MiR-146与免疫及自身免疫性疾病

MicroRNAs (miRNAs)介导的基因表达对于维持正常的细胞周期、分化、增殖、凋亡以及维持免疫系统的稳定性方面发挥着非常重要作用.MiR-146家族包含miR-146a和miR-146b,在不同的造血细胞中具有不同的表达谱.研究发现miR-146与炎症、自身免疫性疾病密切相关,负性调节炎症和固有免疫反应,可作为...     

MicroRNA-21在自身免疫性疾病中的调节作用与机制

MicroRNAs(miRNAs)是一类具有调控功能的小分子非编码RNA,其介导的基因表达对于维持正常细胞的增殖、分化、凋亡以及维持免疫系统的稳定有着重要作用.大量研究结果表明,miR-21通过Toll样受体(TLR)信号途径参与了固有免疫应答和炎症调节,而且它还可以通过多种方式对免疫细胞的生长、分化等产生影响.近年来,关于miR-21在自身免疫性疾病中的作用及其机制研究备受关注,本文对miR-21调节免疫反应及其对几种常见自身免疫性疾病的调节作用进行了综述.     

microRNA调控CD4~+T淋巴细胞分化与成熟的机制研究进展

小RNA(miRNA)是免疫系统的重要调节物,免疫细胞的谱系发育、增殖、分化、迁移和效应作用均受到miRNA的调控。miRNA主要通过靶作用于转录因子的mRNA形成复杂而精细的调控网络,不同的Th亚群受不同miRNA的调节,同时,某些miRNA如miR-155、miR-146a、miR-17-92簇等也可在多个不同的辅助T(Th)细胞亚群中起特定的调控作用,维持这些Th细胞亚群之间的分化平衡。miRNA的异常表达将导致Th细胞亚群之间的分化平衡被打破或功能失调,从而引发炎症或自身免疫性疾病。本文就免疫应答过程中miRNA对初始CD4+T细胞的活化及Th细胞亚群分化的重要调节作用进行综述。     

microRNA-155通过靶向抑制C/EBP-β和TAB2调控趋化因子的表达

目的明确microRNA(miR)-155对趋化因子CCL5、CXCL9、CXCL10、CCL20和CCL22表达的调控作用及其靶基因。方法培养RAW264.7细胞,向细胞内转染寡聚核苷酸(包括miR-ctrl、miR-155 mimics和miR-155 inhibitor)或靶基因保护子(包括C/EBP-β-TP~(miR-155)、TAB2-TP~(miR-155)和SOCS1-TP~(miR-155)),并用1μg/ml LPS刺激细胞活化,用RT-PCR、ELISA和Western blotting方法检测趋化因子及miR-155靶基因表达情况。结果 (1)miR-155抑制LPS活化的RAW264.7细胞分泌CXCL9、CXCL10和CCL20(P0.05),而促进上述细胞分泌CCL22(P0.05);(2)C/EBP-β和TAB2分别是miR-155调控CXCL9和CXCL10表达的靶基因。结论 miR-155可通过调控趋化因子的表达参与调控免疫炎症反应。     

miR-155 在T 细胞分化中的作用

<正>微小RNA(microRNA,miRNA)是一类非编码小分子RNA,稳定存在于人体各种体液中,通过转录后的水平精细调控基因时序性表达,参与细胞的分化、增殖和凋亡等过程。近年来体液中的miRNA作为一种新型的疾病诊断指标已有大量的研究报道,并显示出良好的应用前景~[1,2]。miR-155作为miRNA的重要成员之一,广泛参与T细胞的活化、增殖、分化过程。成熟的miR-155主要参与机体适应性免疫应答及免疫耐受,在自身免疫性疾病、感染     

