线粒体DNA突变与衰老关系的研究进展

衰老的分子机制复杂,目前的研究尚未能对衰老的关键轴心获得一致而明晰的理论认识,各种衰老假说相继被提出,其中具有代表性的为端粒学说。端粒-p53-线粒体衰老轴线自从被提出,已经获得越来越多的实验论证,较多的研究也表明线粒体DNA突变与衰老有着密切的相关性,但突变与衰老之间的因果关系存在较大争议。我们简要综述了近年来线粒体DNA突变与衰老关系的相关研究进展。     

线粒体DNA异常与肿瘤

能量代谢重编程是肿瘤细胞一个重要的标志特征,而由线粒体DNA(mitochondrial DNA,mtDNA)结构及功能异常引起的线粒体功能障碍是其机制之一。人类mtDNA为位于线粒体基质中由16569bp组成的双链闭合环状分子,编码与氧化磷酸化电子传递链相关的13种多肽以及与线粒体蛋白合成相关的22种tRNA和2种rRNA。近年来,人们发现多种肿瘤组织及细胞中存在mtDNA序列的多类型突变或拷贝数的变异,且mtDNA的这些异常与肿瘤的发生发展、早期诊断及放化疗监测等密切相关。异常的mtDNA因削弱线粒体产能、增加细胞内活性氧(reactive oxygen species,ROS)水平、打破Ca2+稳态,从而赋予肿瘤细胞代谢重编程、凋亡抵抗等侵袭性进程。针对mtDNA异常在肿瘤发生发展中的作用及机制研究,将为肿瘤的早期诊断及靶向治疗提供新的策略。     

线粒体DNA与DNA甲基化的关系

线粒体DNA（mitochondrial DNA,mtDNA）遗传信息量虽小,却控制着线粒体一些最基本的性质,对细胞及其功能有着重要影响。mtDNA的损伤与衰老、肿瘤等疾病的发生有关。DNA甲基化是调节基因表达的重要方式之一。mtDNA基因的表达受核DNA（nuclear DNA,nDNA）的调控,mtDNA和nDNA协同作用参与机体代谢调节和发病。本文就近年来mtDNA与DNA甲基化的关系作一综述。     

DNA甲基转移酶与肿瘤关系的研究进展

DNA甲基化修饰在基因的表观遗传调控中发挥重要作用,而DNA甲基转移酶(DNMT)为DNA甲基化模式建立和维持所必需。哺乳动物细胞主要含3种DNMT,DNMT1的主要功能是维持甲基化,DNMT3a和DNMT3b则催化DNA的从头甲基化。DNMT活性与功能改变导致的基因表达异常与多种肿瘤的发生和发展密切相关,由此成为肿瘤治疗和新型抗肿瘤药物研发的重要分子靶点。     

家蚕微卫星DNA的研究进展

概述了分子标记技术,就其中的微卫星标记技术的原理、方法与特点进行了介绍,重点就该技术在家蚕中的研究进展进行了综述,并展望了该技术在家蚕的遗传分析、辅助选择育种等应用中的前景。     

线粒体DNA甲基化研究进展

DNA甲基化是表观遗传修饰的重要方式之一.线粒体是真核细胞内的关键细胞器,线粒体DNA(mt DNA)编码部分线粒体基因,其mt DNA的甲基化修饰可能引起所编码基因的异常表达,从而参与调节生理和病理过程.本文就目前mt DNA甲基化及其在疾病中的研究进展进行总结.     

线粒体DNA突变与肿瘤发生的关系

线粒体DNA（mitochondrial DNA,mtDNA）是真核细胞内的核外遗传物质。事实证明,由于线粒体特殊的生物学结构与功能,和核基因（nDNA）相比,mtDNA更容易发生突变和氧化损伤。目前研究已经发现许多肿瘤组织中mtDNA结构和拷贝量发生了变化。文章主要对mtDNA突变、整合和不稳定性与肿瘤发生的关系以及可能的机理进行了综述。     

原生动物线粒体DNA的研究进展

目前已完成了多种原生动物mtDNA全序列的测定,对线粒体基因组有了较全面和深入的认识。本文总结了原生动物线粒体基因组结构、基因组成及基因表达等方面的研究进展,有助于进一步了解原始线粒体基因组的组成及其mtDNA进化,并为细胞的起源和真核生物进化的研究提供有价值的线索。     

胃癌和甲状腺疾病相关性研究进展

胃癌是我国常见的恶性肿瘤之一。多种因素与胃癌的发生相关,如环境、饮食、幽门螺杆菌感染、慢性萎缩性胃炎和肠上皮化生等。随着对胃癌研究的深入,国外学者发现胃癌的发病率在碘摄入不足或者摄入过多的地区有逐渐增高的趋势,而碘是甲状腺疾病发病的重要因素。最新的研究发现,胃癌和甲状腺疾病的关系可能受到地域因素的影响,但目前缺乏对此关系的大样本临床研究。本文试对这些研究的最新进展作一综述。     

miRNA 与胃癌的关系研究进展

微小RNA(miRNA)是长度为22nt左右的非编码RNA,具有转录后调节的功能,对细胞的增殖、凋亡和分化起到重要作用。胃癌是世界第四大常见肿瘤,高居癌症死亡的第二位。越来越多的研究表明miRNA在肿瘤中起着原癌基因或抑癌基因的作用,本文将阐述miRNA与胃癌的关系的研究进展。     

miRNA与胃癌的关系研究进展

微小RNA（miRNA）是长度为22nt左右的非编码RNA,具有转录后调节的功能,对细胞的增殖、凋亡和分化起到重要作用。胃癌是世界第四大常见肿瘤,高居癌症死亡的第二位。越来越多的研究表明miRNA在肿瘤中起着原癌基因或抑癌基因的作用,本文将阐述miRNA与胃癌的关系的研究进展。     

