核酶在AIDS基因治疗中的研究新进展

利用核酶的核心酸内切酶活性将核酶应用于AIDS基因治疗的研究，近几年来有了许多新的突破，本文主要在核酶作用的位点、载体选择和宿主细胞选择及提高核酶作用有效率等方面对这一领域中新的研究进展作一综述性介绍。     

基因治疗研究中的一些基本问题

基因治疗研究中的一些基本问题郑冰，邱信芳自１９９０年９月１４日首次对一例由于腺苷脱氨酶（ＡＤＡ）缺乏而患有重症联合性免疫缺陷症的４岁女孩进行临床基因治疗获得成功以来，基因治疗在短短的３年多时间里有了飞速的发展。到１９９４年６月为止，共有６３种临床方案...     

周围神经损伤与再生中的巨噬细胞

非神经细胞在周围神经损伤和再生中的作用早已引起人们的关注。近年来 ,越来越多的学者对神经损伤和再生中的巨噬细胞进行了有关的研究 ,使人们对巨噬细胞在这一过程中的聚集、识别、吞噬及其与轴突再生、其他非神经元细胞间的关系有了更深入的认识。本文谨对目前有关这方面的研究作一简要综述。1.　巨噬细胞在周围神经损伤和再生过程中的趋化聚集众所周知 ,非神经组织在受到炎性刺激时 ,中性粒细胞的数量在 1～ 2 h内激增 ,6 h达到高峰 ,然后开始下降。巨噬细胞的反应同中性粒细胞相似 ,只是较中性粒细胞少 ,且在组织中持续的时间较粒细胞…     

损伤后中枢神经元nNOS基因表达调节的意义

一氧化氮合酶(NOS)是催化L-精氨酸转化为一氧化氮(NO)的唯一限速酶,分为神经元型(nNOS),内皮型(eNOS)和诱导型(iNOS)。三种类型的NOS都广泛存在于中枢神经系统,nNOS主要存在于神经元,在多数情况下低水平表达,调节许多正常的生理功能,机体一旦受到病理性刺激,nNOS即可大量生成,催化产生的NO对神经元具有保护或损伤的双重作用,本文就中枢神经损伤时nNOS基因表达的意义做一综述。     

杆状病毒在基因治疗中的应用进展

基因治疗的核心技术之一是获得高效、安全的基因转移载体.目前的非病毒载体(脂质体、多聚物、纳米载体等)和病毒载体(腺病毒、腺相关病毒、疱疹病毒和逆转录病毒等)都还各自存在着某些缺陷,而杆状病毒由于安全性高、可插入基因片段大、操作性好等优点展现了在基因治疗中的巨大应用前景,开辟了杆状病毒应用的新领域[1].就杆状病毒作为基因载体在体内外和癌症基因治疗中的应用进展及其相关问题(如介导体内基因表达时遇到的障碍和解决措施等)作一综述.     

脂质体在基因治疗中的应用及前景

脂质体作为基因的运载工具，用于基因治疗，具有无毒性，无致瘤性等优点，这是逆转录病毒载体等不可比拟的，脂质体是一种具有广泛应用前景的体内基因转移的工具。本文总结的近几年来应用脂质体进行体内外基因转移的研究进展，并归纳了几种提高脂质体转化效率和通过毛细血管进入淋巴组织效率的方法。     

基因治疗在肝脏移植中的应用进展

基因治疗应用于动物肝移植的研究已经具有可行性,有望在减少移植排异、诱导免疫耐受等方面取得突破,从而提高移植肝的存活时间,推动肝移植的发展.     

基因治疗在肌腱愈合中的应用

肌腱损伤修复后,常因肌腱粘连而导致功能障碍,这是目前尚未解决的一个难题。随着分子生物学理论的发展,人们对生物组织中部分基因的调控、表达和蛋白质的合成过程,以及在肌腱愈合过程中对肌腱的形态和生物力学特性的影响有了一定的认识[1]。对肌腱愈合机制的研究已经进入基因水平。本文就这方面的研究进展进行综述。1基因治疗概述基因治疗就是将外源基因导入靶细胞并有效表达,从而达到治疗疾病的目的。根据对宿主病变细胞基因采取的措施不同,基因治疗分为基因置换,基因修正,基因增量和基因失活。在基因治疗中,载体和转移方法是比较重要的两…     

