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21.
Large conductance Ca2+-activated potassium channels (BK) are targets for research that explores therapeutic means to various diseases, owing to the roles of the channels in mediating multiple physiological processes in various cells and tissues. We investigated the pharmacological effects of curcumin, a compound isolated from the herb Curcuma longa, on BK channels. As recorded by whole-cell patch-clamp, curcumin increased BK (α) and BK (α+β1) currents in transfected HEK293 cells as well as the current density of BK in A7r5 smooth muscle cells in a dose-dependent manner. By incubating with curcumin for 24 hours, the current density of exogenous BK (α) in HEK293 cells and the endogenous BK in A7r5 cells were both enhanced notably, though the steady-state activation of the channels did not shift significantly, except for BK (α+β1). Curcumin up-regulated the BK protein expression without changing its mRNA level in A7r5 cells. The surface expression and the half-life of BK channels were also increased by curcumin in HEK293 cells. These effects of curcumin were abolished by MG-132, a proteasome inhibitor. Curcumin also increased ERK 1/2 phosphorylation, while inhibiting ERK by U0126 attenuated the curcumin-induced up-regulation of BK protein expression. We also observed that the curcumin-induced relaxation in the isolated rat aortic rings was significantly attenuated by paxilline, a BK channel specific blocker. These results show that curcumin enhances the activity of the BK channels by interacting with BK directly as well as enhancing BK protein expression through inhibiting proteasomal degradation and activating ERK signaling pathway. The findings suggest that curcumin is a potential BK channel activator and provide novel insight into its complicated pharmacological effects and the underlying mechanisms. 相似文献
22.
自然生态系统与人类感知的交互作用是景感生态学关注的焦点,与生态系统服务的供需紧密关联。生态系统、生态过程、生态系统服务以及人的需求均具有一定的时空尺度特征,因此,由这些过程产生的"景感"也具有时空尺度特征,并依赖于这个过程的尺度特征相互作用。梳理生态系统服务供需关系与景感营造规划的尺度特征,探索二者相互联系,进而提出基于景感生态学理论,通过景感营造实现生态系统服务供需平衡的多尺度实现路径。从空间维度,体现从"社区-城市-流域-区域"的多尺度景感规划框架,从应用维度,体现从生态系统服务需求探索-关键指标体系识别-多源谜码数据感知-景感营造与规划设计的具体流程。通过多尺度的联合景感营造,调整自然供给水平与人类不同尺度的生态系统服务需求以期达到平衡,从而实现人类生存环境福利与居民福祉提升的目标。在此基础上,结合雄安新区规划建设实例,从多尺度景感营造的角度为城市绿色生态建设与可持续发展提出优化建议。主要结论:(1)基于"社区-城市-流域-区域"的多尺度景感分析框架,将景感要素与生态系统服务供需思想融入城市规划,在不同尺度上趋善优化,对于实现可持续发展城市规划和管理具有重要指示意义;(2)雄安新区规划设计需更系统和细致地考虑人类感知需求,通过多尺度景感营造设计,共同实现雄安新区的可持续发展与人居环境提升。其中,在社区尺度,需重点关注社区植被配置和居民的休闲游憩;在新区尺度重点关注绿地系统网络构建;在大清河流域尺度重点关注河流健康与水文调节;在京津冀区域尺度需注重山体通风廊道与生态屏障的构建与优化。 相似文献
23.
