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选择性缄默症女孩的沙盘游戏治疗个案报告
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作者 王剑 李玉荣 单晓楠 《中小学心理健康教育》 2014年第18期33-36,共4页
一、背景(一)受理小E,某小学一年级学生,由老师推荐而来,入学以来在班级中从不讲话,与同伴、教师交往方面有严重困难。(二)成长经历及现状自然情况:小E,7岁,独生女,核心家庭,健康状况良好。成长经历:小E出生后与父母一起... 一、背景(一)受理小E,某小学一年级学生,由老师推荐而来,入学以来在班级中从不讲话,与同伴、教师交往方面有严重困难。(二)成长经历及现状自然情况:小E,7岁,独生女,核心家庭,健康状况良好。成长经历:小E出生后与父母一起生活,与妈妈关系亲密;从小内向、怕生,与外界接触不多,出门会害怕、哭泣;坐、走路、说话等发育比同龄孩子较晚;父母均有喝斥制止小E的行为。父母的关注点:父母关心孩子的学习,认为孩子脑子笨,学习成绩不好;表示其在家表现正常,能讲话。初步印象:肤色较黑,面容黯淡,异常拘谨,神情呆滞,恐惧不安。 展开更多
关键词 沙盘游戏 选择性缄 默症 个案报告
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维甲酸受体激动剂AM80抗阿尔治海默症最新研究进展
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作者 乔爱敏 王宜海 程鹏 《沈阳药科大学学报》 CSCD 北大核心 2017年第11期1028-1032,共5页
目的综述AM80他米巴罗汀(tamibarotene,AM80)抗阿尔治海默症(Alzheimer's Disease,AD)药理作用及其作用机制、不良反应以及临床用药安全等最新研究进展。方法通过阅读近几年国内外的相关文献,对AM80抗阿尔治海默症最新研究报道进行... 目的综述AM80他米巴罗汀(tamibarotene,AM80)抗阿尔治海默症(Alzheimer's Disease,AD)药理作用及其作用机制、不良反应以及临床用药安全等最新研究进展。方法通过阅读近几年国内外的相关文献,对AM80抗阿尔治海默症最新研究报道进行详细的归纳总结。结果 AM80是一个合成的维甲酸受体激动剂,具有很好的抗阿尔治海默症作用。AM80作为一个多靶点药物,它通过转录调控多种与AD发病相关的基因;能够减少β淀粉样肽在脑部的沉积;还能够改善AD小鼠的学习记忆功能;有效弥补脑内乙酰胆碱的减少;并且能够增加小胶质细胞对Aβ(beta amyloid)的降解功能并伴随脑部炎症的减少。结论 AM80有望成为一个安全和有效的预防和治疗AD的药物,具有广泛的临床应用前景。 展开更多
关键词 他米巴罗汀 阿尔治海默症 维甲酸受体
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基于老年人失智症预防的游戏APP设计研究
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作者 舒啸 白晓霞 《信息与电脑》 2020年第12期113-115,共3页
失智症(Dementia)是一种因脑部伤害或疾病所导致的渐进性认知功能退化病症,是疾病现象而非正常老化现象。随着全球人口老龄化趋向日益明显,老年人失智症的病患率逐年飙升,对失智症进行预防及治疗成为全社会面临的共同难题,而我国在这方... 失智症(Dementia)是一种因脑部伤害或疾病所导致的渐进性认知功能退化病症,是疾病现象而非正常老化现象。随着全球人口老龄化趋向日益明显,老年人失智症的病患率逐年飙升,对失智症进行预防及治疗成为全社会面临的共同难题,而我国在这方面的需求更加紧迫与广泛。笔者致力于设计面向罹患失智症高风险族群的移动设备端游戏APP,试图通过提前训练脑力、活化脑细胞达到预防失智症发生的目的。 展开更多
关键词 失智 阿茨海默症 老龄化问题 游戏APP设计
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不同程度血尿酸水平对老年人群认知功能损害的影响 被引量:7
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作者 刘佳 王洁妤 +3 位作者 李耘 钱玉英 张仲迎 张丽 《北京医学》 CAS 2017年第8期810-814,共5页
目的探讨不同水平血尿酸与老年人群的认知功能损害的关系。方法本研究入组年龄>60岁人群共1 304例,其中男性816例,女性488例,收集年龄、受教育年限、吸烟史、疾病信息、BMI等一般资料,行简易智能精神状态量表检查(MMSE)、抑郁量表、H... 目的探讨不同水平血尿酸与老年人群的认知功能损害的关系。方法本研究入组年龄>60岁人群共1 304例,其中男性816例,女性488例,收集年龄、受教育年限、吸烟史、疾病信息、BMI等一般资料,行简易智能精神状态量表检查(MMSE)、抑郁量表、Hachinski缺血量表,并测定血尿酸和低密度脂蛋白指标。按照男女性别分类以及血尿酸水平(360μmol/L)分层进行一般线性模型和Logistic回归分析,并调整了年龄,受教育年限及心血管疾病危险因素。结果 (1)在男性人群中,血尿酸水平与MMSE值呈显著正相关(beta=2.58,P<0.05),但在女性人群中不显著。按照尿酸水平分层,在低水平尿酸组(<360μmol/L),两组人群的血尿酸水平与MMSE值成显著正相关(P均<0.05),但在较高血尿酸组(≥360μmol/L),两组人群均无此相关性。(2)在低血尿酸水平组中,较高的血尿酸能显著降低认知功能损害的风险,该相关性在男女人群中都存在(男性OR=0.69,95%CI:0.53~0.90,P<0.001,女性OR=0.77,95%CI:0.52~0.90,P=0.001)。而在较高水平血尿酸组中,血尿酸与认知功能损害风险无统计学意义(P均>0.05)。结论血尿酸对认知功能具有保护作用,但该相关性可能仅在一定水平内发挥作用。 展开更多
关键词 认知功能障碍 尿酸 阿茨海默症 氧化应激
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Genetic predisposition to inflammation:a new risk factor of Alzheimer's disease 被引量:1
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作者 万赢 王刚 陈生弟 《Neuroscience Bulletin》 SCIE CAS CSCD 2008年第5期314-322,共9页
Inflammation has been shown to play an important role in the progression of Alzheimer's disease (AD). Recent epidemical study indicates that the incidence of AD in some populations is substantially influenced by th... Inflammation has been shown to play an important role in the progression of Alzheimer's disease (AD). Recent epidemical study indicates that the incidence of AD in some populations is substantially influenced by the gene polymorphisms of the inflammation mediators. Meanwhile, an ensured risk factor, the ApoE ε4 allele is also reported to directly promote inflammation. Accordingly, it appears that an individual genetic background has partly determined his predisposition for AD by the extent of the inflammation response to the chronic stimulus by β-amyloid peptide (Aβ) deposits and other antigen stressor in the elderly. Hence we present a hypothesis that the inflammation genotypes may contribute to AD susceptibility. This may provide a new orientation both for future identification of individuals at risk and for personalized medication. 展开更多
