microRNAs:心血管疾病重要的调控因子

微RNA（microRNA,miRNA）是一类内源性19—25个核苷酸大小的非编码RNA分子,在进化中具有高度保守性,并且能够通过碱基匹配原则识别靶基因3’非翻译区的靶位点,从而抑制编码蛋白靶基因的翻译或（和）降解靶基因。目前的研究表明,miRNA在生物体发育、心血管疾病以及肿瘤发生等过程中起重要作用。本文对miRNA在心血管系统生理病理中的作用做一综述。     

microRNAs: tiny regulators with great potential.

Animal genomes contain an abundance of small genes that produce regulatory RNAs of about 22 nucleotides in length. These microRNAs are diverse in sequence and expression patterns, and are evolutionarily widespread, suggesting that they may participate in a wide range of genetic regulatory pathways.     

微小RNA与免疫调节

微小RNA(miRNA)是一类22核苷酸的高度保守的小分子非编码RNA,主要通过与靶mRNA的3′非编码区碱基互补配对结合而引起靶RNA降解或翻译抑制.越来越多的研究显示,miRNA在免疫反应中具有新型调节作用,包括调节免疫细胞的发育和分化、B细胞抗体的产生、炎性介质的释放、细胞信号转导等.miRNA在维持机体免疫系统...     

Bone marrow mesenchymal stem cells for post-myocardial infarction cardiac repair: microRNAs as novel regulators

Transplantation of bone marrow-derived mesenchymal stem cells (MSCs) is safe and may improve cardiac function and structural remodelling in patients following myocardial infarction (MI). Cardiovascular cell differentiation and paracrine effects to promote endogenous cardiac regeneration, neovascularization, anti-inflammation, anti-apoptosis, anti-remodelling and cardiac contractility, may contribute to MSC-based cardiac repair following MI. However, current evidence indicates that the efficacy of MSC transplantation was unsatisfactory, due to the poor viability and massive death of the engrafted MSCs in the infarcted myocardium. MicroRNAs are short endogenous, conserved, non-coding RNAs and important regulators involved in numerous facets of cardiac pathophysiologic processes. There is an obvious involvement of microRNAs in almost every facet of putative repair mechanisms of MSC-based therapy in MI, such as stem cell differentiation, neovascularization, apoptosis, cardiac remodelling, cardiac contractility and arrhythmias, and others. It is proposed that therapeutic modulation of individual cardiovascular microRNA of MSCs, either mimicking or antagonizing microRNA actions, will hopefully enhance MSC therapeutic efficacy. In addition, MSCs may be manipulated to enhance functional microRNA expression or to inhibit aberrant microRNA levels in a paracrine manner. We hypothesize that microRNAs may be used as novel regulators in MSC-based therapy in MI and MSC transplantation by microRNA regulation may represent promising therapeutic strategy for MI patients in the future.     

tRNAs as regulators in gene expression

Transfer RNAs (tRNAs) hold a central place in protein synthesis by interpreting the genetic information stored in DNA into the amino acid sequence of protein, thus functioning as “adaptor” molecules. In recent years, however, various studies have shown that tRNAs have additional functions beyond participating in protein synthesis. When suffering from certain nutritional stresses, tRNAs change the level of aminoacylation to became uncharged, and these uncharged tRNAs act as effector molecules to regulate global gene expression, so that the stressed organism copes with the adverse environmental stresses. In budding yeast and certain mammalian cells, the retrograde movement of mature tRNAs from cytoplasm to nucleus serves as a mechanism for the surveillance system within the nucleus to continue monitoring the integrity of tRNAs. On the other hand, this retrograde action effectively reduces the global protein synthesis level under conditions of nutritional starvation. Quite recently, various publications have shown that tRNAs are not stable molecules in an absolute sense. Under certain physiological or environmental stresses, they are specifically cleaved into fragments of different lengths in the anticodon loop or anticodon left arm. These cleavages are not a meaningless random degradation phenomenon. Instead, a novel class of signal molecules such as tRNA halves or sitRNAs may be produced, which are closely correlated with the modulation of global gene expression. Investigation of the regulatory functions of tRNAs is a frontier, which seeks to reveal the structural and functional diversity of tRNAs as well as their vital functions during the expression of genetic information. Supported by National Natural Science Foundation of China (Grant Nos. 30870530 and 30570398) and the National Key Basic Research Program of China (Grant No. 2005CB724600)     

Transition-state regulators: sentinels of Bacillus subtilis post-exponential gene expression

When Bacillus subtilis encounters a nutrient-depleted environment, it expresses a wide variety of genes that encode functions in alternative pathways of metabolism and energy production. Expression of these genes first occurs during the transition from active growth into stationary phase and is controlled by a class of proteins termed transition-state regulators. In several instances, a given gene is redundantly controlled by two or more of these regulators and many of these regulators control genes in numerous different pathways. The AbrB, Hpr and Sin proteins are the best-studied examples of these regulatory molecules. Their role is to prevent inappropriate and possibly detrimental functions from being expressed during exponential growth when they are not needed. They serve as elements integrating sporulation with ancillary stationary-phase phenomena and appear to participate in the timing of early sporulation events and in fine-tuning the magnitude of gene expression in response to specific environmental conditions.     

Bioactive carotenoids: potent antioxidants and regulators of gene expression

Abstract

Carotenoi ds are plant pigments, some of which act as a vital source of vitamin A to all animals, that appear to have additional benefits to primates. They are potent antioxidants and photoprotectants and can additionally modulate gene activity resulting in protection from experimentally-induced inflammatory damage and neoplastic transformation. Anti-neoplastic properties appear tightly correlated to their ability to induce the gap junctional protein connexin 43 (Cx43). This when upregulated leads to decreased proliferation and decreased indices of neoplasia in animal and human cells. Delivery of natural carotenoids can be compromised by poor bioavailability. To overcome this, a synthetic water-dispersible derivative of astaxanthin has been synthesized and shown to be: highly bioavailable; a potent antioxidant; protective against experimental ischemia-reperfusion injury and capable of inducing Cx43, suggesting antineoplastic potential. The ability to deliver biologically active carotenoids at high concentration and with good reproducibility appears to have been achieved.     

Bioactive carotenoids: potent antioxidants and regulators of gene expression

Carotenoids are plant pigments, some of which act as a vital source of vitamin A to all animals, that appear to have additional benefits to primates. They are potent antioxidants and photoprotectants and can additionally modulate gene activity resulting in protection from experimentally-induced inflammatory damage and neoplastic transformation. Anti-neoplastic properties appear tightly correlated to their ability to induce the gap junctional protein connexin 43 (Cx43). This when upregulated leads to decreased proliferation and decreased indices of neoplasia in animal and human cells. Delivery of natural carotenoids can be compromised by poor bioavailability. To overcome this, a synthetic water-dispersible derivative of astaxanthin has been synthesized and shown to be: highly bioavailable; a potent antioxidant; protective against experimental ischemia-reperfusion injury and capable of inducing Cx43, suggesting antineoplastic potential. The ability to deliver biologically active carotenoids at high concentration and with good reproducibility appears to have been achieved.     

Amino acids as regulators of gene expression: molecular mechanisms

Regulation of gene expression by nutrients in mammals is an important mechanism allowing them to adapt their physiological functions according to the supply of nutrient in the diet. It has been shown recently that amino acids are able to regulate by themselves the expression of numerous genes. CHOP, asparagine synthetase, and IGFBP-1 regulation following AA starvation will be described in this review with special interest in the molecular mechanisms involved.