Molecular detection of monocyte chemotactic protein-1 polymorphism in spontaneous bacterial peritonitis patients.

Aim: To investigate the association of the functional monocyte chemotactic protein-1 (MCP-1) promoter polymorphism (A-2518G) with spontaneous bacterial peritonitis (SBP).

Methods: Fifty patients with post-hepatitis C liver cirrhosis and ascites were categorized into two groups; group I included 25 patients with SBP and group II included 25 patients free from SBP. In addition, a group of 20 healthy volunteers were included.

Naproxen and cromolyn as new glycogen synthase kinase 3β inhibitors for amelioration of diabetes and obesity: an investigation by docking simulation and subsequent in vitro/in vivo biochemical evaluation.

Naproxen and cromolyn were investigated as new inhibitors of glycogen synthase kinase-3β (GSK-3β) in an attempt to explain their hypoglycemic properties. Study included simulated docking experiments, in vitro enzyme inhibition assay, and in vivo validations. Both drugs not only were optimally fitted within a GSK-3β binding pocket via several attractive interactions with key amino acids but also exhibited potent in vitro enzymatic inhibitory activities of IC50 1.

Evaluation of naproxen and cromolyn activities against cancer cells viability, proliferation, apoptosis, p53 and gene expression of survivin and caspase-3.

We previously reported the inhibitory profiles of naproxen and cromolyn against glycogen synthase kinase-3β, which partly explain the molecular mechanisms of their anti-cancer properties. In this study, we performed a detailed biochemical evaluation of the two drugs against colorectal adenocarcinoma (Caco2), hepatocellular carcinoma (HepG2), mammary gland carcinoma (MCF7), epitheloid cervix carcinoma (Hela), lung carcinoma (A5W9) and epidermoid larynx carcinoma (Hep2) cell lines. Additionally, we performed cellular viability tests using trypan blue, proliferation MTT assay, apoptosis, p53 and real-time polymerase chain reaction for gene expression of survivin and caspase-3.

Famotidine inhibits glycogen synthase kinase-3β: an investigation by docking simulation and experimental validation.

Famotidine was investigated as an inhibitor of glycogen synthase kinase-3β (GSK-3β) in an attempt to explain the molecular mechanism of its hypoglycemic side effects. The investigation included simulated docking experiments, in vitro enzyme inhibition assay, glycogen sparing studies using animal models and single dose oral glucose tolerance test (OGTT). Docking studies showed how famotidine is optimally fit within the binding pocket of GSK-3β via numerous attractive interactions with some specific amino acids.

Inhibition of glycogen synthase kinase by curcumin: Investigation by simulated molecular docking and subsequent in vitro/in vivo evaluation.

Curcumin was investigated as an inhibitor of glycogen synthase kinase-3beta (GSK-3beta) in an attempt to explain some of its interesting multiple pharmacological effects, such as its anti-diabetic, anti-inflammatory, anti-cancer, anti-malarial and anti-alzheimer's properties. The investigation included simulated docking experiments to fit curcumin within the binding pocket of GSK-3beta followed by experimental in vitro and in vivo validations. Curcumin was found to optimally fit within the binding pocket of GSK-3beta via several attractive interactions with key amino acids.

Pharmacophore modeling, quantitative structure-activity relationship analysis, and in silico screening reveal potent glycogen synthase kinase-3beta inhibitory activities for cimetidine, hydroxychloroquine, and gemifloxacin.

The pharmacophoric space of glycogen synthase kinase-3beta (GSK-3beta) was explored using two diverse sets of inhibitors. Subsequently, genetic algorithm and multiple linear regression analysis were employed to select optimal combination of pharmacophores and physicochemical descriptors that access self-consistent and predictive quantitative structure-activity relationship (QSAR) against 132 training compounds ( r (2) 123 = 0.663, F = 24.

Olanzapine inhibits glycogen synthase kinase-3beta: an investigation by docking simulation and experimental validation.

Olanzapine was investigated as an inhibitor of glycogen synthase kinase-3beta (GSK-3beta) in an attempt to evaluate its effect on blood glucose level. The investigation included simulated docking experiments to fit olanzapine within the binding pocket of GSK-3beta followed by in vitro enzyme inhibition assay as well as in vivo subchronic animal treatment. Olanzapine was found to readily fit within the binding pocket of GSK-3beta in a low energy orientation characterized with optimal attractive interactions bridging the tricyclic thienobenzodiazepine nitrogen and sulfur atoms of olanzapine and the residue of VAL-135 of GSK-3beta.