关键词 Alzheimer's disease INFLAMMATION PREDISPOSITION polymorphism inflammation mediators ApoE ε4 allele identification personalized medication
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New lead discovery for novel M_1 agonists:pharmacophore model based on DISCO computation and virtual screening
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作者 高广涛 牛彦 +2 位作者 王栋 雷小平 胡应和 《Journal of Chinese Pharmaceutical Sciences》 CAS 2008年第1期75-78,共4页
To discover new lead compounds for M1 agonists. Ten typical M1 agonists were superimposed to build a M1 agonists 3D-pharmacophore model using distance-comparisons (DISCO) method without the previous knowledge of the... To discover new lead compounds for M1 agonists. Ten typical M1 agonists were superimposed to build a M1 agonists 3D-pharmacophore model using distance-comparisons (DISCO) method without the previous knowledge of the three-dimensional structure of M1 receptor. Virtual screening strategy was used to analyze the Available Chemicals Directory-Screening Compounds (ACD-SC) to identify possible new hits. Twenty-two compounds which fit the pharmacophore model well and are not similar with known M1 agonists were purchased in order to evaluate their M1 receptor agonist activity. One of them shows M1 receptor agonist activity with EC50 of 4.90 μmol/L and maximum response. Multiple of 10.0 which shows it worthy of further study as a new lead compound for M1 agonists. 展开更多
关键词 DISCO M1 agonists Pharmacophore model Virtual screening Alzheimer's disease
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Alzheimer’s disease classification based on sparse functional connectivity and non-negative matrix factorization
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作者 Li Xuan Lu Xuesong Wang Haixian 《Journal of Southeast University(English Edition)》 EI CAS 2019年第2期147-152,共6页
A novel framework is proposed to obtain physiologically meaningful features for Alzheimer's disease(AD)classification based on sparse functional connectivity and non-negative matrix factorization.Specifically,the ... A novel framework is proposed to obtain physiologically meaningful features for Alzheimer's disease(AD)classification based on sparse functional connectivity and non-negative matrix factorization.Specifically,the non-negative adaptive sparse representation(NASR)method is applied to compute the sparse functional connectivity among brain regions based on functional magnetic resonance imaging(fMRI)data for feature extraction.Afterwards,the sparse non-negative matrix factorization(sNMF)method is adopted for dimensionality reduction to obtain low-dimensional features with straightforward physical meaning.The experimental results show that the proposed framework outperforms the competing frameworks in terms of classification accuracy,sensitivity and specificity.Furthermore,three sub-networks,including the default mode network,the basal ganglia-thalamus-limbic network and the temporal-insular network,are found to have notable differences between the AD patients and the healthy subjects.The proposed framework can effectively identify AD patients and has potentials for extending the understanding of the pathological changes of AD. 展开更多
关键词 Alzheimer's disease sparse representation non-negative matrix factorization functional connectivity
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The pathogenesis of Alzheimer and pharmaceutical research on prevention 被引量:1
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作者 Danyang Liu Lihui Sun Jie Lian Haiyan Zhang Hongbo Yao 《International Journal of Technology Management》 2013年第8期104-106,共3页
