Pro-urokinase promotes angiogenesis but does not reduce neuronal apoptosis in infarcted cerebral tissue

Ischemic stroke is most commonly caused by vascular occlusion due to thrombosis or arterial embolism. Recently, thrombolysis has been used with increasing frequency for the treatment of acute ischemic stroke. Among the drugs used for thrombolysis, only recombinant tissue plasminogen activator is widely accepted internationally （Albers et al., 2008）. In China, urokinase has been widely used for thrombolysis after acute ischemic stroke. Pro-uro- kinase is the precursor of urokinase. Compared with urokinase, pro-uroki- nase has greater ability to dissolve thrombus and is safer to use.

Transfusion of CXCR4-priming endothelial progenitor cells reduces cerebral ischemic damage and promotes angiogenesis and neurogenesis in db/db diabetic mice

Previous studies suggest that reduction and dysfunction of circulating endothelial progenitor cells(EPCs),and dysregulation in stromal cell derived factor-1/CXC-chemokine receptor 4(SDF-1/ CXCR4) axis in diabetes could be therapeutic targets for diabetic ischemic stroke.This study investigated the efficacy of CXCR4-priming EPCs on cerebral repair following ischemic stroke in db/db diabetic mice.Bone marrow derived EPCs from db/+ control mice were transfected with adenovirus(1×10~7 IU) carrying CXCR4(Ad-CXCR4-EPCs)or null(Ad- null-EPCs).The db/db mice were divided into three groups for EPCs injection(2×10~5 cells/100μl): Ad-CXCR4-EPCs,Ad-null-EPCs or saline(vehicle), via tail vein 2 hrs after middle cerebral artery occlusion (MCAO) surgery.Cerebral blood flow(CBF) was measured with laser Doppler flowmeter.Mice were sacrificed at 2 or 7 days thereafter.Level of circulating EPCs was measured by flow cytometry. Ischemic damage,cerebral microvascular density (MVD),angiogenesis and neurogenesis were determined by histological staining with Fluoro-J,CD31, CD31 +BrdU,NeuN +BrdU,GFAP+BrdU,respectively. Results(table) showed:1) Levels of CXCR4 expression were reduced in the brain and EPCs of db/db mice as measured by real-time RT-PCR and western blot analyses(data not shown);2) The level of circulating EPCs was more in the mice treated with Ad-CXCR4-EPCs;3)EPC transfusion improved CBF,increased MVD,angiogenesis and neurogenesis in peri-infarct area,and decreased ischemic damage.The efficacies were better in Ad-CXCR4 -EPCs group.Data suggest that transfusion of Ad-CXCR4-EPCs could be a therapeutic avenue for ischemia stroke in diabetes.

CD137-CD137L signaling promotes angiogenesis in atherosclerosis plaque of mice through activating nuclear factor of activated T cells c1

Objective To explore whether CD137-CD137L signaling can promote angiogenesis in atherosclerosis plaque via activating nuclear factor of activated T cells c1(NFATc1).Methods Apolipoprotein E knock out mice were divided into the following groups:control group(n=5),CD137 activated group(n=5)and CD137 in-

An NIR photothermal-responsive hybrid hydrogel for enhanced wound healing

Moderately regulating vascularization and immune microenvironment of wound site is necessary to achieve scarless wound healing of the skin.Herein,we have prepared an angiogenesis-promoting and scar-preventing band-aid with a core-shell structure,that consists of MXene-loaded nanofibers(MNFs)as the core and dopamine-hyaluronic acid hydrogel(H)as the shell(MNFs@V-H@DA)to encapsulate a growth factor(vascular endothelial growth factor,VEGF,abbreviated as V)and H2S donor(diallyl trisulfide,DATS,abbreviated as DA).The continuous release of DA from this system produced H2S,which would successfully induce macrophages to polarize into M2-lile phenotype,regulating the immune microenvironment and inhibiting an excessive inflammatory response at the wound sites.It is conducive to the proliferation of skin cells,facilitating the wound healing.In addition,an appropriate amount of VEGF can be released from the MXene nanofibrous skeleton by adjusting the time of near-infrared(NIR)light exposure,preventing excessive neovascularization and extracellular matrix deposition at the wound sites.Collectively,this NIR photothermal-responsive band-aid achieved scarless wound healing through gradient-controlled vascularization and a related immune sequential reaction of damaged skin tissue.