基因治疗在自身免疫疾病研究中的应用

基因治疗是20世纪90年代出现的一种新型治疗技术，它的发展为现代治疗学开辟了一条新的途径。自身免疫病是由于自身免疫系统紊乱而引起的，对自身免疫病的基因治疗工作现阶段聚焦在自身免疫病致病机理的研究上，通过树突状细胞和抗原特异性T细胞作为输送媒介，目前已经获得了可靠的、有效的和靶定的基因治疗结果。     

蛋白转导在基因治疗中的应用

蛋白转导是近几年生命科学领域发现的一种独特现象,具有蛋白转导功能的蛋白通过几个短的碱性小肽组成的蛋白转导域(proteintransductiondomain,PTD)的介导,能将与其共价连接的DNA、多肽或蛋白质以及其他大分子物质通过非经典途径穿过细胞膜甚至血脑屏障,并在细胞间自由传递。PTD这种能携带融合蛋白自由进入细胞的独特功能为人类一些疾病的基因治疗提供了一种新的运载工具,在基因治疗中有着美妙的应用前景。     

中枢神经系统疾病的基因治疗

基因治疗正在成为常规方法难以治愈的中枢神经系统疾病的新的治疗手段。本文概要介绍了中枢神经系统疾病基因治疗的方法和途径；中枢神经系统疾病基因治疗的病毒载体以及目前中枢神经系统疾病基因治疗研究的状况。     

Immune response after central nervous system injury

Traumatic injuries of the central nervous system (CNS) affect millions of people worldwide, and they can lead to severely damaging consequences such as permanent disability and paralysis. Multiple factors can obstruct recovery after CNS injury. One of the most significant is the progressive neuronal death that follows the initial mechanical impact, leading to the loss of undamaged cells via a process termed secondary neurodegeneration. Efforts to define treatments that limit the spread of damage, while important, have been largely ineffectual owing to gaps in the mechanistic understanding that underlies the persisting neuronal cell death. Inflammation, with its influx of immune cells that occurs shortly after injury, has been associated with secondary neurodegeneration. However, the role of the immune system after CNS injury is far more complex. Studies have indicated that the immune response after CNS injury is detrimental, owing to immune cell-produced factors (e.g., pro-inflammatory cytokines, free radicals, neurotoxic glutamate) that worsen tissue damage. Our lab and others have also demonstrated the beneficial immune response that occurs after CNS injury, with the release of growth factors such as brain-derived growth factor (BDNF) and interleukin (IL-10) and the clearance of apoptotic and myelin debris by immune cells^1–4. In this review, we first discuss the multifaceted roles of the immune system after CNS injury. We then speculate on how advancements in single-cell RNA technologies can dramatically change our understanding of the immune response, how the spinal cord meninges serve as an important site for hosting immunological processes critical for recovery, and how the origin of peripherally recruited immune cells impacts their function in the injured CNS.     

The survivability time of central nervous system cells]

Our investigations show that vital functions of some neurons and glial cells may survive for 4-8 hours after death and disappear in parallel with destructive changes in cells. Up-to-date morphological techniques demonstrate that neurons and other cells of the CNS preserve biological activity not for several minutes as believed so far but up to 4-8 hours. It is too early to judge about functional importance of this phenomenon and further investigations into this problem are necessary. Temporal parameters of RNA synthesis in the brain cells give additional knowledge about CNS cells survival and this may be of interest for reanimatology and transplantology.     

