SET蛋白及其对雄激素合成的调节作用

SET蛋白在多种组织细胞中表达,包括中枢神经系统、肾上腺以及性腺的类固醇合成细胞.SET蛋白是细胞内多任务因子,参与多种生物过程,包括细胞周期、细胞凋亡、核DNA复制、基因转录以及表观遗传调节、肿瘤生成和转移等,在睾丸和卵巢中参与调节雄激素合成.SET蛋白负性调节PP2A的活性,但并不改变PP2A的表达量;通过增强CYP17A1和3β-HSD的转录促进雄激素的合成.CKⅡ和SET相互结合,使SET磷酸化,增强了SET对PP2A的抑制作用;hnRNPA2通过RNP1序列与SET结合,增强SET对PP2A的抑制作用,调节雄激素合成.     

LH调节女性雄激素生成的分子信号通路研究进展

卵巢雄激素合成于卵泡膜细胞,并依赖于黄体生成激素（LH）的刺激作用,由LH下游众多信号通路精密调控,包括传统的环磷酸腺苷-蛋白激酶A-环磷酸腺苷反应元件结合蛋白（cAMP-PKA-CREB）、PKA-细胞外调节蛋白激酶（ERK）、Ras-Raf-MEK-ERK、磷脂酰肌醇3激酶（PI3K）-Akt等信号通路。卵泡发育过程中,磷脂酶Cβ-磷酸肌醇（PLCβ-IP）通路经非腺苷酸环化酶依赖途径激活,介导LH峰作用下颗粒细胞的最终分化。近年研究发现,Wnt、mTORC1等经典信号通路也与卵巢雄激素调节有关,并与其他经典信号通路之间存在复杂的网状交互作用,共同调控卵泡膜细胞雄激素生成。转录调节因子SET作为多任务蛋白,在多种组织中广泛表达,在卵泡膜细胞中通过抑制下游PP2A增加雄激素生成酶P450c17裂解酶活性,促进雄激素合成。LH调控通路过度激活与多种内分泌疾病（如多囊卵巢综合征）有关,并参与妊娠期糖尿病、胰岛素抵抗等多种病理过程。阐明卵泡膜细胞雄激素调控通路对解释雄激素相关疾病尤为重要,是寻找相应疾病治疗方法的基础。就LH作用于卵巢卵泡膜细胞调节雄激素生成的主要通路进行综述。     

细胞分化抑制因子-1与胃癌

细胞分化抑制因子(inhibitors of differentiation,Id),又称DNA结合抑制因子(inhibitors of DNA binding),是一种螺旋-环-螺旋(helix-loop-helix,HLH)蛋白,对促进细胞分化的碱性HLH(basic helix-loop-helix,bHLH)转录因子起负性调节作用。近年研究显示,Id-1蛋白为细胞周期循环从G1期进入S期所必需的蛋白,适当条件下可抑制细胞凋亡[1],Id-1的过表达也可通过钝化肿瘤抑制因子等方式促进细胞的增殖和分裂。Id-1与多种肿瘤发生相关,在乳腺癌、卵巢癌、黑色素瘤、甲状腺癌、膀胱癌、食管鳞状细胞癌、结肠癌、直肠癌及胰腺癌等肿瘤中高表…     

P27、Skp2与肿瘤

肿瘤的发生是正常细胞染色体严重损伤的复杂过程，包括抑癌基因的失活，原癌基因的不正常激活，DNA转录表达失控，DNA损伤等。不论何种原因造成的细胞转化其最终表现均为细胞周期调控机制紊乱，分化受阻导致肿瘤发生。细胞周期受细胞周期蛋白（cyclin）、细胞周期蛋白依赖性激酶（CDK）以及其抑制剂（CKI）的共同调控。P27是一种新发现的CKI，P27的活性改变影响细胞周期过程，进而影响细胞的增殖。细胞S期激酶相关蛋白2（Skp2），     

