NLE

NLE
  • 文章类型: Journal Article
    核糖体生物发生是真核细胞中的一个基本过程。NOTCHLESS(NLE)参与酵母中60S核糖体的生物发生,但它在拟南芥中的作用(A.thaliana)仍然是排他性的。这里,我们发现拟南芥NLE(AtNLE)在系统发育上是高度保守的,编码WD40重复蛋白。AtNLE在活跃分裂的组织中表达。AtNLE-GFP位于细胞核中。AtNLE与AtMDN1的MIDAS结构域发生物理相互作用,AtMDN1是一种参与拟南芥60S核糖体亚基生物发生的蛋白质。表达不足的突变体nle-2在根分生组织中显示短根和细胞数量减少。此外,无效突变体nle-1是胚胎致死的,有缺陷的胚胎在早期球形阶段被捕获。这项工作表明AtNLE与AtMDN1相互作用,并且AtNLE在根和胚胎发育中起作用。
    Ribosome biogenesis is a fundamental process in eukaryotic cells. NOTCHLESS (NLE) is involved in 60S ribosome biogenesis in yeast, but its role in Arabidopsis (A. thaliana) remains exclusive. Here, we found that Arabidopsis NLE (AtNLE) is highly conservative in phylogeny, which encoding a WD40-repeat protein. AtNLE is expressed in actively dividing tissues. AtNLE-GFP is localized in the nucleus. AtNLE physically interacts with the MIDAS domain of AtMDN1, a protein involved in the biogenesis of the 60S ribosomal subunit in Arabidopsis. The underexpressing mutant nle-2 shows short roots and reduced cell number in the root meristem. In addition, the null mutant nle-1 is embryo lethal, and defective embryos are arrested at the early globular stage. This work suggests that AtNLE interacts with AtMDN1, and AtNLE functions in root and embryo development.
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  • 文章类型: Meta-Analysis
    目的:抗SSA/RO抗体与妊娠的关系已有报道,我们的目标是可视化抗SSA/RO的母婴结局率。
    方法:我们系统地从Pubmed,科克伦,Embase,和WebofScience数据库,妊娠不良结局的汇总发生率,用RStudio进行95%置信区间(CI)。
    结果:从电子数据库中检索了890条记录,包括1675例患者和1920例妊娠。对于产妇结局,终止妊娠的汇总估计率为4%,5%为自然流产,26%的早产,50%为剖宫产手术。而对于胎儿结局,围产期死亡的汇总估计率为4%,3%为宫内发育迟缓,6%用于心内膜弹性纤维增生症,6%为扩张型心肌病,7%为先天性心脏传导阻滞,12%为先天性心脏传导阻滞复发,19%为新生儿皮肤红斑狼疮,肝胆疾病为12%,血液学表现为16%。进行了先天性心脏传导阻滞患病率的亚组分析,诊断方法和研究区域在一定程度上影响异质性。
    结论:对来自真实世界研究的数据的累积分析证实,抗SSA/RO妇女的不良妊娠结局,作为这些妇女的诊断和后续治疗的参考和指南,从而增强母婴健康。需要对真实世界队列进行其他研究来验证这些结果。
    OBJECTIVE: The relationship between anti-SSA/RO antibodies and pregnancy has been reported previously, and we aim to visualize the rates of maternal and infant outcomes with anti-SSA/RO.
    METHODS: We systematically searched records from Pubmed, Cochrane, Embase, and Web of Science databases, pooled incidence rates of adverse outcomes of pregnancy, and 95% confidence intervals (CIs) were performed with RStudio.
    RESULTS: A total of 890 records comprising 1675 patients and 1920 pregnancies were searched from the electronic databases. For maternal outcomes, the pooled estimate rates were 4% for termination of pregnancy, 5% for spontaneous abortion, 26% for preterm labor, and 50% for cesarean operation. While for fetal outcomes, the pooled estimate rates were 4% for perinatal death, 3% for intrauterine growth retardation, 6% for endocardial fibroelastosis, 6% for dilated cardiomyopathy, 7% for congenital heart block, 12% for congenital heart block recurrence, 19% for cutaneous neonatal lupus erythematosus, 12% for hepatobiliary disease and 16% for hematological manifestations. A subgroup analysis of congenital heart block prevalence was performed, diagnostic method and study region were found to affect heterogeneity to some extent.
