环状RNA在肿瘤癌变中的作用机制和临床意义

<正>环状RNA(circRNA)是一种特殊的内源性非编码RNA,1976年在类病毒中被首次发现,随后在病毒和真核生物中也相继发现了circRNA。circRNA与线性RNA的不同之处在于其3'端与5'端相连,形成闭合的共价环状结构,该结构使circRNA较线性RNA更加保守和稳定~(〔1〕)。最初cireRNA被认为是由选择性剪接错误产生,最新研究表明circRNA的形成受ALU双反     

非编码RNA在心肌缺血再灌注损伤中的作用

心肌缺血再灌注损伤可诱导心肌细胞死亡并导致心脏功能丧失。随着生物信息学和基因测序技术的不断发展,发现越来越多具有生物学功能的非编码RNA参与到心肌缺血再灌注损伤的发生、发展之中,主要以microRNA、long non-coding RNA和circRNA研究为主。阐明非编码RNA在心肌缺血再灌注损伤中的发病机制有助于探索缺血性心血管疾病的新治疗策略。     

微小RNA对缺血再灌注损伤心肌线粒体作用的研究进展

心肌缺血再灌注损伤是造成心肌结构损伤、功能障碍的一种病理生理过程,进一步发展会导致级联的多器官功能障碍。线粒体是一种结构功能复杂且对外界环境反应敏感的细胞器,其稳态的维持依赖于正常形态、功能及数量的相对稳定状态。线粒体质量与代谢异常和心血管疾病尤其是心肌缺血再灌注损伤的发生密切相关。微小RNA是近年来研究较多的在缺血再灌注损伤心肌线粒体保护中具有重要作用的调控因子。本文通过微小RNA对心肌缺血再灌注损伤时线粒体形态、功能、线粒体自噬和线粒体DNA几个方面的调控机制与相关前沿进展进行综述,为微小RNA参与缺血再灌注心肌线粒体损伤的后续研究提供一定的理论依据。     

微小RNA参与心肌缺血再灌注损伤的作用机制及研究进展

心肌缺血再灌注损伤是影响冠心病尤其是急性心肌梗死血运重建治疗效果的重要原因之一,近年来,众多研究发现微小RNA在心肌缺血再灌注过程中发挥调控作用,上调或者下调靶微小RNA的表达可减轻心肌缺血再灌注损伤,为临床上心肌保护提供了新的治疗靶点,现将围绕微小RNA在心肌缺血再灌注损伤中的调控机制及临床应用等方面的新进展进行综述。     

CircRNA对骨代谢及骨质疏松症的调控作用

环状RNA (circular RNA,circRNA)是一类特殊的非编码RNA,其3'和5'末端通过反向剪接以共价键结合形成闭合圆环结构,具有高度的稳定性、保守性和特异性。近年来,随着研究的不断的深入,circRNA在基因调控中的作用逐渐明确。circRNA主要通过海绵吸附微小RNA (microRNA,miRNA),在转录和转录后水平上发挥调控作用。研究表明circRNA参与调控成骨细胞、破骨细胞和间充质干细胞(mesenchymal stromal cells,MSCs)的功能和分化,进而在骨代谢的调控中发挥重要作用。同时circRNA还参与了骨质疏松症的调控过程。本文主要通过综述circRNA与骨代谢和骨质疏松症的相关研究,以明确circRNA在维持骨骼健康中的作用。     

单核细胞趋化蛋白-1与心肌缺血再灌注损伤的关系

心肌缺血/再灌注损伤是一个重要的临床问题,而临床上对心肌缺血/再灌注损伤的防治尚缺乏有效的方法.近年发现单核细胞趋化蛋白-1在心肌缺血再灌注的早期出现并呈动态变化,抑制其出现和发展会影响心肌缺血再灌注动物的表现和预后.对单核细胞趋化蛋白-1进行干预可能成为未来新的治疗方向.     

