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science China(Life sciences) 2023年第5期66卷 893-1066页

作者： Aging Biomarker Consortium Hainan Bao Jiani Cao Mengting Chen Min Chen Wei Chen Xiao Chen Yanhao Chen Yu Chen Yutian Chen Zhiyang Chen Jagadish K Chhetri Yingjie Ding Junlin Feng Jun Guo Mengmeng Guo Chuting He Yujuan Jia Haiping Jiang Ying Jing Dingfeng Li Jiaming Li Jingyi Li Qinhao Liang Rui Liang Feng Liu Xiaoqian Liu Zuojun Liu Oscar Junhong Luo Jianwei Lv Jingyi Ma Kehang Mao Jiawei Nie Xinhua Qiao Xinpei Sun Xiaoqiang Tang Jianfang Wang Qiaoran Wang Siyuan Wang Xuan Wang Yaning Wang Yuhan Wang Rimo Wu Kai Xia Fu-Hui Xiao Lingyan Xu Yingying Xu Haoteng Yan Liang Yang Ruici Yang Yuanxin Yang Yilin Ying Le Zhang Weiwei Zhang Wenwan Zhang Xing Zhang Zhuo Zhang Min Zhou Rui Zhou Qingchen Zhu Zhengmao Zhu Feng Cao Zhongwei Cao Piu Chan Chang Chen Guobing Chen Hou-Zao Chen Jun Chen Weimin Ci Bi-Sen Ding Qiurong Ding Feng Gao Jing-Dong JHan Kai Huang Zhenyu Ju Qing-Peng Kong Ji Li Jian Li Xin Li Baohua Liu Feng Liu Lin Liu Qiang Liu Qiang Liu Xingguo Liu Yong Liu Xianghang Luo Shuai Ma Xinran Ma Zhiyong Mao Jing Nie Yaojin Peng Jing Qu Jie Ren Ruibao Ren Moshi Song Zhou Songyang Yi Eve Sun Yu Sun Mei Tian Shusen Wang Si Wang Xia Wang Xiaoning Wang Yan-Jiang Wang Yunfang Wang Catherine CL Wong Andy Peng Xiang Yichuan Xiao Zhengwei Xie Daichao Xu Jing Ye Rui Yue Cuntai Zhang Hongbo Zhang Liang Zhang Weiqi Zhang Yong Zhang Yun-Wu Zhang Zhuohua Zhang Tongbiao Zhao Yuzheng Zhao Dahai Zhu Weiguo Zou Gang Pei Guang-Hui Liu Aging Biomarker Consortium(ABC) Beijing 100101China CAS Key Laboratory of Genomic and Precision medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China department of Dermatology Xiangya HospitalCentral South UniversityChangsha 410008China Hunan Key Laboratory of Aging Biology Xiangya HospitalCentral South UniversityChangsha 410008China National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangsha 410008China Clinic Center of Human Gene Research Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Hubei Clinical Research Center of Metabolic and Cardiovascular Disease Huazhong University of Science and TechnologyWuhan 430022China Hubei Key Laboratory of Metabolic Abnormalities and Vascular Aging Huazhong University of Science and TechnologyWuhan 430022China Stem Cell Translational Research Center Tongji HospitalTongji University School of MedicineShanghai 200065China department of Nuclear medicine Daping HospitalThird Military Medical UniversityChongqing 400042China CAS Key Laboratory of Nutrition Metabolism and Food SafetyShanghai Institute of Nutrition and HealthUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China Shanghai Key Laboratory of Maternal Fetal medicine Clinical and Translational Research Center of Shanghai First Maternity and Infant HospitalFrontier Science Center for Stem Cell ResearchShanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China The department of Endovascular Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Key Laboratory of Regenerative medicine of Ministry of Education Institute of Ageing and Regenerative MedicineJ

Aging biomarkers are a combination of biological parameters to(i)assess age-related changes,(ii)track the physiological aging process,and(iii)predict the transition into a pathological *** a broad spectrum of aging biomarkers has been developed,their potential uses and limitations remain poorly *** immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research:How old are we?Why do we get old?And how can we age slower?This review aims to address this ***,we summarize our current knowledge of biomarkers developed for cellular,organ,and organismal levels of aging,comprising six pillars:physiological characteristics,medical imaging,histological features,cellular alterations,molecular changes,and secretory *** fulfill all these requisites,we propose that aging biomarkers should qualify for being specific,systemic,and clinically relevant.

