Search

Bacterial adhesion and colonization on stainless steel (SSL) based surgical instruments, hospital equipment, orthopedic implants, water purification and food processing units are a major problem. Imparting rechargeable antibacterial properties to SSL offers the prospect of a reusable and clean surface. In this study, the SSL surface was functionalized with a hydantoin-based antibacterial polymer that prevents bacterial adhesion and colonization. A new hydantoin monomer with three halogen binding sites, (Z)-N-((4-(2,5-dioxoimidazolidin-4-ylidene)methyl)phenyl)methacrylamide (DMPM), was synthesized, characterized and copolymerized with a commercially available 3-(methacryloyloxy)propyltrimethoxysilane monomer to develop the antibacterial polymer. The SSL surface was treated with piranha solution and the copolymer was covalently immobilized on the surface. The modified surface was examined for its antibacterial and anti-biofilm activity. The modified surface exhibited total kill (6 log reduction) of bacteria such as S. aureus and E. coli in 10 and 12 min respectively. The anti-biofilm activity of the modified surface was evaluated using a combination of fluorescence-based metabolic activity and scanning electron microscopy imaging suggested the comprehensive damage of S. aureus and E. coli biofilm architecture.

A series of 2, 3-dihydroquinazolinone derivatives were synthesized, characterized and their anticancer activity was determined. Among the compounds synthesized and screened, one compound (17) showed potent anticancer activity against human head and neck squamous cell carcinoma cell line, SCC131 and was non-toxic to normal cells. The compound inhibited the growth of SCC131 cells, with an IC50 of 1.75 μM, triggered apoptotic mode of cell death and caused tumor regression of SCC131 tumor xenografts in athymic mice. To decipher the target for the lead compound, a high throughput qPCR array was performed. Results showed that the compound 17, inhibited the expression of a vital transcription factor HNF4A, involved in regulation of metabolic pathways. Thus, the present work has identified a lead compound 17, with potent anticancer activity, minimal normal cell toxicity and a plausible target and hence definitely holds future prospects as an anticancer agent.

In this study, we have identified one microRNA, microRNA 493 (miR-493), which could simultaneously and directly regulate multiple genes downstream of the insulin-like growth factor 1 receptor (IGF1R) pathway, including IGF1R, by binding with complementary sequences in the 3' untranslated region (UTR) of mRNAs of IGF1R, insulin receptor substrate 1 (IRS1), and mitogen-activated protein kinase 1 (MAPK1), thereby potentiating their inhibitory function at multiple levels in development and progression of cancers. This binding was further confirmed by pulldown of miR with AGO-2 antibody. Further, results from head and neck samples showed that miR-493 levels were significantly downregulated in tumors, with a concomitant increase in the expression of IGF1R and key downstream effectors. Functional studies from miR-493 overexpression cells and nude-mouse models revealed the tumor suppressor functions of miR-493. Regulation studies revealed that Snail binds to the miR-493 promoter and represses it. We found the existence of a dynamic negative feedback loop in the regulation of IGF1R and miR-493 mediated via Snail. Our study showed that nicotine treatment significantly decreases the levels of miR-493-with a concomitant increase in the levels of Snail-an indication of progression of cells toward tumorigenesis, reestablishing the role of tobacco as a major risk factor for head and neck cancers and elucidating the mechanism behind nicotine-mediated tumorigenesis.