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941.
Fahui Li Lihui Zhang Jinhong Feng Lei Zhang 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):2017
Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a novel therapeutic target for the development of cholesterol-lowering drugs. In the discovery of PCSK9/LDLR (low-density lipoprotein receptor) protein-protein interaction (PPI) impairing small molecules, a total of 47 phenylbenzo[d][1,3] dioxole-based compounds were designed and synthesised. The result revealed that the 4-chlorobenzyl substitution in the amino group is important for the PPI disrupting activity. In the hepatocyte-based functional tests, active compounds such as A12, B1, B3, B4 and B14, restored the LDLR levels on the surface of hepatic HepG2 cells and increased extracellular LDL uptake in the presence of PCSK9. It is notable that molecule B14 exhibited good performance in all the evaluations. Collectively, novel structures targeting PCSK9/LDLR PPI have been developed with hypolipidemic potential. Further structural modification of derived active compounds is promising in the discovery of lead compounds with improved activity for the treatment of hyperlipidaemia-related disorders. 相似文献
942.
Xiao Zhang Xixin He Qiuhe Chen Junfeng Lu Simona Rapposelli Rongbiao Pi 《Bioorganic & medicinal chemistry》2018,26(3):543-550
Alzheimer’s disease (AD), a complex chronic progressive central nervous system degenerative disease and a public health problem of the world, often characters cognitive dysfunction accompaning aggression and depression, and may lead to death. More attentions should be paid on it because there is no modified strategy against AD till now. AD is featured with the loss of cholinergic neurons, the amyloid-beta peptide (Aβ) plaques and the neurofibrillary tangles and several hypotheses were established to explain the pathogenesis of AD. Hydroxycinnamic acids, including caffeic acid (CA) and ferulic acid (FA) are widely distributed in natural plants and fruits. CA and FA exert various pharmacological activities, including anti-inflammatory, antioxidant, neuroprotection, anti-amyloid aggregation and so on. All these pharmacological activities are associated with the treatment of AD. Here we summarized the pharmacological activities of CA and FA, and their hybrids as multi-target-directed ligands (MTDLs) against AD. The future application of CA and FA was also discussed, hoping to provide beneficial information for the development of CA- and FA-based MTDLs against AD. 相似文献
943.
癫痫发作敏感大鼠前深梨状皮层T区GABA免疫反应活性变化 总被引:1,自引:0,他引:1
γ-氨基丁酸(γ-aminobutyric acid,GABA)是脑内最重要的抑制性神经递质,在阻断兴奋扩布及传导中起重要作用,其参与抗癫痫作用已被证实.有研究表明:前深梨状皮层T区是颞叶癫痫的始动部位.我们从前的工作已证明:惊厥剂量的红藻氨酸(Kainic acid,A)诱发SD大鼠出现急性癫痫发作后的5~7 d,动物出现癫痫发作敏感性长期增强,而蝎毒(scorpion venom,V)可通过增强海马结构内GABA的表达,对抗其癫痫发作敏感性的形成.本研究采用免疫组化技术,并探讨其与癫痫发作敏感长期增强的可能关系,检测癫痫发作敏感大鼠和经SV处理后癫痫发作敏感性明显降低的大鼠前深梨状皮层T区的GABA免疫反应活性变化. 相似文献
944.
Zhang Hao Wang Jin-Yan Chen Yi-Juan Siemann Evan Ji Xiang-Yun Jiang Jie-Xian Wan Nian-Feng 《BioControl》2022,67(1):1-13
BioControl - The effects of plant volatiles on parasitoids are important with regards to the tri-trophic interactions among host plants, insect herbivores, and their natural enemies. However, the... 相似文献
945.
Zhang Qi Li Yanan Yin Chunping Yu Jiaxu Zhao Juan Yan Lirong Wang Qiujun 《Neurochemical research》2022,47(6):1751-1764
Neurochemical Research - Postoperative cognitive dysfunction (POCD) remains one of the most common complications following anesthesia and surgery (AS) in the elderly population. Calcium-mediated... 相似文献
946.
BioMetals - To investigate the metabolic changes in type C hepatic encephalopathy (CHE) rats after reducing manganese (Mn) intake. A total of 80 Sprague–Dawley rats were divided into control... 相似文献
947.
为了探讨沙漠中固沙灌木种群共存和演替机制, 本文基于古尔班通古特沙漠东南缘固定沙丘上白梭梭(Haloxylon persicum)和梭梭(H. ammodendron)种群的地理位置和生长发育阶段信息(幼株、营养株、生殖株和死株), 采用点格局分析方法(g(r)函数)及Monte-Carlo随机模拟检验和零模型选取的方法, 分析了固沙灌木白梭梭和梭梭种群不同生长发育阶段在0-20 m尺度内的空间分布格局及种间关联性。结果表明: (1)两个种群在研究尺度范围内呈聚集分布, 随着尺度的增大, 其聚集强度逐渐减弱; (2)两个种群整体上呈负关联关系, 尺度越大负关联关系越显著; (3)白梭梭种群生长发育阶段相差越大, 个体间正关联关系越显著; 梭梭种群生长发育阶段越接近, 个体间正关联关系越显著; (4)两个种群中龄级较大的个体(如营养株、生殖株和死株)会对对方种群中龄级较小的幼株产生一定的抑制作用; 同时, 随着两个种群中个体的成长, 双方受到的抑制作用逐渐减弱, 主要表现为正关联和无关联。总体而言, 古尔班通古特沙漠固定沙丘白梭梭和梭梭种群的分布格局整体上为聚集分布, 随龄级增加聚集性减弱, 受生境异质性和扩散限制的影响明显。种间关系多为负相关, 种内不同生长发育阶段之间均为正关联关系。 相似文献
948.
949.
Chiyu Li Jia Chen Xiaoyan Li Xin Zhang Ying Liu Sirui Zhu Long Wang Heping Zheng Sheng Luan Jiada Li Feng Yu 《植物学报(英文版)》2022,64(10):1901-1915
Plant shoot phototropism is triggered by the formation of a light-driven auxin gradient leading to bending growth. The blue light receptor phototropin 1(phot1) senses light direction, but how this leads to auxin gradient formation and growth regulation remains poorly understood. Previous studies have suggested phot1’s role for regulated apoplastic acidification, but its relation to phototropin and hypocotyl phototropism is unclear. Herein, we show that blue light can cause phot1 to interact with... 相似文献
950.
Chromatin modifications have been comprehensively illustrated to play important roles in gene regulation and cell diversity in recent years. Given the rapid accumulation of genome-wide chromatin modification maps across multiple cell types, there is an urgent need for computational methods to analyze multiple maps to reveal combinatorial modification patterns and define functional DNA elements, especially those are specific to cell types or tissues. In this current study, we developed a computational method using differential chromatin modification analysis (dCMA) to identify cell-type-specific genomic regions with distinctive chromatin modifications. We then apply this method to a public data set with modification profiles of nine marks for nine cell types to evaluate its effectiveness. We found cell-type-specific elements unique to each cell type investigated. These unique features show significant cell-type-specific biological relevance and tend to be located within functional regulatory elements. These results demonstrate the power of a differential comparative epigenomic strategy in deciphering the human genome and characterizing cell specificity. 相似文献