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Tripartite motif protein 25 (TRIM25) expression was altered in various human cancers. Herein, we found that the expression of TRIM25 was elevated in hepatocellular carcinoma (HCC) tissues and cell lines. Knockdown of TRIM25 increased the sensitivity of HCC HepG2 cells to epirubicin (EPI), as indicated by reduced cell viability, enhanced cell apoptosis, and downregulated P‐glycoprotein (P‐gp) and multiple drug‐resistance protein 1 (MRP1). Moreover, TRIM25 knockdown strengthened the effects of EPI on phosphatase and tensin homolog (PTEN) and phosphorylated (p)‐AKT. However, overexpression of TRIM25 exerted an opposite effect, weakening the sensitivity of Huh7 to EPI, and obviously increasing PTEN and reducing p‐AKT. Most important, all the changes induced by TRIM25 overexpression in Huh7 were reversed with additional treatment of LY294002 (an AKT pathway inhibitor). Notably, coimmunoprecipitation experiments confirmed the interaction between TRIM25 and PTEN. Knockdown of TRIM25 resulted in reduced ubiquitination of PTEN protein. Collectively, our data suggested that TRIM25 enhanced EPI resistance via modulating PTEN/AKT pathway, and targeting TRIM25 may enhance the sensitivity of HCC cells toward chemotherapy drugs. 相似文献
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Gao Kai Liu Meiyou Li Yuan Wang Lei Zhao Chao Zhao Xian Zhao Jinyi Ding Yi Tang Haifeng Jia Yanyan Wang Jingwen Wen Aidong 《Journal of molecular histology》2021,52(3):449-459
Journal of Molecular Histology - Currently, the excessive activation of N-methyl-D-aspartate receptors (NMDARs) is considered to be a crucial mechanism of brain injury. Lycium barbarum A (LyA) is a... 相似文献
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Weiwei Li Jianjie Chu Tingting Fan Wei Zhang Minna Yao Zeqiong Ning Mingming Wang Jin Sun Xian Zhao Aidong Wen 《Bioorganic & medicinal chemistry letters》2019,29(14):1831-1835
In this investigation, a series of 1-phenyl-3-(5-(pyrimidin-4-ylthio)-1,3,4- thiadiazol-2-yl)urea receptor tyrosine kinase inhibitors were synthesized by a simple and efficient structure-based design. Structure-activity relationship (SAR) analysis of these compounds based on cellular assays led to the discovery of a number of compounds that showed potent activity against human chronic myeloid leukemia (CML) cell line K562, but very weak or no cellular toxicity through monitoring the growth kinetics of K562 cell during a period of 72 h using the real-time live-cell imaging. Among these compounds, 1-(5-((6-((3-morpholinopropyl) amino)pyrimidin-4-yl)thio)-1,3,4-thiadiazol-2-yl)-3-(4-(trifluoromethyl)phenyl)urea (7) exhibited the least cellular toxicity and better biological activity in cellular assays (K562, IC50: 0.038 μM). Compound 7 also displayed very good induced-apoptosis effect for human CML cell line K562 and exerted its effect via a significantly reduced protein phosphorylation of PI3K/Akt signal pathway by Human phospho-kinase array analysis. In vitro results indicate that 1-phenyl-3-(5-(pyrimidin-4-ylthio)-1,3,4- thiadiazol-2-yl)urea derivatives are lead molecules for further development as treatment of chronic myeloid leukemia and cancer. 相似文献
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【目的】为持续有效防控白背飞虱,研究云南东部白背飞虱种群对常用5种杀虫剂的敏感性及药剂的田间防治效果。【方法】采用室内稻茎浸渍法测定白背飞虱种群对5种杀虫剂的敏感性,同期通过田间小区试验评价5种杀虫剂对白背飞虱种群的防治效果。【结果】与敏感种群比较,噻虫嗪、噻嗪酮、吡虫啉、吡蚜酮和毒死蜱对滇东白背飞虱种群的LC_(50)分别为0.208、0.459、0.608、3.108、1.256 mg·L~(-1),抗性倍数分别为2.2、10.4、5.6、6.5、5.3倍;白背飞虱对噻虫嗪无抗性,对吡虫啉、吡蚜酮和毒死蜱为低水平抗性,对噻嗪酮为中等水平抗性;5种杀虫剂药后1、5和10 d对白背飞虱种群的田间防控效果均有显著差异。除了吡蚜酮外,其他药剂的防效均在80%以上,其中以吡虫啉和噻嗪酮的持续期较长,药后10 d仍在90%以上;噻虫嗪和吡虫啉药后1和5 d的防效达90%以上;吡蚜酮药效在供试药剂中防效最低,在64.88%~77.82%之间。【结论】滇东师宗白背飞虱种群对噻嗪酮为中等水平抗性,对吡虫啉、吡蚜酮和毒死蜱均为低水平抗性,对噻虫嗪无抗性,田间防控效果以吡虫啉和噻嗪酮为最好。建议滇东稻区可以使用吡虫啉和噻嗪酮药剂防控白背飞虱,注意控制吡蚜酮的使用次数与用量。 相似文献
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Structures of SARS-CoV-2 spike protein alert noteworthy sites for the potential approaching variants
Xiaorui Xing Lei Wang Zhen Cui Wangjun Fu Tao Zheng Lili Qin Pingju Ge Aidong Qian Nan Wang Shuai Yuan 《中国病毒学》2022,37(6):938-941
