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We recently discovered a novel nargenicin A1 analog, 23-demethyl 8,13-deoxynargenicin (compound 9), with potential anti-cancer and anti-angiogenic activities against human gastric adenocarcinoma (AGS) cells. To identify the key molecular targets of compound 9, that are responsible for its biological activities, the changes in proteome expression in AGS cells following compound 9 treatment were analyzed using two-dimensional gel electrophoresis (2-DE), followed by MALDI/TOF/MS. Analyses using chemical proteomics and western blotting revealed that compound 9 treatment significantly suppressed the expression of cyclophilin A (CypA), a member of the immunophilin family. Furthermore, compound 9 downregulated CD147-mediated mitogen-activated protein kinase (MAPK) signaling pathway, including c-Jun N-terminal kinase (JNK) and extracellular signal-regulated protein kinase 1/2 (ERK1/2) by inhibiting the expression of CD147, the cellular receptor of CypA. Notably, the responses of AGS cells to CypA knockdown were significantly correlated with the anticancer and antiangiogenic effects of compound 9. CypA siRNAs reduced the expression of CD147 and phosphorylation of JNK and ERK1/2. In addition, the suppressive effects of CypA siRNAs on proliferation, migration, invasion, and angiogenesis induction of AGS cells were associated with G2/M cell cycle arrest, caspase-mediated apoptosis, inhibition of MMP-9 and MMP-2 expression, inactivation of PI3K/AKT/mTOR pathway, and inhibition of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression. The specific interaction between compound 9 and CypA was also confirmed using the drug affinity responsive target stability (DARTS) and cellular thermal shift assay (CETSA) approaches. Moreover, in silico docking analysis revealed that the structure of compound 9 was a good fit for the cyclosporin A binding cavity of CypA. Collectively, these findings provide a novel molecular basis for compound 9-mediated suppression of gastric cancer progression through the targeting of CypA.  相似文献   
43.
Chronic inflammation represents a long-term reaction of the body's immune system to noxious stimuli. Such a sustained inflammatory response sometimes results in lasting damage to healthy tissues and organs. In fact, chronic inflammation is implicated in the development and progression of various diseases, including cardiovascular diseases, respiratory diseases, metabolic diseases, neurodegenerative diseases, and even cancers. Targeting nonresolving inflammation thus provides new opportunities for treating relevant diseases. In this review, we will go over several chronic inflammation-associated diseases first with emphasis on the role of inflammation in their pathogenesis. Then, we will summarize a number of natural products that exhibit therapeutic effects against those diseases by acting on different markers in the inflammatory response. We envision that natural products will remain a rich resource for the discovery of new drugs treating diseases associated with chronic inflammation.  相似文献   
44.
陕北±800 kV换流站用地为原循环工业经济园区挖黄土梁卯、填深沟给出的一块台阶式场地,场地覆盖一层厚度0~50 m的素填土,密实度差异较大,土质极不均匀,填土完成约5年半时间,是一种欠固结土,在其自身重度和大气降水的入渗作用下有自行密实的特点,影响位于填方区建(构)筑物地基的承载力和稳定性。基于该工程特殊的岩土地质情况,除挖方区采用天然地基外,从处理填方区大面积欠固结土和消除部分地基土湿陷性、提高地基土承载力、减小场地沉降变形的角度,对不同地基处理及桩基方案进行技术经济综合比选,提出适合本工程的经济合理的地基处理方案。  相似文献   
45.
负载不平衡会导致电能质量差、功率损耗增加、变压器使用寿命缩短等问题,而准确识别用户相别可调整部分用户相别,尽可能达到三相负载平衡,因此提出一种基于主成分分析与Wasserstein距离的低压用户相别识别方法.首先利用主成分分析提取低压用户电压主成分进行聚类,然后计算聚类中值与关口各相电压Wasserstein距离进行相别归属.实测数据证明该方法对相别识别准确性较高,且相较于传统相似度算法在判别相别时具有明显区分度.  相似文献   
46.
In recent years, highly efficient oil/water separation materials have brought much attention. It requests superhydrophobic surfaces with a rapid and facile separation process, excellent durability, and large-scale fabrication. Herein, a facile vapor-liquid sol-gel, and free radical polymerization reaction method to prepare the durable and robust superhydrophobic cotton fabric is proposed. Moreover, the fabric can be used for highly efficient and various oil/water separation. It is prepared via a simple two-step process, including a vapor-liquid sol-gel process to deposit with thiols particles, and then followed a free radical polymerization reaction to graft 2,2,3,4,4,4-hexafluorobutyl methacrylate. Scanning electron microscopy and Fourier transform infrared spectrometry prove that the rough structures are generated from the hydrolysis condensation reaction between tetraethyl orthosilicate and 3-mercaptopropyltriethoxysilane. As a result, the synthetic chemical composition provided by the natural fabric and silica nanoparticles synergistically construct a superhydrophobic surface with water contact angles and shedding angle of 158° and 9°, respectively. Additionally, the treated fabric exhibits excellent chemical resistance and self-cleaning ability. Remarkably, the fabric still retains superhydrophobic and excellent mechanical robustness after 30 cycles of various oil/water separation. In summary, the resultant fabrics with excellent chemical resistance, remarkable mechanical robustness, and versatile separation abilities have potential applications in various oil/water separations.  相似文献   
47.
48.
九月,秋高气爽的日子,同时也是“第十六届德国埃森国际焊接与切割展览会”盛大举办的日子。这个极负盛名的国际展会每四年举行一次,享誉全球,吸引着来自世界知名的焊接与切割生产厂商、用户集聚德国埃森,共同分享世界先进的焊接与切割技术。本届德国埃森国际焊接展于9月12—17日在德国埃森市举办。  相似文献   
49.
粉煤灰基混凝剂的制备及在大麻废水中的应用   总被引:6,自引:0,他引:6  
米杰  鲍卫仁 《煤炭转化》2004,27(2):76-79
采用酸溶法以粉煤灰为基础原料 ,通过添加一定量的硫铁矿烧渣 ,制备成粉煤灰基复合混凝剂 ,确定了最佳工艺条件 .实验结果表明 ,影响混凝剂制备的主要因素是粉煤灰与硫铁矿渣的质量比、酸用量、浸取时间和温度 .此混凝剂对大麻废水中 CODcr去除率达 88% ,色度去除率可达 96.6%以上 ,具有沉淀快和污泥体积小等优点 .  相似文献   
50.
环戊烯催化氧化合成戊二醛及其动力学   总被引:6,自引:0,他引:6  
对在非水溶剂存在下过氧化氢一步催化氧化环戊烯制备戊二醛过程中的催化体系进行了研究。考察了具有脱水功能的B2O3的作用及用量,确立了具有优良催化性能的催化体系WO3-B2O3;实验测定了反应动力学数据,采用非线性回归Powel共扼法求得了反应动力学方程。在推荐的催化剂体系和工艺条件下,环戊烯转化率67%,戊二醛收率63%,选择性91%。  相似文献   
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