MicroRNA:新的心血管疾病生物标志物

近年来MicroRNA(miRNA)一直是医学生物学研究的热点。它作为一类非编码的小RNA,参与基因的转录和表达调控,因此人体的众多生命活动和疾病的发生、发展都与miRNA的变化密不可分。miRNA的作用因细胞特异性和目标mRNA的不同而异,miRNA可以通过影响细胞的分裂、增殖、凋亡和再生等表型的变化,参与疾病的损伤与修复过程。特别是近期研究人员进行了基于miRNA的疾病诊治研究,结果预示了良好的应用前景。     

人工 microRNA 技术研究进展

RNA干扰（RNAi）是由双链RNA触发的在mRNA水平进行的特异靶序列的基因沉默现象,广泛存在于动物、植物和病毒中,主要包括小干扰RNA（siRNA）及微小RNA（miRNA）两种作用途径。人工miRNA（amiRNA）是将天然miRNA的成熟序列替换成人工设计的靶向其他感兴趣基因的反义序列,通过天然miRNA的生成和作用途径达到RNAi的效果,具有干扰效果明显、作用迅速、毒性低等优点,拥有广阔的应用前景。我们对基于amiRNA的基因沉默技术进行了较为系统的介绍和总结,梳理了该技术的优缺点和适用范围,并展望了其进一步发展的方向和应用前景。     

线粒体自噬在感染性疾病中的作用机制研究进展

线粒体自噬作为一种选择性自噬方式是近年研究的热点.细胞通过自噬机制选择性清除受损伤或不必需的线粒体,从而维持其功能稳态.近年来,越来越多的研究聚焦于病原体通过胁迫线粒体自噬在机体感染过程中调节先天免疫信号通路,从而影响感染性疾病的进程.本文分别从线粒体自噬在病毒、细菌和真菌感染性疾病中的作用机制研究进展进行综述,以期为...     

表观遗传生物标志物在人类疾病早期诊治中的研究进展

表观遗传修饰异常见于人类的多种疾病(如肿瘤、老年性疾病、发育源性疾病等),影响着这些疾病的发生发展。已有的研究表明,异常表观遗传改变可以作为疾病状态和疾病预测的生物标志物。表观遗传修饰改变的可逆性和可控性也为疾病早期的预防和治疗提供了新策略。本文对DNA甲基化修饰、组蛋白共价修饰、非编码RNA等三种表观遗传方式在肿瘤、老年性疾病和发育源性疾病的研究,以及三者作为表遗传生物标志物在疾病早期诊断和治疗的应用展开介绍,以期为肿瘤、老年性和发育源性相关疾病的诊断与治疗提供借鉴和 参考。     

中国新发传染病研究的开拓者们——《微生物学通报》创刊40周年纪念

自20世纪70年代初以来,全球有大量的新发传染病出现,仅有重要影响的新发传染病就达45种以上,其中有至少3个团队因相关病原体的发现获得了诺贝尔医学或生理学奖;期间,不论我国处于"文化大革命"时期,还是处于改革开放和经济社会快速发展时期,总有一批科学家战斗在新发传染病应对的第一线。特别是那些在中国新发传染病研究领域的开拓者们,他们努力跟踪国内外传染病疫情进展,进行着新发传染病及其病原体的证实工作。本文借祝贺《微生物学通报》创刊40周年之际,对这些科学家在此期间的开创性工作进行初步整理,并加以简要评述;历史不会忘记他们为我国的医学事业所做出的重要贡献,也会激励一代又一代的微生物学和医学工作者。     

Identification of candidate microRNA biomarkers in renal fibrosis: a meta-analysis of profiling studies

Abstract

The prognostic, diagnostic and therapeutic value of microRNA (miRNA) expression aberrations in renal fibrosis has been studied in recent years. However, the miRNA expression profiling efforts have led to inconsistent results between the studies. The aim of this study was to perform a meta-analysis on the renal fibrosis miRNA expression profiling studies to identify candidate diagnostic biomarkers. We performed comprehensive literature searches in several databases to identify miRNA expression studies of renal fibrosis in animal models and humans. The miRNAs expression data were extracted from 20 included studies, and both miRNA vote-counting strategy and Robust Rank Aggregation method were utilized to identify significant miRNA meta-signatures. The predicted and validated targets of miRNA meta-signature were obtained by using MultiMiR package in 11 databases. Then a gene set enrichment analysis (KEGG, PANTHER pathways and GO processes) were carried out with GeneCodis web tool to recognize pathways that are most strongly influenced by modified expressions of these miRNAs. We recognized in both meta-analysis approaches a significant miRNA meta-signature of five up-regulated (miR-142-3p, miR-223-3p, miR-21-5p, miR-142-5p and miR-214-3p) and two down-regulated (miR-29c-3p and miR-200a-3p) miRNAs. Enrichment analysis confirmed that miRNA meta-signature cooperatively target functionally related genes in signalling and developmental pathways in renal fibrosis. This meta-analysis identified seven highly significant and consistently dysregulated miRNAs from 20 datasets, as the focus of future investigations to discover their potential influence to renal fibrosis and their clinical utility as biomarkers and/or as therapeutic mediators against chronic kidney disease..     

