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Sample records for nf4bf4 showed conclusively

  1. Densities and viscosities for ionic liquids mixtures containing [eOHmim][BF4], [bmim][BF4] and [bpy][BF4

    International Nuclear Information System (INIS)

    Song, Dayong; Chen, Jing

    2014-01-01

    Highlights: • Targets of this research are ILs mixtures. • Densities and viscosities were measured for three ILs mixtures. • Excess molar properties were deduced from the experiments. • Viscosities were discussed by the ideal Grunberg and Nissan mixing law. - Abstract: Densities and viscosities of binary ionic liquids mixtures, 1-(2-hydroxyethyl)-3-methylimidazolium tetrafluoroborate ([eOHmim][BF 4 ]) + 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim][BF 4 ]), 1-(2-hydroxyethyl)-3-methylimidazolium tetrafluoroborate ([eOHmim][BF 4 ]) + N-butylpyridinium tetrafluoroborate ([bpy][BF 4 ]) and 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim][BF 4 ]) + N-butylpyridinium tetrafluoroborate ([bpy][BF 4 ]) were measured over the entire mole fraction from T = (298.15 to 343.15) K. The excess molar volumes were calculated and correlated by Redlich–Kiser polynomial expansions. The viscosities for pure ionic liquids were analyzed by means of the Vogel–Tammann–Fulcher equation and ideal mixing rules were applied for the ILs mixtures

  2. Investigation of toxic effects of imidazolium ionic liquids, [bmim][BF4] and [omim][BF4], on marine mussel Mytilus galloprovincialis with or without the presence of conventional solvents, such as acetone.

    Science.gov (United States)

    Tsarpali, Vasiliki; Belavgeni, Alexia; Dailianis, Stefanos

    2015-07-01

    This study investigated the cytotoxic, oxidative and genotoxic effects of two commonly used imidazolium ionic liquids (ILs), [bmim][BF4] (1-butyl-3-methylimidazolium) and [omim][BF4] (1-methyl-3-octylimidazolium tetrafluoroborate), on the marine mussel Mytilus galloprovincialis, as well as whether acetone could mediate their toxic profile. In this context, mussels were firstly exposed to different concentrations of [bmim][BF4] or [omim][BF4], with or without the presence of acetone (at a final concentration of 0.06% v/v), for a period of 96h, in order to determine the concentration that causes 50% mussel mortality (LC50 values) in each case. Thereafter, mussels were exposed to sub- and non-lethal concentrations of ILs for investigating their ability to cause lysosomal membrane impairment (with the use of neutral red retention assay/NRRT), superoxide anion and lipid peroxidation byproduct (malondialdehyde/MDA) formation, as well as DNA damage and formation of nuclear abnormalities in hemocytes. The results showed that [omim][BF4] was more toxic than [bmim][BF4] in all cases, while the presence of acetone resulted in a slight attenuation of its toxicity. The different toxic behavior of ILs was further revealed by the significantly lower levels of NRRT values observed in [omim][BF4]-treated mussels, compared to those occurring in [bmim][BF4] in all cases. Similarly, [bmim][BF4]-mediated oxidative and genotoxic effects were observed only in the highest concentration tested (10mgL(-1)), while [omim][BF4]-mediated effects were enhanced at lower concentrations (0.01-0.05mgL(-1)). Overall, the present study showed that [bmim][BF4] and [omim][BF4] could induce not only lethal but also nonlethal effects on mussel M. galloprovincialis. The extent of [bmim][BF4] and/or [omim][BF4]-mediated effects could be ascribed to the length of each IL alkyl chain, as well as to their lipophilicity. Moreover, the role of acetone on the obtained toxic effects of the specific ILs was

  3. Toxicity of two imidazolium ionic liquids, [bmim][BF4] and [omim][BF4], to standard aquatic test organisms: Role of acetone in the induced toxicity.

    Science.gov (United States)

    Tsarpali, Vasiliki; Dailianis, Stefanos

    2015-07-01

    The main goal of this study was to investigate the toxicity of the imidazolium-based ionic liquids (ILs), [bmim][BF4] (1-butyl-3-methylimidazolium tetrafluoroborate) and [omim][BF4] (1-octyl-3-methylimidazolium tetrafluoroborate), in battery of standard aquatic toxicity test organisms. Specifically, exposure of the algae Scenedesmus rubescens, crustaceans Thamnocephalus platyurus and Artemia franciscana, rotifers Brachionus calyciflorus and Brachionus plicatilis and bivalve Mytilus galloprovincialis to different concentrations of [bmim][BF4], [omim][BF4] and/or a binary mixture of [bmim][BF4]-[omim][BF4] (1:1) with or without acetone (carrier solvent), revealed that solvent can differentially mediate ILs' toxic profile. Acetone's ability to differentially affect ILs' cation's alkyl chain length, as well as the hydrolysis of [BF4(-)] anions was evident. Given that the toxic potency of the tested ILs seemed to be equal or even higher (in some cases) than those of conventional organic solvents, the present study revealed that the characterization of imidazolium-based ILs as "green solvents" should not be generalized, at least in case of their natural occurrence in mixtures with organic solvents, such as acetone. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Investigation of toxic effects of imidazolium ionic liquids, [bmim][BF{sub 4}] and [omim][BF{sub 4}], on marine mussel Mytilus galloprovincialis with or without the presence of conventional solvents, such as acetone

