Evaluation of Withania somnifera based supplement for immunomodulatory and antiviral properties against viral infection.

Background: Viral mediated diseases are continuously posing potent threat to human health. Nutraceuticals are being employed as novel therapeutics during viral outbreaks. MAM granules consist of Curcuma longa, Withania somnifera, and Piper nigrum, is one such patented Siddha nutraceutical supplement that has been proposed to be a therapeutic agent against viral diseases.

Decoding genetic and pathophysiological mechanisms in amyotrophic lateral sclerosis and primary lateral sclerosis: A comparative study of differentially expressed genes and implicated pathways in motor neuron disorders.

Motor Neuron Disorders (MNDs), characterized by the degradation and loss of function of motor neurons, are recognized as fatal conditions with limited treatment options and no known cure. The present study aimed to identify the pathophysiological functions and affected genes in patients with MNDs, specifically Amyotrophic Lateral Sclerosis (ALS) and Primary Lateral Sclerosis (PLS). The GSE56808 dataset comprised three sample groups: six patients diagnosed with ALS (GSM1369650, GSM1369652, GSM1369654, GSM1369656, GSM1369657, GSM1369658), five patients diagnosed with PLS (GSM1369648, GSM1369649, GSM1369653, GSM1369655, GSM1369659), and six normal controls (GSM1369642, GSM1369643, GSM1369644, GSM1369645, GSM1369646, and GSM1369647).

Comparative Analysis of Machine Learning Algorithms Evaluating the Single Nucleotide Polymorphisms of Metabolizing Enzymes with Clinical Outcomes Following Intravenous Paracetamol in Preterm Neonates with Patent Ductus Arteriosus.

Aims: Pharmacogenomics has been identified to play a crucial role in determining drug response. The present study aimed to identify significant genetic predictor variables influencing the therapeutic effect of paracetamol for new indications in preterm neonates.

Background: Paracetamol has recently been preferred as a first-line drug for managing Patent Ductus Arteriosus (PDA) in preterm neonates.

Identification of potential circadian genes and associated pathways in colorectal cancer progression and prognosis using microarray gene expression analysis.

Colorectal cancer (CRC) is third cancer causing death in the world. CRC is associated with disrupting the circadian rhythm (CR), closely associating the CRC progression and the dysregulation of genes involved in the biological clock. In this study, we aimed to understand the circadian rhythm changes in patients diagnosed with CRC.

Molecular characterization of circadian gene expression and its correlation with survival percentage in colorectal cancer patients.

Colorectal cancer (CRC) is a form of cancer characterized by many symptoms and readily metastasizes to different organs in the body. Circadian rhythm is one of the many processes that is observed to be dysregulated in CRC-affected patients. In this study, we aim to identify the dysregulated physiological processes in CRC-affected patients and correlate the expression profiles of the circadian clock genes with CRC-patients' survival rates.

Elucidating the functional impact of G137V and G144R variants in Maroteaux Lamy's Syndrome by Molecular Dynamics Simulation.

Mucopolysaccharidoses VI (Maroteaux Lamy syndrome) is a metabolic disorder due to the loss of enzyme activity of N-acetyl galactosamine-4-sulphatase arising from mutations in the ARSB gene. The mutated ARSB is the origin for the accumulation of GAGs within the lysosome leading to severe growth deformities, causing lysosomal storage disease. The main focus of this study is to identify the deleterious variants by applying bioinformatics tools to predict the conservation, pathogenicity, stability, and effect of the ARSB variants.

Computational Structural Validation of Mutations and Evaluation of Machine Learning Algorithms in Predicting the Therapeutic Outcomes of Warfarin.

Aim: The study aimed to identify the key pharmacogenetic variable influencing the therapeutic outcomes of warfarin using machine learning algorithms and bioinformatics tools.

Background: Warfarin, a commonly used anticoagulant drug, is influenced by cytochrome P450 (CYP) enzymes, particularly . MLAs have been identified to have great potential in personalized therapy.

A new horizon in the phosphorylated sites of AGA: the structural impact of C163S mutation in aspartylglucosaminuria through molecular dynamics simulation.

