Drug-induced injury has attracted increasing attention in public health issues. Among them, hepatotoxicity has been regarded as the leading clinical problem caused by drug toxicity. However, owing to the complexity of the involved pathophysiological mechanisms and the lack of noninvasive, straightforward, and real-time tools, drug-induced hepatotoxicity has rarely been predicted satisfactorily....

Background Transthyretin amyloidosis is a protein aggregation disorder caused by deposition of transthyretin, a tetrameric plasma protein in charge of the transport of thyroxin and retinol in plasma and cerebrospinal fluid. Kinetic stabilization of the TTR tetramer has proved to be a valid therapeutic strategy to prevent the release of unstable TTR monomers and their aggregation into oligomers ...

Egalitarian motives form a powerful force in promoting prosocial behavior and enabling large-scale cooperation in the human species [1]. At the neural level, there is substantial, albeit correlational, evidence suggesting a link between dopamine and such behavior [2, 3]. However, important questions remain about the specific role of dopamine in setting or modulating behavioral sensitivity to pr...

Drug-induced injury has attracted increasing attention in public health issues. Among them, hepatotoxicity has been regarded as the leading clinical problem caused by drug toxicity. However, owing to the complexity of the involved pathophysiological mechanisms and the lack of noninvasive, straightforward, and real-time tools, drug-induced hepatotoxicity has rarely been predicted satisfactorily....

Microfluidic human organ models, microphysiology systems (MPS), are currently being developed as predictive models of drug safety and efficacy in humans. To design and validate MPS as predictive of human safety liabilities requires safety data for a reference set of compounds, combined with in vitro data from the human organ models. To address this need, we have developed an internet database, ...

Inhibition of catechol-O-methyltransferase (COMT; EC 2.1.1.6) is a new therapeutic strategy in the treatment of Parkinson's disease. However, nothing is known about the effects of COMT inhibition on levodopa (L-dopa)-induced toxicity in dopamine (DA) neurons. Therefore we evaluated the effects of the selective COMT inhibitors Ro 41-0960, OR-486, and tolcapone alone and in combination with L-dop...

Catechol-O-methyl tranferase (COMT; E.C.2.1.1.6) is widely distributed enzyme in nature that plays an essential role in the metabolism of catechol neurotransmitters and catechol linked foreign entities. As L-DOPA, a key medicine in Parkinsonism is being catabolised by COMT, this justified the interest in developing improved COMT inhibitors as significant adjunct to L-DOPA therapy. Although tolc...