The relationship between microsatellite polymorphism and recombination hot spots in the human genome

Although previous studies have failed to detect an association between microsatellite polymorphism and broadscale recombination rates in the human genome, there are several possible reasons why such a relationship could exist. For instance, there might be a direct link if recombination is mutagenic to microsatellite sequences or if polymorphic microsatellites act as recombination signals. Alternatively, recombination could exert an indirect effect by uncoupling of natural selection at linked loci, promoting polymorphism. As recombination is concentrated in narrow hotspot regions in the human genome, we investigated the relationship between microsatellite polymorphism and recombination hot spots. By using data from a common allele frequency database, we found several polymorphism estimates to be similar for hot spots and the genomic average. However, this is likely explained by an ascertainment bias because markers with high polymorphism information content are usually selected for genotyping in human populations and pedigrees. In contrast, by using an unbiased set of shotgun sequence data, we found an excess of microsatellite polymorphism in recombination hot spots of 14%. However, when other genomic variables are taken into account in a generalized model and using wavelet analysis, the effect is no longer detectable and the only firm predictor of microsatellite polymorphism is the incidence of SNPs and indels. One possible neutral explanation to these observations is that there is a common denominator affecting the local rate of mutation in unique as well as in repetitive DNA, for example, base composition.     

Causal link between microsatellite instability and hMRE11 dysfunction in human cancers

Maintenance of genomic integrity is essential for cell survival, and genomic instability is a commonly recognized intrinsic property of all cancers. Microsatellite instability (MSI) represents a frequently occurring and easily traceable simple form of sequence variation, signified by the contraction or expansion of specific DNA sequences containing short tandem repeats. MSI is frequently detected in tumor cells with DNA mismatch repair (MMR) deficiency. It is commonly conceived that instability at individual microsatellite loci can arise spontaneously in cells independent of MMR status, and different microsatellite loci are generally not affected uniformly by MMR deficiency. It is well recognized that MMR deficiency per se is not sufficient to initiate tumorigenesis; rather, the biological effects have to be exerted by mutations in genes controlling cell survival, DNA damage response, and apoptosis. Recently, shortening of an intronic hMRE11 poly(T)11 tract has been associated with MMR deficiency, raising the possibility that hMRE11 may be inactivated by defective MMR. However, the molecular nature underlying this association is presently unknown, and review of the current literature suggests that hMRE11 is most likely involved with the MMR pathway in a more complex fashion than simply being a MMR target gene. An alternative scenario is proposed to better reconcile the differences among various studies. The potential role of hMRE11 in telomere repeats stability is also discussed.     

Different instability of the CAG microsatellite in two haplotype groups of human mitochondrial DNA polymerase gamma

Two single nucleotide polymorphisms of the mitochondrial DNA polymerase gamma gene (POLG1), rs2238296 (T/C) and rs758130 (T/C), were analyzed in individuals of different ethnicity (Russians and Buryats) with known genotypes of the CAG microsatellite located in the same gene. It was shown that microsatellite alleles with repeat numbers other than 10 were significantly more frequent within the TT haplotype. A phylogenetic analysis of human and chimpanzee POLG1 intron 2 sequences suggested that the haplotype TT, which is more heterogeneous regarding the CAG repeat polymorphism, is evolutionally younger than the haplotype CC. These data may be useful in the further research of the association between the CAG microsatellite polymorphism of POLG1 and male infertility.     

肠道微生物代谢产物—S-雌马酚与人类健康关系研究进展

大豆异黄酮是一种年销量很大、市场普及率较高的保健品。具有抗氧化、抗肿瘤等功能,对延缓女性衰老和改善更年期综合征有很好效果。但研究表明,大豆异黄酮的保健功能主要归功于其肠道代谢产物S-雌马酚。S-雌马酚是豆类食品在肠道内经特定微生物代谢后产生的一种高度稳定小分子,其与雌激素的结构和功能高度相似,能与β-雌激素(ER-β)受体结合。具有防治更年期综合征、心血管疾病和多种雌素依赖性癌症的功能。到目前为止,雌马酚的功能及其与人类健康之间的关系还有待进一步研究。本文结合国内外最新研究进展,着重介绍雌马酚的生理功能及其与各类疾病的研究进展,展望雌马酚在各类疾病防治中可能发挥的重要作用。     

肠道菌群与2型糖尿病相关性的研究进展

摘要：糖尿病是一种常见的代谢性疾病,发病率高,易引起严重的微血管、大血管并发症,造成多重器官损伤;缺乏有效的治疗手段,患者生存质量普遍偏低,致残率、致死率走高;发病机制异常复杂,目前仍未能完全阐明。近年来,大量报道显示,肠道菌群作为人体不可分割的部分,参与了宿主的健康维持和疾病发生,与2型糖尿病的发生、发展有着直接的关系。本文就肠道菌群与2型糖尿病的相关性研究进展进行简要综述,为肠道菌群及2型糖尿病的相关研究提供参考。