Fas/FasL系统与心肌缺血-再灌注损伤

心肌缺血再灌注损伤是心血管介入治疗中较棘手的问题,如何减少心肌缺血再灌注损伤是目前的研究重点。Fas/FasL系统是体内直接启动细胞凋亡的死亡信号传导系统,大量研究表明其在心肌缺血再灌注损伤中起关键作用。现就Fas/FasL系统在心肌缺血-再灌注损伤中的作用作一综述。     

冠状动脉内皮细胞在缺血再灌注损伤时的变化和曲美他嗪的保护作用

随着人们对冠状动脉内皮细胞研究的深入，发现其在心肌缺血再灌注损伤中起到了重要的作用。通过研究在体、离体心肌缺血再灌注损伤模型以及缺氧处理分离培养的内皮细胞，明确了缺血再灌注可引起冠状动脉内皮细胞形态、结构、功能的改变。钙离子内流、氧自由基产生、中性粒细胞聚集、抗凝血及抗氧化系统损伤是心肌缺血再灌注损伤机制的重要组成部分，而冠状动脉内皮细胞与心肌缺血再灌注损伤机制已经密不可分。     

长链非编码RNA参与心肌缺血再灌注损伤白勺研究进展

心肌梗死后的再灌注治疗有效保护了心肌,却造成了心肌缺血再灌注损伤。近来大量的研究证实,长链非编码RNA参与了心肌缺血再灌注损伤的病理过程,长链非编码RNA可以通过调节基因表达调节心肌细胞坏死、凋亡、自噬,长链非编码RNA可以调节心肌梗死后心律失常,长链非编码RNA也可以作为心肌梗死的临床诊断标志物及治疗靶点。本文将对长链非编码RNA参与心肌缺血再灌注损伤的研究进展作一综述。     

神经调节蛋白-1在心肌缺血再灌注中的研究进展

心肌缺血再灌注损伤过程中，心肌缺血梗死会导致心肌细胞不可逆的损伤，而缺血组织恢复血流灌注时，会引起再灌注区心肌细胞及局部血管网显著地病理生理变化，这些变化共同作用可促使进一步的组织损伤。目前临床药物和介入手术等治疗方法不能有效恢复心肌梗死后心脏的功能或失活的心肌。神经调节蛋白-1不仅在心脏组织的结构完整性中发挥重要作用，还可以通过抑制炎症反应与氧化应激、促进心脏血管形成、调节心肌重构等方式减轻心肌损伤，这使人们认识到其在治疗心肌缺血再灌注中的巨大潜力。本文将对神经调节蛋白-1在心肌缺血再灌注损伤中的研究进展进行综述和展望。     

Functional RNA elements in the dengue virus genome

Dengue virus (DENV) genome amplification is a process that involves the viral RNA, cellular and viral proteins, and a complex architecture of cellular membranes. The viral RNA is not a passive template during this process; it plays an active role providing RNA signals that act as promoters, enhancers and/or silencers of the replication process. RNA elements that modulate RNA replication were found at the 5' and 3' UTRs and within the viral coding sequence. The promoter for DENV RNA synthesis is a large stem loop structure located at the 5' end of the genome. This structure specifically interacts with the viral polymerase NS5 and promotes RNA synthesis at the 3' end of a circularized genome. The circular conformation of the viral genome is mediated by long range RNA-RNA interactions that span thousands of nucleotides. Recent studies have provided new information about the requirement of alternative, mutually exclusive, structures in the viral RNA, highlighting the idea that the viral genome is flexible and exists in different conformations. In this article, we describe elements in the promoter SLA and other RNA signals involved in NS5 polymerase binding and activity, and provide new ideas of how dynamic secondary and tertiary structures of the viral RNA participate in the viral life cycle.     

Effect of intestinal ischemia-reperfusion injury on protein levels of leptin and orexin-A in peripheral blood and central secretory tissues

AIM: To explore the effect of intestinal ischemia-reperfusion injury on protein levels of leptin and orexin-A in peripheral blood and their central secretory tissues and to find out the role leptin and orexin-A play in acute inflammatory responses. METHODS: An intestinal ischemia-reperfusion (I/R) injury model of rats was established and rats were divided randomly into six groups: sham-operation group, 60 min ischemia/30 min reperfusion group (I60'R30'), I60'R90', I60'R150', I60'R240' and I60'R360', 9 rats each group. Two highly-sensitive radioimmunoassays for leptin and orexin-A were established and used to check the change of their concentrations in peripheral blood and central secretory tissues before and after intestinal I/R injury. RESULTS: Compared with the serum leptin level before injury, it decreased significantly in I60'R30' group and increased significantly in I60'R360' group; compared to sham-operation group after injury, serum leptin level increased significantly in I60'R360' group; compared to sham-operation group after injury, adipose leptin levels decreased significantly in I60'R30' and I60'R90' groups, while increased significantly in I60'R360' group. There was no significant difference between the expression levels of orexin-A before and after I/R injury. CONCLUSION: Leptin has a time-dependent response and orexin-A has a delayed response to acute inflammatory stimuli such as intestinal I/R injury and they may participate in metabolic disorders in injury as inflammatory cytokines.     

