Biology subjects

Jaiswal, V.

Publications and source records attributed to Jaiswal, V..

5 recordsLinked to original sources

bioRxiv2026

Deciphering the Therapeutic Potential of Resveratrol Against Pancreatic Cancer Through Network Pharmacology

Resveratrol, a naturally occurring polyphenol, exhibits anticancer, anti-inflammatory, and antioxidant properties. However, its molecular mechanisms in pancreatic cancer remain incompletely understood, necessitating integrative approaches such as network pharmacology and molecular docking. Potential resveratrol targets were identified using Swiss Target Prediction, while pancreatic cancer-related genes were retrieved from GeneCards and NCBI Gene databases. Overlapping targets were obtained through Venn analysis, followed by protein- protein interaction network construction, hub gene selection, and enrichment analysis. Molecular docking validated compound-target interactions. A total of 100 predicted resveratrol targets and 1,447 pancreatic cancer- associated genes were screened, yielding 39 overlapping genes. Network analysis identified hub genes including EGFR, SRC, MTOR, PIK3CA, PIK3CB, BCL2, and PTGS2. Gene Ontology enrichment indicated roles in cell proliferation, apoptosis regulation, inflammatory response and metabolic regulation while KEGG pathway analysis highlighted the PI3K-Akt, ErbB, and EGFR inhibitor resistance signaling as being closely associated with pancreatic cancer pathway. Docking analysis revealed strong binding of resveratrol with KRAS (-8.2 kcal/mol), EGFR (-7.9 kcal/mol), and MTOR (-7.7 kcal/mol), stabilized by hydrogen bonding. The interaction with KRAS, although not among the predicted targets. Expression profiling validated upregulation of hub genes in tumor samples. Resveratrol exerts multi-targeted effects in pancreatic cancer by modulating oncogenic pathways, particularly KRAS and PI3K/Akt/mTOR signaling. Its favourable safety profile and robust hub gene interactions highlight its potential as a supplementary therapeutic drug, necessitating further preclinical and clinical confirmation.

bioinformatics↗

bioRxiv2024

Evaporation of bacteria-laden surrogate respiratory fluid droplets: On a hydrophilic substrate versus contact-free environment confers differential bacterial infectivity

The transmission of viruses/ bacteria cause infection predominantly via aerosols. The transmission mechanism of respiratory diseases is complex, including direct or indirect contact, large droplet, and airborne routes apart from close contact transmission. With this pretext, we have investigated two modes of droplet evaporation to understand its significance in airborne disease transmission; a droplet in a contact-free environment, which evaporates and forms droplet nuclei, and a droplet on a hydrophilic substrate (fomite). The study examines mass transport, the deposition pattern of bacteria in the precipitates, and their survival and virulence. The osmotic pressure increases with the salt concentration, inactivating the bacteria embedded in the precipitates with accelerated evaporation. Further, the bacterias degree of survival and enhanced pathogenicity are compared for both evaporation modes. The striking differences in pathogenicity are attributed to the evaporation rate, oxygen availability, and reactive oxygen species (ROS) generation.

microbiology↗

bioRxiv2022

Enhanced transcriptional strength of HIV-1 subtype C minimizes gene expression noise and confers stability to the viral latent state

