神经元钙稳态失衡在阿尔茨海默病发病中的进展木

淀粉样蛋白的沉积与Tau蛋白磷酸化是阿尔茨海默病发病的关键分子机制,神经元胞内钙离子的变化可影响其生成和代谢;另一方面,这些蛋白的改变会进一步导致神经元钙稳态的失调,致使突触损伤、神经细胞凋亡及认知功能下降.本文就神经元钙稳态失衡在阿尔茨海默病发病中的进展进行综述.     

氧化应激对溶酶体储存与转运甲醛的影响

内源甲醛代谢失调被认为是导致阿尔茨海默病的危险因素之一,甲醛蓄积会引起神经细胞的死亡和认知功能的降低.研究表明,细胞内甲醛分布于溶酶体内,而溶酶体功能异常与神经退行性疾病密切相关.本文采用甲醛特异荧光探针,在氧化应激条件下,检测到小鼠脑微血管内皮细胞株bEnd.3和小鼠神经瘤母细胞株N2a溶酶体内甲醛明显升高;在慢性脑低灌注大鼠动物模型中,其脑神经细胞的溶酶体内甲醛也升高(P0.01);LeuLeuOMe处理bEnd.3细胞,使其溶酶体膜通透性增加,导致细胞内甲醛蓄积,而胞外甲醛降低.以上结果证明,溶酶体具有储存和转运甲醛的功能,如果溶酶体出现结构与功能的异常,会导致甲醛代谢失调,造成认知损害.     

神经元钙稳态失衡在阿尔茨海默病发病中的进展

淀粉样蛋白的沉积与Tau蛋白磷酸化是阿尔茨海默病发病的关键分子机制,神经元胞内钙离子的变化可影响其生成和代谢;另一方面,这些蛋白的改变会进一步导致神经元钙稳态的失调,致使突触损伤、神经细胞凋亡及认知功能下降。本文就神经元钙稳态失衡在阿尔茨海默病发病中的进展进行综述。     

国家“重大新药创制”科技重大专项重点关注靶点分析解读——β- 分泌酶

阿尔茨海默病是一种可导致记忆减退、认知功能障碍等症状的神经退行性疾病。研究显示,阿尔茨海默病与β- 淀粉样蛋白的过量产生和聚集密切相关,而β- 分泌酶是催化β- 淀粉样蛋白产生的关键酶,抑制β- 分泌酶可减少β- 淀粉样蛋白在脑中的蓄积,从而延缓阿尔茨海默病的病情发展。近年来,β- 分泌酶抑制剂作为一种理想的阿尔茨海默病治疗策略,受到了越来越多的关注。结合汤森路透数据库资源——Thomson Reuters Integrity 和Cortellis for Competitive Intelligence,对β- 分泌酶的机制、相关药物研究进展、适应证、研发机构、交易、专利、文献等情报进行数据层面的分析。     

tau蛋白异常与阿尔茨海默病的关系

阿尔茨海默病(Alzheimer disease,AD)是最常见的一种老年性痴呆症,以进行性记忆丧失和认知功能障碍为临床特征,神经原纤维缠结(neurofibrillary tangle,NFT)为其主要病理学特征之一,tau蛋白的各种异常与NFT的形成密切相关。对tau蛋白的各种异常导致AD发生的研究已取得重要进展,包括tau蛋白的异常磷酸化、异常糖基化、异常截断作用及基因突变等。本文旨在概述tau蛋白的各种异常改变及其可能机制。     

溶酶体离子通道蛋白在神经退行性疾病发生发展中的作用及机制研究

溶酶体离子通道蛋白异常引起溶酶体功能障碍是导致阿尔茨海默病(Alzheimer’s disease,AD)和帕金森病(Parkinson’s disease,PD)等神经退行性疾病的重要因素.溶酶体离子通道蛋白调节溶酶体内离子稳态、溶酶体膜电压以及溶酶体的酸度.溶酶体离子通道蛋白的结构或功能缺陷会引起溶酶体降解功能障碍,导致神经退行性疾病的发生发展.在这篇综述中,我们总结了各种离子通道蛋白调节溶酶体功能的过程及机制,以及离子通道蛋白异常参与神经退行性疾病的过程和机制.调节离子通道蛋白改善溶酶体的功能、促进异常聚集蛋白的清除,是神经退行性疾病治疗的潜在途径.     

