Ezetimibe blocks the internalization of NPC1L1 and cholesterol in mouse small intestine

The multiple transmembrane protein Niemann-Pick C1 like1 (NPC1L1) is essential for intestinal cholesterol absorption. Ezetimibe binds to NPC1L1 and is a clinically used cholesterol absorption inhibitor. Recent studies in cultured cells have shown that NPC1L1 mediates cholesterol uptake through vesicular endocytosis that can be blocked by ezetimibe. However, how NPC1L1 and ezetimibe work in the small intestine is unknown. In this study, we found that NPC1L1 distributed in enterocytes of villi and transit-amplifying cells of crypts. Acyl-CoA cholesterol acyltransferase 2 (ACAT2), another important protein for cholesterol absorption by providing cholesteryl esters to chylomicrons, was mainly presented in the apical cytoplasm of enterocytes. NPC1L1 and ACAT2 were highly expressed in jejunum and ileum. ACAT1 presented in the Paneth cells of crypts and mesenchymal cells of villi. In the absence of cholesterol, NPC1L1 was localized on the brush border of enterocytes. Dietary cholesterol induced the internalization of NPC1L1 to the subapical layer beneath the brush border and became partially colocalized with the endosome marker Rab11. Ezetimibe blocked the internalization of NPC1L1 and cholesterol and caused their retention in the plasma membrane. This study demonstrates that NPC1L1 mediates cholesterol entering enterocytes through vesicular endocytosis and that ezetimibe blocks this step in vivo.     

Association of N-Terminal Pro-Brain Natriuretic Peptide with Cognitive Function and Depression in Elderly People with Type 2 Diabetes

Background

Type 2 diabetes mellitus is associated with risk of congestive heart failure (CHF), cognitive dysfunction and depression. CHF itself is linked both to poor cognition and depression. The ventricular N-terminal pro-brain natriuretic peptide (NT-proBNP) is a marker of CHF, suggesting potential as a marker for cognitive impairment and/or depression. This was tested in the Edinburgh Type 2 Diabetes Study (ET2DS).

Methodology and Principal Findings

Cross-sectional analysis of 1066 men and women aged 60–75 with type 2 diabetes. Results from seven neuropsychological tests were combined in a standardised general cognitive ability factor, ‘g’. A vocabulary-based test estimated pre-morbid cognitive ability. The Hospital Anxiety and Depression Scale (HADS) assessed possible depression. After adjustment for age and sex, raised plasma NT-proBNP was weakly associated with lower ‘g’ and higher depression scores (ß −0.09, 95% CI −0.13 to −0.03, p = 0.004 and ß 0.08, 95% CI 0.04 to 0.12, p<0.001, respectively). Comparing extreme quintiles of NT-proBNP, subjects in the highest quintile were more likely to have reduced cognitive ability (within the lowest tertile of ‘g’) and ‘possible’ depression (HADS depression ≥8) (OR 1.80; 95% CI: 1.20, 2.70; p = 0.005 and OR 2.18; 95% CI: 1.28, 3.71; p = 0.004, respectively). Associations persisted when pre-morbid ability was adjusted for, but as expected were no longer statistically significant following the adjustment for diabetes-related and vascular co-variates (β −0.02, 95% CI −0.07 to 0.03, p>0.05 for ‘g’; β 0.03, 95% CI −0.02 to 0.07, p>0.05 for depression scores).

Conclusion

Raised plasma NT-proBNP was weakly but statistically significantly associated with poorer cognitive function and depression. The prospective phases of the ET2DS will help determine whether or not NT-proBNP can be considered a risk marker for subsequent cognitive impairment and incident depression and whether it provides additional information over and above traditional risk factors for these conditions.     

山西云顶山自然保护区野生种子植物区系研究

山西云顶山自然保护区位于吕梁山脉中段,有野生种子植物926种,隶属于391属、85科,其中裸子植物2科、4属、6种,被子植物83科、387属、920种(其中双子叶植物72科、311属、756种;单子叶植物11科、76属、164种).种子植物属的区系成分复杂多样,以温带成分占绝对优势,温带属共275属,占总属数的82.08％.种子植物种的区系成分中,温带分布占绝对优势,达566种,占总种数的62.61％,中国特有分布次之,有306种,它们是构成云顶山自然保护区森林植被和灌丛植被的建群种和优势种的主要成分.经与有关山地植物区系和植被组成比较后得出,云顶山自然保护区与庞泉沟自然保护区具有较高的同质性和密切的联系,与五台山次之,而与中条山具有明显的差异.云顶山自然保护区有国家二级保护植物野大豆,还有山西省重点保护植物山西乌头、红景天和党参3种.     

汾河流域中下游湿地植被优势种种间关联性分析

采用x2检验、Pearson相关系数及Spearman秩相关系数检验等数量分析方法对汾河流域中下游湿地植被的34个优势种,共561个种对间的关联性进行定量研究.结果表明:x2检验有178个种对呈正相关,256个种对呈负相关,正负关联比为0.70;Pearson相关系数检验有157个种对呈正相关,402个种对呈负相关,正负关联比为0.39;Spearman秩相关系数检验有216个种对呈正相关,343个种对呈负相关,正负关联比为0.63;与x2检验和Pearson相关系数相比,Spearman秩相关系数检验具有较高的灵敏度.561个种对中负关联居多,达到极显著或显著的种对少,说明汾河流域中下游湿地植被群落处于演替初期.根据这34个优势种群对环境的适应方式和主导生态因素辅助以PCA排序,可将它们划分为4种生态种组.     