    Energy Technology Data Exchange (ETDEWEB)

    Tsarpali, Vasiliki; Belavgeni, Alexia; Dailianis, Stefanos, E-mail: sdailianis@upatras.gr

    2015-07-15

    Highlights: • The toxic effects of [bmim][BF{sub 4}] and [omim][BF{sub 4}] on mussels were investigated. • Both ILs could induce lethal and nonlethal effects on Mytilus galloprovincialis. • Different extent of IL-mediated adverse effects was observed in mussel hemocytes. • The alkyl chain length and lipophilicity of ILs are crucial for their toxicity. • Acetone influences the oxidative and genotoxic effects of [omim][BF{sub 4}]. - Abstract: This study investigated the cytotoxic, oxidative and genotoxic effects of two commonly used imidazolium ionic liquids (ILs), [bmim][BF{sub 4}] (1-butyl-3-methylimidazolium) and [omim][BF{sub 4}] (1-methyl-3-octylimidazolium tetrafluoroborate), on the marine mussel Mytilus galloprovincialis, as well as whether acetone could mediate their toxic profile. In this context, mussels were firstly exposed to different concentrations of [bmim][BF{sub 4}] or [omim][BF{sub 4}], with or without the presence of acetone (at a final concentration of 0.06% v/v), for a period of 96 h, in order to determine the concentration that causes 50% mussel mortality (LC{sub 50} values) in each case. Thereafter, mussels were exposed to sub- and non-lethal concentrations of ILs for investigating their ability to cause lysosomal membrane impairment (with the use of neutral red retention assay/NRRT), superoxide anion and lipid peroxidation byproduct (malondialdehyde/MDA) formation, as well as DNA damage and formation of nuclear abnormalities in hemocytes. The results showed that [omim][BF{sub 4}] was more toxic than [bmim][BF{sub 4}] in all cases, while the presence of acetone resulted in a slight attenuation of its toxicity. The different toxic behavior of ILs was further revealed by the significantly lower levels of NRRT values observed in [omim][BF{sub 4}]-treated mussels, compared to those occurring in [bmim][BF{sub 4}] in all cases. Similarly, [bmim][BF{sub 4}]-mediated oxidative and genotoxic effects were observed only in the highest

  5. Characterization of plasticized PMMA–LiBF4 based solid polymer ...

    Indian Academy of Sciences (India)

    Unknown

    Polymer electrolyte films prepared from poly(methyl methacrylate) and LiBF4 with different con- centrations of ... 1. Introduction. Many types of ionically conducting polymers, generally ... 2. Experimental. Thin films of PMMA–LiBF4–DBP in different mole ratios ... remains very close to that of a liquid electrolyte. It is con-.

  6. Crystal structure and characterization of the novel NH+⋯N hydrogen bonded polar crystal [NH2(CH2)4NH][BF4

    Science.gov (United States)

    Wojtaś, M.; Gaģor, A.; Czupiński, O.; Medycki, W.; Jakubas, R.

    2012-03-01

    Dielectric properties and phase transitions of the piperazinium tetrafluoroborate ([NH2(CH2)4NH][BF4], abbreviated as PFB) crystal are related to the one-dimensional arrangement of the cations linked by the bistable NH+⋯N hydrogen bonds and molecular motions of the [BF4]- units. The crystal structure of [NH2(CH2)4NH][BF4] is monoclinic at room temperature with the polar space group Pn. The polar/acentric properties of the room temperature phase IV have been confirmed by the piezoelectric and pyroelectric measurements. DSC measurements show that the compound undergoes three first-order structural phase transitions: at 421/411 K (heating/cooling), at 386/372 K and at 364/349 K. 1H and 19F NMR measurements indicate the reorientational motions of [BF4]- anions and piperazinium(+) cations as well as the proton motion in the hydrogen-bonded chains of piperazine along the [001] direction. Over the phase I the isotropic reorientational motions or even self-diffusion of the cations and anions are expected. The conductivity measurements in the vicinity of the II-I PT indicate a superionic phase over the phase I.