miR-155、miR-34a和miR-30a在弥漫大B细胞淋巴瘤中的表达及意义

目的 分析miR-155、miR-34a和miR-30a在弥漫大B细胞淋巴瘤(diffuse large B-celllymphoma,DLBCL)中的表达水平,并探讨其与DLBCL临床病理特征的关系以及在DLBCL发生发展中扮演的角色.方法 应用RT-PCR方法检测46例DLBCL中miR-155、miR-34a及miR-30a的表达水平,用间期荧光原位杂交技术分析患者MYC和p53基因的异常情况,用免疫组织化学技术(Envision法)对DLBCL进行CD3、CD10、CD20、BCL-6、MUM-1标记.根据Hans的分类方法分为生发中心B细胞型(GCB型)和非生发中心B细胞型(non-GCB型).结果 与正常对照组相比,miR-155在DLBCL中显著高表达.miR-155在non-GCB型的表达明显高于GCB型.miR-155在MYC基因重排组表达降低.miR-34a在p53基因丢失组的表达较p53基因正常组显著降低.与BCL-6蛋白阴性表达组相比,miR-30a在BCL-6蛋白阳性组明显低表达.结论 miR-155在正常人群与DLBCL以及DLBCL的不同亚型之间表达不同,对DLBCL的诊断分型有一定参考价值.miR-34a对疾病预后判断有一定指导意义.miR-155、miR-34a和miR-30a可能是DLBCL潜在的治疗靶点.     

优生遗传信息

1．炎症与癌症的关系：炎症刺激了一种microRNA的分子（miR-155）水平的提高，使基因自发突变率增高。此miR-155只有22个碱基，但可调控基因的表达。     

ILC 细胞与自身炎症性疾病

固有淋巴细胞(ILCs)是一群参与固有免疫的异质性淋巴细胞,多分布于黏膜屏障部位,接受局部微环境细胞因子的信号后,通过分泌细胞因子及其他介质,发挥早期的免疫监视和免疫调节作用。ILCs细胞多为组织驻留淋巴细胞,参与黏膜免疫的形成,在淋巴细胞的发育、组织损伤的修复及上皮屏障的维持方面发挥重要作用。但由于其数量或功能异常,将参与炎症、自身免疫性疾病、代谢性疾病、哮喘、过敏等多种疾病的发生发展。鉴于不同ILC亚群在免疫监视、组织修复、稳态维持和炎症应答中的重要作用,ILCs细胞有望成为免疫治疗或炎症相关疾病治疗的靶点。本文就ILC细胞亚群的表型、发育和功能特点、ILCs细胞在炎症、组织稳态和修复中的作用、与自身炎症性疾病发生发展的关系及相关治疗策略等新进展做一综述。     

miR-155在哮喘患儿痰液的表达及对哮喘小鼠气道炎症的影响

目的探讨miR-155在哮喘患儿及哮喘小鼠中的表达及其对气道炎症的作用。方法应用realtime PCR方法检测哮喘患儿和健康儿童痰液,以及卵清蛋白诱导的哮喘小鼠和正常小鼠肺组织中miR-155的表达;化学合成miR-155模拟物与阴性对照,并分别鼻滴至哮喘小鼠,HE染色验证哮喘小鼠模型的成功建立,免疫荧光方法和western blot方法检测各组小鼠肺组织TNF-α与NF-κB的蛋白表达。结果与对照组相比,哮喘患儿痰液及哮喘小鼠肺组织中miR-155表达显著降低(P0.01);HE染色显示哮喘模型组小鼠炎症细胞浸润明显高于正常对照组,哮喘小鼠模型成功建立。miR-155模拟物滴入后,哮喘小鼠肺组织TNF-α与NF-κB的蛋白表达显著降低(P0.01)。结论 miR-155在支气管哮喘患儿及支气管哮喘小鼠模型中低表达,miR-155模拟物能够抑制哮喘小鼠的气道炎症。     

miR-155通过Nrf2通路调控CCI大鼠坐骨神经病理性疼痛和炎症反应

目的明确miR-155对CCI(chronic constriction injury)介导的坐骨神经炎症反应的调控作用与机制。方法以大鼠为研究对象,建立坐骨神经CCI模型,注射miR-155 inhibitor处理。通过机械缩足阈值(paw withdrawal threshold,PWT)和热缩足潜伏期(paw withdrawal latency,PWL)评估神经疼痛行为学。qPCR检测L4～L6大鼠背侧脊髓miR-155、Nrf2、IL-6、IL-1β和TNF-α的表达。ELISA检测IL-6、IL-1β和TNF-α在近端背根神经节(L4～L6)中的水平。双荧光素酶报告基因试验验证miR-155与Nrf2的相互作用关系。Western blot检测Nrf2的蛋白表达水平。结果 PWT和PWL在CCI大鼠术后1～3周显著降低,而miR-155的表达显著升高(P 0.05)。miR-155 inhibitor处理后,miR-155表达显著下调,且抑制miR-155能够上调PWT和PWL(P 0.05)。CCI处理显著升高IL-6、IL-1β和TNF-α水平,而抑制miR-155能明显逆转这一变化(P0.05)。此外,Nrf2是miR-155的下游靶标,且降低miR-155的表达可明显提高CCI下调的Nrf2的水平(P0.05)。沉默Nrf2能够部分逆转miR-155抑制对CCI引起的坐骨神经病理性疼痛和炎症反应的影响。结论 miR-155抑制可能通过激活Nrf2缓解CCI大鼠坐骨神经炎症反应及神经疼痛,为坐骨神经慢性卡压损伤的治疗策略研发提供了新的思路。     

