Amyloid β-degrading cryptidases: insulin degrading enzyme, presequence peptidase, and neprilysin

The accumulation of aggregates of amyloidogenic peptides is associated with numerous human diseases. One well studied example is the association between deposition of amyloid beta (Abeta) and Alzheimer's disease. Insulin degrading enzyme and neprilysin are involved in the clearance of Abeta, and presequence peptidase is suggested to play a role in the degradation of mitochondrial Abeta. Recent structural analyses reveal that these three peptidases contain a catalytic chamber (crypt) that selectively encapsulates and cleaves amyloidogenic peptides, hence the name cryptidase. The substrate selectivity of these cryptidases is determined by the size and charge distribution of their crypt as well as the conformational flexibility of substrates. The interaction of Abeta with the catalytic core of these cryptidases is controlled by conformational changes that make the catalytic chambers accessible for Abeta binding. These new structural and biochemical insights into cryptidases provide potential therapeutic strategies for the control of Abeta clearance.     

A combined artificial chromosome-stem cell therapy method in a model experiment aimed at the treatment of Krabbe’s disease in the Twitcher mouse

Mammalian artificial chromosomes (MACs) are safe, stable, non-integrating genetic vectors with almost unlimited therapeutic transgene-carrying capacity. The combination of MAC and stem cell technologies offers a new strategy for stem cell-based therapy, the efficacy of which was confirmed and validated by using a mouse model of a devastating monogenic disease, galactocerebrosidase deficiency (Krabbe’s disease). Therapeutic MACs were generated by sequence-specific loading of galactocerebrosidase transgenes into a platform MAC, and stable, pluripotent mouse embryonic stem cell lines were established with these chromosomes. The transgenic stem cells were thoroughly characterized and used to produce chimeric mice on the mutant genetic background. The lifespan of these chimeras was increased twofold, verifying the feasibility of the development of MAC-stem cell systems for the delivery of therapeutic genes in stem cells to treat genetic diseases and cancers, and to produce cell types for cell replacement therapies. Received 29 July 2008; received after revision 22 September 2008; accepted 24 September 2008     

脂质体作为钆中子俘获治疗肿瘤药物载体的跨膜动力学及机理研究

制备和表征了包埋Gd-EDTA的脂质体,测定了pH,离子强度,缓冲液组成及温度对Gd-EDTA脂质体的影响,比较了Gd-EDTA脂质体和Gd-EDTA被肿瘤细胞摄入的动力学曲线。结果表明,Gd-EDTA脂质体在37℃和生理条件下最稳定,肿瘤细胞摄入Gd-EDTA脂质体速率是Gd-EDTA的8倍,而释放Gd的速率,Gd-EDTA脂质体远远低于Gd-EDTA,这些结果提供了脂质体包埋Gd-EDTA作为钆中子俘获治疗药物的可能性。     

R—藻红蛋白光动力杀伤的形态学机制研究

在荧光显微镜下观察新型光敏剂Ｒ藻红蛋白的荧光在肿瘤细胞中的分布,探讨以藻红蛋白为光敏药物的光动力损伤可能发生的细胞水平机制,以及培养液酸度和藻红蛋白浓度对其与细胞结合、进入及光动力杀伤的关系．结果表明在ｐＨ５ 时,藻红蛋白与瘤细胞有最好的结合．其结合部位随藻红蛋白浓度的增加,逐渐以分布在胞膜、胞浆和胞核为主,表现为一个动态进入细胞的过程．光动力杀伤作用与其进入细胞的数量成正相关,从形态学上证明了Ｒ藻红蛋白介导的光动力治疗作用与藻红蛋白进入瘤细胞状态紧密相关．     

基因治疗及其研究进展情况

本文综述了基因治疗的步骤,基因治疗的对象及基因治疗的现状及前景。基因治疗的步骤包括基因诊断;治疗基因与载体的连接;基因转移。其中载体是基因治疗中的一个重大关键技术问题。目前基因治疗已进入理性化阶段,世界上许多国家对基因治疗前景看好,投资加强。     

Photophysics, photochemistry and photobiology of hypocrellin photosensitizers

Hypocrellins are novel photosensitizers from China, which are demonstrated to have significant anti- tumor and anti-virus activity and to be potential photo- dynamic therapy (PDT) agents. As compared with hemato- porphyrin, the only approved photosensitizer, hypocrellins have several advantages, such as easy preparation and easy purification, high triplet quantum yield, high singlet-oxygen quantum yield, high phototoxicity but low dark toxicity, and rapid clearance from normal issues. This article reviews briefly the photophysics, photochemistry and photobiology of hypocrellins on the basis of the domestic and international research results.     

泡沫封堵能力试验研究

借助岩心驱替流程试验,研究了含油模型水驱之后注泡沫、复合泡沫及聚合物驱后注单一泡沫、复合泡沫的泡沫体系封堵能力,结果表明,单一泡沫驱在水驱残余油条件下,难以形成有效的封堵,而复合泡沫体系在各种残余油条件下均能形成有效的封堵调剖能力,证明复合泡沫体系是一种性能良好的调剖驱油剂。     

二乙二醇乙醚—异氰酸酯封端反应

对二乙二醇乙醚与２,４－甲 二异氰酸酯的封端反应进行了研究,探讨了温度、催化剂及溶剂等对封端反应的影响,利用经外光谱和ＤＳＣ等分析手段进行了表征,结果表明,利用二乙二醇乙醚对２,４－甲苯二异氰酸酯的反应进行顺利,解封温度适中。     

Ca_3(PO_4)_2和Ca_5(PO_4)_3(OH)的表面处理及血液相容性

根据含32 P复合新型材料应用于内辐射治疗肿瘤的设想 ,以非标P模拟32 P ,用IR、接触角测定、复钙时间测试等方法研究了Ca3(PO4) 2 和Ca5(PO4) 3(OH)粉末的表面处理的效果、泄漏情况及血液相容性 结果表明 :Ca3(PO4) 2 和Ca5(PO4) 3(OH)粉末经硅烷偶联剂KH - 570处理后 ,表面形成偶联剂膜 ,有效提高粉末的疏水性 ,并明显降低P在水中的溶出量 ;同时可以提高粉末的血液相容性 ;当KH - 570溶液的浓度为 1 5%～ 2 0 % ,且KH - 570用量是粉末的 2phr时 ,表面处理的效果较佳     

Modifiers of radiosensitivity

Conclusion Many different methods exist by which the radiosensitivity of cells, and hence of normal tissues and tumours, can be manipulated. Several of these can be traced to a common redox pathway involving competition between oxidising and reducing species. Others involve the biochemical enzyme systems required for removal of DNA lesions. At the present time most of these approaches are still actively undergoing basic research studies and have not found full application in cancer clinics. For any such approach to be of therapeutic use there must be a rationale for a differential effectiveness in tumours and normal tissues.