环状RNA在心血管疾病中的研究进展

环状RNA(circRNA)是新近发现的一类特殊非编码RNA(ncRNA)分子,可在机体不同组织内大量且特异性表达,深入研究发现,circRNA具有重要的生物功能,并可参与各种疾病如神经系统疾病、心血管疾病(CVD)以及癌症的发生或出现异常表达[1]。本研究就circRNA的形成机制、生物学功能以及circRNA在CVD中的研究进展予以综述。1 circRNA概述1.1 circRNA的来源与结构早在20世纪70年代就已经在植物感染的病毒中发现circRNA的存在[1-2]。Danan等[2]2012年发现,circRNA大量存在于古生菌中,且具有一定的生物学功能,才使得circRNA成为继微小RNA(miRNA)和长链ncRNA后ncRNA分子研究领域中的新热点。     

环状RNA与胰腺癌的关系

胰腺癌是恶性程度较高的消化系统肿瘤,其诊断和治疗都很困难,5年生存率5%。环状RNA(circRNA)是继微RNA(miRNA)、长链非编码RNA(lncRNA)之后,近年来研究较为热门的非编码RNA。circRNA在多种恶性肿瘤中表达异常,并被证实与肿瘤的发生、增殖、侵袭以及预后有关,具有组织特异性,有望成为诊断标志物及靶向治疗的靶点。该文就circRNA与胰腺癌的关系作一综述。     

环状RNA与心血管疾病的研究进展

非编码RNA(nc RNA)是一种基因组转录产生的且不编码蛋白质的RNA,它包括环状RNA(circRNA)、微小RNA(miRNA)、长链ncRNA(lncRNA)和小干扰RNA(siRNA)等多种RNA,它们之间网状结构的动力平衡是调节内稳态所需要的,其中一种的异常调节就可能导致疾病的发生。circRNA是天然生成的内源性ncRNA家族中的一员,具有特殊的环状结构,不易被核酸酶降解、分布广泛、多样化、稳定和高度保守等特点使其逐渐成为ncRNA研究的热点。已有研究表明circRNA与人类疾病密切相关,其中就包括心血管疾病,并在疾病中起着重要作用。本文旨在对circRNA在心血管某些疾病方面的研究进展以及面临的问题进行综述。     

环状RNA与自身免疫性疾病

环状RNA(circRNA)是形成共价闭合的RNA环的非编码RNA,circRNA的发现揭示了转录后基因表达调控的新的层面。目前对circRNA功能的认知虽然有限,但已发现的一些关于circRNA的信息已显示出其具有吸附微小RNA (miRNA)的海绵作用和调节基因表达的作用。目前报道得最清楚的是关于circRNA CDR1as可作为miR-7的海绵的研究。miRNA在自身免疫性疾病的发病及进程中起着重要的作用,而circRNA又可作为海绵吸附miRNA,具有基因表达调控的作用,因此circRNA与自身免疫性疾病密切相关并且可能成为自身免疫性疾病的潜在治疗靶点。未来的研究可深入探究circRNA和自身免疫性疾病之间的关系。本文对circRANs的识别和功能进行综述,并介绍circRNA与人类疾病之间的关联,探索circRNA在自身免疫性疾病的潜在作用。     

CircRNA对骨代谢及骨质疏松症的调控作用

环状RNA (circular RNA,circRNA)是一类特殊的非编码RNA,其3'和5'末端通过反向剪接以共价键结合形成闭合圆环结构,具有高度的稳定性、保守性和特异性。近年来,随着研究的不断的深入,circRNA在基因调控中的作用逐渐明确。circRNA主要通过海绵吸附微小RNA (microRNA,miRNA),在转录和转录后水平上发挥调控作用。研究表明circRNA参与调控成骨细胞、破骨细胞和间充质干细胞(mesenchymal stromal cells,MSCs)的功能和分化,进而在骨代谢的调控中发挥重要作用。同时circRNA还参与了骨质疏松症的调控过程。本文主要通过综述circRNA与骨代谢和骨质疏松症的相关研究,以明确circRNA在维持骨骼健康中的作用。     

环状RNA在呼吸系统疾病中的研究进展

环状RNA(circRNA)作为新型内源性非编码RNA,在高度分化的真核生物中基因广泛表达,通过反向剪接形成共价闭环结构,具有高度稳定性和组织特异性。近些年,随着高通量测序技术和生物信息学的发展,circRNA被大量发现并逐渐成为RNA领域的研究热点。目前已有研究证明circRNA与慢性阻塞性肺疾病、肺动脉高压、肺癌等...     

