Emerging role of interleukin-13 in cardiovascular diseases: A ray of hope

Despite the great progress made in the treatment for cardiovascular diseases (CVDs), the morbidity and mortality of CVDs remains high due to the lack of effective treatment strategy. Inflammation is a central pathophysiological feature of the heart in response to both acute and chronic injury, while the molecular basis and underlying mechanisms remains obscure. Interleukin (IL)-13, a pro-inflammatory cytokine, has been known as a critical mediator in allergy and asthma. Recent studies appraise the role of IL-13 in CVDs, revealing that IL-13 is not only involved in more obvious cardiac inflammatory diseases such as myocarditis but also relevant to acute or chronic CVDs of other origins, such as myocardial infarction and heart failure. The goal of this review is to summarize the advancement in our knowledge of the regulations and functions of IL-13 in CVDs and to discuss the possible mechanisms of IL-13 involved in CVDs. We highlight that IL-13 may be a promising target for immunotherapy in CVDs.     

CARD9 Regulation and its Role in Cardiovascular Diseases

Caspase recruitment domain-containing protein 9 (CARD9) is an adaptor protein expressed on myeloid cells and located downstream of pattern recognition receptors (PRRs), which transduces signals involved in innate immunity. CARD9 deficiency is associated with increased susceptibility to various fungal diseases. Increasing evidence shows that CARD9 mediates the activation of p38 MAPK, NF-κB, and NLRP3 inflammasome in various CVDs and then promotes the production of proinflammatory cytokines and chemokines, which contribute to cardiac remodeling and cardiac dysfunction in certain cardiovascular diseases (CVDs). Moreover, CARD9-mediated anti-apoptosis and autophagy are implicated in the progression of CVDs. Here, we summarize the structure and function of CARD9 in innate immunity and its various roles in inflammation, apoptosis, and autophagy in the pathogenesis of CVDs. Furthermore, we discuss the potential therapies targeting CARD9 to prevent CVDs and raise some issues for further exploring the role of CARD9 in CVDs.     

Targeting non-coding RNAs in unstable atherosclerotic plaques: Mechanism,regulation, possibilities,and limitations

Cardiovascular diseases (CVDs) caused by arteriosclerosis are the leading cause of death and disability worldwide. In the late stages of atherosclerosis, the atherosclerotic plaque gradually expands in the blood vessels, resulting in vascular stenosis. When the unstable plaque ruptures and falls off, it blocks the vessel causing vascular thrombosis, leading to strokes, myocardial infarctions, and a series of other serious diseases that endanger people''s lives. Therefore, regulating plaque stability is the main means used to address the high mortality associated with CVDs. The progression of the atherosclerotic plaque is a complex integration of vascular cell apoptosis, lipid metabolism disorders, inflammatory cell infiltration, vascular smooth muscle cell migration, and neovascular infiltration. More recently, emerging evidence has demonstrated that non-coding RNAs (ncRNAs) play a significant role in regulating the pathophysiological process of atherosclerotic plaque formation by affecting the biological functions of the vasculature and its associated cells. The purpose of this paper is to comprehensively review the regulatory mechanisms involved in the susceptibility of atherosclerotic plaque rupture, discuss the limitations of current approaches to treat plaque instability, and highlight the potential clinical value of ncRNAs as novel diagnostic biomarkers and potential therapeutic strategies to improve plaque stability and reduce the risk of major cardiovascular events.     

Role of interleukin‐15 in cardiovascular diseases

Interleukin (IL)‐15 is a recently identified cytokine, which belongs to the interleukin‐2(IL‐2) family, and plays an important role in innate and adaptive immunoreaction. Given the fact that the structure of IL‐15 is partially similar to IL‐2, they share some common biological effects, including immunoregulation. IL‐2 was proven to protect cardiac function in mouse myocardial infarction models. Cardiovascular diseases (CVDs) dominate the cause of mortality worldwide. Besides atherosclerosis, inflammation is also widely involved in the pathogenesis of many CVDs including hypertension, heart failure (HF) and aneurysm. IL‐15, as a pro‐inflammatory cytokine, is up‐regulated in some cardiovascular diseases, such as myocardial infarction and atherosclerosis. The current understanding of IL‐15, including its signal pathway and cellular function, was described. Furthermore, IL‐15 has a protective effect in myocardial infarction and myocarditis by decreasing cardiomyocyte death and improving heart function. The inhibited effect of IL‐15 in ductus arteriosus (DA) should be focused on. IL‐15 promoted atherogenesis. IL‐15 may be a good target in treatment of cardiovascular diabetology. Finally, future research direction of IL‐15 deserves attention. Since IL‐15 plays several roles in CVDs, understanding the role of the IL‐15/IL‐15R system may provide a scientific basis for the development of new approaches that use IL‐15 for the treatment of CVDs.     

