CircRNAs在骨关节炎发生发展中的作用

环状RNA(circular RNAs,circ RNAs)是一类在真核细胞中广泛存在的非编码RNA。与传统的线性RNA不同,环状RNA无5’末端帽子和3’末端多聚A尾,而是形成一个共价闭合的环状结构。最初,人们认为circ RNAs是前体m RNA(pre-m RNA)发生错误剪接而形成的低丰度RNA分子,没有给予足够重视。随着高通量RNA测序技术和生物信息学的发展,大量circ RNAs被鉴定出来,对其认识也逐渐深入,发现circ RNAs具有重要的生物学功能,在充当mi RNA"海绵"、调控基因转录与表达等方面发挥着重要作用。近几年研究发现,circ RNAs在骨关节炎(osteoarthritis,OA)关节软骨与正常软骨中表达出现差异。部分表达差异的circ RNAs参与调节了与OA发生发展密切相关的软骨细胞外基质(extracellular matrix,ECM)降解、炎症反应、软骨细胞凋亡等过程。尤其是,小干扰RNA(small interfering RNAs,si RNAs)沉默circ RNA-CER后,可促进软骨细胞ECM生成,提示circ RNAs可能成为治疗OA的新靶点。本文将在简单综述circ RNAs的生物合成、主要生物功能的基础上,重点综述circ RNAs与OA发生发展之间的关系,以期为OA的诊断和特异性治疗提供新靶点和新治疗措施。     

环状RNA的研究新进展

环状RNA(circular RNA,circ RNA)作为非编码RNA家族成员,具有特征性的共价闭合环结构。circ RNA在各种生物中广泛表达,具有种属、组织、疾病及发育阶段相关的特异性,与各种疾病,尤其是恶性肿瘤的发生发展密切相关。circ RNA的主要功能是作为海绵吸附mi RNA发挥生物学功能,同时还具有调控转录和转录后过程、可变剪接、编码蛋白以及充当蛋白诱饵等作用。目前已有多种预测方法用于circ RNA的鉴定。现就circ RNA的特征、分类、形成、功能、计算方法学以及在疾病发生中的最新研究成果进行全面阐述。     

环形RNA研究进展

环形RNA(circular RNA,circ RNA)广泛存在于各种生物细胞中,并且具有结构稳定、表达量丰富以及在不同组织及其不同发育阶段具有表达特异性等特征。目前认为,circ RNA可以在转录后水平调控基因表达,但是circ RNA的产生机制及其代谢途径仍然不是很清楚。迄今研究认为,circ RNA的主要生物学作用是作为微小RNA(micro RNA,miRNA)海绵体调控miRNA的表达。此外,circ RNA在肿瘤、动脉粥样硬化、糖尿病、帕金森病等多种疾病的发生发展中发挥了一定的作用。深入了解circ RNA的作用机制及其功能,有助于深入了解疾病的发生、发展机理,设计更好的预防、诊断和治疗疾病新策略。     

环状RNA的特性、生物合成和主要功能

环状RNA(circular RNAs,circ RNAs)是非编码RNA的一种,与线性RNA不同,其主要特征为通过反式剪接使3′端与5′端以共价键相连接,形成一个闭环结构。Circ RNAs主要来源于外显子或内含子,分别通过反式剪接和套索内含子产生。Circ RNAs广泛存在于生物体内,它们种类丰富、进化保守并且可以稳定存在。这些特点使circ RNAs具有许多潜在的功能,例如充当微RNA(micro RNA,mi RNA)海绵、与RNA结合蛋白相结合形成RNA蛋白复合物、调控基因转录等。该文综述了国内外相关最新报道,旨在阐述circ RNAs的特性、生物合成及其主要功能。     

环状RNA与人类疾病

环状RNA(circular RNAs,circRNAs)是一类广泛存在于各种生物细胞中具有调控基因表达功能的非编码RNA,具有结构稳定和组织特异性表达等特征.有些circRNA分子富含微小RNA结合位点,可通过充当竞争性内源RNA的角色来发挥作用,如CDR1as对miR-7的海绵作用与肺癌、乳腺癌、胶质瘤及肌萎缩性脊髓侧索硬化等疾病发生相关.c ANRIL可通过影响多梳家族参与动脉粥样硬化的发生.大量circRNA的发现及其结构和功能的阐明不仅可以使我们更加深入地了解疾病的发生机制,而且为相关疾病的预防、诊断和治疗提供了新的方向.     

环状RNA的生物学功能及其在胃肠肿瘤发生中的作用

环状RNA(circular RNA,circ RNA)是广泛存在于真核生物转录组的内源性非编码RNA.与线性RNA不同,circ RNA不易被酶解,具有更加稳定的结构.circ RNA具有微小RNA(micro RNA,mi RNA)海绵、RNA结合蛋白海绵、调节转录以及翻译蛋白质等多种生物学功能,能够在转录水平或转录后水平调节基因的表达.近期的研究发现,circ RNA在调控肿瘤细胞增殖、迁移和侵袭过程中扮演着重要的角色.胃肠肿瘤是我国常见且死亡率高的恶性肿瘤,研究者在胃肠肿瘤中发现大量异常表达的circ RNA(如:hsa_circ_0014717、hsa_circ_0001017、hsa_circ_0061276、hsa_circ_0125965和hsa_circ_KLDHC10等).本文首先阐述circ RNA的形成机制和生物学功能;然后结合国内外胃肠肿瘤相关circ RNA的最新研究进展和本课题组相关研究成果,对circ RNA影响胃肠肿瘤发生的机制作一综述,并希望能以此为胃肠肿瘤的诊断和治疗提供新的理论依据.     

