Genetic and Epigenetic Basis of Drug-Induced Liver Injury.

Drug-induced liver injury (DILI) is a rare but severe adverse drug reaction seen in pharmacotherapy and a major cause of postmarketing drug withdrawals. Advances in genome-wide studies indicate that genetic and epigenetic diversity can lead to inter-individual differences in drug response and toxicity. It is necessary to identify how the genetic variations, in the presence of environmental factors, can contribute to development and progression of DILI. Studies on microRNA, histone modification, DNA methylation, and single nucleotide polymorphisms related to DILI were retrieved from databases and were analyzed for the current research and updated to develop this narrative review. We have compiled some of the major genetic, epigenetic, and pharmacogenetic factors leading to DILI. Many validated genetic risk factors of DILI, such as variants of drug-metabolizing enzymes, HLA alleles, and some transporters were identified. In conclusion, these studies provide useful information in risk alleles identification and on implementation of personalized medicine.

Synthesis and characterization of diopside particles and their suitability along with chitosan matrix for bone tissue engineering in vitro and in vivo.

The scaffolds for bone tissue engineering should be porous to harbor the growth of new tissue ingrowths, biodegradable with no toxic end products, and biocompatible with no cytotoxicity. In this study we report that Diopside (CaMgSi2O6) (Dp) particles can be synthesized at a more economical route using the agricultural waste rice straw. Along with chitosan (CS) matrix, the CS/Dp scaffolds were synthesized and evaluated for their physico-chemical properties by SEM, EDS, XRD, FT-IR studies. Addition of Dp particles to chitosan matrix decreased water retention capacity but there was no change in their degradation properties. Dp particles in CS/Dp scaffolds exhibited good affinity for protein adsorption. Apatite forming ability of the CS/Dp scaffolds depicted their bioactivity. These scaffolds were found to be compatible with human osteoblastic cells (MG-63) and the cells were able to attach and proliferate with extended morphology on the CS/Dp membranes. The CS/Dp scaffolds supported up regulation of mRNA expression of osteoblast differentiation marker genes such alkaline phosphatase (ALP), type I collagen (COL-I) in the presence of osteogenic environment suggesting their osteo-conductive nature. In vivo rat model system identified that the CS/Dp scaffolds are biocompatible and may have the property of recruiting cells due to deposition of collagen. Hence, these studies suggest that the prepared CS/Dp scaffolds have potential applications towards bone tissue engineering.