关键词： aging senescence biomarker clock

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Airborne fine particulate matter induces cognitive and emotional disorders in offspring mice exposed during pregnancy

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science Bulletin 2021年第6期66卷 578-591,M0004页

作者： Chao Zhao Peisi Xie Ting Yong Wei Huang Jianjun Liu Desheng Wu Fenfen Ji Min Li Doudou Zhang Ruijin Li Chuan Dong Juan Ma Zheng Dong Sijin Liu Zongwei Cai State Key Laboratory of Environmental and Biological Analysis Department of ChemistryHong Kong Baptist UniversityHong Kong 999077China Key Laboratory of Modern Toxicology of Shenzhen Shenzhen Center for Disease Control and PreventionShenzhen 518000China school of Chinese medicine Hong Kong Baptist UniversityHong Kong 999077China department of Functional neurology&Neurosurgery First Affiliated Hospital of Shenzhen UniversityShenzhen Second People’s HospitalShenzhen University School of MedicineShenzhen 518000China Institute of Environmental science Shanxi UniversityTaiyuan 030000China State Key Laboratory of Environmental Chemistry and Ecotoxicology Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China

Gestational exposure to PM_(2.5) is associated with adverse postnatal ***_(2.5) can enter alveoli by using intratracheal instillation,even penetrate through lung cells into the blood ***,they are transferred across the placenta and fetal blood brain barrier,causing the adverse birth outcomes of *** study demonstrated that the gestational exposure resulted in cognitive and emotional disorders in female offspring although the offspring were not exposed to PM_(2.5).Placental metabolic pathways modulated fetal brain development and played a pivotal role for maternal-placentalfetal interactions in the fetal programming of adult behavioral and mental *** of fetus,offspring hippocampus and placenta from the mice exposed to PM_(2.5) were investigated using a comprehensive approach including mass spectrometry-based lipidomics and three-dimensional *** exposure induced the neuro-degeneration in hippocampus,impairment of placental cytoarchitecture,and reprogramming of lipidome,which might affect the modulation of maternal-fetal cross-talk and result in the behavior disorders of *** variation of spatial distribution of lipids was profoundly affected in dorsal pallium and hippocampal formation regions of fetal brain,offspring hippocampus,as well as labyrinth and junctional zones of *** abundance alteration of lipid markers associated with neurodegenerative diseases was validated in transgenic mouse model with Alzheimer’s disease and human cerebrospinal fluid from patients with Parkinson’s *** finding could help with the selection of more suitable heterogeneous-related substructures targeting PM_(2.5) exposure and the exploration of PM_(2.5)-induced toxicological effects on neurodegenerative diseases.

关键词： Airborne fine particulate matter Gestational exposure Lipid metabolism Mass spectrometry imaging Cognitive and emotional disorders

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he Natural Progression of Parkinson＇s Disease in a Small Cohort with 15 Drug-na＇~＇ve Patients

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Chinese Medical Journal 2015年第13期128卷 1761-1764页

作者： Ying Liu Jin-Hu Fan Xiang Gao Li Ma You-Lin Qiao Lin Zhang department of neurology Dalian Municipal Friendship Hospital Dalian Liaoning 116001 China department of Cancer Epidemiology Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100021 China department of medicine Channing Laboratory Brigham and Women's Hospital and Harvard Medical School Boston MA 02115 USA department of Nutrition Harvard University School of Public Health Boston MA 02115 USA department of Epidemiology Dalian Medical University Dalian Liaoning 116044 China department of neurology University of California Davis School of Medicine Sacramento CA 95817 USA