  7. Separation of toluene from n-heptane by liquid–liquid extraction using binary mixtures of [bpy][BF4] and [4bmpy][Tf2N] ionic liquids as solvent

    International Nuclear Information System (INIS)

    García, Silvia; Larriba, Marcos; García, Julián; Torrecilla, José S.; Rodríguez, Francisco

    2012-01-01

    Highlights: ► Binary mixtures of ionic liquids as extraction solvents of aromatics. ► [4bmpy][Tf 2 N] shows higher capacity but lower selectivity than sulfolane. ► [bpy][BF 4 ] shows lower capacity but higher selectivity than sulfolane. ► Mixed {[4bmpy][Tf 2 N] + [bpy][BF 4 ]} improves both extractive properties. - Abstract: The use of binary mixture of ionic liquids N-butylpyridinium tetrafluoroborate ([bpy][BF 4 ]), and 1-butyl-4-methylpyridinium bis(trifluoromethylsulfonyl)imide ([4bmpy][Tf 2 N]) in the liquid–liquid extraction of toluene from n-heptane has been investigated at 313.2 K and atmospheric pressure. The experimental capacity of extraction and selectivity for this binary mixture has proved to be intermediate to those corresponding to the pure ionic liquids, and they can be predicted using a logarithmic–linear model of solubility. Furthermore, the results showed that the use of binary mixture of {[bpy][BF 4 ] + [4bmpy][Tf 2 N]} at a mole solvent composition around 0.7 for [bpy][BF 4 ] improves both the capacity of extraction of toluene and the selectivity with respect to those of sulfolane, the organic solvent taken as a benchmark. Thus, this mixed ionic liquid could be likely to be used in the extraction of aromatic from aliphatic in replacement to sulfolane.

  8. Tumor cell-released TLR4 ligands stimulate Gr-1+CD11b+F4/80+ cells to induce apoptosis of activated T cells.

    Science.gov (United States)

    Liu, Yan-Yan; Sun, Ling-Cong; Wei, Jing-Jing; Li, Dong; Yuan, Ye; Yan, Bin; Liang, Zhi-Hui; Zhu, Hui-Fen; Xu, Yong; Li, Bo; Song, Chuan-Wang; Liao, Sheng-Jun; Lei, Zhang; Zhang, Gui-Mei; Feng, Zuo-Hua

    2010-09-01

    Gr-1(+)CD11b(+)F4/80(+) cells play important roles in tumor development and have a negative effect on tumor immunotherapy. So far, the mechanisms underlying the regulation of their immunosuppressive phenotype by classical and alternative macrophage activation stimuli are not well elucidated. In this study, we found that molecules from necrotic tumor cells (NTC-Ms) stimulated Gr-1(+)CD11b(+)F4/80(+) cells to induce apoptosis of activated T cells but not nonstimulated T cells. The apoptosis-inducing capacity was determined by higher expression levels of arginase I and IL-10 relative to those of NO synthase 2 and IL-12 in Gr-1(+)CD11b(+)F4/80(+) cells, which were induced by NTC-Ms through TLR4 signaling. The apoptosis-inducing capacity of NTC-Ms-stimulated Gr-1(+)CD11b(+)F4/80(+) cells could be enhanced by IL-10. IFN-gamma may reduce the apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells only if their response to IFN-gamma was not attenuated. However, the potential of Gr-1(+)CD11b(+)F4/80(+) cells to express IL-12 in response to IFN-gamma could be attenuated by tumor, partially due to the existence of active STAT3 in Gr-1(+)CD11b(+)F4/80(+) cells and NTC-Ms from tumor. In this situation, IFN-gamma could not effectively reduce the apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells. Tumor immunotherapy with 4-1BBL/soluble programmed death-1 may significantly reduce, but not abolish the apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells in local microenvironment. Blockade of TLR4 signaling could further reduce the apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells and enhance the suppressive effect of 4-1BBL/soluble form of programmed death-1 on tumor growth. These findings indicate the relationship of distinct signaling pathways with apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells and emphasize the importance of blocking TLR4 signaling to prevent the induction of T cell apoptosis by Gr-1(+)CD11b(+)F4/80(+) cells.

  9. Crystal structure and characterization of the novel NH+⋯N hydrogen bonded polar crystal [NH2(CH2)4NH][BF4

    International Nuclear Information System (INIS)

    Wojtaś, M.; Gagor, A.; Czupiński, O.; Medycki, W.; Jakubas, R.