    CONCLUSIONS: Cumulative analysis of data from real-world studies confirmed adverse pregnancy outcomes of women with anti-SSA/RO, serves as a reference and a guide for the diagnosis and subsequent treatment of these women, thereby enhancing maternal and infant health. Additional studies with real-world cohorts are required to validate these results.
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  • 文章类型: Journal Article
    MicroRNAs(miRNA)是通过多种机制指导基因表达的转录后调控的非编码内源性RNA。活性主要是通过与信使RNA(mRNA)的3'非翻译区(UTR)结合,导致降解和翻译抑制。与其他小RNA不同,miRNA不需要完美的碱基配对,因此,可以调节广泛的网络,然而具体的,基因。尽管我们才刚刚开始深入了解miRNA的全部生物学功能,它们参与疾病的发生和发展已经引起了对治疗发展的极大兴趣。越来越多的证据表明,基于miRNA的治疗,恢复或抑制miRNA的表达和活性,保持伟大的承诺。然而,尽管早期的承诺和令人兴奋的潜力,在过渡到临床应用之前,通常涉及miRNA靶向剂递送的关键障碍仍有待克服。交付可以克服的限制包括,但不限于,体内稳定性差,不适当的生物分布,内源性RNA机制的破坏和饱和,和不良的副作用。可以开发病毒载体和非病毒递送系统来规避这些挑战。病毒载体是有效的递送剂,但毒性和免疫原性限制了其临床应用。在这里,我们回顾了非病毒miRNA递送系统的机制和策略的最新进展,并对基于miRNA的治疗方法的未来提供了展望。
    MicroRNAs (miRNAs) are non-coding endogenous RNAs that direct post-transcriptional regulation of gene expression by several mechanisms. Activity is primarily through binding to the 3\' untranslated regions (UTRs) of messenger RNAs (mRNA) resulting in degradation and translation repression. Unlike other small-RNAs, miRNAs do not require perfect base pairing, and thus, can regulate a network of broad, yet specific, genes. Although we have only just begun to gain insights into the full range of biologic functions of miRNA, their involvement in the onset and progression of disease has generated significant interest for therapeutic development. Mounting evidence suggests that miRNA-based therapies, either restoring or repressing miRNAs expression and activity, hold great promise. However, despite the early promise and exciting potential, critical hurdles often involving delivery of miRNA-targeting agents remain to be overcome before transition to clinical applications. Limitations that may be overcome by delivery include, but are not limited to, poor in vivo stability, inappropriate biodistribution, disruption and saturation of endogenous RNA machinery, and untoward side effects. Both viral vectors and nonviral delivery systems can be developed to circumvent these challenges. Viral vectors are efficient delivery agents but toxicity and immunogenicity limit their clinical usage. Herein, we review the recent advances in the mechanisms and strategies of nonviral miRNA delivery systems and provide a perspective on the future of miRNA-based therapeutics.
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  • 文章类型: Journal Article
    Necrotizing meningoencephalitis (NME), necrotizing leukoencephalitis (NLE), and granulomatous meningoencephalomyelitis (GME) are idiopathic inflammatory diseases in the central nervous system (CNS) of dogs. In our previous study, the proportion of inflammatory cells, except for CD3-positive T cells, were not different in parenchymal and perivascular lesions in the brain. However, breed specificities, clinical courses, and specific lesions were distinct among these diseases. Thus, similarities and differences in the pathologies of these diseases have been implied. In this study, the messenger RNA (mRNA) and/or protein expression levels of cytokines and chemokine receptors were investigated in NME (n = 2), NLE (n = 4), and GME (n = 2) cases, and their relationship in the formation of specific lesions was discussed. The mRNA and protein expression levels of interferon (IFN)-γ and interleukin (IL)-17 were marked in NME and GME, respectively. The mRNA expression levels of CXCR3 and CCR2 were also marked in NME and GME, respectively. The results of double-labeling immunofluorescence, used to identify cells producing IL-17 in these lesions, showed that most CD163-positive macrophages/microglia but fewer CD3-positive T cells were IL-17 positive in GME. These results indicate that IFN-γ plays a key role in NME lesions and that the macrophages/microglia that infiltrate brain lesions producing IL-17 are more important in GME than T cells.
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