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131.
Jia-Jia Liu Hui Zhang Juan Sun Zhong-Chang Wang Yu-Shun Yang Dong-Dong Li Fei Zhang Hai-Bin Gong Hai-Liang Zhu 《Bioorganic & medicinal chemistry》2012,20(20):6089-6096
A series of novel 4,5-dihydropyrazole derivatives (3a–3t) containing hydroxyphenyl moiety as potential V600E mutant BRAF kinase (BRAFV600E) inhibitors were designed and synthesized. Docking simulation was performed to insert compounds 3d (1-(5-(5-chloro-2-hydroxyphenyl)-3-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)ethanone) and 3m (1-(3-(4-chlorophenyl)-5-(3,5-dibromo-2-hydroxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl)ethanone) into the crystal structure of BRAFV600E to determine the probable binding model, respectively. Based on the preliminary results, compound 3d and 3m with potent inhibitory activity in tumor growth may be a potential anticancer agent. Results of the bioassays against BRAFV600E, MCF-7 human breast cancer cell line and WM266.4 human melanoma cell line all showed several compounds had potent activities IC50 value in low micromolar range, among them, compound 3d and compound 3m showed strong potent anticancer activity, which were proved by that 3d: IC50 = 1.31 μM for MCF-7 and IC50 = 0.45 μM for WM266.5, IC50 = 0.22 μM for BRAFV600E, 3m: IC50 = 0.97 μM for MCF-7 and IC50 = 0.72 μM for WM266.5, IC50 = 0.46 μM for BRAFV600E, which were comparable with the positive control Erlotinib. 相似文献
132.
In recent years there have been more widely and deeply studies in investigating melamine toxicity. Generally, it is believed that the main target of melamine is the urinary system. However, previous studies revealed that it also had additional biological actions. Obviously, the toxicity mechanisms of melamine have not been fully clarified. It is well known that fetus and infant periods play the most fundamental role in the brain development. And melamine can pass through the placental and blood-brain barrier, and then exerts toxic effects on the central nervous system. This article reviewed the reports about the topic in recent years, for better understanding the dangers of melamine to infants and providing experimental data for further study. 相似文献
133.
Ya-Jun Li Wen-Qi Jiang Hui-Lan Rao Jia-Jia Huang Yi Xia Hui-Qiang Huang Tong-Yu Lin Zhong-Jun Xia Su Li Zhi-Ming Li 《PloS one》2012,7(12)
Background
B-cell activation factor (BAFF) and BAFF-receptor (BAFF-R) play crucial roles in the viability and proliferation of malignant lymphoma cells. Limited information exists regarding expression profiles and the prognostic role of BAFF and BAFF-R in follicular lymphoma (FL). We sought to determine the expression profiles of BAFF and BAFF-R in FL and to evaluate the correlation of BAFF and BAFF-R expression with clinicopathologic characteristics and outcome of FL. Correlation between expression levels of BAFF detected by immunohistochemical (IHC) and serum levels of BAFF was also evaluated.Methods
Paraffin-embedded specimens from 115 patients were immunohistochemically examined for BAFF and BAFF-R expression. Expression levels were dichotomized into low versus high categories based on immunostaining intensity. The correlation of BAFF and BAFF-R expression with clinicopathologic characteristics and patient outcome was assessed. Serum levels of BAFF in 35 of the 115 patients with IHC data were measured by Enzyme-linked Immunosorbent assay (ELISA).Results
BAFF and BAFF-R were expressed in 88.7% (102/115) and 87.8% (101/115) of the cases, respectively. BAFF expression was significantly correlated with only one clinicopathologic feature: Ann Arbor stage. No significant correlation was found between expression levels of BAFF detected by IHC and serum levels of BAFF detected by ELISA. High expression of BAFF-R, but not BAFF, was significantly correlated with inferior progression-free survival (PFS; P = 0.013) and overall survival (OS; P = 0.03). High expression of BAFF-R, bulky disease, and elevated lactate dehydrogenase were correlated with inferior PFS and OS in multivariate analysis. A prognostic scoring system incorporating these 3 risk factors identified 3 distinct prognostic groups with 5-year PFS of 59.4%, 41.9%, and 10.7% and OS of 91.3%, 79.7%, and 45.8%, respectively.Conclusions
Most patients with FL variably express BAFF and BAFF-R. High expression of BAFF-R, but not BAFF, may be an independent risk factor for PFS and OS in FL. 相似文献134.
