非编码RNA调控心脏重构与再生

近年来, 越来越多的证据表明, 大量的非编码RNA(non-coding RNAs, ncRNAs)在基因的表达调控、细胞和机体的生理功能维持与病理环境调节方面都有重要作用, 其中主要包括微小RNA(microRNAs, miRNAs) 和长链非编码RNA(long non-coding RNAs, lncRNAs).心脏重构与再生是心血管疾病领域的关键问题, 其调控过程非常复杂, 包括表观遗传、转录、转录后及翻译水平的调控. 大量研究发现在转录后水平, miRNAs 通过负性调节靶标的表达调控心脏发育、疾病及再生进程. 近期研究揭示, lncRNAs 在心脏发育和疾病中具有潜在的作用, 可通过表观遗传、转录及转录后水平发挥作用. lncRNAs 已成为继miRNAs 之后的又一重要的调节性非编码RNA. 就非编码RNA 在心脏重构及再生进程中的调控作用进行综述.     

饮食中的miRNAs及其对摄食者机体代谢调控的研究进展

miRNAs(microRNAs)是一类内源性非编码单链RNAs,广泛存在于真核生物和病毒中,通过与目标mRNAs分子的3′端非编码区域的碱基进行互补配对,引起靶miRNAs降解或抑制其翻译,来实现对基因进行转录后的表达调控。本文对植物性miRNAs对动物代谢调控的影响、乳品中miRNAs对胎儿机体代谢调控的影响进行了梳理,使人们了解饮食miRNAs作为一种信号分子在细胞间传导、调控并影响摄入者的生理机能以及病理表现的作用机制,进而为研究食品营养与食品贮藏、加工提供新的思路。     

miRNA与子宫内膜容受性

microRNAs(miRNAs)是一种内源性非编码小RNA,以完全或非完全互补的方式与其靶mRNA相结合,通过影响靶基因转录或翻译来调控细胞发育、分化、增殖、凋亡及疾病的发生发展等.在胚胎着床的子宫内膜容受性形成及蜕膜化过程中,胚胎滋养层细胞对子宫内膜的有控性侵袭是胎儿正常发育的基础.虽然,目前对miRNA与子宫内膜容受性的关系仍不十分清楚,但是已有一些研究表明,在正常妊娠胎盘、绒毛和正常子宫内膜中,一些miRNA与靶基因存在一定的的互作关系.本文简要综述了miRNA与子宫内膜容受性相关的研究进展.     

蛋白翻译后SUMO化修饰在动脉粥样硬化中的作用与机制

动脉粥样硬化是过程复杂的慢性炎症性疾病,涉及内皮激活、内皮功能障碍和局部炎症反应等多个关键病理步骤.小分子类泛素修饰因子(small ubiquitin-like modifier,SUMO)化修饰是真核细胞中常见的较新发现的蛋白翻译后修饰,参与多种细胞进程生物学事件,如DNA的转录活性细胞增殖分化、蛋白质的稳定性和定位细胞凋亡以及细胞信号转导等.近期研究发现, SUMO化在动脉粥样硬化发生发展的多个环节中起到重要的调控作用.针对动脉粥样硬化上述几个过程中涉及的蛋白翻译后SUMO化修饰对病程发展的调控作用及其机制的研究现状作一综述.     

接受美学视角下译者在文学翻译中的作用

按照接受美学的观点,翻译过程中译者面临两次接受过程,第一次接受过程是译者本身与原作之间的交流,译文读者与译文的交流和对话是第二次接受活动,这只有在翻译完成之后才能实现.但是译者在翻译过程中必须考虑读者的存在,预测读者的接受水平和审美情趣.因此,在整个翻译过程中,译者的作用是明显的,他不仅充当原作的特殊读者,而且是阐释者和文学再创造者.     

p53振子的形成机制及microRNA对p53目标基因表达的精细调控

肿瘤抑制因子p53调控着大量的基因,在肿瘤抑制中起着关键作用.实验结果表明,当DNA受损后,p53的表达呈现周期性振荡.已有的一些p53振子的理论模型,其振子产生机制通常依赖于p53和Mdm2之间相互作用的时滞因素.考虑基因表达的转录和翻译过程,运用动力学方程建模的方法,给出一种新模型,并利用Hopf分叉理论,给出p53振子产生的条件.数值模拟结果表明,与已有的时滞模型相比,该模型对参数具有更好的鲁棒性,较好地解释了p53振子的产生机制.最近的许多实验表明,p53调控着miR-34家族中大量microRNA的表达,这些microRNA又在后转录水平上对p53的下游目标基因起着调控作用.在这一模型基础上,研究microRNA加入p53调控网络后所起的调控作用,数值模拟结果初步表明,microRNA对p53下游目标基因表达起到了精细调控作用.     

