Evaluation of the synergistic potential and mechanisms of action for designed cationic antimicrobial peptides.

Antimicrobial peptides (AMPs) have emerged as promising candidates in combating antimicrobial resistance - a growing issue in healthcare. However, to develop AMPs into effective therapeutics, a thorough analysis and extensive investigations are essential. In this study, we employed an approach to design cationic AMPs , followed by their experimental testing.

PARP inhibition suppresses topoisomerase 1 poisoning induced Caspase-3 dependent cell death in zebrafish embryos.

In the present study the role of poly(ADP)ribosylation on rubitecan induced caspase dependent cell death was evaluated. We show that Top1 poisoning by rubitecan induces caspase mediated apoptosis which was reduced by PARP inhibitor olaparib in zebrafish embryo. Collectively our data introduces zebrafish as a valuable model for PARP related biomedical research.

Low-dose trans-resveratrol induce poly(ADP)-ribosylation-dependent increase of the PPAR-γ protein expression level in the in vitro model of non-alcoholic fatty liver disease.

An effect of low-dose resveratrol treatment on lipid metabolism and pro-inflammatory processes has been studied, using an in vitro model of Non-Alcoholic-Fatty Liver Disease. The model system consisted of lipid-loaded monolayer cultures of hepatocytes (Hepa1-6) and macrophages (RAW264.7), as both cell types are present in the liver.

Genotoxic effects of topoisomerase poisoning and PARP inhibition on zebrafish embryos.

Topoisomerase poisons are known to stabilize covalent enzyme-DNA intermediates forming covalent cleavage complexes, which are highly cytotoxic especially for dividing cells and thus, make topoisomerases targets for cancer therapy. Topoisomerases have been extensively studied in mammalian model systems, whereas in other vertebrate models including zebrafish, they still remain less characterized. Here we show similarities in the genotoxic effects of zebrafish and mammalian systems towards topoisomerase I (Top1) poisons and PARP inhibitor - olaparib.

Automodification of PARP-1 mediates its tight binding to the nuclear matrix.

Poly(ADP-ribose) polymerase-1 (PARP-1), a nuclear enzyme that catalyzes the NAD(+)-dependent addition of ADP-ribose polymers on a variety of nuclear proteins, has been shown to be associated with the nuclear matrix. As yet, the properties and conditions of this association are unclear. Here, we show the existence of two PARP-1 pools associated with the nuclear matrix of rat liver and the ability of PARP-1 automodification to facilitate its binding to the nuclear matrix.