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81.
Won‐Jun Jang Sung Keun Jung Tam Thuy Lu Vo Chul‐Ho Jeong 《Journal of cellular and molecular medicine》2019,23(2):1106-1115
The concept of drug repositioning has recently received considerable attention in the field of oncology. In the present study, we propose that paroxetine can be used as a potent anticancer drug. Paroxetine, one of the selective serotonin reuptake inhibitors (SSRIs), has been widely prescribed for the treatment of depression and anxiety disorders. Recently, SSRIs have been reported to have anticancer activity in various types of cancer cells; however, the underlying mechanisms of their action are not yet known. In this study, we investigated the potential anticancer effect of paroxetine in human colorectal cancer cells, HCT116 and HT‐29. Treatment with paroxetine reduced cell viability, which was associated with marked increase in apoptosis, in both the cell lines. Also, paroxetine effectively inhibited colony formation and 3D spheroid formation. We speculated that the mode of action of paroxetine might be through the inhibition of two major receptor tyrosine kinases – MET and ERBB3 – leading to the suppression of AKT, ERK and p38 activation and induction of JNK and caspase‐3 pathways. Moreover, in vivo experiments revealed that treatment of athymic nude mice bearing HT‐29 cells with paroxetine remarkably suppressed tumour growth. In conclusion, paroxetine is a potential therapeutic option for patients with colorectal cancer. 相似文献
82.
Dae‐Won Ki Maurice Ducret Awouafack Chin Piow Wong Hien Minh Nguyen Quang Minh Thai Lien Huong TonNu Hiroyuki Morita 《化学与生物多样性》2019,16(3)
A new tribromoiododiphenyl ether ( 1 ) and eight known brominated diphenyl ethers ( 2 – 9 ) were isolated from the MeOH extract of the sponge Arenosclera sp. collected in Vietnam, using repeated open column chromatography and preparative thin layer chromatography. The chemical structure of the new compound 1 was determined by analyses of spectroscopic (1D‐ and 2D‐NMR, and MS) data and by comparison of our data with those reported in the literature. Compounds 1 , 3 , and 8 exhibited strong antibacterial activities against the Gram‐positive bacteria Bacillus subtilis and Staphylococcus aureus and the Gram‐negative bacterium Klebsiella pneumoniae with MIC values ranging from 0.8 to 6.3 μm , while compounds 5 and 7 only displayed activities against Gram‐positive bacteria with MIC values from 0.5 to 3.1 μm . Compound 2 showed activities against the four tested bacteria with MIC values ranging from 0.5 to 6.3 μm . 相似文献
83.
Hunhee Lim Donghun Kim Min‐Jae Choi Edward H. Sargent Yeon Sik Jung Jin Young Kim 《Liver Transplantation》2019,9(48)
Quantum‐dot (QD) photovoltaics (PVs) offer promise as energy‐conversion devices; however, their open‐circuit‐voltage (VOC) deficit is excessively large. Previous work has identified factors related to the QD active layer that contribute to VOC loss, including sub‐bandgap trap states and polydispersity in QD films. This work focuses instead on layer interfaces, and reveals a critical source of VOC loss: electron leakage at the QD/hole‐transport layer (HTL) interface. Although large‐bandgap organic materials in HTL are potentially suited to minimizing leakage current, dipoles that form at an organic/metal interface impede control over optimal band alignments. To overcome the challenge, a bilayer HTL configuration, which consists of semiconducting alpha‐sexithiophene (α‐6T) and metallic poly(3,4‐ethylenedioxythiphene) polystyrene sulfonate (PEDOT:PSS), is introduced. The introduction of the PEDOT:PSS layer between α‐6T and Au electrode suppresses the formation of undesired interfacial dipoles and a Schottky barrier for holes, and the bilayer HTL provides a high electron barrier of 1.35 eV. Using bilayer HTLs enhances the VOC by 74 mV without compromising the JSC compared to conventional MoO3 control devices, leading to a best power conversion efficiency of 9.2% (>40% improvement relative to relevant controls). Wider applicability of the bilayer strategy is demonstrated by a similar structure based on shallow lowest‐unoccupied‐molecular‐orbital (LUMO) levels. 相似文献
84.
85.
Song Mei Ling Kim Keun Tae Motamedi Gholam K. Cho Yong Won 《Sleep and biological rhythms》2019,17(4):447-454
Sleep and Biological Rhythms - Narcoleptics tend to have a low quality of life (QoL). Few studies have compared QoL in narcolepsy against other sleep disorders. The purpose of this study was to... 相似文献
86.
87.
