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Neuroscience Bulletin 2024年第3期40卷 283-292页

作者： Yunyi Lan Xinyan Han Fei Huang hailian shi Hui Wu Liu Yang Zhibi Hu Xiaojun Wu Shanghai Key Laboratory of Compound Chinese Medicines The Ministry of Education Key Laboratory for Standardization of Chinese MedicinesThe State Administration of TCM Key Laboratory for New Resources and Quality Evaluation of Chinese MedicineInstitute of Chinese Materia MedicaShanghai University of Traditional Chinese MedicineShanghai201203China Central Laboratory Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai200021China

Early growth response protein 1(Egr-1)triggers the transcription of many genes involved in cell growth,differentiation,synaptic plasticity,and ***,its mechanism in neuronal survival and degeneration is still poorly *** study demonstrated that Egr-1 was down-regulated at mRNA and protein levels in the central nervous system(CNS)of experimental autoimmune encephalomyelitis(EAE)***-1 knockout exacerbated EAE progression in mice,as shown by increased disease severity and incidence;it also aggravated neuronal apoptosis,which was associated with weakened activation of the BDNF/TGFβ1/MAPK/Akt signaling pathways in the CNS of EAE ***,Egr-1 siRNA promoted apoptosis but mitigated the activation of BDNF/TGFβ1/MAPK/Akt signaling in SH-SY5Y *** results revealed that Egr-1 is a crucial regulator of neuronal survival in EAE by regulating TGFβ1-mediated signaling activation,implicating the important role of Egr-1 in the pathogenesis of multiple sclerosis as a potential novel therapy target.

关键词： Early growth response protein 1 Transforming growth factor-beta 1 Multiple sclerosis Experimental autoimmune encephalomyelitis Neurodegeneration

Targeting proprotein convertase subtilisin/kexin type 9(PCSK9):from bench to bedside

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Signal Transduction and Targeted Therapy 2024年第2期9卷 509-557页

作者： Xuhui Bao Yongjun Liang Hanman Chang Tianji Cai Baijie Feng Konstantin Gordon Yuekun Zhu hailian shi Yundong He Liyi Xie Institute of Therapeutic Cancer Vaccines Fudan University Pudong Medical CenterShanghaiChina Shanghai Key Laboratory of Regulatory Biology School of Life SciencesEast China Normal UniversityShanghaiChina Department of Oncology Fudan University Pudong Medical CenterShanghaiChina Center for Clinical Research Fudan University Pudong Medical CenterShanghaiChina Clinical Research Center for Cell-based Immunotherapy Fudan UniversityShanghaiChina Department of Pathology Duke University Medical CenterDurhamNCUSA Center for Medical Research and Innovation Fudan University Pudong Medical CenterShanghaiChina Institute for Food Safety and Health Illinois Institute of TechnologyChicagoILUSA Department of Sociology University of MacaoTaipaMacaoChina Medical Institute Peoples’Friendship University of RussiaMoscowRussia A.Tsyb Medical Radiological Research Center ObninskRussia Department of Colorectal Surgery The First Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjiangChina Shanghai Key Laboratory of Compound Chinese Medicines Institute of Chinese Materia MedicaShanghai University of Traditional Chinese MedicineZhangjiang Hi-tech ParkShanghaiChina Department of Radiation Oncology Fudan University Shanghai Cancer CenterShanghaiChina Department of Oncology Shanghai Medical CollegeFudan UniversityShanghaiChina

