Biology subjects

Siddiqui, A. H.

Publications and source records attributed to Siddiqui, A. H..

4 recordsLinked to original sources

bioRxiv2026

Mechanotherapeutic Potential of Survivin in Glioblastoma

Glioblastoma Multiforme (GBM) is a highly aggressive brain cancer characterized by rapid proliferation and extensive remodeling of the extracellular matrix (ECM), leading to progressive tissue stiffening. Although ECM stiffness is known to promote GBM progression, the molecular mechanisms linking mechanical cues to tumor growth remain insufficiently defined. In this study, transcriptomic comparison of GBM tumors and non-neoplastic brain tissue revealed coordinated upregulation of cell cycle regulators and matrisome-associated genes, with survivin (BIRC5) identified as a central node linking proliferative signaling and ECM remodeling networks. Analysis of GBM patient specimens further showed strong nuclear survivin expression in regions with elevated collagen deposition. To directly evaluate stiffness-dependent regulation of survivin, GBM cells were cultured on fibronectin-infused hydrogels with tunable stiffness. Stiff matrices increased survivin expression along with cyclin D1 and cyclin A, consistent with increased cell cycle progression. Pharmacologic inhibition or siRNA-mediated suppression of survivin reduced stiffness-induced proliferation and attenuated expression of matrisome components, including collagens and lysyl oxidase. These findings indicate that survivin functions as a mechanosensitive regulator that coordinates cell cycle progression with ECM production in stiff tumor microenvironments. Collectively, this study identifies survivin as a key mediator linking ECM stiffness to GBM growth and matrisome remodeling. Targeting survivin and its effectors may offer a mechanosensitive strategy to limit GBM growth.

pathology↗

bioRxiv2026

Expression of Calca gene-derived peptides in the murine taste system

Taste cell regeneration and taste signaling are regulated by myriad growth factors and signaling molecules secreted by neurons and taste papillae - resident cells. The Calcitonin Related Polypeptide Alpha (Calca) gene is a source of four biologically active peptides with varied physiological roles. Alternative splicing of the Calca messenger RNA generates either prepro calcitonin gene related peptide (CGRP) or preprocalcitonin encoding transcripts. Proteolytic processing of preprocalcitonin generates procalcitonin, calcitonin and katacalcin. Calcitonin is a ligand for the G-protein coupled receptor calcitonin receptor (CALCR) while CGRP is a ligand for the CGRP receptor (CGRP1R) formed by the calcitonin receptor like receptor (CALCRL)-receptor activity modifying protein 1 (RAMP1) complex. Interestingly, procalcitonin too, is a ligand for the CGRP1R where it can antagonize CGRP. CGRP expression in taste and trigeminal neurons has been documented and is posited to regulate taste signaling. Single cell and bulk RNASeq of taste papillae revealed that the preprocalcitonin but not the Cgrp transcript is expressed in Tas1r3-expressing type II taste cells, while CGRP1R subunits are expressed in taste stem/progenitor cells and by subsets of fibroblasts and immune cells in the lingual mesenchyme. We confirmed this expression pattern using quantitative polymerase chain reaction (qPCR) and histological techniques. qPCR of geniculate and nodose-petrosal ganglia revealed that both express Cgrp and CGRP1R subunit mRNAs, but not preprocalcitonin and Calcr. This interesting expression patterns suggests that procalcitonin and CGRP might reciprocally regulate the CGRP1R in the taste papillae and potentially influence taste signaling, taste cell regeneration and the taste microbiome.

neuroscience↗

bioRxiv2025

CT Radiomic Signatures of Neutrophil Extracellular Traps in Ischemic Stroke Thrombi

BackgroundRadiomic and transcriptomic analyses have independently identified features linked to mechanical thrombectomy (MT) outcomes in acute ischemic stroke (AIS). In this study, we integrate paired radiomic and transcriptomic profiling of AIS clots to identify Neutrophil Extracellular Trap (NET) enrichment as a predictor of first-pass MT success. We further assess the potential to non-invasively detect NET enrichment using pre-thrombectomy CT imaging. MethodsWe performed radiomic and transcriptomic analysis of 32 stroke clots retrieved by MT (n=16 each of modified first pass [mFP] success and failure). Clots were segmented from pre-MT CTA and nCCT scans and radiomic features (RFs) were extracted using pyRadiomics. Normality, equal variance, and two-sample testing were completed to identify which RFs were significantly different between mFP outcomes. Differentially expressed genes (DEGs) were identified between transcriptomes of mFP success and failure using the criteria of logFC[≥]1.5 and q<0.05. A NET enrichment score was computed from expression data and correlated with RFs to identify a RF signature predictive of NET enrichment. Immunofluorescence (IF) staining was completed on retrieved clot tissue to provide ground truth labeling of NETs. Results44 DEGs were identified between mFP outcomes. From ontology analysis, NET Formation, Neutrophil Degranulation, and the NET Signaling Pathway were among the most enriched terms in the mFP failure group, with related genes downregulated in the mFP success group. 40 RFs were significantly different between mFP outcomes. Of these, 6 were found to be correlated with and predictive of clot NET enrichment. IF quantification validated that transcriptomic NET signatures accurately reflected NET presence within clot tissues. ConclusionOur findings indicate that NET enrichment within thrombi is associated with reduced mFP success, and that radiomic features extracted from pre-thrombectomy CT imaging can serve as non-invasive biomarkers of clot NET content. This radiomic signature may aid in pre-procedural decision-making, including thrombolytic therapy planning and thrombectomy device selection.

pathology↗

bioRxiv2023

Evaluating Minocycline as a Neuroprotective Agent in an Aged Female Rat MCAO Stroke Model

The middle cerebral artery occlusion (MCAO) suture model is widely accepted ischemic stroke model. However, researchers routinely use young male rats, ignoring that stroke risk is increased in older, post-menopausal women. To this end, we implemented (120-minute) transient- and permanent-occlusion MCAO models in female retired-breeder rats, examining the endpoint across 1-30 days to identify the optimal time course for the model. We found that in both groups the physical infarct (measured by triphenyltetrazolium chloride -TTC staining), which is present initially, was not detectable 30 days post-MCAO (even if some neurologic symptoms persist). Across shorter time-points (namely 24 hours and 7 days) we found that neurologic scores generally reach a plateau/maximum at {bsim}7 days, then infarct size gradually decreases over time for rats receiving a permanent MCAO. Across 3 transient occlusion times (60 minutes, 90 minutes, and 120 minutes), the longest gave the most robust result. Overall, the permeant and 120-minute transient MCAO evaluated at 7 days was optimal. Using these two models, we evaluated the neuroprotective qualities of the antibiotic, minocycline. We found that those in the treatment groups experienced a greater improvement in neurologic scores and a larger decrease in infarct size after daily treatment for seven days. This improvement was more prominent in the transiently occluded treatment group than in the permanently occluded group.

neuroscience↗