, a PPI network was constructed. Orthologous gene PPI network analysis results reveal the hubs and important KRs: pmk-1, daf-21, gpb-1, crh-1, enpl-1, eef-1G, acdh-8, hif-1, pmk-2, andaha-1 in C. elegans. Modules were identified for determining the role of the orthologous genes at various levels in the created network. We also identified 9 commonly enriched pathways between humans and C. elegans linked with CVDs that include autophagy (animal), the ErbB signalling pathway, the FoxO signalling pathway, the MAPK signalling pathway, ABC transporters, the biosynthesis of unsaturated fatty acids, fatty acid metabolism, glutathione metabolism, and metabolic pathways. This study provides the first systematic genomic approach to explore the CVD-associated genes and pathways that are present in C. elegans, supporting the use of C. elegans as a prominent animal model organism for cardiovascular diseases.

bioinformatics↗

bioRxiv2022

Human endogenous retrovirus-R envelope is a host restriction factor against severe acute respiratory syndrome-coronavirus-2

Coronavirus induced disease-19 (COVID-19), caused by the SARS-CoV-2 remains a major global health challenge. Human endogenous retroviruses (HERVs) represent retroviral elements that got integrated into the ancestral human genome. HERVs are important in development and diseases, including cancer, inflammation and viral infections. Here, we analyzed the expression of several HERVs in SARS-CoV-2 infected cells and observed increased activity of HERV-E, HERV-V, HERV-FRD, HERV-MER34, HERV-W and HERV-KHML2. In contrast, HERV-R-envelope was downregulated in cell-based models and COVID-19 patient PBMCs. HERV-R overexpression inhibited SARS-CoV-2 replication, suggesting its antiviral action. Further studies demonstrated the role of extracellular signal-regulated kinase (ERK) in regulating HERV-R antiviral activity. Cross-talk between the ERK and p38 MAPK controls HERV-R envelope synthesis, which in turn modulates the replication of SARS-CoV-2. These findings establish the importance of HERV-R envelope as a host restriction factor against SARS-CoV-2 and illustrate the advantage of integration and evolutionary maintenance of retroviral-elements in the human genome.

microbiology↗

bioRxiv2020

Chronic exposure to IL6 leads to deregulation of glycolysis and fat accumulation in the zebrafish liver

BACKGROUND AND AIMS Inflammation is a constant in Non-Alcoholic Fatty Liver Disease (NAFLD) and is usually considered a consequence. We propose that inflammation can be a cause for NAFLD. Obesity is strongly associated with (NAFLD), but not always. NAFLD in lean individuals is more common in certain populations, especially Asian-Indians. Lean healthy Indians also have a higher basal circulating IL6 suggesting a link with inflammation. We propose that inflammation-induced fatty liver could be relevant for studying obesity-independent NAFLD. Commonly used high-fat diet-induced NAFLD animal models are not ideal for testing this hypothesis.APPROACH AND RESULTS In this study we used a transgenic zebrafish with chronic systemic overexpression of human IL6 (IL6-OE) and found accumulation of triglyceride in the liver. We performed comparative transcriptomics and proteomics on the IL6-OE liver and found an expression signature distinct from the diet-based NAFLD models. We discovered a deregulation of glycolysis/gluconeogenesis pathway, especially a robust down regulation of the glycolytic enzyme aldolase b in the IL6-OE liver. Metabolomics of the IL6-OE liver showed accumulation of hexose monophosphates and their derivatives, which can act as precursors for triglyceride synthesis. Patients with the genetic disease Hereditary Fructose Intolerance (HFI) caused by ALDOLASE B deficiency also have a higher propensity to develop fatty liver disease.CONCLUSIONS Our study demonstrates a causative role for inflammation in intrahepatic lipid accumulation. Further, our results suggest that IL6-driven repression of glycolysis/gluconeogenesis, specifically aldolase b, may be a novel mechanism for development of fatty liver, especially in obesity-independent NAFLD.Competing Interest StatementThe authors have declared no competing interest.List of AbbreviationsNAFLDNon-Alcoholic Fatty Liver DiseaseIL6Interleukin 6OEOverexpressionHFIHigh Fructose IntoleranceNASHNon-Alcoholic SteatohepatitisSLESystemic Lupus ErythematosusIBDInflammatory Bowel DiseaseRARheumatoid ArthritisHFDHigh Fat dietqRT-PCRQuantitative Real-Time Polymerase Chain ReactionPPARPeroxisome Proliferator-Activated ReceptorDHAPDihydroxyacetone PhosphateView Full Text

molecular biology↗