Evaluation of DNA binding, DNA cleavage, protein binding and in vitro cytotoxic activities of bivalent transition metal hydrazone complexes

Divalent Co, Ni and Cu hydrazone complexes containing [N′-(phenyl(pyridine-2-yl)methylidene) benzohydrazide] ligand were synthesised and characterised. Interactions of these complexes with DNA revealed an intercalative mode of binding between them. Further, all the hydrazone chelates showed moderate ability to cleave pUC19 DNA. Synchronous fluorescence spectra proved that the interaction of metal complexes with bovine serum albumin (BSA) resulted in a conformational change of the latter. Assay on the cytotoxicity of the above complexes against HeLa tumor cells and NIH 3T3 normal cells revealed that the complexes are toxic only against tumor cells but not to normal cells. In all the biological assays, the complex with copper ion as the metal center showed enhanced activities than the other two.     

Immunogenic characterization and protection against Streptococcus mutans infection induced by intranasal DNA prime–protein boost immunization

Mucosal immune responses act as the first line of defense against dental caries. In this study, an optimal vaccination strategy was developed to enhance anti-caries mucosal immune responses. Mice and rats were vaccinated intranasally firstly with plasmid pCIA-P encoding PAc antigen of Streptococcus mutans and then with rPAc, or with pCIA-P for twice, or with rPAc protein for twice, respectively. The potential of inducing mucosal and systemic immune responses to special antigens was measured by ELISA. In addition, antibody type, cytokine production and protection effectiveness against dental caries were also evaluated. Although all immunized groups developed immune responses, the antibody responses in the DNA prime–protein boost group were stronger compared with those elicited by either the DNA vaccine or the protein vaccine. In particular, the Th1-biased response that was established by the DNA immunization was diverted to Th1/Th2-mixed response following the rPAc protein boost. Moreover, protection against S. mutans challenge was obtained in the rats treated with the DNA prime–protein boost regimen, as shown by a significant reduction in dental caries lesion, compared with the control groups immunized with the DNA or protein only. All these findings may provide useful information about effective mucosal vaccines against dental caries.     

DNA芯片(DNA chip)

一种通过光刻技术或其他技术将DNA片段或基因集成在固体基底(玻璃或尼龙、硅片)表面而形成的阵列.通常1cm2的阵列可包含几百、几千甚至几万个DNA片段,故也叫微阵列(microarray).它是分子生物学和微加工技术进步的产物. DNA芯片在生命科学研究中发挥着重要的作用.其应用范围涉及:基因表达谱分析、基因突变检测、DNA(基因)序列测定、疾病机理分析、疾病诊断、药物筛选、环境因素对机体的作用机理、毒物基因组学、食品卫生、病原体检测和生物样品的制备等.此外,它还将生命科学中许多不连续的过程如样品制备、化学反应和检测等步骤在芯片上实现其连续和微型化,建立缩微芯片实验室(Lab-on-A-chip). DNA芯片与PCR芯片、毛细管电泳芯片及介电电泳芯片等一起通称生物芯片(biochip). (本文编辑:邵隽一)     

DNA微阵列(DNA microarrays)

一种mRNA表达得高通量差异筛选工具。将cDNA或寡核苷酸文库高密度地固定在微芯片上 ,与由 2种不同细胞群体产生的荧光标记cDNA混合物进行杂交 ,最后由激光共聚焦扫描仪分析结果。DNA微阵列可用于监测不同生理与病例状态下的基因表达谱 ,研制新药和研究药理与毒理 ,研究环境因素与基因的交互作用 ,以及临床检验等等用途。DNA微阵列(DNA microarrays)@方福德!100005北京$中国医学科学院基础医学研究所     

DNA拓扑异构酶（DNA topoisomerase）

能够将线状、环状、单链或双链DNA分子进行拓扑变换（引入正超螺旋或负超螺旋）的酶，为DNA复制所必需。该酶的作用大致相当于核酸内切酶和连接酶作用的总和。DNA拓扑异构酶有两型：Ⅰ型能将DNA超螺旋的一条链暂时性切断，使链的末端沿着螺旋轴转动从而使超螺旋得到松弛，然后再把单链切口连接起来，作用过程中不需ATP供能。Ⅱ型能将DNA双链暂时性切断，将负超螺旋引入，     