HMGB1在心肌缺血再灌注损伤中作用的研究进展

高迁移率族蛋白1(HMGB1)是一种核蛋白,几乎存在于所有细胞的细胞核中,可调节染色质结构、DNA复制和基因转录等。它对细胞正常发育起到至关重要的作用。当HMGB1作为一种损伤相关分子模式从细胞内向外释放时,在介导炎症反应中扮演重要角色。心肌缺血再灌注损伤是一种多种细胞及细胞因子参与的病理生理过程,涉及的信号分子及通路极其复杂。随着疾病分子生物学水平的发展,研究发现HMGB1在心肌缺血再灌注损伤中起关键作用。阐明HMGB1在心肌缺血再灌注损伤中的作用有助于探寻新的治疗靶点。该文对HMGB1在心肌缺血再灌注损伤中作用的研究进展作一综述。     

Synthesis of circular RNA in bacteria and yeast using RNA cyclase ribozymes derived from a group I intron of phage T4.

Studies on the function of circular RNA and RNA topology in vivo have been limited by the difficulty in expressing circular RNA of desired sequence. To overcome this, the group I intron from the phage T4 td gene was split in a peripheral loop (L6a) and rearranged so that the 3' half intron and 3' splice site are upstream and a 5' splice site and 5' half intron are downstream of a single exon. The group I splicing reactions excise the internal exon RNA as a circle (RNA cyclase ribozyme activity). We show that foreign sequences can be placed in the exon and made circular in vitro. Expression of such constructs (RNA cyclase ribozymes) in Escherichia coli and yeast results in the accumulation of circular RNA in these organisms. In yeast, RNA cyclase ribozymes can be expressed from a regulated promoter like an mRNA, containing 5' leader and 3' trailer regions, and a nuclear pre-mRNA intron. RNA cyclase ribozymes have broad application to questions of RNA structure and function including end requirements for RNA transport or function, RNA topology, efficacy of antisense or ribozyme gene control elements, and the biosynthesis of extremely long polypeptides.     

Celastrol assuages oxygen-glucose deprivation and reoxygenation-induced damage in human brain microvascular endothelial cells through the circDLGAP4/miR-6085/GDF11 pathway

Metabolic Brain Disease - The effect of Celastrol on cerebral ischemia-reperfusion remains unknown. The study aims to explore the role of circular RNA DLGAP4 (circDLGAP4) in cerebral...     

A host-specific function is required for ligation of a wide variety of ribozyme-processed RNAs

Hepatitis delta virus (HDV) replicates its circular RNA genome via a rolling circle mechanism. During this process, cis-acting ribozymes cleave adjacent upstream sequences and thereby resolve replication intermediates to unit-length RNA. The subsequent ligation of these 5'OH and 2',3'-cyclic phosphate termini to form circular RNA is an essential step in the life cycle of the virus. Here we present evidence for the involvement of a host activity in the ligation of HDV RNA. We used both HDV and hammerhead ribozymes to generate a panel of HDV and non-HDV RNA substrates that bear 5' hydroxyl and 2', 3'- cyclic phosphate termini. We found that ligation of these substrates occurred in host cells, but not in vitro or in Escherichia coli. The host-specific ligation activity was capable of joining RNA in both bimolecular and intramolecular reactions and functioned in a sequence-independent manner. We conclude that mammalian cells contain a default pathway that efficiently circularizes ribozyme processed RNAs. This pathway could be exploited in the delivery of stable antisense and decoy RNA to the nucleus.     

New pharmacologic options in the treatment of acute coronary syndromes and myocardial ischemia-reperfusion injury: potential role of levosimendan

Modern and effective therapeutic possibilities have improved the management and outcomes in acute coronary syndromes and acute myocardial infarction. However, substantial morbidity and mortality still remain. Myocardial ischemia-reperfusion injury may contribute to additional damage to myocardial necrosis and apoptosis. Therefore, it has been focused on attention and field of therapeutic actions in the last years. The main mechanisms involved in the pathogenesis of ischemia-reperfusion injury are depressed energy metabolism, elevated oxidative damage, and altered calcium homeostasis. In experimental trials, a variety of drugs have proved effectiveness for the prevention and treatment of the ischemia-reperfusion injury. However, its efficacy, not always confirmed, has not yet been established in clinical practice. On the basis of the strong evidence linking potassium ATP dependent channels opening in the myocardium and its proved cardioprotective role during ischemia, these channels have been pointed out as possible and promising pharmacological targets in this setting. Some evidences suggest that the calcium sensitizing agent levosimendan may have of beneficial and exerts cardioprotective effects on myocardial ischemia and ischemia-reperfusion injury. Further investigation is warranted on this novel application of levosimendan.     