环状RNA在肿瘤癌变中的作用机制和临床意义

<正>环状RNA(circRNA)是一种特殊的内源性非编码RNA,1976年在类病毒中被首次发现,随后在病毒和真核生物中也相继发现了circRNA。circRNA与线性RNA的不同之处在于其3'端与5'端相连,形成闭合的共价环状结构,该结构使circRNA较线性RNA更加保守和稳定~(〔1〕)。最初cireRNA被认为是由选择性剪接错误产生,最新研究表明circRNA的形成受ALU双反     

环状RNA在心血管疾病中的研究现状

随着全基因组分析和RNA测序技术的进步,多种非编码RNA逐渐成为研究热点。环状RNA(circRNA)具有多种细胞功能,其表达的改变与多种病理生理过程及疾病的发生发展相关。circRNA已被证明是心血管疾病方面的重要调节因子,如高血压、动脉粥样硬化、急性心肌梗死、心力衰竭、心脏纤维化等。因此,circRNA有望成为心血管疾病的潜在治疗靶点和生物标志物。在这篇综述中,我们以circRNA的生物学机制为基础,综述了目前有关circRNA作为心血管疾病调节因子和生物标志物的研究进展。     

环状RNA与肿瘤的研究进展

正环状RNA又称环形RNA(circular RNA,circRNA)是一种具有环状结构的长链非编码RNA,广泛分布于类病毒、环状卫星病毒、delta肝炎病毒等。circRNA的特点及功能一直到新近的研究发现才真正被揭示,并且极大程度上改变了我们对肿瘤的看法,尤其是肿瘤的发生发展。到目前为止,研究者们发现了两种主要的circRNA,内含子及外显子     

环状RNA在心血管疾病发病机制中的研究进展

环状RNA(circRNA)是通过将RNA的3′末端连接到5′末端而环化,形成没有聚腺苷酸尾巴的共价闭环结构,具有广泛的分布性,在不同物种及亚细胞间均能发现。目前发现circRNA与心血管疾病、神经系统疾病、癌症等多种疾病的发生与发展密切相关,其作用机制包括充当miRNA海绵、与RNA结合蛋白相互作用、调控基因表达及编码蛋白质。本文从circRNA的生物发生和功能、circRNA在心血管疾病中的研究进展等方面进行综述。     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

Serological survey of HIV and syphilis in pregnant women in Madagascar

Objectives Peripartal transmission of human immunodeficiency virus (HIV) and Treponema pallidum, the causative agent of syphilis, leads to severe consequences for newborns. Preventive measures require awareness of the maternal infection. Although HIV and syphilis testing in Madagascar could be theoretically carried out within the framework of the national pregnancy follow‐up scheme, the required test kits are rarely available at peripheral health centres. In this study, we screened blood samples of pregnant Madagascan women for HIV and syphilis seroprevalence to estimate the demand for systemic screening in pregnancy. Methods Retrospective anonymous serological analysis for HIV and syphilis was performed in plasma samples from 1232 pregnant women that were taken between May and July 2010 in Ambositra, Ifanadiana, Manakara, Mananjary, Moramanga and Tsiroanomandidy (Madagascar) during pregnancy follow‐up. Screening was based on Treponema pallidum haemagglutination tests for syphilis and rapid tests for HIV, with confirmation of positive screening results on line assays. Results Out of 1232 pregnant women, none were seropositive for HIV and 37 (3%) were seropositive for Treponema pallidum. Conclusions Our findings are in line with previous studies that describe considerable syphilis prevalence in the rural Madagascan population. The results suggest a need for screening to prevent peripartal Treponema pallidum transmission, while HIV is still rare. If they are known, Treponema pallidum infections can be easily, safely and inexpensively treated even in pregnancy to reduce the risk of transmission.     