    2012-01-01

    Dielectric properties and phase transitions of the piperazinium tetrafluoroborate ([NH 2 (CH 2 ) 4 NH][BF 4 ], abbreviated as PFB) crystal are related to the one-dimensional arrangement of the cations linked by the bistable NH + ⋯N hydrogen bonds and molecular motions of the [BF 4 ] − units. The crystal structure of [NH 2 (CH 2 ) 4 NH][BF 4 ] is monoclinic at room temperature with the polar space group Pn. The polar/acentric properties of the room temperature phase IV have been confirmed by the piezoelectric and pyroelectric measurements. DSC measurements show that the compound undergoes three first-order structural phase transitions: at 421/411 K (heating/cooling), at 386/372 K and at 364/349 K. 1 H and 19 F NMR measurements indicate the reorientational motions of [BF 4 ] − anions and piperazinium(+) cations as well as the proton motion in the hydrogen-bonded chains of piperazine along the [001] direction. Over the phase I the isotropic reorientational motions or even self-diffusion of the cations and anions are expected. The conductivity measurements in the vicinity of the II–I PT indicate a superionic phase over the phase I. - Graphical abstract: It must be emphasized that the titled compound represents the first organic–inorganic simple salt containing the single-protonated piperazinium cation which was studied by means of the wide variety of experimental techniques. A survey of Cambridge Structural Database (CSD version 5.32 (November 2010) and updates (May 2011)) for structure containing the piperazinium cations yields 248 compounds with the doubly protonated piperazinium(2+) cations and only eight compounds with the singly protonated piperazinium(+) cations. Among these structures only one is the hybrid organic–inorganic material. This is piperazinium nitrate characterized structurally. The crystal packing of [NH 2 (CH 2 ) 4 NH][BF 4 ], phase IV. The dashed lines stand for the hydrogen bonds. The hydrogen bonds to BF4 groups are not included for

  10. Mixing thermodynamic properties of 1-butyl-4-methylpyridinium tetrafluoroborate [b4mpy][BF{sub 4}] with water and with an alkan-1ol (methanol to pentanol)

    Energy Technology Data Exchange (ETDEWEB)

    Ortega, J. [Laboratorio de Termodinamica y Fisicoquimica de Fluidos, Parque Cientifico-Tecnologico, Campus Universitario de Tafira, Universidad de Las Palmas de Gran Canaria, 35071-Las Palmas de Gran Canaria, Canary Islands (Spain)], E-mail: jortega@dip.ulpgc.es; Vreekamp, R.; Penco, E.; Marrero, E. [Laboratorio de Termodinamica y Fisicoquimica de Fluidos, Parque Cientifico-Tecnologico, Campus Universitario de Tafira, Universidad de Las Palmas de Gran Canaria, 35071-Las Palmas de Gran Canaria, Canary Islands (Spain)

    2008-07-15

    This article presents a study of the behaviour in solution of 1-butyl-4-methylpyridinium tetrafluoroborate [b4mpy][BF{sub 4}] in water and in the first five alkanols of the series methanol to pentan-1-ol. The excess enthalpies, H{sub m}{sup E} and volumes, V{sub m}{sup E} were determined at the temperatures (298.15 and 318.15) K. At these temperatures, the [b4mpy][BF{sub 4}] was completely miscible in water, methanol, and ethanol, but only partially miscible in the other alkanols. A solubility study was carried out and the (liquid + liquid) equilibria of the ([b4mpy][BF{sub 4}] + alkanol) systems were experimentally determined, evaluating zones of complete miscibility and determining the UCST in each case. The mixtures with water gave positive values of H{sub m}{sup E} and V{sub m}{sup E}, being also positive the changes of these quantities with temperature. The mixtures with alkanols gave values of H{sub m}{sup E}>0 and V{sub m}{sup E}<0, and for these binary mixtures (dH{sub m}{sup E}/dT){sub p}>0 and (dV{sub m}{sup E}/dT){sub p}<0. For all cases, results were interpreted and compared with data obtained in mixtures with another isomer [b3mpy][BF{sub 4}]. Excess properties were correlated with a suitable equation and the area and volume parameters were calculated for [b4mpy][BF{sub 4}].

  11. Assessing toxic effects of [Omim]Cl and [Omim]BF4 in zebrafish adults using a biomarker approach.

    Science.gov (United States)

    Liu, Tong; Guo, Yingying; Wang, Jinhua; Wang, Jun; Zhu, Lusheng; Zhang, Jun; Zhang, Cheng

    2016-04-01

    In the present study, the toxic effects of 1-octyl-3-methylimidazolium chloride ([Omim]Cl) and 1-octyl-3-methylimidazolium tetrafluoroborate ([Omim]BF4) on the zebrafish livers were studied at 0, 5, 10, 20, and 40 mg L(-1) on the 7th and 14th days. In addition, the concentrations of [Omim]Cl and [Omim]BF4 in the test water, the acute toxicity of the two ionic liquids (ILs), and the influence of anions on the toxicity of the ILs were evaluated. The acute toxicity test results showed 50 % lethal concentration (LC50) values of 152.3 ± 12.1 mg L(-1) for [Omim]Cl and 144.0 ± 11.4 mg L(-1) for [Omim]BF4. At the lowest concentration investigated (5 mg L(-1)), [Omim]Cl and [Omim]BF4 did not significantly affect zebrafish during the exposure period. However, the toxic effects of these substances were enhanced as dosing concentrations and exposure times were increased. Levels of reactive oxygen species (ROS) were significantly enhanced on the 7th day after 20 mg L(-1) and on the 14th day after 10 mg L(-1) of either substance was applied, resulting in oxidative damage, such as lipid peroxidation and DNA damage. The experimental results also indicated little effect of the anions on the toxicity of ILs and consistent toxic effects of [Omim]Cl and [Omim]BF4. Graphical Abstract The graphical abstract for the present study after exposure to [Omim]Cl and [Omim]BF4. The letter R represents the anions Cl(-) and BF4 (.)

