Biology subjects

Parashar, A.

Publications and source records attributed to Parashar, A..

6 recordsLinked to original sources

bioRxiv2026

Arterial Elastin Abundance, Rather Than Orthologue Origin, Modulates Medial Arterial Calcification in Matrix Gla Protein-Deficient Mice

Abstract Calcific deposits in the arterial media have been associated with a number of metabolic and genetic disorders including diabetes, chronic kidney disease and generalized arterial calcification of infancy. While medial calcification and physiologic hard tissue mineralization in the skeleton are both regulated by several common determinants, emerging data suggest that there might be fundamental differences in the mechanisms underlying these two processes. Objective: We previously demonstrated that elastin haploinsufficiency delays medial calcification in MGP-deficient mice. Here, using mice in which a human ELN transgene rescues mouse elastin deficiency, we investigated whether the origin and abundance of arterial elastin differentially affect the initiation and progression of medial calcification. Approach and Results: We pursued a transgenic approach to alter the arterial elastin scaffold in MGP-deficient mice. Our analyses of a humanized MGP-deficient model with 40% reduction of medial elastin content showed a complete absence of the early-stage vascular calcification. Additionally, we showed that mouse and human elastin orthologues affect vascular calcification in a comparable manner. Conclusion: Arterial elastin abundance, rather than orthologue origin, modulates the initiation and progression of medial calcification in MGP-deficient mice. A further reduction in arterial elastin beyond that achieved by elastin haploinsufficiency profoundly delays mineral deposition and maturation, whereas restoration of elastin abundance through transgenic human ELN expression restores arterial calcification.

cell biology↗

bioRxiv2026

Redox heterogeneity as an engine of biodiversity: A quantitative murburn formalism for micro-oxic ecosystems

Biodiversity frequently peaks in fluctuating micro-oxic environments such as marine oxygen minimum zone interfaces, rhizospheric aggregates, sediments, microbial mats, and gut mucus layers. Yet, classical ecological theories do not adequately explain why intermediate oxygen tensions repeatedly favor coexistence and diversification. Herein, we propose a murburn ecological formalism wherein oxygen acts not merely as a metabolic substrate but as a generator of dynamic redox heterogeneity through partial reduction and diffusible reactive species (DRS) and redox-intermediates formation. Integrating empirical observations from marine, gut, soil, and aquatic-interface ecosystems with a reaction-diffusion framework, we show that intermediate oxygen tensions naturally maximize radical-field heterogeneity and produce dynamically shifting fitness landscapes. Numerical simulations demonstrate spontaneous coexistence, biodiversity maxima within micro-oxic zones, localized diversification, and coexistence stabilization without externally imposed niche partitioning. Additional simulations suggest that aquatic macrofauna indirectly enhance biodiversity by restructuring oxygen gradients and generating ecosystem-scale diffusional redox architectures (ESDRA). The framework proposes that fluctuating redox interfaces function as potential ecological zones of elevated adaptive turnover across biological scales.

ecology↗

bioRxiv2025

Designing Functional Dairy Food Products: Peptide-Fortification Approaches to Improve Safety, Quality, and Consumer Acceptance

This study focused on the development of functional dairy products fortified with bioactive peptides derived from Lactobacillus rhamnosus C25-fermented sheep milk and their evaluation during storage. Microencapsulated peptides were incorporated into flavoured milk and srikhand, and their antimicrobial, antioxidant, and sensory properties were monitored over refrigerated storage. Flavoured milk supplemented with free peptides exhibited strong antimicrobial activity, while encapsulated peptides provided a controlled and sustained release, maintaining functionality over six days. In srikhand, both plain and mango-flavoured formulations demonstrated enhanced biofunctional properties, with encapsulated peptides showing gradual peptide release, higher antioxidant activity, and better preservation of sensory quality over 15 days. Sheep milk used for fermentation showed good microbial quality, supporting safe peptide production. Fermentation yielded peptide fractions (<3, <5, and <10 kDa), which were analyzed using RP-HPLC and LC-MS/MS, identifying over 3,100 peptides. In silico screening predicted 34 peptides with antimicrobial potential, including cationic and amphipathic -helical peptides primarily derived from {beta}-casein and {kappa}-casein. Functional assays demonstrated potent antimicrobial activity against Gram-positive and Gram-negative pathogens, particularly in the 5-10 kDa fractions. Antioxidant activity was highest in the 5 kDa retentate, indicating that medium-sized peptides contributed most to radical scavenging. Microencapsulation using sodium alginate improved peptide stability and controlled release, mitigating bitterness and preserving product acceptability. Overall, the study highlights the potential of L. rhamnosus C25-fermented sheep milk peptides as natural bioactive ingredients for functional dairy products with enhanced shelf life, antimicrobial efficacy, and antioxidant capacity. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=135 SRC="FIGDIR/small/673363v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@1c368bdorg.highwire.dtl.DTLVardef@118db8org.highwire.dtl.DTLVardef@6f4addorg.highwire.dtl.DTLVardef@9c2ddc_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2025

