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161.
Identification,Design and Bio-Evaluation of Novel Hsp90 Inhibitors by Ligand-Based Virtual Screening
JianMin Jia XiaoLi Xu Fang Liu XiaoKe Guo MingYe Zhang MengChen Lu LiLi Xu JinLian Wei Jia Zhu ShengLie Zhang ShengMiao Zhang HaoPeng Sun QiDong You 《PloS one》2013,8(4)
Heat shock protein 90 (Hsp90), whose inhibitors have shown promising activity in clinical trials, is an attractive anticancer target. In this work, we first explored the significant pharmacophore features needed for Hsp90 inhibitors by generating a 3D-QSAR pharmacophore model. It was then used to virtually screen the SPECS databases, identifying 17 hits. Compound S1 and S13 exhibited the most potent inhibitory activity against Hsp90, with IC50 value 1.61±0.28 μM and 2.83±0.67 μM, respectively. Binding patterns analysis of the two compounds with Hsp90 revealed reasonable interaction modes. Further evaluation showed that the compounds exhibited good anti-proliferative effects against a series of cancer cell lines with high expression level of Hsp90. Meanwhile, S13 induced cell apoptosis in a dose-dependent manner in different cell lines. Based on the consideration of binding affinities, physicochemical properties and toxicities, 24 derivatives of S13 were designed, leading to the more promising compound S40, which deserves further optimization. 相似文献
162.
Lin Xu Yong Zhang Zheng Shan Deng Liang Zhao Xiu Li Wei Ge Hong Wei 《Antonie van Leeuwenhoek》2013,103(3):559-565
During a study of the diversity and phylogeny of rhizobia isolated from root nodules of Oxytropis ochrocephala grown in the northwest of China, four strains were classified in the genus Rhizobium on the basis of their 16S rRNA gene sequences. These strains have identical 16S rRNA gene sequences, which showed a mean similarity of 94.4 % with the most closely related species, Rhizobium oryzae. Analysis of recA and glnA sequences showed that these strains have less than 88.1 and 88.7 % similarity with the defined species of Rhizobium, respectively. The genetic diversity revealed by ERIC-PCR fingerprinting indicated that the isolates correspond to different strains. Strain CCNWQLS01T contains Q-10 as the predominant ubiquinone. The major fatty acids were identified as feature 8 (C18: 1ω7c and/or C18: 1ω6c; 67.2 %). Therefore, a novel species Rhizobium qilianshanense sp. nov. is proposed, and CCNWQLS01T (= ACCC 05747T = JCM 18337T) is designated as the type strain. 相似文献
163.
SIRT1 expression is refractory to hypoxia and inflammatory cytokines in nucleus pulposus cells: Novel regulation by HIF‐1α and NF‐κB signaling 下载免费PDF全文
164.
嗅觉是昆虫的主要感觉模式,在昆虫的重要行为活动如寻找配偶、定位寄主、选择产卵场所等中起着关键作用。昆虫通过触角等外周嗅觉器官感受外界的化学信号并转化为电信号,电信号传输到中枢神经系统进行加工整合,最后通过大脑发出指令调控自身关键的行为。昆虫需要在合适的时机对不同气味作出反应,从而保证其能够在不同生理状态下完成特定的行为。这就要求昆虫的嗅觉系统具有可塑性,即根据不同的生理状态,如日龄、取食状态、交配、节律等对相同气味作出不同的反应。本文综述了不同生理状态对昆虫嗅觉行为和嗅觉神经系统的影响,以及昆虫嗅觉可塑性产生的机制,为加深和扩展人们对昆虫嗅觉系统的认识和建立新的害虫防控策略提供参考。 相似文献
165.
166.
Quercetin and other flavonoids have been reported to exhibit both antioxidant and pro‐oxidant properties. Most studies about the pro‐oxidative ability were conducted in the presence of metal ions, and the essential functional moiety of quercetin responsible for the pro‐oxidative effect is still unclear. In this study, we evaluated the pro‐oxidative abilities in the absence of metal ions of two quercetin derivatives, i.e., quercetin‐3′‐O‐β‐D ‐glucoside ( 1 ) and quercetin‐3‐O‐β‐D ‐glucoside ( 2 ), by assessing DNA cleavage and HO.‐radical production. The binding mode between these compounds and DNA was studied by fluorescence and viscometric titrations. The results showed that 1 can efficiently induce oxidative damage to plasmid DNA, while 2 shows poor activity. Both 1 and 2 bind to DNA via groove‐binding. These results proved that the α‐hydroxy‐β‐oxo‐α,β‐enone moiety contributes to the pro‐oxidative activity of quercetin. 相似文献
167.
