Objective:It aims to evaluate the diagnostic ability of CGRP and other blood indicators in vestibular migraine(VM)patients,and to explain the potential pathological effects of these biomarkers.The hypothesis of VM bei...Objective:It aims to evaluate the diagnostic ability of CGRP and other blood indicators in vestibular migraine(VM)patients,and to explain the potential pathological effects of these biomarkers.The hypothesis of VM being a variant of migraine was examined.Methods:A total of 32 VM patients,35 migraine patients,and 30 healthy control subjects(HC)were selected for this cross-sectional study.Detailed statistics on demographic data,clinical manifestations,calcitonin gene-related peptide(CGRP)and common clinical laboratory indicators were measured within 24 hours from the onset of the conditions.Receptor operating characteristic(ROC)curve and area under the curve(AUC)were analyzed for biomarkers.The risk factors of VM and migraine were determined through univariate and multivariate analyses.Results:Compared with HC,serum CGRP levels(p(VM)=0.012,p(Migraine)=0.028)increased and Mg^(2+)levels(p(VM)<0.001,p(Migraine)<0.001)deceased in VM patients and migraine patients.In multiple logistic regression,VM was correlated with CGRP[odds ratio(OR)=1.07;95%confidence interval(CI),1.02-1.12;P=0.01]and Mg^(2+)[odds ratio(OR)=0.03;95%CI,0.07-0.15;P<0.001].Migraine was correlated with CGRP[odds ratio(OR)=1.07;95%CI,1.02-1.12;P=0.01]and Mg^(2+)[odd ratio(OR=0.01;95%CI,0-0.02;P<0.001)].Mg^(2+)discriminated good differentiation between VM and migraine groups,with AUC of 0.649(95%CI,0.518 to 0.780).The optimal threshold for Mg^(2+)to diagnose VM was 0.805.Conclusions:This study demonstrated that CGRP and Mg^(2+)may be promising laboratory indicators to discriminate HC from VM/migraine,while Mg^(2+)may be uded as a discriminator between VM and migraine.展开更多
The endoplasmic reticulum(ER)membrane protein complex(EMC)is responsible for monitoring the biogenesis and synthetic quality of membrane proteins with tail-anchored or multiple transmembrane domains.The EMC subunit EM...The endoplasmic reticulum(ER)membrane protein complex(EMC)is responsible for monitoring the biogenesis and synthetic quality of membrane proteins with tail-anchored or multiple transmembrane domains.The EMC subunit EMC6 is one of the core members of EMC and forms an enclosed hydrophilic vestibule in cooperation with EMC3.Despite studies demonstrating that deletion of EMC3 led to rhodopsin mislocalization in rod photoreceptors of mice,the precise mechanism leading to the failure of rhodopsin trafficking remains unclear.Here,we generated the first rod photoreceptor-specific knockout of Emc6(RKO)and cone photoreceptor-specific knockout of Emc6(CKO)mouse models.Deficiency of Emc6 in rod photoreceptors led to progressive shortening of outer segments(OS),impaired visual function,mislocalization and reduced expression of rhodopsin,and increased gliosis in rod photoreceptors.In addition,CKO mice displayed the progressive death of cone photoreceptors and abnormal localization of cone opsin protein.Subsequently,proteomics analysis of the RKO mouse retina illustrated that several cilium-related proteins,particularly anoctamin-2(ANO2)and transmembrane protein 67(TMEM67),were significantly down-regulated prior to OS degeneration.Detrimental rod photoreceptor cilia and mislocalized membrane disc proteins were evident in RKO mice.Our data revealed that in addition to monitoring the synthesis of rhodopsin-dominated membrane disc proteins,EMC6 also impacted rod photoreceptors'ciliogenesis by regulating the synthesis of membrane proteins associated with cilia,contributing to the mislocalization of membrane disc proteins.展开更多
基金National Natural Science Foundation of China(No.82071549)Key Program of the Natural Science Fund in Heilongjiang Province(No.ZD2019H006)National Key Research&Development Program of China(No.2016YFC1307205).