Coronary heart diseases: Assessment of risk associated with work exposure to ultralow-frequency magnetic fields

The present analysis was stimulated by previous findings on the possible influence of natural ultralow-frequency (ULF; 0.001–10 Hz) geomagnetic field variations on the cardiovascular system and indications of an effect of man-made ULF magnetic fields on the rate of myocardial infarction. In the present study, we considered the occupational health hazards of the strongest ULF magnetic fields in densely populated urban areas. Measurements of ULF magnetic field fluctuations produced by trains powered by DC electricity were performed by means of a computer-based, highly sensitive, three-component magnetometer. We found that the magnitude of magnetic field pulses inside the driver's cab of electric locomotives (ELs) could be ≥ 280 μT in the horizontal component perpendicular to the rails and up to approximately 130 μT in the vertical component, and, in the driver's compartment of electric motor unit (EMU) trains, they were approximately 50 and 35 μT, respectively. We have investigated the relationships between the occupational exposure to ULF magnetic field fluctuations produced by electric trains and cardiovascular diseases (CVDs) among railroad workers in the former Soviet Union. We have analyzed medical statistical data for a period of 3 years for approximately 45,000 railroad workers and 4,000 engine drivers. We have also analyzed 3 years of morbidity data for three subgroups of engine drivers (∼4,000 in each group) operating different types of trains. We find that EL drivers have a twofold increase in risk (2.00 ± 0.27) of coronary heart diseases (CHDs) compared with EMU drivers. Because our analysis of major CVDs shows that the examined subpopulations of drivers can be considered to have had equal exposure to all known risk factors, the elevated CHD risk among EL drivers could be attributed to the increased occupational exposure to ULF magnetic fields. © 1996 Wiley-Liss, Inc.     

环状RNA:潜在的新型miRNA活性调控分子

环状RNA(circular RNA,circRNA)是近年来RNA领域最新的研究热点.它是一类由特殊的选择性剪切产生且在真核细胞中广泛表达的环形内源性RNA分子.研究发现,circRNA富含microRNA(miRNA)结合位点,可以发挥竞争性内源RNA作用,作为miRNA"海绵"来解除对其靶基因的抑制效应.近年来,circRNA作为一种新型调控分子调控miRNA功能的发挥,受到众多研究者的青睐.本文综述circRNA的产生机制,及其调控miRNA的最新研究进展与研究方法等.     

circRNA-14723 promotes hepatocytes proliferation in rat liver regeneration by sponging rno-miR-16-5p

Circular RNA (circRNA) is a subclass of noncoding RNA (ncRNA) detected within mammalian tissues and cells. However, its regulatory role during the proliferation phase of rat liver regeneration (LR) remains unreported. This study was designed to explore their regulatory mechanisms in cell proliferation of LR. The circRNA expression profile was detected by high-throughput sequencing. It was indicated that 260 circRNAs were differentially expressed during the proliferation phase of rat LR. Among them, circ-14723 displayed a significantly differential expression. We further explored its regulatory mechanism in rat hepatocytes (BRL-3A cells). First, EdU, flow cytometry and western blot (WB) indicated that knocking down circ-14723 inhibited BRL-3A cells proliferation. Second, RNA-Pulldown and dual-luciferase report assay showed that circ-14723 could sponge rno-miR-16-5p. At last, WB showed that the reported target genes of rno-miR-16-5p, CCND1, and CCNE1 were downregulated after knocking down circ-14723. In conclusion, we found that circ-14723 exerted a critical role in G1/S arrest to promote cell proliferation via rno-miR-16-5p/CCND1 and CCNE1 axis in rat LR. This finding further revealed the regulatory mechanisms of circRNA on cell proliferation of LR, and might provide a potential target for clinical problems.     

