microRNA在COPD中的研究进展

microRNA 是一种短的内源性单链非编码 RNA 分子,主要在转录后水平通过与靶mRNA互补配对的方式抑制 mRNA的翻译或直接降解靶 mRNA.多于1000多种 microRNA存在于人体的基因组中,并调控大于60%基因的表达.许多研究证明,microRNA在 COPD中表达谱的改变影响疾病的自然病程和病理生理过程.因此,microRNA 成为 COPD 诊断和治疗的研究热点.现对microRNA在COPD中的作用机制、表达及 microRNA与COPD严重程度的关系作一综述.     

microRNA与胆固醇代谢

microRNA(miRNA)是一种长度约为22个核苷酸的非编码小分子RNA.microRNA通过与靶mRNA的3'端非编码区的种子序列互补配对而在转录后水平上对基因的表达进行调控,microRNA参与生物体内许多复杂的生理过程,如细胞分化、凋亡、个体发育等,并与人类多种疾病如病毒感染、糖尿病、心血管疾病和癌症等密切相关.随着越来越多的microRNA被发现,其在生物体物质代谢方面的调节作用也逐渐被认识.文章将介绍近年采关于microRNA的研究进展及其在胆固醇代谢中的作用及应用前景.     

肿瘤抑制因子microRNA126的研究进展

大量研究表明,microRNA作为一种重要的转录后基因调控元件,在多种疾病尤其是肿瘤的发生发展中发挥重要作用.microRNA126被认为是一种肿瘤抑制因子,在多种肿瘤如胃癌、结肠癌、肺癌、宫颈癌以及乳腺癌等肿瘤中有明显的抑制作用.此外rnicroRNA126在其他疾病如哮喘、血管炎症等也有着重要作用.本文对micro...     

细粒棘球蚴重组蛋白P29(rEg.P29)诱导下差异表达microRNA的筛选及分析北大核心CSCD

目的对细粒棘球蚴重组蛋白P29(rEg.P29)诱导小鼠差异表达的microRNA进行筛选和分析,以期为rEg.P29免疫前后宿主免疫细胞的分化研究提供线索。方法将6-8周龄SPF级BALB/c小鼠随机分为2组,rEg.P29免疫组和对照组,每组12只。rEg.P29免疫组于小鼠腹部多点免疫重组蛋白100μl(含rEg.P2910μg),共免疫2次,第1次免疫2周后进行第2次免疫。提取第2周(第1次免疫后2周)、第6周(第1次免疫后4周)、第8周(第1次免疫后6周)各组小鼠外周血淋巴细胞,分离microRNA用于建库测序,利用生物信息学方法筛选rEg.P29诱导下差异表达的microRNA分子,并进行注释分析。结果测序所得数据经拼接组装比对,共获得成熟的microRNA序列342条,其中已知的microRNA序列206条,未知信息序列36条。在已知的microRNA分子中,差异表达共55个,其中上调31个,下调24个;在新发现的microRNA分子中,差异表达11个,其中上调5个,下调6个。靶基因预测结果显示,表达上调microRNA调控的靶基因有14279个,表达下调microRNA调控的靶基因13911个。GO富集注释结果显示,在上调分子中,生物学进程(BP)获得18条注释信息,其中16个microRNA调控的826个靶基因被注释到细胞分化(cell differentiation)条目下;在下调分子中,生物学进程(BP)获得21条注释信息,其中25个microRNA调控的712个靶基因被注释到细胞分化(cell differentiation)条目下。KEGG通路分析结果显示,无论是表达上调还是下调的分子,其靶基因的代谢通路均显著富集到Th1 and Th2 cell differentiation、Th17 cell differentiation、B cell receptor signaling pathway等与细胞分化相关的信号通路以及与肿瘤相关的信号通路上。结论在rEg.P29诱导下小鼠免疫细胞存在差异表达的microRNA分子,这些分子可能与免疫细胞的分化相关。     

microRNA表达谱与消化器官肿瘤的发生、诊断及治疗

microRNA (miRNA)是一种大小约21-23个碱基的、非蛋白编码单链小分子RNA,下调参与许多重要细胞活动(包括发育、增殖、分化、凋亡)基因的表达.近期的研究发现,miRNA在肿瘤的发生和发展中起着重要的作用,miRNA具有癌基因和抑癌基因的作用.已发现若干miRNA直接参与消化器官(包括肝、结肠、胰腺、胃、胆管)肿瘤的发生和发展,miRNA表达谱与消化器官肿瘤的诊断、病理分级、临床分期、疾病进展、预后和对治疗的反应性等相关.miRNA表达谱可以鉴定能抑制下游活化的癌基因信号途径或作用于与肿瘤发生和发展有关的蛋白编码基因的miRNA靶基因,miRNA介导的治疗还可能用于肿瘤的预防和治疗.     

