Biomedical subjects

Sandeep Kumar

Publications and source records attributed to Sandeep Kumar.

3 recordsLinked to original sources

PubMed2025

Development and validation of a high-density 'Amahysnp' genotyping array in grain amaranth (Amaranthus hypochondriacus).

BACKGROUND: Grain amaranth has recently gained global attention as a promising crop alternative to traditional cereals due to its nutritional value and adaptability to various growing conditions. Although gene banks conserve extensive collections of amaranth germplasm, the genomic and phenotypic characterization of these resources is limited, which hinders their full utilization in breeding programs. A major challenge is the lack of high-throughput genotyping assays essential for comprehensive genomic characterization and trait mapping. High-density SNP arrays have become standard tools for genome-wide analysis across multiple loci, enabling molecular breeding across a range of crop species. RESULTS: In this study, we developed a 64 K high-throughput SNP genotyping array named "AmahySNP", using Affymetrix® Axiom® technology. The array contains 64,069 high-density SNPs distributed across both genic (55.17%) and non-genic (44.83%) regions of the Amaranthus hypochondriacus genome. The genic region includes 8,879 genes, which consist of 4,830 single-copy genes and 4,049 multi-copy genes distributed across 16 scaffolds. These genes cover various functional regions, including exons (10.5%), introns (40.1%), 5'UTRs (1.6%), and 3'UTRs (2.9%), respectively. The AmahySNP array was effectively utilized for population structure analysis, genetic diversity studies, core development, and genome wide association studies (GWAS) in amaranth germplasm. A representative core set of 112 accessions was identified, which includes two released varieties (Annapurna and Suvarna) and 100 diverse accessions from 12 different regions, representing 12% of the total 917 accessions evaluated. Phylogenetic analysis revealed three major genetic clusters, independent of their geographical origins. GWAS conducted using 22,763 polymorphic SNPs from 540 genotypes identified 13 novel loci associated days to flowering (DTF) trait, seven of which were located within annotated genes. CONCLUSIONS: The AmahySNP 64 K SNP chip a valuable genomic tool for amaranth research and breeding with a strong potential to accelerate its genetic improvement. It enables high-throughput genotyping for a wide range of applications, including GWAS and other genomic studies, and will significantly advance the exploration of natural genetic variations. Ultimately, this resource will empower amaranth breeders to develop improved amaranth cultivars with enhanced crop yield, resilience, and nutritional quality, contributing to global food security and sustainable agriculture.

Amaranthus↗

PubMed2025

Innovative strategies for mitochondrial dysfunction in myeloproliferative neoplasms a step toward precision medicine.

Myeloproliferative neoplasms (MPNs) are clonal disorders of hematopoietic stem cells characterized by aberrant proliferation of myeloid lineages, driven primarily by mutations in JAK2, CALR, and myeloproliferative leukemia, leading to constitutive activation of the JAK-STAT pathway. Emerging evidence highlights mitochondrial dysfunction as a key factor in MPN pathogenesis, contributing to increased reactive oxygen species production, mitochondrial DNA mutations, and dysregulated mitochondrial dynamics, which collectively promote clonal expansion and apoptosis resistance. Targeting mitochondrial pathways has gained attention as a therapeutic strategy, with approaches including mitochondria-targeted antioxidants, metabolic inhibitors, and modulation of mitophagy and mitochondrial fission/fusion dynamics. However, challenges such as drug delivery specificity, therapeutic resistance, and off-target effects remain significant. Recent advances in precision medicine, incorporating genomic, transcriptomic, and proteomic profiling, offer a more personalized approach to MPN treatment by tailoring interventions to individual mutation patterns. Additionally, novel therapeutic strategies, including gene editing technologies, RNA-based therapies, and nanoparticle-mediated drug delivery systems, hold promise for overcoming current treatment limitations. The integration of artificial intelligence in drug discovery and biomarker identification further enhances the potential for targeted therapies. Future research should focus on refining these strategies, developing reliable biomarkers for patient stratification, and exploring combination therapies that enhance treatment efficacy while minimizing adverse effects. By addressing mitochondrial dysfunction as an underlying driver of MPNs, these emerging approaches have the potential to improve disease management, extend patient survival, and enhance quality of life. Also, this new approach of precision medicine allows patient stratification and ensures that treatments are formed according to the individual disease biology of each patient, which results in overall better outcomes.

combination drug therapy↗

PubMed2023

A DUAL MTOR/NAD+ ACTING GEROTHERAPY.

The geroscience hypothesis states that a therapy that prevents the underlying aging process should prevent multiple aging related diseases. The mTOR (mechanistic target of rapamycin)/insulin and NAD+ (nicotinamide adenine dinucleotide) pathways are two of the most validated aging pathways. Yet, it's largely unclear how they might talk to each other in aging. In genome-wide CRISPRa screening with a novel class of N-O-Methyl-propanamide-containing compounds we named BIOIO-1001, we identified lipid metabolism centering on SIRT3 as a point of intersection of the mTOR/insulin and NAD+ pathways. In vivo testing indicated that BIOIO-1001 reduced high fat, high sugar diet-induced metabolic derangements, inflammation, and fibrosis, each being characteristic of non-alcoholic steatohepatitis (NASH). An unbiased screen of patient datasets suggested a potential link between the anti-inflammatory and anti-fibrotic effects of BIOIO-1001 in NASH models to those in amyotrophic lateral sclerosis (ALS). Directed experiments subsequently determined that BIOIO-1001 was protective in both sporadic and familial ALS models. Both NASH and ALS have no treatments and suffer from a lack of convenient biomarkers to monitor therapeutic efficacy. A potential strength in considering BIOIO-1001 as a therapy is that the blood biomarker that it modulates, namely plasma triglycerides, can be conveniently used to screen patients for responders. More conceptually, to our knowledge BIOIO-1001 is a first therapy that fits the geroscience hypothesis by acting on multiple core aging pathways and that can alleviate multiple conditions after they have set in.

Preprint↗