Epilepsy is a brain condition characterized by the recurrence of unprovoked seizures.Recent studies have shown that complement component 3(C3)aggravate the neuronal injury in epilepsy.And our previous studies revealed...Epilepsy is a brain condition characterized by the recurrence of unprovoked seizures.Recent studies have shown that complement component 3(C3)aggravate the neuronal injury in epilepsy.And our previous studies revealed that TRPV1(transient receptor potential vanilloid type 1)is involved in epilepsy.Whether complement C3 regulation of neuronal injury is related to the activation of TRPV1 during epilepsy is not fully understood.We found that in a mouse model of status epilepticus(SE),complement C3 derived from astrocytes was increased and aggravated neuronal injury,and that TRPV 1-knockout rescued neurons from the injury induced by complement C3.Circular RNAs are abundant in the brain,and the reduction of circRad52 caused by complement C3 promoted the expression of TRPV 1 and exacerbated neuronal injury.Mechanistically,disorders of neuron-glia interaction mediated by the C3-TRPV1 signaling pathway may be important for the induction of neuronal injury.This study provides support for the hypothesis that the C3-TRFV1 pathway is involved in the prevention and treatment of neuronal injury and cognitive disorders.展开更多
Objective:Myeloma bone disease(MBD)is the most common complication of multiple myeloma(MM).Our previous study showed that the serum levels of C3/C4 in MM patients were significantly positively correlated with the seve...Objective:Myeloma bone disease(MBD)is the most common complication of multiple myeloma(MM).Our previous study showed that the serum levels of C3/C4 in MM patients were significantly positively correlated with the severity of bone disease.However,the mechanism of C3 a/C4 a in osteoclasts MM patients remains unclear.Methods:The formation and function of osteoclasts were analyzed after adding C3 a/C4 a in vitro.RNA-seq analysis was used to screen the potential pathways affecting osteoclasts,and the results were verified by Western blot,q RT-PCR,and pathway inhibitors.Results:The osteoclast area per view induced by 1μg/m L(mean±SD:50.828±12.984%)and 10μg/m L(53.663±12.685%)of C3 a was significantly increased compared to the control group(0μg/m L)(34.635±8.916%)(P<0.001 and P<0.001,respectively).The relative m RNA expressions of genes,OSCAR/TRAP/RANKL/cathepsin K,induced by 1μg/m L(median:5.041,3.726,1.638,and 4.752,respectively)and 10μg/m L(median:5.140,3.702,2.250,and 5.172,respectively)of C3 a was significantly increased compared to the control group(median:3.137,2.004,0.573,and 2.257,respectively)(1μg/m L P=0.001,P=0.003,P<0.001,and P=0.008,respectively;10μg/m L:P<0.001,P=0.019,P<0.001,and P=0.002,respectively).The absorption areas of the osteoclast resorption pits per view induced by 1μg/m L(mean±SD:51.464±11.983%)and 10μg/m L(50.219±12.067%)of C3 a was also significantly increased(33.845±8.331%)(P<0.001 and P<0.001,respectively)compared to the control.There was no difference