Yong‐Han Kim In‐Won Lee Yu‐Jin Jo Nam‐Hyung Kim Suk Namgoong 《Molecular reproduction and development》2019,86(8):972-983
Mammalian oocytes lack centrioles but can generate bipolar spindles using several different mechanisms. For example, mouse oocytes have acentriolar microtubule organization centers (MTOCs) that contain many components of the centrosome, and which initiate microtubule polymerization. On the contrary, human oocytes lack MTOCs and the Ran‐mediated mechanisms may be responsible for spindle assembly. Complete knowledge of the different mechanisms of spindle assembly is lacking in various mammalian oocytes. In this study, we demonstrate that both MTOC‐ and Ran‐mediated microtubule nucleation are required for functional meiotic metaphase I spindle generation in porcine oocytes. Acentriolar MTOC components, including Cep192 and pericentrin, were absent in the germinal vesicle and germinal vesicle breakdown stages. However, they start to colocalize to the spindle microtubules, but are absent in the meiotic spindle poles. Knockdown of Cep192 or inhibition of Polo‐like kinase 1 activity impaired the recruitment of Cep192 and pericentrin to the spindles, impaired microtubule assembly, and decreased the polar body extrusion rate. When the RanGTP gradient was perturbed by the expression of dominant negative or constitutively active Ran mutants, severe defects in microtubule nucleation and cytokinesis were observed, and the localization of MTOC materials in the spindles was abolished. These results demonstrate that the stepwise involvement of MTOC‐ and Ran‐mediated microtubule assembly is crucial for the formation of meiotic spindles in porcine oocytes, indicating the diversity of spindle formation mechanisms among mammalian oocytes. 相似文献
88.
Mannheimia succiniciproducens MBEL55E isolated from bovine rumen is a capnophilic gram-negative bacterium that efficiently produces succinic acid, an industrially important four carbon dicarboxylic acid. In order to design a metabolically engineered strain which is capable of producing succinic acid with high yield and productivity, it is essential to optimize the whole metabolism at the systems level. Consequently, in silico modeling and simulation of the genome-scale metabolic network was employed for genome-scale analysis and efficient design of metabolic engineering experiments. The genome-scale metabolic network of M. succiniciproducens consisting of 686 reactions and 519 metabolites was constructed based on reannotation and validation experiments. With the reconstructed model, the network structure and key metabolic characteristics allowing highly efficient production of succinic acid were deciphered; these include strong PEP carboxylation, branched TCA cycle, relative weak pyruvate formation, the lack of glyoxylate shunt, and non-PTS for glucose uptake. Constraints-based flux analyses were then carried out under various environmental and genetic conditions to validate the genome-scale metabolic model and to decipher the altered metabolic characteristics. Predictions based on constraints-based flux analysis were mostly in excellent agreement with the experimental data. In silico knockout studies allowed prediction of new metabolic engineering strategies for the enhanced production of succinic acid. This genome-scale in silico model can serve as a platform for the systematic prediction of physiological responses of M. succiniciproducens to various environmental and genetic perturbations and consequently for designing rational strategies for strain improvement. 相似文献
89.
To investigate the effect of Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) on human cancer cells, we sought to identify and analyze potential target genes that were differentially expressed in the presence and absence of LMP1. Our cDNA microarray analysis revealed that expression of early growth response gene-1 (Egr-1) was increased by LMP1 expression in MCF7 and Jurkat cells. An NFkappaB inhibitor (SN50) antagonized LMP1-induced enhancement of Egr-1 expression, indicating that LMP1 induced Egr-1 via NFkappaB. Furthermore, three lines of evidence indicated that Egr-1 was required for LMP1-induced cancer cell survival. First, Egr-1 expression enhanced the survival of doxorubicin-treated MCF7 cells. Second, inhibition of Egr-1 expression by siRNA (siEgr-1) effectively suppressed LMP-1-induced survival of MCF7 cells. Third, Egr-1 knockdown decreased LMP1-induced expression of Bfl-1. Similar relationships among EBV infection, Egr-1 and drug resistance were also observed in tissues of peripheral T-cell lymphoma-unspecified (PTCL-u) patients. 相似文献
90.
Recently, negative effects of phosphatase in tumorigenesis and metastasis have been suggested in various tumor types. In this study, we showed that RhoA activation modulated phosphatase during senescence-like arrest in human prostate cancer cells. Under senescence-inducing condition, decreased Erk phosphorylation was detected in caRhoA-transfected cells and inactivation of Erk, but not p38, prevented doxorubicin-induced cell senescence. Cells were induced to senescence by inhibition of phosphatase activity (VHR, MKP3, or PP2A) without additional cellular stress. Of interest, caRhoA prevented doxorubicin-induced decrease of phosphatase. Thus, we postulate that RhoA signaling may protect cells against cellular senescence by maintaining phosphatase activity and Erk dephosphorylation. 相似文献