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小RNA包括siRNA和miRNA两种,前者是伴随着RNAi现象发现的,是对外源基因剪切加工形成的,是生物维持自身基因组稳定性的一种机制,而miRNA是基因组中固有的,是在转录后水平调节基因表达的重要机制。小RNA的作用方式有两种:介导目标RNA降解和抑制蛋白质翻译。前者要求小RNA与目标RNA精确互补,而后者只要求部分互补,采取何种机制取决于互补程度而不是其来源。RNAi作为下调基因表达的手段,在功能基因组学中已有广泛的应用。对血液肿瘤发病相关基因,尤其对染色体易位造成的相关融合基因、凋亡相关基因及多药耐药基因的干扰研究表明,该技术不但是研究机制的有力手段,而且具有临床应用前景。对microRNA的研究发现,它在多种血液肿瘤如多种淋巴瘤和白血病中存在表达的变化,并与多种癌基因相关,提示它广泛参与血液肿瘤的发病机制。本文就RNA干扰和小RNA的发现和作用,以及小RNA在血液肿瘤研究中的应用作一综述。  相似文献   

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Protein–protein interactions within protein networks shape the human interactome, which often is promoted by specialized protein interaction modules, such as the postsynaptic density‐95 (PSD‐95), discs‐large, zona occludens 1 (ZO‐1) (PDZ) domains. PDZ domains play a role in several cellular functions, from cell–cell communication and polarization, to regulation of protein transport and protein metabolism. PDZ domain proteins are also crucial in the formation and stability of protein complexes, establishing an important bridge between extracellular stimuli detected by transmembrane receptors and intracellular responses. PDZ domains have been suggested as promising drug targets in several diseases, ranging from neurological and oncological disorders to viral infections. In this review, the authors describe structural and genetic aspects of PDZ‐containing proteins and discuss the current status of the development of small‐molecule and peptide modulators of PDZ domains. An overview of potential new therapeutic interventions in PDZ‐mediated protein networks is also provided.  相似文献   

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Background: RNA interference (RNAi) represents a promising new approach to combat viral infections, and recent developments in the field of gene therapy have increased the feasibility of clinical applications. Objective: to explore the utility of RNAi for the treatment of the ultimately life-threatening liver disease caused by hepatitis C virus (HCV), which affects approximately 170 million people worldwide. Methods: A review of current developments in liver-directed gene delivery and the potential application of RNAi for the treatment of HCV. In addition, the involvement of microRNAs (miRNA) in HCV infection and the potential therapeutic implications are emphasized. Conclusions: RNAi technologies have fuelled rapid progress in the basic understanding of HCV biology and revealed numerous new viral and host-cell factors as potential targets for therapy. Together with the improvement of gene delivery technology and the discovery of the critical role of miRNA in HCV infection, RNAi and miRNA-based antiviral strategies hold great promise for the future.  相似文献   

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Cooperative properties of cytochromes P450   总被引:1,自引:0,他引:1  
Cytochromes P450 form a large and important class of heme monooxygenases with a broad spectrum of substrates and corresponding functions, from steroid hormone biosynthesis to the metabolism of xenobiotics. Despite decades of study, the molecular mechanisms responsible for the complex non-Michaelis behavior observed with many members of this superfamily during metabolism, often termed ‘cooperativity’, remain to be fully elucidated. Although there is evidence that oligomerization may play an important role in defining the observed cooperativity, some monomeric cytochromes P450, particularly those involved in xenobiotic metabolism, also display this behavior due to their ability to simultaneously bind several substrate molecules. As a result, formation of distinct enzyme–substrate complexes with different stoichiometry and functional properties can give rise to homotropic and heterotropic cooperative behavior. This review aims to summarize the current understanding of cooperativity in cytochromes P450, with a focus on the nature of cooperative effects in monomeric enzymes.  相似文献   

