Biology subjects

Verma, I.

Publications and source records attributed to Verma, I..

7 recordsLinked to original sources

bioRxiv2026

Brief, repeated isoflurane anaesthesia elicits sex-dependent behavioural, cerebrovascular, and microglial alterations in mice

General anaesthetics are indispensable tools in biomedical research, yet growing evidence shows that their effects on brain function extend beyond the transient loss of consciousness for which they are used. Although numerous preclinical studies have examined the impact of a single anaesthetic exposure, far less is known about the cumulative consequences of repeated administration protocols, despite their widespread use in longitudinal imaging, behavioural testing, and disease model studies. Here, we show that brief, repeated isoflurane exposures induce alterations in behaviour, cerebrovascular patterns, and microglial phenotype in adult CD1 mice, with several responses exhibiting pronounced sex specificity. Repeated anaesthesia suppressed locomotor activity selectively in females and impaired ethologically important maintenance behaviours, including nesting and burrowing, in both sexes. These behavioural effects were accompanied by sex-dependent changes in cerebral blood flow dynamics, with females displaying elevated cerebrovascular flow, yet males showing higher reactivity to isoflurane exposure. At the molecular level, repeated isoflurane exposure altered endothelial marker expression without modifying capillary density and shifted microglia toward a hyporeactive state. Together, these data reveal that even short, routine anaesthetic events produce biologically meaningful and sex-dependent effects on neural, vascular, and immune systems. These results indicate that the anaesthetic regimen is an often overlooked but influential factor that deserves careful consideration in pre-clinical neuroscience.

neuroscience↗

bioRxiv2025

Epigenetic Modulation of Host Immunity related genes in Pulmonary Tuberculosis: A Comprehensive Analysis of DNA Methylation Profiles in Peripheral Blood Mononuclear Cells

BackgroundIn the last few years, there has been increasing evidence in the literature for promoter hypermethylation of various host genes following infection with various pathogens. Therefore, in the present study, the role of epigenetic reprogramming of host cells through DNA methylation was evaluated which indicates that the disease progression takes place through changes in host immune response related genes. ObjectiveTo elucidate the differential genome-wide DNA methylation profile of peripheral blood mononuclear cells in pulmonary tuberculosis (PTB) patients. Materials and methodsTo decipher the methylation profile of PBMCs in PTB patients whole genome bisulphite sequencing was performed using 4 DNA samples from each study group i.e. PTB, healthy controls and diseased controls. Briefly, the samples were subjected to bisulphite conversion followed by library preparation and whole genome bisulphite sequencing. The data then were analysed for differential methylation analysis followed by gene set enrichment analysis to select DMRs for validation by sanger sequencing. Further the GEOR2 online server was used to investigate the mRNA expression of selected genes associated with hypermethylated DMRs in promoter region. ResultsDifferential methylation region analysis was performed for the following comparisons. TB v/s Diseased (Hypermethylated=1756; Hypomethylated=1886), TB v/s Healthy( Hypermethylated=2203; Hypomethylated=2466), Diseased v/s Healthy ( Hypermethylated=1656; Hypomethylated=3936). Further gene set enrichment analysis showed that the hypermetylated regions belonged to genes that are involved in immune responses mainly T cell functioning and T cell mediated immune processes. There were 8 DMR belonging to TAF8,FZD5, HLA-DRB, MIR483, PVRIG, SH2B2, ZAP70, TNFRSF13C simultaneously (n=10 from each study group). mRNA expression analysis with GEOR2 (Datasets used n= 12) revealed significant downregulation of TNFRSF13C, ZAP70, PVRIG Among the selected genes associated with hypermethylated DMRs in promoter region. (e) ConclusionThe altered differential methylation profile of PBMCs from TB patients shows that on onset the active disease there occurs aberrant methylation of expression regulating regions that in turn results in decreased T cell functions and hence suboptimal immune responses in TB

molecular biology↗

bioRxiv2024

Synovial fluid transcriptome dynamics in osteoarthritis progression: Implications in pathogenesis

