小鼠胚胎干细胞向脂肪细胞分化的分子机制

随着肥胖患者不断增多,通过研究小鼠胚胎干细胞向脂肪细胞分化的分子机制,探讨肥胖发生机制已成为研究热点.研究认为,过氧化物酶体增殖物激活受体(PPARγ)、CCAAT增强子结合蛋白(C/EBPα)及脂肪细胞决定和分化依赖因子1和类固醇调控元件结合蛋白(ADD1/SREBP-1c)为前脂肪细胞系向脂肪细胞分化的关键转录因子,其他的调节因子如糖皮质激素(GC)、丝裂原活化蛋白激酶P38(P38MAPK)、生长激素(GH)等大多通过这些关键转录因子发挥诱导或抑制作用.     

肝X受体在脂肪生成和脂肪细胞形成中的作用

肝X受体(LXRs)是核受体超家族成员,其通过激活固醇调节元件结合蛋白-1c,促进脂肪的从头合成。此外,LXRs与脂肪细胞的形成亦有密切联系。LXRs的激活可能参与了前脂肪细胞向脂肪细胞分化。介绍肝X受体在脂肪生成和脂肪细胞形成过程中所起的作用及其分子机制,旨在为胚胎干细胞向脂肪细胞定向诱导分化以及多囊卵巢综合征等肥胖相关疾病的发病机制研究提供方向。     

转录因子C/EBPβ功能研究进展

CCAAT/增强子结合蛋白β(CCAAT/enhancer binding protein beta,C/EBPβ),也称作核因子白细胞介素-6(nuclear factor for IL-6,NF-IL6),是转录因子CCAAT/增强子结合蛋白( CCAAT/enhancer binding proteins,C/EBPs)家族的重要成员,其C端具有高度保守的DNA结合域和二聚化功能域,主要通过对靶细胞基因转录的调节参与细胞增殖与分化、肿瘤发生与凋亡、机体炎症反应等重要生命活动[1].现就C/EBPβ的功能及对人体疾病作用机制的研究进展综述如下.1 C/EBPβ在脂肪细胞形成中作用脂肪细胞的形成由复杂的转录因子网状系统所控制,而KLF4则是脂肪细胞形成必要的早期调节基因.Birsoy等[2]认为,C/EBPβ通过一个严密控制的负反馈圈抑制Krox20和KLF4的表达,KLF4基因沉默可以抑制脂肪细胞形成并可下调C/EBPβ水平.C/EBPβ和δ是诱导脂肪细胞形成最早的转录因子,他们通过调节其邻近的启动子元件转录激活了过氧化物酶体增殖物激活受体γ( peroxisome proliferators activated receptor gamma,PPARγ)和C/EBPα基因,而PPARγ和C/EBPα基因作为多效的转录激活因子则能够启动脂肪细胞.     

肝X 受体在脂肪生成和脂肪细胞形成中的作用

肝X 受体（LXRs）是核受体超家族成员,其通过激活固醇调节元件结合蛋白-1c,促进脂肪的从头合成。此外,LXRs与脂肪细胞的形成亦有密切联系。LXRs的激活可能参与了前脂肪细胞向脂肪细胞分化。介绍肝X受体在脂肪生成和脂肪细胞形成过程中所起的作用及其分子机制,旨在为胚胎干细胞向脂肪细胞定向诱导分化以及多囊卵巢综合征等肥胖相关疾病的发病机制研究提供方向。     

血管紧张素Ⅱ对前脂肪细胞分化相关转录因子表达的影响

目的探讨血管紧张素Ⅱ(angiotensin Ⅱ,AngⅡ)对前脂肪细胞分化过程中转录因子PPARγ、C/EBPα、SREBP1-c/ADD-1表达的调节从而研究AngⅡ调节前脂肪细胞分化可能的分子机制。方法 3T3-L1前脂肪细胞体外传代培养及诱导分化,用RT-PCR技术检测诱导分化过程中不同浓度AngⅡ处理6d对前脂肪细胞分化相关转录因子PPARγ、C/EBPα、SREBP1-c/ADD-1 mRNA表达水平的影响。结果 RT-PCR结果显示,100 nmol/L的AngⅡ处理细胞6 d后,PPARγ、C/EBPα、SREBP1-c/ADD-1 mRNA的相对表达量与对照组(AngⅡ添加浓度为0 nmol/L)有显著性差异(P<0.05),比对照组相应的转录因子分别增加了48%、50%、43%。结论前脂肪细胞分化过程中AngII能够上调PPARγ、C/EBPα、SREBP1-c/ADD-1 mRNA的表达量,AngⅡ可能通过影响PPARγ、C/EBPα和SREBP1-c/ADD-1的表达来调节前脂肪细胞的分化过程。     

辛伐他汀对人骨髓基质细胞成骨、成脂分化的作用及其机制

[目的]研究辛伐他汀对体外培养的成人骨髓基质细胞成骨分化和成脂分化的影响,并探讨其作用机制。[方法]分离健康成人骨髓基质细胞进行培养,传代后骨分化诱导组和脂肪分化诱导组分别添加10-7mol/L的辛伐他汀,同时进行空白对照。实时荧光定量PCR检测转录因子Cbfa1在成骨细胞中的分化,PPARγ2和LPL在脂肪细胞分化过程中的表达;碱性磷酸酶(ALP)检测试剂盒检测成骨细胞ALP比活性;流式细胞仪、油红O(oilredO)染色检测细胞成脂分化能力。[结果]骨分化诱导组Cbfa1表达(P﹤0.01)、ALP比活性(P﹤0.05)均高于对照组,脂肪分化诱导组PPARγ2(P﹤0.01)、LPL(P﹤0.05)表达均低于对照组;流式细胞仪脂肪细胞计数及脂肪细胞形成脂滴能力实验组均低于对照组。[结论]10-7mol/L辛伐他汀能促进Cbfa1的表达,增强成骨细胞ALP比活性和细胞外基质矿化;抑制PPARγ2、LPL的表达及脂肪细胞分化。     

