Objective To investigate the role of interferon ?on smooth muscle cells proliferation and migration after balloon injury. Methods Animal model of rabbit iliac artery balloon injury was set up, smooth muscle cells derived from injured artery were cultured. Smooth muscle cells were divided into four groups ( control, TGF ? 1, IFN ?, TGF ? 1 and IFN ?).Cells from each group were treated with medium or TGF ? 1 (10 ng/ml) and/or IFN ?(500 u/ml) for 72 h separately. Smooth muscle cell proliferation was determined by cell count and MTT, migration of smooth muscle cells was also detected. Matrix metalloproteinase 2 was also detected by zymography. Results Our results showed that, compared with group control(2.875?0.323?10 5 cells/ml,279.9?8.129 ?m), TGF ? 1 increased cell count (4.188?0.239?10 5 cells/ml, P

The beta-secretase is one of prospective targets against Alzheimer's disease (AD). A three-dimensional quan titative structure-activity relationship (3D-QSAR) model of Hydroethylamines (HEAs) as beta-secretase inhibitors was established using Topomer CoMFA. The multiple correlation coefficient of fitting, cross validation and external validation were r2 = 0.928, q(loo)2 = 0.605 and r(pred)2 = 0.626, respectively. The 3D-QSAR model was used to search R groups from ZINC database as the source of structural fragments. As a result, a series of R groups with relatively high activity contribution was obtained to design a total of 15 new compounds, with higher activity than that of the template molecule. The molecular docking was employed to study the interaction mode between the new compounds as ligands and beta-secretase as receptors, displaying that hydrogen bond and hydrophobicity played important roles in the binding affinity between the new compounds and beta-secretase. The results showed that Topomer CoMFA and To pomer Search could be effectively used to screen and design new molecules of HEAs as beta-secretase inhibitors, and the designed compounds could provide new candidates for drug design targeting AD.
Amyloid Precursor Protein Secretases ; antagonists & inhibitors ; Drug Design ; Hydrophobic and Hydrophilic Interactions ; Ligands ; Molecular Docking Simulation ; Quantitative Structure-Activity Relationship

Objective:To explore expression of each member of miR17-92 cluster in peripheral blood mononuclear cells(PBMCs)of patients with gout,to predict their possible targets and pathways of action,and to evaluate their possible mechanism and clinical significance in gout.Methods:A total 67 gouty arthritis(GA)patients were selected,including 22 patients with acute gout arthritis(AG)and 45 patients with intermittent gout(IG),and 35 normal health control(HC)were selected in Affiliated Hospital of North Sichuan Medical College.RT-qPCR measured expressions of miR17-92 cluster,IFN-γ,IL-10 and some members of JAK-STAT pathway,and relevant laboratory indicators were collected to analyze correlation between each other.Results:Relative expressions of miR17,miR18a,miR19a,miR20a and miR19b were significantly changed in AG,IG and HC(H=8.753,P<0.05;H=6.338,P<0.05;H=6.523,P<0.05;H=9.061,P<0.05;H=9.729,P<0.01).JAK3 and STAT2 expressions were statistically different in AG,IG and HC groups(H=10.349,P<0.01;H=14.801,P<0.01).Expression of IFN-γ was statistically different among AG,IG and HC groups(H=8.734,P<0.05).In AG patients,miR18a expression was inversely correlated with IBIL,Crea,MO and HGB.miR19a ex-pression was negatively associated and TC,UA and HGB.miR20a expression was negatively associated with Crea.miR19b expression was negatively associated with UA and HGB.In IG patients,miR17 expression was negatively associated with IBIL,WBC,LY and MO.miR18a expression was positively associated with ALP,miR19a expression was negatively associated with TC and UA,and miR20a expression was negatively associated with ADA and UA.Conclusion:miR17-92 cluster may regulate development and partici-pate in clinical pathology of gout by targeting JAK-STAT pathway.