Browsing by Author "Nair, RS"
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Item A gold nano particle coated porcine cholecyst-derived bio scaffold for cardiac tissue engineering(Colloids and surfaces: B Biointerfaces, 2017-06) Nair, RS; Ameer, JM; Alison, MR; Anilkumar, TVExtracellular matrices of xenogeneic origin have been extensively used for biomedical applications, despite the possibility of heterogeneity in structure. Surface modification of biologically derived biomaterials using nanoparticles is an emerging strategy for improving topographical homogeneity when employing these scaffolds for sophisticated tissue engineering applications.Recently, as a tissue engineering scaffold, cholecyst derived extracellular matrix (C-ECM) has been shown to have several advantages over extracellular matrices derived from other organs such as jejunum and urinary bladder. This study explored the possibility of adding gold nanoparticles, which have a large surface area to volume ratio on C-ECM for achieving homogeneity in surface architecture, a requirement for cardiac tissue engineering. In the current study, gold nanoparticles (AuNPs) were synthesized and functionalised for conjugating with a porcine cholecystic extracellular matrix scaffold. The conjugation of nanoparticles to C-ECM was achieved by 1-ethyl-3-(3-dimethyl aminopropyl)-carbodiimide/N-hydroxysuccinimide chemistry and further characterized by Fourier transform infrared spectroscopy, environmental scanning electron microscopy, energy dispersive X-ray spectroscopy and thermogravimetric analysis. The physical properties of the modified scaffold were similar to the original C-ECM. Biological properties were evaluated by using H9c2 cells, a cardiomyoblast cell line commonly used for cellular and molecular studies of cardiac cells. The modified scaffold was found to be a suitable substrate for the growth and proliferation of the cardiomyoblasts. Further, the non-cytotoxic nature of the modified scaffold was established by direct contact cytotoxicity testing and live/dead staining. Thus, the modified C-ECM appears to be a potential biomaterial for cardiac tissue engineering.Item Increased sensitivity of BRCA defective triple negative breast tumors to plumbagin through induction of DNA Double Strand Breaks (DSB)(SCIENTIFIC REPORTS, 2016) Nair, RS; Kumar, JM; Jose, J; Somasundaram, V; Hemalatha, SK; Sengodan, SK; Nadhan, R; Anilkumar, TV; Srinivas, PWe have earlier shown that Plumbagin (PB) can induce selective cytotoxicity to BRCA1 defective ovarian cancer cells; however, the effect of this molecule in BRCA1 mutated breast cancers has not been analyzed yet. Here, we report that reactive oxygen species (ROS) induced by PB resulted in DNA DSB and activates downstream signaling by ATR/ATM kinases and subsequent apoptosis. PB reduces DNA-dependent protein kinase (DNA-PK) expression and inhibits NHEJ (Non Homologous End Joining) activity in BRCA1 defective breast cancer cells. Also, PB induces apoptosis in two different BRCA1 conditional knock out murine models: MMTV-Cre; BRCA1(Co/Co) and WAP-Cre; BRCA1(Co/Co), at 2 mg/kg body weight, but 32 mg/kg of carboplatin (CN) was needed to induce apoptosis in them. This is the first study where two different tissue specific promoter driven transgenic mice models with BRCA1 exon 11 deletions are used for preclinical drug testing. The apoptosis induced by PB in HR (Homologous Recombination) defective triple negative BRCA1 mutant cell lines and in mouse models occur by inducing ROS mediated DNA DSB. The toxicity profile as compared with CN in transgenic mice provides evidence for PB's safer disposition as a therapeutic lead in breast cancer drug development.Item Structure activity relationship of plumbagin in BRCA1 related cancer cells(MOLECULAR CARCINOGENESIS, 2013) Thasni, KA; Ratheeshkumar, T; Rojini, G; Sivakumar, KC; Nair, RS; Srinivas, G; Banerji, A; Somasundaram, V; Srinivas, PIt has been shown earlier that plumbagin, a naturally occurring naphthaquinone has specific anticancer activity in BRCA1 blocked ovarian cancer cells. Plumbagin can induce estrogen dependent cell signaling and apoptosis in BRCA1 blocked ovarian cancer cells. Being a reactive oxygen species (ROS) generator and apoptosis inducing agent, plumbagin has immense potential as a promising anticancer agent. In this study we analyzed whether there would be increased anticancer activity if the positions of the functional groups on plumbagin were altered and further to analyze the detailed molecular mechanism of action of the lead molecule. Methods like MTT assay, apoptosis analysis by flow cytometry, assessment of mitochondrial membrane potential-m, suppression subtractive hybridization, microarray, molecular docking and estrogen receptorDNA binding activity by electrophoresis mobility shift assay (EMSA) were adopted for assessing the anticancer activity. Consequently we found that, plumbagin was the most potent anticancer agent when compared to structurally related compounds. The anti-cancer activities were in the order plumbagin>1,4-naphthaquinone>juglone>lawsone>menadione. Molecular docking studies showed that plumbagin could be well docked in the receptor ligand complex of TRAILDR5 complexes to activate the extrinsic pathway of apoptosis. Since the antiproliferative activity of plumbagin could be reduced by inhibiting ER, we speculated that plumbagin interferes with the binding of ER to ERE and we confirmed this by EMSA. This study clearly indicates that plumbagin can induce multiple pathways of apoptosis and cell cycle arrest in BRCA1 blocked cells compared to unblocked cells. (c) 2012 Wiley Periodicals, Inc.Item Surface Modification of Polypropylene Mesh with a Porcine Cholecystic Extracellular Matrix Hydrogel for Mitigating Host Tissue Reaction(. ACS Applied Bio Materials, 2021-03) Raj, R; Shenoy, SJ; Mony, MP; Pratheesh, KV; Nair, RS; Geetha, CS; Sobhan, PK; Purnima, C; Anilkumar, TVPolypropylene (PP) meshes are widely used for repairing skeletal muscle defects like abdominal hernia despite the chances of undesirable pro-inflammatory tissue reactions that demand revision surgeries in about 45% of cases. Attempts have been made to address the problem by modifying the mesh surface and architecture. These procedures have yielded only incremental improvements in the management of overall postoperative complications, and the search for a clinically viable therapeutic strategy continues. This study deployed a tissue engineering approach for mitigating PP-induced adverse tissue reaction by dip-coating the mesh with a hydrogel formulation of the porcine cholecystic extracellular matrix (CECM). The biomaterial properties of the CECM hydrogel-coated PP (C-PP) meshes were studied and their biocompatibility was evaluated by in vitro and in vivo tests based on ISO standards. Further, the nature of tissue reactions induced by the hydrogel-coated mesh and a commercial PP hernia repair graft was compared in a rat model of partial-thickness abdominal wall defect. Histomorphologically, in comparison with the PP graft-induced tissue reaction, C-PP caused a favorable graft-acceptance response characterized by reduced numbers of pro-inflammatory M1 macrophages and cytotoxic lymphocytes. Remarkably, the differential inflammatory response of the C-PP graft-assisted healing was associated with a fibrotic reaction predominated by deposition of type I collagen rather than type III collagen, as desired during skeletal muscle repair. It was concluded that the CECM hydrogel is a potential biomaterial for surface modification of polymeric biomedical devices.