between the C4 a and control groups.RNA-seq analysis showed that C3 a promoted the proliferation of osteoclasts using the phosphoinositide 3-kinase(PI3 K)signaling pathway.The relative expressions of PIK3 CA/phosphoinositide dependent kinase-1(PDK1)/serum and glucocorticoid inducible protein kinases(SGK3)genes and PI3 K/PDK1/p-SGK3 protein in the C3 a group were significantly higher than in the control group.The activation role of C3 a in osteoclasts of MM patients was reduced by the SGK inhibitor(EMD638683).Conclusions:C3 a activated osteoclasts by regulating the PI3 K/PDK1/SGK3 pathways in MM patients,which was reduced using a SGK inhibitor.Overall,our results identified potential therapeutic targets and strategies for MBD patients。展开更多
目的探讨孕早期血清补体C3、C4水平与系统性红斑狼疮(SLE)孕妇不良妊娠结局的关系。方法在2019年1月至2023年11月进行了一项回顾性队列研究,纳入了来自西安交通大学第一附属医院妇产科的100例SLE孕妇作为研究对象。浊度免疫测定试验对...目的探讨孕早期血清补体C3、C4水平与系统性红斑狼疮(SLE)孕妇不良妊娠结局的关系。方法在2019年1月至2023年11月进行了一项回顾性队列研究,纳入了来自西安交通大学第一附属医院妇产科的100例SLE孕妇作为研究对象。浊度免疫测定试验对所有患者测定血清补体C3、C4水平。比较不良妊娠结局和良好妊娠结局患者血清补体C3、C4水平差异,并通过Logistic模型分析影响SLE孕妇妊娠结局的临床因素。结果共计有48例(48.0%)患者发生不良妊娠结局。在不良妊娠结局患者中血清补体C3和C4水平显著低于良好妊娠结局患者(P<0.001);这种降低趋势主要表现在发生早产和未发生早产以及小于胎龄儿(small for gestational age infant,SGA)和非SGA患者中。经多因素Logistic模型分析,血清补体C3水平降低、不使用AZA和子痫前期是影响SLE患者不良妊娠结局的独立危险因素(P<0.05)。经受试者操作特征(ROC)曲线分析,血清补体C3、C4预测不良妊娠结局的曲线下面积(AUC)为0.832、0.757(P<0.001)。以血清补体C3、C4的正常值下限75 mg/dL、9 mg/dL进行分组,组间间隔为10 mg/dL和1 mg/dL;随着血清补体C3、C4水平的下降,不良妊娠结局的发生率增加,尤其在以血清补体C3分组的患者中。Spearman相关性分析显示孕早期血清补体C3(r=–0.342,P<0.001)、C4(r=–0.387,P<0.001)水平与SLE疾病活动度评分呈显著负相关性。结论孕早期血清补体(尤其是补体C3)水平降低是影响SLE孕妇不良妊娠结局的重要危险因素,因此孕早期补体C3、C4水平降低的患者可能更容易发生不良妊娠结局,但是该结果需要在更大的患者群体中进一步证实。展开更多
基金by the National Natural Science Foundation of China(81571481 and 82060588)the Natural Science Foundation of Hubei Province,China(2017CFA017)+1 种基金the Wuhan Science and Technology Project(2019020701011444)the Medical Science Advancement Program of Wuhan University(TFJC2018001 and TFLC2018001).
文摘Epilepsy is a brain condition characterized by the recurrence of unprovoked seizures.Recent studies have shown that complement component 3(C3)aggravate the neuronal injury in epilepsy.And our previous studies revealed that TRPV1(transient receptor potential vanilloid type 1)is involved in epilepsy.Whether complement C3 regulation of neuronal injury is related to the activation of TRPV1 during epilepsy is not fully understood.We found that in a mouse model of status epilepticus(SE),complement C3 derived from astrocytes was increased and aggravated neuronal injury,and that TRPV 1-knockout rescued neurons from the injury induced by complement C3.Circular RNAs are abundant in the brain,and the reduction of circRad52 caused by complement C3 promoted the expression of TRPV 1 and exacerbated neuronal injury.Mechanistically,disorders of neuron-glia interaction mediated by the C3-TRPV1 signaling pathway may be important for the induction of neuronal injury.This study provides support for the hypothesis that the C3-TRFV1 pathway is involved in the prevention and treatment of neuronal injury and cognitive disorders.