Back to the future: antibody-based strategies for the treatment of infectious diseases

Before antibiotics, sera from immune animals and humans were used to treat a variety of infectious diseases, often with successful results. After the discovery of antimicrobial agents, serum therapy for bacterial infections was rapidly forsaken. In the last two decades, problems with treatment of newly emerged, reemerged, or persistent infectious diseases necessitated researchers to develop new and/or improved antibody-based therapeutic approaches. This article reviews some information on the use of antibodies for the treatment of infectious diseases, with special reference to the most seminal discoveries and current advances as well as available treatment approaches in this field.     

Elevated levels of circulating pancreatic polypeptide in inflammatory and infectious disorders

Circulating levels of pancreatic polypeptide (PP) were found to be elevated when compared to healthy controls in 54% of patients with chronic inflammatory connective tissue disorders (SLE, rheumatoid arthritis, scleroderma, mixed connective tissue disease and temporal arteritis) and in 96% of patients with acute viral or bacterial infections. Significant positive correlations were obtained between the serum values of PP and those of haptoglobin or orosomucoid. Accompanying successful anti-inflammatory treatment of patients with autoimmune disorders, a reduction of PP levels was observed. The findings suggest that the magnitude of increase in PP was associated with the degree of the inflammatory activity. Raised PP levels may contribute to the alterations in carbohydrate and lipid metabolism observed during active inflammatory diseases in man.     

Th1/Th2与PCT检测在感染性疾病诊断中的临床应用

病原微生物引起的感染性疾病是临床中极为常见的一类疾病,此类疾病的预后主要取决于感染的病原微生物类型及疾病的严重程度。早期诊断和积极干预可在很大程度上改善感染性疾病患者的预后。因此,快速、有效地识别感染的病原微生物并对其进行靶向治疗,避免抗生素的滥用显得尤为重要。Th1/Th2在感染性疾病中的作用越来越得到重视,而降钙素原(PCT)是临床感染性疾病诊断和鉴别诊断的早期指标,且具有高度的敏感性和特异性。Th1/Th2和PCT的联合检测对感染性疾病的诊断、病情评估和疗效监测都具有重要的意义。     

Sorting of Drosophila small silencing RNAs partitions microRNA* strands into the RNA interference pathway

In flies, small silencing RNAs are sorted between Argonaute1 (Ago1), the central protein component of the microRNA (miRNA) pathway, and Argonaute2 (Ago2), which mediates RNA interference. Extensive double-stranded character—as is found in small interfering RNAs (siRNAs)—directs duplexes into Ago2, whereas central mismatches, like those found in miRNA/miRNA* duplexes, direct duplexes into Ago1. Central to this sorting decision is the affinity of the small RNA duplex for the Dcr-2/R2D2 heterodimer, which loads small RNAs into Ago2. Here, we show that while most Drosophila miRNAs are bound to Ago1, miRNA* strands accumulate bound to Ago2. Like siRNA loading, efficient loading of miRNA* strands in Ago2 favors duplexes with a paired central region and requires both Dcr-2 and R2D2. Those miRNA and miRNA* sequences bound to Ago2, like siRNAs diced in vivo from long double-stranded RNA, typically begin with cytidine, whereas Ago1-bound miRNA and miRNA* disproportionately begin with uridine. Consequently, some pre-miRNA generate two or more isoforms from the same side of the stem that differentially partition between Ago1 and Ago2. Our findings provide the first genome-wide test for the idea that Drosophila small RNAs are sorted between Ago1 and Ago2 according to their duplex structure and the identity of their first nucleotide.     

The COVID-19 epidemic and other notifiable infectious diseases in China

Many infection control measures have been implemented to prevent the spread of SARS-CoV-2 during COVID-19 pandemic. We aimed to investigate the impact of COVID-19 epidemic on the other notifiable infectious diseases in China, including respiratory infectious diseases, diseases transmitted through the digestive tract and animal-borne diseases. Compared with 2019, the overall decline rate of respiratory infectious diseases in 2020 is the highest (60–90%), and the diseases transmitted by the digestive tract and animal-borne diseases are similar at 20–30%. Both hepatitis and sexually transmitted diseases decreased significantly in February, and there were basically no significant changes in other months compared with previous years. The series of measures taken by China government to prevent the spread of SARS-CoV-2 are also very effective in preventing the spread of respiratory infectious diseases. But they also have a certain degree of prevention against notifiable infectious diseases spread by other routes.     