BackgroundOsteoarthritis, a degenerative joint disease associated with various pathological manifestations in the joint including cartilage loss, alterations in subchondral bone and synovial inflammation. ObjectiveThis study aimed to elucidate the transcriptional and molecular changes in synovial fluid associated with OA progression, focusing on differential gene expression and pathway enrichment across OA grades. MethodologyPatients with different OA grades were recruited from PGIMER, Chandigarh, following the KL classification. Microarray analysis was conducted to study the transcriptional profiles in different OA grades using a fold-change (FC) cutoff of 2 and a p-value cutoff of 0.05, followed by pathway analysis performed using GSEA and STRING database. Selected genes from microarray and pathway analysis were validated using qRT-PCR. ResultsMicroarray analysis reveals distinct gene expression patterns corresponding to different OA stages (KL grade 2 to KL grade 4). Notably, the upregulation of AMTN and DKK2, alongside the downregulation of MSLN, highlighted their roles in pathological mineralization and disrupted bone remodeling in OA. Pathway enrichment analysis revealed significant changes in immune response, inflammation related pathways and cellular processes such as autophagy and programmed cell death, indicating their involvement in disease progression. Furthermore, mitochondrial dysfunction and impaired autophagy were linked to increased inflammation in advanced OA. ConclusionThese findings suggest that targeting mineralization and inflammatory pathways could offer novel therapeutic avenues for OA management.

pathology↗

bioRxiv2023

Dormant Mycobacterium tuberculosis reactivates ex vivo in blood from HIV infected individuals

Reports of tuberculosis in Human Immunodeficiency Virus infected patients despite high CD4+ T-cell counts suggest different mechanisms of reactivation. In vitro developed dormant Mycobacterium tuberculosis H37Rv were cultured in HIV blood and normal blood. Colony forming units analysis was performed and expression of mycobacterial Resuscitation Promomoting Factor genes was analyzed by qRT-PCR. The in vitro developed dormant M. tb resuscitated in HIV blood as evident from increase in CFUs and up-regulation in the expression of mycobacterial rpf genes. Reactivation of dormant tubercle bacilli following HIV infection in spite of high CD4+ T-cell counts could be due to some viral or host factors which needs further studies.

biochemistry↗

bioRxiv2022

Metabolic switching and cell wall remodelling of Mycobacterium tuberculosis during bone tuberculosis

Bone tuberculosis is widely characterized by irreversible bone destruction caused by Mycobacterium tuberculosis. Mycobacterium has the ability to adapt to various environmental stresses by altering its transcriptome in order to establish infection in the host. Thus, it is of critical importance to understand the transcriptional profile of M. tuberculosis during infection in the bone environment compared to axenic cultures of exponentially growing M.tb. In the current study, we characterized the in vivo transcriptome of M. tuberculosis within abscesses or necrotic specimens obtained from patients with bone TB using whole genome microarrays in order to gain insight into the M. tuberculosis adaptive response within this host microenvironment. A total of 914 mycobacterial genes were found to be significantly over-expressed and 1688 were repressed (fold change>2; p-value [≤]0.05) in human bone TB specimens. Overall, the mycobacteria displayed a hypo-metabolic state with significant (p[≤]0.05) downregulation of major pathways involved in translational machinery, cellular and protein metabolism and response to hypoxia. However, significant enrichment (p [≤]0.05) of amino-sugar metabolic processes, membrane glycolipid biosynthesis, amino acid biosynthesis (serine, glycine, arginine and cysteine) and accumulation of mycolyl-arabinogalactan-peptidoglycan complex suggests possible mycobacterial survival strategies within the bone lesions by strengthening its cell wall and cellular integrity. Data were also screened for M.tb virulence proteins using Virulent Pred and VICM Pred tools, which revealed five genes (Rv1046c, Rv1230c, DppD, PE_PGRS26 and PE_PGRS43) with a possible role in the pathogenesis of bone TB. Next, an osteoblast cell line model for bone TB was developed allowing for significant intracellular multiplication of M.tb. Interestingly, three virulence genes (Rv1046c, DppD and PE_PGRS26) identified from human bone TB microarray data were also found to be overexpressed by intracellular M. tuberculosis in osteoblast cell lines. Overall, these data demonstrate that M. tuberculosis alters its transcriptome as an adaptive strategy to survive in the host and establish infection in bone. Additionally, the in vitro osteoblast model we describe may facilitate our understanding of the pathogenesis of bone TB. Author SummaryMusculoskeletal tuberculosis is the third most common manifestation of extra-pulmonary tuberculosis and massive bone destruction along with vertebral discs are one of the hallmarks of this disease. Mycobacterium tuberculosis, the causative agent, has the tremendous potential to adapt itself to different host environments due to its ability to alter the expression of genes/proteins belonging to different pathways. This study shows that the mycobacterial infection in bone is driven by the increased expression of genes belonging to cell wall remodelling and DNA damage repair pathways important for its survival. Further data analysis showed that some of these genes are coding for proteins possessing virulence potential that may be essential for survival of M. tuberculosis under such hostile environment of bone. We also developed an in vitro model of bone tuberculosis using an osteoblast cell line and validated the expression of these virulence factors. Identification of such virulence factors in the bone environment by M. tuberculosis may aid to identify new therapeutic targets for bone TB. Further, development of cell line model for bone TB is important to understand some unknown facets of this disease.

