小分子药物BNTA通过上调Insig1缓解高胆固醇引起的骨关节炎

骨关节炎(osteoarthritis,OA)是运动系统常见的退行性疾病,具有高发病率和高致残率。骨关节炎的发病机制目前尚不明确,既往研究认为骨关节炎发病主要与创伤因素相关,而近期研究表明,以胆固醇代谢异常为主的代谢性因素同样与骨关节炎密切相关,骨关节炎的治疗以早期对症治疗和晚期手术治疗为主,尚无针对病因的特效药物。既往研究中发现,有一种具有软骨保护作用的小分子药物BNTA,其在创伤引起的骨关节炎中具有较好的疗效,但其对高胆固醇引起的骨关节炎的作用尚不明确。本研究为探究BNTA对高胆固醇引起的骨关节炎的治疗作用及其机制,采用高胆固醇饮食构建了大鼠骨关节炎模型,取膝关节石蜡切片进行组织学评估,使用油红O染色评估大鼠软骨细胞内的脂质积聚情况,使用RT-qPCR、免疫荧光和免疫组化评估软骨细胞合成代谢、分解代谢及胆固醇代谢相关基因和蛋白质的表达。结果显示,BNTA可缓解高胆固醇大鼠骨关节炎模型中的病理表现,改善OARSI评分。在大鼠软骨细胞中,BNTA可促进合成代谢相关基因col2、sox9、acan的表达,抑制分解代谢相关基因mmp13、adamts5的表达,可改善高胆固醇引起的大鼠软骨细胞脂质积聚。在大鼠软骨细胞和高胆固醇大鼠骨关节炎模型中BNTA均可上调Insig1表达。本研究证实,高胆固醇可在体内和体外实验中加重骨关节炎,可引起大鼠软骨细胞脂质积聚增加。在体内和体外实验中BNTA均能缓解高胆固醇引起的骨关节炎表型,改善软骨细胞内的异常脂质积聚,其作用可能为通过上调Insig1抑制细胞内的胆固醇生物合成,从而缓解脂质异常积聚。     

青藏高原丽蝇科昆虫物种多样性初探

本文从种数、特有物种和区系构成等角度分析了青藏高原丽蝇科昆虫的物种多样性。青藏高原已知丽蝇5亚科35属120种,占中国已知种数的44.28%,其中特有种55种,占该地区总种数的45.83%;区系构成以特有种、古北界 东洋界共同种及典型的东洋界种和古北界种为主,但澳洲界、新北界、非洲界和新热带界共同种也占一定比例。文中讨论了该地区特有种丰富的原因及地质历史环境对其的影响,分析了区系构成中各种区系成分的比例及形成原因。     

The effects of a mutant connexin 26 on epidermal differentiation

To elucidate the mode of action of dominant mutant connexins in causing inherited skin diseases, transgenic mice were produced that express the true Vohwinkel syndrome-associated mutant Cx26 (D66H), from a keratin 10 promoter, specifically in the suprabasal epidermal keratinocytes. Following birth, the transgenic mice developed keratoderma similar to that of human carriers of Cx26 (D66H). Expression of the transgene resulted in a loss of Cx26 and Cx30 at intercellular junctions of epidermal keratinocytes and accumulation of these connexins in the cytoplasm. Injection of primary mouse keratinocytes with Lucifer Yellow showed no difference in terms of dye spreading between transgenic and non transgenic keratinocytes in vitro. Expression of the mutant Cx26 (D66H) did not interfere with the formation of the epidermal water barrier during late embryonic development. Attempts to produce transgenic mice expressing the wild type form of Cx26 from the K10 promoter failed to produce viable animals although transgenic embryos were recovered at days 9 and 12 of gestation, suggesting that the transgene might be embryonic lethal.     

Influence of complex nutrients, temperature and pH on bacteriocin production by Lactobacillus sakei CCUG 42687

The effects of process conditions and growth kinetics on the production of the bacteriocin sakacin P by Lactobacillus sakei CCUG 42687 have been studied in pH-controlled fermentations. The fermentations could be divided into phases based on the growth kinetics, phase one being a short period of exponential growth, and three subsequent ones being phases of with decreasing specific growth rate. Sakacin P production was maximal at 20 °C. At higher temperatures (25–30 °C) the production ceased at lower cell masses, when less glucose was consumed, resulting in much lower sakacin P concentrations. With similar media and pH, the maximum sakacin P concentration at 20 °C was seven times higher than that at 30 °C. The growth rate increased with increasing concentrations of yeast extract, and the maximum concentration and specific production rate of sakacin P increased concomitantly. Increasing tryptone concentrations also had a positive influence upon sakacin P production, though the effect was significantly lower than that of yeast extract. The maximum sakacin P concentration obtained in this study was 20.5 mg l⁻¹. On the basis of the growth and production kinetics, possible metabolic regulation of bacteriocin synthesis is discussed, e.g. the effects of availability of essential amino acids, other nutrients, and energy. Received: 7 June 1999 / Received revision: 15 September 1999 / Accepted: 17 September 1999     

Production of sakacin P by Lactobacillus sakei in a completely defined medium

In order to investigate factors influencing the production of the bacteriocin, sakacin P, Lactobacillus sakei CCUG 42687 was grown in a completely defined medium (DML-B) with 33 components. Although the maximum sakacin P concentration obtained was higher on a complex medium due to higher cell mass, the production per cell mass was higher in DML-B. Sakacin P was produced at 4-30 degrees C, with the highest specific production at low temperatures. More sakacin P was produced at uncontrolled pH compared with cultivation at pH 6.3. Tween-80 had a positive effect on sakacin P production, while addition of sodium chloride and trace metals had negative effects. The decrease in sakacin P concentration during the late growth and stationary phases was shown to be cell-independent and promoted at high temperature and pH. Some differences in production levels of sakacin P were found among six strains of Lactobacillus sakei tested.     