文摘Objective:It aims to evaluate the diagnostic ability of CGRP and other blood indicators in vestibular migraine(VM)patients,and to explain the potential pathological effects of these biomarkers.The hypothesis of VM being a variant of migraine was examined.Methods:A total of 32 VM patients,35 migraine patients,and 30 healthy control subjects(HC)were selected for this cross-sectional study.Detailed statistics on demographic data,clinical manifestations,calcitonin gene-related peptide(CGRP)and common clinical laboratory indicators were measured within 24 hours from the onset of the conditions.Receptor operating characteristic(ROC)curve and area under the curve(AUC)were analyzed for biomarkers.The risk factors of VM and migraine were determined through univariate and multivariate analyses.Results:Compared with HC,serum CGRP levels(p(VM)=0.012,p(Migraine)=0.028)increased and Mg^(2+)levels(p(VM)<0.001,p(Migraine)<0.001)deceased in VM patients and migraine patients.In multiple logistic regression,VM was correlated with CGRP[odds ratio(OR)=1.07;95%confidence interval(CI),1.02-1.12;P=0.01]and Mg^(2+)[odds ratio(OR)=0.03;95%CI,0.07-0.15;P<0.001].Migraine was correlated with CGRP[odds ratio(OR)=1.07;95%CI,1.02-1.12;P=0.01]and Mg^(2+)[odd ratio(OR=0.01;95%CI,0-0.02;P<0.001)].Mg^(2+)discriminated good differentiation between VM and migraine groups,with AUC of 0.649(95%CI,0.518 to 0.780).The optimal threshold for Mg^(2+)to diagnose VM was 0.805.Conclusions:This study demonstrated that CGRP and Mg^(2+)may be promising laboratory indicators to discriminate HC from VM/migraine,while Mg^(2+)may be uded as a discriminator between VM and migraine.
基金supported by The National Natural Science Foundation of China(No.82121003,81970841,82101160)the program of Science and Technology International Cooperation Project of Qinghai province(China)(No.2022-HZ-814)+2 种基金the CAMS Innovation Fund for Medical Sciences(No.2019-12M-5-032)Sichuan Intellectual Property Office(China)(No.2022-ZS-0070)the Department of Chengdu Science and Technology(Sichuan,China)(No.2021-YF05-01316-SN).
文摘The endoplasmic reticulum(ER)membrane protein complex(EMC)is responsible for monitoring the biogenesis and synthetic quality of membrane proteins with tail-anchored or multiple transmembrane domains.The EMC subunit EMC6 is one of the core members of EMC and forms an enclosed hydrophilic vestibule in cooperation with EMC3.Despite studies demonstrating that deletion of EMC3 led to rhodopsin mislocalization in rod photoreceptors of mice,the precise mechanism leading to the failure of rhodopsin trafficking remains unclear.Here,we generated the first rod photoreceptor-specific knockout of Emc6(RKO)and cone photoreceptor-specific knockout of Emc6(CKO)mouse models.Deficiency of Emc6 in rod photoreceptors led to progressive shortening of outer segments(OS),impaired visual function,mislocalization and reduced expression of rhodopsin,and increased gliosis in rod photoreceptors.In addition,CKO mice displayed the progressive death of cone photoreceptors and abnormal localization of cone opsin protein.Subsequently,proteomics analysis of the RKO mouse retina illustrated that several cilium-related proteins,particularly anoctamin-2(ANO2)and transmembrane protein 67(TMEM67),were significantly down-regulated prior to OS degeneration.Detrimental rod photoreceptor cilia and mislocalized membrane disc proteins were evident in RKO mice.Our data revealed that in addition to monitoring the synthesis of rhodopsin-dominated membrane disc proteins,EMC6 also impacted rod photoreceptors'ciliogenesis by regulating the synthesis of membrane proteins associated with cilia,contributing to the mislocalization of membrane disc proteins.