细胞分化抑制因子-1与胃癌

细胞分化抑制因子（inhibitors of differentiation，Id），又称DNA结合抑制因子（inhibitorsofDNAbinding），是一种螺旋-环-螺旋（helix—loop—helix，HLH）蛋白，对促进细胞分化的碱性HLH（basichelix—loop—helix，bHLH）转录因子起负性调节作用。近年研究显示，Id-1蛋白为细胞周期循环从G1期进入S期所必需的蛋白，适当条件下可抑制细胞凋亡，Id-1的过表达也可通过钝化肿瘤抑制因子等方式促进细胞的增殖和分裂。Id-1与多种肿瘤发生相关，在乳腺癌、卵巢癌、黑色素瘤、甲状腺癌、膀胱癌、食管鳞状细胞癌、结肠癌、直肠癌及胰腺癌等肿瘤中高表达，胃癌中亦高表达。已有证据表明Id-1表达和肿瘤的分化程度及恶性生物学特性相关，但Id-1在肿瘤发生、发展过程中的变化情况及其致癌机制仍不清楚。     

SETD2在恶性肿瘤中的表达及致癌机制的研究进展

组蛋白赖氨酸三甲基转移酶(SET domain containing 2,SETD2)基因位于人类第三号染色体短臂的2区1带(3p21.31)位点,长度约为147kb,编码人源含SET结构域蛋白SETD2,能特异性催化组蛋白H3第36位赖氨酸的三甲基化(Trimethylation of lysine 36 of Histone H3,H3K36me3)。SETD2参与DNA转录延伸、损伤修复、可变剪切、基因表达修饰、免疫应答、胚胎发育和血管生成等生物学过程。SETD2在肾细胞癌、胃癌、间皮瘤等多种肿瘤中都发生了突变或失活,主要通过抑制转录延伸、损伤修复、细胞周期进展、凋亡和细胞代谢等过程促进肿瘤的发生发展。SETD2的表达水平与癌症的临床病理参数和患者生存结局也密切相关。在肿瘤治疗上,SETD2的突变或失活可增强G2M细胞周期阻断剂、PI3K(磷脂酰肌醇3-激酶)-AKT(蛋白激酶B)抑制剂和铂类的抑癌效果,西奈芬近衍生物可直接靶向抑制SETD2蛋白,因此SETD2被认为是潜在的表观遗传治疗靶点,在相关癌症的诊疗研究中有较大的研究前景。     

P27、Skp2与肿瘤

肿瘤的发生是正常细胞染色体严重损伤的复杂过程,包括抑癌基因的失活,原癌基因的不正常激活,DNA转录表达失控,DNA损伤等.不论何种原因造成的细胞转化其最终表现均为细胞周期调控机制紊乱,分化受阻导致肿瘤发生.细胞周期受细胞周期蛋白(cyclin)、细胞周期蛋白依赖性激酶(CDK)以及其抑制剂(CKI)的共同调控.P27是一种新发现的CKI,P27的活性改变影响细胞周期过程,进而影响细胞的增殖.细胞s期激酶相关蛋白2(skp2),在许多细胞周期调控因子的泛素依赖性蛋白水解途径中起到特异性识别底物的作用,参与细胞周期的调控.大量研究发现,在一些恶性实体肿瘤中,P27常呈低表达,而skp2则高表达,且P27的表达与skp2呈负相关.因此推断P27的表达下调与Skp2的表达增加有关.     

MicroRNA在肿瘤分子诊断中的应用

MicroRNA(miRNA)在大多真核生物中表达,通过抑制翻译或诱导靶mRNA降解。miRNA是一种新的转录后基因表达调控模式,在复杂疾病形成过程中发挥着重要作用,调节了多种生物学过程,包括生长发育、信号转导、免疫调节、细胞凋亡、增殖及肿瘤发生等。越来越多的证据表明异常表达的miRNA是人类疾病的标志,包括肿瘤。差异表达的miRNA可能作为疾病早期诊断、分子分型及预后判断的指标,同时也可能成为多种肿瘤耐药新的治疗靶标。因此,miRNA在肿瘤中可能作为诊断、预测和治疗的生物标志。     

