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991.
Ho Shin Kim Van-Hai Hoang Mannkyu Hong Kyung Chul Kim Jihyae Ann Cong-Truong Nguyen Ji Hae Seo Hoon Choi Jun Yong Kim Kyu-Won Kim Woong Sub Byun Sangkook Lee Seungbeom Lee Young-Ger Suh Jie Chen Hyun-Ju Park Tae-Min Cho Ji Young Kim Jeewoo Lee 《Bioorganic & medicinal chemistry》2019,27(7):1370-1381
On the basis of deguelin, a series of the B,C-ring truncated surrogates with N-substituted amide linkers were investigated as HSP90 inhibitors. The structure activity relationship of the template was studied by incorporating various substitutions on the nitrogen of the amide linker and examining their HIF-1α inhibition. Among them, compound 57 showed potent HIF-1α inhibition and cytotoxicity in triple-negative breast cancer lines in a dose-dependent manner. Compound 57 downregulated expression and phosphorylation of major client proteins of HSP90 including AKT, ERK and STAT3, indicating that its antitumor activity was derived from the inhibition of HSP90 function. The molecular modeling of 57 demonstrated that 57 bound well to the C-terminal ATP-binding pocket in the open conformation of the hHSP90 homodimer with hydrogen bonding and pi-cation interactions. Overall, compound 57 is a potential antitumor agent for triple-negative breast cancer as a HSP90 C-terminal inhibitor. 相似文献
992.
Mammalian Genome - Increasing evidence shows that miRNAs play pivotal roles in cardiovascular diseases, including heart failure (HF). The aim of this study was to investigate the role of miR-129-5p... 相似文献
993.
Murakami Shinsuke Nakatani Jun Nakajima Kenichi Amasawa Eri Ii Ryota Hayashi Kiyotada Yoshikawa Naoki Daigo Ichiro Kishita Yusuke Ihara Tomohiko Shobatake Koichi Kudoh Yuki Motoshita Masaharu Kanemoto Keiichiro Hara Minako Kashiwagi Aiichiro Hashimoto Seiji Shigetomi Yosuke Kanzaki Masayuki Kikuchi Yasunori Ohno Hajime Fukushima Yasuhiro 《The International Journal of Life Cycle Assessment》2019,24(8):1544-1552
The International Journal of Life Cycle Assessment - 相似文献
994.
995.
Yun Ren Dan Chen Wenjie Li Dan Zhou Tao Luo Guoqiang Yuan Jing Zeng Ye Cao Zhongshan He Ting Zou Qiming Deng Shiquan Wang Aiping Zheng Jun Zhu Yueyang Liang Huainian Liu Lingxia Wang Ping Li Shuangcheng Li 《The Plant journal : for cell and molecular biology》2019,98(2):315-328
Meiosis is essential for eukaryotic sexual reproduction and plant fertility, and crossovers (COs) are essential for meiosis and the formation of new allelic combinations in gametes. In this study, we report the isolation of a meiotic gene, OsSHOC1, and the identification of its partner, OsPTD1. Osshoc1 was sterile both in male and female gametophytes, and it showed a striking reduction in the number of meiotic COs, indicating that OsSHOC1 was required for normal CO formation. Further investigations showed that OsSHOC1 physically interacted with OsPTD1 and that the latter was also required for normal CO formation and plant fertility. Additionally, the expression profiles of both genes were consistent with their functions. Our results suggest that OsSHOC1 and OsPTD1 are essential for rice fertility and CO formation, possibly by stabilizing the recombinant intermediates during meiosis. 相似文献
996.
997.