WW Hu WJ Syu WY Chen RC Ruaan YC Cheng CC Chien C Li CA Chung CW Tsao 《Bioconjugate chemistry》2012,23(8):1587-1599
To improve transfection efficiency of nonviral vectors, biotinylated chitosan was applied to complex with DNA in different N/P ratios. The morphologies and the sizes of formed nanoparticles were suitable for cell uptake. The biotinylation decreased the surface charges of nanoparticles and hence reduced the cytotoxicity. The loading capacities of chitosan were slightly decreased with the increase of biotinylation, but most of the DNA molecules were still complexed. Using different avidin-coated surfaces, the interaction between biotinylated nanoparticles to the substrate may be manipulated. The in vitro transfection results demonstrated that biotinylated nanoparticles may be bound to avidin coated surfaces, and the transfection efficiencies were thus increased. Through regulating the N/P ratio, biotinylation levels, and surface avidin, the gene delivery can be optimized. Compared to the nonmodified chitosan, biotinylated nanoparticles on biomaterial surfaces can increase their chances to contact adhered cells. This spatially controlled gene delivery improved the gene transfer efficiency of nonviral vectors and could be broadly applied to different biomaterial scaffolds for tissue engineering applications. 相似文献
135.
To investigate the structure ofEscherichia coli ribosomal protein S13 in 30S ribosomal subunits, we have previously generated 22 S13 specific monoclonal antibodies and mapped their specific epitopes to the S13 sequence. The availability of these S13 epitopesin situ has been further examined by incubating these monoclonal antibodies with 30S ribosomal subunits and analyzing formation of monoclonal antibody-linked ribosome dimers by sucrose gradients centrifugation. We have found that none of the 22 monoclonal antibodies makes ribosome dimers individually as do typical antisera. However, one monoclonal antibody, designated AS13-MAb 2, reacts with 30S ribosomal subunits to form immunocomplexes sedimenting faster than subunit monomers. When AS13-MAb 2 is paired with any one of three monoclonal antibodies directed to the S13 C-terminal epitopes, dimer formation is observed. Other pairs of monoclonal antibodies directed to distinct S13 epitopes have been tested similarly for dimer formation. Monoclonal antibody AS13-MAb 22, directed to the N-terminal region of 22 residues, also causes subunits to form typical dimers, but only if paired with one of the three monoclonal antibodies directed to the S13 C-terminal region. The close proximity of the epitopes recognized by AS13-MAbs 2 and 22 has been established by the mutual competition between the antibodies binding to intact 30S subunits. These results corroborate our previous observation, using polyclonal antibodies, that S13 has more than one epitope exposed on 30S subunits. Our finding that sequences on both ends of the S13 molecule are immunochemically accessible provides information about the molecular organization of S13in situ. 相似文献
136.
草鱼EST-SSR标记及5个不同地域群体的遗传结构分析 总被引:2,自引:0,他引:2
以草鱼(Ctenopharyngodon idella)脑、肌肉、肝等组织构建cDNA文库,经测序获得unigenes序列45 318个,从中筛选微卫星序列共5 556个,据此设计EST-SSR引物118对,其中19对引物能够扩增出带型清晰且多态性较高的谱带。用这19个EST-SSR标记研究3个长江水系群体(石首、监利和长沙)和2个珠江水系群体(清远和肇庆)草鱼的遗传结构。结果表明,5个群体的平均多态信息含量(PIC)为0.415 4~0.460 4,显示草鱼群体的遗传多样性偏低;平均观测杂合度(Ho)为0.415 8~0.501 3,平均期望杂合度为(He)0.450 6~0.502 8,其中,长沙群体平均期望杂合度最高,为0.502 8,监利群体的平均观察杂合度和平均期望杂合度均最低,分别为0.415 8和0.450 6,即长沙群体的遗传多样性最高,监利群体的遗传多样性最低;对数据进行F-检验,结果表明,群体间的遗传分化程度低。Hardy-Weinberg平衡的卡方检验结果表明,5个群体均一定程度上偏离了平衡;聚类分析显示长沙群体、石首群体与监利群体聚成一支;肇庆群体与清远群体聚成一支,这与草鱼群体的流域分布一致。 相似文献
137.
Chun-Mei Wan Xiao-Jian Yang Jia-Jia Du Ying Lu Zhi-Bo Yu Yue-Guang Feng Xiao-Yun Wang 《Biochemistry. Biokhimii?a》2014,79(5):440-449
Homologs of vitamin K epoxide reductase (VKOR) exist widely in plants. However, only VKOR of Arabidopsis thaliana has been the subject of many studies to date. In the present study, the coding region of a VKOR from Solanum lyco-persicum (JF951971 in GenBank) was cloned; it contained a membrane domain (VKOR domain) and an additional soluble thioredoxin-like (Trx-like) domain. Bioinformatic analysis showed that the first 47 amino acids in the N-terminus should act as a transit peptide targeting the protein to the chloroplast. Western blot demonstrated that the protein is localized in thylakoid membrane with the Trx-like domain facing the lumen. Modeling of three-dimensional structure showed that SlVKOR has a similar conformation with Arabidopsis and cyanobacterial VKORs, with five transmembrane segments in the VKOR domain and a typical Trx-like domain in the lumen. Functional assay showed that the full-length of SlVKOR with Trx-like domain without the transit peptide could catalyze the formation of disulfide bonds. Similar transit peptides at the N-terminus commonly exist in plant VKORs, most of them targeting to chloroplast according to prediction. Comparison of sequences and structures from different plants indicated that all plant VKORs possess two domains, a transmembrane VKOR domain and a soluble Trx-like domain, each having four conservative cysteines. The cysteines were predicted to be related to the function of catalyzing the formation of disulfide bonds. 相似文献
138.
