Cucurbitacins mitigate vascular neointimal hyperplasia by suppressing cyclin A2 expression and inhibiting VSMC proliferation

Background:Restenosis frequently occurs after percutaneous angioplasty in patients with vascular occlusion and seriously threatens their health.Substantial evidence has revealed that preventing vascular smooth muscle cell proliferation using a drug-eluting stent is an effective approach to improve restenosis.Cucurbitacins have been demonstrated to exert an anti-proliferation effect in various tumors and a hypoten-sive effect.This study aims to investigate the role of cucurbitacins extracted from Cucumis melo L.(CuECs)and cucurbitacin B(CuB)on restenosis.Methods:C57BL/6 mice were subjected to left carotid artery ligation and subcu-taneously injected with CuECs or CuB for 4 weeks.Hematoxylin-Eosin,immuno-fluorescence and immunohistochemistry staining were used to evaluate the effect of CuECs and CuB on neointimal hyperplasia.Western blot,real-time PCR,flow cytometry analysis,EdU staining and cellular immunofluorescence assay were em-ployed to measure the effects of CuECs and CuB on cell proliferation and the cell cycle in vitro.The potential interactions of CuECs with cyclin A2 were performed by molecular docking.Results:The results demonstrated that both CuECs and CuB exhibited significant inhibitory effects on neointimal hyperplasia and proliferation of vascular smooth muscle cells.Furthermore,CuECs and CuB mediated cell cycle arrest at the S phase.Autodocking analysis demonstrated that CuB,CuD,CuE and CuI had high binding en-ergy for cyclin A2.Our study also showed that CuECs and CuB dramatically inhibited FBS-induced cyclin A2 expression.Moreover,the expression of cyclin A2 in CuEC-and CuB-treated neointima was downregulated.Conclusions:CuECs,especially CuB,exert an anti-proliferation effect in VSMCs and may be potential drugs to prevent restenosis.

Isogeometric Analysis with Local Adaptivity for Vibration of Kirchhoff Plate

Based on our proposed adaptivity strategy for the vibration of Reissner-Mindlin plate,we develop it to apply for the vibration of Kirchhoff plate.The adaptive algorithm is based on the Geometry-Independent Field approximaTion(GIFT),generalized from Iso-Geometric Analysis(IGA),and it can characterize the geometry of the structure with NURBS(Non-Uniform Rational B-Splines),and independently apply PHT-splines(Polynomial splines over Hierarchical T-meshes)to achieve local refinement in the solution field.TheMAC(Modal AssuranceCriterion)is improved to locate unique,as well as multiple,modal correspondence between different meshes,in order to deal with error estimation.Local adaptivity is carried out by sweeping modes from low to high frequency.Numerical examples showthat a proper choice of the spline space in solution field(with GIFT)can deliver better accuracy than using NURBS solution field.In addition,for vibration of heterogeneous Kirchhoff plates,our proposed method indicates that the adaptive local h-refinement achieves a better solution accuracy than the uniform h-refinement.