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:探讨血清补体C1q/肿瘤坏死因子相关蛋白(Complement-C1q/tumor necrosis factor-related protein 3,CTRP3)水平与甲状腺功能亢进患者骨代谢的相关性。方法:回顾性收集本院2021年10月至2023年10月期间收治的85例甲状腺功能亢进患者...目的:探讨血清补体C1q/肿瘤坏死因子相关蛋白(Complement-C1q/tumor necrosis factor-related protein 3,CTRP3)水平与甲状腺功能亢进患者骨代谢的相关性。方法:回顾性收集本院2021年10月至2023年10月期间收治的85例甲状腺功能亢进患者的临床资料。依据骨密度检测结果将85例甲状腺功能亢进患者分为合并骨质疏松组(n=20)和未合并骨质疏松组(n=65)。收集两组的基线资料及入院时甲状腺激素指标(游离三碘甲状腺原氨酸、游离四碘甲状腺原氨酸、促甲状腺激素、总三碘甲状腺原氨酸、血清总甲状腺素)、血清CTRP3水平、骨代谢(骨特异性碱性磷酸酶、骨钙素、Ⅰ型前胶原氨基前肽、碱性磷酸酶、N端骨钙素)。分析血清CTRP3水平与甲状腺功能亢进患者骨代谢指标的相关性。结果:骨质疏松组血清CTRP3水平明显低于未合并骨质疏松组,且血清骨特异性碱性磷酸酶、骨钙素、Ⅰ型前胶原氨基前肽、碱性磷酸酶、N端骨钙素水平均明显高于未合并骨质疏松组(P<0.05)。经双变量Pearson相关性分析显示,血清CTRP3水平与骨特异性碱性磷酸酶、骨钙素、Ⅰ型前胶原氨基前肽、碱性磷酸酶、N端骨钙素水平呈负相关(P<0.05)。结论:血清CTRP3水平与甲状腺功能亢进患者与骨代谢指标(骨特异性碱性磷酸酶、骨钙素、Ⅰ型前胶原氨基前肽、碱性磷酸酶、N端骨钙素)有关。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:探讨血清补体C1q/肿瘤坏死因子相关蛋白(Complement-C1q/tumor necrosis factor-related protein 3,CTRP3)水平与甲状腺功能亢进患者骨代谢的相关性。方法:回顾性收集本院2021年10月至2023年10月期间收治的85例甲状腺功能亢进患者的临床资料。依据骨密度检测结果将85例甲状腺功能亢进患者分为合并骨质疏松组(n=20)和未合并骨质疏松组(n=65)。收集两组的基线资料及入院时甲状腺激素指标(游离三碘甲状腺原氨酸、游离四碘甲状腺原氨酸、促甲状腺激素、总三碘甲状腺原氨酸、血清总甲状腺素)、血清CTRP3水平、骨代谢(骨特异性碱性磷酸酶、骨钙素、Ⅰ型前胶原氨基前肽、碱性磷酸酶、N端骨钙素)。分析血清CTRP3水平与甲状腺功能亢进患者骨代谢指标的相关性。结果:骨质疏松组血清CTRP3水平明显低于未合并骨质疏松组,且血清骨特异性碱性磷酸酶、骨钙素、Ⅰ型前胶原氨基前肽、碱性磷酸酶、N端骨钙素水平均明显高于未合并骨质疏松组(P<0.05)。经双变量Pearson相关性分析显示,血清CTRP3水平与骨特异性碱性磷酸酶、骨钙素、Ⅰ型前胶原氨基前肽、碱性磷酸酶、N端骨钙素水平呈负相关(P<0.05)。结论:血清CTRP3水平与甲状腺功能亢进患者与骨代谢指标(骨特异性碱性磷酸酶、骨钙素、Ⅰ型前胶原氨基前肽、碱性磷酸酶、N端骨钙素)有关。
