miRNA与干细胞的生物学行为

背景：以往对干细胞的研究主要集中在基因方面，但目前越来越多的证据表明，miRNA在干细胞的自我更新和分化过程中发挥着重要的调控作用。 目的：介绍miRNA的形成及其对干细胞自我更新和多向分化的影响。 方法：以“microRNA，stem cell”为检索词，应用计算机检索Elsevier数据库2000-01/2010-05文章；以“miRNA，干细胞”为检索词检索中国期刊全文数据库2000-01/2010-05文章。 结果与结论：不同组织不同细胞存在自身特异的miRNA表达谱及序列特征，这可以作为某些组织或细胞的特异性分子标志。在细胞的不同发育阶段，miRNA组成不同，决定细胞的分化方向以及分化时相，是细胞“定时”、“定向”分化的“开关”。在各种干细胞中均存在特异性的miRNA，并且在干细胞的不同分化阶段亦有特异性miRNA表达，它们是保持干细胞自我更新和多向分化特性的关键分子之一。miRNA作为一种新的调控基因表达的小分子RNA，为干细胞的研究提供了一种新的途径。     

miRNA与Notch信号通路在心脏发育中的作用

背景：miRNA具有调控细胞增殖、分化和生物体生长发育等功能。Notch信号通路在细胞增殖、分化和器官组织发育也起重要作用。miRNA与Notch信号通路分别在心脏发育中的作用及两者之间关系的研究可能会为干细胞移植治疗某些心脏疾病提供新思路。 目的：综述miRNA和Notch信号通路在心脏发育中作用研究的新进展。 方法：应用计算机在Google Scholar、PubMed数据库和ScienceDirect-Home数据库进行检索,英文检索词“miRNA,Notch signaling pathway,cardiac development,stem cells”。 结果与结论：miRNA通过调节靶基因mRNA或抑制翻译而发挥作用,具有调控细胞增殖、分化等生物学功能,在心脏的发育发挥重要作用。Notch信号通路在决定细胞分化方向和心脏正常发育起重要作用。而miRNA-1可抑制Notch信号中Dll1受体表达而促进小鼠胚胎干细胞向心肌细胞分化。深入了解miRNA或Notch信号通路在心脏发育中的机制及两者之间的联系,明确其在调控干细胞分化为心肌细胞的作用,可能会为干细胞移植治疗某些心脏疾病提供新的干预靶点。     

干细胞维持多潜能性的能力与机制

背景：近年研究发现,成体细胞能够重新编程回到胚胎状态,这为利用成体干细胞治疗疾病提供了可能。现在虽然有不少关于干细胞增殖能力及自我更新的研究报道,但对其机制还缺乏深入的了解。 目的：对国内外关于干细胞维持多潜能性的能力与机制研究作一综述。 方法：应用计算机检索PubMed数据库中1993-01/2010-03关于干细胞维持多潜能性能力机制的文章,在标题和摘要中以“stem cells, pluripotency, mechanism”为检索词进行检索。选择文章内容与干细胞多潜能性能力维持机制有关者,同一领域文献则选择择近期发表或发表在权威杂志文章。初检得到122篇文献,根据纳入标准选择33篇文献进行综述。 结果与结论：干细胞主要通过一些主要的转录因子的表达、表观遗传学的调控和一些microRNAs(miRNAs)的作用来维持其多潜能性和自我更新能力。转录因子调节网络中的主要成员Oct4、Nanog及Sox2和一些表观遗传学修饰如组蛋白和DNA的甲基化以及miRNAs共同作用来抑制那些促进干细胞分化的基因表达和激活那些有助于维持干细胞多能性维持的基因表达,进而形成一个相互调控和依存的网络来维持干细胞的多能性和自我更新。     