  12. Oxygen evolution from BF3/MnO4-.

    Science.gov (United States)

    Yiu, Shek-Man; Man, Wai-Lun; Wang, Xin; Lam, William W Y; Ng, Siu-Mui; Kwong, Hoi-Ki; Lau, Kai-Chung; Lau, Tai-Chu

    2011-04-14

    MnO(4)(-) is activated by BF(3) to undergo intramolecular coupling of two oxo ligands to generate O(2). DFT calculations suggest that there should be a spin intercrossing between the singlet and triplet potential energy surfaces on going from the active intermediate [MnO(2)(OBF(3))(2)](-) to the O···O coupling transition state.

  13. OsNF-YC2 and OsNF-YC4 proteins inhibit flowering under long-day conditions in rice

    KAUST Repository

    Kim, SoonKap

    2015-11-05

    OsNF-YC2 and OsNF-YC4 proteins regulate the photoperiodic flowering response through the modulation of three flowering-time genes ( Ehd1, Hd3a , and RFT1 ) in rice. Plant NUCLEAR FACTOR Y (NF-Y) transcription factors control numerous developmental processes by forming heterotrimeric complexes, but little is known about their roles in flowering in rice. In this study, it is shown that some subunits of OsNF-YB and OsNF-YC interact with each other, and among them, OsNF-YC2 and OsNF-YC4 proteins regulate the photoperiodic flowering response of rice. Protein interaction studies showed that the physical interactions occurred between the three OsNF-YC proteins (OsNF-YC2, OsNF-YC4 and OsNF-YC6) and three OsNF-YB proteins (OsNF-YB8, OsNF-YB10 and OsNF-YB11). Repression and overexpression of the OsNF-YC2 and OsNF-YC4 genes revealed that they act as inhibitors of flowering only under long-day (LD) conditions. Overexpression of OsNF-YC6, however, promoted flowering only under LD conditions, suggesting it could function as a flowering promoter. These phenotypes correlated with the changes in the expression of three rice flowering-time genes [Early heading date 1 (Ehd1), Heading date 3a (Hd3a) and RICE FLOWERING LOCUS T1 (RFT1)]. The diurnal and tissue-specific expression patterns of the subsets of OsNF-YB and OsNF-YC genes were similar to those of CCT domain encoding genes such as OsCO3, Heading date 1 (Hd1) and Ghd7. We propose that OsNF-YC2 and OsNF-YC4 proteins regulate the photoperiodic flowering response by interacting directly with OsNF-YB8, OsNF-YB10 or OsNF-YB11 proteins in rice.

  14. Endothelial glutathione-S-transferase A4-4 protects against oxidative stress and modulates iNOS expression through NF-κB translocation

    International Nuclear Information System (INIS)

    Yang Yongzhen; Yang Yusong; Xu Ya; Lick, Scott D.; Awasthi, Yogesh C.; Boor, Paul J.

    2008-01-01

    Our recent work in endothelial cells and human atherosclerotic plaque showed that overexpression of glutathione-S-tranferases (GSTs) in endothelium protects against oxidative damage from aldehydes such as 4-HNE. Nuclear factor (NF)-κB plays a crucial role during inflammation and immune responses by regulating the expression of inducible genes such as inducible nitric oxide synthase (iNOS). 4-HNE induces apoptosis and affects NF-κB mediated gene expression, but conflicting results on 4-HNE's effect on NF-κB have been reported. We compared the effect of 4-HNE on iNOS and the NF-κB pathway in control mouse pancreatic islet endothelial (MS1) cells and those transfected with mGSTA4, a α-class GST with highest activity toward 4-HNE. When treated with 4-HNE, mGSTA4-transfected cells showed significant upregulation of iNOS and nitric oxide (NO) through (NF)-κB (p65) translocation in comparison with wild-type or vector-transfected cells. Immunohistochemical studies of early human plaques showed lower 4-HNE content and upregulation of iNOS, which we take to indicate that GSTA4-4 induction acts as an enzymatic defense against high levels of 4-HNE, since 4-HNE accumulated in more advanced plaques, when detoxification and exocytotic mechanisms are likely to be overwhelmed. These studies suggest that GSTA4-4 may play an important defensive role against atherogenesis through detoxification of 4-HNE and upregulation of iNOS

  15. Hexadecyltrimethylammonium bromide (CTA-Br) and 1-butyl-3-methylimidazolium tetrafluoroborate (bmim-BF4) in aqueous solution: An ephemeral binary system.

