Identification and stability analysis of potential ADP-ribose modification sites on vascular endothelial growth factor (VEGF) through molecular dynamics simulation.

Post-translational modifications (PTMs) are crucial covalent processes that alter protein properties, achieved through proteolytic cleavage or addition of modifying groups like acetyl, phosphoryl, glycosyl, or methyl to amino acids. ADP-ribosylation is a reversible post-translational modification, where ADP-ribose units are covalently attached to target protein side chains. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that plays a key role in physiological and pathological conditions.

Temporal phosphoproteomic analysis of VEGF-A signaling in HUVECs: an insight into early signaling events associated with angiogenesis.

Vascular endothelial growth factor-A (VEGF-A) is one of the primary factors promoting angiogenesis in endothelial cells. Although defects in VEGF-A signaling are linked to diverse pathophysiological conditions, the early phosphorylation-dependent signaling events pertinent to VEGF-A signaling remain poorly defined. Hence, a temporal quantitative phosphoproteomic analysis was performed in human umbilical vein endothelial cells (HUVECs) treated with VEGF-A-165 for 1, 5 and 10 min.

Intermittent cold exposure upregulates regulators of cardiac mitochondrial biogenesis and function in mice.

Hypothermic conditions enhance the incidence of cardiovascular diseases due to increased blood pressure. Cold-induced adaptive thermogenesis increased mitochondrial biogenesis and function in skeletal muscles and adipocytes. Here, we studied the effect of intermittent cold exposure on the regulators of cardiac mitochondrial biogenesis, function, and its regulation by SIRT-3.

Effect of acute cold exposure on cardiac mitochondrial function: role of sirtuins.

Cardiac function depends mainly on mitochondrial metabolism. Cold conditions increase the risk of cardiovascular diseases by increasing blood pressure. Adaptive thermogenesis leads to increased mitochondrial biogenesis and function in skeletal muscles and adipocytes.

SARS-CoV-2 variants infectivity prediction and therapeutic peptide design using computational approaches.

The outbreak of severe acute respiratory coronavirus 2 (SARS-CoV-2) has created a public health emergency globally. SARS-CoV-2 enters the human cell through the binding of the spike protein to human angiotensin converting enzyme 2 (ACE2) receptor. Significant changes have been reported in the mutational landscape of SARS-CoV-2 in the receptor binding domain (RBD) of S protein, subsequent to evolution of the pandemic.

screening of the phytochemicals present in L. as the inhibitors of snake venom phospholipase A (PLA).

Millions of people suffer from snake bite envenomation, and its management is a challenge, even today. Medicinal plants have attracted the researcher's attention for their outstanding advantages in treating many diseases, including snake venom poisoning. L, is a plant popularly known for its various pharmacological effects especially, anti-snake venom property.

Hypocholesterolaemia as a prognostic factor in venomous snakebite: a retrospective study from a single centre in Kerala, India.

Background: Studies have suggested a association between serum cholesterol values and severity of envenoming. The objective of the study was to correlate the serum cholesterol levels with severity of envenoming in victims of snakebite, across snake species in our patient population.

Methods: Retrospective secondary data analysis of health records of a cohort of snakebite victims treated at Little Flower Hospital, Angamaly, Kerala during June 2006-January 2008 was performed.

Metabolite Effect on Angiogenesis: Insights from Transcriptome Analysis.

Metabolic status of the cells is important in the expression of the angiogenic phenotype in endothelial cells. Our earlier studies demonstrated the effects of metabolites such as lactate, citrate and lipoxygenase products, on VEGFA-VEGFR2 signaling pathway. Though this link between metabolite status and molecular mechanisms of angiogenesis is becoming evident, it is not clear how it affects genome-level expression in endothelial cells, critical to angiogenesis.

Pharmacogenetic variants influence vitamin K anticoagulant dosing in patients with mechanical prosthetic heart valves.

Vitamin K antagonists (VKAs) are class I oral anticoagulants that are widely prescribed following surgical heart valve implantation. The objective of this study was to quantify the relative effects of and genotypes in predicting VKA dosing. A total of 506 South Indian patients with mechanical prosthetic heart valves who were prescribed oral VKAs, such as warfarin or acenocoumarol, were genotyped.

1, 25-(OH)D protects against ER stress and miRNA dysregulation in Mus musculus neurons.

