71 research outputs found

    Phosphatidylethanolamine binding protein 1 enhances sensitivity of gastric cancer cell to 5-fluorouracil via inhibition of cell proliferation, migration and invasion

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    Purpose: To determine the association between phosphatidylethanolamine binding protein 1, which is an Raf kinase inhibitor protein (RKIP), and 5-fluorouracil (5-FU) via analysis of the association between RKIP and clinical responses in individuals treated using fluorouracil-based chemotherapy.Methods: Human gastric cancer cell lines MGC-803 and SGC-7901 were used in this study. Cell viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis and migration were determined with flow cytometry and Transwell chamber assays, respectively. The mRNA and protein expressions of apoptosis-related factors were assayed using realtime polymerase chain reaction (RT-PCR) and Western blotting, respectively, while the expression of RKIP was determined by immunohistochemical staining.Results: Chemotherapeutic drug (5-FU) treatment induced low RKIP expression levels in tumorigenic GC cells, thereby sensitizing the cells to apoptosis (8.57 vs 1.25 %, p < 0.01). The highest RKIP level correlated well with initiation of apoptosis (4.20 vs 1.25 %, p < 0.01). Following in vitro downregulation of RKIP, there was increase in the viability and proliferation of RKIP-inhibited cells over time, and these changes were linked to alterations in cell cycle phases and increased optical density in MTT proliferation assay (1.55 vs 1.18, p < 0.01). In vitro Transwell assay measurement revealed an association between RKIP downregulation and enhancement of cell migration potential (652 vs 436, p < 0.01). Ectopic RKIP expression restored the apoptotic sensitivity of resistant cells (14.30 vs 1.36 %, p <0.01). This sensitization was annulled by upregulation of survival routes. Reduction of RKIP by expression of antisense and siRNA conferred resistance on cancer cells sensitive to 5-FU-mediated apoptosis (6.88 vs 2.13 %, p < 0.01).Conclusion: Thus, RKIP is a promising therapeutic strategy for improving the efficacy of clinically relevant chemotherapeutic drugs for GC. Keywords: Gastric cancer, Raf kinase inhibitor protein, Cell proliferation, Invasion, Apoptosis, Chemotherapy,  Phosphatidylethanolamine binding protein

    Secondary relaxation dynamics in rigid glass-forming molecular liquids with related structures

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    The dielectric relaxation in three glass-forming molecular liquids, 1-methylindole (1MID), 5H-5-Methyl-6,7-dihydrocyclopentapyrazine (MDCP), and Quinaldine (QN) is studied focusing on the secondary relaxation and its relation to the structural α-relaxation. All three glass-formers are rigid and more or less planar molecules with related chemical structures but have dipoles of different strengths at different locations. A strong and fast secondary relaxation is detected in the dielectric spectra of 1MID, while no resolved β-relaxation is observed in MDCP and QN. If the observed secondary relaxation in 1MID is identified with the Johari-Goldstein (JG) β-relaxation, then apparently the relation between the α- and β-relaxation frequencies of 1MID is not in accord with the Coupling Model (CM). The possibility of the violation of the prediction in 1MID as due to either the formation of hydrogen-bond induced clusters or the involvement of intramolecular degree of freedom is ruled out. The violation is explained by the secondary relaxation originating from the in-plane rotation of the dipole located on the plane of the rigid molecule, contributing to dielectric loss at higher frequencies and more intense than the JG β-relaxation generated by the out-of-plane rotation. MDCP has smaller dipole moment located in the plane of the molecule; however, presence of the change of curvature of dielectric loss, ε″(f), at some frequency on the high-frequency flank of the α-relaxation reveals the JG β-relaxation in MDCP and which is in accord with the CM prediction. QN has as large an in-plane dipole moment as 1MID, and the absence of the resolved secondary relaxation is explained by the smaller coupling parameter than the latter in the framework of the C

    Electronic structure of pristine and Ni-substituted LaFeO3_3 from near edge x-ray absorption fine structure experiments and first-principles simulations

