http://nopr.niscpr.res.in/handle/123456789/64929 Sat, 10 Oct 2026 18:13:46 GMT 2026-10-10T18:13:46Z http://nopr.niscpr.res.in/handle/123456789/64939 Title: CircHelz inhibition protects against angiotensin II-induced cardiac fibrosis via miR-29b modulation Authors: Wang, Yixiong; Tao, Feng; Xiao, Chuanyu; Zhang, Wei; Xie, Qiang; Guo, Chuanlong; Tu, Jiancheng Abstract: Cardiac fibrosis is a critical pathological process underlying numerous cardiovascular diseases and contributes to heart failure and other severe complications. Circular RNAs (circRNAs) have been established as functional regulators of cardiovascular diseases, yet their specific roles in cardiac fibrosis remain unclear. This study was developed to explore the CircHelz/miR-29b regulatory axis in angiotensin II (Ang II)-induced cardiac fibrosis. CircHelz levels in Ang II-induced cardiac fibroblasts (CFs) were detected by qPCR, and siRNA was employed to disrupt its expression. The functional roles of CircHelz were explored through 5-Ethynyl-2-deoxyuridine (EdU) uptake, Transwell, and immunofluorescence assays. Bioinformatics and dual-luciferase reporter assays were used to identify and verify CircHelz binding partners. Following Ang II stimulation and CircHelz silencing of mouse CFs, the cells were transfected with anmiR- 29b-inhibitor, and the levels of fibrosis-related indicators, cytokines, and adhesion factors were assessed by Western blotting and qPCR. The results showed increased CircHelz expression after Ang II treatment. Mechanistically, CircHelz was identified as an endogenous sponge capable of targeting miR-29b and thereby interfering with its expression. CircHelz silencing promoted proliferation, migration and α-SMA expression in CFs by enhancing the activity of miR-29b, and reduced the expression levels of cardiac fibrosis related indicators. These findings support the ability of CircHelz to bind to miR-29b as a competing endogenous RNA, thereby promoting cardiac fibrosis. As such, CircHelz inhibition holds promise as a therapeutic strategy for Ang II-induced cardiac fibrosis. Page(s): 7-16 Fri, 01 Nov 2024 00:00:00 GMT http://nopr.niscpr.res.in/handle/123456789/64939 2024-11-01T00:00:00Z http://nopr.niscpr.res.in/handle/123456789/64938 Title: The HMG-CoA reductase inhibitory potential of fatty acid amides Authors: Ediriweera, Meran Keshawa; Anandappa, Joshua Miguel; Zhang, Baohua Abstract: HMG-CoA reductase (HMGCR) plays a key role as the rate-limiting enzyme in cholesterol biosynthesis. Fatty acid amides possess a range of biochemical and physiological functions. In an attempt to identify potential inhibitors of HMGCR, three fatty acid amides - namely stearamide, oleamide, and butyramide were investigated. Results demonstrated that these amides inhibited the activity of HMGCR, with stearamide being the most potent, followed by oleamide and butyramide. Stearamide appears to demonstrate a competitive mode of inhibition for HMGCR. Notably, these fatty acid amides interacted with key amino acid residues in the catalytic region of HMGCR through hydrogen bonding and hydrophobic interactions. These findings highlight the necessity for further research to delve into the effects of fatty acid amides on HMGCR inhibition in both in vitro and in vivo. Page(s): 17-24 Fri, 01 Nov 2024 00:00:00 GMT http://nopr.niscpr.res.in/handle/123456789/64938 2024-11-01T00:00:00Z http://nopr.niscpr.res.in/handle/123456789/64937 Title: Structural analysis of Glucose-6-Phosphate Dehydrogenase (G6PD) variants from Northeast India and natural antioxidants as a pharmacological agent to alleviate G6PD deficiency associated challenges- An in silico approach Authors: Basumatary, Noymi; Basumatary, Nerswn; Baruah, Dipankar; Sarma, Paresh Kumar; Sarmah, Jatin Abstract: The present study focuses on the structural deviation of four Glucose-6-phosphate dehydrogenase (G6PD) variants viz., Orissa, Kalyan-Kerala, Mahidol and A+ detected in Northeast Indian population and to assess the probable efficacy of natural antioxidants to combat G6PD deficiency associated challenges. G6PD deficiency caused by mutations in the g6pd gene, results in hemolysis of the Red Blood Corpuscles (RBCs) under oxidative stress. Over sixty years have passed since the identification of G6PD-associated enzymopathy; nonetheless, a treatment for the deficiency remains unavailable. Thus, the potential of natural antioxidants as a remedial agent against these variants were evaluated in silico. The three dimensional (3D) structures of the variants were modeled and validated. Molecular docking of variants with the natural antioxidants was performed using AutoDock Vina, wherein the binding affinities with G6PD Orissa, Kalyan-Kerala, Mahidol and A+ ranged between -5.2 to -9.2 kcal/mol, -5.1 to -9.8 kcal/mol, -5.2 to -9.4 kcal/mol and -5.0 to -10.5 kcal/mol, respectively. Drug-likeness and toxicity analyses were done using SwissADME and ProTox-II, respectively. Molecular dynamics simulation of the variants and the variant-antioxidant complexes done using GROMACS showed best fit in Orissa-Myricetin, Kalyan-Kerala-Apigenin, Mahidol-Catechin, and A+-Diadzen. Kalyan-Kerala-Apigenin was observed to have the least deviation compared to WT G6PD. Page(s): 25-37 Fri, 01 Nov 2024 00:00:00 GMT http://nopr.niscpr.res.in/handle/123456789/64937 2024-11-01T00:00:00Z http://nopr.niscpr.res.in/handle/123456789/64936 Title: Force fields for simulating intrinsically disordered proteins: Assessing conformational sampling and structural dynamics Authors: Sharma, Babli; Das, Debatri; Mattaparthi, Venkata Satish Kumar Abstract: Intrinsically disordered proteins (IDPs) lack a defined three-dimensional (3-D) structure but play crucial roles in biological pathways. They exist as conformational ensembles and experimental methods struggle to capture their dynamic nature, making molecular dynamics (MD) simulations a valuable tool. However, force field accuracy and sampling algorithms limit simulation fidelity. Most protein force fields are too stable to accurately model unstructured proteins like IDPs. Empirical force fields-based computer simulations are increasingly used to study the biophysics of disordered proteins, with the choice of force field significantly influencing simulation outcomes for studying the conformational ensemble of IDPs. This study evaluates three AMBER force fields (ff99SBildn-TIP3P, ff99SB-TIP3P, and ff19SB-OPC) for simulating an IDP (Histatin 5) and a partially folded protein (Trp-cage). Extensive MD simulations compared the structural dynamics and conformational sampling across all the force fields for these two systems. The results show ff99SBildn-TIP3P as the most balanced force field, efficiently sampling ordered and disordered regions in these proteins. We evaluated the performance of the force fields with enhanced sampling metrices including RMSD, RMSF, Rg and SASA. Our results reveal ff99SBildn-TIP3P model better samples the disorder regions in Histatin 5 than the other force fields. This study highlights the importance of understanding force field strengths and limitations for IDP simulations. By selecting suitable force fields, researchers can better simulate the IDPs and understand their complex behavior Page(s): 38-45 Fri, 01 Nov 2024 00:00:00 GMT http://nopr.niscpr.res.in/handle/123456789/64936 2024-11-01T00:00:00Z