Wen-Ching Lin Chih-Chun Wen Yung-Hsiang Chen Pei-Wen Hsiao Jiunn-Wang Liao Ching-I Peng Ning-Sun Yang 《PloS one》2015,10(6)
For the development of “medical foods” and/or botanical drugs as defined USA FDA, clear and systemic characterizations of the taxonomy, index phytochemical components, and the functional or medicinal bioactivities of the reputed or candidate medicinal plant are needed. In this study, we used an integrative approach, including macroscopic and microscopic examination, marker gene analysis, and chemical fingerprinting, to authenticate and validate various species/varieties of Wedelia, a reputed medicinal plant that grows naturally and commonly used in Asian countries. The anti-inflammatory bioactivities of Wedelia extracts were then evaluated in a DSS-induced murine colitis model. Different species/varieties of Wedelia exhibited distinguishable morphology and histological structures. Analysis of the ribosomal DNA internal transcribed spacer (ITS) region revealed significant differences among these plants. Chemical profiling of test Wedelia species demonstrated candidate index compounds and distinguishable secondary metabolites, such as caffeic acid derivatives, which may serve as phytochemical markers or index for quality control and identification of specific Wedelia species. In assessing their effect on treating DSS induced-murine colitis, we observed that only the phytoextract from W. chinensis species exhibited significant anti-inflammatory bioactivity on DSS-induced murine colitis among the various Wedelia species commonly found in Taiwan. Our results provide a translational research approach that may serve as a useful reference platform for biotechnological applications of traditional phytomedicines. Our findings indicate that specific Wedelia species warrant further investigation for potential treatment of human inflammatory bowel disease. 相似文献
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J. -K. Huang K. C. Keudell Su-Jin. Seong W. E. Klopfenstein L. Wen M. O. Bagby R. A. Norton R. F. Vesonder 《Biotechnology letters》1996,18(2):193-198
Summary A new microbial isolate, Bacillus sp. U88, transformed 12-hydroxyoctadecanoic acid to 12,15-, 12,16- and 12,17-dihydroxyoctadecanoic acids when grown aerobically in 1 % yeast extract medium at 30°C and shaken at 250 rpm for 5 days. These three dihydroxyfatty acids were derivatized with Trimethylsilyl ether and identified by GC-MS analysis. The yield of 12,15-, 12,16- and 12,17-dihydroxyoctadecanoic acids after 5 day incubation were 2.8 %, 7.1 % and 1.1 %, respectively.Names are necessary to report factually on available data; however the USDA neither guarantees nor warrants the standard of the product, and the use of the name by USDA implies no approval of the product to the exclusion of other that may also be suitable. 相似文献
26.
Tropomyosin (Tpm) is a dimeric coiled-coil protein that binds to filamentous actin, and regulates actin-myosin interaction by moving between three positions corresponding to the blocked, closed, and open states. To elucidate how Tpm undergoes transitions between these functional states, we have built structural models and conducted extensive molecular dynamics simulations of the Tpm-actins/myosin complex in the closed and open states (total simulation time >1.4 μs). Based on the simulation trajectories, we have analyzed the dynamics and energetics of a truncated Tpm interacting with actins/myosin under the physiological conditions. Our simulations have shown distinct dynamics of four Tpm periods (P3-P6), featuring pronounced biased fluctuations of P4 and P5 toward the open position in the closed state, which is consistent with a conformational selection mechanism for Tpm-regulated myosin binding. Additionally, we have identified key residues of Tpm specifically binding to actins/myosin in the closed and open state. Some of them were validated as functionally important in comparison with past functional/clinical studies, and the rest will make promising targets for future mutational experiments. 相似文献
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Ling Wang Yu Wang Yiguang Tian Jinling Shang Xiaoou Sun Hongzhuan Chen Hao Wang Wen Tan 《Bioorganic & medicinal chemistry》2017,25(1):360-371
A series of novel chalcone-rivastigmine hybrids were designed, synthesized, and tested in vitro for their ability to inhibit human acetylcholinesterase and butyrylcholinesterase. Most of the target compounds showed hBChE selective activity in the micro- and submicromolar ranges. The most potent compound 3 exhibited comparable IC50 to the commercially available drug (rivastigmine). To better understand their structure activity relationships (SAR) and mechanisms of enzyme-inhibitor interactions, kinetic and molecular modeling studies including molecular docking and molecular dynamics (MD) simulations were carried out. Furthermore, compound 3 blocks the formation of reactive oxygen species (ROS) in SH-SY5Y cells and shows the required druggability and low cytotoxicity, suggesting this hybrid is a promising multifunctional drug candidate for Alzheimer’s disease (AD) treatment. 相似文献