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排序方式: 共有1107条查询结果,搜索用时 46 毫秒
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Cong Wang Liping Jiang Saiqi Wang Hongge Shi Junwei Wang Ran Wang Yongmei Li Yinhui Dou Ying Liu Guiqin Hou Yu Ke Hongmin Liu 《PloS one》2015,10(6)
Jesridonin, a small molecule obtained through the structural modification of Oridonin, has extensive antitumor activity. In this study, we evaluated both its in vitro activity in the cancer cell line EC109 and its in vivo effect on tumor xenografts in nude mice. Apoptosis induced by Jesridonin was determined using an MTT assay, Annexin-V FITC assay and Hoechest 33258 staining. Apoptosis via mitochondrial and death receptor pathways were confirmed by detecting the regulation of MDM2, p53, and Bcl-2 family members and by activation of caspase-3/-8/-9. In addition, vena caudalis injection of Jesridonin showed significant inhibition of tumor growth in the xenograft model, and Jesridonin-induced cell apoptosis in tumor tissues was determined using TUNEL. Biochemical serum analysis of alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), total protein (TP) and albumin (ALB) indicated no obvious effects on liver function. Histopathological examination of the liver, kidney, lung, heart and spleen revealed no signs of JD-induced toxicity. Taken together, these results demonstrated that Jesridonin exhibits antitumor activity in human esophageal carcinomas EC109 cells both in vitro and in vivo and demonstrated no adverse effects on major organs in nude mice. These studies provide support for new drug development. 相似文献
3.
Daorong Feng Dou Yeon Youn Xiaoping Zhao Yanguang Gao William J. Quinn rd Alus M. Xiaoli Yan Sun Morris J. Birnbaum Jeffrey E. Pessin Fajun Yang 《PloS one》2015,10(6)
In non-alcoholic fatty liver disease (NAFLD) and insulin resistance, hepatic de novo lipogenesis is often elevated, but the underlying mechanisms remain poorly understood. Recently, we show that CDK8 functions to suppress de novo lipogenesis. Here, we identify the mammalian target of rapamycin complex 1 (mTORC1) as a critical regulator of CDK8 and its activating partner CycC. Using pharmacologic and genetic approaches, we show that increased mTORC1 activation causes the reduction of the CDK8-CycC complex in vitro and in mouse liver in vivo. In addition, mTORC1 is more active in three mouse models of NAFLD, correlated with the lower abundance of the CDK8-CycC complex. Consistent with the inhibitory role of CDK8 on de novo lipogenesis, nuclear SREBP-1c proteins and lipogenic enzymes are accumulated in NAFLD models. Thus, our results suggest that mTORC1 activation in NAFLD and insulin resistance results in down-regulation of the CDK8-CycC complex and elevation of lipogenic protein expression. 相似文献
4.
Multimeric BLM is dissociated upon ATP hydrolysis and functions as monomers in resolving DNA structures 总被引:1,自引:0,他引:1
Ya-Nan Xu Nicolas Bazeille Xiu-Yan Ding Xi-Ming Lu Peng-Ye Wang Elisabeth Bugnard Virginie Grondin Shuo-Xing Dou Xu Guang Xi 《Nucleic acids research》2012,40(19):9802-9814
Bloom (BLM) syndrome is an autosomal recessive disorder characterized by an increased risk for many types of cancers. Previous studies have shown that BLM protein forms a hexameric ring structure, but its oligomeric form in DNA unwinding is still not well clarified. In this work, we have used dynamic light scattering and various stopped-flow assays to study the active form and kinetic mechanism of BLM in DNA unwinding. It was found that BLM multimers were dissociated upon ATP hydrolysis. Steady-state and single-turnover kinetic studies revealed that BLM helicase always unwound duplex DNA in the monomeric form under conditions of varying enzyme and ATP concentrations as well as 3′-ssDNA tail lengths, with no sign of oligomerization being discerned. Measurements of ATPase activity further indicated that BLM helicase might still function as monomers in resolving highly structured DNAs such as Holliday junctions and D-loops. These results shed new light on the underlying mechanism of BLM-mediated DNA unwinding and on the molecular and functional basis for the phenotype of heterozygous carriers of BLM syndrome. 相似文献
5.
Haojie Wang Fei He Bing Liang Yuanhu Jing Pei Zhang Weichao Liu Bowen Zhu Dongmei Dou 《Journal of cellular and molecular medicine》2021,25(19):9141-9153
Atherosclerosis (AS) is the main aetiology of coronary heart disease, cerebral infarction and peripheral vascular disease in humans. Long-noncoding RNA (LincRNA)-p21 has been reported to participate in the development of AS. Therefore, this study was designed to investigate the mechanism of LincRNA-p21 on suppressing the development of AS. We fed ApoE−/− mice with a high-fat diet to induce an AS mouse model where the lesion area of AS and the extent of lipid deposition were measured. The binding of LincRNA-p21 and miR-221 or miR-221 and SIRT1 was measured using a dual luciferase reporter gene assay and RIP. Following loss- and gain- function assays, CCK8, EdU, Transwell assay and scratch test were performed to determine the biological processes of human aortic endothelial cells (HAECs). miR-221 was highly expressed while SIRT1 was poorly expressed in AS. LincRNA-p21 acted as a sponge for miR-221. miR-221 targeted and negatively regulated the expression of SIRT1. LincRNA-p21 promoted the deacetylation of Pcsk9 by SIRT1 by competitively binding to miR-221, whereby promoting HAEC proliferation, migration and tube formation. In conclusion, LincRNA-p21 acted as a molecular sponge for miR-221 to promote deacetylation of the promoter region of Pcsk9 by SIRT1, therefore preventing the development of AS. 相似文献
6.
