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排序方式: 共有197条查询结果,搜索用时 15 毫秒
21.
Yibao Ma Yuanxi Xu Bryan D. Yestrepsky Roderick J. Sorenson Meng Chen Scott D. Larsen Hongmin Sun 《PloS one》2012,7(10)
Staphylococcus aureus is a major human pathogen and one of the more prominent pathogens causing biofilm related infections in clinic. Antibiotic resistance in S. aureus such as methicillin resistance is approaching an epidemic level. Antibiotic resistance is widespread among major human pathogens and poses a serious problem for public health. Conventional antibiotics are either bacteriostatic or bacteriocidal, leading to strong selection for antibiotic resistant pathogens. An alternative approach of inhibiting pathogen virulence without inhibiting bacterial growth may minimize the selection pressure for resistance. In previous studies, we identified a chemical series of low molecular weight compounds capable of inhibiting group A streptococcus virulence following this alternative anti-microbial approach. In the current study, we demonstrated that two analogs of this class of novel anti-virulence compounds also inhibited virulence gene expression of S. aureus and exhibited an inhibitory effect on S. aureus biofilm formation. This class of anti-virulence compounds could be a starting point for development of novel anti-microbial agents against S. aureus. 相似文献
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Cong Wang Liping Jiang Saiqi Wang Hongge Shi Junwei Wang Ran Wang Yongmei Li Yinhui Dou Ying Liu Guiqin Hou Yu Ke Hongmin Liu 《PloS one》2015,10(6)
Jesridonin, a small molecule obtained through the structural modification of Oridonin, has extensive antitumor activity. In this study, we evaluated both its in vitro activity in the cancer cell line EC109 and its in vivo effect on tumor xenografts in nude mice. Apoptosis induced by Jesridonin was determined using an MTT assay, Annexin-V FITC assay and Hoechest 33258 staining. Apoptosis via mitochondrial and death receptor pathways were confirmed by detecting the regulation of MDM2, p53, and Bcl-2 family members and by activation of caspase-3/-8/-9. In addition, vena caudalis injection of Jesridonin showed significant inhibition of tumor growth in the xenograft model, and Jesridonin-induced cell apoptosis in tumor tissues was determined using TUNEL. Biochemical serum analysis of alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), total protein (TP) and albumin (ALB) indicated no obvious effects on liver function. Histopathological examination of the liver, kidney, lung, heart and spleen revealed no signs of JD-induced toxicity. Taken together, these results demonstrated that Jesridonin exhibits antitumor activity in human esophageal carcinomas EC109 cells both in vitro and in vivo and demonstrated no adverse effects on major organs in nude mice. These studies provide support for new drug development. 相似文献
24.
Previously, we showed that overexpression of ubiquilin reduces protein aggregates and toxicity of expanded polyglutamine proteins. Here, we investigated the mechanism of ubiquilin's protective effect. Immunofluorescence microscopy and immunoprecipitation studies indicated that ubiquilin colocalized and coimmunoprecipitated more with GFP-huntingtin-exon-1-fusion proteins containing a 74-polyglutamine tract than with GFP-huntingtin-fusion proteins containing a 28-polyglutamine tract or with GFP protein alone. Furthermore, overexpression of ubiquilin selectively enhanced the turnover of the expanded GFP-huntingtin-fusion protein. These results suggest that elevating ubiquilin levels could aid in the selective disposal of potentially toxic expanded polyglutamine proteins that are thought to cause several human diseases. 相似文献
25.
Graham F. Smith Michael D. Altman Brian Andresen James Baker Jason D. Brubaker Hongmin Chen Yiping Chen Matthew Childers Anthony Donofrio Heidi Ferguson Christian Fischer Thierry O. Fischmann Craig Gibeau Alexander Hicks Sue Jin Sam Kattar Melanie A. Kleinschek Erica Leccese Alan Northrup 《Bioorganic & medicinal chemistry letters》2017,27(12):2721-2726
Interleukin-1 receptor associated kinase 4 (IRAK4) has been implicated in IL-1R and TLR based signaling. Therefore selective inhibition of the kinase activity of this protein represents an attractive target for the treatment of inflammatory diseases. Medicinal chemistry optimization of high throughput screening (HTS) hits with the help of structure based drug design led to the identification of orally-bioavailable quinazoline based IRAK4 inhibitors with excellent pharmacokinetic profile and kinase selectivity. These highly selective IRAK4 compounds show activity in vivo via oral dosing in a TLR7 driven model of inflammation. 相似文献
26.
