Schwann cells in peripheral nerves react to traumatic nerve injury by attempting to grow and regenerate.Howeve r,it is unclear what factors play a role in this process.In this study,we searched a GEO database and foun...Schwann cells in peripheral nerves react to traumatic nerve injury by attempting to grow and regenerate.Howeve r,it is unclear what factors play a role in this process.In this study,we searched a GEO database and found that expression of platelet factor 4 was markedly up-regulated after sciatic nerve injury.Platelet factor is an important molecule in cell apoptosis,diffe rentiation,survival,and proliferation.Further,polymerase chain reaction and immunohistochemical staining confirmed the change in platelet factor 4 in the sciatic nerve at different time points after injury.Enzyme-linked immunosorbent assay confirmed that platelet factor 4 was secreted by Schwann cells.We also found that silencing platelet factor 4 decreased the proliferation and migration of primary cultured Schwann cells,while exogenously applied platelet factor 4 stimulated Schwann cell prolife ration and migration and neuronal axon growth.Furthermore,knocking out platelet factor 4 inhibited the prolife ration of Schwann cells in injured rat sciatic nerve.These findings suggest that Schwann cell-secreted platelet factor 4 may facilitate peripheral nerve repair and regeneration by regulating Schwann cell activation and axon growth.Thus,platelet factor 4 may be a potential therapeutic target for traumatic peripheral nerve injury.展开更多
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
目的:探讨aMAP(age-male-ALBI-platelet,aMAP)、天门冬氨酸氨基转移酶/血小板比率指数(aspartate aminotransferase-to-platelet ratio index,APRI)、基于4因子的肝纤维化指数(fibrosis index based on the 4 factors,FIB-4)及肝硬度值(...目的:探讨aMAP(age-male-ALBI-platelet,aMAP)、天门冬氨酸氨基转移酶/血小板比率指数(aspartate aminotransferase-to-platelet ratio index,APRI)、基于4因子的肝纤维化指数(fibrosis index based on the 4 factors,FIB-4)及肝硬度值(liver stiffness measurement,LSM)评估乙型肝炎(乙肝)肝硬化患者食管胃静脉曲张(esophageal gastric varices,EGV)程度的价值。方法:选取2018年4月到2022年5月期间在上海交通大学医学院附属瑞金医院确诊并接受治疗的乙肝肝硬化患者114例,对其进行肝功能、血常规、LSM、胃镜等检查,根据计算公式计算aMAP、APRI、FIB-4。根据胃镜结果将患者分为无EGV组(39例)、轻度EGV组(30例)、中度EGV组(23例)及重度EGV组(22例),比较4组间的aMAP、APRI、FIB-4。采用受试者操作特征曲线(receiver operator characteristic curve,ROC曲线)分析aMAP、APRI、FIB-4及LSM评估乙肝肝硬化患者EGV程度的价值。结果:EGV患者(包括轻度、中度及重度EGV组)的aMAP、APRI、FIB-4、LSM均显著高于无EGV的患者,差异有统计学意义(P<0.05)。轻度、中度及重度EGV组间的aMAP、APRI、FIB-4差异均有统计学意义(P<0.05);轻度EGV组与中度、重度EGV组间LSM差异有统计学意义(P<0.05)。aMAP评估EGV程度的ROC曲线下面积(the area under ROC curve,AUROC)为0.76,灵敏度为85.9%,特异度为65.7%;APRI、FIB-4和LSM评估EGV程度的AUROC分别为0.86、0.85、0.79,灵敏度分别为81.30%、82.80%、88.40%,特异度分别为82.90%、77.10%、66.80%。aMAP、APRI、FIB-4和LSM对肝硬化患者是否合并EGV有较好诊断价值(P<0.05)。aMAP、APRI、FIB-4对乙肝肝硬化患者的EGV程度有一定诊断价值(P<0.05),但特异度较低。结论:aMAP、APRI、FIB-4及LSM诊断乙肝肝硬化患者伴EGV的价值较高,而aMAP、APRI及FIB-4对其EGV程度有一定评估价值,可作为不适合做胃镜患者评估EGV的补充参考,为EGV的预防及治疗提供依据。展开更多
Objective： To explore the role of interleukin 4（IL-4）, expressions of cyclooxygenase-2 （COX-2） and platelet-derived growth factor （PDGF） in the model of chronic obstructive pulmonary disease （COPD）, in the lu...Objective： To explore the role of interleukin 4（IL-4）, expressions of cyclooxygenase-2 （COX-2） and platelet-derived growth factor （PDGF） in the model of chronic obstructive pulmonary disease （COPD）, in the lungs of rats. Methods： Male Wistar rats were used to build up the model of COPD. Rats were randomly divided into the control group and model group, the IL-4 group and the dexamethasone group. The expressions of COX-2, PDGF-A and PDGF-B in the lung tissue were detected by western blotting and RT-PCR. Results： The expressions of COX-2, PDGF-A and PDGF-B in the model group were increased significantly. Those expressions in the IL-4 and dexamethasone group were notably decreased. Conclusion： IL-4 and dexamethasone could interfere in the establishment of COPD. The expressions of COX-2 and PDGF in the lung tissue of COPD were increased significantly and IL-4 and dexamethasone could decrease those expressions.展开更多
