Biology subjects

Kothari, V.

Publications and source records attributed to Kothari, V..

17 recordsLinked to original sources

bioRxiv2025

Withania somnifera root extract reduces susceptibility of the model worm Caenorhabditis elegans to different types of stressors

BackgroundWithania somnifera, commonly known as Ashwagandha, is one of the most widely prescribed plants in the Indian system of traditional medicine. Its roots are believed to impart comprehensive health benefits supporting lifespan and healthspan through its anti-stress, immunomodulatory, and neuroprotective activity. Scientific validation of its claimed biological effects is warranted. MethodsThe nematode worm Caenorhabditis elegans was challenged with heat or certain neurotoxic/mitotoxic chemical stressors, and worm activity (healthspan) was compared between W. somnifera root extract (WSRE)-exposed and control worm populations, through an automated worm tracker. ResultsPrevious exposure of worms to WSRE conferred prophylactic benefit on them in face of subsequent challenge with rotenone, MnCl2, or levamisole. Worms pre-exposed to either of these toxins were able to recover faster in presence of WSRE. This extract was also able to reduce the susceptibility of wild type worms to heat-induced paralysis, and that of transgenic worms to beta-amyloid mediated paralysis. ConclusionsAdaptogenic potential of W. somnifera roots was demonstrated in worm model. WSRE can be said to possess a wide anti-stress spectrum as it protected the worms against different stressors inducing toxicity through different mechanisms including interference with acetylcholine and dopamine neurons and function. Our results support the candidature of W. somnifera roots as a potent nutraceutical.

pharmacology and toxicology↗

bioRxiv2025

Berberine, the major bioactive compound from Berberis aristata, attenuates virulence of multidrug resistant Chromobacterium violaceum at non-lethal concentrations by targeting bacterial efflux and denitrification machinery

Berberis aristata root extract, and berberine were assessed for their anti-pathogenic activity against multidrug resistant Chromobacterium violaceum. Berberine was found to be more potent than the parent extract with respect to attenuation of the pathogens virulence against the model host Caenorhabditis elegans. It also performed better than six different antibiotics, when compared at same concentration. Berberine was able to modulate multiple traits of the target pathogen, such as, biofilm formation, haemolytic activity, efflux/transport activity, and exopolysaccharide production. Repeated exposure of C. violaceum to berberine did not induce resistance. Whole transcriptome analysis of the berberine-treated C. violaceum revealed differential expression of genes associated with stress response, efflux, denitrification, and metalloproteases. Downregulation of two genes of the denitrification pathway, nirK and norB, was confirmed through RT-PCR too.

microbiology↗

bioRxiv2025

Identification and Characterization of PLUTO-201, a Novel Long Non-Coding RNA Associated with Poor Outcomes in Prostate Cancer

Background: Despite extensive investigation, the factors promoting aggressive prostate cancer are poorly understood. In particular, despite a few prominent examples, the role of long non-coding RNAs (lncRNAs) is largely unknown. Methods: We performed a comprehensive analysis of whole-genome transcriptome data to identify differential expression across 1,567 patients with prostate cancer, then correlated differential expression with risk of metastatic recurrence. We characterized the lncRNA most associated with metastasis in vitro and in vivo to investigate the mechanism by which it promotes aggressive prostate cancer. Results: We have identified a novel lncRNA, Prostate Cancer Associated hnRNPK Interacting Transcript (PCAHIT), which is strongly associated with metastasis and poor overall survival in men with prostate cancer. We find that overexpression/knockdown of PCAHIT in pre-clinical models of prostate cancer modulates proliferation rates and markers of an aggressive phenotype through regulation of steroid biosynthesis and expression of the MHC class I complex, driving increased growth in androgen-depleted conditions and decreased susceptibility to T cell-mediated cytotoxicity. We further find that the heterogeneous nuclear ribonucleoprotein hnRNPK directly binds PCAHIT and is indispensable for its activity. Conclusions: Overall, our findings indicate that PCAHIT is a driver of aggressive prostate cancer phenotypes and poor clinical outcomes through suppression of the immune response and increased androgen-independent cancer growth. PCAHIT is a potential biomarker of aggressive disease.

