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抗CV2/CRMP5抗体阳性副肿瘤性脑脊髓炎合并神经精神狼疮一例
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作者 林静涵 代大伟 +2 位作者 陈泓旭 潘永惠 张黎明 《中国神经免疫学和神经病学杂志》 CAS 2024年第3期237-239,共3页
1病例报告,患者女,55岁,小学文化水平。因“反应迟钝5 d,双下肢无力1 d”于2021-3-19入院。5 d前无诱因出现反应迟钝,表现为记忆力下降,偶有答非所问但能正常交流,病程中伴有吞咽困难、头晕、视物旋转、言语笨拙,可疑抽搐发作(全面强直... 1病例报告,患者女,55岁,小学文化水平。因“反应迟钝5 d,双下肢无力1 d”于2021-3-19入院。5 d前无诱因出现反应迟钝,表现为记忆力下降,偶有答非所问但能正常交流,病程中伴有吞咽困难、头晕、视物旋转、言语笨拙,可疑抽搐发作(全面强直发作)1次。 展开更多
关键词 副肿瘤综合征 神经系统 脑脊髓炎 抗CV2/crmp5抗体 红斑狼疮 系统性
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Evaluating new biomarkers for diabetic nephropathy:Role ofα2-macroglobulin,podocalyxin,α-L-fucosidase,retinol-binding protein-4,and cystatin C
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作者 Jing-Jing Li Ru-La Sa +1 位作者 Yu Zhang Zhao-Li Yan 《World Journal of Diabetes》 SCIE 2024年第6期1212-1225,共14页
BACKGROUND The intricate relationship between type 2 diabetes mellitus(T2DM)and diabetic nephropathy(DN)presents a challenge in understanding the significance of various biomarkers in diagnosis.AIM To elucidate the ro... BACKGROUND The intricate relationship between type 2 diabetes mellitus(T2DM)and diabetic nephropathy(DN)presents a challenge in understanding the significance of various biomarkers in diagnosis.AIM To elucidate the roles and diagnostic values ofα2-macroglobulin(α2-MG),podocalyxin(PCX),α-L-fucosidase(AFU),retinol-binding protein-4(RBP-4),and cystatin C(CysC)in DN.METHODS From December 2018 to December 2020,203 T2DM patients were enrolled in the study.Of these,115 were diagnosed with DN(115 patients),while the remaining 88 patients were classified as non-DN.The urinary levels ofα2-MG,PCX,and AFU and the serum concentrations RBP-4 and CysC were measured in conjunction with other relevant clinical indicators to evaluate their potential correlations and diagnostic utility.RESULTS After adjustments for age and gender,significant positive correlations were observed between the biomarkers CysC,RBP-4,α2-MG/urinary creatinine(UCr),PCX/UCr,and AFU/UCr,and clinical indicators such as urinary albumin-to-creatinine ratio(UACR),serum creatinine,urea,24-h total urine protein,and neutrophil-to-lymphocyte ratio(NLR).Conversely,these biomarkers exhibited negative correlations with the estimated glomerular filtration rate(P<0.05).Receiver operating characteristic(ROC)curve analysis further demonstrated the diagnostic performance of these biomarkers,with UACR showcasing the highest area under the ROC curve(AUC^(ROC))at 0.97.CONCLUSION This study underscores the diagnostic significance ofα2-MG,PCX,and AFU in the development of DN.The biomarkers RBP-4,CysC,PCX,AFU,andα2-MG provide promising diagnostic insights,while UACR is the most potent diagnostic biomarker in assessing DN. 展开更多
关键词 Α2-MACROGLOBULIN Podocalysin Α-L-FUCOSIDASE Retinol binding protein-4 Cystatin C Diabetic nephropathy
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Bone morphogenetic protein-6 suppresses TGF-β_(2)-induced epithelial-mesenchymal transition in retinal pigment epithelium
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作者 Xuan Liu Ming Liu +5 位作者 Meng Ji Bo Ma Yu-Cen Hou Xin-Yue Yao Qiao-Chu Cheng Li Chen 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2024年第4期646-652,共7页
