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91.
92.
Bryan D. Yestrepsky Yuanxi Xu Meghan E. Breen Xiaoqin Li Walajapet G. Rajeswaran Jenny G. Ryu Roderick J. Sorenson Yasuhiro Tsume Michael W. Wilson Wenpeng Zhang Duxin Sun Hongmin Sun Scott D. Larsen 《Bioorganic & medicinal chemistry》2013,21(7):1880-1897
Resistance to antibiotics is an increasingly dire threat to human health that warrants the development of new modes of treating infection. We recently identified 1 (CCG-2979) as an inhibitor of the expression of streptokinase, a critical virulence factor in Group A Streptococcus that endows blood-borne bacteria with fibrinolytic capabilities. In this report, we describe the synthesis and biological evaluation of a series of novel 5,6-dihydrobenzo[h]quinazolin-4(3H)-one analogs of 1 undertaken with the goal of improving the modest potency of the lead. In addition to achieving an over 35-fold increase in potency, we identified structural modifications that improve the solubility and metabolic stability of the scaffold. The efficacy of two new compounds 12c (CCG-203592) and 12k (CCG-205363) against biofilm formation in Staphylococcus aureus represents a promising additional mode of action for this novel class of compounds. 相似文献
93.
Tae-Hwan Ha HyungChul Ryu Sung-Eun Kim Ho Shin Kim Jihyae Ann Phuong-Thao Tran Van-Hai Hoang Karam Son Minghua Cui Sun Choi Peter M. Blumberg Robert Frank Gregor Bahrenberg Klaus Schiene Thomas Christoph Sven Frormann Jeewoo Lee 《Bioorganic & medicinal chemistry》2013,21(21):6657-6664
A series of 2-thio pyridine C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides were investigated as hTRPV1 antagonists. Among them, compound 24S showed stereospecific and excellent TRPV1 antagonism of capsaicin-induced activation. Further, it demonstrated strong anti-allodynic in a rat neuropathic pain model. Consistent with its action in vitro being through TRPV1, compound 24S blocked capsaicin-induced hypothermia in mice. Docking analysis of 24S with our hTRPV1 homology model was performed to identify its binding mode. 相似文献
94.
该文报道了短尖拟青藓[Sciuro-hypnum ornellanum (Molendo) Ignatov & Huttunen]在新疆阿尔泰山的分布,这是该种在中国的首次记录。详细介绍了拟青藓属[Sciuro-hypnum (Hampe) Hampe]的由来,讨论了短尖拟青藓的形态特征及其地理分布,对其与形态相近种进行了比较分析,并提供了中国拟青藓属分种检索表。该种的发现不仅为中国青藓科植物研究提供了新资料,同时也进一步佐证了中国新疆植物区系与俄罗斯、中亚及欧洲的密切联系。 相似文献
95.
目的研究小鼠肾缺血再灌注损伤的发病机制。方法建立小鼠肾缺血再灌注损伤模型。12只雄性C57BL/6随机分为2个组(n=6),分别为假手术组(Sham),肾缺血再灌注损伤模型组(IRI)。IRI组血管夹夹闭左肾动脉,置于32℃温箱后1h松开血管夹,去除右肾。Sham组操作同上,但不夹闭左肾动脉。再灌注24h后处死小鼠,收集血清和肾脏标本。测定血清肌酐(Cr)和血尿素氮(BUN)。PAS染色后显微镜下观察肾脏形态学变化,Western印迹分析ERK、p-ERK的表达,PCR检测MCP-1、IFN-γ。结果与假手术组(Sham)相比,IRI组血清肌酐、血尿素氮明显升高,病理检查可见肾脏内肾小管上皮细胞明显肿胀坏死、蛋白管型形成明显,还可观察到炎性细胞浸润明显增加。ERK、p-ERKWestern印迹结果PCR显示MCP-1、TNF-α也明显上调,但ERK表达不变。结论在肾缺血再灌注中,ERK激活介导的炎性后府可能参与了肾扣伤。 相似文献
96.
