Background:The effect of platelet factor 4(PF4)on bone marrow mesenchymal stem cells(BMMSCs)and osteoporosis is poorly understood.Therefore,this study aimed to evaluate the effects of PF4-triggered bone destruction in...Background:The effect of platelet factor 4(PF4)on bone marrow mesenchymal stem cells(BMMSCs)and osteoporosis is poorly understood.Therefore,this study aimed to evaluate the effects of PF4-triggered bone destruction in mice and determine the underlying mechanism.Methods:First,in vitro cell proliferation and cell cycle of BMMSCs were assessed using a CCK8 assay and flow cytometry,respectively.Osteogenic differentiation was confirmed using staining and quantification of alkaline phosphatase and Alizarin Red S.Next,an osteoporotic mouse model was established by performing bilateral ovariectomy(OVX).Furthermore,the PF4 concentrations were obtained using enzymelinked immunosorbent assay.The bone microarchitecture of the femur was evaluated using microCT and histological analyses.Finally,the key regulators of osteogenesis and pathways were investigated using quantitative real-time polymerase chain reaction and Western blotting.Results:Human PF4 widely and moderately decreased the cell proliferation and osteogenic differentiation ability of BMMSCs.Furthermore,the levels of PF4 in the serum and bone marrow were generally increased,whereas bone microarchitecture deteriorated due to OVX.Moreover,in vivo mouse PF4 supplementation triggered bone deterioration of the femur.In addition,several key regulators of osteogenesis were downregulated,and the integrinα5-focal adhesion kinase-extracellular signalregulated kinase(ITGA5-FAK-ERK)pathway was inhibited due to PF4 supplementation.Conclusions:PF4 may be attributed to OVX-i nduced bone loss triggered by the suppression of bone formation in vivo and alleviate BMMSC osteogenic differentiation by inhibiting the ITGA5-FAK-ERK pathway.展开更多
Objective:To investigate the effect of Chaihu Shugan decoction(CSD)on gastric smooth muscle cells(GSMCs)apoptosis in rats with functional dyspepsia(FD).Methods:48Sprague-Dawley(SD)rats were randomly assigned into six ...Objective:To investigate the effect of Chaihu Shugan decoction(CSD)on gastric smooth muscle cells(GSMCs)apoptosis in rats with functional dyspepsia(FD).Methods:48Sprague-Dawley(SD)rats were randomly assigned into six groups:a normal control group,a model group,apositive control(domperidone)group and low-,middle-and high-dose CSD groups.A rat model of FD was established by constantly squeezing their tails.The rats were administered CSD(0.16g/mL,0.32g/mL,0.64g/mL)or domperidone(0.3 g/L)via intragastric gavage for four weeks.The gastric emptying rate was detected at 4 weeks post-administration.Apoptosis of GSMCs was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)staining and the mitochondrial morphology was observed by transmission electron microscopy.The expression of Bcl-2and Bax was measured by immunohistochemistry.Results:FD resulted in marked reduction of gastric emptying rate,severe gastric tissue damage and mitochondria injury,but were reversed by CSD treatment(P<0.05).The apoptosis-induced protein Bax was markedly down-regulated by CSD,whereas the expression of the anti-apoptotic Bcl-2 protein was notably increased(P<0.05).Furthermore,CSD could protect the FD rats against GSMCs apoptosis manifested by a decreased in TUNEL-positive cells(P<0.05).Conclusion:CSD could alleviate GSMCs apoptosis in FD rats,possibly by the modulation of Bcl-2 and Bax expression,and the suppression of mitochondria injury.展开更多
This study used the pseudo-spinodal mechanism to obtain the ultrafineαphase for designing highstrength titanium alloy.Diffusion multiple experiments were designed to find the composition range of TM-x Mo-y V alloy(TM...This study used the pseudo-spinodal mechanism to obtain the ultrafineαphase for designing highstrength titanium alloy.Diffusion multiple experiments were designed to find the composition range of TM-x Mo-y V alloy(TM:Ti-4.5 Al-2 Cr-2.5 Nb-2 Zr-1 Sn)for obtaining ultrafineαphase.CALPHAD results confirm that when the alloy composition is located near the intersection of theαandβphase free energy curves,the alloy will undergo pseudo-spinodal transformation and obtain the ultrafineαphase.The designed TM-6 Mo-3 V alloy has a yield strength of 1411 MPa and an elongation of 6.5%.The strength of the alloy depends on the thickness,fraction of theαphase and the solid solution strengthening effect of the alloying elements.The deformation mechanism of the alloy is the dislocation slip of theαandβphases and the twin deformation of theαphase.The large number ofα/βinterfaces produced by the fineαphase is the main reason for limiting the ductility of the alloy.The use of the pseudo-spinodal mechanism combined with diffusion multiple experiments and CALPHAD is an effective method for designing high-strength titanium alloys.展开更多