Usefulness of oral cytopathology in the diagnosis of infectious diseases

P. H. Braz‐Silva, M. H. C. G. Magalhães, V. Hofman, K. L. Ortega, M. I. Ilie, G. Odin, P. Vielh and P. Hofman Usefulness of oral cytopathology in the diagnosis of infectious diseases In recent years, the incidence of oral opportunistic infections has increased, partly due to the widespread implementation of organ and bone marrow transplantation and the increase in the prevalence of human immunodeficiency virus (HIV) infection. Cytology can be used as a rapid, inexpensive and simple routine procedure in diagnosing infectious diseases of the mouth. Moreover, ancillary methods can be applied to cytological samples, increasing the specificity and sensitivity for the diagnosis of infectious diseases. This review describes the cytopathological features of the main viral, fungal, bacterial and parasitic infections of the mouth. Cytological techniques of specimen collection, identification of infectious agents by cytomorphological approaches and ancillary methods, and diagnostic pitfalls will be discussed.     

Serodiagnosis of infectious diseases with antigen microarrays

AIMS: To generate protein microarrays by printing microbial antigens on slides to enable the simultaneous determination in human sera of antibodies directed against Toxoplasma gondii, rubella virus, cytomegalovirus and herpes simplex virus (HSV) types 1 and 2. METHODS AND RESULTS: Antigens were printed on activated glass slides using high-speed robotics. The slides were incubated with serum samples and subsequently with fluorescently labelled secondary antibodies. Human IgG and IgM bound to the printed antigens were detected using confocal scanning microscopy and quantified with internal calibration curves. The microarray assay could detect as little as 0.5 pg of both IgG and IgM bound onto the glass surface. Precision profiles ranged from 1.7 to 18.5% for all the antigens. Microarrays and commercial ELISAs were utilized to detect serum antibodies against the ToRCH antigens in a panel of characterized human sera. Overall >80% concordance was obtained between microarray and ELISA kits in the classification of sera. CONCLUSIONS: These results indicate that the microarray is a suitable assay format for the serodiagnosis of infectious diseases. SIGNIFICANCE AND IMPACT OF STUDY: Antigen microarrays can be optimized for clinical use, their performance is equivalent to ELISA but they offer significant advantages in throughput, convenience and cost.     

The potential of using blood circular RNA as liquid biopsy biomarker for human diseases

Circular RNA (circRNA) is a novel class of single-stranded RNAs with a closed loop structure. The majority of circRNAs are formed by a back-splicing process in pre-mRNA splicing. Their expression is dynamically regulated and shows spatiotemporal patterns among cell types, tissues and developmental stages. CircRNAs have important biological functions in many physiological processes, and their aberrant expression is implicated in many human diseases. Due to their high stability, circRNAs are becoming promising biomarkers in many human diseases, such as cardiovascular diseases, autoimmune diseases and human cancers. In this review, we focus on the translational potential of using human blood circRNAs as liquid biopsy biomarkers for human diseases. We highlight their abundant expression, essential biological functions and significant correlations to human diseases in various components of peripheral blood, including whole blood, blood cells and extracellular vesicles. In addition, we summarize the current knowledge of blood circRNA biomarkers for disease diagnosis or prognosis.     

Clinical significance of circulating microRNAs as diagnostic biomarkers for coronary artery disease

Coronary artery disease (CAD) is one of the biggest threats to human life. Circulating microRNAs (miRNAs) have been reported to be linked to the pathogenesis of CAD, indicating the possible role in CAD diagnosis. The present study aimed to explore the expression profile of plasma miRNAs and estimate their value in diagnosis for CAD. 67 Non‐CAD control subjects and 88 CAD patients were enrolled. We conducted careful evaluation by RT‐PCR analysis, Spearman rank correlation coefficients analysis, Receiver Operating Characteristic (ROC) curves analysis and so on. The plasma levels of six miRNAs known to be related to CAD were measured and three of them showed obvious expression change. Circulating miR‐29a‐3p, miR‐574‐3p and miR‐574‐5p were all significantly increased. ROC analysis revealed the probability of the three miRNAs as biomarkers with AUCs (areas under the ROC curve) of 0.830, 0.792 and 0.789, respectively. They were significantly correlated with each other in CAD patients, suggesting the possibility of joint diagnosis. The combined AUC was 0.915, much higher than each single miRNA. Therefore, our study revealed three promising biomarkers for early diagnosis of CAD. The combination of these miRNAs may act more effectively than individual ones for CAD diagnosis.