Sun Y Li T Chen H Zhang K Zheng K Mu Y Yan G Li W Shen J Luo G 《The Journal of biological chemistry》2004,279(36):37235-37240
Glutathione peroxidase (GPX) is one of the most crucial antioxidant enzymes in a variety of organisms. Here we described a new strategy for generating a novel GPX mimic by combination of a phage-displayed random 15-mer peptide library followed by computer-aided rational design and chemical mutation. The novel GPX mimic is a homodimer consisting of a 15-mer selenopeptide with an appropriate catalytic center, a specific binding site for substrates, and high catalytic efficiency. Its steady state kinetics was also studied, and the values of k(cat)/K(m)(GSH) and k(cat)/ K(mH(2)O(2)) were found to be similar to that of native GPX and the highest among the existing GPX mimics. Moreover, the novel GPX mimic was confirmed to have a strong antioxidant ability to inhibit lipid peroxidation by measuring the content of malondialdehyde, cell viability, and lactate dehydrogenase activity. Importantly, the novel GPX mimic can penetrate into the cell membrane because of its small molecular size. These characteristics endue the novel mimic with potential perspective for pharmaceutical applications. 相似文献
168.
Effects of Irrigation and Nitrogen on the Performance of Aerobic Rice in Northern China 总被引:1,自引:0,他引:1
Chang-Ying Xue Xiao-Guang Yang B.A.M. Bouman Wei Deng Qiu-Ping Zhang Jie Yang Wei-Xiong Yan Tian-Yi Zhang A-Ji Rouzi Hua-Qi Wang Pu Wang 《植物学报(英文版)》2008,50(12):1589-1600
Aerobic rice is a new production system in which specially-developed varieties are grown under non-flooded, non-puddled, and non-saturated soil conditions. In 2003-2004, irrigation x Nitrogen experiments were carried out near Beijing using variety HD297. Water treatments included four irrigation levels, and Nitrogen treatments included different fertilizer N application rates and different numbers of N splits. The highest yields were 4460 kg/ha with 688 mm of total (rain plus irrigation) water input in 2003 and 6 026 kg/ha with 705 mm of water input in 2004. Because of the quite even distribution of rainfall in both years, the four irrigation treatments did not result in large differences of soil water conditions. There were few significant effects of irrigation on biomass accumulation, but yield increased with the total amount of water applied. High yields coincided with high harvest index and high percentages of grain filling. The application of fertilizer N either reduced biomass and yield or kept it at the same level as 0 N and consistently reduced the percentage grain filling and 1 000-grain weight. With the highest water application, five splits of N gave higher yield than three splits, whereas three splits gave higher yield than five splits with lower water applications. 相似文献
169.
Zhang Y Zhang X Xia H Xue Y Wang J Tian B Wei Z Lu C 《Acta biochimica et biophysica Sinica》2008,40(6):533-538
Cassettes harboring luciferase reporter driven by Bombyx mori cytoplasmic actin gene promoter (A3) (671 bp) and B. mori nuclear polyhedrosis virus immediate-early promoter (IE-1) (580 bp) were transferred to the bacmid AcΔEGT to generate the recombinant Autographa californica nuclear polyhedrosis viruses, AcNPVA3Luc and AcNPVIELuc, respectively. Recombinant baculoviruses were injected into the hemocoele of newly ecdysed 5th instar larvae. The activities of the A3 and IE-1 promoters in various tissues were measured by luciferase activity assay and normalized by the copy number of recombinant virus. Results showed that the activity of the A3 promoter was approximately 10-fold higher than the IE-1 promoter. The promoter activities of A3 and IE-1 were highest in the silk gland, followed by fat body, middle gut, Malpighian tubule, and hemocyte. In silk gland, activity of the two promoters was highest in posterior silk gland, followed by middle and anterior silk glands. The difference in promoter activities reflects the growth speed of tissue in silkworm larvae. The activity of the A3 promoter remained unchanged and was not inhibited significantly by viral factors at least 3–4 d post injection of rAcNPV. 相似文献
170.
Jiao Zhan Xi Zhu Wei Zhou Hui Chen Chenliu He Qiang Wang 《Molecular microbiology》2016,102(4):738-751
Thylakoid formation1 protein (Thf1) is a multifunctional protein that is conserved in all photosynthetic organisms. In this study, we used the model cyanobacterium Synechococcus sp. PCC7942 (hereafter Synechococcus) to show that the level of Thf1 is altered in response to various stress conditions. Although this protein has been reported to be involved in thylakoid formation, the thylakoid membrane in the thf1 deletion strain (ΔThf1) was not affected. Compared with the WT, ΔThf1 showed reduced PS II activity, with increased levels of D1 under high light (HL) conditions, which was resulted from blocked D1 degradation by the FtsH protease and thus inhibits PS II repair. PS I was found to be more seriously affected than PS II in ΔThf1, even under low light conditions, suggesting that PS I damage could be the primary effect of thf1 deletion in Synechococcus. Further analysis revealed that the ΔThf1 mutant had a lower PS I subunit content and lower PS I stability under HL conditions. Further sucrose gradient fractionation of the membrane protein complexes and crosslinking and immunoblot analysis indicated that Thf1 interacts with PS I. Together, our results reveal that Thf1 interacts with PS I and thereby stabilizes PS I in Synechococcus. 相似文献