    Science.gov (United States)

    Comelles, Francesc; Ribosa, Isabel; Gonzalez, Juan José; Garcia, M Teresa

    2017-03-15

    Mixtures of the cationic surfactant hexadecyltrimethylammonium bromide (CTA-Br) and the ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate (bmim-BF 4 ) in aqueous solutions are expected to behave as typical binary cationic surfactant system taking into account the surface activity displayed by the ionic liquid, instead of considering the IL as a water cosolvent. Surface tension and conductivity measurements have been conducted as a function of the total concentration of the mixtures at different surfactant mole fraction (α CTA-Br ) to investigate the surface active properties. Turbidity immediately appearing when the compounds are mixed in water suggests the spontaneous formation of the low soluble compound hexadecyltrimethylammonium tetrafluoroborate (CTA-BF 4 ), together with the salt formed by the respective counterions bmim + and Br - in solution. For α CTA-Br ≠0.5, furthermore of the mentioned compounds, the spare bmim-BF 4 (for α CTA-Br Br (for α CTA-Br >0.5), are also present in the aqueous solution. Systems containing excess of bmim-BF 4 show a low critical aggregate concentration (cac), but an unexpected high surface tension at cac (γ cac ≈53-56mN/m), as pure CTA-BF 4 . For systems containing excess of CTA-Br, cac increases but γ cac decreases up to 36mN/m. Mixtures of pure CTA-BF 4 and bmim-BF 4 or CTA-Br behave as typical binary surfactant systems. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Green synthesis of 2,3,4,9-tetrahydro-1H-carbazoles/ 2,3-dimethylindoles catalyzed by [bmim (BF 4] ionic liquid in methanol

    Directory of Open Access Journals (Sweden)

    Tamatakallu O. Shrungesh Kumar

    2013-03-01

    Full Text Available 1-butyl-3-methylimidazolium tetrafluoroborate [bmim (BF 4] ionic liquid has been used as catalyst for the synthesis of tetrahydrocarbazoles and 2, 3-dimethylindoles with excellent yields in a shorter reaction time. The results show that the [bmim (BF 4] ionic liquid is very efficient in the Fischer indole synthesis due to its operational simplicity, high yields, dual catalyst-solvent properties and reused for five consecutive reactions without significant loss of catalytic efficiency. The applicability of the methodology for large-scale reaction highlights its potentiality for industrial scale synthesis. The main advantage of this procedure is that the products could be obtained in pure form after filtration and evaporation of MeOH solvent.

  17. [Cu(I)(bpp)]BF4: the first extended coordination network prepared solvothermally in an ionic liquid solvent.

    Science.gov (United States)

    Jin, Kun; Huang, Xiaoying; Pan, Long; Li, Jing; Appel, Aaron; Wherland, Scot; Pang, Long

    2002-12-07

    Use of an ionic liquid [bmim][BF4] (bmim = 1-butyl-3-methylimidazolium) as solvent has resulted in the first extended coordination structure, the two-dimensional network [Cu(bpp)]BF4 [bpp = 1,3-bis(4-pyridyl)propane], produced via a solvothermal route.

  18. FTIR Spectroscopic and DC Ionic conductivity Studies of PVDF-HFP: LiBF4: EC Plasticized Polymer Electrolyte Membrane

    Science.gov (United States)

    Sangeetha, M.; Mallikarjun, A.; Jaipal Reddy, M.; Siva Kumar, J.

    2017-08-01

    In the present paper; the FTIR and Temperature dependent DC Ionic conductivity studies of polymer (80 Wt% PVDF-HFP) with inorganic lithium tetra fluoroborate salt (20 Wt% LiBF4) as ionic charge carrier and plasticized with various weight ratios of Ethylene carbonate plasticizer (10 Wt% to 70 Wt% EC) as gel polymer electrolytes. Solution casting method is used for the preparation of plasticized polymer-salt electrolyte films. FTIR analysis shows the good complexation between PVDF-HFP: LiBF4 and the presence of functional groups in the plasticized polymer-salt electrolyte membrane. Also the analysis and results show that the highest DC ionic conductivity of 1.66 × 10-3 SCm -1 was found at 373 K for a particular concentration of 80 Wt% PVDF-HFP: 20 Wt% LiBF4: 40 Wt% EC porous gel type polymer-salt plasticized porous membrane. Increase of temperature results expansion and segmental motion of polymer chain that generates free volume in turn promotes hopping of the lithium ions satisfying Vogel-Tammann-Fulcher equation.

  19. Empirical parameters for solvent acidity, basicity, dipolarity, and polarizability of the ionic liquids [BMIM][BF4] and [BMIM][PF6].