TOR(target of rapamycin)介导的翻译调控

TOR是细胞营养状态、能量状态的传感器,其信号转导系统参与了细胞外营养成分、生长因子等对细胞生长的调控,它通过调控蛋白质翻译过程的多个环节,如通过调控S6KI、4E-BPI、eEF2等多种因子的生物功能,从而在蛋白质翻译的起始、延伸等多个水平调控体内蛋白质的翻译,从而影响细胞的生长以及细胞周期的调控。     

水稻中Intronic MicroRNA与其宿主基因功能关系分析

根据已有的水稻基因组注释,对水稻中已知的437个pre-miRNAs的基因组背景加以分析,有98个(～22%)与蛋白编码基因相重叠,其中69个(～16%)位于蛋白编码基因的内含子区域,即intronic microRNAs(in-miRNAs).对这些in-miRNAs的靶基因进行Gene Ontology(GO)富集分析,结果显示in-miRNAs对蛋白质氨基酸磷酸化,DNA整合,蛋白质水解,恒温保持,防御响应等生物学过程中的基因有明显的调控作用.最后,对宿主基因及靶基因的功能进行整合分析发现有4个in-miRNAs所调控的靶基因与其宿主基因参与了相同的生物过程.我们推断,in-miRNAs可能会在这些生物过程中,通过下调靶基因的表达来协助或抑制其宿主基因的功能.     

热预适应对大鼠肌肉组织中m6A修饰的影响

为了解大鼠肌肉中m⁶A修饰在热预适应过程中的变化，并初步探讨m⁶A在热预适应过程中发挥的作用.选用24只成年雄性SD大鼠，随机分为2组，12只为预热组，12只为对照组.热预处理组是42℃热处理15 min,每天3次，连续5 d,对照组不做任何处理.处理结束后检测关键酶的转录和翻译表达水平，以及总m⁶A的变化.与对照组相比，热预处理组的甲基转移酶METTL3和METTL14,KIAA1429的mRNA表达水平均有不同程度上升，METTL3最为显著；去甲基化酶FTO和ALKBH5的mRNA水平下降，FTO蛋白表达水平下降极显著；LC-MS检测发现m⁶A修饰水平升高.在热预适应过程中，大鼠骨骼肌中m⁶A甲基化修饰增强，去甲基化减弱，总体m⁶A水平升高，表明m⁶A信号通路在大鼠肌肉预适应过程中可能发挥正调控作用.     

译者主体性视角下鲁迅与林语堂翻译思想浅较

受到时代、传统、文化与环境等因素的影响,翻译过程中译者往往会根据自己的翻译意图和文化背景对原作进行必要的加工和再创作,这一现象在文学翻译中尤为突出。近年来,译者主体性研究日益受到学界的重视。本文通过对文学翻译中译者主体性的具体表现形式进行深入全面的阐释,对鲁迅和林语堂的翻译思想进行比较研究,从而探视文化意识、翻译目的和审美取向在文学翻译中的重要作用。     

Clinical and pathological features of miR-10b and RHOC gene expression in hepatocellular carcinoma

Aberrant expression of microRNAs （miRNAs） was reported frequently in different human cancers. The major role of miRNA is targeting 31-UTR of coding gene and causing translational repression or mRNA degradation. miR-10b overexpression was reported to promote breast cancer metastasis by up-regulating RHOC expression. But its expression in hepatocellular carcinoma （HCC） remains unclear. Our study indicated that the expression of miR-10b was different in HCC and adjacent tissue samples, and reduced expression of miR-10b in HCC was related tovein invasion. High-level expression of RHOC was also related to vein invasion in HCC. But no correlation was found between miR-10b and RHOC expression. These results suggest that miR-10b and RHOC are independent predictors of HCC invasion and metastasis.     

Widespread changes in protein synthesis induced by microRNAs

Animal microRNAs (miRNAs) regulate gene expression by inhibiting translation and/or by inducing degradation of target messenger RNAs. It is unknown how much translational control is exerted by miRNAs on a genome-wide scale. We used a new proteomic approach to measure changes in synthesis of several thousand proteins in response to miRNA transfection or endogenous miRNA knockdown. In parallel, we quantified mRNA levels using microarrays. Here we show that a single miRNA can repress the production of hundreds of proteins, but that this repression is typically relatively mild. A number of known features of the miRNA-binding site such as the seed sequence also govern repression of human protein synthesis, and we report additional target sequence characteristics. We demonstrate that, in addition to downregulating mRNA levels, miRNAs also directly repress translation of hundreds of genes. Finally, our data suggest that a miRNA can, by direct or indirect effects, tune protein synthesis from thousands of genes.     