Exosomes in Mesenchymal Stem Cells,a New Therapeutic Strategy for Cardiovascular Diseases?

Cardiovascular diseases (CVDs) are still a major cause of people deaths worldwide, and mesenchymal stem cells (MSCs) transplantation holds great promise due to its capacity to differentiate into cardiovascular cells and secrete protective cytokines, which presents an important mechanism of MSCs therapy for CVDs. Although the capability of MSCs to differentiate into cardiomyocytes (CMCs), endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) has been well recognized in massive previous experiments both in vitro and in vivo, low survival rate of transplanted MSCs in recipient hearts suggests that therapeutic effects of MSCs transplantation might be also correlated with other underlying mechanisms. Notably, recent studies uncovered that MSCs were able to secret cholesterol-rich, phospholipid exosomes which were enriched with microRNAs (miRNAs). The released exosomes from MSCs acted on hearts and vessels, and then exerted anti-apoptosis, cardiac regeneration, anti-cardiac remodeling, anti-inflammatory effects, neovascularization and anti-vascular remodeling, which are considered as novel molecular mechanisms of therapeutic potential of MSCs transplantation. Here we summarized recent advances about the role of exosomes in MSCs therapy for CVDs, and discussed exosomes as a novel approach in the treatment of CVDs in the future.     

Small but significant: Insights and new perspectives of exosomes in cardiovascular disease

Cardiovascular diseases (CVDs) are a major health problem worldwide, and health professionals are still actively seeking new and effective approaches for CVDs treatment. Presently, extracellular vesicles, particularly exosomes, have gained its popularity for CVDs treatment because of their function as messengers for inter‐ and extra‐cellular communications to promote cellular functions in cardiovascular system. However, as a newly developed field, researchers are still trying to fully understand the role of exosomes, and their mechanism in mediating cardiac repair process. Therefore, a comprehensive review of this topic can be timely and favourable. In this review, we summarized the basic biogenesis and characterization of exosomes and then further extended the focus on the circulating exosomes in cellular communication and stem cell‐derived exosomes in cardiac disease treatment. In addition, we covered interactions between the heart and other organs through exosomes, leading to the diagnostic characteristics of exosomes in CVDs. Future perspectives and limitations of exosomes in CVDs were also discussed with a special focus on exploring the potential delivery routes, targeting the injured tissue and engineering novel exosomes, as well as its potential as one novel target in the metabolism‐related puzzle.     

环状RNA在肝细胞癌中的作用及机制

肝细胞癌（hepatocellular carcinoma,HCC）治疗困难、预后很差,是肿瘤相关死亡中的第4大癌症,严重危害人类生命健康,但其具体发病机制却仍未完全阐明。因此,探索能调控肝细胞癌发生发展,作为肝细胞癌的诊断标志物或能预测患者预后的关键分子仍十分必要。环状RNA是前体mRNA通过反向剪接产生的由3′, 5′ 磷酸二酯键首尾连接形成的共价闭合环状结构,主要有外显子circRNA（exonic circRNA,ecircRNA）、环状内含子RNA（circular intronic RNA,ciRNA）及外显子 内含子circRNA（exon-intron circRNA,EIciRNA）三大类。由于环状RNA具有普遍性、高度保守性和稳定性,其可以参与多种癌症的发生发展过程,并且可作为肿瘤的早期诊断标志物及预后因子,因此,这是一类新型且非常有潜力应用于临床诊治各阶段的分子。近年来,有大量关于环状RNA与肝细胞癌的研究。这些研究表明,环状RNA在肝细胞癌发生发展进程中发挥的作用十分重要,并且其机制多样。因此,本文主要关注环状RNA在肝细胞癌中的最新进展,总结不同环状RNA分子对于肝细胞癌细胞恶性表型、肿瘤干细胞及肿瘤微环境中免疫细胞的作用,以及其在肝细胞癌临床转移、分期、诊断、预后等各阶段中发挥的功能及其具体作用机制。此外,本文还提出了目前研究中存在的一些问题和不足,以期为未来的研究提供一些新的思路及策略。     

