Cyclosporine A (CsA) has shown efficacy against immunity-related diseases despite its toxicity in various organs, including the liver, emphasizing the need to elucidate its underlying hepatotoxicity m Show more
Cyclosporine A (CsA) has shown efficacy against immunity-related diseases despite its toxicity in various organs, including the liver, emphasizing the need to elucidate its underlying hepatotoxicity mechanism. This study aimed to capture the alterations in genome-wide expression over time and the subsequent perturbations of corresponding pathways across species. Six data from humans, mice, and rats, including animal liver tissue, human liver microtissues, and two liver cell lines exposed to CsA toxic dose, were used. The microtissue exposed to CsA for 10 d was analyzed to obtain dynamically differentially expressed genes (DEGs). Single-time points data at 1, 3, 5, 7, and 28 d of different species were used to provide additional evidence. Using liver microtissue-based longitudinal design, DEGs that were consistently up- or down-regulated over time were captured, and the well-known mechanism involved in CsA toxicity was elucidated. Thirty DEGs that consistently changed in longitudinal data were also altered in 28-d rat in-house data with concordant expression. Some genes (e.g. Show less
A comprehensive computational strategy that combined QSAR modelling, molecular docking, and ADMET analysis was used to discover potential inhibitors for β-secretase 1 (BACE-1). A dataset of 1,138 comp Show more
A comprehensive computational strategy that combined QSAR modelling, molecular docking, and ADMET analysis was used to discover potential inhibitors for β-secretase 1 (BACE-1). A dataset of 1,138 compounds with established BACE-1 inhibitory activities was used to build a QSAR model using mol2vec descriptors and support vector regression. The obtained model demonstrated strong predictive performance (training set: Show less