cancer biology↗

bioRxiv2025

Soluble TREM2 is a biomarker but not a mediator of fibrosing steatohepatitis

BackgroundTriggering receptor expressed on myeloid cells 2 (TREM2), a transmembrane, lipid-sensing protein expressed by Kupffer cells, is thought to play a role in metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). Plasma levels of the TREM2 cleavage product, soluble TREM2 (sTREM2), are strongly associated with MASLD severity. We investigated the role of TREM2 in MASH pathogenesis and whether sTREM2 acts both as biomarker and mediator of MASH. MethodsAdult C57BL/6J mice were assigned to normal, high-fat (HF), or high-fat and high-cholesterol (HFHC) diets for 15, 30, 90, and 180 days. Plasma sTrem2 levels, liver pathology, and hepatic RNA expression were assessed. To test whether sTrem2 is a mediator of MASH, C57BL/6J mice were injected retro-orbitally with a liver-targeted adeno-associated virus, TBG-AAV8-sTrem2, resulting in secretion of sTrem2 by hepatocytes, or empty TBG-AAV8-control, and subsequently fed HFHC diet for 15, 90, or 180 days. ResultsHFHC-fed mice developed fibrosing steatohepatitis at 180 days together with a 15-fold increase in plasma sTrem2 levels. In the livers of HFHC-fed mice, crown-like structures (CLSs) consisting of TREM2+ macrophages surrounded necrotic, steatotic hepatocytes and their remnant lipid droplets, which contained prominent crystals containing cholesterol. TBG-AAV8-sTrem2-injected mice had higher levels of plasma sTrem2 than TBG-AAV8-control-injected mice, but there were no differences in liver weight, body weight, hepatic fibrosis, hepatic inflammation, hepatic cholesterol crystals, or plasma cholesterol levels. ConclusionTREM2+ macrophages characterize the CLSs that surround necrotic hepatocytes and their remnant lipid droplets and cholesterol crystals in fibrosing steatohepatitis-MASH. Plasma sTrem2 is a biomarker, but not a causal mediator, of MASH.

molecular biology↗

bioRxiv2024

Withania somnifera root extract (LongeFera-TM) confers beneficial effects on health and lifespan of the model worm Caenorhabditis elegans

Withania somnifera is among the most widely prescribed medicinal plants in traditional Indian medicine. Hydroalcoholic extract of the roots of this plant was investigated for its effects on the overall health and lifespan of the model worm Caenorhabditis elegans. Extract-exposed worms registered longer lifespan, higher fertility, better motility and metabolic activity. Whole transcriptome analysis of the extract-treated worms revealed the differential expression of the genes associated with lifespan extension, eggshell assembly and integrity, progeny formation, yolk lipoproteins, collagen synthesis, cuticle molting, etc. This extract seems to exert its beneficial effect on C. elegans partly by triggering remodeling of the developmentally programmed apical extracellular matrix (aECM). Differential expression of certain important genes (cpg-2, cpg-3, sqt- 1, dpy-4, dpy-13, and col-17) was confirmed through PCR assay too. Some of the differently expressed genes (gfat-2, unc-68, dpy-4, dpy-13, col-109, col-169, and rmd-1) in worms experiencing pro-health effect of the extract were found through cooccurrence analysis to have their homologous counterpart in humans. Our results validate the potential of W. somnifera extract as a phytopharmaceutical.

molecular biology↗

bioRxiv2024

Identification of anthelmintic activity in a small chemical library through random screening using the worm Caenorhabditis elegans as a model helminth

Parasitic helminths contribute notably to the global infection burden, particularly in developing and underdeveloped nations. Anthelmintic agents currently available for therapeutic purpose are not many in number, and owing to development of resistance against them among parasitic worms, their utility spectrum is also shrinking. Hence, there is an urgent need for discovery of new anthelmintic compounds. This study subjected a small library of 181 compounds to a random screening for identification of compounds with anthelmintic activity against the model worm Caenorhabditis elegans. This screening effort identified 50 compounds capable of killing 100% of the worm population in less than 24 hours, at 25-50 ppm. Further investigation on these hits is warranted to identify potential anthelmintic leads.

