👤 Mamdoh S Moawadh

Variants linked to the risk of ischemic stroke have been discovered through genome-wide association studies (GWASs). These variations frequently have little consequences that lack apparent biological significance. Hence, these findings demonstrate that exome sequencing can be highly relevant to stroke, even though stroke is a complex phenotype with various diseases and risk factors. In this case-control investigation, we used ARMS genotyping to investigate the distribution of polymorphic variations in genes associated with stroke susceptibility. In addition to examine the novel gene variations associated with ischemic stroke we utilized the Illumina NovaSeq 6000 platform for whole-exome sequencing (WES). Results identified 11 novel gene variants in the GSTT4 gene by targeted whole-exome sequencing, including one deletion GSTT4p.Asn232LysfsTer6, one insertion c.688₆₈₉insCG, and 9 SNVs c.699 T > C, c.701C > G, c.708G > T, c.710 T > G, c.712A > G, c.712A > G, c.718A > T, c.719G > A, c.721A > T, c.722G > T in the ischemic stroke patients. We also identified several rare, intermediate, and most common gene variants in cholesterol associated genes LDLR, LDLRAD2, LDLRAD3, APOA2, APOA3, APOA4, APOA5, and PCSK9. Also, several common gene variants were reported in MTHFR, KLF14, eNOS3, and ACE by whole-exome sequencing. Furthermore, the eNOS3-GG and eNOS3-GT genotypes were associated with susceptibility to ischemic stroke (OR = 1.95, This case-control study identified 11 novel GSTT4 variants and several known polymorphisms associated with ischemic stroke risk in Saudi patients. These findings highlight population-specific genetic factors that warrant further functional and large-scale validation. Show less

Alzheimer's disease (AD) is a significant global healthcare challenge, particularly in the elderly population. This neurodegenerative disorder is characterized by impaired memory and progressive decline in cognitive function. BACE1, a transmembrane protein found in neurons, oligodendrocytes, and astrocytes, exhibits varying levels across different neural subtypes. Abnormal BACE1 activity in the brains of individuals with AD leads to the formation of beta-amyloid proteins. The complex interplay between myelin sheath formation, BACE1 activity, and beta-amyloid accumulation suggests a critical role in understanding the pathological mechanisms of AD. The primary objective of this study was to identify molecular inhibitors that target Aβ. Structure-based virtual screening (SBVS) was employed using the MCULE database, which houses over 2 million chemical compounds. A total of 59 molecules were selected after the toxicity profiling. Subsequently, five compounds conforming to the Egan-Egg permeation predictive model of the ADME rules were selected and subjected to molecular docking using AutoDock Vina on the Mcule drug discovery platform. The top two ligands and the positive control, 5HA, were subjected to molecular dynamics simulation for five nanoseconds. Toxicity profiling, physiochemical properties, lipophilicity, solubility, pharmacokinetics, druglikeness, medicinal chemistry attributes, average potential energy, RMSD, RMSF, and Rg analyses were conducted to identify the ligand MCULE-9199128437-0-2 as a promising inhibitor of BACE1. Show less