细粒棘球蚴重组蛋白P29(rEg.P29)诱导下差异表达microRNA的筛选及分析

目的对细粒棘球蚴重组蛋白P29(rEg.P29)诱导小鼠差异表达的microRNA进行筛选和分析,以期为rEg.P29免疫前后宿主免疫细胞的分化研究提供线索。方法将6-8周龄SPF级BALB/c小鼠随机分为2组,rEg.P29免疫组和对照组,每组12只。rEg.P29免疫组于小鼠腹部多点免疫重组蛋白100μl(含rEg.P29 10μg),共免疫2次,第1次免疫2周后进行第2次免疫。提取第2周(第1次免疫后2周)、第6周(第1次免疫后4周)、第8周(第1次免疫后6周)各组小鼠外周血淋巴细胞,分离microRNA用于建库测序,利用生物信息学方法筛选rEg.P29诱导下差异表达的microRNA分子,并进行注释分析。结果测序所得数据经拼接组装比对,共获得成熟的microRNA序列342条,其中已知的microRNA序列206条,未知信息序列36条。在已知的microRNA分子中,差异表达共55个,其中上调31个,下调24个;在新发现的microRNA分子中,差异表达11个,其中上调5个,下调6个。靶基因预测结果显示,表达上调microRNA调控的靶基因有14 279个,表达下调microRNA调控的靶基因13 911个。GO富集注释结果显示,在上调分子中,生物学进程(BP)获得18条注释信息,其中16个microRNA调控的826个靶基因被注释到细胞分化(cell differentiation)条目下;在下调分子中,生物学进程(BP)获得21条注释信息,其中25个microRNA调控的712个靶基因被注释到细胞分化(cell differentiation)条目下。KEGG通路分析结果显示,无论是表达上调还是下调的分子,其靶基因的代谢通路均显著富集到Th1 and Th2 cell differentiation、Th17 cell differentiation、B cell receptor signaling pathway等与细胞分化相关的信号通路以及与肿瘤相关的信号通路上。结论在rEg.P29诱导下小鼠免疫细胞存在差异表达的microRNA分子,这些分子可能与免疫细胞的分化相关。     

芪苈强心对心肌梗死后心力衰竭大鼠miRNA表达的调控作用

目的利用microRNA芯片杂交技术研究芪苈强心对心肌梗死后心力衰竭大鼠microRNA表达的调控作用,为进一步探索芪苈强心保护心脏功能的作用通路提供新的视角。方法通过结扎雄性SD大鼠左前降支建立急性心梗后心力衰竭模型,分为假手术组,心衰模型组和芪苈强心组,药物干预前后分别行超声心动图检查。治疗6周后处死动物、取材,行microRNA芯片杂交,筛选差异表达microRNA,实时荧光定量PCR验证芯片结果。对差异表达microRNA进行靶基因预测及进一步生物信息学分析。结果芪苈强心显著提高心衰大鼠左室射血分数(60.2±5.3%vs.36.5±5.9%,p0.01)。心衰模型组与假手术组比较,22个microRNA表达上调,5个下调;芪苈强心组与心衰模型组比较,2个microRNA表达上调,21个下调。实时荧光定量PCR结果与芯片筛查结果一致。对其中11个差异倍数较大的microRNA行靶基因预测,共1782个靶基因,显著富集于470个GO生物学过程条目、120个GO细胞组成条目和115个GO分子功能条目(p0.05);KEGG分析中,66条信号通路被有效富集(p0.05),包括趋化因子信号转导通路、凋亡信号通路、HIF-1信号通路、TNF信号通路等。结论在心梗后心力衰竭模型中,芪苈强心调控多个microRNA的表达,多靶点、多途径地发挥保护心脏、逆心肌重塑的作用。     

人退变腰椎间盘特异性表达microRNA的靶基因及JNK信号转导通路在椎间盘退变中的分子生物学机制

目的探讨筛选人退变腰椎间盘特异性表达microRNA靶基因JNK信号转导通路在椎间盘退变过程中的分子生物学机制。方法选取腰椎退行性疾病患者10例为研究组,术中均切除退变髓核组织块。选取腰椎爆裂性骨折接受前路减压髓核切除术患者4例为对照组,术中均切除正常髓核组织块。收集到的髓核组织分别进行髓核细胞分离、培养、鉴定,并提取总RNA;使用microRNA微阵列芯片方法筛选得到差异表达的microRNA,采用实时q PCR技术验证其中高表达者,采用Targetscan6.2软件进行靶基因预测,并分析靶基因和差异表达基因功能明显相关的信号通路;定量PCR方法对筛选的结果进行验证。结果在人退变腰椎间盘组织中microRNA.494和microRNA.513a.5p呈明显的高表达,比值分别为2.8351、2.1157,与验证结果一致。预测靶基因分别为MKK4、Jun D,分别处于JNK信号通路的上游和下游,参与JNK信号传导。结论 microRNA.494和microRNA.513a.5p在人退变腰椎间盘中高表达,相应的靶基因为MKK4、Jun D;JNK信号转导通路在人退变腰椎间盘发病机制中发挥关键的正负反馈调节作用。     

microRNA与胰岛素抵抗

microRNA是一类长度约为21～23个核苷酸的非编码小分子RNA,通过与靶分子mRNA3’端非编码区域（3＇UTRs）互补配对结合降解靶基因mRNA或者抑制其翻译,在转录后水平对靶基因发挥负性调控作用.最近许多研究表明,microRNA在胰岛素抵抗中发挥非常重要的作用,主要通过调节参与胰岛素信号通路的关键蛋白影响胰岛素的外周作用.microRNA与胰岛素抵抗密切相关,可能成为在分子水平治疗胰岛素抵抗及其相关代谢性疾病的一个新靶点.     

MicroRNA在气道炎症性疾病中的研究进展

微小RNA(microRNA)是一类长约22nt的内源性非编码小RNA,microRNA与靶mRNA特定碱基结合引起靶mRNA的降解或抑制其翻译,进而调控基因转录后的表达.近年来的一些研究表明microRNA与肺的发育、炎症反应和以慢性阻塞性肺疾病、哮喘为代表的气道炎症性疾病密切相关,现就microRNA在该领域的研究进展作一综述.     

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.     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

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.