神经干细胞转基因移植治疗帕金森病的可能与可行*

背景：神经干细胞分化为何种类型的神经细胞,不仅取决于细胞自身基因调控,更受所处环境中外来信号的影响。 目的：就神经干细胞生物学特性、分化以及转基因移植治疗帕金森病的研究进展进行综述。 方法：由第一作者应用计算机检索PubMed数据库1992-01/2009-12及中国期刊网全文数据库2003-01/2010-12有关神经干细胞生物学特性、分化以及转基因移植治疗帕金森病的文章,英文检索词为“neural stem cell(NSCs), neural stem cell transplant, Parkinson’s disease(PD)”,中文检索词为“神经干细胞,干细胞移植,帕金森病”。排除重复性研究及Meta分析,共保留30篇文献进行综述。 结果与结论：转基因神经干细胞移植治疗帕金森病是目前公认的最有前景的治疗方案。在低氧条件下转基因培养的神经干细胞,能高效地诱导分化为多巴胺能神经元,为移植治疗帕金森病提供细胞源。但神经干细胞的生物学特性、诱导分化等还有待进一步分析。同时应用于人体治疗的生物安全性问题也逐渐引起人们的重视,如致瘤性等问题均在进一步探索中。     

间充质干细胞培养与分化诱导的特点及机制

背景：间充质干细胞是目前备受关注的一类具有多向分化潜能的成体干细胞。 目的：对间充质干细胞分离、鉴别、生物学特性及应用前景做一综述。 方法：应用计算机检索Medline数据库(1996-01/2010-03),以“mesenchymal stem cell” 为检索词;同时检索CNKI数据库(1979/2010-02),以“间充质干细胞、培养、分化”为检索词。 结果与结论：共收集400篇关于间充质干细胞分离、培养、鉴定和分化的文献,中文86篇,英文314篇。排除发表时间较早、重复及类似研究,纳入36篇符合标准的文献。发现间充质干细胞分离、培养、鉴定虽然有多种方法,但还没有统一的标准,细胞分化诱导的机制仍不清楚,应用也存在诸多问题。     

干细胞治疗中枢神经系统疾病

干细胞是指未分化的细胞,具有自我复制和分化为多种功能体细胞的特性。按其起源,可分为两大类:胚胎干细胞(embryonic stem cell,ESC)和成体干细胞(adult stem cells,ASC)。ESC能发育分化形成完整的机体以及各种组织细胞,又称全能ESC。ASC来源于机体组织,具有干细胞的一些特性,但其分化潜能有限,故又称多能干细胞。如:骨髓干细胞、间充质干细胞(mesenchymal stem cell,MSC)、肌肉干细胞及神经干细胞(neural stem cell,NSC)等。多向分化潜能的特点使干细胞被应用于细胞替代治疗。由于神经组织的不可再生性,干细胞替代疗法成为最有前…     

胚胎干细胞及在生殖医学中的应用

背景：有报道胚胎干细胞体外培养可分化为原始生殖细胞并进一步生成配子,受精后发育为胚泡,并产生成活的子代。 目的：阐述近年胚胎干细胞在生殖医学中的研究进展。 方法：应用计算机检索清华同方系列数据库2000/2009有关生殖细胞、中药的相关研究文章,检索词：生殖细胞、中药,并限定文章语言种类为中文;同时应用计算机检索Pubmed数据库1998/2009相关文章,检索词：embryonic stem cells,stem cells,germ cells,oocyte,sperm,differentiation,限定文章语言种类为“English”。 结果与结论：胚胎干细胞在体外分化受到内、外源因素的影响,可以诱导分化为精子和卵母细胞,是研究哺乳动物早期胚胎发育的理想模型;目前研究体外培养原始生殖细胞和配子是可行的,但体外培养生殖细胞的特性和功能仍不确定,要应用于临床需进一步确定其安全性和有效性。     