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目的 了解本地区细菌感染性疾病常见病原菌对各类抗菌药物的耐药状况,为临床合理用药提供依据.方法 根据美国国家临床实验室标准化委员会(NCCLS)推荐的抗菌药物分组原则选择抗菌药物,并采用琼脂纸片扩散法对常见病原菌进行药敏实验.结果 常见病原菌依次为大肠埃希菌、肺炎克雷伯菌、金黄色葡萄球菌、铜绿假单胞菌、鲍曼不动杆菌、粪肠球菌、溶血葡萄球菌、阴沟肠杆菌和表皮葡萄球菌.耐甲氧西林的金黄色葡萄球菌、溶血葡萄球菌和表皮葡萄球菌分别为34.5%、83.3%和66.7%,溶血葡萄球菌和表皮葡萄球菌对庆大霉素、四环素、环丙沙星和复方新诺明的耐药性强于金黄色葡萄球菌.粪肠球菌对青霉素类保持高度敏感,对氨苄西林和高水平庆大霉素的耐药率分别为3.5%和21.1%.大肠埃希菌、肺炎克雷伯菌、阴沟肠杆菌产超广谱β-内酰胺酶(ESBLs)率分别为21.7%、23.9%和14.6%,大肠埃希菌和肺炎克雷伯菌对青霉素类、头孢菌素、氨基糖甙类和氯霉素的耐药性均低于阴沟肠杆菌.鲍曼不动杆菌对哌拉西林、头孢他啶、亚胺培南、阿米卡星和环丙沙星的耐药性比铜绿假单胞菌更强.结论 及时掌握常见病原菌耐药特点和耐药菌株(MDR)发展趋势对制定各种感染的经验治疗方案和指导临床合理应用抗菌药物具有重要参考意义.  相似文献   

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目的研究WS-8810抗菌卫生整理剂对处理普通病房床单的抗菌效果。方法采用压印法采样和常规细菌培养方法,对WS-8810抗菌卫生整理剂处理的普通病房床单进行抗菌效果观察。结果含有阳离子型抗菌剂的WS-8810抗菌卫生整理剂处理的病房床单对自然菌的平均抗菌有效率为97.6%。对用该抗菌卫生整理剂处理的病房床单布样抽样作无菌检验,无菌率达到91.4%,未经抗菌卫生整理剂处理的布样无菌比例为0%。结论该抗菌卫生整理剂处理的病房床单显示出明显抗菌效果,抗菌率为97.6%(90%)消毒合格。  相似文献   

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Triple-negative breast cancer develops from malignant cells within the interior lining of milk ducts or, less frequently, in the stromal tissues and accounts for ≈15% of all breast cancers. Breast cancer is highly prevalent with the overall number of cases expected to reach 27.78 million by 2040, according to the World Health Organization. MiRNAs serve a novel role in management of breast cancer through their ability to indirectly control the translation of coding mRNA and regulate the expression of specific genes, which allows it to play a significant role in cancer therapeutics. However, inherent characteristics of miRNA including rapid clearance via renal excretion, degradation by nucleases in plasma, and additional factors limit its clinical application. To reduce these limitations, miRNA can be administered in conjunction small molecules with nanocarriers, which then allow it to impart its benefits including inhibition of epithelial–mesenchymal transitions, and inhibiting tumor angiogenesis. This review highlights the current application of nanocarrier-based delivery approach of miRNA/siRNA for triple negative breast cancer treatment.  相似文献   

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miRNAs are short, nonprotein coding RNAs that regulate target gene expression principally by causing translational repression and/or mRNA degradation. miRNAs are involved in most mammalian biological processes and have pivotal roles in controlling the expression of factors involved in basal and stimulus-induced signaling pathways. Considering their central role in the regulation of gene expression, miRNAs represent therapeutic drug targets. Here we describe how miRNAs are involved in the regulation of aspects of innate immunity and inflammation, what happens when this goes awry, such as in the chronic inflammatory lung diseases cystic fibrosis and asthma, and discuss the current state-of-the-art miRNA-targeted therapeutics.  相似文献   

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The effectiveness of a behavioral parent training (BPT) intervention for improving maternal self-efficacy, maternal stress, and the quality of mother–toddler interactions has been demonstrated (Gross, Fogg, & Tucker, 1995). The 1-year follow-up of the 46 parents of toddlers (assigned to an intervention or comparison group) who participated in that study is reported. It was hypothesized that (a) BPT would lead to enduring positive changes in parenting self-efficacy, parenting stress, and parent–toddler interactions; and (b) the amount of parent participation in the intervention would be correlated with greater gains in parent–child outcomes at 1 year. All the families were retained and significant gains in maternal self-efficacy, maternal stress, and mother–child interactions were maintained. Minimal BPT effects were found for fathers. BPT dosage was related to reductions in mother critical statements and negative physical behaviors at 1-year postintervention. The findings are consistent with self-efficacy theory and support parenting self-efficacy as a target for BPT in families of young children. © 1998 John Wiley & Sons, Inc. Res Nurs Health 21:199–210, 1998  相似文献   

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