Biology subjects

Vittal, R.

Publications and source records attributed to Vittal, R..

3 recordsLinked to original sources

bioRxiv2025

Parkia javanica extracts exhibits tissue regeneration potential in Zebrafish (Danio rerio)

Parkia javanica is a medicinal plant acknowledged for its diverse pharmacological features, but its biological effects, like regeneration and wound-healing properties, in the zebrafish animal model (Danio rerio) is unexplored. The purpose of this study was to determine the caudal fin tissue regeneration and antioxidant potential in response to Parkia javanica fruit and bark extracts on Danio rerio. The Danio rerio caudal fin was amputated and subsequently was treated with Parkia javanica fruit and bark extracts at 0.346{micro}g/mL and 2.86{micro}g/mL respectively. The regenerative effects of Parkia javanica fruit and bark extracts were evaluated through morphological analysis and dorso-ventral patterning. Additionally, the antioxidant properties of Parkia javanica fruit and bark extracts, along with the mechanistic insights, were evaluated using qRT-PCR. We found that both the Parkia javanica fruit and bark extracts displayed substantial antioxidant capacity with upregulation of key genes like Cat and Sod1. Further, the extracts demonstrated significant fin regeneration compared to the control group. We observed that both the Parkia javanica fruit and bark extracts possess tissue regeneration properties by upregulating key genes, like Anxa2a, Anxa2b, and Wnt3a. All these findings provide novel insights into the molecular mechanisms underlying the tissue repair and regeneration effects of Parkia javanica fruit and bark extracts and may pave the way for the development of novel regenerative therapeutic strategies. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=128 SRC="FIGDIR/small/681930v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@9a579org.highwire.dtl.DTLVardef@14edd37org.highwire.dtl.DTLVardef@9d7addorg.highwire.dtl.DTLVardef@ed79da_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2025

Characterization of bronchovascular-bundle mesenchymal stromal cells regulating antibody-secreting cell niche in rejecting lung allografts

A transplanted lung offers a permissive milieu for local adaptive immune cell responses. Here, we characterize a transcriptionally and anatomically distinct adult lung-resident mesenchymal stromal population (MSC) that supports a pro-survival niche for antibody-secreting cells in rejecting lung allografts through a novel IL-6 trans-signaling/CXCL12 axis. By using a mouse orthotopic lung transplant model and Blimp1EYFP recipients, we identify spatial localization of antibody-secreting cells (ASCs) and terminally differentiated plasma cells (PCs) along the bronchovascular bundles (BVBs). A previously described Foxf1+Gli1+Itga8- subset of collagen- expressing MSCs, which forms a 3-dimensional network along the bronchovascular bundles (BVB-MSCs), was found to be the major source of the PC survival factors CXCL12 and IL-6. Cxcl12iCre/ERT2Rosa26tdTomatomice utilized as donors, validated the expansion of this population in a rejecting graft and their intimate association with ASCs. CXCL12 expression was increased in murine allografts and in Foxf1+ mesenchymal cells (MCs) isolated from human CLAD patients. IL-6 trans-signaling/STAT3 signaling axis was shown to upregulate CXCL12 secretion in human MCs, and Olamkicept-mediated neutralization of IL-6 trans-signaling in murine RAS attenuates CXCL12 expression, intra-graft ASC population, and fibrogenesis. Our findings represent the first delineation of specialized CXCL12-expressing mesenchymal stromal cells in adult lungs and the contribution of IL-6 trans-signaling driven CXCL12 expression to sustaining intra-graft ASC niches and allograft fibrogenesis. One Sentence SummaryWe characterize CXCL12-expressing mesenchymal cells and their role in a pro-survival niche for antibody-secreting cells in rejecting lung allografts.

pathology↗

bioRxiv2024

Single-cell multi-omic analysis of post-transplant mesenchymal cells reveals molecular signatures and putative regulators of lung fibrosis

Survival after lung transplantation is limited by chronic progressive graft failure, termed chronic lung allograft dysfunction (CLAD). Graft-resident mesenchymal cells (MCs) drive CLAD pathogenesis and exhibit stable, dysregulated signaling; however, the transcriptomic and epigenomic drivers behind this fibrogenic transformation remain elusive. Here, we utilize single-cell multi-omic technologies to study gene expression and chromatin accessibility of MCs from the lavage fluid of lung transplant recipients with and without CLAD, obtained either early post-transplantation or after disease onset. MCs obtained after CLAD onset (CLAD-MCs) demonstrated a unique transcriptomic signature compared to non-CLAD controls; a logistic regression model trained on these profiles classified the disease status of individual cells with > 98% accuracy using a set of signature genes. Chromatin accessibility and motif scan analysis identified the CCAAT-enhancer-binding proteins family of transcription factors, specifically CEBPD, as a key marker of the CLAD-enriched subtype. Footprint analysis of early time-point MCs revealed minimal differences in accessibility, suggesting that CEBPD-associated regulatory changes emerge over time after transplantation. Integration and unsupervised clustering identified 8 distinct cell states, and a compositional shift was noted uniquely in CLAD-MCs. Knocking down CEBPD with siRNA in CLAD-MCs partially reverted the CLAD transcriptomic signature, confirming its importance in the dysregulated molecular state of CLAD-associated MCs. scRNA-seq analysis on human lung CLAD tissue provided in situ validation of key genes and CEBPD expression changes noted in CLAD-MCs. Our results provide deeper insights into the transcriptomic and epigenomic changes in post-transplant MCs, nominating biomarkers and disease-associated factors with implications for future therapeutic efforts.

bioinformatics↗