A Simultaneous Inhibition of ID1 and ID3 Protects Against Pulmonary Fibrosis

BackgroundIdiopathic pulmonary fibrosis (IPF) is a fatal lung disease for which novel therapeutic approaches are desperately needed. Inhibitor of DNA binding (ID) proteins are regulated by Transforming Growth Factor-{beta}. However, the regulation and the effects of ID proteins in IPF remain poorly understood. We aimed to assess the expression of ID proteins in IPF and determine the effects of ID proteins on human lung fibroblasts (HLF) in vitro and pulmonary fibrosis in vivo. MethodsThe expression of ID proteins in lungs and lung fibroblasts from mice and human patients with pulmonary fibrosis was evaluated. The effects of ID1/ID3 inhibition and overexpression on HLF were assessed. Genetic and pharmacological approaches were used in vivo to determine the role of ID1/ID3 in pulmonary fibrosis. ResultsID1/ID3 levels were elevated in HLFs isolated from pulmonary fibrosis-diseased patients and mice. ID1/ID3 knockdown decreased IPF-diseased HLF proliferation and differentiation into myofibroblasts. Bleomycin-exposed ID1/ID3 KO mice displayed improved lung function and presented with decreased lung fibrosis when compared to WT mice. A pharmacological inhibitor of ID1/ID3 decreased IPF-diseased HLF proliferation and differentiation in vitro and attenuated pulmonary fibrosis in vivo. A lung specific inhibition of ID1/ID3, using adeno-associated viruses expressing short hairpins targeting ID1 and ID3, reversed pulmonary fibrosis in mice. Mechanistically, ID1/ID3 inhibition decreased fibroblast proliferation through cell cycle genes and inhibited fibroblast differentiation through the MEK/ERK pathway. ConclusionsOur data indicate that a simultaneous inhibition of ID1 and ID3 attenuates pulmonary fibrosis. ID1/ID3 inhibition holds potential as a novel therapeutic treatment for IPF.

pathology↗

bioRxiv2024

Osteocyte-derived erythroferrone regulates liver hepcidin during stress erythropoiesis

Our knowledge of which bone marrow cells affect red cell production is still incomplete. To explore the role of osteocytes in the process we performed bulk RNAseq of osteocytes isolated from control and phlebotomized mice. The top-upregulated gene following phlebotomy was Fam132b, erythroferrone (Erfe). Erfe expression in osteocytes was also upregulated after erythropoietin (EPO) treatment and hypoxia in vitro. To explore if osteocytes contribute to the systemic ERFE levels, we generated two mouse models. We first transplanted wild-type BM in Erfe-/- mice creating a model where ERFE is produced in the BM but not by osteocytes. After phlebotomy, liver hepcidin suppression was significantly lower in mice where the osteocytes could not produce ERFE. To confirm that osteocytes are responsible for this difference, we generated mice lacking EPO receptors in osteocytes by crossing Eporflox/flox and Dmp1-Cre mice. After phlebotomy, these mice showed reduced hepcidin suppression in the liver and higher circulating serum hepcidin levels compared to controls. Our work identified a novel function of osteocytes in suppressing systemic hepcidin levels during stress erythropoiesis.

immunology↗

bioRxiv2022

2D-QSAR and Molecular Docking based virtual screening of the herbal molecules against Alzheimers Disorder: An approach to predict CNS activity

Acetylcholinesterase (AChE) is one of the key enzyme targets that have been used clinically for the management of Alzheimers Disorder (AD). Numerous reports in the literature predict and demonstrate in-vitro, and in-silico anticholinergic activity of synthetic and herbal molecules, however, the majority of them failed to reproduce the results in preclinical or clinical settings. To address these issues, we developed a 2D-QSAR model that could not only efficiently predict the AChE inhibitory activity of herbal molecules but also predicted their potential to cross BBB to exert their beneficial effects during AD. Applying this model, virtual screening of the herbal molecules was performed and amentoflavone, asiaticoside, astaxanthin, bahouside, biapigenin, glycyrrhizin, hyperforin, hypericin, and tocopherol were predicted as the most promising herbal molecules for inhibiting AChE. Results were validated through molecular docking studies against human AChE (PDB ID: 4EY7). To determine whether or not these molecules can cross BBB to inhibit AChE within the CNS for being beneficial for the management of AD, we determined a CNS PPO score, which was found in the range of 1 to 3.76. Overall, the best results were observed for amentoflavone and our results demonstrated a PIC50 value of 7.377 nM, molecular docking score of -11.5 kcal/mol, and CNS MPO score of 3.76. In conclusion, we successfully developed a reliable and efficient 2D-QSAR model and predicted amentoflavone to be the most promising molecule that could inhibit human AChE enzyme within the CNS and could prove beneficial for the management of AD.

bioinformatics↗