microbiology↗

bioRxiv2024

Silversol (a colloidal nanosilver formulation) inhibits growth of antibiotic-resistant Staphylococcus aureus by disrupting its physiology in multiple ways

Antibacterial effect of a colloidal nanosilver formulation Silversol(R) was investigated against an antibiotic-resistant strain of Staphylococcus aureus. Lower concentrations of the test formulation exerted bacteriostatic and, its higher concentrations exerted bactericidal effect against this pathogen. Silversol(R) at sub-lethal concentration was found to disturb multiple physiological traits of S. aureus such as growth, antibiotic susceptibility, membrane permeability, efflux, protein synthesis and export, biofilm and exopolysaccharide production, etc. Transcriptome data revealed the genes coding for transcriptional regulators, efflux machinery, transferases, {beta}-lactam resistance, oxidoreductases, metal homeostasis, virulence factors, and arginine biosynthesis to get expressed differently under influence of the test formulation. Genes (argG and argH) involved in arginine biosynthesis emerged among the major targets of Silversol(R) in S. aureus.

microbiology↗

bioRxiv2024

Deciphering the molecular mechanisms underlying anti-pathogenic potential of a polyherbal formulation Enteropan against multi-drug resistant Pseudomonas aeruginosa

Anti-pathogenic potential of a polyherbal formulation Enteropan(R) was investigated against a multidrug resistant strain of the bacterium Pseudomonas aeruginosa. Enteropan-pre-exposed P. aeruginosa displayed reduced ([~]70%{downarrow}) virulence towards the model host Caenorhabditis elegans. Enteropan affected various traits like biofilm formation, protein synthesis and secretion, quorum-modulated pigment production, antibiotic susceptibility, nitrogen metabolism etc. in this pathogen. P. aeruginosa could not develop complete resistance to the virulence-attenuating activity of Enteropan even after repeated exposure to this polyherbal formulation. Whole transcriptome analysis showed 17% of P. aeruginosa genome to get differentially expressed under influence of Enteropan. Major mechanisms through which Enteropan exerted its anti-virulence activity were found to be generation of nitrosative stress, oxidative stress, envelop stress, quorum modulation, disturbance of protein homeostasis and metal homeostasis. Network analysis of the differently expressed genes resulted in identification of 10 proteins with high network centrality as potential targets from among the down-regulated genes. Differential expression of genes coding for five (rpoA, tig, rpsB, rpsL, and rpsJ) of these targets was validated through RT-PCR too, and they can further be pursued as potential targets by various drug discovery programmes.

microbiology↗

bioRxiv2023

Identification of anti-pathogenic activity among in silico predicted small molecule inhibitors of Pseudomonas aeruginosa LasR or Nitric Oxide Reductase (NOR)

Antibiotic resistant Pseudomonas aeruginosa strains cause considerable morbidity and mortality. Identification of novel targets in this notorious pathogen is urgently warranted to facilitate discovery of new anti-pathogenic agents acting against it. Attacking non-essential targets is believed to be a potential anti-virulence strategy. This study attempted to identify small molecule inhibitors of two important proteins LasR and nitric oxide reductase (NOR) in P. aeruginosa. This bacterial pathogen possesses multiple quorum sensing (QS) systems to regulate expression of many of its genes including those associated with virulence. Among these QS systems, Las system can be said to be the master regulator, whose receptor protein is LasR. Similarly, NOR plays crucial role in detoxification of reactive nitrogen species. This study attempted in silico identification of potential LasR or NOR inhibitors through a virtual screen employing AtomNet(R), a proprietary deep learning neural network. Following virtual screening of a large number of compounds for their affinity to LasR or NOR, a final subset of <100 compounds was created by clustering and filtering the top scoring compounds. These compounds were evaluated for their in vivo anti-pathogenic activity by challenging the model host Caenorhabditis elegans with P. aeruginosa in presence or absence of test compounds. Survival of the worm population in 24-well assay plates was monitored over a period of 5 days microscopically. Of the 96 predicted LasR inhibitors, 11 exhibited anti-Pseudomonas activity (23-96% inhibition of bacterial virulence as per third-day end point) at 25-50 {micro}g/ml. Of the 85 predicted NOR inhibitors, 8 exhibited anti-Pseudomonas activity (40-85% inhibition of bacterial virulence as per second-day end point) at 25-50 {micro}g/ml. Further investigation on molecular mode of action of active compounds is warranted.