Proprotein convertase subtilisin/kexin type 9(PCSK9)has evolved as a pivotal enzyme in lipid metabolism and a revolutionary therapeutic target for hypercholesterolemia and its related cardiovascular diseases(CVD).This comprehensive review delineates the intricate roles and wide-ranging implications of PCSK9,extending beyond CVD to emphasize its significance in diverse physiological and pathological states,including liver diseases,infectious diseases,autoimmune disorders,and notably,*** exploration offers insights into the interaction between PCSK9 and low-density lipoprotein receptors(LDLRs),elucidating its substantial impact on cholesterol homeostasis and cardiovascular *** also details the evolution of PCSK9-targeted therapies,translating foundational bench discoveries into bedside applications for optimized patient *** advent and clinical approval of innovative PCSK9 inhibitory therapies(PCSK9-iTs),including three monoclonal antibodies(Evolocumab,Alirocumab,and Tafolecimab)and one small interfering RNA(siRNA,Inclisiran),have marked a significant breakthrough in cardiovascular *** therapies have demonstrated unparalleled efficacy in mitigating hypercholesterolemia,reducing cardiovascular risks,and have showcased profound value in clinical applications,offering novel therapeutic avenues and a promising future in personalized medicine for cardiovascular ***,emerging research,inclusive of our findings,unveils PCSK9’s potential role as a pivotal indicator for cancer prognosis and its prospective application as a transformative target for cancer *** review also highlights PCSK9’s aberrant expression in various cancer forms,its association with cancer prognosis,and its crucial roles in carcinogenesis and cancer *** conclusion,this synthesized review integrates existing knowledge and novel insights on PCSK9,providing a holistic perspective on its transformative impact in reshaping therapeutic paradigms acr

关键词： PCSK9 metabolism convert

Bear bile powder alleviates Parkinson’s disease-like behavior in mice by inhibiting astrocyte-mediated neuroinflammation

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Chinese Journal of Natural Medicines 2023年第9期21卷 710-720页

作者： WANG Lupeng BAI Yuyan TAO Yanlin SHEN Wei ZHOU Houyuan HE Yixin WU Hui HUANG Fei shi hailian WU Xiaojun Shanghai Key Laboratory of Compound Chinese Medicines The Ministry of Education(MOE)Key Laboratory for Standardization of Chinese MedicinesThe State Administration of TCM(SATCM)Key Laboratory for New Resources and Quality Evaluation of Chinese MedicineInstitute of Chinese Materia MedicaShanghai University of Traditional Chinese MedicineShanghai 201203China

Parkinson’s disease(PD)is a common neurodegenerative disease in middle-aged and elderly *** particular,increasing evidence has showed that astrocyte-mediated neuroinflammation is involved in the pathogenesis of *** a precious traditional Chinese medicine,bear bile powder(BBP)has a long history of use in clinical *** has numerous activities,such as clearing heat,calming the liver wind and anti-inflammation,and also exhibits good therapeutic effect on convulsive ***,whether BBP can prevent the development of PD has not been ***,this study was designed to explore the effect and mechanism of BBP on suppressing astrocyte-mediated neuroinflammation in a mouse model of ***-like behavior was induced in the mice by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)(30 mg·kg−1)for five days,followed by BBP(50,100,and 200 mg·kg−1)treatment daily for ten *** stimulated rat C6 astrocytic cells were used as a cell model of *** results indicated that BBP treatment significantly ameliorated dyskinesia,increased the levels of tyrosine hydroxylase(TH)and inhibited astrocyte hyperactivation in the substantia nigra(SN)of PD ***,BBP decreased the protein levels of glial fibrillary acidic protein(GFAP),cyclooxygenase 2(COX2)and inducible nitric oxide synthase(iNOS),and up-regulated the protein levels of takeda G protein-coupled receptor 5(TGR5)in the ***,BBP significantly activated TGR5 in a dose-dependent manner,and decreased the protein levels of GFAP,iNOS and COX2,as well as the mRNA levels of GFAP,iNOS,COX2,interleukin(IL)-1β,IL-6 and tumor necrosis factor-α(TNF-α)in LPS-stimulated C6 ***,BBP suppressed the phosphorylation of protein kinase B(AKT),inhibitor of NF-κB(IκBα)and nuclear factor-κB(NF-κB)proteins in vivo and in *** also observed that TGR5 inhibitor triamterene attenuated the anti-neuroinflammatory effect of BBP on LPS-stimulated C6 ***

关键词： Parkinson's disease Bear bile powder Astrocyte Neuroinflammation Takeda G protein-coupled receptor 5