Senile Dementia is the illness with a symptom of ongoing cognitive obstacle and loss of memory function. With our population aging, dementia and depression in old age is increasing rapidly. It is estimated that by 202... Senile Dementia is the illness with a symptom of ongoing cognitive obstacle and loss of memory function. With our population aging, dementia and depression in old age is increasing rapidly. It is estimated that by 2020, depressive disorder will become the second largest human disease leading to crippling. By 2040, globally the number of people with dementia will reach 81.1 million while the number of dementia patients in China will be the sum of that in all developed countries. Its incidence increases exponentially with age and the incidence of the elderly over 85 reach up to 8% -10%. Among all dementia patients, people with Alzheimer' s disease (Alzheimer' s disease, AD) accounted for 50 % -70%, the rest is vascular dementia (vascular dementia, VD) and mixed dementia. In the United States, Alzheimer' s disease has become the fourth leading cause of death followed after cardiovascular disease, cancer and stroke. Through comprehensive control strategy, we can improve the mental health level of old people, so as to protect the physical and mental health, improving the life quality of old people. 展开更多
关键词 PATHOGENESIS ALZHEIMER PHARMACEUTICAL Cholinergic drugs
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Pathway and mechanism of oxidative stress in Alzheimer's disease
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作者 蔡志友 晏勇 《Journal of Medical Colleges of PLA(China)》 CAS 2007年第5期320-324,F0003,共6页
Current hypotheses of pathogenesis of neuronal degeneration in Alzheimer's disease (AD) have been proposed, including formation of free radicals, oxidative stress, mitochondrial dysfunction, inflammatory processes... Current hypotheses of pathogenesis of neuronal degeneration in Alzheimer's disease (AD) have been proposed, including formation of free radicals, oxidative stress, mitochondrial dysfunction, inflammatory processes, genetic factors, environmental impact factors, apoptosis, and so on. Especially, oxidative stress plays an essential role in AD pathogenesis by the function of linking agent. Oxidative stress in AD mainly includes lipid peroxidation, protein oxidation and DNA oxidation. Lipid peroxidation plays a key role in the development and progression of AD. Protein oxidation is an important mechanism in AD. Oxidative damage to DNA may plays an important role in aging and AD. 展开更多
关键词 Alzheimer's disease oxidative stress
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基于CiteSpace的何首乌炮制历史沿革及现代研究进展分析
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作者 王一俊 王丽明 +3 位作者 刘霁虹 付志飞 张紫鑫 韩立峰 《中草药》 CAS CSCD 北大核心 2024年第17期6089-6106,共18页
目的分析何首乌Polygonum multiflourum的现代研究热点和炮制历史沿革,总结何首乌的化学成分现代药理毒理研究,为国内何首乌的研究方向和研究思路提供参考。方法基于Web of Science、中国知网、万方及维普数据库进行文献检索,时间限定为... 目的分析何首乌Polygonum multiflourum的现代研究热点和炮制历史沿革,总结何首乌的化学成分现代药理毒理研究,为国内何首乌的研究方向和研究思路提供参考。方法基于Web of Science、中国知网、万方及维普数据库进行文献检索,时间限定为1994年1月1日—2023年11月1日,共纳入2395篇符合标准的文献,以及通过查询历代中医药相关书籍以及近年来对于何首乌的研究成果与发表的文献,对年发文量,国家(地区)、机构、关键词时序图聚类、突现词进行分析。结果何首乌研究中文文献发文量较多,平缓,英文文献发文量快速增长,中文和英文文献对于何首乌研究的热度大体相同。中国、美国和韩国是发文量最多的国家,两者主要的研究机构集中于中医药大学。两者研究内容主要集中于化学成分和药理作用方面,其中以何首乌的肝损伤或肝毒性研究最多。结论何首乌的肝毒性是目前最需要解决的问题,此外何首乌的抗阿茨海默症、调血脂、免疫调节、调节胰岛素抵抗、抗炎和抗肿瘤等药理作用的研究不能搁置,同时炮制是历代何首乌减毒的关键因素,可能成为何首乌摆脱其肝毒性诟病的突破口和新方向。 展开更多
关键词 何首乌 炮制 CITESPACE 抗阿茨海默症 调血脂 免疫调节 调节胰岛素抵抗 抗炎 抗肿瘤
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Neurotoxicity and Biomarkers of Lead Exposure: a Review 被引量:10
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作者 Kang-sheng Liu Jia-hu Hao +2 位作者 Yu Zeng Fan-chun Dai Ping-qing Gu 《Chinese Medical Sciences Journal》 CAS CSCD 2013年第3期178-188,共11页