To explore the effects of platelet factor 4(PF4) on hematopoietic reconstitution and its mechanism in syngenic bone marrow transplantation (BMT). The syngenic B MT mice models were established. 20 and 26 h before irr...To explore the effects of platelet factor 4(PF4) on hematopoietic reconstitution and its mechanism in syngenic bone marrow transplantation (BMT). The syngenic B MT mice models were established. 20 and 26 h before irradiation, the mice were injected 20 μg/kg PF4 or PBS twice into abdominal cavity, then the donor bone marrow nuclear cells (BMNC) were transplanted. On the 7th day, spleen clone forming units (CFU S) were counted. On the 7th, 14th and 21st day after BMT, the BMNC and megakaryoryocytes in bone marrow tissue were counted and the percentage of hematopoietic tissue and expression level of heparan sulfate in bone marrow tissue were assessed. In PF4 treated groups, the CFU S counts on the 7th day were higher than those in BMT groups after BMT. The BMNC and megakaryoryocyte counts and the percentage of hematopoietic tissue and heparan sulfate expression level were higher than those in BMT group on the 7th, 14th and 21st day after BMT ( P <0.01 or P <0.05). PF4 could accelerate hematopoietic reconstitution of syngenic bone marrow transplantation. The promotion of the heparan sulfate expression in bone marrow may be one of mechanisms of PF4.展开更多
基金supported by the National Natural Science Foundation of China,Nos.31730031,32130060the National Natural Science Foundation of China,No.31971276(to JH)+1 种基金the Natural Science Foundation of Jiangsu Province,No.BK20202013(to XG)the Natural Science Foundation of Jiangsu Higher Education Institutions of China(Major Program),No.19KJA320005(to JH)。
文摘Schwann cells in peripheral nerves react to traumatic nerve injury by attempting to grow and regenerate.Howeve r,it is unclear what factors play a role in this process.In this study,we searched a GEO database and found that expression of platelet factor 4 was markedly up-regulated after sciatic nerve injury.Platelet factor is an important molecule in cell apoptosis,diffe rentiation,survival,and proliferation.Further,polymerase chain reaction and immunohistochemical staining confirmed the change in platelet factor 4 in the sciatic nerve at different time points after injury.Enzyme-linked immunosorbent assay confirmed that platelet factor 4 was secreted by Schwann cells.We also found that silencing platelet factor 4 decreased the proliferation and migration of primary cultured Schwann cells,while exogenously applied platelet factor 4 stimulated Schwann cell prolife ration and migration and neuronal axon growth.Furthermore,knocking out platelet factor 4 inhibited the prolife ration of Schwann cells in injured rat sciatic nerve.These findings suggest that Schwann cell-secreted platelet factor 4 may facilitate peripheral nerve repair and regeneration by regulating Schwann cell activation and axon growth.Thus,platelet factor 4 may be a potential therapeutic target for traumatic peripheral nerve injury.
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.