基金Beijing Natural Science Foundation,Grant/Award Number:L222145CAMS Innovation Fund for Medical Sciences,Grant/Award Number:2019-I2M-5-038+2 种基金Clinical Medicine Plus X-Young Scholars Project,Peking Universitythe Fundamental Research Funds for the Central Universities,Grant/Award Number:PKU2023LCXQ017National Natural Science Foundation of China,Grant/Award Number:81700935。
文摘Background:The effect of platelet factor 4(PF4)on bone marrow mesenchymal stem cells(BMMSCs)and osteoporosis is poorly understood.Therefore,this study aimed to evaluate the effects of PF4-triggered bone destruction in mice and determine the underlying mechanism.Methods:First,in vitro cell proliferation and cell cycle of BMMSCs were assessed using a CCK8 assay and flow cytometry,respectively.Osteogenic differentiation was confirmed using staining and quantification of alkaline phosphatase and Alizarin Red S.Next,an osteoporotic mouse model was established by performing bilateral ovariectomy(OVX).Furthermore,the PF4 concentrations were obtained using enzymelinked immunosorbent assay.The bone microarchitecture of the femur was evaluated using microCT and histological analyses.Finally,the key regulators of osteogenesis and pathways were investigated using quantitative real-time polymerase chain reaction and Western blotting.Results:Human PF4 widely and moderately decreased the cell proliferation and osteogenic differentiation ability of BMMSCs.Furthermore,the levels of PF4 in the serum and bone marrow were generally increased,whereas bone microarchitecture deteriorated due to OVX.Moreover,in vivo mouse PF4 supplementation triggered bone deterioration of the femur.In addition,several key regulators of osteogenesis were downregulated,and the integrinα5-focal adhesion kinase-extracellular signalregulated kinase(ITGA5-FAK-ERK)pathway was inhibited due to PF4 supplementation.Conclusions:PF4 may be attributed to OVX-i nduced bone loss triggered by the suppression of bone formation in vivo and alleviate BMMSC osteogenic differentiation by inhibiting the ITGA5-FAK-ERK pathway.
基金supported by the National Natural Science Foundation of China(No.81360544)
文摘Objective:To investigate the effect of Chaihu Shugan decoction(CSD)on gastric smooth muscle cells(GSMCs)apoptosis in rats with functional dyspepsia(FD).Methods:48Sprague-Dawley(SD)rats were randomly assigned into six groups:a normal control group,a model group,apositive control(domperidone)group and low-,middle-and high-dose CSD groups.A rat model of FD was established by constantly squeezing their tails.The rats were administered CSD(0.16g/mL,0.32g/mL,0.64g/mL)or domperidone(0.3 g/L)via intragastric gavage for four weeks.The gastric emptying rate was detected at 4 weeks post-administration.Apoptosis of GSMCs was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)staining and the mitochondrial morphology was observed by transmission electron microscopy.The expression of Bcl-2and Bax was measured by immunohistochemistry.Results:FD resulted in marked reduction of gastric emptying rate,severe gastric tissue damage and mitochondria injury,but were reversed by CSD treatment(P<0.05).The apoptosis-induced protein Bax was markedly down-regulated by CSD,whereas the expression of the anti-apoptotic Bcl-2 protein was notably increased(P<0.05).Furthermore,CSD could protect the FD rats against GSMCs apoptosis manifested by a decreased in TUNEL-positive cells(P<0.05).Conclusion:CSD could alleviate GSMCs apoptosis in FD rats,possibly by the modulation of Bcl-2 and Bax expression,and the suppression of mitochondria injury.
基金the National Key Technologies R&D Program of China(Nos.2018YFB0704100 and 2016YFB0701301)the National Natural Science Foundation of China(Nos.51901251 and 51671218)the Natural Science Foundation of Hunan Province China(No.2020JJ5750)。
文摘This study used the pseudo-spinodal mechanism to obtain the ultrafineαphase for designing highstrength titanium alloy.Diffusion multiple experiments were designed to find the composition range of TM-x Mo-y V alloy(TM:Ti-4.5 Al-2 Cr-2.5 Nb-2 Zr-1 Sn)for obtaining ultrafineαphase.CALPHAD results confirm that when the alloy composition is located near the intersection of theαandβphase free energy curves,the alloy will undergo pseudo-spinodal transformation and obtain the ultrafineαphase.The designed TM-6 Mo-3 V alloy has a yield strength of 1411 MPa and an elongation of 6.5%.The strength of the alloy depends on the thickness,fraction of theαphase and the solid solution strengthening effect of the alloying elements.The deformation mechanism of the alloy is the dislocation slip of theαandβphases and the twin deformation of theαphase.The large number ofα/βinterfaces produced by the fineαphase is the main reason for limiting the ductility of the alloy.The use of the pseudo-spinodal mechanism combined with diffusion multiple experiments and CALPHAD is an effective method for designing high-strength titanium alloys.
