Biology subjects

Bihari, C.

Publications and source records attributed to Bihari, C..

4 recordsLinked to original sources

bioRxiv2026

Phytometabolite-Enriched Edible Plant-Derived Extracellular Vesicles Exhibit Source-Specific Bioactives with Distinct Pharmacological Potential

Edible plant derived extracellular vesicles (PDEVs) are emerging as biocompatible, orally deliverable nanocarriers with therapeutic potential; however, their phytometabolite cargo, gastrointestinal stability, and source specific biological functions remain poorly characterized. Here, PDEVs were isolated from four phytochemically distinct plant based foods (black carrot, ginger, garlic, and turmeric), selected for their diverse bioactivity, and characterized by transmission electron microscopy, nanoparticle tracking analysis, and zeta potential. Gastrointestinal stability was evaluated in simulated digestion model. Source specific phytometabolites were profiled by untargeted LC MS MS metabolomics. Functionally validated in ammonia stressed epithelial cells and steatotic hepatocytes. PDEVs exhibited characteristic cup shaped morphology with particle sizes ranging from 60 to 214 nm and zeta potentials of -6.0 to -49.0 mV. PDEVs retained colloidal stability, supporting their suitability for oral delivery. We identified 572 phytometabolites with distinct source specific signatures, including lignin and quercetin in carrot EVs, [6] gingerol and silymarin in ginger EVs, diosgenin in garlic EVs, and curcumin in turmeric EVs. These metabolites found associated to antioxidant, anti inflammatory, epithelial barrier, lipid metabolic, and apoptotic pathways. Functional validation demonstrated carrot EVs significantly enhanced epithelial barrier integrity by increasing claudin (>8-fold, p<0.05), occludin (>2-fold, p<0.05). Ginger EVs restored ZO 1 while suppressing cyclin D1 and MMP9(p<0.05). Garlic and turmeric EVs attenuated inflammatory signaling by reducing STAT3, AKT1, and TNF , whereas turmeric EVs additionally decreased caspase 3 and PTGS2(p<0.01). In steatotic hepatocytes, garlic EVs significantly reduced PNPLA3 (p<0.001) and SREBP 1c while increasing PPAR- (p=0.002). Hence, our results indicate that edible PDEVs are gastrointestinally stable, phytometabolite enriched nanocarriers with distinct source specific functional properties, supporting their potential as orally deliverable nutraceuticals for improving gut liver functions.

pharmacology and toxicology↗

bioRxiv2025

Chenodeoxycholic Acid Modulation via Bacteroides intestinalis AM1 underscores a Novel Approach in Acute Liver Failure

BackgroundAcute liver failure (ALF) is associated with rapid and progressive hepatocellular injury, and severe metabolic-microbial derangements. We investigated early metabolic markers of non-survival, and a potential microbial intervention using Bacteroides intestinalis-AM1, to improve outcomes in ALF. MethodPlasma metabolomics and meta-proteomics were performed in 40 ALF patients and 5 healthy controls (training cohort). A non-survival marker panel was identified and validated in 270 ALF patients (test cohort) using high resolution mass spectrometry and machine learning. It was functionally validated in acetaminophen-induced ALF mouse model. B. intestinalis-AM1 was used to study alteration of gut bacteria and amelioration of liver injury. ResultsALF non-survivors showed a distinct metabolomic signature with elevated primary bile acids {chenodeoxycholic acid (CDCA), cholic acid (CA)}, tryptophan, tyrosine, and enrichment of pathways linked to inflammation, cell death, and stress response (p<0.01, FDR<0.01, FC>1.5). Non-survivors had higher alpha/beta diversity (p<0.05) with increase in Proteobacteria, Firmicutes, Actinobacteria (p<0.05); functionally associated with energy, amino acid and xenobiotic metabolism (p<0.05). A gut microbiota derangement in converting primary to secondary bile acids was evident as CDCA and cytotoxic metabolites (4-(2-Amino phenyl)-2,4-dioxobutanoate, L-Tyrosine) were higher. Elevated CDCA (logFC>10) levels correlated with mortality in ALF patients as well as in mouse model. In the later, administration of B. intestinalis-AM1 bacteria, (10^9) reduced CDCA and CA levels by enhancing FXR, FGF15, SLC10A1 gene expression, attenuating inflammation (IL-1beta, TLR4-signalling), necroptosis, and modulating glutathione(oxidative-repair), tryptophan(inflammation), and histidine (tissue repair) metabolism. ConclusionHigh levels of chenodeoxycholic acid (CDCA) represent a poor prognostic indicator in ALF patients. B. intestinalis-AM1, a primary-to-secondary bile acid converter, effectively reduce CDCA levels, activated FXR, reduced inflammation and protected hepatocytes, highlighting its therapeutic potential in ALF.