环状RNA在肝细胞癌中的作用及机制

肝细胞癌（hepatocellular carcinoma,HCC）治疗困难、预后很差,是肿瘤相关死亡中的第4大癌症,严重危害人类生命健康,但其具体发病机制却仍未完全阐明。因此,探索能调控肝细胞癌发生发展,作为肝细胞癌的诊断标志物或能预测患者预后的关键分子仍十分必要。环状RNA是前体mRNA通过反向剪接产生的由3′, 5′ 磷酸二酯键首尾连接形成的共价闭合环状结构,主要有外显子circRNA（exonic circRNA,ecircRNA）、环状内含子RNA（circular intronic RNA,ciRNA）及外显子 内含子circRNA（exon-intron circRNA,EIciRNA）三大类。由于环状RNA具有普遍性、高度保守性和稳定性,其可以参与多种癌症的发生发展过程,并且可作为肿瘤的早期诊断标志物及预后因子,因此,这是一类新型且非常有潜力应用于临床诊治各阶段的分子。近年来,有大量关于环状RNA与肝细胞癌的研究。这些研究表明,环状RNA在肝细胞癌发生发展进程中发挥的作用十分重要,并且其机制多样。因此,本文主要关注环状RNA在肝细胞癌中的最新进展,总结不同环状RNA分子对于肝细胞癌细胞恶性表型、肿瘤干细胞及肿瘤微环境中免疫细胞的作用,以及其在肝细胞癌临床转移、分期、诊断、预后等各阶段中发挥的功能及其具体作用机制。此外,本文还提出了目前研究中存在的一些问题和不足,以期为未来的研究提供一些新的思路及策略。     

外泌体传递环状RNA介导肿瘤化疗耐药

环状RNA(circular RNA,circRNA)作为非编码RNA家族的重要成员,是一类共价闭环结构的单链RNA,没有多聚腺苷酸尾和5'-与-3'末端,显示出高度稳定性、丰富性和物种保守性等特点.近年来研究发现,circRNA与肿瘤化疗耐药、恶性进展等在内的多种生物学进程密切相关,发挥着极其重要的作用.外泌体是由机...     

Circular RNA in renal diseases

Circular RNA (circRNA) is a newly described type of non‐coding RNA. Active research is greatly enriching the current understanding of the expression and role of circRNA, and a large amount of evidence has implicated circRNA in the pathogenesis of certain renal diseases, such as renal cell carcinoma, acute kidney injury, diabetic nephropathy and lupus nephritis. Studies have found evidence that circRNAs regulate programmed cell death, invasion, and metastasis and serve as biomarkers in renal diseases. Recently, circRNAs were identified in exosomes secreted by the kidneys. Nevertheless, the function of circRNA in renal diseases remains ambiguous. Given that circRNAs are regulators of gene expression, they may be involved in the pathology of multiple renal diseases. Additionally, emerging evidence is showing that circulating circRNAs may serve as novel biomarkers for renal disease. In this review, we have summarized the identification, biogenesis, degradation, and functions of circRNA and have evaluated the roles of circRNA in renal diseases.     

Insights into circular RNAs: Biogenesis,function and their regulatory roles in cardiovascular disease

As a distinctive member of the noncoding RNA family, circular RNAs (circRNAs) are generated from single-stranded, covalently closed structures and are ubiquitous in mammalian cells and tissues. Due to its atypical circular architecture, it was conventionally deemed insignificant dark matter for a prolonged duration. Nevertheless, studies conducted over the last decade have demonstrated that this abundant, structurally stable and tissue-specific RNA has been increasingly relevant in diverse diseases, including cancer, neurological disorders, diabetes mellitus and cardiovascular diseases (CVDs). Therefore, regulatory pathways controlled by circRNAs are widely involved in the occurrence and pathological processes of CVDs through their function as miRNA sponges, protein sponges and protein scaffolds. To better understand the role of circRNAs and their complex regulatory networks in CVDs, we summarize current knowledge of their biogenesis and function and the latest research on circRNAs in CVDs, with the hope of paving the way for the identification of promising biomarkers and therapeutic strategies for CVDs.