The stochastic fluctuations in gene expression emanating from HIV-1 long terminal repeat (LTR), amplified by the Tat positive feedback circuit, determine the choice between viral infection fates: active transcription (ON) or transcriptional silence (OFF). The emergence of several transcription factor binding site (TFBS) variant strains in HIV-1 subtype C (HIV-1C), especially those containing the duplication of NF-{kappa}B motif, mandates the evaluation of the effect of enhanced transcriptional strength on gene expression noise and its influence on viral fate-selection switch. Using a panel of subgenomic LTR-variant strains containing varying copy numbers of the NF-{kappa}B motif (ranging from 0 to 4), we employed flow cytometry, mRNA quantification, and pharmacological perturbations to demonstrate an inverse correlation between promoter strength and gene expression noise in Jurkat T-cells and primary CD4+ T-cells. The inverse correlation is consistent in clonal cell populations, at constant intracellular concentrations of Tat, and when NF-{kappa}B levels were regulated pharmacologically. Further, we show that strong LTRs containing at least two copies of the NF-{kappa}B motif in the enhancer establish a stabler latent state and demonstrate rapid latency reversal than weak LTRs containing fewer motifs. An engineered LTR containing three copies of the C-{kappa}B motif (CCC), an element unique for HIV-1C, demonstrated significantly higher levels of gene expression noise compared to the canonical HHC-LTR or two other engineered LTRs containing three copies of the H-{kappa}B (HHH) or F-{kappa}B (FFF) motif. This result suggests the indispensable nature of the C-{kappa}B motif for HIV-1C despite higher-level gene expression noise. We also demonstrate a cooperative binding of NF-{kappa}B to the motif cluster in HIV-1C LTRs containing two, three, or four NF-{kappa}B motifs (H = 2.61, 3.56, and 3.75, respectively). The present work alludes to a possible evolution of HIV-1C LTR towards gaining transcriptional strength associated with attenuated gene expression noise with implications for viral latency. Author SummaryOver the past two consecutive decades, HIV-1C has been undergoing directional evolution towards augmenting the transcriptional strength of the LTR by adding more copies of the existing TFBS by sequence duplication. Additionally, the duplicated elements are genetically diverse, suggesting broader-range signal receptivity by variant LTRs. HIV-1 promoter is inherently noisy, and the stochastic fluctuations in gene expression of variant LTRs may influence the ON/OFF latency decisions. The evolving NF-{kappa}B motif variations of HIV-1C offer a powerful opportunity to examine how the transcriptional strength of the LTR might influence gene expression noise. Our work here shows that the augmented transcriptional strength of HIV-1C LTR leads to a concomitantly reduced gene expression noise, consequently leading to stabler latency maintenance and rapid latency reversal. The present work offers a novel lead towards appreciating the molecular mechanisms governing HIV-1 latency.

microbiology↗

bioRxiv2020

Integrated genomic view of SARS-CoV-2 in India

India first detected SARS-CoV-2, causal agent of COVID-19 in late January-2020, imported from Wuhan, China. March-2020 onwards; importation of cases from rest of the countries followed by seeding of local transmission triggered further outbreaks in India. We used ARTIC protocol based tiling amplicon sequencing of SARS-CoV-2 (n=104) from different states of India using a combination of MinION and MinIT from Oxford Nanopore Technology to understand introduction and local transmission. The analyses revealed multiple introductions of SARS-CoV-2 from Europe and Asia following local transmission. The most prevalent genomes with patterns of variance (confined in a cluster) remain unclassified, here, proposed as A4-clade based on its divergence within A-cluster. The viral haplotypes may link their persistence to geo-climatic conditions and host response. Despite the effectiveness of non-therapeutic interventions in India, multipronged strategies including molecular surveillance based on real-time viral genomic data is of paramount importance for a timely management of the pandemic.

microbiology↗

bioRxiv2020

Grain number and genotype drive nitrogen-dependent yield response in the C4 model Setaria italica (L.) P. Beauv.

Fertiliser nitrogen (N) drives crop yields and requires the breeding and selection of cultivars that are inherently highly N responsive. For major cereal crops such as wheat (Triticum aestivum L.) breeding over time has led to enhanced N use in modern cultivars however there remains a gap in understanding the N responsiveness of minor cereals grains, many of which are highly relevant to global food security. Here we investigate response to increasing N availability in a diverse population of Setaria italica (L., foxtail millet) accessions demonstrating that N-driven yield increase is dependent on grain number rather than individual grain weight. Within the population, some accessions responded strongly to increased N availability while others show little yield improvement under high N. Genetic markers were generated to enable investigation of N responsiveness at a genome-wide level, highlighting likely underlying causal loci, especially for grains per plant. Despite the lack of response in terms of yield increase, a non-responsive accession shows a strong transcriptional response suggesting different metabolic functioning under high vs low N. Our results show major differences in N responsiveness in S. italica and provide novel insight into the genetic and molecular basis for this variation. One sentence summaryNitrogen dependent yield response in Setaria italica L. is driven by grain number and genotypes with low N yield responsive genotypes being more transcriptionally dynamic under varied N levels post-flowering compared to high N yield responsive genotypes.

plant biology↗