Background: The pathophysiology of neurodegenerative diseases (NDDs) is closely associated with cellular oxidative stress which can result in the accumulation of toxic proteins in the endoplasmic reticulum (ER) leading to ER stress and subsequent unfolded protein response (UPR) signaling, a mechanism that aggravate these disorders. Vitamin D has been suggested to have important neuroprotective role and its administration has been shown to reduce neuronal injury, neurotoxicity and oxidative stress in various animal systems.

Objective: The current study was undertaken to examine the effect of vitamin D on UPR in ER stress induced Mus musculus neuronal cells.

Identification of potential lead compounds against BACE1 through in-silico screening of phytochemicals of Medhya rasayana plants for Alzheimer's disease management.

Alzheimer's disease is a progressive and irreversible neurodegenerative disease that accounts for 70-80% of dementia in the elderly. According to recent clinical data, the incidence of the disease is exponentially increasing with age. Beta-site amyloid precursor protein cleaving enzyme1 (BACE1) is an important molecule involved in the pathogenesis of Alzheimer's disease due to its early role in the amyloid cascade.

screening and epitope mapping of leptospiral outer membrane protein-Lsa46.

Leptospirosis is one of the neglected diseases caused by the spirochete, . Leptospiral surface adhesion (Lsa) proteins are surface exposed outer membrane proteins present in the pathogen. It acts as laminin and plasminogen binding proteins which enable them to infect host cells.

Identification of Hub Genes and Key Pathways Associated with Anti- Resistant Glioblastoma Using Gene Expression Data Analysis.

Anti- therapy is considered to be a useful therapeutic approach in many tumors, but the low efficacy and drug resistance limit its therapeutic potential and promote tumor growth through alternative mechanisms. We reanalyzed the gene expression data of xenografts of tumors of bevacizumab-resistant glioblastoma multiforme (GBM) patients, using bioinformatics tools, to understand the molecular mechanisms of this resistance. An analysis of the gene set data from three generations of xenografts, identified as 646, 873 and 1220, differentially expressed genes (DEGs) in the first, fourth and ninth generations, respectively, of the anti--resistant GBM cells.

Potential protease inhibitors and their combinations to block SARS-CoV-2.

COVID-19, which has emerged recently as a pandemic viral infection caused by SARS-coronavirus 2 has spread rapidly around the world, creating a public health emergency. The current situation demands an effective therapeutic strategy to control the disease using drugs that are approved, or by inventing new ones. The present study examines the possible repurposing of existing anti-viral protease inhibitor drugs.

Multiple Targets Directed Multiple Ligands: An In Silico and In Vitro Approach to Evaluating the Effect of Triphala on Angiogenesis.

Angiogenesis is critical in both physiological and pathological conditions and targeting angiogenesis is a promising strategy for the development of therapies against cancer; however, cells develop resistance to anti-angiogenic therapy, necessitating a more effective strategy. Natural medicines have been used in anti-cancer therapy for many years, but the mechanisms behind these have not generally been explored. Triphala churna (THL), an Indian ayurvedic herbal formulation made from the dried fruits of three medicinal plants, is used as a herbal drug for the treatment of various diseases, including cancer.

Prioritizing rs7294 as a mirSNP contributing to warfarin dosing variability.

The role of mirSNPs in the 3'UTR of and genes that could influence warfarin dose variability via a discrete miRNA-mediated mechanism remains unexplained. Genotypic data in the 1000 Genomes dataset were analyzed for pair-wise linkage disequilibrium and allelic enrichment. MirSNP rs7294 in the 3'UTR of gene displayed varying strengths of linkage disequilibrium with rs9923231 and rs9934438 across populations, albeit consistently associated with higher warfarin dose requirements based on genome-wide association studies, meta-analysis and population-based association studies.

Temporal VEGFA responsive genes in HUVECs: Gene signatures and potential ligands/receptors fine-tuning angiogenesis.

Vascular Endothelial Growth Factor-A (VEGFA) signaling is crucial to the cellular processes involved in angiogenesis. Previously, we assembled a network of molecular reactions induced by VEGFA in human umbilical vein endothelial cell populations. Considering transcriptome as a read-out of the transcriptional and epigenomic regulatory network, we now present an analysis of VEGFA-induced temporal transcriptome datasets from 6 non-synchronized studies.

Molecular docking and dynamic studies of crepiside E beta glucopyranoside as an inhibitor of snake venom PLA2.