细胞周期蛋白在恶性肿瘤中的表达及其在肿瘤治疗中的作用

细胞周期蛋白(Cyclins)是细胞周期调节的核心分子,与细胞周期蛋白依赖性激酶(CDKs)、细胞周期蛋白依赖性激酶抑制因子(CKIs)等组成细胞周期调控网络系统。细胞周期调控机制的异常与肿瘤的发生发展密切相关,细胞周期蛋白的异常表达与CDKs结合形成的复合物,将导致细胞周期紊乱、细胞增殖失控,最终促使多种细胞癌变。Cyclins在多种恶性肿瘤中高表达,并在肿瘤的治疗中发挥重要作用。     

DNA依赖的蛋白激酶复合物研究进展

DNA依赖的蛋白激酶复合物 (DNA PK)是重组修复系统中最重要的组成部分 ,主要修复由电离辐射所引起的DNA双链断裂 (DSBs) ,并且可以通过磷酸化多种蛋白质底物 ,广泛参与转录及细胞凋亡等过程。同时 ,DNA PK在肿瘤细胞中所引起的对放疗和部分抗癌药物的抵抗性也得到了人们的重视。我们就DNA PK在肿瘤发生发展及治疗中的作用综述如下。1 DNA PK作用的分子机制 :对DSBs的修复主要存在2种形式 ,即单细胞生物的同源末端连接 (homologousendjoining,HEJ)和多细胞生物的非同源末端连接(nonhomologousendjoining ,NHEJ)。前者主要由R…     

Calcium intake in the elderly: validation of a dietary questionnaire

Epidemiological studies of calcium and osteoporosis have been hampered by the lack of a suitable tool for assessing calcium intake. This report describes a new frequency and amount questionnaire for measuring present and past calcium intake in the elderly. The validity of the questionnaire was tested against two commonly used standards of dietary assessment, five-day duplicate diets and seven-day weighed dietary inventories. The resulting correlation coefficients were, respectively, r = 0.76 and r = 0.69, while that for repeatability was r = 0.84. Furthermore, the questionnaire categorized subjects into thirds of the distribution of intake with almost no gross misclassification. It is suggested that the present findings may be extended to the majority of normal, healthy elderly subjects, implying wide application for the questionnaire in the assessment of calcium intake in the elderly.     

Self-reported health problems among Swedish miners one year after unemployment

Unemployment is considered to be a public health concern sincedeterioration in the health of the unemployed is often anticipated.However, for some groups, such as miners, unemployment mightimprove health due to a cessation of potentially harmful occupationalexposures. This study evaluates the health of 79 miners in oneSwedish iron-ore mine, and 226 age-matched controls from thegeneral population, during one year after the closure of themine. The participants received a questionnaire regarding medicalhistory and subjective symptoms at the beginning of the studyperiod, and after one year. Statistically significant negativeeffects on self-reported health attributable to unemploymentwere not found, although neuropsychiatric symptoms were morecommon among the unemployed miners. The miners reported a statisticallysignificant improvement in grip force (p=0.031). They had asignificantly higher prevalence of symptoms associated withmining related exposures when compared with the population controls;pain in the upper extremities [relative risk (RR)=2.27, 95%confidence interval (Cl)=1.44–3.59), back pain (RR=1.84;Cl=1.237–2.75), vasospastic disease of the fingers (RR=2.05;Cl=1.18–3.57) and obstructive respiratory symptoms (attacksof dyspnea and wheezing: RR=3.67; Cl=1.167–11.6).     

Excès de cas humains et animaux de tularémie en France au cours de l’hiver 2007–2008 : émergence ou phénomène isolé ?

Context

Tularemia is a zoonosis affecting humans and hares in France. We describe the results of surveillance in both species, in 2007 and 2008.

Methods

Human tularemia cases are mandatorily notifiable in France since 2003. In hares, surveillance relies on volunteer hunter associations in all districts of the country. Data from mandatory reports and volunteer surveillance in 2007/2008 were analyzed and compared with previous results.

Results

In 2007/2008, 144 cases were reported in humans and 117 cases in hares. This was a 100% increase compared to previous years. Human cases differed from those of previous years only by the frequency of contact with breeding animals. Human cases without any documented risk exposure were also more frequent.

Conclusion

An increase of tularemia cases occurred in 2007/2008 in both species. Complementary studies are needed to identify the species reservoir in France to understand the causes of this peak of cases.     