DNA加合物

ＤＮＡ加合物（ＤＮＡ－ａｄｄｕｃｔ）　亦称ＤＮＡ加成物。进入机体的许多致癌物,由于其自身理化性状,而无法与ＤＮＡ直接结合,需经生物体内氧化酶的作用,转变为有活性的代谢产物,再与ＤＮＡ发生化学加成反应,该反应形成的产物,即称ＤＮＡ加合物。如苯－ＤＮＡ加合物等（文钊　供稿　参考文献：方福德编著．医学分子生物学词典．北京医科大学．中国协和医科大学联合出版社,１９９６∶１１）DNA加合物     

DNA硬盘

来自哈佛大学维斯生物工程研究所的科学家们，将大约5．34万个单词的书——《再生》，编码到了DNA序列中，连同一起的还有11张JPG格式的图片和一段程序。然后，他们用DNA测序来阅读这本书。他们的实验证实，DNA能够被用来长期存储数字信息。     

破译DNA

在涉及克隆、基因、遗传等有关人类繁衍的生命话题时,有一个英文名词会频频显现,那就是"DNA"。DNA 是什么?它对人类到底有些什么影响……     

DNA疫苗

本文介绍了 DNA疫苗的特性及其引起免疫应答的性质 ,影响疫苗效果的若干因素及应用前景。 DNA疫苗能引起强而持久的细胞免疫及体液免疫。它诱导 MHC- 限制的 CD8 T细胞的 CTL反应及 MHC- 限制CD4 T细胞的 Th1反应 ,并能激活 B细胞产生中和抗体。 DNA疫苗既可用于预防 ,亦可用于治疗 ,可应用于感染性疾病、变态反应及癌肿的防治。     

DNA芯片

一种通过光刻技术或其他技术将ＤＮＡ片段或基因集成在固体基底 (玻璃或尼龙、硅片 )表面而形成的阵列。通常1ｃｍ2 的阵列可包含几百、几千甚至几万个ＤＮＡ片段 ,故也叫微阵列 (ｍｉｃｒｏａｒｒａｙ)。它是分子生物学和微加工技术进步的产物。ＤＮＡ芯片在生命科学研究中发挥着重要的作用。其应用范围涉及 :基因表达谱分析、基因突变检测、ＤＮＡ(基因 )序列测定、疾病机理分析、疾病诊断、药物筛选、环境因素对机体的作用机理、毒物基因组学、食品卫生、病原体检测和生物样品的制备等。此外 ,它还将生命科学研究中许多不连续的过程如样…     

DNA疫苗

ＤＮＡ疫苗是近年来发展起来的新型疫苗,它是指将含有编码抗原基因的真核表达质粒经直接接种体内后,被体细胞摄取,并表达出相应的抗原,然后激发机体产生保护性免疫。1　ＤＮＡ疫苗的优越性自Ｕｌｍｅｒ等发现裸ＤＮＡ经肌肉接种可引发机体免疫反应之后,ＤＮＡ疫苗的研究被广泛开展。对有些疾病如乙型病毒性肝炎和艾滋病方面已积累了丰富的数据【1～5】,对某些肿瘤的防治也有很大进展。它与一般疫苗相比较具有以下优点:(1)可提供天然的抗原形式,被机体免疫系统识别而产生中和抗体。一次注射即可诱导长期或终生免疫。(2)全面激活机体免疫应答,…     

Safety and immunogenicity of pneumococcal protein vaccine candidates: Monovalent choline-binding protein A (PcpA) vaccine and bivalent PcpA–pneumococcal histidine triad protein D vaccine

Background

Pneumococcal vaccines based on protein antigens may provide expanded protection against Streptococcus pneumoniae.

Objective

To evaluate safety and immunogenicity in adults of pneumococcal vaccine candidates comprising S. pneumoniae pneumococcal histidine triad protein D (PhtD) and pneumococcal choline-binding protein A (PcpA) in monovalent and bivalent formulations.

Methods

This was a phase I, randomized, observer-blinded, placebo-controlled, step-wise dose-escalation study. Following a pilot safety study in which participants received one intramuscular injection of either aluminum hydroxide (AH)–adjuvanted PcpA (25 μg) or PhtD–PcpA (10 μg each), participants in the main study received AH–adjuvanted PcpA (25 μg), AH–adjuvanted PhtD–PcpA (10, 25, or 50 μg each), unadjuvanted PhtD–PcpA (25 μg each), or placebo as 2 injections 30 days apart. Assignment of successive dose cohorts was made after blinded safety reviews after each dose level. Safety endpoints included rates of solicited injection site and systemic reactions, unsolicited adverse events (AEs), serious AEs (SAEs), and safety laboratory tests. Immunogenicity endpoints included levels of anti-PhtD and anti-PcpA antibodies (ELISA).

