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101.
Robarge MJ Bom DC Tumey LN Varga N Gleason E Silver D Song J Murphy SM Ekema G Doucette C Hanniford D Palmer M Pawlowski G Danzig J Loftus M Hunady K Sherf BA Mays RW Stricker-Krongrad A Brunden KR Harrington JJ Bennani YL 《Bioorganic & medicinal chemistry letters》2005,15(6):1749-1753
The chemoattractant receptor-homologous molecule expressed on T(H)2 cells (CRTH-2), also found on eosinophils and basophils, is a prostaglandin D2 receptor involved in the recruitment of these cell types during an inflammatory response. In this report, we describe the synthesis and optimization of a ramatroban isostere that is a selective and potent antagonist of CRTH-2 which may be useful in the treatment of certain diseases. 相似文献
102.
Xian Qi Yuning Pan Yuanfang Qin Rongqiang Zu Fengyang Tang Minghao Zhou Hua Wang Yongchun Song 《中国病毒学》2012,27(5):292-298
Currently, three predominant subtypes of influenza virus are prevalent in pig populations worldwide: H1N1, H3N2, and H1N2. European avian-like H1N1 viruses, which were initially detected in European pig populations in 1979, have been circulating in pigs in eastern China since 2007. In this study, six influenza A viruses were isolated from 60 swine lung samples collected from January to April 2011 in eastern China. Based on whole genome sequencing, molecular characteristics of two isolates were determined. Phylogenetic analysis showed the eight genes of the two isolates were closely related to those of the avian-like H1N1 viruses circulating in pig populations, especially similar to those found in China. Four potential glycosylation sites were observed at positions 13, 26, 198, 277 in the HA1 proteins of the two isolates. Due to the presence of a stop codon at codon 12, the isolates contained truncated PB1-F2 proteins. In this study, the isolates contained 591Q, 627E and 701N in the polymerase subunit PB2, which had been shown to be determinants of virulence and host adaptation. The isolates also had a D rather than E at position 92 of the NS1, a marker of mammalian adaptation. Both isolates contained the GPKV motif at the PDZ ligand domain of the 3′ end of the NS1, a characteristic marker of the European avian-like swine viruses since about 1999, which is distinct from those of avian, human and classical swine viruses. The M2 proteins of the isolates have the mutation (S31N), a characteristic marker of the European avian-like swine viruses since about 1987, which may confer resistance to amantadine and rimantadine antivirals. Our findings further emphasize the importance of surveillance on the genetic diversity of influenza A viruses in pigs, and raise more concerns about the occurrence of cross-species transmission events. 相似文献
103.
104.
Toll-like receptor (TLR) 2 and TLR5, but not TLR4, are required for Helicobacter pylori-induced NF-kappa B activation and chemokine expression by epithelial cells 总被引:11,自引:0,他引:11
Smith MF Mitchell A Li G Ding S Fitzmaurice AM Ryan K Crowe S Goldberg JB 《The Journal of biological chemistry》2003,278(35):32552-32560
105.
The discovery of potent, selective, and orally bioavailable hNK1 antagonists derived from pyrrolidine 总被引:2,自引:0,他引:2
Lin P Chang L Devita RJ Young JR Eid R Tong X Zheng S Ball RG Tsou NN Chicchi GG Kurtz MM Tsao KL Wheeldon A Carlson EJ Eng W Burns HD Hargreaves RJ Mills SG 《Bioorganic & medicinal chemistry letters》2007,17(18):5191-5198
SAR studies on amides, ureas, and vinylogous amides derived from pyrrolidine led to the discovery of several potent hNK(1) antagonists. One particular vinylogous amide (45b) had excellent potency, selectivity, pharmacokinetic profile, and functional activity in vivo. An in vivo rhesus macaque brain receptor occupancy PET study for compound 45b revealed an estimated Occ(90) approximately 300 ng/ml. 相似文献
106.
Kim TY Shin SK Song MY Lee JE Park KS 《Biochemical and biophysical research communications》2012,417(3):1030-1034
Transient receptor potential melastatin 7 (TRPM7) channels are divalent cation-selective ion channels that are permeable to Ca(2+) and Mg(2+). TRPM7 is ubiquitously expressed in vertebrate cells and contains both an ion channel and a kinase domain. TRPM7 plays an important role in regulating cellular homeostatic levels of Ca(2+) and Mg(2+) in mammalian cells. Although studies have shown that the kinase domain of TRPM7 is required for channel activation and can phosphorylate other target proteins, a systematic analysis of intact TRPM7 channel phosphorylation sites expressed in mammalian cells is lacking. We applied mass spectrometric proteomic techniques to identify and characterize the key phosphorylation sites in TRPM7 channels. We identified 14 phosphorylation sites in the cytoplasmic domain of TRPM7, eight of which have not been previously reported. The identification of phosphorylation sites using antibody-based immunopurification and mass spectrometry is an effective approach for defining the phosphorylation status of TRPM7 channels. The present results show that TRPM7 channels are phosphorylated at multiple sites, which serves as a mechanism to modulate the dynamic functions of TRPM7 channels in mammalian cells. 相似文献
107.
108.
Activation of Toll-like receptor 4 is associated with insulin resistance in adipocytes 总被引:3,自引:0,他引:3
Song MJ Kim KH Yoon JM Kim JB 《Biochemical and biophysical research communications》2006,346(3):739-745
Chronic inflammation is closely associated with metabolic disorders such as obesity and type 2 diabetes, however, the underlying mechanism is unclear. Toll-like receptors (TLRs) play a key role in innate immune response as well as inflammatory signals. Here, we observed that mRNA level of TLR4 was induced during adipocyte differentiation and remarkably enhanced in fat tissues of obese db/db mice. In addition, activation of TLR4 with either LPS or free fatty acids stimulated NFkappaB signaling and expression of inflammatory cytokine genes, such as TNFalpha and IL-6 in 3T3-L1 adipocytes. Furthermore, we discovered that TLR4 activation in 3T3-L1 adipocytes provoked insulin resistance. Taken together, these results suggest that activation of TLR4 in adipocyte might be implicated in the onset of insulin resistance in obesity and type 2 diabetes. 相似文献
109.
双探针原位杂交揭示稻属BB、cc 和EE基因组之间的分化
李常宝1 张大明1* 葛颂1 卢宝荣2 洪德元1 相似文献
110.
从江浙蝮蛇中分离纯化的碱性磷脂酶A2在pH9.5,0.05mmol/LCHES缓冲液中,用汽相悬滴扩散的方法,获得了适用于高分辨率X射线结构分析的单晶.经X200B面探测器分析,表明该晶体属于正交晶系,P2I2I2I空间群,晶胞参数为a=97.13,b=103.69,c=23.27.并收集了一套衍射数据,独立衍射点数12001个,数据完整度为86.2%,Rmerge为0.0459.最高分辨率达2.0,根据分子量与晶胞体积估算,一个不对称单位含两个分子. 相似文献