同型半胱氨酸与阿尔茨海默病的相关性研究

阿尔茨海默病（alzheimer＇s disease,AD）是一种慢性、进行性中枢神经系统变性导致的痴呆,是痴呆最常见的病因和最常见的老年痴呆,以渐进性记忆障碍、认知功能障碍、人格改变及语言障碍等神经精神症状为特征。     

系统生物学在认知功能障碍研究中的应用

认知功能障碍可导致患者日常生活能力、社会适应能力明显下降,严重影响患者的生活质量。根据近年来众多研究显示,认知功能障碍的发生发展与基因、蛋白质、微生物等内环境因素的失调和紊乱有关。基于系统生物学的研究,梳理了近年来国内外研究学者在代谢组学、蛋白质组学、基因组学和肠道微生物组学层面对认知功能障碍的研究,并对系统生物学在认知功能障碍中的应用前景进行了展望,以期为认知功能障碍相关研究提供参考。     

Drebrin与认知功能障碍

树突棘和突触的病理改变在认知功能障碍发病机制中具有十分重要的作用,研究表明大脑发育调节蛋白（developmentregulationbrainprotein,Drebrin）能够调节树突棘和突触的形态和重塑。Drebrin的减少可能通过树突棘内细胞骨架变化,使树突棘的形态结构受到影响,导致突触功能和结构的变化。但目前阿尔茨海默病（Alzheimer’Sdisease,AD）脑内突触病理变化的具体机制及Drebrin和突触之间的关系仍不明确。探讨Drebrin与认知功能的关系及其机制,对临床上早期干预认知功能障碍、寻找AD的有效诊断治疗措施具有重要意义。     

清栓酶治疗脑血栓冠心病微循环变化初步观察

本文报导40例脑心血管疾病在清栓酶治疗前后进行甲皱微循环对比观察,其中脑血栓组20例,冠心病组20例,两组均在清栓酶治疗2～3疗程后复查,分别对其甲皱微循环微血管袢的形态及功能,血液流态和微血管周围变化等三方面进行治疗前后对比观察,结果发现,治疗前甲皱微循环改变是明显的,临床症状较重,治疗后甲皱微循环障碍均得到了明显改善,临床症状也随着减轻或消失。治疗前后比较,其差异有显著的意义 P<0.05,P<0.01.从临床对比观察所见,脑心血管疾病的微循环改变与病情有关,其改变与病情轻重相吻合,与疾病转归相一致,提示微血管病变是动脉硬化临床可识别的象征.微循环障碍与疾病的发生发展有着内在联系,是脑心血管疾病的病因和发病的中间环节.治疗后微循环障碍的明显改善,提示清栓酶有着较好的改善微循环的功能.     

Phospholipid profile of rat testis, its unique high level of monolysocardiolipin and its lipolytic capabilities in vitro. A chromatographic analysis

The phospholipid profiles of testes and heart of 1-, 3-, and 6-month-old rats and their in vitro response to the endogenous phospholipases at pH 7.4 and 38 degrees C for 60 min were analyzed by TLC technology and densitometry. A noticeable high level of monolysocardiolipin (MLCL) was shown in rat testes of all samples analyzed (1-, 3-, and 6-month-old), both control and incubated. In contrast, rat heart control samples revealed a high level of CL and no MLCL was detected. MLCL was only produced subsequent to in vitro incubation of whole tissue homogenate at pH 7.4 and 38 degrees C for 60 min, with concurrent reduction of CL. Alkenyl phosphatidyl ethanolamine (PE) was the major plasmalogen of rat testes. Following in vitro incubation, (a) a very low level of lyso PE plasmalogen was produced only in 3- and 6-month-old rat testes, (b) ceramide was also produced in all testes analyzed with concurrent reduction of sphingomyelin indicating the action of sphingomyelinase. These data clearly illustrate, for the first time, the presence of high levels of MLCL in all rat testes studied which probably is related to the physiological activity in vivo and requires further investigation.     