AIM:To evaluate the effect of bone morphogenetic protein-6(BMP-6)on transforming growth factor(TGF)-β_(2)-induced epithelial-mesenchymal transition(EMT)in retinal pigment epithelium(RPE).METHODS:Adult retinal pigment... AIM:To evaluate the effect of bone morphogenetic protein-6(BMP-6)on transforming growth factor(TGF)-β_(2)-induced epithelial-mesenchymal transition(EMT)in retinal pigment epithelium(RPE).METHODS:Adult retinal pigment epithelial cell line(ARPE-19)were randomly divided into control,TGF-β_(2)(5μg/L),and BMP-6 small interfering RNA(siRNA)group.The cell morphology was observed by microscopy,and the cell migration ability were detected by Transwell chamber.The EMT-related indexes and BMP-6 protein levels were detected by Western blotting.Furthermore,a BMP-6 overexpression plasmid was constructed and RPE cells were divided into the control group,TGF-β_(2)+empty plasmid group,BMP-6 overexpression group,and TGF-β_(2)+BMP-6 overexpression group.The EMT-related indexes and extracellular regulated protein kinases(ERK)protein levels were detected.RESULTS:Compared with the control group,the migration of RPE cells in the TGF-β_(2) group was significantly enhanced.TGF-β_(2) increased the protein expression levels ofα-smooth muscle actin(α-SMA),fibronectin and vimentin but significantly decreased the protein levels of E-cadherin and BMP-6(P<0.05)in RPE.Similarly,the migration of RPE cells in the BMP-6 siRNA group was also significantly enhanced.BMP-6 siRNA increased the protein expression levels ofα-SMA,fibronectin and vimentin but significantly decreased the protein expression levels of E-cadherin(P<0.05).Overexpression of BMP-6 inhibited the migration of RPE cells induced by TGF-β_(2) and prevented TGF-β_(2) from affecting EMT-related biomarkers(P<0.05).CONCLUSION:BMP-6 prevents the EMT in RPE cells induced by TGF-β_(2),which may provide a theoretical basis for the prevention and treatment of proliferative vitreoretinopathy. 展开更多
关键词 bone morphogenetic protein-6 epithelialmesenchymal transition transforming growth factor-β_(2) retinal pigment epithelial cells cell migration
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延龄草皂苷对脑缺血大鼠梗死灶周围皮层少突胶质细胞GSK-3/β-catenin/CRMP2信号表达的影响 被引量:1
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作者 庄雨明 杨乐 +5 位作者 欧阳俊摇 邹海艳 冯雪枫 陆允 李明聪 赵晖 《中国中医药信息杂志》 CAS CSCD 2023年第10期108-115,共8页
目的观察延龄草皂苷(TSTT)对脑缺血大鼠梗死灶周围皮层少突胶质细胞GSK-3/β-catenin/CRMP2信号表达的影响,探讨其改善脑缺血损伤的作用机制。方法采用线栓法制备局灶性脑缺血大鼠模型,将大鼠随机分为假手术组、模型组、TSTT 65 mg/kg组... 目的观察延龄草皂苷(TSTT)对脑缺血大鼠梗死灶周围皮层少突胶质细胞GSK-3/β-catenin/CRMP2信号表达的影响,探讨其改善脑缺血损伤的作用机制。方法采用线栓法制备局灶性脑缺血大鼠模型,将大鼠随机分为假手术组、模型组、TSTT 65 mg/kg组、TSTT 33 mg/kg组和金纳多组,各给药组灌胃相应药物,连续15 d。HE染色观察脑组织病理变化,LFB染色观察脑组织神经纤维损伤,免疫荧光染色检测梗死灶周围皮层2′,3′-环核苷酸-3′-磷酸二酯酶(CNPase)、蛋白聚糖(NG2)、糖原合成酶激酶-3β(GSK-3β)、β-连环蛋白(β-catenin)表达,实时荧光定量PCR检测梗死灶周围皮层GSK-3、β-catenin、脑衰蛋白反应调节蛋白-2(CRMP2)基因表达。结果与假手术组比较,模型组大鼠患侧脑组织明显坏死,神经细胞大量死亡,胞体皱缩,单位面积神经细胞数量显著减少(P<0.01),神经纤维丢失、排列混乱,髓鞘中有大量空泡,神经纤维相对积分光密度显著减少(P<0.01);与模型组比较,TSTT 65、33 mg/kg组大鼠神经细胞形态有所改善,单位面积神经细胞数量显著增加(P<0.05,P<0.01),神经纤维排列较有序,髓鞘中空泡较少,神经纤维相对积分光密度显著增加(P<0.01)。免疫荧光染色结果显示,与假手术组比较,模型组大鼠梗死灶周围皮层CNPase阳性表达显著降低,NG2阳性表达显著升高(P<0.01),NG2/GSK-3β、NG2/β-catenin、CNPase/GSK-3β、CNPase/β-catenin阳性细胞显著增加(P<0.01);与模型组比较,TSTT 65、33 mg/kg组大鼠梗死灶周围皮层CNPase、NG2表达显著升高,CNPase/GSK-3β、NG2/GSK-3β阳性细胞显著减少,CNPase/β-catenin、NG2/β-catenin阳性细胞显著增加(P<0.05,P<0.01)。实时荧光定量PCR结果显示,与假手术组比较,模型组大鼠梗死灶周围皮层GSK-3αmRNA表达显著升高(P<0.05),β-catenin、CRMP2 mRNA表达显著降低(P<0.05,P<0.01);与模型组比较,TSTT 65 mg/kg组大鼠梗死灶周围皮层GSK-3α、GSK-3βmRNA表达显著降低,β-catenin和CRMP2 mRNA表达显著升高(P<0.05)。结论TSTT可减轻脑缺血大鼠脑组织损伤,保护少突胶质细胞,促进少突胶质前体细胞存活,其机制可能与下调GSK-3表达,上调β-catenin、CRMP2表达有关。 展开更多
关键词 延龄草皂苷 脑缺血 少突胶质细胞 少突胶质前体细胞 GSK-3/β-catenin/crmp2信号通路
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An overview on CV2/CRMP5 antibody-associated paraneoplastic neurological syndromes 被引量:1
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作者 Sai Wang Haiman Hou +5 位作者 Yao Tang Shuang Zhang Gege Wang Ziyan Guo Lina Zhu Jun Wu 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第11期2357-2364,共8页