Highlights
1 Deletion of residues 156–157 warps the neighboring beta-sheet and leads NTD and RBD to shift.
2 T859N stabilizes the packing of the 630 loop motif to make RBD standing transition more difficult.
3 The overall structures of the closed state S complex from different variants resemble each other.
4 Mutations in FPPR may affect the overall structure of the trimeric spike protein. 相似文献
1 Deletion of residues 156–157 warps the neighboring beta-sheet and leads NTD and RBD to shift.
2 T859N stabilizes the packing of the 630 loop motif to make RBD standing transition more difficult.
3 The overall structures of the closed state S complex from different variants resemble each other.
4 Mutations in FPPR may affect the overall structure of the trimeric spike protein. 相似文献
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Myosin Va binding to neurofilaments is essential for correct myosin Va distribution and transport and neurofilament density
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Rao MV Engle LJ Mohan PS Yuan A Qiu D Cataldo A Hassinger L Jacobsen S Lee VM Andreadis A Julien JP Bridgman PC Nixon RA 《The Journal of cell biology》2002,159(2):279-290
The identification of molecular motors that modulate the neuronal cytoskeleton has been elusive. Here, we show that a molecular motor protein, myosin Va, is present in high proportions in the cytoskeleton of mouse CNS and peripheral nerves. Immunoelectron microscopy, coimmunoprecipitation, and blot overlay analyses demonstrate that myosin Va in axons associates with neurofilaments, and that the NF-L subunit is its major ligand. A physiological association is indicated by observations that the level of myosin Va is reduced in axons of NF-L-null mice lacking neurofilaments and increased in mice overexpressing NF-L, but unchanged in NF-H-null mice. In vivo pulse-labeled myosin Va advances along axons at slow transport rates overlapping with those of neurofilament proteins and actin, both of which coimmunoprecipitate with myosin Va. Eliminating neurofilaments from mice selectively accelerates myosin Va translocation and redistributes myosin Va to the actin-rich subaxolemma and membranous organelles. Finally, peripheral axons of dilute-lethal mice, lacking functional myosin Va, display selectively increased neurofilament number and levels of neurofilament proteins without altering axon caliber. These results identify myosin Va as a neurofilament-associated protein, and show that this association is essential to establish the normal distribution, axonal transport, and content of myosin Va, and the proper numbers of neurofilaments in axons. 相似文献
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Rao MV Garcia ML Miyazaki Y Gotow T Yuan A Mattina S Ward CM Calcutt NA Uchiyama Y Nixon RA Cleveland DW 《The Journal of cell biology》2002,158(4):681-693
The COOH-terminal tail of mammalian neurofilament heavy subunit (NF-H), the largest neurofilament subunit, contains 44-51 lysine-serine-proline repeats that are nearly stoichiometrically phosphorylated after assembly into neurofilaments in axons. Phosphorylation of these repeats has been implicated in promotion of radial growth of axons, control of nearest neighbor distances between neurofilaments or from neurofilaments to other structural components in axons, and as a determinant of slow axonal transport. These roles have now been tested through analysis of mice in which the NF-H gene was replaced by one deleted in the NF-H tail. Loss of the NF-H tail and all of its phosphorylation sites does not affect the number of neurofilaments, alter the ratios of the three neurofilament subunits, or affect the number of microtubules in axons. Additionally, it does not reduce interfilament spacing of most neurofilaments, the speed of action potential propagation, or mature cross-sectional areas of large motor or sensory axons, although its absence slows the speed of acquisition of normal diameters. Most surprisingly, at least in optic nerve axons, loss of the NF-H tail does not affect the rate of transport of neurofilament subunits. 相似文献
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SUMMARY
1. We previously showed that actin is transported in an unassembled form with its associated proteins actin depolymerizing factor, cofilin, and profilin. Here we examine the specific activities of radioactively labeled tubulin and neurofilament proteins in subcellular fractions of the chicken sciatic nerve following injection of L-[35S]methionine into the lumbar spinal cord.2. At intervals of 12 and 20 days after injection, nerves were cut into 1-cm segments and separated into Triton X-100-soluble and particulate fractions. Analysis of the fractions by high-resolution two-dimensional gel electrophoresis, immunoblotting, fluorography, and computer densitometry showed that tubulin was transported as a unimodal wave at a slower average rate (2–2.5 mm/day) than actin (4–5 mm/day). Moreover, the specific activity of soluble tubulin was five times that of its particulate form, indicating that tubulin is transported in a dimeric or small oligomeric form and is assembled into stationary microtubules.3. Neurofilament triplet proteins were detected only in the particulate fractions and transported at a slower average rate (1 mm/day) than either actin or tubulin.4. Our results indicate that the tubulin was transported in an unpolymerized form and that the neurofilament proteins were transported in an insoluble, presumably polymerized form. 相似文献
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