👤 Zeba Siddiqi

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

The liver plays a crucial role in maintaining lipid homeostasis by converting toxic free fatty acids into VLDL, which the body uses for energy. Even minor changes in VLDL formation and secretion can result in serious health conditions such as atherosclerosis and non-alcoholic fatty liver disease. Despite the importance of VLDL, the proteins and signaling pathways involved in its regulation remain largely unknown. This study aims to develop a novel methodology to study intracellular VLDL transport events and explore the role of liver fatty acid-binding protein (LFABP) in VLDL transport and secretion. Current methods to study VLDL are often tedious, time-consuming, and expensive, underscoring the need for an alternative approach. We designed a new immunofluorescence-based assay to track the formation and secretion of VLDL in cells over time using fluorescently tagged TopFluor oleic acid. Confocal microscopy confirmed that TopFluor oleic acid enters hepatocytes and colocalizes with the ER, Golgi, and plasma membrane. Additionally, the collection of cell culture media revealed that TopFluor was incorporated into VLDL particles, as confirmed by fluorescence readings and ApoB100 immunoblots. This novel assay provides a valuable tool for further research into the mechanisms of VLDL regulation and the development of potential therapeutic targets for related diseases. Utilizing this assay, we identified LFABP as a key regulatory protein in post-Golgi VLDL trafficking. Our data suggest that LFABP plays a crucial role in this process, and its functional impairment leads to reduced VLDL secretion. Show less

Apolipoprotein E (ApoE) and monocyte chemoattractant protein-1 (MCP-1) are inflammatory markers associated with premature atherosclerosis, which leads to increased cardiovascular disease risk among people with HIV (PWH). We aimed to evaluate the association between the plasma levels of these inflammatory markers and ischemic stroke in young PWH. We conducted a prospective case-control study at the University Teaching Hospital in Lusaka, Zambia, between March 2022 and October 2024, comparing young PWH with non-cardioembolic ischemic stroke (cases) to age- and sex-matched PWH without a history of stroke (controls). Standardized data collection instruments were used to collect information on other known risk factors for stroke, including demographic, clinical, laboratory, and imaging parameters. ELISA was done to measure ApoE and MCP-1 levels in the plasma of individuals in both the case and control groups. We analyzed results for 50 cases and 50 controls. Compared to controls, cases were more likely to have (1) traditional stroke risk factors such as hypertension (42 vs. 2%, The results suggest that lower plasma ApoE levels are independently associated with non-cardioembolic ischemic stroke in young PWH. Additional studies with larger sample sizes are needed to further explore the contribution of these inflammatory markers in young-onset HIV-associated stroke. Show less

The co-occurrence of plasma cell neoplasm (PCN) and lymphoplasmacytic lymphoma (LPL) is rare, and their clonal relationship remains unclear. To evaluate the clinicopathologic characteristics of concomitant LPL/PCN. Retrospectively analyzed clinical and laboratory data of 14 cases. Three patients initially presented with immunoglobulin (Ig) M paraprotein, 1 with IgG paraprotein, and 10 had simultaneous diagnoses of PCN and LPL. In 13 cases, flow cytometry detected both LPL and PCN in marrow biopsies. Furthermore, immunohistochemistry highlighted the 2 neoplastic populations, demonstrating an increased proportion of plasma cells and their expression of cyclin D1, CD56, and/or a non-IgM isotype restriction. All cases exhibited discordant heavy-chain isotypes between LPL and PCN. Thirteen of the 14 cases (92.9%) had concordant light-chain restrictions between the 2 neoplasms, and the remaining case (7.1%) showed discordant light-chain restrictions. Of the 12 patients with follow-up, 5 were treated with myeloma regimens, 2 with LPL regimens, 3 with combined therapy, and 2 with observation alone. Follow-up ranged from 2 to 146 months (median, 12.5 months). One patient died of PCN progression, one died of comorbidity, and 10 patients were alive with or without disease. Survival analysis showed no significant difference from the control. The discordant heavy-chain isotype restrictions between PCN and LPL suggest biclonal B-cell neoplasms, which is supported by PCN's phenotypic distinction, such as the expression of cyclin D1 and/or CD56. However, our series exhibited a tendency toward concordant light-chain restrictions between the 2 neoplasms, raising the possibility that PCN may evolve from LPL through class switching. Show less

Beta-site amyloid-β precursor protein-cleaving enzyme 1 (BACE1) is a transmembrane aspartic protease and has shown potential as a possible therapeutic target for Alzheimer's disease. This aggravating disease involves the aberrant production of β amyloid plaques by BACE1 which catalyzes the rate-limiting step by cleaving the amyloid precursor protein (APP), generating the neurotoxic amyloid β protein that aggregates to form plaques leading to neurodegeneration. Therefore, it is indispensable to inhibit BACE1, thus modulating the APP processing. In this study, we present a workflow that utilizes a multi-stage virtual screening protocol for identifying potential BACE1 inhibitors by employing multiple artificial neural network-based models. Collectively, all the hyperparameter tuned models were assigned a task to virtually screen Maybridge library, thus yielding a consensus of 41 hits. The majority of these hits exhibited optimal pharmacokinetic properties confirmed by high central nervous system multiparameter optimization (CNS-MPO) scores. Further shortlisting of 8 compounds by molecular docking into the active site of BACE1 and their subsequent in-vitro evaluation identified 4 compounds as potent BACE1 inhibitors with IC50 values falling in the range 0.028-0.052 μM and can be further optimized with medicinal chemistry efforts to improve their activity. Show less