基金supported by the National Natural Science Foundation of China(Grant Nos.81770110,81900131,and 82000219)the Anticancer Major Special Project of Tianjin(Grant No.12ZCDZSY18000)+4 种基金the Tianjin Municipal Natural Science Foundation(Grant Nos.18JCYBJC27200 and 18JCQNJC80400)the Tianjin Education Commission Research Project(Grant Nos.2018KJ043 and 2018KJ045)the Tianjin Health and Family Planning Commission(Grant No.15KG150)the Youth Incubation Fund of Tianjin Medical University General Hospital(Grant No.ZYYFY2019020)the Tianjin Science and Technology Planning Project(Grant No.20YFZCSY00060)。
文摘Objective:Myeloma bone disease(MBD)is the most common complication of multiple myeloma(MM).Our previous study showed that the serum levels of C3/C4 in MM patients were significantly positively correlated with the severity of bone disease.However,the mechanism of C3 a/C4 a in osteoclasts MM patients remains unclear.Methods:The formation and function of osteoclasts were analyzed after adding C3 a/C4 a in vitro.RNA-seq analysis was used to screen the potential pathways affecting osteoclasts,and the results were verified by Western blot,q RT-PCR,and pathway inhibitors.Results:The osteoclast area per view induced by 1μg/m L(mean±SD:50.828±12.984%)and 10μg/m L(53.663±12.685%)of C3 a was significantly increased compared to the control group(0μg/m L)(34.635±8.916%)(P<0.001 and P<0.001,respectively).The relative m RNA expressions of genes,OSCAR/TRAP/RANKL/cathepsin K,induced by 1μg/m L(median:5.041,3.726,1.638,and 4.752,respectively)and 10μg/m L(median:5.140,3.702,2.250,and 5.172,respectively)of C3 a was significantly increased compared to the control group(median:3.137,2.004,0.573,and 2.257,respectively)(1μg/m L P=0.001,P=0.003,P<0.001,and P=0.008,respectively;10μg/m L:P<0.001,P=0.019,P<0.001,and P=0.002,respectively).The absorption areas of the osteoclast resorption pits per view induced by 1μg/m L(mean±SD:51.464±11.983%)and 10μg/m L(50.219±12.067%)of C3 a was also significantly increased(33.845±8.331%)(P<0.001 and P<0.001,respectively)compared to the control.There was no difference between the C4 a and control groups.RNA-seq analysis showed that C3 a promoted the proliferation of osteoclasts using the phosphoinositide 3-kinase(PI3 K)signaling pathway.The relative expressions of PIK3 CA/phosphoinositide dependent kinase-1(PDK1)/serum and glucocorticoid inducible protein kinases(SGK3)genes and PI3 K/PDK1/p-SGK3 protein in the C3 a group were significantly higher than in the control group.The activation role of C3 a in osteoclasts of MM patients was reduced by the SGK inhibitor(EMD638683).Conclusions:C3 a activated osteoclasts by regulating the PI3 K/PDK1/SGK3 pathways in MM patients,which was reduced using a SGK inhibitor.Overall,our results identified potential therapeutic targets and strategies for MBD patients。
文摘目的探讨孕早期血清补体C3、C4水平与系统性红斑狼疮(SLE)孕妇不良妊娠结局的关系。方法在2019年1月至2023年11月进行了一项回顾性队列研究,纳入了来自西安交通大学第一附属医院妇产科的100例SLE孕妇作为研究对象。浊度免疫测定试验对所有患者测定血清补体C3、C4水平。比较不良妊娠结局和良好妊娠结局患者血清补体C3、C4水平差异,并通过Logistic模型分析影响SLE孕妇妊娠结局的临床因素。结果共计有48例(48.0%)患者发生不良妊娠结局。在不良妊娠结局患者中血清补体C3和C4水平显著低于良好妊娠结局患者(P<0.001);这种降低趋势主要表现在发生早产和未发生早产以及小于胎龄儿(small for gestational age infant,SGA)和非SGA患者中。经多因素Logistic模型分析,血清补体C3水平降低、不使用AZA和子痫前期是影响SLE患者不良妊娠结局的独立危险因素(P<0.05)。经受试者操作特征(ROC)曲线分析,血清补体C3、C4预测不良妊娠结局的曲线下面积(AUC)为0.832、0.757(P<0.001)。以血清补体C3、C4的正常值下限75 mg/dL、9 mg/dL进行分组,组间间隔为10 mg/dL和1 mg/dL;随着血清补体C3、C4水平的下降,不良妊娠结局的发生率增加,尤其在以血清补体C3分组的患者中。Spearman相关性分析显示孕早期血清补体C3(r=–0.342,P<0.001)、C4(r=–0.387,P<0.001)水平与SLE疾病活动度评分呈显著负相关性。结论孕早期血清补体(尤其是补体C3)水平降低是影响SLE孕妇不良妊娠结局的重要危险因素,因此孕早期补体C3、C4水平降低的患者可能更容易发生不良妊娠结局,但是该结果需要在更大的患者群体中进一步证实。