上下视野空间选择性注意的ERP研究

该文主要研究上、下视野空间选择性注意早期所诱发的ＥＲＰ反应,探讨注意上、下视野视觉信息处理的特征与差别。１０名被试的主要实验果为：１）对上、下视野的选择注意产生类似于注意左、右视野时Ｐ１、Ｎ１,Ｐ２的相对增强;２）偶极子定位显示,上、下视野刺激的早期注意反应（Ｐ１）以交叉方式投射到枕区,即下视野刺激的注意反应偏向枕区的背侧,而上视野刺激的注意反应偏向枕区的腹侧;３）上下视野的早期注意反应（Ｐ１）具     

Novel 16S rRNA gene analyses reveal new in vitro effects of insoluble barley fibres on the human faecal microbiota

Aims:  The aim of this work was to analyse the growth of human faecal microbiota on barley dietary fibres (DF). It is generally accepted that insoluble DF are health promoting, but the information is scarce about how these fibres affect the gastrointestinal (GI) microbiota. A major reason for the limited knowledge is that there are currently no proper tools to analyse the complete GI microbiota.
Methods and Results:  Here we present a novel 16S rRNA gene analytical approach that enables the analyses of the complete microbiota, including the part that has not yet been characterized. The basic principle of the method is use of 16S rRNA gene signature sequences to determine both the phylogenetic relatedness and the distribution of bacteria in the samples analysed.
Using this approach, we analysed the microbiota after in vitro fermentation of different barley fractions with human faeces. Our main finding was that groups of actinobacteria were selectively enriched by growth on the insoluble DF fractions.
Conclusions:  Our novel analytical approaches revealed new enrichment patterns in the taxa that respond to insoluble DF.
Significance and Impact of the Study:  Our results may have major implications for future understanding of insoluble DF health effects.     

Phosphorylation of eIF4E Confers Resistance to Cellular Stress and DNA-Damaging Agents through an Interaction with 4E-T: A Rationale for Novel Therapeutic Approaches

Phosphorylation of the eukaryotic translation initiation factor eIF4E is associated with malignant progression and poor cancer prognosis. Accordingly, here we have analyzed the association between eIF4E phosphorylation and cellular resistance to oxidative stress, starvation, and DNA-damaging agents in vitro. Using immortalized and cancer cell lines, retroviral expression of a phosphomimetic (S209D) form of eIF4E, but not phospho-dead (S209A) eIF4E or GFP control, significantly increased cellular resistance to stress induced by DNA-damaging agents (cisplatin), starvation (glucose+glutamine withdrawal), and oxidative stress (arsenite). De novo accumulation of eIF4E-containing cytoplasmic bodies colocalizing with the eIF4E-binding protein 4E-T was observed after expression of phosphomimetic S209D, but not S209A or wild-type eIF4E. Increased resistance to cellular stress induced by eIF4E-S209D was lost upon knockdown of endogenous 4E-T or use of an eIF4E-W73A-S209D mutant unable to bind 4E-T. Cancer cells treated with the Mnk1/2 inhibitor CGP57380 to prevent eIF4E phosphorylation and mouse embryonic fibroblasts derived from Mnk1/2 knockout mice were also more sensitive to arsenite and cisplatin treatment. Polysome analysis revealed an 80S peak 2 hours after arsenite treatment in cells overexpressing phosphomimetic eIF4E, indicating translational stalling. Nonetheless, a selective increase was observed in the synthesis of some proteins (cyclin D1, HuR, and Mcl-1). We conclude that phosphorylation of eIF4E confers resistance to various cell stressors and that a direct interaction or regulation of 4E-T by eIF4E is required. Further delineation of this process may identify novel therapeutic avenues for cancer treatment, and these results support the use of modern Mnk1/2 inhibitors in conjunction with standard therapy.     

多巴胺D2受体基因多态性位点与海洛因依赖的关系

目的:探讨多巴胺D2受体(Dopamine D2 receptors,DRD2)基因3'非翻译区Taq ⅠA、启动子区-141 Ins/Del 2个多态性位点和海洛因依赖的相关性.方法:采用聚合酶链反应-限制性片段长度多态(PCR-RFLP)技术检测320例海洛因依赖患者及300例健康对照组的TaqⅠA和-141 Ins/Del2个多态性位点的基因型.采用HaploView4.0及SPSS11.5软件分析这2个多态性位点的基因型、等位基因频率及组间差异.结果:DRD2基因Taq ⅠA位点的基因型及等位基因频率分布在海洛因依赖组与正常对照组存在显著性差异(p<0.01),海洛因依赖组TaqⅠA位点的等位基因A1频率显著高于正常对照组(x2=11.156,p=0.001,OR=1.463,95%CI=1.170～1.830);DRD2基因-141 Ins/Del位点的基因型及等位基因频率分布在海洛因依赖组与正常对照组之间无统计学差异(p<0.05).结论:DRD2基因TaqⅠA位点多态性可能与海洛因依赖有关,携带有TaqⅠA多态性位点A1等位基因的个体可能更容易对海洛因产生依赖.     

传统中草药对肠道益生微生物的作用研究进展

探讨传统中草药对肠道益生微生物的调整作用,重点概述了不同种类与剂量中草药对益生微生物生长的影响及相应的研究方法。在上述基础上对中草药与肠道益生微生物的作用机制、研究前景和发展趋势进行了展望。