In the second phase of the work, information from the SARs of the benzothiophene series and data available in literature, we explored the in vitro pharmacological properties of the 6-substituted-7-fluoro-benzothiophene hydroxamates
and the 5-susbtituted-benzofuran hydroxamates. (C) 2015 Elsevier Ltd. All rights reserved.”
“The most common heritable genetic disease in the United States, cystic fibrosis (CF), is caused by mutations in the CF transmembrane conductance regulator (CFTR), a chloride channel that interacts with and regulates a number of other proteins. The bacteria Pseudomonas aeruginosa infects 80% of patients causing decreased pulmonary function and life expectancy. It is not known how malfunction of the chloride channel allows for preferential colonization of patients by a single pathogen. Batimastat in vitro The hypothesis that CFTR interacts with toll-like receptor 4 (TLR4) to phagocytize bacteria was tested. selleck compound A competitive antagonist of TLR4, MKLPS, was studied for its effect in gentamicin-protection-based bacterial invasion assays. Pre-incubation (15 min 50 mu g/mL) with
MKLPS did not alter the rate of phagocytosis of P. aeruginosa by cultured epithelia. However, further studies with GFP-transfected P. aeruginosa revealed prominent antibiotic resistant microcolonies were formed. If CFTR is involved in phagocytosis of the bacteria, then internalization was predicted to decrease in iodide efflux. Surprisingly, cultured epithelia exposed to P. aeruginosa for 15 min showed increased cAMP-activated iodide efflux through CFTR. In addition, 15-min exposure to bacterial cell wall component, LPS, purified from P. aeruginosa also increased
CFTR iodide efflux in a dose-dependent manner (50, 100 and 200 mu g/mL LPS had 25%, 37% and 47% increase). In a reversal of this phenomenon, shorter 5-min exposure to 100 mu g/mL LPS resulted in a 25% decrease in forskolin-activated CFTR channel activity compared to controls. This data is consistent with a model in which CFTR is removed from the plasma membrane during phagocytosis of P. aeruginosa followed AC220 by recruitment of channels to the membrane to replace those removed during phagocytosis. More studies are needed to confirm this model, but this is the first report of a bacterial product causing a biphasic time-dependent and a dose-dependent alteration of CFTR channel activity. (C) 2010 Elsevier Inc. All rights reserved.”
“When Monascus MX was grown under blue light instead of in the dark, citrinin production increased from 478 mg l(-1) to 698 mg l(-1). To explain this, the expression of the pksCT gene, which encodes citrinin polyketide synthase, and of 5 ORFs around it, were monitored. Blue light enhanced citrinin production by upregulating the expression of orf1, orf3, and orf4, indicating that pksCT was not the key gene responsible for the quantity of citrinin production in blue light.