Alternative treatments from plant-derived small molecules for neutralizing the venom lethality in snake envenomation are prevalent now. Elephantopus scaber, a tropical plant species has been recognized for its various pharmacological activities and especially anti-snake venom property; however, the molecular basis for this property is not understood. It is reported that snake venom PLA2 is a toxic factor with pharmacological effects independent of their catalytic activity.

Expression of Leptospira membrane proteins Signal Peptidase (SP) and Leptospira Endostatin like A (Len A) in BL-21(DE3) is toxic to the host cells.

Heterologous expression of Integral Membrane Proteins (IMPs) is reported to be toxic to the host system in many studies. Even though there are reports on various concerns like transformation efficiency, growth properties, protein toxicity, inefficient expression and protein degradation in IMP overexpression, no studies so far addressed these issues in a comprehensive way. In the present study, two transmembrane proteins of the pathogen , namely Signal peptidase (SP), and Leptospira Endostatin like A (Len-A) were taken along with a cytosolic protein Hydrolase (HYD) to assess the differences in transformation efficiency, protein toxicity, and protein stability when over expressed in ().

Value of VKORC1 (-1639G>A) rs9923231 genotyping in predicting warfarin dose: A replication study in South Indian population.

Objective: Warfarin is the most commonly prescribed oral anticoagulant, although having a narrow therapeutic index and wide interindividual variability. The aim of this study was to replicate the utility of VKORC1 (-1639G>A) rs9923231 genotyping in predicting the mean daily dose and to evaluate its ability to categorize warfarin-treated patients to high-, intermediate-, or low-dose categories in the South Indian population.

Materials And Methods: A cohort of 222 warfarin-treated patients was genotyped using restriction fragment length polymorphism method.

Heterologous Expression, Purification and Characterization of an Oligopeptidase A from the Pathogen Leptospira interrogans.

Oligopeptidases are enzymes involved in the degradation of short peptides (generally less than 30 amino acids in size) which help pathogens evade the host defence mechanisms. Leptospira is a zoonotic pathogen and causes leptospirosis in mammals. Proteome analysis of Leptospira revealed the presence of oligopeptidase A (OpdA) among other membrane proteins.

Lack of association of mirSNP rs11174811 in AVPR1A gene with arterial blood pressure and hypertension in South Indian population.

Epigenetic regulation of arterial blood pressure mediated through mirSNPs in renin-angiotensin aldosterone system (RAAS) genes is a less explored hypothesis. Recently, the mirSNP rs11174811 in the 3'UTR of the AVPR1A gene was associated with higher arterial blood pressure in a large study population from the Study of Myocardial Infarctions Leiden (SMILE). The aim of the present study was to replicate the association of mirSNP rs11174811 with blood pressure outcomes and hypertension in a south Indian population.

Anti-angiogenic effect of chebulagic acid involves inhibition of the VEGFR2- and GSK-3β-dependent signaling pathways.

Inhibition of angiogenesis is a useful strategy to prevent cancer growth by targeting new vessels that grow to nourish actively proliferating tumor cells. Endothelial cells can use a number of different pathways to cause angiogenesis, and each step in these pathways can be targeted. The use of multi-targeted drugs is gaining much importance in this scenario.

Evaluating genomic DNA extraction methods from human whole blood using endpoint and real-time PCR assays.

The extraction of genomic DNA is the crucial first step in large-scale epidemiological studies. Though there are many popular DNA isolation methods from human whole blood, only a few reports have compared their efficiencies using both end-point and real-time PCR assays. Genomic DNA was extracted from coronary artery disease patients using solution-based conventional protocols such as the phenol-chloroform/proteinase-K method and a non-phenolic non-enzymatic Rapid-Method, which were evaluated and compared vis-a-vis a commercially available silica column-based Blood DNA isolation kit.

VEGF-A/VEGFR2 signaling network in endothelial cells relevant to angiogenesis.

Vascular endothelial growth factor-A (VEGF-A) is essential for endothelial cell functions associated with angiogenesis. Signal transduction networks initiated by VEGFA/VEGFR2, the most prominent ligand-receptor complex in the VEGF system, leads to endothelial cell proliferation, migration, survival and new vessel formation involved in angiogenesis. Considering its biomedical importance, we have developed the first comprehensive map of endothelial cell-specific signaling events of VEGFA/VEGFR2 system pertaining to angiogenesis.