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991.
Jared Cumming Suresh Babu Ying Huang Carolyn Carrol Xia Chen Leonard Favreau William Greenlee Tao Guo Matthew Kennedy Reshma Kuvelkar Thuy Le Guoqing Li Nansie McHugh Peter Orth Lynne Ozgur Eric Parker Kurt Saionz Andrew Stamford Corey Strickland Dawit Tadesse Qi Zhang 《Bioorganic & medicinal chemistry letters》2010,20(9):2837-2842
With collaboration between chemistry, X-ray crystallography, and molecular modeling, we designed and synthesized a series of novel piperazine sulfonamide BACE1 inhibitors. Iterative exploration of the non-prime side and S2′ sub-pocket of the enzyme culminated in identification of an analog that potently lowers peripheral Aβ40 in transgenic mice with a single subcutaneous dose. 相似文献
992.
Yong Ling Xiaolei Ye Hui Ji Yihua Zhang Yisheng Lai Sixun Peng Jide Tian 《Bioorganic & medicinal chemistry》2010,18(10):3448-3456
Novel furoxan-based nitric oxide (NO)-releasing derivatives (11a–p) of farnesylthiosalicylic acid (FTA) were synthesized. Compounds 11d, 11f, 11k, and 11m–o displayed anti-tumor activities superior to FTA and sorafenib in most cancer cells tested. Analysis of six compounds revealed that 11d, 11f, 11n, 11o, and 11p, but not 11a that had low anti-tumor activity, produced high levels of NO, associated with their strong anti-tumor activity. Furthermore, the anti-tumor activity of 11f was partially mimicked by the furoxan moiety, but reduced by pre-treatment with hemoglobin. Importantly, treatment with 11f inhibited Ras-related signaling in cancer cells. Apparently, the high anti-tumor activity of 11f was attributed to the synergic effect of high levels of NO production and inhibition of Ras-related signaling in cancer cells. Our findings suggest that the furoxan/FTA hybrids may hold greater promise as therapeutic agents for the intervention of human cancers. 相似文献
993.
生长激素受体(growth hormone receptor,GHR)是细胞因子/造血因子受体超级家族的一员。它通过二聚体的形式和生长激素(growth hormone,GH)相结合,然后诱发Janus激酶2(Janus kinase 2,JAK2)等细胞因子酪氨酸磷酸化并通过4条不同的途径将信号传入细胞内从而产生一系列的生理效应。现在了解GHR的结构特征、组织分布的基础上,对其介导的信号转导途径作进一步的阐明。 相似文献
994.
一种利用STO饲养层细胞制备拟胚体的新方法 总被引:2,自引:0,他引:2
建立了一种利用STO饲养层细胞制备拟胚体的新方法。该方法选用生长至80%饱和密度的STO细胞,经丝裂霉素C(10 mg/ml)处理4 h后以8×104 cm-2的密度接种培养12 h,制备饲养层,再将ES-D3细胞以1×104 cm-2的密度接种其上,首先用含mLIF的DMEM培养液培养24 h,再更换拟胚体诱导培养液,5~9天后获得了各成熟阶段的拟胚体。形态结构和分化潜能等研究表明,该方法制备的拟胚体结构典型,具有产生3个胚层谱系来源的功能细胞的潜能。与传统拟胚体制作方法如悬滴培养法相比,具有操作简便,拟胚体形成率高,重复性好等优点,是开展哺乳动物早期胚胎发育和干细胞分化研究的理想工具。 相似文献
995.
非点源污染物在沟渠湿地中的累积和植物吸收净化 总被引:21,自引:0,他引:21
对有机质和总氮在沟渠湿地底泥中的垂直分布和水平分布的研究表明,40 cm以下深度的芦苇(Phragmites communis)和茭草(Zizania latifolia)湿地底泥对有机质和总氮有显著的持留和累积作用;但表层底泥中含量随季节变化大,最高与最低值相差近2倍以上.有机质和总氮之间有极显著的相关关系,在芦苇和茭草湿地底泥中的相关系数分别为0.9876和0.9335.水体中总氮与NH4+-N和NO3-N也显著相关,表明总氮的主要成分是有机氮,其矿化作用是无机氮的重要来源.每年秋季芦苇收割以后,可带走氮818 kg·hm-2和磷103.6 kg·hm-2,茭草可带走氮131 kg·hm-2和磷28.9 kg·hm-2.茭白对氮的吸收能力高,试验表明,利用茭白取代野生植物,既能取得很好的净化效果,又可被农民主动回收,解决植物的二次污染问题. 相似文献
996.