Development in in vitro toxicology

There are three principal pressures driving the development of in vitro toxicology: (1) the need for more efficient testing systems to cope with the large number of xenobiotics currently being developed; (2) public pressure to reduce animal experimentation; and (3) a need for a better understanding of the mechanisms of toxicity. Within this, in vitro toxicology is focused on local, systemic, and target-organ toxicity. It is becoming increasingly apparent that a step or decision-tree approach using input of a variety of experimental data (physicochemical properties, biokinetics, cytotoxicity) provides the most efficient system for predicting toxicity. Examples of the use of in vitro toxicity systems for prediction of systemic toxicity and target-organ (liver) toxicity are presented.Originally presented at ECCP 93.     

新疆某院2016年住院疾病分类统计分析

目的 分析2016年新疆某院住院疾病分类构成及分布特点,为临床医护人员了解某院疾病的构成及分布提供数据。方法 采集某院2016年住院疾病分类统计数据,进行整理、统计、分析。结果 某院2016年共出院32728人,按系统疾病排序,居于前10位的依次是循环系统疾病、呼吸系统疾病、妊娠分娩及产褥期情况、消化道疾病、内分泌系统疾病、泌尿生殖系统疾病、中毒及损伤,结缔组织及骨骼疾病、神经系统疾病、肿瘤。前10位的系统疾病合计28223人,占出院总数的86.24%,是某院的主流病种。在32728例住院患者中,男性15259占总数的46.62%,女性17469占总数的53.38%,男女之比0.87∶1。前十位系统疾病分类年龄段分析,15~44岁、45~59岁、60岁及以上3个年龄段的住院患者较多,占住院患者疾病分类总数的78.68%。构成比中60岁及以上年龄段比重最大,占总数的39.94%。结论 通过对某院2016年住院疾病的构成分析,可以了解某院医疗辐射区域各系统疾病的构成以及年龄段分布情况,为某院对系统疾病的研究和防治提供可靠的统计数据。     

Apoptosis and changes in contractile protein pattern in the skeletal muscle in heart failure

Chronic heart failure is characterized as a clinical disorder by exercise intolerance. There are two factors that are independently responsible for the reduced exercise capacity: (a) a shift from myosin heavy chain 1 (MHC1) to MHC2a and MHC2b and (b) muscle atrophy. We have demonstrated, both in experimental models of heart failure and in man, that the more severe the heart failure, the greater the magnitude of skeletal muscle apoptosis. In the monocrotaline treated rat, that develops a severe right‐sided heart failure, the increased number of apoptotic nuclei was paralleled by increasing levels of circulating TNFα. In agreement with some recent observations showing that sphingolipids can mediate programmed cell death, we found that in animals with heart failure and high number of apoptotic nuclei, circulating levels of sphingosine were significantly increased. In a study conducted in patients with heart failure we found a correlation between exercise capacity limitation and skeletal myocytes apoptosis. There was also a correlation between degree of muscle atrophy and magnitude of apoptosis. The shift in MHCs, although with a different mechanism, is also responsible for the reduced exercise capacity in these patients. In fact there is a strong correlation between indices of severity of CHF and MHC composition. Muscle fatigue, appears earlier in patients that have a greater skeletal muscle expression of ‘fast’ MHCs. We have also demonstrated that MHCs shift and apoptosis can be prevented by using angiotensin II converting enzyme inhibitors and angiotensin II receptor blockers.     

休克过程中肾上腺髓质素变化的研究进展

Adrenomedullin (AM) is a new peptidergic regulator of vascular function. AM serves as a hormone, which has many biological properties, plays an important role in the many pathophysiological processes, especially shock. This review will highlight the structure, biological properties of AM and the relationship between AM and shock.     