Variabilité des concentrations plasmatiques de l’angiotensinogène et risque d’hypertension artérielle chez le rat transgénique

Aim

Genetic polymorphisms of the human angiotensinogen gene are frequent and may induce up to 30% increase of plasma angiotensinogen concentrations with a blood pressure increase of up to 5 mmHg. Their role for the pathogenesis of human arterial hypertension remains unclear. High plasma angiotensinogen levels could increase the sensitivity to other blood pressure stressors.

Methods

Male transgenic rats with a 9-fold increase of plasma angiotensinogen concentrations and male non-transgenic rats aged 10 weeks were treated or not with NG-Nitro-L-arginine-methyl ester for 3 weeks in their drinking water (n = 3/group). Systolic blood pressure and body weight were measured at baseline and at the end of the study when left ventricular weight and ventricular expression of angiotensin I-converting enzyme and procollagen Iα1 were determined (polymerase chain reaction).

Results

At baseline, transgenic rats had +18 mmHg higher bood pressure and –8% lower body weight compared to non-transgenic rats (P < 0.05) without significant changes for the vehicle groups throughout the study (P > 0.05). NG-Nitro-L-arginine-methyl ester increased blood pressure, left ventricular weight and left ventricular weight indexed for body weight by +41%, +17.6% and +18.6% (P < 0.05) in transgenic and +25%, +5.3% and +6.7% (P > 0.05) in non-transgenic rats compared to untreated animals, respectively. Cardiac gene expression showed no differences between groups (P > 0.05).

Conclusion

Increased plasma angiotensinogen levels may sensitize to additional blood pressure stressors. Our preliminary results point towards an independent role of angiotensinogen in the pathogenesis of human hypertension and associated end-organ damage.     

Morphological and immunocytochemical heterogeneity of cultured pinealocytes from one-week-and two-month-old rats: Planimetric and densitometric investigations

Abstract: In vitro preparations of rat pinealocytes are widely used for biochemical analyses of signal transduction processes. This paper deals with morphological and immunocytochemical features of such preparations. Special attention was paid to the problems of whether pinealocytes represent a heterogeneous cell population and how such heterogeneity may develop during ontogeny. The investigations were performed with cells which were obtained from the pineal organ of one-week-and two-month-old rats, attached to synthetic peptide-coated coverslips or tissue culture chamber slides, and maintained under in vitro conditions overnight. The attached cells were then fixed with paraformaldehyde. These preparations yielded monolayers of spherical cells of different sizes; most cells were isolated, but some of them were aggregated and formed small clusters. On the average, the cells from the one-week-old animals were smaller than the cells from the two-month-old animals. Immunocytochemical demonstration of S-antigen, a pinealocyte-specific marker, showed that the majority of the cells from two-month-old animals were intensely or moderately labelled. Pinealocytes from one-week-old animals were less S-antigen immunoreactive. Only very few cells (less than 1% displayed glial fibrillary acidic protein (GFAP)-immunoreactivity. Planimetric investigations of the cell size and semiquantitative densitometric investigations of the intensity of the S-antigen immunoreaction revealed that (i) pinealocytes kept in vitro form a heterogeneous cell population, and that (ii) this heterogeneity increases during postnatal development from one-week-old to two-month-old animals. Two groups of pinealocytes can be distinguished based on their developmental fate: pinealocytes of one group grow dramatically, but show only a moderate increase in S-antigen immunoreactivity, and pinealocytes of the other group retain their size, but display a distinct increment in S-antigen immunoreacti vitv.     

MUTATION FREQUENCY IN NURSES AND PHARMACISTS WORKING WITH CYTOTOXIC DRUGS

Individuals occupationally exposed to cytotoxic drugs may be at risk owing to the effects of these agents on DNA. As an index of DNA damage, in vivo mutations were measured in lymphocytes from 24 oncology nurses or pharmacists and 24 matched controls. Mutation frequency was significantly increased in exposed individuals and appeared to be related to duration of exposure. However, the overall magnitude of the increase was small and its biological significance remains to be determined.