Mechanisms of injury in the central nervous system

Neurotoxicants with similar structural features or common mechanisms of chemical action frequently produce widely divergent neuropathologic outcomes. Methylmercury (MeHg) produces marked cerebellar dysmorphogenesis during critical periods of development. The pathologic picture is characterized by complete architectural disruption of neuronal elements within the cerebellum. MeHg binds strongly to protein and soluble sulphydryl groups. Binding to microtubular -SH groups results in catastrophic depolymerization of immature tyrosinated microtubules. However, more mature acetylated microtubules are resistant to MeHg-induced depolymerization. In contrast to MeHg, the structurally similar organotin trimethyltin (TMT) elicits specific apoptotic destruction of pyramidal neurons in the CA3 region of the hippocampus and in other limbic structures. Expression of the phylogenetically conserved protein stannin is required for development of TMT-induced lesions. Inhibition of expression using antisense oligonucleotides against stannin protects neurons from the effects of TMT, suggesting that this protein is required for expression of neurotoxicity. However, expression of stannin alone is insufficient for induction of apoptotic pathways in neuronal populations. The aromatic nitrocompound 1,3-dinitrobenzene (DNB) has 2 independent nitro groups that can redox cycle in the presence of molecular oxygen. Despite its ability to deplete neural glutathione stores, DNB produces edematous gliovascular lesions in the brain stem of rats. Glial cells are susceptible despite high concentrations of reduced glutathione compared with neuronal somata in the central nervous system (CNS). The severity of lesions produced by DNB is modulated by the activity of neurons in the affected pathways. The inherent discrepancy between susceptibility of neuronal and glial cell populations is likely mediated by differential control of the mitochondrial permeability transition in astrocytes and neurons. Lessons learned in the mechanistic investigation of neurotoxicants suggest caution in the evaluation and interpretation of structure-activity relationships, eg, TMT, MeHg, and DNB all induce oxidative stress, whereas TMT and triethyltin produce neuronal damage and myelin edema, respectively. The precise CNS molecular targets of cell-specific lipophilic neurotoxicants remain to be determined.     

Nestin in central nervous system cells

This literature review reflects current knowledge on the intermediate filament protein nestin, which most authors regard as a marker of “neural stem/progenitor cells.” The structural-functional characteristics of nestin and its presence in various central nervous system cells at different stages of ontogenesis in normal and pathological conditions are discussed. __________ Translated from Morfologiya, Vol. 131, No. 1, pp. 85–90, January–February, 2007. Director: Corresponding Member of the Russian Academy of Medical Sciences Professor V. A. Otellin     

小胶质细胞对坐骨神经损伤后的反应

目的 探讨对小细胞对周围神经损伤的反应。方法 用Thymosin β4抗体标汜小胶质细胞,在大鼠坐骨神经切断后1、2、3、4、6、8、10、12、14、18、20d,检测其脊髓及脑干内小胶质细胞、并对有变化者用电镜观察。结果 发现在坐骨神经损伤后第1天开始至第20天,在相应脊髓节段同侧灰质及脑干的薄束核内见到许多体积增大、数量增多的Thymosin β4标记阳性细胞即激活的小胶质细胞。激活的小胶质细胞数量在损伤后第3天达到高峰,然后逐渐下降,至第20天后才消失;与相应脊髓节段相比较,薄束核内激活的小胶质细胞数量要少些。电镜观察发现,这些激活的小胶质细胞多位于神经元胞体的周围并与神经元有密切的接触。结论 周围神经损伤,可引起相应中枢部位的小胶质细胞激活与增殖．其作用可能与保护受损的神经元、维护神经元的周围环境有关。     

Involvement of inflammatory cytokines in central nervous system injury

Pro-inflammatory cytokines, interleukin (IL) 1 and tumor necrosis factor (TNF), possess a wide range of biological actions in various tissues. In recent years, there has been increasing evidence that these cytokines are involved in inflammatory reactions in central nervous system (CNS) diseases. Although many studies have demonstrated that IL-1, TNF, and their mRNA are up-regulated in the CNS after injury, the functional roles of these cytokines in the injury are far from completely understood. Overexpression of these cytokines, such as observed during the early stage of injury, can be harmful for the injured tissue. However, low levels of these cytokines, observed during the recovery stage after injury, can enhance repair processes of the injured tissues.     

Birth injury of the cranium and central nervous system

Abstract Birth injury of the scalp, skull and central nervous system (CNS) is a well-recognized complication of a difficult delivery. The rate of birth trauma has dropped precipitously and now accounts for less than 2% of neonatal deaths. Despite this dramatic decrease in birth-trauma mortality significant injuries still occur. A variety of risk factors clearly predispose certain infants to birth-related injury. Recent neuroradiology studies indicate that intracranial hemorrhage, even in asymptomatic infants, is not rare. Pathologists' (neuropathologists and forensic pathologists) appreciation of the spectrum of birth injuries and their sequelae is critical in order to be able to distinguish these from inflicted injuries and post-mortem changes.