循环miR-155作为肿瘤生物标志物的研究进展

microRNAs(mi RNAs)是一类在转录后水平影响生物体基因表达的小分子非编码RNA,参与调控机体正常发育和疾病发生发展等过程。新近研究发现,循环mi RNA由于具有取样方便和高度稳定性等优点,迅速成为目前的研究热点。micro RNA-155(mi R-155)在多种肿瘤中高表达。循环mi R-155已被证实与多种肿瘤的发生、发展相关,可作为一种分子标志物用于肿瘤的早期诊断和实时监测。该文围绕循环mi R-155作为肿瘤标志物的研究进展予以综述。     

肌细胞特异性microRNAs生物学效应研究进展

micro RNAs(mi RNAs)是一类含有20~22个核苷酸的非编码单链小分子RNA,发挥转录后水平负调控基因表达和翻译的作用,具有生物学功能多样性,可作为多种疾病诊断和预后重要分子标志。该文介绍了肌细胞特异性mi RNAs,如mi R-1、mi R-133、mi R-145、mi R-206基因等染色体分布、序列、组织表达丰度、主要通路,并对肌细胞特异性mi RNAs在气管平滑肌、血管平滑肌、心肌等细胞中的生物学效应研究进展进行综述。     

靶向Wnt1的miRNA与circRNA及其靶基因间相互作用的生物信息学分析

为对靶向Wnt1的7种mi RNAs进行circ RNAs及其靶基因的预测,同时分析其与circ RNAs及靶基因间的相互作用,分别采用Starbase及mi RWALK软件,对文献报道的靶向Wnt1基因的let-7e、mi R-21、mi R-34a、mi R-122、mi R-148a、mi R-148b与mi R-152等7种mi RNAs的circ RNAs和对应的靶基因进行生物信息学预测.利用Cytoscape 3.2.1对这7种mi RNAs和预测所得到的circ RNAs及对应的靶基因进行网络分析.并进一步对预测到的靶基因通过DAVID软件进行通路分析.Starbase软件对这7种不同mi RNAs所预测的靶circ RNAs的数量分别为58、15、41、20、28、28、28个.分别比较mi RWALK中7~9个以上软件共有的mi RNAs及其与靶基因的关系,发现CHD7基因是唯一一个在三种不同预测范围内与mi R-21、mi R-148a、mi R-148b和mi R-152等4种mi RNAs相对应的靶基因.CNOT6、NBEA、ZFYVE26与ZDHHC17是在两种不同预测范围内与至少4个mi RNAs相对应的靶基因.在7种mi RNAs所预测靶基因相关的KEGG信号通路中,7~9个软件以上共有的信号通路为Focal adhesion信号通路、MAPK信号通路、Notch信号通路与TGF-beta信号通路.在MAPK信号通路中DUSP1与MRPS35_hsa_circ_001042均分别是与mi R-21、mi R-148a、mi R-148b及mi R-152等4种mi RNAs相互作用的靶基因与circ RNA.本研究对靶向Wnt1的mi RNAs及其相互作用的circ RNAs、靶基因与信号通路等进行了网络分析与预测,为进一步分析它们之间的相互作用奠定了基础.     

CircRNA肿瘤相关生物学功能的研究进展

环状RNA(circRNA)是一类具有环状结构的非编码RNA(noncoding RNAs, ncRNA),广泛存在于多种生物细胞中,具有结构稳定、序列保守及细胞或组织特异性表达等特征。已被证实circRNA在许多癌症中存在表达异常,参与了恶性肿瘤的发生发展。CircRNA在细胞中的分布与其功能发挥密切相关。研究表明,胞核分布的circRNA可以参与调节mRNA转录和表观遗传调控,胞质分布的circRNA具有充当"miRNA海绵"、与RNA结合蛋白结合、影响蛋白质翻译、编码蛋白质等功能。本文对circ RNA在肿瘤中发挥的相关生物学功能进行综述,以期为后续研究提供一定的理论依据。     

A Unique Protease Cleavage Site Predicted in the Spike Protein of the Novel Pneumonia Coronavirus (2019-nCoV) Potentially Related to Viral Transmissibility

正Dear Editor,In December 2019, a novel human coronavirus caused an epidemic of severe pneumonia(Coronavirus Disease 2019,COVID-19) in Wuhan, Hubei, China(Wu et al. 2020; Zhu et al. 2020). So far, this virus has spread to all areas of China and even to other countries. The epidemic has caused 67,102 confirmed infections with 1526 fatal cases     

Curcuminoids as inhibitors of thioredoxin reductase: A receptor based pharmacophore study with distance mapping of the active site