Development in in vitro toxicology

There are three principal pressures driving the development of in vitro toxicology: (1) the need for more efficient testing systems to cope with the large number of xenobiotics currently being developed; (2) public pressure to reduce animal experimentation; and (3) a need for a better understanding of the mechanisms of toxicity. Within this, in vitro toxicology is focused on local, systemic, and target-organ toxicity. It is becoming increasingly apparent that a step or decision-tree approach using input of a variety of experimental data (physicochemical properties, biokinetics, cytotoxicity) provides the most efficient system for predicting toxicity. Examples of the use of in vitro toxicity systems for prediction of systemic toxicity and target-organ (liver) toxicity are presented.     

Recent advances in immunohistochemistry in gynaecological pathology

Recent years have witnessed significant developments in the use of immunohistochemistry in diagnostic gynaecological pathology. This review details the most significant of these. In ovarian pathology, differential cytokeratin staining (CK7 and 20) assists in distinguishing between a primary ovarian adenocarcinoma and a metastatic adenocarcinoma, especially of colorectal origin. The development of markers characteristic of ovarian sex cord-stromal tumours (especially alpha-inhibin) facilitates diagnosis of these neoplasms which is often difficult by morphology alone due to the wide differential diagnosis. In the uterus, the distinction between a primary endometrial and endocervical adenocarcinoma may be facilitated by use of a small panel of antibodies, including CEA, ER and vimentin. Newly developed antibodies such as CD10 and h-caldesmon may be of use in the diagnosis of uterine mesenchymal lesions, especially in the distinction between endometrial stromal and smooth muscle lesions. Proliferation markers, such as MIB1, are of value in the cervix in the diagnosis of preinvasive squamous and glandular lesions. Recent studies have shown that cervical adenoma malignum exhibits a gastric phenotype. Advances have also been made in trophoblastic disease with the development of antibodies reactive against trophoblast such as alpha-inhibin, mel-Cam and p57. A newly developed monoclonal antibody HMGIC which is expressed in vulvovaginal aggressive angiomyxoma may prove to be of value in the often difficult distinction of this lesion from its histological mimics.     

Prevalence of diarrhea viruses in hospitalized children in Hong Kong in 2008

A total of 209 stool samples were collected from pediatric patients admitted for acute gastroenteritis in a hospital in Hong Kong, during an 8‐month period from January to August 2008, and were tested for the presence of rotavirus, norovirus, sapovirus, adenovirus, and astrovirus using a multiplex RT‐PCR assay. The most common virus was rotavirus group A (59 of 209, 28%, mainly serotypes G1, G2, G3, and G9), followed by norovirus group II (48 of 209, 23%), adenovirus (7 of 209, 3%, serotypes 2, 3, and 41), and sapovirus (2 of 209, 1%). Interestingly, none of the specimens in this study were positive for astrovirus. One sample was found to have a dual infection with both norovirus group II and adenovirus. The results support the importance of norovirus as a causative agent of diarrhea in children, which may be underestimated by the current routine diagnostic testing. J. Med. Virol. 81:1903–1911, 2009. © 2009 Wiley‐Liss, Inc.     

Transmural changes in mast cell density in rat heart after infarct induction in vivo

The cardiac distribution of mast cells was investigated after the induction of acute myocardial infarction in the rat. The left anterior descending coronary artery (LAD) was occluded by ligation in the infarct group, whereas in sham rats only a superficial ligature was placed beside the LAD. Rats of both groups were killed at 4, 7, 14, 21, 35, and 85 days following surgery. Hearts were excised and formalin-fixed. Mast cell densities were monitored in subepicardial and subendocardial layers of the left ventricle (LV) in 6 μm thick toluidine blue-stained cross-sections. In control (non-operated) animals, mast cell densities were comparable in the LV subepicardial and subendocardial layers (1·5–2·0 cells per mm²). Following infarction, the mast cell density at the subepicardial site of the infarction gradually increased, reaching a maximum of 25 cells per mm² on day 21, while a non-significant increase was observed at the subendocardial site. In the non-infarcted regions, the mast cell density increased transiently to reach a maximum of 7 cells per mm² on day 35 in the subepicardial layer. Again, changes in mast cell density in the subendocardial layer were non-significant. In the sham group, a gradual increase to 9 cells per mm² on day 21 and a subsequent decrease to 5 cells per mm² on day 85 were observed in the subepicardial layers. These findings indicate a massive accumulation of mast cells in the subepicardial layers of the infarcted region and a small but significant effect of the surgical procedure on cardiac mast cell deposition, especially in the outer layers of the left ventricle.