Paraneoplastic neurological syndrome refers to certain malignant tumors that have affected the distant nervous system and caused corresponding dysfunction in the absence of tumor metastasis.Patients with this syndrome... Paraneoplastic neurological syndrome refers to certain malignant tumors that have affected the distant nervous system and caused corresponding dysfunction in the absence of tumor metastasis.Patients with this syndrome produce multiple antibodies,each targeting a different antigen and causing different symptoms and signs.The CV2/collapsin response mediator protein 5(CRMP5)antibody is a major antibody of this type.It damages the nervous system,which often manifests as limbic encephalitis,chorea,ocular manifestation,cerebellar ataxia,myelopathy,and peripheral neuropathy.Detecting CV2/CRMP5 antibody is crucial for the clinical diagnosis of paraneoplastic neurological syndrome,and anti-tumor and immunological therapies can help to alleviate symptoms and improve prognosis.However,because of the low incidence of this disease,few repo rts and no reviews have been published about it so far.This article intends to review the research on CV2/CRMP5antibody-associated paraneoplastic neurological syndrome and summarize its clinical features to help clinicians comprehensively understand the disease.Additionally,this review discusses the curre nt challenges that this disease poses,and the application prospects of new detection and diagnostic techniques in the field of paraneoplastic neurological syndrom e,including CV2/CRMP5-associated paraneoplastic neurological syndrome,in recent years. 展开更多
关键词 AUTOIMMUNITY crmp5 CV2 CV2/crmp5 antibody paraneoplastic neurological syndromes paraneoplastic syndromes TUMOR
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Hypertrophic cardiomyopathy secondary to deficiency in lysosomeassociated membrane protein-2: A case report
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作者 Ye-Tong Zhao Xiu-Qun Cao Xiao-Lin Mu 《World Journal of Cardiology》 2023年第11期609-614,共6页
BACKGROUND Danon disease(DD),in which mutations in the X-linked lysosome-associated membrane protein-2(LAMP-2)gene result in hypertrophic cardiomyopathy,is a rare disease,reported primarily in small samples or cases.H... BACKGROUND Danon disease(DD),in which mutations in the X-linked lysosome-associated membrane protein-2(LAMP-2)gene result in hypertrophic cardiomyopathy,is a rare disease,reported primarily in small samples or cases.However,with the development of cardiac magnetic resonance imaging and genetic technology in recent years,the number of reports has increased.CASE SUMMARY We report a case of DD in an adolescent male patient,confirmed by genetic testing.The patient was admitted to our hospital with complaints of a three-year history of chest tightness and shortness of breath.His preliminary clinical diagnosis is hypertrophic cardiomyopathy.Our report includes the patient’s clinical course from hospital admission to death,step-by-step diagnosis,treatment course,and noninvasive imaging features.We highlight how a noninvasive diagnostic approach,based solely on clinical and imaging“red flags”for DD,can be used to achieve a diagnosis of DD with a high degree of confidence.CONCLUSION DD is a very dangerous cardiomyopathy,and it is necessary to achieve early diagnosis and treatment. 展开更多
关键词 Danon disease Lysosome-associated membrane protein-2 gene CARDIOMYOPATHY HYPERTROPHY Cardiac magnetic resonance imaging Myocardial strain Case report
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红景天苷对局灶性脑缺血/再灌注大鼠轴突再生及Akt/GSK-3β/CRMP-2表达的影响 被引量:10
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作者 张小琴 苗学蒸 +3 位作者 周丽英 许力伟 赖文芳 洪桂祝 《中国药理学通报》 CAS CSCD 北大核心 2017年第9期1320-1324,共5页