The studies of the natural progression of Parkinson＇s disease （PD） in Chinese populations have been lacking. To address this issue and obtain a preliminary data, we conducted a PD progression assessment in 15 adults with de novo PD from a nutritional intervention trial （NIT） cohort in Lin County China. Methods： Using the Copiah County screening questionnaire and United Kingdom Parkinson＇s Disease Society brain Bank diagnostic criteria, we surveyed the available N IT cohort members in 2000 and diagnosed 86 patients as PD. In 2010, we resurveyed all PD patients and confirmed definite PD diagnosis in 15 cases with the rest of them being dead （54）： having probable （10） PD or vascular Parkinsonism （3）; relilsing to participate （2）; or being away （2）. In both surveys, we used Hoehn and Yahr （HY） scale and assessed the disease progression. Unified Parkinson＇s Disease Rating Scale （UPDRS） was added to the second survey. Results： In 2010, the average disease duration for 15 definite PD patients was 13.6 ~ 7.3 years. Over a 10-year time span, 9 out of 15 patients remained at the same HY stage while the remaining 6 progressed. Rigidity （47% vs. 100%; P 0.002） and postural instability （7% vs. 47%; P - 0.005） worsened significantly. The mean UPDRS motor scores in 2010 were 39.4 ± 23.7. Conclusions： Overall worsening of motor timction in PD seems to be the rule in this untreated cohort, and their rate of progression seemed to be slower than those reported in the western populations.

关键词： Drug-naive Epidemiology Parkinson's Disease Progression

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Progressive paradoxical sleep deprivation impairs partial memory following learning tasks in rats

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Neural Regeneration Research 2008年第6期3卷 598-603页

作者： Chunmin Zhu Xiangrong Yao Weisheng Zhang Yanfeng Song Yiping Hou Laboratory of neurobiology Department of Anatomy Histology and Embryology School of Basic Medical Sciences Lanzhou University Lanzhou 730000 Gansu Province China department of neurology Anning Branch of Lanzhou General Hospital of Lanzhou Military Area Command of Chinese PLA Lanzhou 730070 Gansu Province China department of Anal-Rectal Surgery Gansu Province Hospital Lanzhou 730000 Gansu Province China

BACKGROUND： Complex learning tasks result in a greater number of paradoxical sleep phases, which can improve memory. The effect of paradoxical sleep deprivation, induced by ＂flower pot＂ technique, on spatial reference memory and working memory require further research. OBJECTIVE： To observe the effect of progressive paradoxical sleep deprivation in rats, subsequent to learning, on memory using the Morris Water Maze. DESIGN, TIME AND SETTING： Controlled observation experiment. The experiment was performed at the Laboratory of neurobiology, department of Anatomy, Histology and Embryology, school of Basic Medical sciences, Lanzhou University from December 2006 to October 2007. MATERIALS： Twenty-eight, male, Wistar rats, 3-4 months old, were provided by the Experimental Animal Center of Lanzhou University. The Morris Water Maze and behavioral analyses system was purchased from Genheart Company, Beijing, China. METHODS： All animals, according to a random digits table, were randomly divided into paradoxical sleep deprivation, tank control, and home cage control groups. Paradoxical sleep deprivation was induced by the ＂flower pot＂ technique for 72 hours, housing the rats on small platforms over water. Rats in the ＂tank control＂ and ＂home cage control＂ groups were housed either in a tank with large platforms over the water or in normal cages without paradoxical sleep deprivation. MAIN OUTCOME MEASURES： Morris Water Maze was employed for task learning and spatial memory testing. Rats in all groups were placed at six random starting points each day for four consecutive days. Each placement was repeated for two trials; the first trial represented reference memory and the second working memory. Rats in the first trial were allowed to locate the submerged platform within 120 seconds. Data, including swimming distance, escape latency, swimming velocity, percentage of time in correct quarter, and memory scores were recorded and analyzed automatically by behavioral analyses systems

关键词： paradoxical sleep deprivation Morris Water Maze spatial reference memory working memory

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A novel SIRT6 activator ameliorates neuroinflammation and ischemic brain injury via EZH2/FOXC1 axis

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Acta Pharmaceutica Sinica B 2021年第3期11卷 708-726页

作者： Tailin He Jialin Shang Chenglong Gao Xin Guan Yingyi Chen Liwen Zhu Luyong Zhang Cunjin Zhang Jian Zhang Tao Pang State Key Laboratory of Natural medicines Jiangsu Key Laboratory of Drug ScreeningJiangsu Key Laboratory of Drug Discovery for Metabolic DiseasesChina Pharmaceutical UniversityNanjing 210009China Medicinal Bioinformatics Center Shanghai Jiao Tong University School of MedicineShanghai 200025China department of neurology of Drum Tower hospital Medical School and the State Key Laboratory of Pharmaceutical BiotechnologyNanjing UniversityNanjing 210008China