139.
Baochang Fan F.X. Reymond Sutandy Guan-Da Syu Stefani Middleton Guanghui Yi Kuan-Yi Lu Chien-Sheng Chen C. Cheng Kao 《Molecular & cellular proteomics : MCP》2015,14(11):2878-2886
Heterogeneous ribonucleoprotein K (hnRNP K) binds to the 5′ untranslated region of the hepatitis C virus (HCV) and is required for HCV RNA replication. The hnRNP K binding site on HCV RNA overlaps with the sequence recognized by the liver-specific microRNA, miR-122. A proteome chip containing ∼17,000 unique human proteins probed with miR-122 identified hnRNP K as one of the strong binding proteins. In vitro kinetic study showed hnRNP K binds miR-122 with a nanomolar dissociation constant, in which the short pyrimidine-rich residues in the central and 3′ portion of the miR-122 were required for hnRNP K binding. In liver hepatocytes, miR-122 formed a coprecipitable complex with hnRNP K. High throughput Illumina DNA sequencing of the RNAs precipitated with hnRNP K was enriched for mature miR-122. SiRNA knockdown of hnRNP K in human hepatocytes reduced the levels of miR-122. These results show that hnRNP K is a cellular protein that binds and affects the accumulation of miR-122. Its ability to also bind HCV RNA near the miR-122 binding site suggests a role for miR-122 recognition of HCV RNA.MicroRNAs (miRNAs) are a class of noncoding RNA of ∼22-nucleotides in length that can regulate gene expression by either targeting RNA for degradation or suppressing their translation through base pairing to the RNAs (1). Since their discovery in 1993 in Caenorhabditis elegans, miRNAs have been found in many species and are involved in the regulation of proliferation, differentiation, apoptosis, and development (1, 2). Moreover, miRNAs are also critical factors in the development of cancers, neurodegenerative diseases, and infectious diseases (3).MiR-122 is a highly abundant RNA in hepatocytes that regulates lipid metabolism, regeneration, and neoplastic transformation (4–6). In addition, miR-122 is required for the replication of the hepatitis C virus (HCV), a positive-strand RNA virus that infects over 170 million people worldwide (7–9). MiR-122 binds to a conserved sequence in the 5′ untranslated region (UTR) of the HCV RNA to increase the stability of the HCV RNA (10). Silencing of miR-122 can abolish HCV RNA accumulation in non-human primates (11). The expression of human miR-122 in non-hepatic cells can confer the ability to replicate HCV RNA (12). MiR-122 is one of the most critical host factors for HCV replication.We previously reported that the HCV RNA sequence that anneals to miR-122 is recognized by the heterogeneous ribonucleoprotein K (hnRNP K), a multifunctional RNA-binding protein known to be involved in RNA processing, translation, and the replication of several RNA viruses (13–15). In an unbiased screen for proteins from human proteome chips containing over 17,000 proteins, we identified 40 proteins that bind mature miR-122, including hnRNP K. Recombinant hnRNP K recognizes short pyrimidine sequences in miR-122 in vitro and a similar sequence in the HCV 5′ UTR. In hepatocytes endogenous hnRNP K can form a coprecipitable complex with miR-122, whether or not the cells contain replicating HCV. HnRNP K is thus a protein that binds a mature microRNA. 相似文献
140.
ROP(Rho of plant)作为植物中唯一具有信号传递功能的小GTP结合蛋白,在极性生长、发育和环境应答等过程中具有重要作用.本文采用酵母双杂交技术,从水稻 幼穗筛选出2种与水稻ROP家族成员OsRac5互作蛋白的基因OsMY1和OsMY2.序列分析显示,OsMY1与OsMY2的核苷酸、氨基酸序列的相似性分别为14%和49%,均含有卷曲螺旋结构域;GST pull down分析显示,OsMY1可以和激活型OsRac5在体外结合;实时定量PCR分析显示,OsMY1和OsMY2在水稻生长发育时期的根、茎、叶中广泛表达,尤其在幼穗中的表达量显著高于其它组织.干旱、低温、高盐等非生物胁迫和植物激素吲哚乙酸(IAA)、脱落酸(ABA)、赤霉素(GA)处理能不同程度地上调OsMY1和OsMY2 基因在水稻幼苗中的表达,但油菜素内酯(BR)、水杨酸(SA)、6-苄氨基嘌呤 (6-BA)对2种基因的表达没有显著的影响.本文为进一步研究OsMY1和OsMY2基因在水稻生长发育、植物激素和胁迫应答中的功能提供了重要依据,为研究OsMY1、 OsMY2和OsRac5蛋白质相互作用的功能联系和作用机制奠定了基础. 相似文献