Biology subjects

Beevi, S. S.

Publications and source records attributed to Beevi, S. S..

4 recordsLinked to original sources

bioRxiv2025

Protein Biomarker in Focal Cortical Dysplasia: Molecular Clues to Pathogenesis

Focal Cortical Dysplasia (FCD) is a major cause of drug-resistant epilepsy (DRE), particularly in pediatric and young adult populations characterized by structural abnormalities in cortical development. This study investigated 60 patients with histologically confirmed FCD, combining clinical, histopathological, and molecular data to identify subtype-specific molecular signatures. we investigated a panel of candidate protein biomarkers (AKT, PTEN, mTOR, HTR6, RHEB, KCNT1, RALA, DEPDC5) across FCD subtypes using patient-derived tissue samples. Our results reveal subtype-specific alterations in biomarker expression, particularly within the mTOR signaling pathway, supporting its central role in cortical malformations. Key dysregulated genes AKT, mTOR, PTEN, RHEB, DEPDC5, KCNT1, RALA, and HTR6 involved in mTOR signaling, neuronal excitability, and cortical development. Western blotting and IHC revealed marked upregulation of AKT and mTOR in FCD III, consistent with mTOR pathway hyperactivation. In contrast, KCNT1, RALA, and DEPDC5 were significantly downregulated across all subtypes, suggesting disrupted inhibitory signaling and GATOR1 complex dysfunction. ELISA assays validated increased expression of AKT, mTOR, and HTR6, particularly in higher-grade lesions. This study bridges clinical, histopathological, and protein-level data, providing novel insight into the molecular basis of FCD and highlighting candidate biomarkers for future diagnostic and therapeutic applications

neuroscience↗

bioRxiv2025

Stem Cell Secretomes from Surgical Waste: A Novel Approach to Cancer Therapy : An In Vitro Study

IntroductionCancer is the second leading cause of mortality in India, with conventional chemotherapy often limited by drug resistance, off-target toxicity, and metastasis promotion. These treatments indiscriminately attack rapidly dividing cells, including healthy tissues and immune cells, leading to severe side effects and weakened antitumor immunity. Hence, alternative strategies are needed to selectively target cancer cells while minimizing collateral damage. MethodsMesenchymal stem cells (MSCs) were isolated, cultured up to passage 4 (P4), and characterized via flow cytometry and immunocytochemistry for stemness markers. Their differentiation potential was validated using adipogenic and chondrogenic lineage assays. The MSC-derived secretome, collected under hypoxic conditions, was analyzed for its cytotoxic effects on cancer cells using MTT, TMRM staining, and scratch assays. NanoLC-MS/MS profiling and STRING-DB analysis identified key proteins involved in apoptosis, tumor suppression, and DNA damage response. ResultsP2 secretomes exhibited the highest protein concentration and strongest cytotoxic effects. UCSC-derived secretomes showed superior anti-cancer activity, significantly reducing cancer cell viability, mitochondrial membrane potential, and migration. Dose-dependent studies revealed up to 95% cancer cell death with UCSC secretome, while ADSC secretome achieved 80%. In contrast, HEK293-derived secretomes had minimal effects. LC-MS profiling identified tumor-suppressive and apoptosis-inducing proteins, with unique protein signatures distinguishing UCSC and ADSC secretomes. STRING analysis mapped key regulatory pathways in tumor inhibition. ConclusionMSC-derived secretomes, particularly from UCSCs, effectively target aggressive breast cancer cells while sparing normal cells, offering a promising alternative to conventional therapies. Future research should optimize secretome formulations, identify key bioactive components, and validate their efficacy in in vivo models and clinical trials to advance this therapy toward clinical applications.

cell biology↗

bioRxiv2020

Computational and Molecular Dynamics Simulation ApproachTo Analyze the Impact of XPD Gene Mutation on Protein Stability and Function

XPD acts as a functional helicase and aids in unwinding double helix around damaged DNA, leading to efficient DNA repair. Mutations of XPD give rise to DNA-repair deficiency diseases and cancer proneness. In this study, cancer-causing missense mutation that could inactivate helicase function and hinder its binding with other complexes were analysed using bioinformatics approach. Rigorous computational methods were employed to understand the molecular pathogenic profile of mutation. The mutant model with the desired mutation was built with I-TASSER. GROMACS 5.0.1 was used to evaluate the effect of a mutation on protein stability and function. Of the 276 missense mutations, 64 were found to be disease-causing. Out of these 64, seven were of cancer-causing mutations. Among these, we evaluated K48R mutation in a computational simulated environment to determine its impact on protein stability and function since K48 position was ascertained to be highly conserved and substitution with arginine could impair the XPD activity. Molecular Dynamic Simulation and Essential Dynamics analysis showed that K48R mutation altered protein structural stability and produced conformational drift. Our predictions thus revealed that K48R mutation could impair the XPD helicase activity and affect its ability to repair the damaged DNA, thus augmenting the risk for cancer.

bioinformatics↗

bioRxiv2020

In Vitro Patients Derived Glioma Culture Model: Identification of Aggressive, Drug Resistant Phenotype Among Low-Grade Gliomas

BackgroundClinical management of glioma is crucial irrespective of tumor grade. Despite newer treatment modalities, the prognosis of glioma is abysmal and, survival statistics are not remarkable. In vitro glioma culture is emerging as a standard model to get insight into phenotypic transformation, drug response, and tumor relapse. In this viewpoint, this study established comprehensive patient-specific short-term cultures comprising low-grade, and high-grade glioma, and evaluated their pertinence in the potential disease management. Methods50 patients with MRI diagnosed glioma were recruited for this study. Primary glioma cultures established from fresh surgical tumor tissues, which were then evaluated for their intrinsic growth kinetics, response to temozolomide, and expression profile of Glial-Mesenchymal Transition (GMT) markers along with an oncogenic marker, cMyc. ResultsShort-term glioma culture was successfully established in 40 clinical samples. Glioma culture, irrespective of tumor grade, displayed two distinct patterns of growth kinetics - one with shorter doubling time (high-proliferating) and another group with longer doubling time (low-proliferating). Significant distinctive features were noticed between these two groups in terms of response to temozolomide, the expression pattern of GMT markers and their association with 1p/19q co-deletion and p53 expression. ConclusionOur findings effectively demonstrated the practicality of the development of short-term glioma culture toward a functional approach for personalized medicine. Our study revealed the presence of a highly proliferative, drug-resistant phenotype irrespective of tumor grade. Hence, short-term culture could be an important prognostic tool for predicting patient clinical responses and cue about imminent tumor relapse.

cancer biology↗