肿瘤干细胞的耐药性与耐药机制

背景：肿瘤干细胞不仅与肿瘤的多药耐药性有密切的关系,而且有着复杂的多药耐药机制。 目的：对肿瘤干细胞及其耐药性和耐药机制的关系进行总结,为肿瘤的临床治疗提供新的思路。 方法：应用计算机检索FMJS和Pubmed西文数据库检索(2003/2010),以“cancer stem cell,multiple drug resistance,apoptosis,cell cycle”为检索词;用计算机检索万方数据库(2000/2010),CNKI数据库(2000-2010)以“肿瘤;肿瘤干细胞;多药耐药性”为关键词。共收集到中文文献56篇,外文文献372篇。排除发表时间早、重复及类似研究,纳入29篇符合标准的文献。 结果与结论：对干细胞的研究帮助人们加深对肿瘤的发生、发展及转移的认识。肿瘤组织中可能存在一小部分肿瘤细胞,与正常干细胞一样具有自我更新和无限增殖的能力,但具有特殊的耐药机制。肿瘤干细胞与肿瘤的发生及治疗关系密切。但针对肿瘤干细胞复杂的多药耐药机制尚有待进一步研究。     

1型糖尿病的干细胞治疗：可能成为临床之有效方案？

背景：如何让1型糖尿病达到完全治愈,受到了世界医学界的广泛关注。近年来随着干细胞的认识和不断发展,将干细胞用于1型糖尿病的治疗成为研究热点。 目的：综述近年来国内外1型糖尿病干细胞治疗的相关研究进展。 方法：应用计算机检索1997-01/2009-06 PubMed数据库(网址http://www.ncbi.nlm.nih.gov/PubMed)相关文章,检索词为“Type 1 diabetes,embryonic stem cells,pancreatic stem cells,mesenchymal stem cells,hematopoietic stem cells”,并限定文章语言种类为English。同时计算机检索1997-01/2009-06中国期刊全文数据库(网址http://www.wanfangdata.com.cn)相关文章,检索词为“1型糖尿病,胚胎干细胞,胰腺干细胞,间充质干细胞,造血干细胞”,并限定文章语言种类为中文。共检索到文献134篇。 结果与结论：1型糖尿病是T细胞介导的胰岛β细胞破坏的自身免疫性疾病,需应用外源性胰岛素来控制血糖,目前没有根治办法。干细胞是一类具有自我复制能力的多潜能细胞,能诱导分化成胰岛素分泌细胞,已经成为人们寻找诱导β细胞替代物的新资源。目前干细胞的研究可分为胚胎干细胞和成体干细胞。胚胎干细胞的研究大都是动物实验,在体内环境下的扩增和分化不易控制,且来源于胚胎,伦理学上未得到普遍认同,限制了临床研究。成体干细胞中研究较多的是胰腺干细胞、间充质干细胞和造血干细胞。胰腺干细胞没有明确的表面标志,取材困难,不易采集纯化,用于临床的难度较大;间充质干细胞的来源比较丰富,但对于它的跨胚层分化仍有争议,而且分化后的细胞在体内的功能维持时间还不确定;造血干细胞是目前研究最广泛、应用最成熟的成体干细胞,不仅来源丰富,易采集,而且能抑制自身排斥反应,拥有广泛的应用前景,必将成为1型糖尿病的研究热点。     

