BACKGROUND Umbilical cord(UC)mesenchymal stem cell(MSC)transplantation is a potential therapeutic intervention for atherosclerotic vascular disease.Integrin beta 3(ITGB3)promotes cell migration in several cell types.H...BACKGROUND Umbilical cord(UC)mesenchymal stem cell(MSC)transplantation is a potential therapeutic intervention for atherosclerotic vascular disease.Integrin beta 3(ITGB3)promotes cell migration in several cell types.However,whether ITGBmodified MSCs can migrate to plaque sites in vivo and play an anti-atherosclerotic role remains unclear.AIM To investigate whether ITGB3-overexpressing MSCs(MSCs^(ITGB3))would exhibit improved homing efficacy in atherosclerosis.METHODS UC MSCs were isolated and expanded.Lentiviral vectors encoding ITGB3 or green fluorescent protein(GFP)as control were transfected into MSCs.Sixty male apolipoprotein E-/-mice were acquired from Beijing Vital River Lab Animal Technology Co.,Ltd and fed with a high-fat diet(HFD)for 12 wk to induce the formation of atherosclerotic lesions.These HFD-fed mice were randomly separated into three clusters.GFP-labeled MSCs(MSCs^(GFP))or MSCs^(ITGB3)were transplanted into the mice intravenously via the tail vein.Immunofluorescence staining,Oil red O staining,histological analyses,western blotting,enzymelinked immunosorbent assay,and quantitative real-time polymerase chain reaction were used for the analyses.RESULTS ITGB3 modified MSCs successfully differentiated into the“osteocyte”and“adipocyte”phenotypes and were characterized by positive expression(>91.3%)of CD29,CD73,and CD105 and negative expression(<1.35%)of CD34 and Human Leukocyte Antigen-DR.In a transwell assay,MSCs^(ITGB3)showed significantly faster migration than MSCsGFP.ITGB3 overexpression had no effects on MSC viability,differentiation,and secretion.Immunofluorescence staining revealed that ITGB3 overexpression substantially enhanced the homing of MSCs to plaque sites.Oil red O staining and histological analyses further confirmed the therapeutic effects of MSCs^(ITGB3),significantly reducing the plaque area.Enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction revealed that MSC^(ITGB3)transplantation considerably decreased the inflammatory response in pathological tissues by improving the dynamic equilibrium of pro-and anti-inflammatory cytokines.CONCLUSION These results showed that ITGB3 overexpression enhanced the MSC homing ability,providing a potential approach for MSC delivery to plaque sites,thereby optimizing their therapeutic effects.展开更多
Pumped storage units are the main parts in China’s power construction,as a hot issue concerned by the industry.The pump turbine involves the two-way flows and a multiple condition operation,and its operation flow pat...Pumped storage units are the main parts in China’s power construction,as a hot issue concerned by the industry.The pump turbine involves the two-way flows and a multiple condition operation,and its operation flow pattern is very complex.The particle image velocimetry(PIV)is a very effective test technique to determine the internal flow field of pump turbines.This paper discusses the key problems of the pump turbine,based on the PIV experiments under typical conditions of the pump turbine,especially for problems such as the S-shape problem,the hump problem,the pressure fluctuation problem and the cavitation problem.In the internal flow fields under typical conditions are determined.The vortices induced and their development are observed in the PTV test.The flow phenomenon is shown at each operating point.The typical problems of the pump turbine are closely related to the vortex distribution in the internal flow field.From the PIV test results under several working conditions and from the comparisons between the optimal condition and the part load condition,it is seen that the vortex distributions are very different.Vortices at the vane-less area between the guide vane and the runner are closely related to the strong pressure pulsation,the first hump and the S-shape curve.From the PIV results of the cavitation working points,it is seen that the flow angle is changed in the vane-less region and the runner leading edge because of the cavitation bubbles and that the flow angle deviates from the optimal setting angle.From the computational fluid dynamics(CFD)result of the second hump working points,it is concluded that the vortex shedding on the runner leading edge is the main cause of the second hump.展开更多
基金National Natural Science Foundation of China,No.82100301Key Science and Technology Research Program of Hebei Provincial Department of Health,No,20221014.