Aspartylglucosaminuria (AGU) is a lysosomal storage disorder caused by insufficient aspartylglucosaminidase (AGA) activity leading to chronic neurodegeneration. We utilized the PhosphoSitePlus tool to identify the AGA protein's phosphorylation sites. The phosphorylation was induced on the specific residue of the three-dimensional AGA protein, and the structural changes upon phosphorylation were studied molecular dynamics simulation.

Determination of potential combination of non-β-lactam, β-lactam, and β-lactamase inhibitors/β-lactam enhancer against class D oxacillinases producing Acinetobacter baumannii: Evidence from in-vitro, molecular docking and dynamics simulation.

Carbapenem-resistant Acinetobacter baumannii, a predominant nosocomial pathogen in hospitals of intensive care units, is associated with bacteremia and ventilator-associated pneumonia with a high-risk mortality rate. To increase the effectiveness of the β-lactam (BL) antibiotics, the use of β-lactamase inhibitors (BLI) acts as a booster when given in combination with BL antibiotics. To this aspect, we selected BL antibiotics of cefiderocol, cefepime, non-BL antibiotic eravacycline, BLI of durlobactam, avibactam, and a β-lactam enhancer (BLE) of zidebactam.

Unravelling the Relacatib activity against the CTSK proteins causing pycnodysostosis: a molecular docking and dynamics approach.

Pycnodysostosis is an atypical autosomal recessive condition of Lysosomal storage disorder that originated due to the deficit of the enzyme Cathepsin K which is vital for normal osteoclast action in bone resorption. Abnormal degradation of type 1 collagen and accumulation of toxic undigested collagen fibers in lysosomes of the osteoclast cells resulting in high bone density, brittle bones, and a short stature is caused in CTSK protein-carrying individuals. The broad aim of this study is to identify the most significant variant through various computational pipelines.

Computational screening and structural analysis of Gly201Arg and Gly201Asp missense mutations in human cyclin-dependent kinase 4 protein.

The regulatory proteins, cyclins, and cyclin-dependent kinases (CDKs) control the cell cycle progression. CDK4 gene mutations are associated with certain cancers such as melanoma, breast cancer, and rhabdomyosarcoma. Therefore, understanding the mechanisms of cell cycle control and cell proliferation is essential in developing cancer treatment regimens.

The targeted next-generation sequence revealed SMAD4, AKT1, and TP53 mutations from circulating cell-free DNA of breast cancer and its effect on protein structure - A computational approach.

Breast cancer biomarkers that detect marginally advanced stages are still challenging. The detection of specific abnormalities, targeted therapy selection, prognosis, and monitoring of treatment effectiveness over time are all made possible by circulating free DNA (cfDNA) analysis. The proposed study will detect specific genetic abnormalities from the plasma cfDNA of a female breast cancer patient by sequencing a cancer-related gene panel (MGM455 - Oncotrack Ultima), including 56 theranostic genes (SNVs and small INDELs).

Elucidating the mechanism of antimicrobial resistance in Mycobacterium tuberculosis using gene interaction networks.

Antimicrobial resistance (AMR) in microorganisms is an urgent global health threat. AMR of Mycobacterium tuberculosis is associated with significant morbidity and mortality. It is of great importance to underpin the resistance pathways involved in the mechanisms of AMR and identify the genes that are directly involved in AMR.

Identification of dysregulated canonical pathways associated with pathogenesis and progression of Amyotrophic Lateral Sclerosis-An integrated bioinformatics approach.

The mechanisms responsible for the pathogenesis and progression of Amyotrophic Lateral Sclerosis (ALS) remain poorly understood, making the diagnosis of ALS challenging. We aimed to find the novel gene biomarkers via computationally analyzing microarray expression studies, in three different cell lineages, namely myotube cells, astrocyte cells and oligodendrocyte cells. Microarray gene expression profiles were obtained and analyzed for three cell types: myotube cell lineage (GSE122261), astrocyte, and oligodendrocyte cell lineage (GSE87385).

Designing, Synthesis, and Anti-Breast Cancer Activity of a Series of New Quinazolin-4(1H)-one Derivatives.