At present, acid rain has become one of the top ten global environmental issues. Acid rain causes slower growth, injury, or decline of forests. Some dramatic effects on forests have been observed in south China since the late 1970s and the situation is deteriorating. We carried out a comparative proteomic analysis on Pinus massoniana Lamb, a staple tree species widely distributed in middle and south China to gain a better understanding of tree response to acid rain at molecular level. Two-year-old P. massoniana saplings were treated with simulated AR (SiAR) or control solution, respectively, for 8 months. The changes in total protein profile of P. massoniana leaves were studied using two-dimensional differential gel electrophoresis (2D-DIGE). Among the total protein spots reproducibly detected on each gel, 65 spots representing 28 proteins were identified to be differentially regulated. These proteins were annotated in various biological functions, such as photosynthesis and energy metabolism, secondary metabolism, protein stability, amino acid and nitrogen metabolism and defense. Down-regulation of four key enzymes in the Calvin cycle identified that biomass loss by SiAR was mainly due to the inhibition of carbon fixation. Primary energy metabolisms involved in sucrose biosynthesis, glycolytic pathway and Krebs cycle, etc., were also disturbed after SiAR treatment. Specifically, most of up-regulated proteins were related to secondary metabolism, protein stability and defense, suggesting that in response to SiAR stress, plants started a variety of metabolic pathways to prevent cells from damage. Different from the herbaceous plants suffering SiAR, it revealed that secondary metabolites in P. massoniana play pivotal roles against SiAR. Protemoic techniques were demonstrated a reliable and robust tool to expand our understanding of differentially expressed proteins associated with acid rain stress on P. massoniana. Functional analysis of these proteins further revealed biochemical and physiological basis of the plant in response to acid rain and would provide strategies for breeding new acid rain tolerant tree species. To our knowledge, it is the first proteome report on the forest plant suffering long-term acid rain stress. 相似文献
97.
Jae Kwang Kim Soo-Yun Park Si Myung Lee Sun-Hyung Lim Hyo Jin Kim Sung-Dug Oh Yunsoo Yeo Hyun Suk Cho Sun-Hwa Ha 《Plant biotechnology reports》2013,7(1):121-128
Substantial equivalence is a critical concept for biosafety assessment of genetically modified (GM) crops. To investigate substantial equivalence among carotenoid-biofortified GM rice and five conventional rice cultivars having common white (three) and red (two) grain colors, profiles of 52 polar metabolites were analyzed using gas chromatography time-of-flight mass spectrometry. The results were compared to evaluate the differences among GM and non-GM rice cultivars using principal components analysis. The GM rice is more comparable to its non-transgenic counterpart rice variety according to the closer co-separation than for other cultivars tested. This suggests that profiling of unintended polar metabolites could be a useful tool to reveal substantial equivalence of GM rice. 相似文献
98.
Kyong-Hoon Ahn Seok-Kyun Kim Jong-Min Choi Sung-Yun Jung Jong-Hoon Won Moon-Jung Back Zhicheng Fu Ji-Min Jang Hae-Chan Ha Dae-Kyong Kim 《PloS one》2013,8(6)
Activation of sphingomyelinase (SMase) by extracellular stimuli is the major pathway for cellular production of ceramide, a bioactive lipid mediator acting through sphingomyelin (SM) hydrolysis. Previously, we reported the existence of six forms of neutral pH–optimum and Mg2+-dependent SMase (N-SMase) in the membrane fractions of bovine brain. Here, we focus on N-SMase ε from salt-extracted membranes. After extensive purification by 12,780-fold with a yield of 1.3%, this enzyme was eventually characterized as N-SMase2. The major single band of 60-kDa molecular mass in the active fractions of the final purification step was identified as heat shock protein 60 (Hsp60) by matrix-assisted laser desorption/ionization time-of-flight mass spectrometric analysis. Proximity ligation assay and immunoprecipitation study showed that Hsp60 interacted with N-SMase2, prompting us to examine the effect of Hsp60 on N-SMase2 and ceramide production. Interestingly, Hsp60 siRNA treatment significantly increased the protein level of N-SMase2 in N-SMase2-overexpressed HEK293 cells. Furthermore, transfection of Hsp60 siRNA into PC12 cells effectively increased both N-SMase activity and ceramide production and increased dopamine re-uptake with paralleled increase. Taken together, these results show that Hsp60 may serve as a negative regulator in N-SMase2-induced dopamine re-uptake by decreasing the protein level of N-SMase2. 相似文献
99.
Mastooreh Chamanian Katarzyna J. Purzycka Paul T. Wille Janice S. Ha David McDonald Yong Gao Stuart F.J. Le Grice Eric J. Arts 《Cell host & microbe》2013,13(2):181-192
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100.
Hye Ran Park Jae Meen Lee Gwanhee Ehm Hui-Jun Yang In Ho Song Yong Hoon Lim Mi-Ryoung Kim Keyoung Ran Kim Woong-Woo Lee Young Eun Kim Jae Ha Hwang Chae Won Shin Hyeyoung Park Jin Wook Kim Han-Joon Kim Cheolyoung Kim Dong Gyu Kim Beom Seok Jeon Sun Ha Paek 《PloS one》2016,11(1)