Appropriate selection and measurement of lead biomarkers of exposure are critically important for health care management purposes,public health decision making,and primary prevention synthesis.Lead is one of the neuro... Appropriate selection and measurement of lead biomarkers of exposure are critically important for health care management purposes,public health decision making,and primary prevention synthesis.Lead is one of the neurotoxicants that seems to be involved in the etiology of psychologies.Biomarkers are generally classified into three groups:biomarkers of exposure,effect,and susceptibility.The main body compartments that store lead are the blood,soft tissues,and bone;the half-life of lead in these tissues is measured in weeks for blood,months for soft tissues,and years for bone.Within the brain,lead-induced damage in the prefrontal cerebral cortex,hippocampus,and cerebellum can lead to a variety of neurological disorders,such as brain damage,mental retardation,behavioral problems,nerve damage,and possibly Alzheimer’s disease,Parkinson’s disease,and schizophrenia.This paper presents an overview of biomarkers of lead exposure and discusses the neurotoxic effects of lead with regard to children and adults. 展开更多
关键词 lead poisoning biological monitoring NEUROTOXICITY NEURODEVELOPMENT
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Spatial learning deficits in amyloid precursor protein 770 transgenic mice
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作者 李辉 沈孝宙 陈永福 《Chinese Medical Journal》 SCIE CAS CSCD 2001年第10期52-55,107,共5页
Objective To determine whether learning deficits could be seen in transgenic mice expressing human amyloid precursor protein 770 (APP 770 ) Methods Female heterozygous transgenic and nontransgenic mice aged 3,... Objective To determine whether learning deficits could be seen in transgenic mice expressing human amyloid precursor protein 770 (APP 770 ) Methods Female heterozygous transgenic and nontransgenic mice aged 3, 6 and 9 months at the start of testing were used, with eight mice in each age group All mice were subjected to various behavioral tasks including the Y maze task and the Morris water maze After behavioral testing, the mice were sacrificed, and their brain tissues were used for measuring the choline acetyltransferase (ChAT) activity Results Nine month old transgenic mice exhibited spatial learning deficits in the Morris water maze and in spontaneous alternation in the Y maze, compared with those of the age matched non transgenic mice The behavioral changes accompanied a reduction of ChAT activity in the cortical and hippocampal regions of transgenic mice On the other hand, these behavioral deficits were not observed in transgenic mice either at 3 or at 6 months of age, in which ChAT activity remained unchanged Conclusions The present results show that the learning impairment observed in 9 month old APP 770 transgenic mice are accompanied by a decrease in cortical and hippocampal ChAT activities This suggests that cholinergic deficits may be involved in the learning impairment observed in these APP 770 mice This model will be a useful tool in advancing our understanding of the relationship between the cholinergic system and the cognitive deficits observed in Alzheimer's disease (AD) 展开更多
关键词 Alzheimer's disease · cholinergic system · learning · transgenic
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Vanadyl complexes work with cinnamaldehyde in promoting cell viability under the β-amyloid burden in SH-SY5Y neural cells 被引量:2
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作者 李雪 白力丹 +4 位作者 董雅琼 常青 武睿 章京 杨晓达 《Journal of Chinese Pharmaceutical Sciences》 CAS CSCD 2016年第10期754-763,共10页