MicroRNA与慢性肾脏病并发动脉粥样硬化相关性与中医药干预研究进展

动脉粥样硬化(As)引起的心血管疾病是慢性肾脏病(CKD)患者主要并发症和主要死亡原因之一。microRNA是一类小的非编码RNA,是参与基因调控网络的重要因子。国内外大量研究表明部分microRNA的异常表达可通过多种机制介导CKD及其心血管并发症如As的病理进程,被确定为CKD As的病理相关因子,应用microRNA作为疾病生物标志物的独特优势和CKD As潜在治疗靶点的作用是现代研究热点。中医认为CKD As病机正虚与邪实夹杂,具有本虚标实的特点,中医药通过调控microRNA干预CKD As符合传统“扶正祛邪”治疗原则与现代中医微观辨证理念,以microRNA为切入点研究中医药防治CKD As的具体机制具有重要意义。本文就国内外microRNA与CKD As病理机制的相关性以及中药复方、中药活性成分调控CKD异常microRNA防治As的作用机制研究进展进行了综述,以期为未来相关研究提供理论参考,以便开发更有效的治疗策略,为临床中医药治疗CKD As提供新的可能途径与干预靶点。     

利用乙醇脱氢酶基因证据揭示稻属CCDD异源四倍体中染色体组的起源

对稻属异源四倍体中染色体组C和D以及稻属现存的所有二倍体染色体组A、B、C、E、F的乙醇脱氢酶基因（Adh1）片段分别进行PCR扩增、克隆和序列测定，并以G染色体组序列作为外类群，采用PAUP运算软件中的简约性方法对所测定的序列进行了系统发育分析．结果表明：（1）3个CCDD四倍体是同一次杂交事件的产物；（2）四倍体中的C染色体组和亚洲二倍体中的C染色体组表现出更近的系统发育关系；（3）D染色体组和E染色体组表现出较近的亲缘关系，二者可能有共同的祖先．     

Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy

Despite antiretroviral therapy, proviral latency of human immunodeficiency virus type 1 (HIV-1) remains a principal obstacle to curing the infection. Inducing the expression of latent genomes within resting CD4(+) T cells is the primary strategy to clear this reservoir. Although histone deacetylase inhibitors such as suberoylanilide hydroxamic acid (also known as vorinostat, VOR) can disrupt HIV-1 latency in vitro, the utility of this approach has never been directly proven in a translational clinical study of HIV-infected patients. Here we isolated the circulating resting CD4(+) T cells of patients in whom viraemia was fully suppressed by antiretroviral therapy, and directly studied the effect of VOR on this latent reservoir. In each of eight patients, a single dose of VOR increased both biomarkers of cellular acetylation, and simultaneously induced an increase in HIV RNA expression in resting CD4(+) cells (mean increase, 4.8-fold). This demonstrates that a molecular mechanism known to enforce HIV latency can be therapeutically targeted in humans, provides proof-of-concept for histone deacetylase inhibitors as a therapeutic class, and defines a precise approach to test novel strategies to attack and eradicate latent HIV infection directly.     

Pervasive roles of microRNAs in cardiovascular biology

First recognized as regulators of development in worms and fruitflies, microRNAs are emerging as pivotal modulators of mammalian cardiovascular development and disease. Individual microRNAs modulate the expression of collections of messenger RNA targets that often have related functions, thereby governing complex biological processes. The wideranging functions of microRNAs in the cardiovascular system have provided new perspectives on disease mechanisms and have revealed intriguing therapeutic targets, as well as diagnostics, for a variety of cardiovascular disorders.     

Gene regulation: ancient microRNA target sequences in plants

MicroRNAs are an abundant class of small RNAs that are thought to regulate the expression of protein-coding genes in plants and animals. Here we show that the target sequence of two microRNAs, known to regulate genes in the class-III homeodomain-leucine zipper (HD-Zip) gene family of the flowering plant Arabidopsis, is conserved in homologous sequences from all lineages of land plants, including bryophytes, lycopods, ferns and seed plants. We also find that the messenger RNAs from these genes are cleaved within the same microRNA-binding site in representatives of each land-plant group, as they are in Arabidopsis. Our results indicate not only that microRNAs mediate gene regulation in non-flowering as well as flowering plants, but also that the regulation of this class of plant genes dates back more than 400 million years.