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103.
Dong-Dong Li Ya-Juan Qin Jian Sun Jing-Ran Li Fei Fang Qian-Ru Du Yong Qian Hai-Bin Gong Hai-Liang Zhu 《PloS one》2013,8(8)
4-Anilinoquinazolines as an important class of protein kinase inhibitor are widely investigated for epidermal growth factor receptor (EGFR) tyrosine kinase or epidermal growth factor receptor 2 (HER2) inhibition. A series of novel 6-salicyl-4-anilinoquinazoline derivatives 9–27 were prepared and evaluated for their EGFR/HER2 tyrosine kinase inhibitory activity as well as their antiproliferative properties on three variant cancer cell lines (A431, MCF-7, and A549). The bioassay results showed most of the designed compounds exhibited moderate to potent in vitro inhibitory activity in the enzymatic and cellular assays, of which compound 21 revealed the most potent dual EGFR/HER2 inhibitory activity, with IC50 values of 0.12 µM and 0.096 µM, respectively, comparable to the control compounds Erlotinib and Lapatinib. Furthermore, the kinase selectivity profile of 21 was accessed and demonstrated its good selectivity over the majority of the close kinase targets. Docking simulation was performed to position compound 21 into the EGFR/HER2 active site to determine the probable binding pose. These new findings along with molecular docking observations could provide an important basis for further development of compound 21 as a potent EGFR/HER2 dual kinase inhibitor. 相似文献
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105.
Gong‐Rak Lee Mi Kyung Shin Dong‐Joon Yoon Ah‐Ram Kim Rina Yu Neung‐Hwa Park In‐Seob Han 《Obesity (Silver Spring, Md.)》2013,21(1):115-122
Objective:
Visceral obesity contributes to the development of obesity‐related disorders such as diabetes, hyperlipidemia, and fatty liver disease, as well as cardiovascular diseases. In this study, we determined whether topical application of capsaicin can reduce fat accumulation in visceral adipose tissues.Methods and Results:
We first observed that topical application of 0.075% capsaicin to male mice fed a high‐fat diet significantly reduced weight gain and visceral fat. Fat cells were markedly smaller in the mesenteric and epididymal adipose tissues of mice treated with capsaicin cream. The capsaicin treatment also lowered serum levels of fasting glucose, total cholesterol, and triglycerides. Immunoblot analysis and RT‐PCR revealed increased expression of adiponectin and other adipokines including peroxisome proliferator‐activated receptor (PPAR) α, PPARγ, visfatin, and adipsin, but reduced expression of tumor necrosis factor‐α and IL‐6.Conclusions:
These results indicate that topical application of capsaicin to obese mice limits fat accumulation in adipose tissues and may reduce inflammation and increase insulin sensitivity. 相似文献106.
Lin Cheng Xing-Kun Jin Wei-Wei Li Shuang Li Xiao-Nv Guo Juan Wang Ya-Nan Gong Lin He Qun Wang 《PloS one》2013,8(1)
Invertebrates rely solely on the innate immune system for defense against pathogens and other stimuli. Fatty acid binding proteins (FABP), members of the lipid binding proteins superfamily, play a crucial role in fatty acid transport and lipid metabolism and are also involved in gene expression induced by fatty acids. In the vertebrate immune system, FABP is involved in inflammation regulated by fatty acids through its interaction with peroxidase proliferator activate receptors (PPARs). However, the immune functions of FABP in invertebrates are not well characterized. For this reason, we investigated the immune functionality of two fatty acid binding proteins, Es-FABP9 and Es-FABP10, following lipopolysaccharide (LPS) challenge in the Chinese mitten crab (Eriocheir sinensis). An obvious variation in the expression of Es-FABP9 and Es-FABP10 mRNA in E. sinensis was observed in hepatopancreas, gills, and hemocytes post-LPS challenge. Recombinant proteins rEs-FABP9 and rEs-FABP10 exhibited distinct bacterial binding activity and bacterial agglutination activity against Escherichia coli and Staphylococcus aureus. Furthermore, bacterial growth inhibition assays demonstrated that rEs-FABP9 responds positively to the growth inhibition of Vibrio parahaemolyticuss and S. aureus, while rEs-FABP10 responds positively to the growth inhibition of Aeromonas hydrophila and Bacillus subtilis. Coating of agarose beads with recombinant rEs-FABP9 and rEs-FABP10 dramatically enhanced encapsulation of the beads by crab hemocytes in vitro. In conclusion, the data presented here demonstrate the participation of these two lipid metabolism-related proteins in the innate immune system of E. sinensis. 相似文献
107.