目的研究红景天苷对局灶性脑缺血/再灌注大鼠轴突再生的影响及可能的机制。方法健康成年♂SD大鼠36只,随机分为假手术组、模型对照组、红景天苷给药组,用线栓法建立局灶性脑缺血/再灌注大鼠模型(MCAO),ZeaLonga标准评分法评价大鼠神经... 目的研究红景天苷对局灶性脑缺血/再灌注大鼠轴突再生的影响及可能的机制。方法健康成年♂SD大鼠36只,随机分为假手术组、模型对照组、红景天苷给药组,用线栓法建立局灶性脑缺血/再灌注大鼠模型(MCAO),ZeaLonga标准评分法评价大鼠神经功能损伤,Western blot法检测大鼠缺血侧脑组织p-Akt(Ser473)、Akt、p-GSK-3β(Ser9)、GSK-3β、p-CRMP-2(Thr514)、CRMP-2蛋白的表达,免疫荧光染色法检测大鼠缺血侧脑组织NF200蛋白的表达。结果与MCAO组比较,红景天苷能明显改善大鼠的神经功能损伤,促进NF200、p-Akt、p-GSK-3β蛋白的表达,抑制p-CRMP-2蛋白表达。结论红景天苷能改善局灶性脑缺血/再灌注大鼠的神经功能缺损,此作用可能与促进Akt、GSK-3β的磷酸化,抑制CRMP-2的磷酸化,进而促进轴突再生有关。 展开更多
关键词 红景天苷 局灶性脑缺血/再灌注 轴突再生 AKT GSK-3Β crmp-2
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CRMP2衍生的ST2-104多肽对阿尔茨海默病大鼠皮质神经元的保护作用 被引量:3
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作者 孟盼盼 张雨晴 +2 位作者 高媛媛 孙莉 李琦 《中风与神经疾病杂志》 CAS 北大核心 2016年第3期203-206,共4页
目的研究ST2-104肽对阿尔茨海默病(AD)大鼠脑皮质内NMDAR1、NMDAR2B、CRMP2、PCRMP2的表达影响,进而改善大鼠的认知功能,对神经元发挥保护作用。方法采用单次单侧脑室微量注射Aβ25-35片段制备AD大鼠模型,具有相同遗传背景的Wistar大鼠... 目的研究ST2-104肽对阿尔茨海默病(AD)大鼠脑皮质内NMDAR1、NMDAR2B、CRMP2、PCRMP2的表达影响,进而改善大鼠的认知功能,对神经元发挥保护作用。方法采用单次单侧脑室微量注射Aβ25-35片段制备AD大鼠模型,具有相同遗传背景的Wistar大鼠作为假手术对照组,分别给予不同剂量的ST2-104多肽和盐酸美金刚治疗。Aβ注射2 d后给药10 d,HE染色法观察脑皮质部分形态变化,甲醇刚果红染色法观察淀粉样物质沉积情况,WB及免疫组化法检测大鼠脑皮质组织NMDAR1、NMDAR2B、CRMP2、P-CRMP2的表达。结果与假手术组相比,模型组淀粉样物质沉积明显增多,脑皮质部分NMDAR2B表达显著增多(P<0.01),NMDAR1表达相对减少,P-CRMP2与CRMP2表达量均无明显差异;ST2-104多肽可以逆转上述现象,降低NMDAR2B表达(与模型组相比,高剂量组P<0.05),增加NMDAR1表达(与模型组相比,高、低剂量均为P<0.05)。结论 (1)ST2-104可能通过减少NMDAR2B表达降低其活性来发挥对AD大鼠皮质神经元的保护作用。 展开更多
关键词 阿尔茨海默病 ST2-104 25-35 NMDAR crmp2
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Aβ_(1-42)对SH-SY5Y细胞T514位点磷酸化CRMP2表达的影响 被引量:1
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作者 朱天瑞 李晓红 +2 位作者 王敏 张媛媛 王栋 《基础医学与临床》 CSCD 北大核心 2011年第6期688-693,共6页
目的探讨β淀粉样蛋白1-42(Aβ1-42)对成神经瘤细胞SH-SY5Y轴突生长状态、细胞微管结构及T514位点磷酸化脑衰蛋白反应调节蛋白2(CRMP2)表达的影响。方法用全反式维甲酸诱导SH-SY5Y细胞,细胞外给予聚集态Aβ1-42致细胞损伤;用MTT法检测... 目的探讨β淀粉样蛋白1-42(Aβ1-42)对成神经瘤细胞SH-SY5Y轴突生长状态、细胞微管结构及T514位点磷酸化脑衰蛋白反应调节蛋白2(CRMP2)表达的影响。方法用全反式维甲酸诱导SH-SY5Y细胞,细胞外给予聚集态Aβ1-42致细胞损伤;用MTT法检测细胞存活率;用细胞化学法测量细胞轴突长度;免疫荧光法观察细胞微管结构及T514位点磷酸化CRMP2的分布;Westen blot分析T514位点磷酸化CRMP2在细胞内的表达。结果 0.1与1μmol/L聚集态Aβ1-42使诱导后SH-SY5Y细胞存活率显著减低(P<0.01);以1μmol/L Aβ1-42处理后,细胞轴突长度缩短(P<0.05)。0.1和1μmol/L Aβ1-42处理后细胞微管结构模糊,T514位点磷酸化CRMP2在细胞内荧光分布面积扩大(P<0.05),强度增加(P<0.01);用0.1和1μmol/L聚集态Aβ1-42处理后细胞内T514位点磷酸化CRMP2表达量显著增加(P<0.01)。结论 Aβ1-42可增加SH-SY5Y细胞内T514位点磷酸化CRMP2的表达,损害微管结构,抑制轴突生长。 展开更多
关键词 Β淀粉样蛋白 脑衰蛋白反应调节蛋白2 SH-SY5Y细胞 全反式维甲酸
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姜黄素对Aβ诱导的AD大鼠海马CRMP-2表达的影响 被引量:4
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作者 尹红蕾 李金凤 +3 位作者 乔立艳 曾志磊 王运良 刘亚君 《中国实用神经疾病杂志》 2012年第23期1-4,共4页
目的探讨姜黄素对Aβ诱导的老年痴呆大鼠认知功能和海马CRMP-2的影响。方法将SD大鼠随机分为空白对照组、AD对照组和姜黄素给药组。Aβ1-40微量注射至大鼠右侧海马制作AD大鼠模型。Morris水迷宫试验测定大鼠学习记忆能力。RT-PCR检测海... 目的探讨姜黄素对Aβ诱导的老年痴呆大鼠认知功能和海马CRMP-2的影响。方法将SD大鼠随机分为空白对照组、AD对照组和姜黄素给药组。Aβ1-40微量注射至大鼠右侧海马制作AD大鼠模型。Morris水迷宫试验测定大鼠学习记忆能力。RT-PCR检测海马内CRMP-2mRNA的表达,Western blotting方法检测海马内CRMP-2和p-CRMP-2蛋白表达,免疫组织化学方法检测海马内轴突蛋白表达。结果姜黄素干预后AD大鼠空间学习记忆能力明显改善(P<0.05)。与空白对照组相比,AD对照组大鼠海马区CRMP-2表达显著降低(P<0.05),轴突蛋白NFP-200阳性纤维排列紊乱,不规则,纤维数目显著减少(P<0.05);而在姜黄素组大鼠海马区可见CRMP-2表达升高,p-CRMP-2表达降低,而轴突蛋白表达明显增加(P<0.01)。结论姜黄素能够改善Aβ1-40诱导的AD模型大鼠空间学习记忆障碍,其机制可能与姜黄素提高CRMP-2的表达并抑制CRMP-2的磷酸化从而促进轴突再生有关。 展开更多
关键词 姜黄素 淀粉样Β蛋白 crmp-2 轴突再生 阿尔茨海默病
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CRMP2可通过改善神经细胞凋亡减轻缺血/再灌注大鼠神经功能缺损 被引量:7
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作者 幸享凤 王恬竹 秦新月 《中国药理学通报》 CAS CSCD 北大核心 2016年第4期548-553,共6页