Occupational health hazards in mining: an overview

This review article outlines the physical, chemical, biological, ergonomic and psychosocial occupational health hazards of mining and associated metallurgical processes. Mining remains an important industrial sector in many parts of the world and although substantial progress has been made in the control of occupational health hazards, there remains room for further risk reduction. This applies particularly to traumatic injury hazards, ergonomic hazards and noise. Vigilance is also required to ensure exposures to coal dust and crystalline silica remain effectively controlled.     

Manufacture and use of nanomaterials: current status in the UK and global trends

This paper provides an overview of the production and use of nanomaterials (NMs), particularly in the UK. Currently, relatively few companies in the UK are identifiable as NM manufacturers, the main emphasis being the bulk markets in metals and metal oxides, and some niche markets such as carbon nanotubes and quantum dots. NM manufacturing in the UK does not reflect the global emphasis on fullerenes, nanotubes and fibres. Some assumptions have been made about the types of NM that are likely to be imported into the UK, which currently include fullerenes, modified fullerenes and other carbon-based NMs including nanotubes. Many university departments, spin-offs and private companies have developed processes for the manufacture of NMs but may only be producing small quantities for research and development (R&D) purposes. However, some have the potential to scale up to produce large quantities. The nanotechnology industry in the UK has strong R&D backup from universities and related institutions. This review has covered R&D trends at such institutions, and appropriate information has been added to a searchable database. While several companies are including NMs in their products, only a few (e.g. manufacturers of paints, coatings, cosmetics, catalysts, polymer composites) are using nanoparticles (NPs) in any significant quantities. However, this situation is likely to change rapidly. There is a need to collect more information about exposure to NPs in both manufacturing and user scenarios. As the market grows, and as manufacturers switch from the micro- to the nanoscale, the potential for exposure will increase. More research is required to quantify any risks to workers and consumers.     

深圳公立医院管理体制改革制度设计

深圳公立医院管理体制改革实行政事分开、管办分开,在理事会架构下按法定机构模式组建市医管中心,落实公立医院运营管理自主权.作者从当前公立医院管理体制的弊端入手,介绍了深圳市进行公立医院管理体制改革的基本思路及改革方案设计的主要举措,深入剖析了的改革方案的特点,并对改革效果进行了预测.     

Effects of nitrogen dioxide on red blood cells of rats: Changes in components of red cell membranes during in vivo exposure to NO2

Red cell membranes, prepared from red blood cells of rats exposed to 4, 10, or 20 ppm nitrogen dioxide (NO₂) for 1 to 10 days, were examined for evidence of changes in membrane components. Appreciable changes were not found in contents of phospholipid and cholesterol during exposure to 10 ppm NO₂. By contrast, protein content altered with the time of exposure. Moreover, changes in protein composition were observed by employing sodium dodecyl sulfate — polyacrylamide gel electrophoresis. Twenty-four-hour exposure to NO₂ at the concentration above 10 ppm resulted in a marked increase in the percentage of lysophosphatidylethanolamine (LysoPE) to the total phospholipids. The prolonged exposure to 10 ppm NO₂ gave rise to a further increase in LysoPE, whereas the percentage of phosphatidylethanolamine (PE) showed a gradual decrease. A 1-day exposure to 4.0 ppm NO₂ also caused an increase in sialic acid content and decreases in those of PE and hexose. In addition to contents of these components the percentage of LysoPE increased 5 days after exposure and the elevated values were maintained up to the end of exposure period. These results demonstrate that red blood cells in circulation exhibit different membrane properties in terms of lipid and carbohydrate composition during 10 days of exposure to 4.0 ppm NO₂.     

Investigating clusters in the workplace and beyond

Clusters of disease are common and occur in the workplace and in the general community. They often arouse considerable concern among the population. Investigations have sometimes lead to exciting new knowledge, but in general the investigation of clusters is difficult and often unrewarding, especially for community clusters. In the workplace, investigations are more likely to find associations and even new causes, but still many clusters remain enigmatic. Despite this, there are many reasons for investigating clusters, including allaying community concern and identifying uncontrolled exposures. A structure for investigating clusters in the workplace is suggested.