👤 Ghulam Nabi

Alzheimer's disease (AD) is a progressive and largely incurable neurodegenerative disorder that affects millions of people worldwide. It is characterised by the accumulation of amyloid-beta plaques and neurofibrillary tangles in the brain. It is commenced by cleavage of amyloid precursor protein (APP) by β-secretase, β-site amyloid precursor protein cleaving enzyme (BACE1; also called Asp2, memapsin 2). Therefore, BACE1 is a prime target for developing therapeutics against AD. In this study, we have identified a small molecule that potentially inhibits the activity of BACE1 by interacting with the active site residues. Also, the flap region seems to be involved in enhancing the stability of the small molecule at the active site. We have used Umibecestat (CNP-520) as a positive control. Our Show less

In the non-obese diabetic (NOD) mouse model of autoimmune diabetes, interleukin (IL)-27 stimulates interferon γ (IFNγ) production by CD4 and CD8 T cells and is essential for disease development. Here, we tested the role of IL-27 in cellular communication. Single-cell RNA sequencing and T cell adoptive transfer showed that IL-27 intrinsically controlled the differentiation of islet-infiltrating CD4 T cells by driving them toward an IL-21 Show less

To perform multiscale correlation analysis between quantitative texture feature phenotypes of pre-biopsy biparametric MRI (bpMRI) and targeted sequence-based RNA expression for hypoxia-related genes. Images from pre-biopsy 3T bpMRI scans in clinically localised PCa patients of various risk categories (n = 15) were used to extract textural features. The genomic landscape of hypoxia-related gene expression was obtained using post-radical prostatectomy tissue for targeted RNA expression profiling using the TempO-sequence method. The nonparametric Games Howell test was used to correlate the differential expression of the important hypoxia-related genes with 28 radiomic texture features. Then, cBioportal was accessed, and a gene-specific query was executed to extract the Oncoprint genomic output graph of the selected hypoxia-related genes from The Cancer Genome Atlas (TCGA). Based on each selected gene profile, correlation analysis using Pearson's coefficients and survival analysis using Kaplan-Meier estimators were performed. The quantitative bpMR imaging textural features, including the histogram and grey level co-occurrence matrix (GLCM), correlated with three hypoxia-related genes (ANGPTL4, VEGFA, and P4HA1) based on RNA sequencing using the TempO-Seq method. Further radiogenomic analysis, including data accessed from the cBioportal genomic database, confirmed that overexpressed hypoxia-related genes significantly correlated with a poor survival outcomes, with a median survival ratio of 81.11:133.00 months in those with and without alterations in genes, respectively. This study found that there is a correlation between the radiomic texture features extracted from bpMRI in localised prostate cancer and the hypoxia-related genes that are differentially expressed. The analysis of expression data based on cBioportal revealed that these hypoxia-related genes, which were the focus of the study, are linked to an unfavourable survival outcomes in prostate cancer patients. Show less