目的探讨CRMP2(collapsin response mediator protein2)对大鼠脑缺血/再灌注损伤后神经细胞凋亡的影响及其可能的机制。方法 192只♂成年SD大鼠分成4组:假手术组(sham)、脑缺血/再灌注组(MCAO)、脑缺血+质粒对照组(MCAO+GFP)、脑缺血+CR... 目的探讨CRMP2(collapsin response mediator protein2)对大鼠脑缺血/再灌注损伤后神经细胞凋亡的影响及其可能的机制。方法 192只♂成年SD大鼠分成4组:假手术组(sham)、脑缺血/再灌注组(MCAO)、脑缺血+质粒对照组(MCAO+GFP)、脑缺血+CRMP2真核质粒干预组(MCAO+CRMP2/GFP)。大鼠MCA阻塞手术前1 d将真核质粒注射入脑内,缺血/再灌注后48 h、1周,采用RT-PCR检测各组大鼠脑组织CRMP2、BCL2、p53、Caspase-3和Caspase-8的mRNA的表达;Western blot检测脑组织CRMP2蛋白的表达;TUNEL染色检测凋亡细胞;免疫组化检测脑源性神经营养因子(brain derived neurotrophic factor,BDNF)的表达;TTC染色检测脑梗死体积并进行神经功能缺损评分。结果脑缺血/再灌注48 h及1周,与sham组比较,MCAO组及MCAO+GFP组CRMP2和BCL2的表达水平明显降低(P<0.01),而Caspase-3、Caspase-8及p53的mRNA表达升高(P<0.01),TUNEL阳性细胞数量明显升高(P<0.01)。MCAO+CRMP2/GFP组CRMP2和BCL2较MCAO及MCAO+GFP组明显增高(P<0.01),同时该组p53、Caspase-3及Caspase-8表达明显降低(P<0.01)。过表达CRMP2使TUNEL阳性细胞数明显减少(P<0.01)。脑缺血/再灌注后BDNF表达升高(P<0.01),而脑内过表达CRMP2使BDNF的水平上调更明显(P<0.01)。TTC染色显示,MCAO+CRMP2/GFP组脑梗死体积较MCAO组及MCAO+GFP组明显减小(P<0.01),且神经功能缺损明显减轻(P<0.01)。结论过表达CRMP2可能通过对线粒体凋亡通路的调控减少了脑缺血/再灌注损伤后的神经细胞凋亡、减少脑梗死体积而起到神经保护作用。 展开更多
关键词 crmp2 脑缺血/再灌注 BDNF 凋亡 神经功能评分 TUNEL
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Three-dimensional kagome structures in a PCL/HA-based hydrogel scaffold to lead slow BMP-2 release for effective bone regeneration 被引量:4
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作者 Se-Hwan Lee Kang-Gon Lee +7 位作者 Jaeyeon Lee Yong Sang Cho Min-Soo Ghim Soojin Kim Su-Jin Heo Yongdoo Park Young-Sam Cho Bu-Kyu Lee 《Bio-Design and Manufacturing》 SCIE EI CAS CSCD 2023年第1期12-25,共14页
Osteoconductive function is remarkably low in bone disease in the absence of bone tissue surrounding the grafting site,or if the bone tissue is in poor condition.Thus,an effective bone graft in terms of both osteocond... Osteoconductive function is remarkably low in bone disease in the absence of bone tissue surrounding the grafting site,or if the bone tissue is in poor condition.Thus,an effective bone graft in terms of both osteoconductivity and osteoinductivity is required for clinical therapy.Recently,the three-dimensional(3D)kagome structure has been shown to be advantageous for bone tissue regeneration due to its mechanical properties.In this study,a polycaprolactone(PCL)kagome-structure scaffold containing a hyaluronic acid(HA)-based hydrogel was fabricated using a 3D printing technique.The retention capacity of the hydrogel in the scaffold was assessed in vivo with a rat calvaria subcutaneous model for 3 weeks,and the results were compared with those obtained with conventional 3D-printed PCL grid-structure scaffolds containing HA-based hydrogel and bulk-type HA-based hydrogel.The retained hydrogel in the kagome-structure scaffold was further evaluated by in vivo imaging system analysis.To further reinforce the osteoinductivity of the kagome-structure scaffold,a PCL kagome-structure scaffold with bone morphogenetic protein-2(BMP-2)containing HA hydrogel was fabricated and implanted in a calvarial defect model of rabbits for 16 weeks.The bone regeneration characteristics were evaluated with hematoxylin and eosin(H&E),Masson’s trichrome staining,and micro-CT image analysis. 展开更多
关键词 Kagome-structure scaffold Retention capacity Biomimetic hydrogel Bone morphogenetic protein-2(BMP-2)
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应用副肿瘤综合征更新标准分析抗CV2/CRMP5抗体相关副肿瘤综合征的临床异质性 被引量:2
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作者 郭燕军 刘磊 +3 位作者 林雪 孟超 江汉秋 王佳伟 《中国神经免疫学和神经病学杂志》 CAS 北大核心 2022年第3期199-204,共6页
目的应用2021年副肿瘤综合征诊断标准分析抗CV2/CRMP5抗体相关副肿瘤综合征的临床表现、影像学和血清学特征。方法收集作者医院2020年6月至2021年1月收治的抗CV2/CRMP5抗体相关副肿瘤综合征患者5例,分析其临床表现、血清学和影像学资料... 目的应用2021年副肿瘤综合征诊断标准分析抗CV2/CRMP5抗体相关副肿瘤综合征的临床表现、影像学和血清学特征。方法收集作者医院2020年6月至2021年1月收治的抗CV2/CRMP5抗体相关副肿瘤综合征患者5例,分析其临床表现、血清学和影像学资料特征。采用2021年更新副肿瘤综合征诊断标准及评分(PNS-Care Score)进行验证。结果5例患者中,其中男1例,女4例,年龄42~59岁。临床表现为快速进展性痴呆伴低热1例,视神经脑脊髓病1例,视神经脊髓病1例,重症肌无力合并胸腺瘤AB型1例,视神经病合并小细胞肺癌1例。3例未发现明确肿瘤。除1例重症肌无力合并胸腺瘤外,余4例患者均行腰穿脑脊液(CSF)检查,其中CSF白细胞升高1例,蛋白升高2例(600~676 mg/L)。1例血清Amphiphysin弱阳性,1例血清抗Hu抗体弱阳性,1例血清和CSF抗CV2/CRMP5抗体均阳性。表现为重症肌无力合并胸腺瘤的患者抗乙酰胆碱受体抗体和抗Titin抗体阳性。5例患者PNS-Care评分8~11分,全部达到确诊副肿瘤综合征标准。结论抗CV2/CRMP5抗体相关神经系统副肿瘤综合征患者存在高度临床异质性,部分患者伴发肿瘤。应加强对本病的认识和长期随访。副肿瘤PNS-Care评分有助于临床诊断。 展开更多
关键词 副肿瘤综合征 神经系统 CV2/crmp5抗体 异质性 自身抗体 塌陷反应调节蛋白
