Biology subjects

Sain, A.

Publications and source records attributed to Sain, A..

6 recordsLinked to original sources

bioRxiv2024

Olive phenolic compounds, potent tankyrase 1 inhibitor exhibit anti colon cancer effects by blocking Wnt/β-catenin pathway

Colon cancer (CC) needs special attention to develop novel targets and therapeutic approaches, as the total number of morbidity and mortality is growing rapidly. Although Olive has been long reported for its anti-CC activities but the mode is not completely understood yet. Here, we targeted tankysare 1 (TNKS), an important mediator of the Wnt/{beta}-catenin pathway, crucial in colon carcinogenesis. Bioinformatics analysis revealed that the mutation and copy number alterations of TNKS is found to be 12% whereas the proteins expression of TNKS is moderate to high in tumor groups vs normal in CC datasets. On the more, TNKS and its positively associated genes are found to be concomitant with several carcinogenesis related biological processes and signaling pathways. Further, three olive phytochemicals (apigenin, luteolin, and quercetin), which were shortlisted by employing filters like drug likeness and toxicity screening, molecular docking and finally molecular dynamics simulations, can target tankyrase 1. These ployphenols demonstrated cytotoxic effect in CC (HT-29) cells either alone or in combination. Further, these compounds successfully reduced {beta}-catenin level and its target genes (CCND1, CDK4, and MYC). Overall, inhibition of the Wnt/{beta}-catenin pathway by targeting tankyrase 1 was revealed as one of the anti-CC mechanisms of olive polyphenols.

cancer biology↗

bioRxiv2023

Apigenin exerts anti-cancer effects in colon cancer possibly by regulating Heat shock protein 90 alpha family class A member 1 (HSP90AA1)

Apigenin, a natural flavonoid, has shown early promise in colon cancer (CC); thus, exploring potential mechanisms of apigenin in CC is obligatory. In this study, shared targets of apigenin and CC were identified through different online tools and subjected to functional enrichment analyses like Gene Ontology and KEGG. Further, the protein-protein interaction network of the shared targets was developed (via STRING); hub/core targets were identified (MCODE application). The top targets of apigenin in CC were identified by molecular docking; further investigated for differential gene and protein expression in CC and their influence on CC patient survival (using TCGA data). Based on the docking score of the 13 hub genes, the top 3 targets (HSP90AA1, MMP9, PTGS2) were selected, and their expression was significantly elevated and related to poor overall survival in CC (except PTGS2). Molecular dynamics simulation further validated protein-ligand interactions and selected HSP90AA1 as the best target of apigenin in CC. Finally, apigenin was found to be involved in the cytotoxicity of CC cells (COLO-205) by reducing HSP90AA1 expression. The results of this study identified HSP90AA1 as one of the prime targets of apigenin in CC, and apigenin might act on HSP90AA1 to exert its anti-cancer mechanism.

cancer biology↗

bioRxiv2022

A specific mesh-like organization of human septin octameric complex drives membrane reshaping and curvature sensitivity

Septins are cytoskeletal proteins interacting with the inner plasma membrane and other cytoskeletal partners. Being key in membrane remodeling processes, they often localize at specific micrometric curvatures. To analyze the behavior of human septins at the membrane, we have used a combination of methods to assay their ultrastructural organization, their curvature sensitivity as well as their role in membrane reshaping. In contrast to budding yeast septins, on membranes, human septins systematically organize into a two-layered mesh of orthogonal filaments instead of generating parallel sheets of filaments observed for budding yeast septins. This peculiar mesh organization is curvature sensitive and drives membrane reshaping as well. The observed membrane deformations together with the filamentous organization are recapitulated in a coarsegrained computed simulation to understand their mechanisms. Our results highlight the specificity of animal septins as opposed to fungal proteins.

biophysics↗

bioRxiv2021

Deformation of membrane vesicles due to chiral surface proteins

Chiral, rod-like molecules can self-assemble into cylindrical membrane tubules and helical ribbons. They have been successfully modeled using the theory of chiral nematics. Models have also predicted the role of chiral lipids in forming nanometer-sized membrane buds in the cell. However, in most theoretical studies, the membrane shapes are considered fixed (cylinder, sphere, saddle, etc.), and their optimum radius of curvatures are found variationally by minimizing the energy of the composite system consisting of membrane and chiral nematics. Numerical simulations have only recently started to consider membrane deformation and chiral orientation simultaneously. Here we examine how deformable, closed membrane vesicles and chiral nematic rods mutually influence each others shape and orientation, respectively, using Monte-Carlo (MC) simulation on a closed triangulated surface. For this, we adopt a discrete form of chiral interaction between rods, originally proposed by Van der Meer et al. (1976) for off-lattice simulations. In our simulation, both conical and short cylindrical tubules emerge, depending on the strength of the chiral interaction and the intrinsic chirality of the molecules. We show that the Helfrich-Prost term, which couple nematic tilt with local membrane curvature in continuum models, can account for most of the observations in the simulation. At higher chirality, our theory also predicts chiral tweed phase on cones, with varying bandwidths. PACS numbers: PACS : 87.16.-b, 87.15.Aa, 81.40.Jj, 87.15.Rn

biophysics↗

bioRxiv2021

Temperature-dependent Self assembly of biofilaments during red blood cell sickling

Molecular self-assembly plays vital role in various biological functions. However, when aberrant molecules self-assemble to form large aggregates, it can give rise to various diseases. For example, the sickle cell disease and Alzheimers disease are caused by self-assembled hemoglobin fibers and amyloid plaques, respectively. Here we study the assembly kinetics of such fibers using kinetic Monte-Carlo simulation. We focus on the initial lag time of these highly stochastic processes, during which self-assembly is very slow. The lag time distributions turn out to be similar for two very different regimes of polymerization, namely, a) when polymerization is slow and depolymerization is fast, and b) the opposite case, when polymerization is fast and depolymerization is slow. Using temperature dependent on- and off-rates for hemoglobin fiber growth, reported in recent in-vitro experiments, we show that the mean lag time can exhibit non-monotonic behaviour with respect to change of temperature.

biophysics↗

bioRxiv2019

Confined filaments in soft vesicles - case of sickle red blood cells

A semi-rigid filament confined in a soft vesicle of similar size can mutually deform each other. An important example from biological context is Hemoglobin-S (HbS) fibers which polymerize inside red blood cell (RBC). The fibers deform the healthy RBC into sickle-like shape causing difficulty in blood flow through capillaries. Using an area difference elasticity (ADE) model for RBC and a worm-like chain model for the HbS fibers, confined within RBC, we study the shape deformations at equilibrium. We also consider multiple filaments and find that confinement can generate multipolar RBC shapes and can also promote helical filament conformations. The same model, in different parameter regime, reproduces tubulation for phospholipid vesicles, as seen in experiments, when microtubules are confined in the vesicle. We conclude that with a decrease in the surface area to volume ratio, and membrane rigidity, the vesicle prefers tubulation over sickling. Our simulations can access various non-axisymmetric shapes, which have been observed experimentally, both in the context of sickle RBC and phospholipid vesicles, but have so far remained beyond the scope of variational methods.

biophysics↗