文摘BACKGROUND Umbilical cord(UC)mesenchymal stem cell(MSC)transplantation is a potential therapeutic intervention for atherosclerotic vascular disease.Integrin beta 3(ITGB3)promotes cell migration in several cell types.However,whether ITGBmodified MSCs can migrate to plaque sites in vivo and play an anti-atherosclerotic role remains unclear.AIM To investigate whether ITGB3-overexpressing MSCs(MSCs^(ITGB3))would exhibit improved homing efficacy in atherosclerosis.METHODS UC MSCs were isolated and expanded.Lentiviral vectors encoding ITGB3 or green fluorescent protein(GFP)as control were transfected into MSCs.Sixty male apolipoprotein E-/-mice were acquired from Beijing Vital River Lab Animal Technology Co.,Ltd and fed with a high-fat diet(HFD)for 12 wk to induce the formation of atherosclerotic lesions.These HFD-fed mice were randomly separated into three clusters.GFP-labeled MSCs(MSCs^(GFP))or MSCs^(ITGB3)were transplanted into the mice intravenously via the tail vein.Immunofluorescence staining,Oil red O staining,histological analyses,western blotting,enzymelinked immunosorbent assay,and quantitative real-time polymerase chain reaction were used for the analyses.RESULTS ITGB3 modified MSCs successfully differentiated into the“osteocyte”and“adipocyte”phenotypes and were characterized by positive expression(>91.3%)of CD29,CD73,and CD105 and negative expression(<1.35%)of CD34 and Human Leukocyte Antigen-DR.In a transwell assay,MSCs^(ITGB3)showed significantly faster migration than MSCsGFP.ITGB3 overexpression had no effects on MSC viability,differentiation,and secretion.Immunofluorescence staining revealed that ITGB3 overexpression substantially enhanced the homing of MSCs to plaque sites.Oil red O staining and histological analyses further confirmed the therapeutic effects of MSCs^(ITGB3),significantly reducing the plaque area.Enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction revealed that MSC^(ITGB3)transplantation considerably decreased the inflammatory response in pathological tissues by improving the dynamic equilibrium of pro-and anti-inflammatory cytokines.CONCLUSION These results showed that ITGB3 overexpression enhanced the MSC homing ability,providing a potential approach for MSC delivery to plaque sites,thereby optimizing their therapeutic effects.
基金supported by the National Natural Science Foundation of China(Grant No.51279172)supported by the China Postdoctoral Science Foundation(Grant No.2020M673568XB),the Deyang Science and Technology Support Program(Grant No.2018CKJ002).
文摘Pumped storage units are the main parts in China’s power construction,as a hot issue concerned by the industry.The pump turbine involves the two-way flows and a multiple condition operation,and its operation flow pattern is very complex.The particle image velocimetry(PIV)is a very effective test technique to determine the internal flow field of pump turbines.This paper discusses the key problems of the pump turbine,based on the PIV experiments under typical conditions of the pump turbine,especially for problems such as the S-shape problem,the hump problem,the pressure fluctuation problem and the cavitation problem.In the internal flow fields under typical conditions are determined.The vortices induced and their development are observed in the PTV test.The flow phenomenon is shown at each operating point.The typical problems of the pump turbine are closely related to the vortex distribution in the internal flow field.From the PIV test results under several working conditions and from the comparisons between the optimal condition and the part load condition,it is seen that the vortex distributions are very different.Vortices at the vane-less area between the guide vane and the runner are closely related to the strong pressure pulsation,the first hump and the S-shape curve.From the PIV results of the cavitation working points,it is seen that the flow angle is changed in the vane-less region and the runner leading edge because of the cavitation bubbles and that the flow angle deviates from the optimal setting angle.From the computational fluid dynamics(CFD)result of the second hump working points,it is concluded that the vortex shedding on the runner leading edge is the main cause of the second hump.