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仙茅苷对局灶性脑缺血/再灌注大鼠轴突再生及Akt/GSK-3β/CRMP-2表达的影响 被引量:6
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作者 傅增辉 姜岩 +4 位作者 刘晶 杜姝 张广萍 陈团团 郭鹏 《神经解剖学杂志》 CAS CSCD 北大核心 2018年第1期48-52,共5页
目的:研究仙茅苷对局灶性脑缺血/再灌注大鼠轴突再生的作用并探讨其机制。方法:健康成年雄性SD大鼠36只,随机分为假手术组、模型对照组、仙茅苷给药组,用线栓法建立局灶性脑缺血/再灌注大鼠模型(MCAO),大鼠神经功能损伤采用Zea-Longa标... 目的:研究仙茅苷对局灶性脑缺血/再灌注大鼠轴突再生的作用并探讨其机制。方法:健康成年雄性SD大鼠36只,随机分为假手术组、模型对照组、仙茅苷给药组,用线栓法建立局灶性脑缺血/再灌注大鼠模型(MCAO),大鼠神经功能损伤采用Zea-Longa标准评价,Western Blot法检测大鼠缺血侧脑组织p-Akt、Akt、p-GSK-3β、GSK-3β、p-CRMP-2、CRMP-2蛋白的表达,免疫荧光染色法检测大鼠缺血侧脑组织NF200蛋白的表达。结果:与MCAO组比较,仙茅苷能明显改善大鼠的神经功能损伤,促进NF200、p-Akt、p-GSK-3β蛋白的表达,抑制p-CRMP-2蛋白表达。结论:仙茅苷能改善局灶性脑缺血/再灌注大鼠的神经功能缺损,可能通过促进Akt、GSK-3β的磷酸化,抑制CRMP-2的磷酸化,进一步促进轴突再生。 展开更多
关键词 仙茅苷 局灶性脑缺血再灌注 AKT GSK-313 crmp-2 大鼠
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Collapsin response mediator protein-2 plays a major protective role in acute axonal degeneration 被引量:5
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作者 Jian-Nan Zhang Jan C.Koch 《Neural Regeneration Research》 SCIE CAS CSCD 2017年第5期692-695,共4页
Axonal degeneration is a key pathological feature in many neurological diseases. It often leads to persistent deficits due to the inability of axons to regenerate in the central nervous system. Therefore therapeutic a... Axonal degeneration is a key pathological feature in many neurological diseases. It often leads to persistent deficits due to the inability of axons to regenerate in the central nervous system. Therefore therapeutic approaches should optimally both attenuate axonal degeneration and foster axonal regeneration. Compelling evidence suggests that collapsin response mediator protein-2(CRMP2) might be a molecular target fulfilling these requirements. In this mini-review, we give a compact overview of the known functions of CRMP2 and its molecular interactors in neurite outgrowth and in neurodegenerative conditions. Moreover, we discuss in detail our recent findings on the role of CRMP2 in acute axonal degeneration in the optic nerve. We found that the calcium influx induced by the lesion activates the protease calpain which cleaves CRMP2, leading to impairment of axonal transport. Both calpain inhibition and CRMP2 overexpression effectively protected the proximal axons against acute axonal degeneration. Taken together, CRMP2 is further characterized as a central molecular player in acute axonal degeneration and thus evolves as a promising therapeutic target to both counteract axonal degeneration and foster axonal regeneration in neurodegenerative and neurotraumatic diseases. 展开更多
关键词 collapsin response mediator protein-2 crmp2 axonal regeneration optic nerve cruch axonaldegeneration CALPAIN axonal transport
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Macrophage inflammatory protein-2 as mediator of inflammation in acute liver injury 被引量:23
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作者 Chao-Chao Qin Yan-Ning Liu +2 位作者 Ying Hu Ying Yang Zhi Chen 《World Journal of Gastroenterology》 SCIE CAS 2017年第17期3043-3052,共10页
Macrophage inflammatory protein(MIP)-2 is one of the CXC chemokines and is also known as chemokine CXC ligand(CXCL2). MIP-2 affects neutrophil recruitment and activation through the p38 mitogen-activatedprotein-kinase... Macrophage inflammatory protein(MIP)-2 is one of the CXC chemokines and is also known as chemokine CXC ligand(CXCL2). MIP-2 affects neutrophil recruitment and activation through the p38 mitogen-activatedprotein-kinase-dependent signaling pathway, by binding to its specific receptors, CXCR1 and CXCR2. MIP-2 is produced by a variety of cell types, such as macrophages, monocytes, epithelial cells, and hepatocytes, in response to infection or injury. In liver injury, activated