The inhibition of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) protein could be a promising treatment for breast cancer. In this regard, docking studies were accomplished on various functionalized organic molecules. Among them, several derivatives of quinazolin-4(1H)-one exhibited anti-breast cancer activity and satisfied the drug likeliness properties.

Computational and structural investigation of Palmitoyl-Protein Thioesterase 1 (PPT1) protein causing Neuronal Ceroid Lipofuscinoses (NCL).

The Neuronal Ceroid Lipofuscinoses (NCL) are a group of progressive neurodegenerative disorders, associated with 14 Ceroid Lipofuscinosis Neuronal genes (CLN1-14). The mutations in the Palmitoyl-Protein Thioesterase 1 (PPT1) protein serve as one of the major reasons for the causative of NCL. The PPT1 involves degrading and modifying cysteine residues in proteins or peptides by removing thioester-linked fatty acyl groups like palmitate prefers acyl chains of 14-18 carbons in length.

Deciphering the effect of mutations in MMAA protein causing methylmalonic acidemia-A computational approach.

Methylmalonic acidemia (MMA) is a rare genetic disorder affecting multiple body systems. We aimed to investigate the pathogenic mutations in MMAA that are associated with isolated methylmalonic acidemia to identify the structural behavior of MMAA upon mutation. The algorithms such as PredictSNP, iStable, ConSurf, and Align GVGD were employed to analyze the consequence of the mutations.

Understanding the activating mechanism of the immune system against COVID-19 by Traditional Indian Medicine: Network pharmacology approach.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmissions are occurring rapidly; it is raising the alarm around the globe. Though vaccines are currently available, the evolution and mutations in the SARS-CoV-2 threaten available vaccines' significance. The drugs are still undergoing clinical trials, and certain medications are approved for "emergency use" or as an "off-label" drug during the pandemic.

A computational overview on phylogenetic characterization, pathogenic mutations, and drug targets for Ebola virus disease.

The World Health Organization declared Ebola virus disease (EVD) as the major outbreak in the 20th century. EVD was first identified in 1976 in South Sudan and the Democratic Republic of the Congo. EVD was transmitted from infected fruit bats to humans via contact with infected animal body fluids.

Investigation of nonsynonymous mutations in the spike protein of SARS-CoV-2 and its interaction with the ACE2 receptor by molecular docking and MM/GBSA approach.

COVID-19 is an infectious and pathogenic viral disease caused by SARS-CoV-2 that leads to septic shock, coagulation dysfunction, and acute respiratory distress syndrome. The spreading rate of SARS-CoV-2 is higher than MERS-CoV and SARS-CoV. The receptor-binding domain (RBD) of the Spike-protein (S-protein) interacts with the human cells through the host angiotensin-converting enzyme 2 (ACE2) receptor.

A systemic approach to explore the mechanisms of drug resistance and altered signaling cascades in extensively drug-resistant tuberculosis.

Background And Aim: The persistence of extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis (MTB) continue to pose a significant challenge to the treatment and control of tuberculosis infections worldwide. XDR-MTB strains exhibit resistance against first-line anti-TB drugs, fluoroquinolones, and second-line injectable drugs. The mechanisms of drug resistance of MTB remains poorly understood.

An integrative analysis to distinguish between emphysema (EML) and alpha-1 antitrypsin deficiency-related emphysema (ADL)-A systems biology approach.

Lung Emphysema is an abnormal enlargement of the air sacs followed by the destruction of alveolar walls without any prominent fibrosis. This study primarily identifies the differentially expressed genes (DEGs), interactions between them, and their significant involvement in the activated signaling cascades. The dataset with ID GSE1122 (five normal lung tissue samples, five of usual emphysema, and five of alpha-1 antitrypsin deficiency-related emphysema) from the gene expression omnibus (GEO) was analyzed using the GEO2R tool.

Effective utilisation of influence maximization technique for the identification of significant nodes in breast cancer gene networks.

Background: Identifying the most important genes in a cancer gene network is a crucial step in understanding the disease's functional characteristics and finding an effective drug.

Method: In this study, a popular influence maximization technique was applied on a large breast cancer gene network to identify the most influential genes computationally. The novel approach involved incorporating gene expression data and protein to protein interaction network to create a customized pruned and weighted gene network.