Junfeng Dou Wei Qin Jing Yuan Aizhong Ding En Xie Yingying Wang 《Bioremediation Journal》2014,18(3):248-257
A pure strain of Microbacterium lacticum DJ-1 capable of anaer-obic biodegradation of ethylbenzene was isolated from soil contaminated with gasoline. Growth of the strain and biodegradation of ethylbenzene in batch cultures led to stoichiometric reduction of nitrate. M. lacticum DJ-1 could degrade 100 mg L?1 of ethylbenzene completely, with a maximum degradation rate of 15.02 ± 1.14 mg L?1 day?1. Increasing the initial concentration of ethy-lbenzene resulted in decreased degradative ability. The cell-specific growth rates on ethylbenzene conformed to the Haldane–Andrew model in the substrate level range of 10–150 mg L?1. Kinetic parameters were determined by nonlinear regression on specific growth rates and various initial substrate concentrat-ions, and the values of the maximum specific growth rate, half saturation constant, and inhibition constant were 0.71 day?1, 34.3 mg L?1, and 183.5 mg L?1, respectively. This is the first report of ethylbenzene biodegradation by a bacterium of Microbacterium lacticum under nitrate-reducing conditions. 相似文献
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8.
The dendritic structure is a disastrous problem of lithium metal batteries as well as other metal rechargeable batteries. The dendritic structures are usually caused by diffusion limitation. Here, a novel strategy is reported to inhibit lithium dendrites based on the understanding of their formation mechanism. An alternating current field perpendicular to the anode is set up, which promotes Li+ movement along the anode surface and prevents ions' deposition on the tips from forming dendrites. Furthermore, an external direct current field parallel to the current is employed, which accelerates the transport of Li+ in electrolytes to mitigate the concentration gradient nearby the anode and thus inhibits the formation of dendritic structures. A simultaneous employment of these two fields gains five times increase of the lifespan of batteries at the high charging current density of 2 mA cm?2, confirming the effectiveness of this strategy in protecting the metal anode and inhibiting lithium dendrites. This strategy may have a wide feasibility since it does not change the materials and structures of batteries. 相似文献
9.
Yulong He Huixia Dou Dingding Gao Ting Wang Mingming Zhang Heyao Wang Yingxia Li 《Bioorganic & medicinal chemistry》2019,27(19):115015
Fatty acid binding protein 4 (FABP4) and fatty acid binding protein 5 (FABP5) are mainly expressed in adipocytes and/or macrophages and play essential roles in energy metabolism and inflammation. When FABP4 function is diminished, FABP5 expression is highly increased possibly as a functional compensation. Dual FABP4/5 inhibitors are expected to provide beneficial synergistic effect on treating diabetes, atherosclerosis, and inflammation-related diseases. Starting from our previously reported selective FABP4 inhibitor 8, structural biology information was used to modulate the selectivity profile and to design potent dual FABP4/5 inhibitors with good selectivity against FABP3. Two compounds A16 and B8 were identified to show inhibitory activities against both FABP4/5 and good selectivity over FABP3, which could also reduce the level of forskolin-stimulated lipolysis in mature 3T3-L1 adipocytes. Compared with compound 8, these two compounds exhibited better anti-inflammatory effects in lipopolysaccharide-stimulated RAW264.7 murine macrophages, with decreased levels of pro-inflammatory cytokines TNFα and MCP-1 and apparently inhibited IKK/NF-κB pathway. 相似文献
10.
全球氮沉降通过影响树木叶片的生理过程影响森林生态系统的结构与组成,但目前关于氮沉降对森林生态系统中不同植物叶片非结构性碳水化合物(NSC)含量的影响还不十分清楚.本研究选取黄土丘陵区人工油松林中油松、辽东栎、忍冬、绣线菊、黄刺玫、茜草、披针苔草7种主要高等植物,比较了3年氮添加(0、3、6、9 g N·m-2·a-1,分别用N0、N3、N6、N9表示)对7种植物叶片中NSC的影响.结果表明: 不同植物叶片可溶性糖、淀粉含量变异很大,二者变异最高的均为黄刺玫,最低的分别为绣线菊和披针苔草;不同植物可溶性糖、淀粉对氮添加的响应存在明显差异.N6处理下茜草的可溶性糖和淀粉的变异高于其他物种,N3和N9处理下绣线菊的变异高于其他物种,可溶性糖和淀粉含量变异最小的物种在不同氮添加水平下不同.随着氮添加水平的增加,油松和披针苔草的可溶性糖含量持续升高,绣线菊持续降低,辽东栎、忍冬和黄刺玫的可溶性糖含量先降低后增加,在N6处理达到最小,而茜草的可溶性糖含量呈现较复杂的变化趋势.氮添加对植物叶片中淀粉含量的影响表现为油松、忍冬和披针苔草的淀粉含量持续增加,绣线菊先降低后增加,在N3处理达到最小,而黄刺玫和茜草则呈现较复杂的变化趋势,辽东栎淀粉含量变化趋势平缓.在氮添加后,土壤pH、有机碳、全氮、全磷与植物叶片NSC含量无相关关系,仅N0和N3水平下上述土壤理化指标会显著影响可溶性糖/淀粉.表明林地不同植物叶片中NSC含量对氮添加的响应明显不同,研究全球氮沉降或氮添加对林地生态系统的影响需要考虑不同植物,尤其不同生活型植物的不同响应. 相似文献