Kupffer cells are known as the major source of MIP-2. MIP-2-recruited and activated neutrophils can accelerate liver inflammation by releasing various inflammatory mediators. Here, we give a brief introduction to the basic molecular and cellular sources of MIP-2, and focus on its physiological and pathological functions in acute liver injury induced by concanavalin A, lipopolysaccharides, irradiation, ischemia/reperfusion, alcohol, and hypoxia, and hepatectomy-induced liver regeneration and tumor colorectal metastasis. Further understanding of the regulatory mechanisms of MIP-2 secretion and activation may be helpful to develop MIP-2-targeted therapeutic strategies to prevent liver inflammation. 展开更多
关键词 Macrophage inflammatory protein-2 Liver injury Polymorphonuclear neutrophils MACROPHAGES INFLAMMATION
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大鼠脊髓顿挫伤后CRMP-2的表达变化
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作者 李宏涛 胡析 +7 位作者 易敏明 许汉江 曾茜 饶莹 钟占琼 官璇 王廷华 张晓 《神经解剖学杂志》 CAS CSCD 北大核心 2015年第6期777-782,共6页
目的:观察大鼠脊髓顿挫伤后脑衰反应蛋白2(CRMP-2)在脊髓组织中的分布及基因表达变化。方法:采用Allen's重物法打击SD大鼠制备脊髓顿挫伤模型。采用BBB评分方法评估大鼠后肢运动功能:采用免疫组织化学技术(IHC)观察CRMP-2在损伤脊... 目的:观察大鼠脊髓顿挫伤后脑衰反应蛋白2(CRMP-2)在脊髓组织中的分布及基因表达变化。方法:采用Allen's重物法打击SD大鼠制备脊髓顿挫伤模型。采用BBB评分方法评估大鼠后肢运动功能:采用免疫组织化学技术(IHC)观察CRMP-2在损伤脊髓中的定位,实时定量PCR(qRT-PCR)方法观察CRMP-2在大鼠脊髓顿挫伤后的基因表达变化。结果:脊髓顿挫伤后,BBB评分结果表明大鼠后肢运动功能明显下降,在损伤后1d,7 d,14 d,21 d和28 d的BBB评分逐渐恢复,但是仍然低于对照组。免疫组织化学染色结果显示:CRMP-2在脊髓前角运动神经元和神经胶质细胞中广泛表达在脊髓损伤后12 h,3 d,7 d,14 d和28 d,CRMP-2免疫阳性细胞数相比sham组均有明显的减少。定量qRT-PCR结果显示:脊髓顿挫伤后CRMP-2基因表达下降,并持续至术后28 d。结论:脊髓顿挫伤后,CRMP-2大量存在于脊髓前角运动神经元及神经胶质细胞中,在损伤脊髓中的基因表达持续下降。结果提示脊髓顿挫伤后CRMP-2可能影响神经细胞的生长,分化和迁移。 展开更多
关键词 脊髓顿挫伤 脑衰反应蛋白2(crmp-2) BBB评分 大鼠
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CRMP2过表达及沉默对Aβ_(25-35)诱导SH-SY5Y细胞损伤的影响
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作者 胡杨 张宇 +2 位作者 吕俊杰 薛欢 高媛媛 《山西医科大学学报》 CAS 2021年第11期1447-1451,共5页
目的探究脑衰反应调节蛋白2(CRMP2)过表达及沉默对Aβ_(25-35)诱导SH-SY5Y细胞损伤的影响。方法将含CRMP2过表达载体、CRMP2空载体、CRMP2沉默载体及CRMP2扰乱载体的慢病毒感染并筛选SH-SY5Y细胞,分别命名为CRMP2过表达组、空载体组、CR... 目的探究脑衰反应调节蛋白2(CRMP2)过表达及沉默对Aβ_(25-35)诱导SH-SY5Y细胞损伤的影响。方法将含CRMP2过表达载体、CRMP2空载体、CRMP2沉默载体及CRMP2扰乱载体的慢病毒感染并筛选SH-SY5Y细胞,分别命名为CRMP2过表达组、空载体组、CRMP2沉默组及扰乱载体组。采用荧光检测和Western blot分别验证感染效率和CRMP2过表达及沉默效果。四组细胞均用终浓度为3μmol/L的Aβ_(25-35)孵育处理24 h诱导细胞损伤,采用MTT实验、LDH实验及Hoechst 33258实验分别检测细胞活性、细胞毒性及细胞凋亡。结果荧光检测结果显示,各组慢病毒感染效率均达95%以上。Western blot检测结果显示,与扰乱载体组相比,CRMP2沉默组CRMP2蛋白表达减少(P<0.01)。与空载体组相比,CRMP2过表达组CRMP2蛋白表达增加(P<0.01)。MTT实验、LDH实验及Hoechst 33258实验结果显示,与扰乱载体组相比,CRMP2沉默组细胞活性增加、细胞毒性降低及细胞凋亡减少(均P<0.05);与空载体组相比,CRMP2过表达组细胞活性降低、细胞毒性增加及细胞凋亡增多(均P<0.01)。结论CRMP2过表达对Aβ_(25-35)诱导的SH-SY5Y细胞损伤具有促进作用,CRMP2沉默对Aβ_(25-35)诱导的SH-SY5Y细胞损伤具有抑制作用。 展开更多
关键词 脑衰反应调节蛋白2(crmp2) Aβ_(25-35) SH-SY5Y细胞 细胞损伤
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Bone morphogenetic protein-2 is a negative regulator of hepatocyte proliferation downregulated in the regenerating liver 被引量:10
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作者 Cui-Ping Xu Wen-Min Ji +1 位作者 Gijs R van den Brink Maikel P Peppelenbosch 《World Journal of Gastroenterology》 SCIE CAS CSCD 2006年第47期7621-7625,共5页
AIM: To characterize the expression and dynamic changes of bone morphogenetic protein (BMP)-2 in hepatocytes in the regenerating liver in rats after partial hepatectomy (PH), and examine the effects of BMP-2 on prolif... AIM: To characterize the expression and dynamic changes of bone morphogenetic protein (BMP)-2 in hepatocytes in the regenerating liver in rats after partial hepatectomy (PH), and examine the effects of BMP-2 on proliferation of human Huh7 hepatoma cells. METHODS: Fifty-four adult male Wistar rats were randomly divided into three groups: A normal control (NC) group, a partial hepatectomized (PH) group and a sham operated (SO) group. To study the effect of liver regeneration on BMP-2 expression, rats were sacrificed before and at different time points after PH or the sham intervention (6, 12, 24 and 48 h). For each time point, six rats were used in parallel. Expression and distribution of BMP-2 protein were determined in regenerating liver tissue by Western blot analysis and immunohistochemistry. Effects of BMP-2 on cell proliferation of human Huh7 hepatoma cell line were assessed using an MTT assay.RESULTS: In the normal liver strong BMP-2 expression was observed around the central and portal veins. The expression of BMP-2 decreased rapidly as measured by both immunohistochemistry and Western blot analysis. This decrease was at a maximum of 3.22 fold after 12 h and returned to normal levels at 48 h after PH. No significant changes in BMP-2 immunoreactivity were observed in the SO group. BMP-2 inhibited serum induced Huh7 cell proliferation.CONCLUSION: BMP-2 is expressed in normal adult rat liver and negatively regulates hepatocyte proliferation. The observed down regulation of BMP-2 following partial hepatectomy suggests that such down regulation may be necessary for hepatocyte proliferation. 展开更多
关键词 Bone morphogenetic protein-2 Partial hepatectomy Liver regeneration Hepatocellular carcinoma
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Drilling Combined with Adipose-derived Stem Cells and Bone Morphogenetic Protein-2 to Treat Femoral Head Epiphyseal Necrosis in Juvenile Rabbits 被引量:7
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作者 Zi-li WANG Rong-zhen HE +7 位作者 Bin TU Jin-shen HE Xu CAO Han-song XIA Hong-liang BA Song WU Cheng PENG Kun XIONG 《Current Medical Science》 SCIE CAS 2018年第2期277-288,共12页
This study was designed to evaluate the effects of drilling through the growth plate and using adipose-derived stem cells (ADSCs) and bone morphogenetic protein-2 (BMP-2) to treat femoral head epiphyseal ischemic ... This study was designed to evaluate the effects of drilling through the growth plate and using adipose-derived stem cells (ADSCs) and bone morphogenetic protein-2 (BMP-2) to treat femoral head epiphyseal ischemic necrosis, which can be done in juvenile rabbits. Passagefour bromodeoxyuridine (BrdU)-labeled ADSCs were cultured, assayed with MTT to determine their viability and stained with alizarin red dye to determine their osteogenic ability. Twomonth-old, healthy male rabbits (1.2 to 1.4 kg, n=45) underwent ischemic induction and were randomly divided into five groups (group A: animal model control; group B: drilling; group C: drilling & ADSCs; group D: drilling & BMP-2; and group E: drilling & ADSCs & BMP-2). Magnetic resonance imaging (MRI), X-ray imaging, hematoxylin and eosin staining and BrdU immunofluorescence detection were applied 4, 6 and 10 weeks after treatment. Approximately 90% of the ADSCs were labeled with BrdU and showed good viability and osteogenic ability. Similar results were observed in the rabbits in groups C and E at weeks 6 and 10. The animals of groups C and E demonstrated normal hip structure and improved femoral epiphyseal quotients and trabecular areas compared with those of the groups A and B (P〈0.01). Group D demonstrated improved femoral epiphyseal quotients and trabecular areas compared with those of groups A and B (P〈0.05). In summary, drilling through the growth plate combined with ADSC and BMP-2 treatments induced new bone formation and protected the femoral head epiphysis from collapsing in a juvenile rabbit model of femoral head epiphyseal ischemic necrosis. 展开更多
关键词 adipose-derived stem cells bone morphogenetic protein-2 bone regeneration DRILLING Perthes' disease
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