文摘目的:探讨aMAP(age-male-ALBI-platelet,aMAP)、天门冬氨酸氨基转移酶/血小板比率指数(aspartate aminotransferase-to-platelet ratio index,APRI)、基于4因子的肝纤维化指数(fibrosis index based on the 4 factors,FIB-4)及肝硬度值(liver stiffness measurement,LSM)评估乙型肝炎(乙肝)肝硬化患者食管胃静脉曲张(esophageal gastric varices,EGV)程度的价值。方法:选取2018年4月到2022年5月期间在上海交通大学医学院附属瑞金医院确诊并接受治疗的乙肝肝硬化患者114例,对其进行肝功能、血常规、LSM、胃镜等检查,根据计算公式计算aMAP、APRI、FIB-4。根据胃镜结果将患者分为无EGV组(39例)、轻度EGV组(30例)、中度EGV组(23例)及重度EGV组(22例),比较4组间的aMAP、APRI、FIB-4。采用受试者操作特征曲线(receiver operator characteristic curve,ROC曲线)分析aMAP、APRI、FIB-4及LSM评估乙肝肝硬化患者EGV程度的价值。结果:EGV患者(包括轻度、中度及重度EGV组)的aMAP、APRI、FIB-4、LSM均显著高于无EGV的患者,差异有统计学意义(P<0.05)。轻度、中度及重度EGV组间的aMAP、APRI、FIB-4差异均有统计学意义(P<0.05);轻度EGV组与中度、重度EGV组间LSM差异有统计学意义(P<0.05)。aMAP评估EGV程度的ROC曲线下面积(the area under ROC curve,AUROC)为0.76,灵敏度为85.9%,特异度为65.7%;APRI、FIB-4和LSM评估EGV程度的AUROC分别为0.86、0.85、0.79,灵敏度分别为81.30%、82.80%、88.40%,特异度分别为82.90%、77.10%、66.80%。aMAP、APRI、FIB-4和LSM对肝硬化患者是否合并EGV有较好诊断价值(P<0.05)。aMAP、APRI、FIB-4对乙肝肝硬化患者的EGV程度有一定诊断价值(P<0.05),但特异度较低。结论:aMAP、APRI、FIB-4及LSM诊断乙肝肝硬化患者伴EGV的价值较高,而aMAP、APRI及FIB-4对其EGV程度有一定评估价值,可作为不适合做胃镜患者评估EGV的补充参考,为EGV的预防及治疗提供依据。
文摘Objective： To explore the role of interleukin 4（IL-4）, expressions of cyclooxygenase-2 （COX-2） and platelet-derived growth factor （PDGF） in the model of chronic obstructive pulmonary disease （COPD）, in the lungs of rats. Methods： Male Wistar rats were used to build up the model of COPD. Rats were randomly divided into the control group and model group, the IL-4 group and the dexamethasone group. The expressions of COX-2, PDGF-A and PDGF-B in the lung tissue were detected by western blotting and RT-PCR. Results： The expressions of COX-2, PDGF-A and PDGF-B in the model group were increased significantly. Those expressions in the IL-4 and dexamethasone group were notably decreased. Conclusion： IL-4 and dexamethasone could interfere in the establishment of COPD. The expressions of COX-2 and PDGF in the lung tissue of COPD were increased significantly and IL-4 and dexamethasone could decrease those expressions.
基金the National Natural ScienceFoundation(Serial No. 3 9870 92 6)
文摘To explore the effects of platelet factor 4(PF4) on hematopoietic reconstitution and its mechanism in syngenic bone marrow transplantation (BMT). The syngenic B MT mice models were established. 20 and 26 h before irradiation, the mice were injected 20 μg/kg PF4 or PBS twice into abdominal cavity, then the donor bone marrow nuclear cells (BMNC) were transplanted. On the 7th day, spleen clone forming units (CFU S) were counted. On the 7th, 14th and 21st day after BMT, the BMNC and megakaryoryocytes in bone marrow tissue were counted and the percentage of hematopoietic tissue and expression level of heparan sulfate in bone marrow tissue were assessed. In PF4 treated groups, the CFU S counts on the 7th day were higher than those in BMT groups after BMT. The BMNC and megakaryoryocyte counts and the percentage of hematopoietic tissue and heparan sulfate expression level were higher than those in BMT group on the 7th, 14th and 21st day after BMT ( P <0.01 or P <0.05). PF4 could accelerate hematopoietic reconstitution of syngenic bone marrow transplantation. The promotion of the heparan sulfate expression in bone marrow may be one of mechanisms of PF4.
