Biology subjects

Nisar, S.

Publications and source records attributed to Nisar, S..

3 recordsLinked to original sources

bioRxiv2026

Neurometabolic correlates of accelerated aging and neurocognitive late effects in long-term survivors of pediatric hodgkin lymphoma and acute lymphoblastic leukemia

Adult survivors of pediatric cancers are at elevated risk for neurocognitive late effects, but how these effects relate to metabolic perturbations in the brain remains unclear. To address this knowledge gap, the present study explored associations between neurometabolite levels and neurocognitive function in adult survivors of Hodgkin lymphoma (HL) and acute lymphocytic leukemia (ALL). Data were collected from a single-center observational study conducted at St. Jude Childrens Research Hospital (SJCRH) between October 2022 and November 2024. Adult survivors of HL (N=11 [5 females]; [≥]5 years post-diagnosis; mean [SD] current age 34 [9.5] years) and ALL (N=24 [16 females]; [≥]5 years post-diagnosis; current age 40 [12.6] years) and community controls (N=35 [17 females]; current age 40 [11] years) completed standardized neurocognitive tests of memory, attention, executive function, and processing speed. Participants also underwent proton magnetic resonance spectroscopy (1H MRS) to quantify neurometabolite levels in the left dorsolateral prefrontal cortex (dlPFC), left hippocampus, and left cerebellum. Analyses used regression models to examine differences in the slope of the relationship between neurometabolite and neurocognitive function or between neurometabolite and age. When comparing HL survivors vs controls, significant interactions were identified for group x age on the ratio of myo-inositol to N-Acetyl aspartic acid (mI/NAA; p=0.007) and group x Gamma-Aminobutyric Acid (GABA) on processing speed (p=0.04) in the left dlPFC. When comparing ALL survivors vs controls, significant interactions were identified for group x myo-inositol on verbal fluency in the left hippocampus (p=0.01) and group x GABA on cognitive flexibility in the left cerebellum (p=0.01). These preliminary findings suggest that neuroinflammation may be a mechanistic underpinning of age-associated neurocognitive impairment in pediatric cancer survivors.

neuroscience↗

bioRxiv2026

Epigallocatechin Gallate (EGCG) as a Protective Agent Against Enzymatic Stromal Degradation in Caprine and Ovine Corneas: Towards Novel Therapeutics for Keratoconus

PurposeKeratoconus (KC) is a progressive corneal ectatic disorder marked by stromal thinning, enzymatic degradation, and oxidative stress. Conventional corneal collagen cross-linking (CXL) therapy poses risks. Epigallocatechin gallate (EGCG), a catechin found in green tea, has been shown to cross-link collagen, inhibit proteases, and modulate inflammation, suggesting its potential as an alternative therapy for KC. This study aimed to (1) evaluate the protective effects of EGCG against collagenase-mediated stromal degradation in caprine and ovine corneas and (2) investigate the use of caprine and ovine cornea as viable ex vivo models for corneal ectasia research. MethodsGoat (n=4) and sheep (n=8) corneoscleral buttons were cultured in an air-liquid interface (ALI). Tissue viability was monitored by transparency grading and histology. The corneal ectasia environment was induced by collagenase type I digestion. An EGCG-rich extract was utilized for the treatments. ResultsGoat and sheep corneas remained intact for 7 days in MEM-based medium, though transparency decreased, with edema (whitening) by Day 7. Histology confirmed stromal loosening and reduced keratocyte cell density but preserved architecture sufficient for enzymatic digestion. EGCG pre-treatment and post-treatment exposure were associated with greater resistance to enzymatic digestion, with greater stromal preservation of quadrants in the EGCG pre-treated quadrant than in PBS pre-treated controls. ConclusionsThis study provides proof of concept that EGCG extract confers protection against enzymatic degradation in goat and sheep corneas, highlighting its potential as a protective agent for corneal ectatic disorders like Keratoconus. Additionally, goat and sheep corneas can represent practical and ethical ex vivo models for short-term ocular research. Future work should focus on cytotoxicity, biomechanical validation, optimized culture conditions, and in vivo studies.

pathology↗

bioRxiv2024

Unraveling a novel dual-function regulatory element showing epistatic interaction with a variant that escapes genome-wide association studies.

Regulation of gene expression has recently been complexified by the identification of Epromoters, a subset of promoters with enhancer function. Here, we uncovered the first dual cis-regulatory element, "ESpromoter," exhibiting both enhancer and silencer function, as a regulator of the nearby genes ATP2B4 and LAX1 in single human T cells. Through integrative approach, we pinpointed functional rs11240391, a severe malaria risk variant that escapes detection in genome-wide association studies, challenging conventional strategies for identifying causal variants. CRISPR-modified cells demonstrated the regulatory effect of ESpromoter and rs11240391 on LAX1 expression and T cell activation. Furthermore, our findings revealed an epistatic interaction between ESpromoter SNPs and rs11240391, impacting severe malaria susceptibility by further reducing LAX1 expression. This groundbreaking discovery challenges the conventional enhancer-silencer dichotomy. It highlights the sophistication of transcriptional regulation and argues for an integrated approach combining genetics, epigenetics, and genomics to identify new therapeutic targets for complex diseases. HIGHLIGHTSO_LINovel dual enhancer-silencer element (ESpromoter) in a single human cell type C_LIO_LIFunctional SNP for severe malaria risk that escapes genome-wide association studies C_LIO_LIGenome editing at the SNP demonstrates a regulatory effect on LAX1 and T cell activation C_LIO_LIEpistatic interaction between SNPs increases the risk of severe malaria C_LI In briefEpistatic interaction between common variants within a novel dual enhancer-silencer regulatory element and the LAX1 promoter variant is responsible for severe malaria susceptibility through T-cell activation.

genomics↗