The Alzheimer's disease (AD) is one of the common cognitive disorders in the elderly. AD shares some similar pathological characters with diabetes mellitus (DM), suggesting potential application of anti-diabetic ... The Alzheimer's disease (AD) is one of the common cognitive disorders in the elderly. AD shares some similar pathological characters with diabetes mellitus (DM), suggesting potential application of anti-diabetic agents, such as vanadyl complexes, in therapeutic treatment of AD. In the present work, we studied the effects of vanadyl acetylacetonate (VO(acac)2) and cinnamaldehyde (CA) on an AD model based on SH-SY5Y neural cells. The experimental results showed that VO(acac)2 at sub-micromolar concentrations could improve the viability of neural cells with or without increased β-amyloid (Aβ) burden; and the combination of VO(acac)2 and CA showed an additive cell protection effects. Further investigation revealed that for SH-SY5Y neural cells, VO(acac)2 could activate PPART-AMPK signal transduction and inhibit GSK 3β, one of the major kinases for Tau hyperphosphorylation. Meanwhile, CA could correct the abnormal mitochondrial morphology due to Aβ-induced excessive mitochondrial fission, thus restoring/enhancing the mitochondrial function. In addition, both VO(acac)2 and CA decreased intracellular reactive oxygen species (ROS) level and inhibited formation of toxic Aβ oligomers. Overall, VO(acac)2 might work with CA in improving the neural cell viability under the Aβ burden, suggesting application of vanadium metallodrugs in AD treatment. 展开更多
关键词 Alzheimer's disease Β-AMYLOID SH-SY5Y cells VANADIUM CINNAMALDEHYDE
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Roles of the prostaglandin E2 receptors EP subtypes in Alzheimer’s disease
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作者 魏丽丽 沈悦娣 +4 位作者 章迎春 胡兴越 卢佩琳 王莉 陈炜 《Neuroscience Bulletin》 SCIE CAS CSCD 2010年第1期77-84,共8页
Neuroinflammation has always been of concern in the pathogenesis of Alzheimer’s disease (AD). As a major inflammatory mediator, prostaglandin E2 (PGE2) plays an important role in the inflammatory process of AD. U... Neuroinflammation has always been of concern in the pathogenesis of Alzheimer’s disease (AD). As a major inflammatory mediator, prostaglandin E2 (PGE2) plays an important role in the inflammatory process of AD. Up to now, there is still controversy on the neuroprotective or neurotoxic role of PGE2. However, the role of PGE2 in neurodegeneration may be far more complex, due to the 4 EP receptor subtypes. This article aims to summarize the relationship between PGE2 receptor EP subtypes and AD. It is believed that a better understanding of the PGE2 receptor EP subtypes may help to clarify the relation between inflammation and AD, and to develop novel therapeutic strategies targeting specific EP receptor for AD treatment. 展开更多
关键词 INFLAMMATION Alzheimer’s disease prostaglandin E2 prostaglandin E2 receptors
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Design and synthesis of benzimidamides as potential BACE1 inhibitors
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作者 高海飞 牛彦 +6 位作者 许凤荣 梁磊 周博 李勇剑 王超 刘鹏 徐萍 《Journal of Chinese Pharmaceutical Sciences》 CAS 2012年第2期124-131,共8页
Computer aided fragment-based lead discovery has been successfully applied to the design of inhibitors of aspartyl protease enzyme β-secretase(BACE1).A benzimidamide fragment,which binds to the two catalytic aspart... Computer aided fragment-based lead discovery has been successfully applied to the design of inhibitors of aspartyl protease enzyme β-secretase(BACE1).A benzimidamide fragment,which binds to the two catalytic aspartic acid residues in the active site of the enzyme,was selected as the starting compound.A novel series of 3-phenethylbenzimidamide inhibitors were designed and synthesized.Although biological evaluation results showed that the compounds displayed poor inhibitory activity towards BACE1,3-phenethylbenzimidamide analogs might be modified as potential BACE1 inhibitors. 展开更多
关键词 Alzheimer's disease BACE1 inhibitors CADD Benzimidamide
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Airborne fine particulate matter induces cognitive and emotional disorders in offspring mice exposed during pregnancy 被引量:5
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作者 Chao Zhao Peisi Xie +12 位作者 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 《Science Bulletin》 SCIE EI CSCD 2021年第6期578-591,M0004,共15页
