0000000000965126
AUTHOR
Haixia Liu
Repurposing a Library of Human Cathepsin L Ligands: Identification of Macrocyclic Lactams as Potent Rhodesain and Trypanosoma brucei Inhibitors.
Rhodesain (RD) is a parasitic, human cathepsin L (hCatL) like cysteine protease produced by Trypanosoma brucei (T. b.) species and a potential drug target for the treatment of human African trypanosomiasis (HAT). A library of hCatL inhibitors was screened, and macrocyclic lactams were identified as potent RD inhibitors (Ki < 10 nM), preventing the cell-growth of Trypanosoma brucei rhodesiense (IC50 < 400 nM). SARs addressing the S2 and S3 pockets of RD were established. Three cocrystal structures with RD revealed a noncovalent binding mode of this ligand class due to oxidation of the catalytic Cys25 to a sulfenic acid (Cys–SOH) during crystallization. The P-glycoprotein efflux ratio was mea…
Acoustic Radiation Force Impulse Elastography for the Non-Invasive Evaluation of Hepatic Fibrosis in Non-Alcoholic Fatty Liver Disease Patients: A Systematic Review & Meta-Analysis
Background In order to better monitor non-alcoholic fatty liver disease (NAFLD) patients at higher risk for HCC, there is a need for non-invasive diagnostic approaches to screen for the presence of advanced fibrosis in these patients. The aim of this systematic review and meta-analysis will be to evaluate the diagnostic efficacy of ARFI elastography in detecting hepatic fibrosis in NAFLD patients. Methods Relevant studies were identified from systematic searches of several major electronic databases (PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials). The primary outcomes were the summary sensitivity, summary specificity, the diagnostic odds ratio, and the summary recei…