    Science.gov (United States)

    del Valle, J C; García Blanco, F; Catalán, J

    2015-04-02

    The empirical solvent scales for polarizability (SP), dipolarity (SdP), acidity (SA), and basicity (SB) have been successfully used to interpret the solvatochromism of compounds dissolved in organic solvents and their solvent mixtures. Providing that the published solvatochromic parameters for the ionic liquids 1-(1-butyl)-3-methylimidazolium tetrafluoroborate, [BMIM][BF4] and 1-(1-butyl)-3-methylimidazolium hexafluorophosphate, [BMIM][PF6], are excessively widespread, their SP, SdP, SA, and SB values are measured herein at temperatures from 293 to 353 K. Four key points are emphasized herein: (i) the origin of the solvatochromic solvent scales--the gas phase, that is the absence of any medium perturbation--; (ii) the separation of the polarizability and dipolarity effects; (iii) the simplification of the probing process in order to obtain the solvatochromic parameters; and (iv) the SP, SdP, SA, and SB solvent scales can probe the polarizability, dipolarity, acidity, and basicity of ionic liquids as well as of organic solvents and water-organic solvent mixtures. From the multiparameter approach using the four pure solvent scales one can draw the conclusion that (a) the solvent influence of [BMIM][BF4] parallels that of formamide at 293 K, both of them miscible with water; (b) [BMIM][PF6] shows a set of solvatochromic parameters similar to that of chloroacetonitrile, both of them water insoluble; and (c) that the corresponding solvent acidity and basicity of the ionic liquids can be explained to a great extent from the cation species by comparing the empirical parameters of [BMIM](+) with those of the solvent 1-methylimidazole. The insolubility of [BMIM][PF6] in water as compared to [BMIM][BF4] is tentatively connected to some extent to the larger molar volume of the anion [PF6](-), and to the difference in basicity of [PF6](-) and [BF4](-).

  20. Bone marrow CD11b(+)F4/80(+) dendritic cells ameliorate collagen-induced arthritis through modulating the balance between Treg and Th17.

    Science.gov (United States)

    Zhang, Lingling; Fu, Jingjing; Sheng, Kangliang; Li, Ying; Song, Shanshan; Li, Peipei; Song, Shasha; Wang, Qingtong; Chen, Jingyu; Yu, Jianhua; Wei, Wei

    2015-03-01

    Tolerogenic dendritic cells (DCs) are well-known to show an immunosuppressive function. In this study we determine the therapeutic effects and potential mechanisms of transferred bone marrow (BM) CD11b(+)F4/80(+) DCs on collagen-induced arthritis (CIA) in mice. Murine BM CD11b(+)F4/80(+) DCs were generated under the stimulation of GM-CSF and IL-4, and the function of BM CD11b(+) F4/80(+) DCs was identified by measuring the levels of IL-10, TGF-beta and indoleamine 2,3-dioxygenase (IDO). BM CD11b(+)F4/80(+) DCs were transferred to CIA mice by intravenous injections. The histopathology of joint and spleen were evaluated. T lymphocyte proliferation, Treg and Th17 subsets were analyzed. The expressions of Foxp3, Helios and RORγt in T lymphocytes co-cultured with BM CD11b(+)F4/80(+) DCs were measured in vitro. We found that BM CD11b(+)F4/80(+) DCs induced by GM-CSF and IL-4 could express high levels of IL-10, TGF-beta and IDO. BM CD11b(+)F4/80(+) DCs significantly reduced the pathologic scores in joints and spleens, which correlated significantly with the reduced T lymphocyte proliferation and Th17 cell number, and with the increased Tregs number. In vitro, OVA-pulsed BM CD11b(+)F4/80(+) DCs promoted Treg cell expansion, enhanced IL-10 and CTLA-4 protein expression, augmented Foxp3 and Helios mRNA expression, and inhibited RORγt and IL-17 mRNA expression. Taken together, BM CD11b(+)F4/80(+) DCs are able to ameliorate the development and severity of CIA, at least partly by inducing Foxp3(+) Treg cell expansion and suppressing Th17 function. The BM CD11b(+)F4/80(+) DCs might have a promising immunotherapeutic potential for autoimmune arthritis. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Thermally Tunable Dual Emission of the d8–d8 Dimer [Pt2(μ-P2O5(BF2)2)4]4

    Czech Academy of Sciences Publication Activity Database

    Hofbeck, T.; Lam, Y.; Ch.; Kalbáč, Martin; Záliš, Stanislav; Vlček, Antonín; Yersin, H.