胃癌肝转移术中射频消融治疗的临床意义

目的：评估胃癌根治术同时性射频消融治疗在治疗胃癌肝转移的临床意义。方法：收集2008年1月至2010年12月19例胃癌肝转移患者,合计转移灶33个,转移灶小于4厘米,且合计不超过4个转移灶。射频消融治疗在术中超声引导下完成。Kap-lan—Meier法分析无病生存期,无肝转移生存期及总生存期。对临床病理学因子及肝转移相关因子采用Log-rank法Cox风险比例模型解析。结果：中位无病生存、无肝转移生存及总生存期为355,394及488天。有3例患者获得长期的无复发生存。单因素分析显示,较早的T分期、N分期,较少的转移灶数量,较小的转移灶直径与良好的预后相关。多因素分析提示,病灶数量与病灶直径为独立预后因子。结论：肝转移射频消融治疗安全性好,对单发的小于4cm转移灶,以及多发病灶合计直径小于4cm者射频消融治疗较为适用,可有显著生存获益。部分患者可迭临床治愈。对于胃癌肝转移的合适病例,射频消融治疗值得推广。     

大鼠髓核细胞原代培养及表型鉴定

目的:探讨Ⅱ型胶原酶联合透明质酸酶消化分离培养髓核细胞及免疫细胞化学表型鉴定的可行性。方法:无菌条件下分离SD大鼠凝胶状髓核,采用Ⅱ型胶原酶联合透明质酸酶消化分离髓核细胞并连续培养,倒置相差显微镜下观察,随后进行免疫细胞化学染色检测不同代次髓核细胞HIF-1、Ⅰ、Ⅱ型胶原、MMP2及蛋白聚糖的表达情况,并给予MTT法测定髓核细胞生长曲线。结果:Ⅱ型胶原酶联合透明质酸酶分离培养原代髓核细胞需要12 d左右贴壁,达95%融合需要34 d,而传代髓核细胞贴壁速率明显增快至10 h,且其倍增时间约为2.5 d;免疫细胞化学显示髓核细胞均表达HIF-1、Ⅰ、Ⅱ型胶原、MMP2和蛋白聚糖,且随着髓核细胞传代其HIF-1α、HIF-1β、Ⅰ型胶原及MMP2表达均增加,但Ⅱ型胶原表达降低,而蛋白聚糖表达无明显差异;MTT法显示随着髓核细胞传代其增殖有所减缓。结论:Ⅱ型胶原酶联合透明质酸酶可成功分离髓核细胞,提高培养效率,且HIF-1α、HIF-1β、Ⅰ、Ⅱ型胶原及MMP2可作为髓核细胞表型分子用于髓核细胞的鉴定。     

护理干预对输尿管镜钬激光碎石术患者生活质量的影响

目的:探讨护理干预对输尿管镜钬激光碎石术患者生活质量的影响。方法:采取前瞻性随机对照的方法,从2008年5月到2010年12月,共有123例接受输尿管镜钬激光碎石术的输尿管结石患者被随机分成对照组和护理干预组。使用世界卫生组织生存质量测定量表简表评价输尿管镜钬激光碎石术对患者生活质量的影响。结果:非护理干预组和护理干预组的世界卫生组织生存质量测定量表简表的生活质量评分手术后比手术前有明显改善(P<0.05)。输尿管镜钬激光碎石术后,护理干预组患者的生活质量优于非护理干预组。结论:护理干预能明显改善输尿管镜钬激光碎石术患者的生活质量。     

基于CASA模型的内蒙古典型草原植被净初级生产力动态模拟

 植被净初级生产力及其对气候变化的响应研究是全球变化的核心内容之一。在利用内蒙古典型草原连续13年的地上生物量资料对基于遥感信息的生态系统碳循环过程CASA(Carnegie-Ames-Stanford Approach)模型验证的基础上, 分析了内蒙古典型草原1982~2002年植被净初级生产力(Net primary productivity, NPP)的时间变异及其影响因子。结果表明: 1) 1982~2002年21年间内蒙古典型草原的平均年NPP为290.23 g C·m^–2·a^–1, 变化范围为 145.80~502.84 g C·m^–2·a^–1; 2)内蒙古典型草原NPP呈增加趋势, 但没有达到显著性水平, 其中1982~1999年的18年间NPP呈现非常显著的增加趋势(p<0.01), NPP增加的直接原因是由于生长旺季生长本身增强所致; 3)内蒙古典型草原NPP与年降水量呈极显著的相关关系, 年降水量显著影响NPP的变异, 而NPP与年均温无显著相关关系。     

活化自然杀伤细胞对间充质干细胞杀伤作用研究

研究NK(natural killer)细胞对人脐血来源的MSCs(mesenehymal stem cells)是否有杀伤作用.重组IL-2激活的NK细胞与脐血来源的MSCs按一定比例共孵育,流式细胞仪收集靶细胞并测定被杀伤细胞的百分率.结果显示NK细胞对脐血来源的MSCs有杀伤作用.     

靶向细胞周期蛋白B1的抗肿瘤研究

细胞周期蛋白B1(cyclin B1,CCNB1)是有丝分裂期(M期)周期蛋白,与细胞周期蛋白依赖性激酶1(cyclin-dependent kinase 1,CDK1)结合形成成熟促进因子(maturation promotingfactor,MPF),MPF的激活为真核细胞启动有丝分裂所必需.CCNB1在肿瘤组织中普遍高表达,该蛋白质作为一种细胞周期进程调节剂在肿瘤细胞内的表达量是判断肿瘤恶性程度高低的指标之一,被视为肿瘤抗原,故靶向CCNB1进行抗肿瘤治疗是肿瘤基因治疗中一个极有潜力的策略.首先分析了CCNB1与肿瘤的相关性,进而从CCNB1活性抑制因子、药物或化合物对CCNB1的抑制作用及CCNB1与抗肿瘤免疫等多方面对靶向CCNB1的抗肿瘤研究进行了综述.