De-Xiang Zhuo Xiao-Wei Zhang Bo Jin Zheng Zhang Bu-Shan Xie Cheng-Lin Wu Kan Gong Ze-Bin Mao 《PloS one》2013,8(6)
Akt/protein kinase B is a pivotal component downstream of phosphatidylinositol 3-kinase (PI3K) pathway, whose activity regulates the balance between cell survival and apoptosis. Phosphorylation of Akt occurs at two key sites either at Thr308 site in the activation loop or at Ser473 site in the hydrophobic motif. The phosphorylated form of Akt (pAkt) is activated to promote cell survival. The mechanisms of pAkt dephosphorylation and how the signal transduction of Akt pathway is terminated are still largely unknown. In this study, we identified a novel protein phosphatase CSTP1(complete s transactivated protein 1), which interacts and dephosphorylates Akt specifically at Ser473 site in vivo and in vitro, blocks cell cycle progression and promotes cell apoptosis. The effects of CSTP1 on cell survival and cell cycle were abrogated by depletion of phosphatase domain of CSTP1 or by expression of a constitutively active form of Akt (S473D), suggesting Ser473 site of Akt as a primary cellular target of CSTP1. Expression profile analysis showed that CSTP1 expression is selectively down-regulated in non-invasive bladder cancer tissues and over-expression of CSTP1 suppressed the size of tumors in nude mice. Kaplan-Meier curves revealed that decreased expression of CSTP1 implicated significantly reduced recurrence-free survival in patients suffered from non-invasive bladder cancers. 相似文献
108.
叶绿素荧光测量分析可以揭示植物叶片光化学效率的变化,已越来越多地应用于植物生态监测。以再生水为主要补给水源的北京门城湖湿地公园为研究区,选取典型湿地挺水植物芦苇(Phragmites australis)、香蒲(Typha angustifolia)和茭白(Zizania latifolia)为研究对象,通过野外测量叶片尺度的叶绿素荧光参数和室内测定对应样点的水体总氮含量指标,研究了再生水补给条件下,不同水氮梯度植物叶绿素荧光的响应特性。结果表明,3种典型挺水植物的初始荧光(Fo)与最大荧光(Fm)随着水体总氮含量的增加呈现上升的趋势;PSII的量子效率(F_v/F_m)与实际量子效率(ΦPSII)受水氮含量的影响先升高,达到15–20 mg·L~(–1)区间时,则与之持平;光化学淬灭(qP)参数则呈现先升高后降低的变化趋势,而非光化学淬灭(NPQ)参数的变化没有明显的规律。当水氮含量为15–20 mg·L~(–1)时,光化学反应减弱,光合作用出现抑制。不同类型植物的荧光参数也有所不同,处于生长期(6月)植物的光合作用显著强于生长成熟期(9月)。 相似文献
109.
Fangyu Cheng Qianying Gong Huimin Yu Gregory Stephanopoulos 《Biotechnology journal》2016,11(4):574-584
Hyaluronic acid (HA) plays important roles in human tissue system, thus it is highly desirable for various applications, such as in medical, clinic and cosmetic fields. The wild microbial producer of HA, streptococcus, was restricted by its potential pathogens, hence different recombinant hosts are being explored. In this work, we engineered Corynebacterium glutamicum, a GRAS (Generally Recognized as Safe) organism free of exotoxins and endotoxins to produce HA with high titer and satisfied Mw. The ssehasA gene encoding hyaluronan synthase (HasA) was artificially synthesized with codon preference of C. glutamicum. Other genes involved in the HA synthetic pathway were directly cloned from the C. glutamicum genome. The operon structures and constitutive or inducible promoters were particularly compared and the preferred environmental conditions were also optimized. Using glucose and corn syrup powder as carbon and nitrogen sources, batch cultures of the engineered C.glutamicum with operon ssehasA‐hasB driven by Ptac promoter were performed in a 5 L fermentor. The maximal HA titer, productivity and yield reached 8.3 g/L, 0.24 g/L/h and 0.22 gHA/gGlucose, respectively; meanwhile the maximal Mw was 1.30 MDa. This work provides a safe and efficient novel producer of HA with huge industrial prospects. 相似文献
110.
Ru-Jia Yan Hai-Qing Gong Pu-Ming Zhang Shi-Gang He Pei-Ji Liang 《Cognitive neurodynamics》2016,10(3):211-223
Dual-peak responses of retinal ganglion cells (RGCs) are observed in various species, previous researches suggested that both response peaks were involved in retinal information coding. In the present study, we investigated the temporal properties of the dual-peak responses recorded in mouse RGCs elicited by spatially homogeneous light flashes and the effect of the inhibitory inputs mediated by GABAergic and/or glycinergic pathways. We found that the two peaks in the dual-peak responses exhibited distinct temporal dynamics, similar to that of short-latency and long-latency single-peak responses respectively. Pharmacological studies demonstrated that the application of exogenous GABA or glycine greatly suppressed or even eliminated the second peak of the cells’ firing activities, while little change was induced in the first peak. Co-application of glycine and GABA led to complete elimination of the second peak. Moreover, application of picrotoxin or strychnine induced dual-peak responses in some cells with transient responses by unmasking a second response phase. These results suggest that both GABAergic and glycinergic pathways are involved in the dual-peak responses of the mouse RGCs, and the two response peaks may arise from distinct pathways that would converge on the ganglion cells. 相似文献