Ischemic stroke is the second leading cause of death worldwide with limited medications and neuroinflammation was recognized as a critical player in the progression of stroke,but how to control the overactive neuroinflammation is still a long-standing ***,we designed a novel SIRT6 activator MDL-811 which remarkably inhibited inflammatory response in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and primary mouse microglia,which were abolished by silencing ***-seq screening identified the forkhead box C1 (Foxc1) is a key gene evoked by MDL-811stimulation and is required for the anti-inflammatory effects of *** found MDL-811-activated SIRT6 directly interacted with enhancer of zeste homolog 2 (EZH2) and promoted deacetylation of EZH2 which could bind to the promoter of Foxc1 and upregulate its expression to modulate ***,our data demonstrated that MDL-811 not only ameliorated sickness behaviors in neuroinflammatory mice induced by LPS,but also markedly reduced the brain injury in ischemic stroke mice in addition to promoting long-term functional ***,MDL-811 also exhibited strong anti-inflammatory effects in human monocytes isolated from ischemic stroke patients,underlying an interesting translational *** together,MDL-811 could be an alternative therapeutic candidate for ischemic stroke and other brain disorders associated with neuroinflammation.

关键词： SIRT6 activator Neuroinflammation Ischemic stroke Deacetylation Microglia Macrophage FOXC1 EZH2

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The efficacy and safety of pramipexole ER versus IR in Chinese patients with Parkinson’s disease: a randomized, double-blind, double-dummy, parallel-group study

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Translational Neurodegeneration 2014年第1期3卷 80-88页

作者： Ying Wang Shenggang Sun Suiqiang Zhu Chunfeng Liu Yiming Liu Qing Di Huifang Shang Yan Ren Changhong Lu Mark Forrest Gordon Nolwenn Juhel Shengdi Chen for the Pramipexole ER Study Team Ruijin hospital affiliated to Shanghai Jiao Tong University school of medicine ShanghaiChina Union hospital affiliated to Tongji Medical College of Huazhong University of science and Technology WuhanChina Tongji hospital affiliated to Tongji Medical College of Huazhong University of science and Technology WuhanChina The second affiliated hospital of Soochow University SuzhouChina Qilu hospital affiliated to Shandong University JinanChina Nanjing brain hospital NanjingChina West China hospital affiliated to Sichuan University ChengduChina First affiliated hospital of China Medical University ShenyangChina Boehringer Ingelheim International Trading(Shanghai)Co LtdShanghaiChina Boehringer Ingelheim Pharmaceuticals IncRidgefieldCTUSA Boehringer Ingelheim France S.A.S ReimsFrance department of neurology Ruijin Hospital affiliated to Shanghai Jiaotong University School of MedicineShanghaiChina 不详

Objective:To evaluate the non-inferiority of pramipexole extended-release(ER)versus immediate-release(IR)in Chinese patients with Parkinson’s disease(PD)in a double-blind,randomized,parallel-group ***:Subjects were Chinese patients with idiopathic PD with diagnosis≥2 years prior to trial,age≥30 years old at diagnosis,and Modified Hoehn and Yahr score 2-4 during‘on’-*** received treatment with pramipexole ER(n=234)or IR(n=239).Non-inferiority was based on the primary endpoint,the change from baseline to end of maintenance(week 18)in the UPDRS(Parts II+III)total ***:For the primary endpoint,the adjusted mean changes(standard error)of UPDRS Parts II+III at week 18 were−13.81(0.655)and−13.05(0.643)for ER and IR formulations,respectively,using ANCOVA adjusted for treatment and centre(fixed effect)and baseline(covariate).The adjusted mean between group difference was 0.8 for the 2-sided 95%CI(−1.047,2.566).Since the lower limit of the 2-sided 95%CI(−1.047)for treatment difference was higher than the non-inferiority margin of−4,non-inferiority between pramipexole ER and IR was *** incidence of adverse events(AEs)was 68.8%in the ER arm and 73.6%in the IR arm with few severe AEs(ER:2.1%;IR:3.8%).Conclusion:Based on the UPDRS II+III score,pramipexole ER was non-inferior to pramipexole *** safety profiles of pramipexole ER and IR were *** results were based on comparable mean daily doses and durations of treatment for both formulations.

