👤 Irshad Ahmad Wani

Coronary artery disease (CAD) is a multifactorial disorder influenced by both genetic and clinical risk factors. Lipid metabolism genes such as apolipoprotein B(APOB) (rs515135) and proprotein convertase subtilisin/kexin type 9 (PCSK9)(rs505151), have been associated with susceptibility to CAD. Study investigates the potential role of these genetic polymorphisms with risk of CAD in the Indian population. A case-control study including 150 CAD cases and 150 controls. Angiographically proven Cases were recruited from the Cardiology Unit, Department of Medicine, Era's Lucknow Medical College. Genotyping was done using specific primers and restriction digestion; statistical analysis included t-tests, odds ratios, and haplotype analysis. CAD cases(mean age 49.93   ±   9.13 years) had higher serum cholesterol and VLDL but lower systolic and diastolic BP compared to controls (mean age 56.47   ±   9.39 years). The APOB G allele showed a significant protective effect against CAD (OR: 0.431, The APOB G allele may serve as a protective factor against CAD, highlighting its potential role in genetic screening for lower disease risk. Further large-scale studies are required to confirm these findings. Show less

Eichhornia crassipes (Mart.) Solms, also known as Pontederia crassipes Mart, has traditionally been used for its sedative, antipsychotic, and memory-enhancing properties. However, its effects against Alzheimer's disease (AD) remain unexplored. Therefore, this study aimed to investigate the in vitro anti-AD properties of methanol (MEECF), ethanol (EEECF), and ethyl acetate (EAEECF) extracts of E. crassipes flowers and to identify potential multi-modal anti-AD phytocompounds using computational drug discovery targeting acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and beta-site amyloid precursor protein cleaving enzyme-1 (BACE-1). Initially, 204 phytocompounds were metabolically annotated through GC-MS analysis of the extracts, and their functional groups and chemical nature were identified using PPS and FT-IR analysis, respectively. Molecular docking identified two hit phytocompounds (CID 4970, fumarine, and CID 106962, cyclopentanemethanamine, 5-amino-2,2,4-trimethyl-) in MEECF and EEECF, which exhibited higher binding affinities toward all targets compared to the control drug donepezil (-5.721 kcal/mol). Further molecular analysis revealed favorable pharmacokinetics, drug-likeness, and no toxicity for these two phytocompounds. Molecular dynamics simulation confirmed their binding stability to the active sites of AChE, BChE, and BACE-1, exhibiting multi-modal inhibitory activity. MEECF, EEECF, and EAEECF showed concentration-dependent antioxidant and AChE and BChE inhibition, supporting the in silico results regarding oxidative stress and cholinergic pathways. These findings suggest the anti-AD potential of E. crassipes flowers, with fumarine and cyclopentanemethanamine, 5-amino-2, 2, 4-trimethyl- identified as multi-modal inhibitors of AChE, BChE, and BACE-1. However, further in vivo research is required to comprehensively evaluate their efficacy in combating AD. Show less

Colorectal cancer is (CRC) one of the leading causes of mortality and morbidity. Various genetic factors have been reported to be involved in the development of colorectal cancers including Axin gene. Axin, a major scaffold protein, plays an important role in various bio signaling pathways. We aim to study mutational pattern of Axin gene in colorectal cancer patients of Kashmiri population. The paired tumor and adjacent normal tissue specimens of 50 consecutive patients with CRC were used in our study. The DNA preparations were evaluated for the occurrence of Axin 1 and Axin 2 gene mutations by direct DNA sequencing. We analyzed exon 1a, 1b, 1c, 2, 4, 6, and 10 of Axin 1 and exon 7 of Axin 2. In this study, we found a novel mutation of G>T (GCT>TCT) transversion in exon 7 of Axin 2 gene at codon G695T (p.alanine > serine) at a frequency of 6% (3/50). In the same exon of Axin 2 gene a single nucleotide polymorphism (SNP) was detected in codon L688L (CCT>CTT) at a frequency of 36% (18/50). In exon 1c of Axin 1 a SNP was detected at codon D726D (GAT>GAC) at a frequency of 62.5% (31/50). Both the SNPs were synonymous hence do not lead to change of amino acid. Although Axin 1 and Axin 2 gene mutations have been found to be involved in the development of colorectal cancers, it seems to be a relatively rare event in Kashmiri population. However, an interesting finding of this study is the novelty of Axin 2 gene mutations which may be a predisposing factor in ethnic Kashmiri population to CRC. Show less