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    We present a joint theoretical and experimental study of the oxygen KK-edge spectra for LaFeO3_3 and homovalent Ni-substituted LaFeO3_3 (LaFe0.75_{0.75}Ni0.25_{0.25}O3_3), using first-principles simulations based on density-functional theory with extended Hubbard functionals and x-ray absorption near edge structure (XANES) measurements. Ground-state and excited-state XANES calculations employ Hubbard on-site UU and inter-site VV parameters determined from first principles and the Lanczos recursive method to obtain absorption cross sections, which allows for a reliable description of XANES spectra in transition-metal compounds in a very broad energy range, with an accuracy comparable to that of hybrid functionals but at a substantially lower cost. We show that standard gradient-corrected exchange-correlation functionals fail in capturing accurately the electronic properties of both materials. In particular, for LaFe0.75_{0.75}Ni0.25_{0.25}O3_3 they do not reproduce its semiconducting behaviour and provide a poor description of the pre-edge features at the O KK edge. The inclusion of Hubbard interactions leads to a drastic improvement, accounting for the semiconducting ground state of LaFe0.75_{0.75}Ni0.25_{0.25}O3_3 and for a good agreement between calculated and measured XANES spectra. We show that the partial substitution of Fe for Ni affects the conduction-band bottom by generating a strongly hybridized O(2p2p)-Ni(3d3d) minority-spin empty electronic state. The present work, based on a consistent correction of self-interaction errors, outlines the crucial role of extended Hubbard functionals to describe the electronic structure of complex transition-metal oxides such as LaFeO3_3 and LaFe0.75_{0.75}Ni0.25_{0.25}O3_3 and paves the way to future studies on similar systems

    Molecular Dynamics Simulation of Structural Characterization of Elastic and Inelastic Deformation in ZrCu Metallic Glasses

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    The nanoscopic deformation behaviors in a ZrCu metallic glass model during loading-unloading process under uniaxial compression have been analyzed on the basis of the molecular dynamics (MD). The reversible degree of shear origin zones (SOZs) is used as the structural indicator to distinguish the elastic deformation and inelastic deformation of ZrCu metallic glass at the atomic level. We find that the formation of SOZs is reversible at the elastic stage but irreversible at the inelastic stage during the loading and unloading processes. At the inelastic stage, the full-icosahedra fraction in SOZs is quickly reduced with increased strain and the decreasing process is also irreversible during the unloading processes

    Hot deformation behavior of 51.1Zr–40.2Ti–4.5Al–4.2V alloy in the single β phase field

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    The hot deformation behavior of a newly developed 51.1Zr–40.2Ti–4.5Al–4.2 V alloy was investigated by compression tests in the deformation temperature range from 800 to 1050 °C and strain rate range from 10−3 to 100 s−1. At low temperatures and high strain rates, the flow curves exhibited a pronounced stress drop at the very beginning of deformation, followed by a slow decrease in flow stress with increasing strain. The magnitude of the stress drop increased with decreasing deformation temperature and increasing strain rate. At high temperatures and low strain rates, the flow curves exhibited typical characteristics of dynamic recrystallization. A hyperbolic-sine Arrhenius-type equation was used to characterize the dependences of the flow stress on deformation temperature and strain rate. The activation energy for hot deformation decreased slightly with increasing strain and then tended to be a constant value. A microstructural mechanism map was presented to help visualize the microstructure of this alloy under different deformation conditions

    Facile synthesis of graphene-AgVO3 nanocomposite with excellent supercapacitor performance

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    The graphene-AgVO3 nanocomposites (GA30) were synthesized by facile one-step chemical-bath method. SEM and TEM images of the synthesized nanocomposites indicate that this method is possible to anchor the AgVO3 nanoparticles onto the graphene surface. Galvanostatic charge-discharge (GCD) shows that specific capacitance, cycle stability, and rate capability of the supercapacitor device can be enhanced with AgVO3 incorporation. The GA30 shows a high energy density of 10 Wh/kg at a power density of 25 W/kg as well as a high power density of 2045 W/kg at an energy density of 6 Wh/kg, which are much higher than those of graphene/activated carbon composites (GC30) and previous reported graphene-based composites. The improvement in specific capacitance, cycle stability, energy density and powder density of the graphene would be attributed to the special microstructure with high-rate transportation of both electrolyte ions and electrons due to the incorporation of AgVO3. (C) 2018 Elsevier B.V. All rights reserved.Ratchadaphiseksomphot Endowment under Outstanding Research Performance Program, Chulalongkorn University Thailand Research Fund RSA6080017 Natural Science Foundation for Distinguished Young Scholars of Hebei Province of China E201620337
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