microbiology↗

bioRxiv2023

Genomic perspectives of SARS CoV-2 in liver disease patients with its clinical correlation: A single centre retrospective study

BackgroundSevere Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2), is a causative agent of current global pandemic of Coronavirus disease-19 (COVID-19). Due to propagated outbreak and global vaccination drive an immense immunological selection pressure has been exerted on SARS CoV-2 leading to evolution of new variants. This study was performed to compare the mutational and clinical profile of liver disease patients infected with different variants of SARS CoV-2. MethodologyThis was a single-centre, retrospective, cohort study in which clinicogenomic analysis of liver disease (LD) patients infected with SARS CoV-2 was performed. Complete demographic and clinical details were retrieved from Hospital Information System (HIS). QC-threshold passed FASTA files containing sequences from COVID-19 patients (n=174) were compared with a reference genome of SARS-CoV-2 isolate named Wuhan-Hu-1 (NCBI Reference Sequence: NC_045512.2) for mutational analysis. ResultsOut of 232 finally analysed patients 137 (59.1%) were LD-CoV (+) and 95 (40.9%) were LD-CoV(-). LD patients with comorbidities were affected more with COVID-19 (p=0.002). On comparing the outcome in the terms of mortality, LD-CoV (+) had 2.29 times (OR 2.29, CI 95%, 1.25-4.29) higher of odds of succumbing to COVID-19 (p=0.006). Multivariate regression analysis revealed, abdominal distention (p=0.05), severe COVID-19 pneumonia (p=0.046) and the change in serum bilirubin levels (p=0.005) as well as Alkaline phosphatase (ALP) levels (p=0.003) to have an association with adverse outcome in LD patients with COVID-19. In Delta (22%) and Omicron (48%) groups, Spike gene harboured maximum mutations. On comparing the mutations between LD-CoV(+/D) and LD-CoV(+/O) a total of nine genes had more mutations in LD-CoV(+/O) whereas three genes had more mutations in LD-CoV(+/D). ConclusionWe concluded that LD patients are more susceptible to COVID-19 as compared to a healthy adult with associated adverse clinical outcomes in terms of mortality and morbidity. Therefore this special group should be given priority while devising and introducing new vaccination and vaccination policies. The infection with different variants did not result in different outcome in our group of patients.

microbiology↗

bioRxiv2020

Multi-omics analysis of aspirin treatment response in mice provide molecular insights and targets linked to liver fibrosis regression.

Background & Aims Aspirin has potent anti-platelet activities and possibly helps regression of fibrosis. We investigated antifibrotic mechanisms of aspirin in the murine CCl4 model and in patients with hepatic fibrosis.Methods Multiomics analysis identified networks and molecular targets regulated by aspirin which were validated in murine model and in patients with liver fibrosis.Results Biochemical/histopathological changes and hepatic fibrosis were greater in CCl4-treated mice compared to CCl4-aspirin (CCl4+ASA) or control mice (p<0.05). In CCl4+ASA mice, integrated proteome-metabolome analysis showed an increase in autophagy, drug metabolism, glutathione and energy metabolism (p<0.05) and decrease in inflammatory pathways, arachidonic acid and butanoate metabolism (p<0.05). Global cross-correlation analysis linked fibrosis markers with protein-metabolite pathways (r2>0.5, p<0.05). Liver proteome enrichment for immune clusters using blood transcription module correlated with histidine and tryptophan metabolism (r2>0.5, p<0.05). Aspirin decreased Ryanodine-receptor-2 (RYR2;oxidative-stress), Arginase-1 (ARG-1;urea cycle), Arachidonate-5-lipoxygenase (ALOX5;leukotriene metabolism), and Kynurenine-3-monooxygenase (KMO;tryptophan metabolism; p<0.05) which correlated with reduction in α-SMA, PDGFR-β and degree of hepatic fibrosis (r2>0.75; p<0.05) in animal and human studies, and, in-vitro analysis. Aspirin modulated intracellular-calcium and oxidative-stress levels by reducing RYR2 expression in activated LX-2 cells. It modulated the liver microbiome and its functions which also correlated with ARG1, ALOX5, RYR2 expression (r2>0.5, p<0.05). Metaproteome analysis showed significant microbiome similarity at phylum level in murine liver tissues and fecal samples. Aspirin increased the abundance of Firmicutes (Ruminococcaceae, Lachnospiraceae, and Clostridiaceae) and their functionality, as assessed by glycerol-3-phosphate dehydrogenase (NAD(P)(+) and dTMP-kinase activity (p<0.05).Conclusions Aspirin demonstrates broad beneficial effects following oxidative injury, inflammation, and hepatic fibrosis. Aspirin induces distinctive hepatic proteome/metabolome and intrahepatic microbiome changes which are indicative of fibrosis regression and could be further explored as therapeutic targets.Competing Interest StatementThe authors have declared no competing interest.View Full Text

molecular biology↗