Gestational exposure to PM_(2.5) is associated with adverse postnatal outcomes.PM_(2.5) can enter alveoli by using intratracheal instillation,even penetrate through lung cells into the blood circulation.Subsequently,t... Gestational exposure to PM_(2.5) is associated with adverse postnatal outcomes.PM_(2.5) can enter alveoli by using intratracheal instillation,even penetrate through lung cells into the blood circulation.Subsequently,they are transferred across the placenta and fetal blood brain barrier,causing the adverse birth outcomes of offspring.This 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 disorders.Samples 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 imaging.The 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 offspring.The 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 placenta.The 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 disease.The 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. 展开更多
关键词 Airborne fine particulate matter Gestational exposure Lipid metabolism Mass spectrometry imaging Cognitive and emotional disorders
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Cinnamaldehyde promotes mitochondrial function and reduces Aβ toxicity in neural cells 被引量:3
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作者 Lidan Bai Xue Li +3 位作者 Qing Chang Rui WU Jing Zhang Xiaoda Yang 《Journal of Chinese Pharmaceutical Sciences》 CAS CSCD 2016年第8期605-613,共9页
Cinnamon and its major active component, cinnamaldehyde, have been shown to be neuroprotective in models of Alzheimer's disease (AD). To further investigate the mechanism of cinnamaldehyde, we investigated the effe... Cinnamon and its major active component, cinnamaldehyde, have been shown to be neuroprotective in models of Alzheimer's disease (AD). To further investigate the mechanism of cinnamaldehyde, we investigated the effects of cinnamaldehyde focusing on mitochondrial function in SH-SYSY neural cells. The results demonstrated that cinnamaldehyde could enhance neural cell viability with or without increased Aβ levels. Cinnamaldehyde facilitated the maintenance of normal mitochondrial morphology, preserved the mitochondrial membrane potential (ATm), and reduced production of reactive oxygen species (ROS). Cinnamaldehyde also decreased the expression of dynamin-related protein 1 (Drpl), a protein critically involved in mitochondrial dynamics. In addition, cinnamaldehyde inhibited Aβ oligomerization, but it had no effects on Tau phosphorylation. In overall, cinnamaldehyde promoted mitochondrial function and inhibited Aβ toxicity, and these two properties may both contribute to the neuroprotective effect. These results suggest that cinnamaldehyde could be a potential nutriceutical in the prevention and even therapeutic treatment of AD as well as other aging-related metabolic syndromes. 展开更多
关键词 Alzheimer's disease oligomers MITOCHONDRIA CINNAMALDEHYDE
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Copper ions influence the toxicity of β-amyloid(1-42) in a concen-tration-dependent manner in a Caenorhabditis elegans model of Alzheimer’s disease 被引量:26
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作者 LUO YunFeng ZHANG Jie +2 位作者 LIU NianQing LUO Yuan ZHAO BaoLu 《Science China(Life Sciences)》 SCIE CAS 2011年第6期527-534,共8页
β-amyloid (Aβ) and copper play important roles in the pathogenesis of Alzheimer’s disease (AD).However,the behavioral correlativity and molecular mechanisms of Aβ and copper toxicity have been investigated less of... β-amyloid (Aβ) and copper play important roles in the pathogenesis of Alzheimer’s disease (AD).However,the behavioral correlativity and molecular mechanisms of Aβ and copper toxicity have been investigated less often.In the present study,we investigated the interaction and toxicity of Aβ1-42 and copper in the Aβ1-42 transgenic Caenorhabditis elegans worm model CL2006.Our data show that the paralysis behavior of CL2006 worms significantly deteriorated after exposure to 10-3 mol L-1 copper ions.However,the paralysis behavior was dramatically attenuated with exposure to 10-4 mol L-1 copper ions.The exogenous copper treatment also partially changed the homeostatic balance of zinc,manganese,and iron.Our data suggest that the accumulation of reactive oxygen species (ROS) was responsible for the paralysis induced by Aβ and copper in CL2006.The ROS generation induced by Aβ and copper appear to be through sod-1,prdx-2,skn-1,hsp-60 and hsp-16.2 genes. 展开更多