改性瓜尔胶的研究进展 总被引:1,自引:0,他引:1
瓜尔胶是一种天然的半乳甘露聚糖,广泛用于食品、日化、医药等行业.改性瓜尔胶的性能具有较大改善,近年来瓜尔胶的改性研究成为热点.论述了瓜尔胶结构和性质以及改性瓜尔胶的研究进展,为瓜尔胶进一步开发研究提供参考. 相似文献
997.
Although the 30K family proteins are important anti-apoptotic molecules in silkworm hemolymph, the underlying mechanism remains to be investigated. This is especially the case in human vascular endothelial cells (HUVECs). In this study, a 30K protein, 30Kc6, was successfully expressed and purified using the Bac-to-Bac baculovirus expression system in silkworm cells. Furthermore, the 30Kc6 expressed in Escherichia coli was used to generate a polyclonal antibody. Western blot analysis revealed that the antibody could react specifically with the purified 30Kc6 expressed in silkworm cells. The In vitro cell apoptosis model of HUVEC that was induced by oxidized low density lipoprotein (Ox-LDL) and in vivo atherosclerosis rabbit model were constructed and were employed to analyze the protective effects of the silkworm protein 30Kc6 on these models. The results demonstrated that the silkworm protein 30Kc6 significantly enhanced the cell viability in HUVEC cells treated with Ox-LDL, decreased the degree of DNA fragmentation and markedly reduced the level of 8-isoprostane. This could be indicative of the silkworm protein 30Kc6 antagonizing the Ox-LDL-induced cell apoptosis by inhibiting the intracellular reactive oxygen species (ROS) generation. Furthermore, Ox-LDL activated the cell mitogen activated protein kinases (MAPK), especially JNK and p38. As demonstrated with Western analysis, 30Kc6 inhibited Ox-LDL-induced cell apoptosis in HUVEC cells by preventing the MAPK signaling pathways. In vivo data have demonstrated that oral feeding of the silkworm protein 30Kc6 dramatically improved the conditions of the atherosclerotic rabbits by decreasing serum levels of total triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). Furthermore, 30Kc6 alleviated the extent of lesions in aorta and liver in the atherosclerotic rabbits. These data are not only helpful in understanding the anti-apoptotic mechanism of the 30K family proteins, but also provide important information on prevention and treatment of human cardiovascular diseases. 相似文献
998.
999.
Background
Lack of clear risk factor identification is the main reason for the persistence of brucellosis infection in the Chinese population, and there has been little assessment of the factors contributing to Brucella contamination of raw whole milk. The purpose of this study was to identify risk factors affecting Brucella contamination of raw milk, and to evaluate effective measures for disease reduction in order to determine preventive strategies.Methods and Findings
A nationwide survey was conducted and samples were obtained from 5211 cows corresponding to 25 sampling locations throughout 15 provinces in China. The prevalence of Brucella in the raw milk samples averaged 1.07% over the 15 Chinese provinces, while the prevalence of positive areas within these regions ranged from 0.23–3.84% among the nine provinces with positive samples. The survey examined factors that supposedly influence Brucella contamination of raw whole milk, such as management style, herd size, abortion rate, hygiene and disease control practices. A binary logistic regression analysis was carried out to determine the association between risk factors for Brucella and contamination of milk samples. Furthermore, a relative effect decomposition study was conducted to determine effective strategies for reducing the risk of Brucella contamination of raw whole milk. Our data indicate that disease prevention and control measures, abortion rate, and animal polyculture are the most important risk factors. Meanwhile, culling after quarantine was identified as an effective protective measure in the current Chinese dairy situation.Conclusions
These results indicate that, although there is a low risk of contamination of milk with Brucella nationwide in China, there are individual regions where contamination is a significant problem. Controlling three factors–culling after quarantine, maintaining a low abortion rate, and avoiding mixing groups of cattle and small ruminants–could effectively reduce the risk of Brucella contamination of raw whole milk. 相似文献1000.
Shiu Lun Au Yeung Chaoqiang Jiang Kar Keung Cheng Benjamin J. Cowling Bin Liu Weisen Zhang Tai Hing Lam Gabriel M. Leung C. Mary Schooling 《PloS one》2013,8(7)