Curcumin is the yellow pigment of turmeric that interacts irreversibly forming an adduct with thioredoxin reductase (TrxR), an enzyme responsible for redox control of cell and defence against oxidative stress. Docking at both the active sites of TrxR was performed to compare the potency of three naturally occurring curcuminoids, namely curcumin, demethoxy curcumin and bis-demethoxy curcumin. Results show that active sites of TrxR occur at the junction of E and F chains. Volume and area of both cavities is predicted. It has been concluded by distance mapping of the most active conformations that Se atom of catalytic residue SeCYS498, is at a distance of 3.56 from C13 of demethoxy curcumin at the E chain active site, whereas C13 carbon atom forms adduct with Se atom of SeCys 498. We report that at least one methoxy group in curcuminoids is necessary for interation with catalytic residues of thioredoxin. Pharmacophore of both active sites of the TrxR receptor for curcumin and demethoxy curcumin molecules has been drawn and proposed for design and synthesis of most probable potent antiproliferative synthetic drugs.     

Comparative morphology of the carpel in the Liliaceae: Hewardieae, Petrosavieae, and Tricyrteae

The young pistils in the melanthioid tribes, Hewardieae, Petrosavieae and Tricyrteae, are uniformly tricarpellate and syncarpous. They lack raphide idioblasts. All are multiovulate, with bitegmic ovules. The Petrosavieae are marked by the presence of septal glands and incomplete syncarpy. Tepals and stamens adhere to the ovary in the Hewardieae and the Petrosavieae but not in the Tricyrteae. Two vascular bundles occur in the stamens of the Hewartlieae and Tricyrtis latifolia. Ventral bundles in the upper part of the ovary of the Hewardieae are continuous with compound septal bundles and placental bundles in the lower part. Putative ventral bundles occur in the alternate position in the Tricyrteae and putative placental bundles in the opposite. position in the Petrosavieae. The dichtomously branched stigma in each carpel of the Tricyrteae is supplied by a bifurcated dorsal bundle.     

Enterovirus 71 3C proteolytically processes the histone H3 N-terminal tail during infection

Highlights
1. The N-terminal tail of histone H3 is specifically cleaved during EV71 infection.
2. Viral protease 3C is identified as a protease responsible for proteolytically processing the N-terminal H3 tail.
3. Our finding reveals a new epigenetic regulatory mechanism for Enterovirus 71 in virus-host interactions.     

Detection of EBV and HHV6 in the Brain Tissue of Patients with Rasmussen’s Encephalitis

Rasmussen’s encephalitis (RE) is a rare pediatric neurological disorder, and the exact etiology is not clear. Viral infection may be involved in the pathogenesis of RE, but conflicting results have reported. In this study, we evaluated the expression of both Epstein-Barr virus (EBV) and human herpes virus (HHV) 6 antigens in brain sections from 30 patients with RE and 16 control individuals by immunohistochemistry. In the RE group, EBV and HHV6 antigens were detected in 56.7% (17/30) and 50% (15/30) of individuals, respectively. In contrast, no detectable EBV and HHV6 antigen expression was found in brain tissues of the control group. The co-expression of EBV and HHV6 was detected in 20.0% (6/30) of individuals. In particular, a 4-year-old boy had a typical clinical course, including a medical history of viral encephalitis, intractable epilepsy, and hemispheric atrophy. The co-expression of EBV and HHV6 was detected in neurons and astrocytes in the brain tissue, accompanied by a high frequency of CD8⁺ T cells. Our results suggest that EBV and HHV6 infection and the activation of CD8⁺ T cells are involved in the pathogenesis of RE.     

Perinatal Vertical Transmission of Chikungunya Virus in Ruili,a Town on the Border between China and Myanmar

正Dear Editor,Chikungunya virus (CHIKV), an arbovirus in the family of Togaviridae, genus Alphavirus, is transmitted by the A.aegyptii or A. albopictus mosquito, and causes disease in humans characterized by fever, rash, and arthralgia (Silva and Dermody 2017; Suhrbier 2019). It was first reported in 1953 in Tanzania, and caused only a few outbreaks and sporadic cases in Africa and Asia in last century. However, in the epidemic in 2004, CHIKV acquired mutations that conferred enhanced transmission by the A. albopictus mosquito(Schuffenecker et al. 2006). Since then, it has successively caused outbreaks in Africa, the Indian Ocean, South East Asia, the South America, and Europe (Zeller et al. 2016).     

Development of a Novel Reverse Transcription Loop-Mediated Isothermal Amplification Method for Rapid Detection of SARS-CoV-2

In conclusion, the novel visual RT-LAMP assay is a simple, rapid, and sensitive approach for detection of SARS-CoV-2, and it is ready for application in primary care and community hospitals or health care centers, and even patients' own houses in response to the current SARS-CoV-2 epidemic because the assay does not require sophisticated equipment and skilled personnel. Furthermore, it is also ready to be used in fields for screening samples from wild animals and environments to facilitate the identification of potential intermediate hosts that mediate the cross-species transmission of SARS-CoV-2 from bats to humans.