microbiology↗

bioRxiv2023

Identifying molecular targets of a colloidal nanosilver formulation (Silversol) in multidrug resistant Pseudomonas aeruginosa

P. aeruginosa is a notorious pathogen. A multi-drug resistant strain of this bacterium was challenged with a colloidal nano-silver formulation- Silversol(R). Its minimum inhibitory concentration against P. aeruginosa was found to be 1.5 ppm, and at sub-MIC of 1 ppm, it was able to alter quorum-sensing regulated pigmentation, exopolysaccharide synthesis and biofilm formation, antibiotic susceptibility, protein synthesis and export, nitrogen metabolism, and siderophore production in this pathogen. Transcriptome analysis of the silver-exposed P. aeruginosa indicated generation of nitrosative stress and disturbance of iron homeostasis to be the major mechanisms associated with anti-Pseudomonas activity of Silversol(R). Network analysis of the differentially expressed genes in silver-treated bacterium identified ten genes as the potential molecular targets: norB, norD, nirS, nirF, nirM, nirQ, nosZ, nosY, narK1, and norE (all associated with nitrogen metabolism or denitrification). Three of them (norB, narK1, and norE) were also validated through RT-PCR.

microbiology↗

bioRxiv2023

Network analysis for identifying potential anti-virulence targets through whole transcriptome analysis of Pseudomonas aeruginosa and Staphylococcus aureus exposed to certain anti-pathogenic polyherbal formulations

Transcriptome of two important pathogens, Pseudomonas aeruginosa and Staphylococcus aureus exposed to two different quorum-modulatory polyherbal formulations were subjected to network analysis to identify the most highly networked differentially expressed genes (hubs) as potential anti-virulence targets. Genes associated with denitrification and sulfur metabolism emerged as the most important targets in P. aeruginosa. Increased build-up of nitrite (NO2) in P. aeruginosa culture exposed to the polyherbal formulation Panchvalkal was confirmed through in vitro assay too. Generation of nitrosative stress and inducing sulfur starvation seems to be effective anti-pathogenic strategies against this notorious gram-negative pathogen. Important targets identified in S. aureus were the transcriptional regulator sarA, immunoglobulin-binding protein Sbi, serine protease SplA, the saeR/S response regulator system, and gamma-haemolysin components hlgB and hlgC. Further validation of the potential targets identified in these pathogens is warranted through appropriate in vitro and in vivo assays in model hosts. Such validated targets can prove vital to many antibacterial drug discovery programmes globally.

microbiology↗

bioRxiv2023

Length of fermentation time affects microbiome composition and biological activity of Panchgavya

ObjectiveThis study aimed at investigating whether the duration of fermenting Panchgavya (PG) preparation in copper vessel affects its biological activity and microbiome composition. MethodsProphylactic potential of PG against bacterial infection was assessed through an in vivo assay employing the nematode worm Caenorhabditis elegans as a model host. Bacterial diversity of the PG samples was revealed through metagenomic analysis. ResultsDuration of fermentation was found to affect biological activity as well as microbiome composition of the PG samples. PG-samples fermented [≥]60 min lost their prophylactic potential, and develop anthelmintic activity. Bacterial phyla whose relative abundance was significantly different between the prophylactic and anthelmintic PG samples were Planctomycetota, Proteabacteria, Bacteroidota, Verrucomicrobiota, Patescibacteria, Acidobacteriota, Chloroflexi, Firmicutes and Campilobacterota. ConclusionThis study validates the prophylactic potential of Panchgavya against bacterial pathogens, and shows that duration of the fermentation time while preparing PG can have profound effect on its biological activities. Biological activities of PG samples seem to have a correlation with their inherent microbial community. Metagenomic profiling can be an effective tool for standardization of PG formulations.