Results

Six adults 18–50 years of age were included in the pilot study and 125 in the main study. No obvious increases in solicited reactions or unsolicited AEs were reported with escalating doses (adjuvanted vaccine) after either injection, or with repeated administration. Adjuvanted vaccine candidates were associated with a higher incidence of solicited reactions (particularly injection site reactions) than unadjuvanted vaccine candidates. However, no SAE or discontinuation due to an AE occurred. Geometric mean concentrations of anti-PhtD IgG and anti-PcpA IgG increased significantly after injection 2 compared with injection 1 at each dose level. No enhancement of immune responses was shown with adjuvanted vaccine candidates compared with the unadjuvanted vaccine candidate. In the dose-escalating comparison, a plateau effect at the 25 μg dose was observed as measured by geometric mean concentrations and by fold increases.

Conclusions

Promising safety profiles and immunogenicity of these monovalent and bivalent protein vaccine candidates were demonstrated in an adult population (ClinicalTrials.gov registry no. NCT01444339).     

DNA浓缩液在HBV DNA检测中的价值

目前检测HBV DNA浓度广泛应用实时荧光定量PCR技术,该方法具有高敏感性、特异性和重复性。在样品前处理中,HBV DNA提取多采用热裂解法,但一些病例抗HBc lgG与抗HBc lgM同时阳性且肝功能有不同程度的异常,而HBV DNA却是阴性,为使低拷贝DNA样品不致漏诊,本文在DNA提取中,加入了DN     

Clara cell protein and surfactant protein B in garbage collectors and in wastewater workers exposed to bioaerosols

Objectives: Inhalation of bioaerosols has been hypothesised to cause toxic pneumonitis that should increase lung epithelial permeability at the bronchioloalveolar level. Serum Clara cell protein (CC16) and serum surfactant protein B (SPB) have been proposed as sensitive markers of lung epithelial injury. This study was aimed at looking for increased lung epithelial permeability by determining CC16 and SPB in workers exposed to bioaerosols from wastewater or garbage. Methods: Subjects (778 wastewater, garbage and control workers; participation 61%) underwent a medical examination, lung function tests [American Thoracic Society (ATS) criteria], and determination of CC16 and SPB. Symptoms of endotoxin exposure and several potential confounders (age, gender, smoking, kidney function, obesity) were looked for. Results were examined with multiple linear or logistic regression. Results: Exposure to bioaerosols increased CC16 concentration in the wastewater workers. No effect of exposure on SPB was found. No clue to work-related respiratory diseases was found. Conclusions: The increase in CC16 in serum supports the hypothesis that bioaerosols cause subclinical toxic pneumonitis, even at low exposure.     

DNA条形码识别——DNA条形码与DNA芯片识别蚊媒准确性的比较

〔目的〕比较DNA条形码和DNA芯片这2种技术平台在口岸医学媒介蚊类识别中的准确性。〔方法〕以20种媒介蚊类的线粒体COI基因序列信息为分析对象,采用NJ邻接法计算公认的DNA条形码区域在物种识别中的准确性,采用DNA芯片技术分析2种长度探针在物种水平识别中的差异。〔结果〕DNA条形码的准确性为98.5%,数据集中95%物种的唯一序列最短长度为50bp左右;DNA芯片的准确性为90%～98.4%,25bp探针比55bp探针更具优势。〔结论〕DNA条形码和DNA芯片都能够准确地识别20种媒介蚊类,DNA条形码芯片技术有望在口岸出入境检验检疫领域得到应用。     

应用DNA分子杂交技术检测乙型肝炎病毒DNA

近年来,由于基因工程技术发展,推动了病毒分子生物学技术的进步。DNA分子探针诊断技术是应用HBV—DNA拼接在大肠杆菌的质粒建立起无性繁殖体系,使HBV—DNA能得到大量复制,并能获得纯系的DNA分子供标记探针应用。由于DNA分子杂交只和同源     

DNA加合物研究进展

据统计，人类每年合成数以千计的新化合物并排放到环境之中，这些化合物许多具有遗传毒性。如何对这些化学物质进行监测和评价是一项十分艰难而重要的工作。用检测周围媒体（大气、水、土壤等）中化合物含量水平来评价有毒物和人体健康之间的关系是不够的，因为这种外剂量...     

法庭上的DNA

DNA即脱氧核糖核酸,它是一种遗传物质,主要存在细胞核中并与组织蛋白结合集中于染色体内。生物细胞的遗传信息就存在于DNA分子众多的基因中间,DNA链上的碱基顺序不同便决定了基因的差异。DNA分子具备无限的生物信息储存能力,它能在生物体生长、发育过程中准确无误地自我复制,并按可靠的遗传原则代代相传,