Shijin Tang Yinping Pan Deshuai Lou Shunlin Ji Liancai Zhu Jun Tan Na Qi Qiong Yang Zhi Zhang Biling Yang Wenyan Zhao Bochu Wang 《Protein science : a publication of the Protein Society》2019,28(5):910-919
7α‐Hydroxysteroid dehydrogenase (7α‐HSDH) is an NAD(P)H‐dependent oxidoreductase belonging to the short‐chain dehydrogenases/reductases. In vitro, 7α‐HSDH is involved in the efficient biotransformation of taurochenodeoxycholic acid (TCDCA) to tauroursodeoxycholic acid (TUDCA). In this study, a gene encoding novel 7α‐HSDH (named as St‐2‐1) from fecal samples of black bear was cloned and heterologously expressed in Escherichia coli. The protein has subunits of 28.3 kDa and a native size of 56.6 kDa, which suggested a homodimer. We studied the relevant properties of the enzyme, including the optimum pH, optimum temperature, thermal stability, activators, and inhibitors. Interestingly, the data showed that St‐2‐1 differs from the 7α‐HSDHs reported in the literature, as it functions under acidic conditions. The enzyme displayed its optimal activity at pH 5.5 (TCDCA). The acidophilic nature of 7α‐HSDH expands its application environment and the natural enzyme bank of HSDHs, providing a promising candidate enzyme for the biosynthesis of TUDCA or other related chemical entities. 相似文献
998.
ABSTRACTSmog pollution has received widely attention in recent years due to its negative effects. There is consensus that the motor vehicle exhaust emission is one of the sources of smog pollution and reduced private car use would significantly improve the air quality and alleviate the smog pollution problem. In this research, we aim to investigate how public smog knowledge and risk perception (physical health risk perception and mental health risk perception) affect public attitude and intention to reduce car use. A questionnaire survey of 334 randomly sampled respondents was designed to test these relationships. The results show that public smog knowledge is positively and significantly related to physical health risk perception, mental health risk perception, attitude and intention to reduce car use. Public smog knowledge has the largest impact on intention to reduce car use. Furthermore, physical health risk perception and mental health risk perception are positively and significantly associated with attitude and intention to reduce car use. In addition, the results also indicated that public smog knowledge is at a low level. Based on the results, implications and suggestions for future research were discussed. 相似文献
999.
Brucella melitensis infection causes acute necrotizing inflammation in pregnant animals; however, the pathophysiological mechanisms leading to placentitis are unknown. Here, we demonstrate that high‐mobility group box 1 (HMGB1) acts as a mediator of placenta inflammation in B. melitensis‐infected pregnant mice model. HMGB1 levels were increased in trophoblasts or placental explant during B. melitensis infection. Inhibition of HMGB1 activity with neutralising antibody significantly reduced the secretion of inflammatory cytokines in B. melitensis‐infected trophoblasts or placenta, whereas administration of recombinant HMGB1 (rHMGB1) increased the inflammatory response. Mechanistically, this decreased inflammatory response results from inhibition of HMGB1 activity, which cause the suppression of both mitogen‐activated protein kinases and nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) activation. Moreover, neutralising antibody to HMGB1 prevented B. melitensis infection‐induced activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in trophoblasts. In contrast, in vitro stimulation of trophoblasts with rHMGB1 caused activation of NADPH oxidase and increased the production of ROS, which contributes to high bacterial burden within trophoblasts or placenta. In vivo, treatment with anti‐HMGB1 antibody increases the number of Brucella survival within placenta in B. melitensis‐infected pregnant mice but successfully reduced the severity of placentitis and abortion. 相似文献
1000.
Lifan Sun Jun Qin Wei Rong Hao Ni Hui-Shan Guo Jie Zhang 《Molecular Plant Pathology》2019,20(3):323-333
The soil-borne vascular pathogen Verticillium dahliae infects many dicotyledonous plants to cause devastating wilt diseases. During colonization, V. dahliae spores develop hyphae surrounding the roots. Only a few hyphae that adhere tightly to the root surface form hyphopodia at the infection site, which further differentiate into penetration pegs to facilitate infection. The molecular mechanisms controlling hyphopodium formation in V. dahliae remain unclear. Here, we uncovered a cellophane surface-induced gene (VdCSIN1) as a regulator of V. dahliae hyphopodium formation and pathogenesis. Deletion of VdCSIN1 compromises hyphopodium formation, hyphal development and pathogenesis. Exogenous application of cyclic adenosine monophosphate (cAMP) degradation inhibitor or disruption of the cAMP phosphodiesterase gene (VdPDEH) partially restores hyphopodium formation in the VdΔcsin1 mutant. Moreover, deletion of VdPDEH partially restores the pathogenesis of the VdΔcsin1 mutant. These findings indicate that VdCSIN1 regulates hyphopodium formation via cAMP-mediated signalling to promote host colonization by V. dahliae. 相似文献