microbiology↗

bioRxiv2020

Proteomic profiling of peripheral blood mononuclear cells isolated from patients with tuberculosis and diabetes copathogenesis -A pilot study

BackgroundDiabetes is an important risk factor for developing tuberculosis. This association leads to exacerbation of tuberculosis symptoms and delayed treatment of both the diseases. Molecular mechanism and biomarkers/drug targets related to copathogenesis of tuberculosis and diabetes, however, still remains to be poorly understood. In this study, proteomics based 2D-MALDI/MS approach was employed to identify host signature proteins which are altered during copathogenesis of tuberculosis and diabetes. MethodsComparative proteome of human peripheral blood mononuclear cells (PBMCs) from healthy controls, tuberculosis and diabetes patients in comparison to comorbid diabetes and tuberculosis patients was analyzed. Gel based proteomics approach followed by in gel trypsin digestion and peptide identification by mass spectrometry was used for signature protein identification. ResultsTotal of 18 protein spots with differential expression in TBDM patients in comparison to other groups were identified. These include Vimentin, tubulin beta chain protein, superoxide dismutase, Actin related protein 2/3 complex subunit 2, PDZ LIM domain protein, Rho-GDP dissociation inhibitor, Ras related protein Rab, dCTPpyrophosphatase 1, Transcription initiation factor TFIID subunit 12, coffilin 1, three isoforms of Peptidylprolylcis-trans isomerase A, three isoforms of Protein S100A9, Protein S100A8 and SH3 domain containing protein. These proteins belonged to four functional categories i.e. structural, cell cycle/growth regulation, signaling and intermediary metabolism. ConclusionProteins identified to be differentially expressed in TBDM patient can act as potent biomarkers and as predictors for copathogenesis of tuberculosis and diabetes.

molecular biology↗

bioRxiv2017

Transparency in Authors’ Contributions and Responsibilities to Promote Integrity in Scientific Publication

In keeping with the growing movement in scientific publishing toward transparency in data and methods, we argue that the names of authors accompanying journal articles should provide insight into who is responsible for which contributions, a process should exist to confirm that the list is complete, clearly articulated standards should establish whether and when the contributions of an individual justify authorship credit, and those involved in the generation of scientific knowledge should follow these best practices.\n\nTo accomplish these goals, we recommend that journals adopt common and transparent standards for authorship, outline responsibilities for corresponding authors, adopt the CRediT (Contributor Roles Taxonomy)1 methodology for attributing contributions, include this information in article metadata, and encourage authors to use the digital persistent identifier ORCID.2 Furthermore, we suggest that research institutions have regular open conversations on authorship criteria and ethics and that funding agencies adopt ORCID and accept CRediT. Scientific societies should further authorship transparency by promoting these recommendations through their meetings and publications programs.

scientific communication and education↗