关键词： Parkinson’s disease Pramipexole ER Pramipexole IR Non-inferiority Unified Parkinson’s Disease Rating Scale(UPDRS) Safety

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The DIRECT consortium and the REST-meta-MDD project:towards neuroimaging biomarkers of major depressive disorder

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Psychoradiology 2022年第1期2卷 32-42页

作者： Xiao Chen Bin Lu Hui-Xian Li Xue-Ying Li Yu-Wei Wang Francisco Xavier Castellanos Li-Ping Cao Ning-Xuan Chen Wei Chen Yu-Qi Cheng Shi-Xian Cui Zhao-Yu Deng Yi-Ru Fang Qi-Yong Gong Wen-Bin Guo Zheng-Jia-Yi Hu Li Kuang Bao-Juan Li Le Li Tao Li Tao Lian Yi-Fan Liao Yan-Song Liu Zhe-Ning Liu Jian-Ping Lu Qing-Hua Luo Hua-Qing Meng Dai-Hui Peng Jiang Qiu Yue-Di Shen Tian-Mei Si Yan-Qing Tang Chuan-Yue Wang Fei Wang Hua-Ning Wang Kai Wang Xiang Wang Ying Wang Zi-Han Wang Xiao-Ping Wu Chun-Ming Xie Guang-Rong Xie Peng Xie Xiu-Feng Xu Hong Yang Jian Yang Shu-Qiao Yao Yong-Qiang Yu Yong-Gui Yuan Ke-Rang Zhang Wei Zhang Zhi-Jun Zhang Jun-Juan Zhu Xi-Nian Zuo Jing-Ping Zhao Yu-Feng Zang the DIRECT consortium Chao-Gan Yan CAS Key Laboratory of Behavioral science Institute of PsychologyChinese Academy of SciencesBeijing 100101China International Big-Data Center for Depression Research Chinese Academy of SciencesBeijing 100101China Magnetic Resonance Imaging Research Center Institute of PsychologyChinese Academy of SciencesBeijing 100101China department of Psychology University of Chinese Academy of SciencesBeijing 100049China Sino-Danish College University of Chinese Academy of SciencesBeijing 101408China Sino-Danish Center for Education and Research Graduate University of Chinese Academy of SciencesBeijing 101408China department of Child and Adolescent Psychiatry NYU Grossman School of MedicineNew YorkNY 10016USA Nathan Kline Institute for Psychiatric Research OrangeburgNew YorkNY 10962USA 9Affiliated Brain Hospital of Guangzhou Medical UniversityGuangzhou 510370China Capital Normal University Beijing 100089China department of Psychiatry Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310020ZhejiangChina department of Psychiatry First Affiliated Hospital of Kunming Medical UniversityKunmingYunnan 650032China Shanghai Mental Health Center Shanghai Jiao Tong University School of MedicineShanghai 200030China Huaxi MR Research Center(HMRRC) Department of RadiologyWest China Hospital of Sichuan UniversityChengduSichuan 610044China Research Unit of Psychoradiology Chinese Academy of Medical SciencesChengduSichuan 610052China department of Psychiatry and National Clinical Research Center for Mental DisordersThe Second Xiangya Hospital of Central South UniversityChangsha 410011HunanChina department of Psychiatry The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400042China Xijing hospital of Air Force Military Medical University Xi’anShaanxi 710032China Center for Cognitive science of Language Beijing Language and Culture UniversityBeijing 100083China affiliated Mental Health Center&Hangzhou Seventh People’s hospital Zhejiang University School of

