Biology subjects

Sethumadhavan, A.

Publications and source records attributed to Sethumadhavan, A..

2 recordsLinked to original sources

bioRxiv2026

Global protein expression profiling in stem cell factor stimulated human Acute megakaryoblastic leukemia cells identifies CFL1, GSN and CCT8 as prognostic biomarkers for Acute Myeloid Leukemia.

Abstract Background: The stem cell factor receptor or c-Kit is a type III receptor tyrosine kinase, activated by its ligand Stem cell factor (SCF). Up on activation, c-kit induces signaling pathways that regulates blood cell proliferation, survival, differentiation, and migration. Several studies reported that c-Kit/SCF signaling, contributes to the development and progression of acute myeloid leukemia (AML) in patients. However, the downstream proteins regulated by c-kit activation and their clinical significance in AML remain poorly explored. Methods: Human Acute megakaryoblastic leukemia (Mo7e) cells, were-stimulated with SCF and global protein expression were profiled using two-dimensional gel electrophoresis coupled with MALDI-TOF and LC-MS/MS. Differentially expressed proteins were functionally characterized and validated using patient data from the TCGA-LAML and matched normal data from GTEx, GEO datasets, and quantitative RT-PCR. Their diagnostic and prognostic significance was assessed using ROC, Cox regression, LASSO, Kaplan Meier survival analyses, and a prognostic nomogram model. Results: Proteomic profiling identified 14 differentially expressed proteins in SCF-stimulated Mo7e cells, which are predicted to involved in cytoskeletal organization, protein folding, metabolism, vesicular trafficking, and translational regulation. Transcriptomic analysis of the TCGA-LAML cohort revealed significant dysregulation of CFL1, CCT8, HSP90B1, MDH2, EIF5A, GSN, and TPI1. Integrated ROC, Cox regression, and LASSO analyses identified CFL1, CCT8, and GSN as the most robust prognostic biomarkers associated with poor overall survival in LAML patients. Their expression patterns were validated in independent GEO datasets and by qRT-PCR in SCF stimulated Mo7e cells. Finally, a three-gene nomogram model was developed and validated to predict the overall survival probability of AML patients at 1-, 3-, and 5-year time points. Conclusions: This study identifies CFL1, CCT8, and GSN as key downstream effectors of c-Kit signaling as prognostic biomarkers for AML. These findings provide mechanistic insights into c-Kit-driven leukemogenesis and establish a clinically relevant three-gene signature for AML risk stratification and potential therapeutic targeting.

cancer biology↗

bioRxiv2025

Sleep deprivation, cytokine dysregulation, and the risk of cardiac arrhythmia in domestic dogs

BackgroundSleep deprivation is increasingly recognized as a potent physiological stressor capable of altering immune function and promoting systemic inflammation. Emerging evidence suggests that these inflammatory changes may contribute to cardiac electrical instability and arrhythmia risk. However, the specific cytokines involved and their mechanistic pathways in domestic dogs remain poorly characterized. This study aimed to (1) identify key cytokines consistently associated with sleep deprivation through a systematic meta-analysis of the literature, and (2) perform a domestic dog-specific network and Gene Ontology enrichment analysis to characterize their interactions and potential mechanistic links to arrhythmogenesis. MethodsA structured search of PubMed and Google Scholar identified 25 articles, of which 24 unique records were screened and seven met all inclusion criteria. From these studies, seven cytokines (IL-6, IL-17A, TNF, IL-1, IL-21, IFN-{gamma}, and CRP) were consistently associated with sleep deprivation and were subjected to domestic dog-specific protein-protein interaction analysis using the STRING database. Network topology and enriched biological processes were evaluated to identify mechanistic pathways connected to cardiac electrophysiology. ResultsNetwork analysis revealed several highly interconnected signalling nodes, including IL-10, IL-1{beta}, JAK1, JAK2, IL-6, STAT3, TNF, IFN-{gamma}, IL-2, and IL-4. Enrichment analysis indicated activation of processes such as chemokine production, positive regulation of osteoclast differentiation, JAK-STAT signalling, membrane protein ectodomain proteolysis, and regulation of vitamin D metabolism. Integration of primary and secondary networks revealed three major clusters cantered on interleukin signalling, TNF-driven pathways, and CRP-associated acute-phase responses. Collectively, these pathways converge on cytokine-mediated mechanisms known to influence myocardial conduction and increase arrhythmia susceptibility. ConclusionsThese findings suggest that sleep deprivation activates coordinated inflammatory networks that may predispose dogs to arrhythmias through multiple interconnected biological pathways. Therapeutic strategies addressing both inflammation and electrical instability may be required to fully manage arrhythmia risk in sleep-deprived canine patients.

physiology↗