microbiology↗

bioRxiv2019

Investigation on the effect of sonic stimulation on Xanthomonas campestris at the whole transcriptome level

A gram-negative bacterium Xanthomonas campestris was subjected to sonic stimulation with sound pertaining to 1000 Hz at three different sound intensities. The X. campestris culture subjected to sonic stimulation at 66 dB produced 1.69 fold higher exopolysaccharide. Whole transcriptome analysis of this sonic-stimulated culture revealed a total of 115 genes expressed differentially in the sonic-stimulated culture, majority of which were coding for different proteins including enzyme. This study demonstrates the property of the test bacterium of being responsive to sonic/vibrational stimulation.

microbiology↗

bioRxiv2019

Investigating the influence of extraction methodology, and certain other experimental parameters on bacterial response to selected quorum-modulatory plant extracts

In context of the global threat of antimicrobial resistance (AMR), a large number of labs throughout the world are investigating plant extracts for their possible anti-pathogenic efficacy. Outcome of protocols employed for screening the plant extracts for such activities are influenced by multiple factors. Among them, this study has found the method used for extraction, size and volume of the assay system, to be important factors. Further we demonstrate the extracts prepared by microwave-and vacuum-assisted extraction methods to be stable with respect to their anti-pathogenic efficacy over a long period of storage.

microbiology↗

bioRxiv2018

Sonic stimulation, and low power microwave radiation can modulate bacterial virulence towards Caenorhabditis elegans

Caenorhabditis elegans worms infected with different pathogenic bacteria were subjected to sonic treatment to investigate whether such sound treatment can exert any therapeutic effect on the infected worms. Sonic therapy corresponding to 400 Hz, and the divine sound om were found to confer protective effect on this nematode worm in face of bacterial infection, particularly that caused by Serratia marcescens or Staphylococcus aureus. The observed effect seemed to occur due to influence of sound on bacteria, and not on the worm. In addition to this, effect of microwave exposure on bacterial virulence was also investigated, wherein microwave exposure was found to reduce virulence of S. aureus towards C. elegans.

microbiology↗

bioRxiv2017

Anti-infective potential of a quorum modulatory polyherbal extract (Panchvalkal) against certain pathogenic bacteria

Anti-infective potential of a polyherbal ayurvedic formulation namely panchvalkal was assayed against three pathogenic bacteria. This formulation was found to exert quorum-modulatory effect on Chromobacterium violaceum, Serratia marcescens, and Staphylococcus aureus at 250-750 g/mL. Besides altering production of the quorum sensing-regulated pigments in these bacteria, the test formulation also had in vitro effect on antibiotic susceptibility, catalase activity and hemolytic potential of the pathogens. In vivo assay confirmed the protective effect of this panchvalkal formulation on Caenorhabditis elegans, when challenged with the pathogenic bacteria. Repeated exposure of S. aureus to panchvalkal did not induce resistance in this bacterium. To the best of our awareness, this the first report on quorum-modulatory potential of panchvalkal formulation, validating the anti-infective potential and moderate prebiotic property of this polyherbal preparation.

microbiology↗

bioRxiv2017

Frequency-dependent response of Chromobacterium violaceum to sonic stimulation, and altered gene expression associated with enhanced violacein production at 300 Hz

Chromobacterium violaceum was subjected to sonic (100-2000 Hz) stimulation, and the effect on its cell yield and quorum sensing regulated pigment (violacein) production was investigated. Sound corresponding to the 300 Hz was found to promote (by 1.52 fold) violacein production the most, with only marginal impact on cell yield. Whole transcriptome analysis revealed that a total of 342 genes (i.e. 4.63% of whole genome) were significantly up-regulated in the sonic stimulated culture. Enhanced violacein production in the sound stimulated culture seems to have stemmed from enhanced expression of the genes involved in glucose metabolism through pentose phosphate pathway, resulting in increased availability of erythrose-4-phosphate, to be used for synthesis of tryptophan, the precursor for violacein synthesis. Multiple ribosomal subunit genes, enzyme coding genes, and those associated with secretion/transport were up-regulated owing to sonic stimulation. This study is a good demonstration of the ability of sound waves to alter bacterial metabolism.

microbiology↗