Jun Qian Shinji Ito Junko Satoh Hongmin Geng Keisuke Tanaka Shunji Hattori 《Bioscience, biotechnology, and biochemistry》2017,81(3):514-522
Bovine type I collagen consists of two α1 and one α2 chains, containing the internal triple helical regions and the N- and C-terminal telopeptides. In industries, it is frequently digested with porcine pepsin to produce a triple helical collagen without the telopeptides. However, the digestion mechanism is not precisely understood. Here, we performed a mass spectrometric analysis of the pepsin digest of the N-terminal telopeptide pQLSYGYDEKSTGISVP (1–16) in the α1 chain. When purified collagen was digested, pQLSYGY (1–6) and pQLSYGYDEKSTG (1–12) were identified, while DEKSTG (7–12) was not. When the N-terminal telopeptide mimetic synthetic peptide pQLSK(MOCAc)GYDEKSTGISK(Dnp)P-NH2 was digested, pQLSK(MOCAc)GYDEKSTG (1–12) and ISK(Dnp)P-NH2 (13?16) were readily identified, pQLSK(MOCAc)GY (1?6) and DEKSTGISK(Dnp)P-NH2 (7?16) were weakly detected, and DEKSTG (7–12) was hardly identified. These results suggest that pepsin preferentially cleaves Tyr6–Asp7 and less preferentially Gly12–Ile13. They also suggest that the former cleavage requires native collagen structure, while the latter cleavage does not. 相似文献
27.
清水苑大洞位于贵州省惠水县摆金镇,遗址发现于1998年9月,因发现丰富石制品、骨制品、灰烬层和哺乳动物化石等遗物而为学术界所关注。2013年9至11月,中国科学院古脊椎动物与古人类研究所和贵州省文物考古研究所联合对清水苑大洞进行考古发掘,发掘区分A、B两区,揭露面积分别为4 m~2和6 m~2。A区揭露地层厚度约90cm,堆积物为灰白-灰黄色-灰黑色砂质黏土,共出土石制品2398件、动物化石及碎骨2000余件。石制品组合以小型石片工业为体,类型包括石核、石器、各类废片、石锤、磨石等,此外还有5件砸击品。石制品原料大多取自围岩内的燧石,剥片以硬锤锤击法为主,石制品以小型居多;刮削器为石器的主要类型,另有少量凹缺器;石器修理多以锤击法向片状毛坯的背面修理为主。~(14)C测年显示遗址形成于距今约11-14 ka BP,为旧-新石器时代过渡期。该遗址的发掘和研究对于探讨更新世末期古人类在贵州中部低海拔地区的适应生存方式具有重要意义。 相似文献
28.
Hongmin Lai Changbin Sun Huaying Tang Xianwei Fan Yili Ma Youzhi Li 《Journal of microbiology (Seoul, Korea)》2009,47(6):736-745
Copper (Cu)-transporting P-type ATPase (CTPA) genes have been documented to play an important role in resistance to heavy
metals. However, our understanding of roles of CTPA genes of the filamentous fungi was based only on sequence similarity prediction
before. In a previous study, we isolated a Penicillum janthinellum strain GXCR of higher tolerance to Cu (200 mM). In this study, we cloned the partial cDNA of CTPA gene, named PcpA, from the strain GXCR. Sequence alignment indicated that the cloned cDNA sequence has the highest identity (94.4%) with a
predictive CTPA gene of Aspergillus clavatus. The PcpA-encoded protein, termed PcpA, has classical functional domains of CTPAs, and shows differences from reported CTPAs in some
specific sequence motifs and transmembrane regions. Expression of the PcpA was induced by extracellular Cu, cadmium (Cd), and silver (Ag). PcpA RNA interference (RNAi) mutants with a reduced level of PcpA mRNA were more sensitive to Cu, iron, Cd, and Ag than the wild-type (WT) strain GXCR. When grown in the presence of Cu, iron,
and Cd, intracellular Cu and iron contents in the PcpA RNAi mutant were significantly (P<0.05) lower than those in the WT; However, intracellular Cd content in the mutant was significantly (P<0.05) higher than that in the WT. Taken together, it can be concluded that the PcpA functions in Cu uptake and homeostasis, iron uptake, and Cd export from the cytosol to the extracytosol. 相似文献
29.
用于药用蛋白生产的外源表达系统 总被引:3,自引:0,他引:3
种表达系统在重组蛋白生产上将长期共存.而通过遗传改造、基因组学、蛋白质组学等研究方法不断改进各种外源蛋白表达系统的性能,不断建立更加优越的外源蛋白表达系统则是大家共同努力的目标. 相似文献
30.