T细胞参与心肌I/R损伤的研究进展

心肌I/R损伤（MI/RI）是治疗心肌梗死过程中的并发症之一,中性粒细胞、巨噬细胞等固有免疫细胞引起的炎性反应是导致MI/RI的重要原因。众多免疫细胞如何在MI/RI中发挥作用是目前研究的热点问题。近年来,越来越多的研究表明T细胞在MI/RI中发挥重要作用。本文将阐述T细胞在MI/RI中的作用及机制的研究进展,并分析目前存在的问题及发展方向。     

Replication of avocado sunblotch viroid: evidence for a symmetric pathway with two rolling circles and hammerhead ribozyme processing.

The structure of a series of RNAs extracted from avocado infected by the 247-nt avocado sunblotch viroid (ASBVd) was investigated. The identification of multistranded complexes containing circular ASBVd RNAs of (+) and (-) polarity suggests that replication of ASBVd proceeds through a symmetric pathway with two rolling circles where these two circular RNAs are the templates. This is in contrast to the replication of potato spindle tuber viroid and probably of most of its related viroids, which proceeds via an asymmetric pathway where circular (+)-strand and linear multimeric (-)-strand RNAs are the two templates. Linear (+) and (-) ASBVd RNAs of subgenomic length (137 nt and about 148 nt, respectively) and one linear (+)-strand ASBVd RNA of supragenomic length (383-384 nt) were also found in viroid-infected tissue. The two linear (+)-strand RNAs have the same 5'- and 3'-terminal sequences, with the supragenomic species being a fusion product of the monomeric and subgenomic (+)-strand ASBVd RNAs. The 3' termini of these two (+)-strand molecules, which at least in the subgenomic RNA has an extra nontemplate cytidylate residue, could represent sites of either premature termination of the (+)-strands or specific initiation of the (-)-strands. The 5' termini of sub- and supragenomic (+)-strand and the 5' terminus of the subgenomic (-)-strand ASBVd RNA are identical to those produced in the in vitro self-cleavage reactions of (+) and (-) dimeric ASBVd RNAs, respectively. These observations strongly suggest that the hammerhead structures which mediate the in vitro self-cleavage reactions are also operative in vivo.     

Relationship between structure of the 5'' noncoding region of viral mRNA and efficiency in the initiation step of protein synthesis in a eukaryotic system.

To determine whether the rate of protein synthesis is controlled by the structure of mRNA near its 5' terminus, protein-synthesizing ability, especially in its initial stage, was compared among RNAs of plant viruses. Those viruses used here contain several definite pieces of single-stranded RNA. Each of these RNAs acts as a messenger. Cucumber mosaic virus (CMV) RNA 5 synthesizes a small amount of a protein, Mr 7000, in an in vitro protein-synthesizing system from wheat germ or reticulocyte. Brome mosaic virus (BMV) RNA 4 synthesizes a large amount of a coat protein under the same conditions. Both RNAs have the same 5'-cap structure and a short noncoding region (10 nucleotides in CMV RNA 5 and 9 in BMV RNA 4) between the 5' terminus and the initiation codon AUG. A sequence complementary to the 3' terminal of 18S ribosomal RNA is contained in BMV RNA 4 but is not apparent in CMV RNA 5. Formation of the initiation complex for protein synthesis by the 5'-terminal-labeled mRNA of cytoplasmic polyhedrosis virus was inhibited by the addition of unlabeled BMV RNA 4 whereas it was only slightly inhibited by unlabeled CMV RNA 5. BMV RNA 4, which has a sequence complementary to rRNA, can form the initiation complex more easily than CMV RNA5. It is concluded that an apparent complementary sequence in the 3' terminal of 18S rRNA in the 5' noncoding region of eukaryotic mRNA and the 5'-cap structure enhance the rate of initiation complex formation in protein synthesis.