Astragaloside Ⅳ Prevents Over-activation of Microglial Cells via Glucocorticoid Receptor Mediated Signaling Pathway

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黄连吴茱萸药对水提物对大鼠结肠癌癌前病变的作用

第十四届全国中药和天然药物学术研讨会

作者： Hongshuai Liu hailian shi Yixin He Hui Wu Beibei Zhang Zhengtao Wang Xiaojun Wu Shanghai University of Traditional Chinese Medicine

＜正＞Excessive activation of microglia that detrimental to neuronal survival is closely associated with many neurodegenerative *** IV（ASI）is a natural saponin molecule found within the roots of Astragalus membranaceus,a famous traditional Chinese medicine,which shows multiple bioactivities including anti-virus,anti-hypertension and

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中国中药杂志 2010年第9期35卷 1185-1188页

作者：董立石海莲季光吴大正上海中医药大学中药研究所上海201203 上海市复方中药重点实验室上海201203 上海中医药大学龙华医院脾胃病研究所上海200032

目的:研究黄连吴茱萸药对对DMH诱导的大鼠结肠癌癌前病变以及结肠上皮增殖和凋亡的作用。方法:采用DMH制备大鼠结肠癌模型;应用形态学的方法测定经过细微分离获得的完整肠腺内细胞的增殖和凋亡变化;应用甲基绿染色和光学显微镜计数中、... 详细信息

目的:研究黄连吴茱萸药对对DMH诱导的大鼠结肠癌癌前病变以及结肠上皮增殖和凋亡的作用。方法:采用DMH制备大鼠结肠癌模型;应用形态学的方法测定经过细微分离获得的完整肠腺内细胞的增殖和凋亡变化;应用甲基绿染色和光学显微镜计数中、降结肠异变肠腺病灶数目。结果:黄连吴茱萸药对能够明显抑制模型组动物ACF的形成。模型组动物中、降结肠肠腺内细胞增殖显著增加,而黄连吴茱萸药对能够明显抑制中、降结肠肠腺内细胞的增殖;模型组动物降结肠肠腺内细胞凋亡明显增加,而中结肠肠腺内细胞凋亡较正常相比无明显差异,而黄连吴茱萸药对能够显著促进中、降结肠肠腺内细胞的凋亡。结论:黄连吴茱萸药对能够显著抑制结肠癌癌前病变ACF的形成,提示其对结肠癌可能具有抑制和临床治疗作用,其作用部分通过抑制细胞增殖和促进细胞凋亡实现。

关键词：黄连吴茱萸结肠癌二甲肼癌前病变大鼠

甜橙黄酮对人胃癌AGS细胞增殖和凋亡的作用及其机制研究

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中国中药杂志 2011年第6期36卷 790-794页

作者：董杨季光曹爱丽施建蓉石海莲谢建群吴大正上海中医药大学中药研究所上海市复方中药重点实验室上海201203 上海中医药大学教学实验中心上海201203 上海中医药大学脾胃病研究所上海200032

目的:探讨甜橙黄酮对人胃癌AGS细胞增殖和凋亡的作用及其机制。方法:采用MTT法观察甜橙黄酮对AGS胃癌细胞生长的抑制作用;流式细胞仪检测甜橙黄酮对细胞周期的影响;Annexin V-FITC/PI标记定量检测细胞凋亡率,DNA片段化分析进一步验证甜... 详细信息

目的:探讨甜橙黄酮对人胃癌AGS细胞增殖和凋亡的作用及其机制。方法:采用MTT法观察甜橙黄酮对AGS胃癌细胞生长的抑制作用;流式细胞仪检测甜橙黄酮对细胞周期的影响;Annexin V-FITC/PI标记定量检测细胞凋亡率,DNA片段化分析进一步验证甜橙黄酮对细胞凋亡的作用;Hoechst 33342染色后倒置荧光显微镜观察凋亡细胞形态;Western blot检测对p21和p53蛋白表达的影响。结果:甜橙黄酮可明显抑制AGS胃癌细胞的增殖,呈时间和剂量依赖性;甜橙黄酮可阻滞细胞于G2/M期和增加AGS胃癌细胞凋亡率,并随剂量增大作用增强;60μmol.L-1甜橙黄酮作用48 h产生凋亡特有的梯形条带;Hoechst 33342染色观察到甜橙黄酮给药组出现细胞核浓缩、边缘化以及凋亡小体等细胞凋亡的形态特征;甜橙黄酮可呈剂量依赖地增强p21和p53蛋白表达。结论:甜橙黄酮可显著抑制人AGS胃癌细胞的增殖,使细胞阻滞于G2/M期,并可诱导细胞凋亡,其机制可能与上调p21和p53蛋白有关。