关键词 Alzheimer’s disease β-amyloid(1-42) copper C. elegans oxidative stress
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A fusion of least squares and empirical likelihood for regression models with a missing binary covariate 被引量:1
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作者 DUAN XiaoGang WANG Zhi 《Science China Mathematics》 SCIE CSCD 2016年第10期2027-2036,共10页
Multiply robust inference has attracted much attention recently in the context of missing response data. An estimation procedure is multiply robust, if it can incorporate information from multiple candidate models, an... Multiply robust inference has attracted much attention recently in the context of missing response data. An estimation procedure is multiply robust, if it can incorporate information from multiple candidate models, and meanwhile the resulting estimator is consistent as long as one of the candidate models is correctly specified. This property is appealing, since it provides the user a flexible modeling strategy with better protection against model misspecification. We explore this attractive property for the regression models with a binary covariate that is missing at random. We start from a reformulation of the celebrated augmented inverse probability weighted estimating equation, and based on this reformulation, we propose a novel combination of the least squares and empirical likelihood to separately handle each of the two types of multiple candidate models,one for the missing variable regression and the other for the missingness mechanism. Due to the separation, all the working models are fused concisely and effectively. The asymptotic normality of our estimator is established through the theory of estimating function with plugged-in nuisance parameter estimates. The finite-sample performance of our procedure is illustrated both through the simulation studies and the analysis of a dementia data collected by the national Alzheimer's coordinating center. 展开更多
关键词 calibration covariate adjustment effect modification missing at random multiple robustness refitting
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The design, synthesis and α7 nicotinic acetylcholine receptors positive allosteric modulative evaluation of 3H-quinazolin-4-one derivatives 被引量:1
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作者 Zongze Huang Xintong Wang +5 位作者 Ying Meng Xin Li Haoran Xiao Xiling Bian KeWei Wang Qi Sun 《Journal of Chinese Pharmaceutical Sciences》 CAS CSCD 2018年第8期540-552,共13页
A series of new 6-substituted 3 H-quinazolin-4-ones(3 a-3 d) were designed, synthesized and evaluated as the type I positive allosteric modulators(PAMs) of human α7 n ACh R expressed in Xenopus ooctyes by two-ele... A series of new 6-substituted 3 H-quinazolin-4-ones(3 a-3 d) were designed, synthesized and evaluated as the type I positive allosteric modulators(PAMs) of human α7 n ACh R expressed in Xenopus ooctyes by two-electrode voltage clamp. However, no compound showed a better efficacious PAM than lead compound 2 in the presence of acetylcholine(100 μM). The structure-activity relationship(SAR) analysis suggested that thiazolo[4,5-d]pyrimidin-7(6 H)-one was the key biological skeleton. 展开更多
关键词 3H-Quinazolin-4-ones α7 nAChR Positive allosteric modulators Structure-activity relationship Schizophrenia disease
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