石刁柏胚性细胞诱导过程中的内源激素和多胺含量变化

用高效液相色谱法分析石刁柏愈伤组织胚性细胞诱导过程中不同时期内源激素和多胺含量的结果表明,在胚性细胞诱导过程中,Put和GA3一直呈上升趋势,胚性细胞出现时,IAA、Put和GA3含量都达到最高水平,显示高含量的IAA以及高比例的Pu“（Spd＋Spm）可能有利于胚性细胞的形成。     

党参体细胞胚胎发生早期阶段内源脱落酸和细胞分裂素的变化

以党参为实验材料,在附加1mg／L2,4-D3％或7％蔗糖的MS培养基上,成功获得体细胞胚胎发生同步化较高的实验体系。用ELISA方法测定了胚性细胞形成球形胚的过程中,内源ABA和CTK的含量变化。结果表明,在这一过程中内源ABA含量持续增加;内源CTK的组分和含量均发生很大变化,表现在组分iPAs在球形胚形成前急剧增加,球形胚形成期急剧下降,组分ZRs在球形胚形成前上升较缓慢,球形胚形成期急剧上升。     

On the differential lipolytic capabilities of rat spleen and cardiac muscle. An in vitro incubation in conjunction with chromatographic and densitometric analysis

The phospholipid profiles of newborn, young adult and aged rat heart and spleen and their in vitro response to endogenous phospholipases at pH 7.4 and 38 degrees C for 60 min were analysed by thin layer chromatography (TLC) technology and densitometry measurement. The noticeable high level of cardiolipin (CL) and its preferential deacylation, as detected by the formation of monolysocardiolipin (MLCL) and concurrent reduction of CL level were the most prevalent lipolytic events of rat cardiac muscle (newborn, young adult and aged) but the least prevalent in rat spleen. The level of ethanolamine plasmalogen (PE) was high in both the rat spleen and cardiac muscle (newborn, young adult and aged). Following in vitro incubation, the reduction in the level of PE and the high level of lyso alkenyl PE produced were most conspicuous in rat spleen (newborn, young adult and aged) and noticeably less in rat cardiac muscle. These data clearly illustrate the differential response of the endogenous substrates (phospholipids) to the endogenous phospholipases of these two tissues, and probably are related to their physiological activities in vivo.     

Determination of endogenous peptides in the porcine brain: possible construction of peptidome,a fact database for endogenous peptides

Peptides play crucial roles in many physiological events. However, a database for endogenous peptides has not yet been developed, because the peptides are easily degraded by proteolytic enzymes during extraction and purification. In this study, we demonstrated that the data for endogenous peptides could be collected by minimizing the proteolytic degradation. We separated porcine brain peptides into 5250 fractions by 2-dimensional chromatography (first ion-exchange and second reversed-phase high-performance liquid chromatography), and 75 fractions of average peptide contents were analyzed in detail by mass spectrometers and a protein sequencer. Based on the analysis data obtained in this study, more than 10000 peptides were deduced to be detected, and more than 1000 peptides to be identified starting from 2 g of brain tissue. Thus, we deduce that it is possible to construct a database for endogenous peptides starting from a gram level of tissue by using 2-dimensional high-performance liquid chromatography coupled with a mass spectrometer.     

The Structure of a New Piperidine Derivative from Buckwheat Seeds (Fagopyrum esculentum Moench)

Streptomyces hygroscopicus No. B–5050-HA, which produces a mixture of six maridomycins, yielded a mutant which produced 75% of the mixture as maridomycin III (MDM III).

Growth of S. hygroscopicus No. B–5050-HA, an improved MDM producer, was almost completely inhibited by 20 µg/ml of valine. This inhibition was counteracted by the addition of isoleucine, threonine, homoserine, methionine, α-amino-n-butyrate and α-ketobutyrate.

A valine resistant mutant, strain AV was isolated and found to produce increased level of MDM III at the expense of other maridomycins. Production of MDM III by the parent strain depended on the addition of isoleucine to the medium, but that by this mutant did not.