关键词：甜橙黄酮胃癌增殖凋亡

黄芪皂苷甲抑制压力过载型心肌肥厚大鼠肾素-血管紧张素的过度激活

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中国中药杂志 2009年第24期34卷 3242-3246页

作者：石海莲马春来刘燕周吉燕胡之璧吴大正上海中医药大学中药研究所上海201203 上海市复方中药重点实验室上海201203 复旦大学附属华山医院上海200040

目的:探讨黄芪皂苷甲(AsⅣ)对压力过载型左心室肥厚大鼠肾素-血管紧张素系统过度激活的影响。方法:采用缩窄大鼠腹主动脉制备压力过载所致的左心室肥厚模型。造模12周后分别给予灌服黄芪皂苷甲(1.0,3.3 ***-1)12周。给药结束后,应用形... 详细信息

目的:探讨黄芪皂苷甲(AsⅣ)对压力过载型左心室肥厚大鼠肾素-血管紧张素系统过度激活的影响。方法:采用缩窄大鼠腹主动脉制备压力过载所致的左心室肥厚模型。造模12周后分别给予灌服黄芪皂苷甲(1.0,3.3 ***-1)12周。给药结束后,应用形态测量学测定左室质量指数;采用ELISA法测定大鼠血浆血管紧张素Ⅱ(AngⅡ)、醛固酮(A ld)含量和心肌组织AngⅡ含量;采用Real tim e PCR测定心肌组织ACE,AT1和AT2mRNA含量;采用W estern b lot法测定心肌组织AT1和AT2的蛋白表达。结果:与模型组相比,黄芪皂苷甲能降低左室质量指数;生化测定结果表明,模型组血浆AngⅡ和A ld含量较假手术组明显增加,心肌组织的AngⅡ含量也较假手术组显著提高。黄芪皂苷甲能降低模型组血浆AngⅡ和A ld含量以及心肌组织的AngⅡ含量;黄芪皂苷甲具有下调模型动物心肌组织血管紧张素转化酶(ACE)的基因表达,上调模型动物心肌组织AT2的基因和蛋白表达,但对模型动物心肌组织中上调的AT1基因和蛋白表达无逆转作用。结论:黄芪皂苷甲能够抑制压力过载型心肌肥厚大鼠肾素-血管紧张素系统的过度激活,这可能是其逆转左室肥厚的途径之一。

关键词：黄芪皂苷甲血管紧张素Ⅱ 心肌肥厚醛固酮血管紧张素转化酶

吴茱萸碱对MDA-MB-231细胞增殖迁移及IL-8表达的影响

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中药药理与临床 2014年第3期30卷 27-30页

作者：李想石海莲谢建群吴晓俊赵淑娟上海中医药大学中药研究所上海市复方中药重点实验室中药新资源与质量标准综合评价国家中医药管理局重点研究室上海中医药大学上海201203 上海中医药大学龙华医院脾胃病研究所上海201203

目的:观察吴茱萸碱对人乳腺癌细胞(MDA-MB-231)增殖和白介素-8(IL-8)含量的影响。方法:采用CCK-8法测定吴茱萸碱对MDA-MB-231细胞增殖的影响;采用Annexin V/PI双染法测定吴茱萸碱对MDA-MB-231细胞凋亡的影响;采用ELISA法测定不同浓度吴... 详细信息