Despite a growing neuroimaging literature on the pathophysiology of major depressive disorder(MDD),repro-ducible findings are lacking,probably reflecting mostly small sample sizes and heterogeneity in analytic *** address these issues,the Depression Imaging REsearch ConsorTium(DIRECT)was *** REST-meta-MDD project,pooling 2428 functional brain images processed with a standardized pipeline across all participating sites,has been the first effort from *** this review,we present an overview of the moti-vations,rationale,and principal findings of the studies so far from the REST-meta-MDD *** from the first round of analyses of the pooled repository have included alterations in functional connectivity within the default mode network,in whole-brain topological properties,in dynamic features,and in functional *** well-powered exploratory observations have also provided the basis for future longitudinal hypothesis-driven *** these fruitful explorations,DIRECT has proceeded to its second stage of data sharing that seeks to examine ethnicity in brain alterations in MDD by extending the exclusive Chinese original sample to other ethnic groups through international collaborations.A state-of-the-art,surface-based preprocessing pipeline has also been introduced to improve *** images from patients with bipolar disorder and schizophrenia will be included to identify shared and unique abnormalities across diag-nosis *** addition,large-scale longitudinal studies targeting brain network alterations following antidepressant treatment,aggregation of diffusion tensor images,and the development of functional magnetic resonance imaging-guided neuromodulation approaches are *** these endeavours,we hope to accelerate the translation of functional neuroimaging findings to clinical use,such as evaluating longitudinal effects of antidepressant medications and developing individualized

关键词： major depressive disorder DIRECT R-fMRI database neuroimaging

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Bone marrow mesenchymal stem cell transplantation downregulates plasma level and the microglia expression of transforming growth factor β1 in the acute phase of cerebral cortex ischemia

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Chronic Diseases and Translational medicine 2020年第4期6卷 270-280页

作者： Zhao-Hui Liang Jian-Juan Gu Wen-Xiu Yu Yun-Qian Guan Mostafa Khater Xiao-Bo Li department of neurology The Second Xiangya Hospital of Central South UniversityChangshaHunan 410011China department of neurology Northern Jiangsu People's HospitalClinical Medical School of Yangzhou UniversityYangzhouJiangsu 225001China department of Obstetrics and Gynecology Northern Jiangsu People's HospitalClinical Medical School of Yangzhou UniversityYangzhouJiangsu 225001China department of Cell Biology Beijing Institute of GeriatricsXuanwu HospitalCapital Medical UniversityBeijing 100053China Pharmacology and Toxicology department Augusta UniversityGeorgia 30912USA

Background:Both bone marrow mesenchymal stem cell(BM-MSC)and transforming growth factor-β1(TGF-β1)have a strong anti-inflammatory capacity in *** their relationship has not been well *** this study,we investigated how intravenous BM-MSC transplantation in rats effected the expression of TGF-β148 h post cerebral ischemia,and we analyzed the main cells that produce TGF-β***:We used a distal middle cerebral artery occlusion(dMCAO)model in twenty Sprague-Dawley(SD)*** rats were randomly divided into two groups:the ischemic control group and the postischemic BM-MSC transplantation *** hour after the dMCAO model was established,the rats were injected in the tail vein with either 1 ml saline or 1×106 BM-MSCs suspended in 1 ml *** were used to detect TGF-β1 content in the brain infarct core area,striatum and the plasma at 48 h after cerebral *** staining of brain tissue sections for TGF-β1,Iba-1,CD68 and NeuN was performed to determine the number and the proportion of double stained cells and to detect possible TGF-β1 producing cells in the brain ***:Forty-eight hours after ischemia,the TGF-β1 content in the infarcted area of the BM-MSC transplantation group(23.94±4.48 pg/ml)was significantly lower than it was in the ischemic control group(34.18±4.32 pg/ml)(F=13.534,P=0.006).The TGF-β1 content in the rat plasma in the BM-MSC transplantation group(75.91±12.53 pg/ml)was significantly lower than it was in the ischemic control group(131.18±16.07 pg/ml)(F=36.779,P=0.0002),suggesting that after transplantation of BM-MSCs,TGF-β1 levels in the plasma decreased,but there was no significant change in the striatum *** staining showed that the total number of nucleated cells(1037.67±222.16 cells/mm2)in the infarcted area after transplantation was significantly higher than that in the ischemic control group(391.67±69.50 cells/mm2)(F=92.421,P<0.01);the number of TGF-β1+cells after transplan

关键词： Cerebral infarction Mesenchymal stem cell Transplantation Transforming growth factor-β1 Microglia

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Surface Functionalized Exosomes as Targeted Drug Delivery Vehicles for Cerebral Ischemia Therapy

Surface Functionalized Exosomes as Targeted Drug Delivery Ve...