The properties of strain AV were discussed.     

鸡内源性类J亚群禽白血病病毒gp85基因的克隆及分析

为深入探讨J亚群禽白血病病毒(Avian leukosis virus subgroup J,ALV-J)的亚群特性,利用ALV-J gp85基因两侧的序列片段为引物,从正常SPF蛋鸡、商品肉鸡和DF1细胞基因组中完整地扩增了内源性类ALV-J gp85基因。肉鸡和DF1细胞内源性类ALV-J gp85基因同源性达99．9％;SPF蛋鸡内源性类ALV-J gp85基因与肉鸡和DF1细胞的内源性类ALV-J gp85基因之间同源性达95．6％、95．3％。三种不同来源的内源性类ALV-J gp85基因DNA与IMC10200株ALV-J的gp85基因的同源性分别为91．8％、94．1％、94．0％;与ALV-J原型株HPRS-103gp85基因的同源性分别为95．6％、98．3％、99．9％。内源性类ALV-J gp85序列与外源性ALV-J gp85基因具有相似或一致的ORF和Jameson-Worrlf抗原表位优势。     

芝麻灌浆特性与灌浆期籽粒中内源激素含量变化研究

在大田栽培条件下,对芝麻品种‘郑芝98N09’的灌浆特性及灌浆期籽粒中内源激素含量变化进行了研究,为芝麻高产优质高效栽培及品质育种提供理论依据。结果表明:(1)第9～17节位芝麻籽粒干物质率最高;下部(8节以下)蒴果在灌浆24d时的蒴果鲜重达最大值(1.596g/蒴),27d时籽粒鲜重达最大值(0.318g/蒴),灌浆最快的时期为灌浆15～33d,干物质积累量达籽粒干重的61.75%;中部(9～20节)蒴果在灌浆27d时的蒴果鲜重达最大值(1.622g/蒴),籽粒鲜重也同期达最大值(0.379g/蒴),灌浆最快的时期为灌浆21～36d,干物质积累量达籽粒干重的74.21%;上部(20节以上)蒴果籽粒干物质积累最快的时期为灌浆9～12d和24～27d两个阶段。(2)中部蒴果GA3含量大于下部和上部蒴果,而ABA和IAA的含量则小于下部和上部蒴果;除GA3/ZR比值外,中部蒴果的ABA/GA3、ABA/ZR、GA3/IAA和ZR/IAA比值都小于下部和上部蒴果。(3)较高的ZR含量和较低的ABA/ZR、ABA/GA3、IAA/GA3和IAA/ZR比值利于胚乳细胞分裂、蒴果发育、籽粒库容建成及籽粒干物质充实。(4)单一激素含量与不同部位蒴果单蒴粒重均达显著或极显著负相关关系,内源激素相互间的关系对下部蒴果粒重增加影响较小,适当提高IAA/ZR、ABA/GA3、IAA/GA3比值,能显著提高中部和上部蒴果的单蒴籽粒干重。     

Apparent effect of rabbit endogenous lentivirus type K acquisition on retrovirus restriction by lagomorph Trim5αs

To test the hypothesis that rabbit endogenous lentivirus type K (RELIK) could play a role in shaping the evolution of TRIM5α, the susceptibility of viruses containing the RELIK capsid (CA) to TRIM5 restriction was evaluated. RELIK CA-containing viruses were susceptible to the TRIM5αs from Old World monkeys but were unaffected by most ape or New World monkey factors. TRIM5αs from various lagomorph species were also isolated and tested for anti-retroviral activity. The TRIM5αs from both cottontail rabbit and pika restrict a range of retroviruses, including HIV-1, HIV-2, FIV, EIAV and N-MLV. TRIM5αs from the European and cottontail rabbit, which have previously been found to contain RELIK, also restricted RELIK CA-containing viruses, whereas a weaker restriction was observed with chimeric TRIM5α containing the B30.2 domain from the pika, which lacks RELIK. Taken together, these results could suggest that the pika had not been exposed to exogenous RELIK and that endogenized RELIK might exert a selective pressure on lagomorph TRIM5α.