Denervation study of synapses of organ of corti of old world monkeys

Fine structural characteristics of synapses in the spiral organ of Corti were examined, with reference to differences between inner and outer haircell systems, and to location of neurons of origin of efferent axons. Surgical interruption of crossed olivocochlear bundle, of vestibular nerve, of facial nerve, and excision of superior cervical ganglia were used to determine the pathways of efferent axons. Interruption of the vestibular nerve near the brainstem results in degeneration of all efferent terminals on outer hair cells. Mid-line lesions at, and caudal to, the facial colliculus result in degeneration of about half of these efferent terminals. Efferent synaptic bulbs to the inner hair-cell system are small, of the order of one micron, and form type 2 junctions with afferent dendrites. They tend to have more large dense-core vesicles (about 80 nm) than the large efferent terminals of the outer hair-cell system, and appear to be the terminals of axons in the habenula perforata, which exhibit varicosities laden with large dense core vesicles. The varicosities are unaffected by excision of the superior cervical ganglia. So far as our material can reveal, it appears that the varicosities in the habenula perforata do not survive vestibular root interruption, nor do the efferent processes in the internal spiral bundle or at the base of inner hair cells. Most interestingly, the afferent processes of the inner hair-cell system, as identified for example by their relation to pre-synaptic bodies in the inner hair cells, are subject to a trans-synaptic reaction after severance of the vestibular root. They undergo a dramatic cytological transformation, characterized by increase of volume, engorgement with microtubules, microfilaments, microvesicles of various sizes, and clusters of lysosomes. Thus, both the efferent and afferent terminals of the inner hair-cell system show marked cytological differences from the corresponding terminals of the outer hair cell system.     

Mechanism of action of tubocurarine on nicotinic cholinoreceptors of neurons of the sympathetic ganglia of rats

Tubocurarine (Tc) effect on membrane currents elicited by acetylcholine (ACh) was studied in isolated superior cervical ganglion neurons of rat using patch-clamp method in the whole-cell recording mode. The "use-dependent" block of ACh current by Tc was revealed in the experiments with ACh applications, indicating that Tc blocked the channels opened by ACh. Mean lifetime of Tc-open channel complex, tau, was found to be 9.8 +/- 0.5 s (n = 7) at -50 mV and 20-24 degrees C. tau exponentially increased with membrane hyperpolarization (e-fold change in tau corresponded to the membrane potential shift by 61 mV). Inhibition of the ACh-induced current by Tc (3-30 microM/1) was completely abolished by membrane depolarization to the level of 80-100 mV. Inhibition of ACh-induced current was augmented at increased ACh doses. It is concluded that the open channel block produced by Tc is likely to be the only mechanism for Tc action on nicotinic acetylcholine receptors in superior cervical ganglion neurons of rat.     

The effect of age of onset of PD on risk of dementia

Background Dementia occurs in the majority of patients with Parkinson’s disease (PD). Late onset of PD has been reported to be associated with a higher risk for dementia. However, age at onset (AAO) and age at baseline assessment are often correlated. The aim of this study was to explore whether AAO of PD symptoms is a risk factor for dementia independent of the general effect of age. Methods Two community-based studies of PD in New York (n = 281) and Rogaland county, Norway (n = 227) and two population-based groups of healthy elderly from New York (n = 180) and Odense, Denmark (n = 2414) were followed prospectively for 3–4 years and assessed for dementia according to DSM-IIIR. All PD and control cases underwent neurological examination and were followed with neurological and neuropsychological assessments. We used Cox proportional hazards regression based on three different time scales to explore the effect of AAO of PD on risk of dementia, adjusting for age at baseline and other demographic and clinical variables. Findings In both PD groups and in the pooled analyses, there was a significant effect of age at baseline assessment on the time to develop dementia, but there was no effect of AAO independent of age itself. Consistent with these results, there was no increased relative effect of age on the time to develop dementia in PD cases compared with controls. Interpretation This study shows that it is the general effect of age, rather than AAO that is associated with incident dementia in subjects with PD. Received in revised form: 22 December 2005     

Limits of deinstitutionalization--perspectives of relatives of psychiatric patients

After a hopeful beginning, the social process of the reintegration of those with severe mental illness has come to a standstill. I am led to wonder whether "the community" really wants to live together with people suffering from severe mental illness, and if so, how closely? As long as the medical treatment of mental illness provided by the general practitioners is fundamentally deficient, as they are not able to prescribe the necessary interventions--such as out-patient psychiatric nursing, and service providers in the out-patient sector are content with offering increasingly intensive forms of care for the less seriously ill at the cost of the Social Welfare System--the reintegration of those with serious mental illness remains an illusion--which is mainly to the benefit of providers of residential care in homes and hostels.