Biology subjects

Nair, A. A.

Publications and source records attributed to Nair, A. A..

3 recordsLinked to original sources

bioRxiv2026

Intracranial Targeting of Cholesterol Processing Reveals a Therapeutic Vulnerability that Reprograms Glioblastoma and Promotes Antitumor Immunity

Glioblastoma (GBM) remains the most lethal primary brain cancer due to its remarkable metabolic plasticity and therapeutic resistance. Here, we identify cholesterol dependency as a therapeutically exploitable vulnerability in GBM using two FDA approved drugs: the H1 histamine antagonist clemastine and the retinoid X receptor agonist bexarotene. Combined treatment induces potent synergistic anti tumor activity across patient-derived glioma models, suppressing proliferation, stemness, and survival at sub IC50 concentrations. Mechanistically, this therapy disrupts cholesterol biosynthesis, transport, and homeostasis, triggering endoplasmic reticulum stress and activation of the unfolded protein response, ultimately leading to autophagy and apoptotic cell death. Orthotopic patient derived glioma models recapitulate these mechanisms in vivo, where local intracranial administration significantly reduces tumor progression and prolongs survival using fourfold lower doses than systemic intraperitoneal delivery. Single cell RNA sequencing revealed activation of regeneration and plasticity programs, accompanied by immune microenvironment remodeling and enhanced inflammatory signaling. Importantly, syngeneic models preserved immune cell composition, supporting future integration with immunotherapeutic strategies. Together, these findings establish cholesterol dysregulation induced metabolic collapse as a promising therapeutic approach for GBM.

cancer biology↗

bioRxiv2022

Comparative Radiopathology of Male Reproductive Organs in Sprague Dawley Rats Administered with Curcuma longa and Ocimum sanctum Against Acute Gamma Irradiation

ObjectiveThe study was designed to evaluate the deleterious e{square}ects of acute lethal gamma irradiation on male reproductive organs of Sprague Dawley rats and the radioprotective potential by Curcuma longa and Ocimum sanctum in experimental set up. Methods25 Male Spraque Dawley rats were taken and randomized into 5 groups (T1, T2, T3, T4, T5). Each group containing 5 animals. The groups were named as Group T1 (Negative Control), Group T2 (irradiation positive control), Group T3 (irradiation and Curcuma longa), Group T4 (irradiation and Ocimum sanctum), Group T5 (irradiation, Curcuma longa and Ocimum sanctum). The rats in groups T1 and T2 were given a daily dosage of normal saline for 14 days. Group T3 and T4 rats received aqueous extracts of Curcuma longa (40 mg/kg) and Ocimum sanctum (40 mg/kg), respectively, whereas group T5 rats received a combination of aqueous extracts of Curcuma longa (40 mg/kg) and Ocimum sanctum (40 mg/kg) for 14 days. prior to gamma irradiation. Animals of group T2, T3, T4, T5 were irradiated with 10 Gy of {gamma} - radiation on 15th day. ResultsExposure of animals to 10 Gy gamma radiation resulted in significant decrease in body weight and testicular weight. Histopathological observations revealed testicular degenerative changes in the seminiferous tubules with primary spermatocytes being most affected and epididymis showed decreased spermatids density with cell debris in the lumen. Pretreatment with Curcuma longa at 40mg/kg for 14 days alleviated the radiation induced pathological changes in testis and epididymis. Curcuma longa demonstrated much better protective effect in combination with Ocimum sanctum in alleviating the radio pathological changes showing the possibility of synergistic effect. However, administration of Ocimum sanctum alone at 40mg/kg for 14 days did not reveal any significant radioprotective property after histomorphological evaluation. ConclusionGamma irradiation of 10 Gy induces severe radio pathological damage to organs of male reproductive system of Spraque Dawley rats. Pre-treatment with Curcuma longa prior to radiotherapy may be effective in preventing radiation-induced damage in the male reproductive organs. Better radioprotection can be achieved with the combination of Curcuma longa and Ocimum sanctum than using alone.

pathology↗

bioRxiv2019

Impact of RNA Extraction and Target Capture Methods on RNA Sequencing Using Formalin-Fixed, Paraffin Embedded Tissues

Formalin fixed paraffin embedded (FFPE) tissues are commonly used biospecimen for clinical diagnosis. However, RNA degradation is extensive when isolated from FFPE blocks making it challenging for whole transcriptome profiling (RNA-seq). Here, we examined RNA isolation methods, quality metrics, and the performance of RNA-seq using different approaches with RNA isolated from FFPE and fresh frozen (FF) tissues. We evaluated FFPE RNA extraction methods using six different tissues and five different methods. The reproducibility and quality of the prepared libraries from these RNAs were assessed by RNA-seq. We next examined the performance and reproducibility of RNA-seq for gene expression profiling with FFPE and FF samples using targeted (Kinome capture) and whole transcriptome capture based sequencing. Finally, we assessed Agilent SureSelect All-Exon V6+UTR capture and the Illumina TruSeq RNA Access protocols for their ability to detect known gene fusions in FFPE RNA samples. Although the overall yield of RNA varied among extraction methods, gene expression profiles generated by RNA-seq were highly correlated (>90%) when the input RNA was of sufficient quality ([≥]DV200 30%) and quantity ([≥] 100 ng). Using gene capture, we observed a linear relationship between gene expression levels for shared genes that were captured using either All-Exon or Kinome kits. Gene expression correlations between the two capture-based approaches were similar using RNA from FFPE and FF samples. However, TruSeq RNA Access protocol provided significantly higher exon and junction reads when compared to the SureSelect All-Exon capture kit and was more sensitive for fusion gene detection. Our study established pre and post library construction QC parameters that are essential to reproducible RNA-seq profiling using FFPE samples. We show that gene capture based NGS sequencing is an efficient and highly reproducible strategy for gene expression measurements as well as fusion gene detection.

genomics↗