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中国神经科学学会第十二届全国学术会议

作者： Tian TIAN Hui-Xin ZHANG Chun-Peng He Yan-Liang Zhu Cui Qi Ning-Ping Huang Zhong-Dang Xiao Zu-Hong Lu Bakhos A.Tannous Jun Gao department of neurobiology Key Laboratory of Human Functional Genomics of Jiangsu Nanjing Medical University Experimental Therapeutics and Molecular Imaging Lab Department of NeurologyMassachusetts General Hospital and Harvard Medical School State Key Laboratory of Bioelectronics School of Biological Science and Medical Engineering Southeast University

Objective The efficient and safe delivery of drugs across the blood-brain barrier（BBB） is a major obstacle in the treatment of ischemic stroke. Exosomes hold great promise as an endogenous drug delivery nanosystem for the treatment of cerebral ischemia given their unique ability to cross the BBB, low immunogenicity, innate stability, and high delivery efficiency. However, exosome insufficient targeting capability limits their clinical applications. In this work, we developed a strategy to modify the c（RGDy K）-conjugated exosomes（c RGD-Exo） targeting integrin αvβ3, which were expressed on reactive cerebral vascular endothelial cells conjugating to the exosome surface. They were then intravenously administered into mice with transient middle cerebral artery occlusion（MCAO）. Methods The exosome system was developed using bio-orthogonal chemistry by TEM, AFM, NTA and zeta potential measurement. In vivo,the protection was analyzed in post-ischemia after injecting c RGD-Exo subjected to MCAO model. The change of apoptosis and inflammation was studied by immunofluorescence. Results（1） c RGD-Exo targeted the lesion region of the ischemic brain and entered microglia, neurons and astrocytes.（2） Curcumin was incorporated into the c RGD-Exo, and administration of these exosomes resulted in a significantly stronger suppression of the inflammatory response in the lesion region, as compared to curcumin treatment alone. Conclusion We developed a targeted delivery system for the treatment of cerebral ischemia based on exosomes. Our exosome modification method is suitable for the rapid and large-scale production of functionalized exosomes, which may lead to their use as drug vehicles for clinical applications in different pathology.

关键词： exosomes drug delivery targeted therapy curcumin cerebral ischemia

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Low frequency stimulation of fastigial nucleus delays amygdaloid kindling seizures in rats

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中国药理通讯 2006年第4期23卷 55-55页

作者： Wang Shuang Wu Deng - Chang Zhu - Ge Zheng - Bing Zhu Yuan- Yuan Chen Zhong department of neurology Second Affiliated Hospital School of MedicineZhejiang University Hangzhou 310009 department of Pharmacology School of MedicineZhejiang University Hangzhou 310058

Aim: Low frequency stimulation (LFS) is a new method to treat pharmacoresistant epilepsy。Previous studies revealed that cerebellar fastigial nucleus is actively involved in epilepsy。In this study, we evaluated the effect of low frequency electrical stimulation of ipsilateral fastigial nucleus on the amygdaloid kindled seizures, which is a sound model of human temporal lobe epilepsy。Methods: Bipolar stainless electrodes were implanted in the right fastigial nucleus and the right amygdala。Daily amygdaloid kindling was delivered by a 2s, 60Hz monophasic square wave stimulation at predetermined threshold intensity。LFS (15rain, 1Hz, monophasic square wave pulse, 0.1ms pulse duration, 100μA) of fastigial nucleus began immediately after the kindling stimulation。Results: Low frequency stimulation of the ipsilateral fastigial nucleus significantly suppressed the progression of seizure stages and reduced afterdischarge duration throughout the course of amygdaloid kindling。The marked suppression induced by LFS of the fastigial nucleus was predominantly due to the significant retardation of progression from stage 0 to stage 1。Conclusion: These findings indicate that brain areas other than the kindling focus, such as the fastigial nucleus, can also used as reasonable targets for LFS to retard seizure development induced by amygdaloid kindling。LFS of the fastigial nucleus may have a significant antiepileptogenic effect, and may be helpful for human temporal lobe epilepsy treatment。

关键词：大鼠顶核低频刺激杏仁核点燃癫痫耐药性癫痫

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