脑源性神经营养因子对幼儿前体脂肪细胞分化的抑制作用

目的 探究脑源性神经营养因子(BDNF)对幼儿脂肪细胞增殖和分化的影响,为儿童肥胖症的治疗提供借鉴。方法 采集正常和肥胖儿童脂肪,real-time qPCR和Western blotting分别检测脂肪组织中BDNF、补体C1q肿瘤坏死因子相关蛋白13(CTRP13)和IL-6 mRNA以及蛋白的表达;分离培养原代前体脂肪细胞,采用不同浓度的BDNF和BDNF siRNA分别处理细胞,MTT和油红O染色分别检测细胞增殖和分化,甘油三酯( TG) 测定试剂盒检测细胞成脂情况,Western blotting 技术检测PPARγ、aP2、CTRP13和IL-6的表达。结果 与正常组相比,肥胖组脂肪组织中IL-6的表达较高,而CTRP13和BDNF的表达较低;BDNF对脂肪细胞的增殖没有影响;BDNF促进CTRP13的表达,抑制脂肪细胞分化和IL-6的表达,而BDNF siRNA则作用相反。结论 肥胖儿童脂肪组织中IL-6表达增高,CTRP13和BDNF表达降低,BDNF可抑制幼儿原代脂肪细胞的分化。     

绿茶和红茶多酚对大鼠脂肪分化相关基因表达影响的比较研究

目的:比较绿茶多酚(GTP)和红茶多酚(BTP)抗肥胖作用及其分子机制。方法:将实验大鼠分为空白对照组,高脂饲料+GTP组,高脂饲料+BTP组,高脂饲料组,定期检测体重,喂饲3个月后,观察脂肪组织和血脂水平变化,并提取附睾脂肪组织,应用RT-PCR技术观察与脂肪细胞分化相关的基因pref-1,aP2,TNF-α,瘦素,PPAR-γ,C/EBP-α在mRNA水平的表达。结果:GTP和BTP均能明显降低体重,减少脂肪。同时,GTP和BTP均能显著地抑制脂肪细胞特殊标记物aP2,TNF-α,瘦素,但两者之间无统计学差异。此外,GTP还上调前脂肪细胞标记物pref-1,且下调转录因子PPAR-γ。结论:GTP和BTP均可通过调节与脂肪细胞分化相关的基因,逆转脂肪细胞的分化,达到抗肥胖的作用,且GTP抗肥胖作用强于BTP。     

胰高糖素肽-1(GLP-1)通过Akt信号通路促进3T3-L1

<正>脂肪细胞体积与脂质代谢及胰岛素抵抗密切相关。研究发现,胰高糖素肽-1(GLP-1)能有效改善脂肪细胞的病理性增大,但其是否参与前脂肪细胞的分化尚缺乏足够证据。本研究探讨了GLP-1对3T3-L1前脂肪细胞分化过程的影响及作用机制。与对照组相比,GLP-1呈剂量依赖性地促进aP2、PPAR-γ蛋白表达,同时在转录     

间充质干细胞分化为脂肪细胞蛋白组学分析

目的 利用蛋白组学技术,分析成脂分化过程中蛋白表达改变,探讨脂肪形成机制.方法 以体外诱导人体骨髓间充质干细胞(mesenchymal stem cells,MSCs)分化脂肪细胞作为模型,收集诱导0,1和3周细胞,制成蛋白裂解液;采用双向电泳结合质谱分析方法,以0周为对照组,比较诱导1周或3周蛋白质表达改变.结果 成脂分化引起44个蛋白表达上调或下调水平超过2倍.这些蛋白功能类型主要属于代谢(39%)、细胞骨架(11%)、氧化还原(6.8%)、蛋白合成与分解(15.9%)、信号传导(6.8%)和分子伴侣(4.5%)等蛋白.结论 生物学信息分析表明,被调节的蛋白在脂肪形成过程中起重要作用;MSCs是研究多能前体细胞向包括前脂肪细胞在内的个体细胞系定向分化的有利工具.     

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.     

The occurrence of antimicrobial substances in toilet,sink and shower drainpipes of clinical units: A neglected source of antibiotic residues

Antibiotics represent one of the most important drug groups used in the management of bacterial infections in humans and animals. Due to the increasing problem of antibiotic resistance, assurance of the antibacterial effectiveness of these substances has moved into the focus of public health. The reduction in antibiotic residues in wastewater and the environment may play a decisive role in the development of increasing rates of antibiotic resistance. The present study examines the wastewater of 31 patient rooms of various German clinics for possible residues of antibiotics, as well as the wastewater of five private households as a reference.To the best of our knowledge, this study shows for the first time that in hospitals with high antibiotic consumption rates, residues of these drugs can be regularly detected in toilets, sink siphons and shower drains at concentrations ranging from 0.02?μg·L^?1 to a maximum of 79?mg·L^?1. After complete flushing of the wastewater siphons, antibiotics are no longer detectable, but after temporal stagnation, the concentration of the active substances in the water phases of respective siphons increases again, suggesting that antibiotics persist through the washing process in biofilms. This study demonstrates that clinical wastewater systems offer further possibilities for the optimization of antibiotic resistance surveillance.     

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.     

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.     

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.     

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.