目的:观察吴茱萸碱对人乳腺癌细胞(MDA-MB-231)增殖和白介素-8(IL-8)含量的影响。方法:采用CCK-8法测定吴茱萸碱对MDA-MB-231细胞增殖的影响;采用Annexin V/PI双染法测定吴茱萸碱对MDA-MB-231细胞凋亡的影响;采用ELISA法测定不同浓度吴茱萸碱对MDA-MB-231细胞IL-8表达的影响;采用细胞划痕实验测定吴茱萸碱对MDA-MB-231细胞迁移的影响。结果:随着吴茱萸碱浓度的增加,作用时间的延长,细胞的增殖活力抑制率逐渐增高,吴茱萸碱分别作用MDA-MB-231细胞24h,48 h和72 h,增殖活力抑制率达到50%时的浓度(IC50)为175.5μmol/L,124.3μmol/L和108.7μmol/L。吴茱萸碱干预MDAMB-231细胞24 h能够呈剂量依赖性促进细胞凋亡。随着吴茱萸碱浓度的增加,作用时间的延长,MDA-MB-231细胞IL-8的含量逐渐增高。吴茱萸碱对MDA-MB-231细胞迁移的抑制作用呈剂量依赖性和时间依赖性。结论:吴茱萸碱具有抑制MDA-MB-231细胞增殖和细胞迁移,并且促进细胞凋亡的作用,但同时其能够上调IL-8表达的副作用也值得关注。

关键词：吴茱萸碱 MDA-MB-231细胞细胞增殖凋亡白介素-8

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血瘀理论与慢性萎缩性胃炎的诊治

中华中医药学刊 2019年第3期37卷 624-627页

作者：殷静易晋宇徐波石海莲费晓燕上海中医药大学附属龙华医院上海200032 上海中医药大学上海201203

慢性萎缩性胃炎(CAG)是一种以胃黏膜上皮腺体结构改变为特征的炎性病变。CAG与两种癌变有着密切联系,即肠型胃癌和胃型胃癌。积极治疗CAG,对于逆转胃癌前病变、降低胃癌发生率有着重要的临床意义。传统医学认为血瘀的存在对本病的发病... 详细信息

慢性萎缩性胃炎(CAG)是一种以胃黏膜上皮腺体结构改变为特征的炎性病变。CAG与两种癌变有着密切联系,即肠型胃癌和胃型胃癌。积极治疗CAG,对于逆转胃癌前病变、降低胃癌发生率有着重要的临床意义。传统医学认为血瘀的存在对本病的发病起重要作用,同时从活血化瘀角度治疗慢性萎缩性胃炎,取得较好疗效。通过梳理相关文献,研究总结慢性萎缩性胃炎的发病、诊治与血瘀相关的研究进展探讨血瘀在慢性萎缩性胃炎诊治中的意义。

关键词：慢性萎缩性胃炎血瘀中医药中医理论

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异甘草酸镁治疗酒精性肝病临床疗效观察

中国社区医师 2014年第36期 49-49页

作者：刘亚芳史海莲苏枫博黑龙江省齐齐哈尔市第一医院消化二科吉林大学第一医院二部放射科吉林大学第二医院脑外科

目的:分析异甘草酸镁治疗酒精性肝病的临床疗效。方法:2012年8月-2014年7月收治酒精性肝病患者60例,随机分为研究组30例和对照组30例,分别予以异甘草酸镁及还原型谷胱甘肽治疗,对比两组临床疗效。结果:治疗后,两组肝功均有不同程度的下... 详细信息

目的:分析异甘草酸镁治疗酒精性肝病的临床疗效。方法:2012年8月-2014年7月收治酒精性肝病患者60例,随机分为研究组30例和对照组30例,分别予以异甘草酸镁及还原型谷胱甘肽治疗,对比两组临床疗效。结果:治疗后,两组肝功均有不同程度的下降,研究组明显低于对照组。研究组治疗有效率高于对照组。结论:异甘草酸镁治疗酒精性肝病疗效确切、显著,且安全性较高,具有较高的临床应用价值。

关键词：异甘草酸镁酒精性肝病临床疗效