    2016-01-01

    Roč. 55, č. 5 (2016), s. 2441-2449 ISSN 0020-1669 R&D Projects: GA MŠk LH13015; GA MŠk LD14129; GA MŠk LL1301 Grant - others:COST(XE) cm1202 Institutional support: RVO:61388955 Keywords : High-resolution fluorescence * phosphorescence spectra * [Pt2(μ-P2O5(BF2)2)4]4− (Pt(pop-BF2)) Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 4.857, year: 2016

  2. Crystal structure and characterization of the novel NH{sup +} Midline-Horizontal-Ellipsis N hydrogen bonded polar crystal [NH{sub 2}(CH{sub 2}){sub 4}NH][BF{sub 4}

    Energy Technology Data Exchange (ETDEWEB)

    Wojtas, M., E-mail: maciej.wojtas@chem.uni.wroc.pl [Faculty of Chemistry, University of Wroclaw, Joliot-Curie 14, 50-383 Wroclaw (Poland); Gagor, A. [W. Trzebiatowski Institute of Low Temperature and Structure Research, Polish Academy of Science, PO Box 1410, 50-950 Wroclaw (Poland); Czupinski, O. [Faculty of Chemistry, University of Wroclaw, Joliot-Curie 14, 50-383 Wroclaw (Poland); Medycki, W. [Institute of Molecular Physics, Polish Academy of Science, Smoluchowskiego 17, 60-179 Poznan (Poland); Jakubas, R. [Faculty of Chemistry, University of Wroclaw, Joliot-Curie 14, 50-383 Wroclaw (Poland)

    2012-03-15

    Dielectric properties and phase transitions of the piperazinium tetrafluoroborate ([NH{sub 2}(CH{sub 2}){sub 4}NH][BF{sub 4}], abbreviated as PFB) crystal are related to the one-dimensional arrangement of the cations linked by the bistable NH{sup +} Midline-Horizontal-Ellipsis N hydrogen bonds and molecular motions of the [BF{sub 4}]{sup -} units. The crystal structure of [NH{sub 2}(CH{sub 2}){sub 4}NH][BF{sub 4}] is monoclinic at room temperature with the polar space group Pn. The polar/acentric properties of the room temperature phase IV have been confirmed by the piezoelectric and pyroelectric measurements. DSC measurements show that the compound undergoes three first-order structural phase transitions: at 421/411 K (heating/cooling), at 386/372 K and at 364/349 K. {sup 1}H and {sup 19}F NMR measurements indicate the reorientational motions of [BF{sub 4}]{sup -} anions and piperazinium(+) cations as well as the proton motion in the hydrogen-bonded chains of piperazine along the [001] direction. Over the phase I the isotropic reorientational motions or even self-diffusion of the cations and anions are expected. The conductivity measurements in the vicinity of the II-I PT indicate a superionic phase over the phase I. - Graphical abstract: It must be emphasized that the titled compound represents the first organic-inorganic simple salt containing the single-protonated piperazinium cation which was studied by means of the wide variety of experimental techniques. A survey of Cambridge Structural Database (CSD version 5.32 (November 2010) and updates (May 2011)) for structure containing the piperazinium cations yields 248 compounds with the doubly protonated piperazinium(2+) cations and only eight compounds with the singly protonated piperazinium(+) cations. Among these structures only one is the hybrid organic-inorganic material. This is piperazinium nitrate characterized structurally. The crystal packing of [NH{sub 2}(CH{sub 2}){sub 4}NH][BF{sub 4}], phase IV. The

  3. Di-ureasil hybrids doped with LiBF{sub 4}: Spectroscopic study of the ionic interactions and hydrogen bonding

    Energy Technology Data Exchange (ETDEWEB)

    Fernandes, Mariana [Departamento de Quimica/CQ-VR, Universidade de Tras-os-Montes e Alto Douro, 5001-801 Vila Real (Portugal); Barbosa, Paula C.; Manuela Silva, M.; Smith, Michael J. [Departamento de Quimica/Centro de Quimica, Universidade do Minho, Campus de Gualtar, 4710-057 Braga (Portugal); Zea Bermudez, Veronica de, E-mail: vbermude@utad.pt [Departamento de Quimica/CQ-VR, Universidade de Tras-os-Montes e Alto Douro, 5001-801 Vila Real (Portugal)

    2011-09-15

    Highlights: {yields} FT-IR and FT-Raman spectroscopy were used to characterize cation interactions in two LiBF{sub 4}-doped di-ureasil networks incorporating POE chains with different length. {yields} Over the range of salt content analyzed the cations bond to amorphous POE chains and form ion contact pairs with BF{sub 4}{sup -}. {yields} A crystalline POE/LiBF{sub 4} complex of unknown stoichiometry emerges at high salt concentration. - Abstract: In the present work Fourier transform infrared and Raman spectroscopy were used to characterize the cation/polymer, cation/cross-link, cation/anion and hydrogen bonding interactions in hybrid electrolytes composed of lithium tetrafluoroborate (LiBF{sub 4}) and di-urea cross-linked poly(oxyethylene) (POE)/siloxane hybrid networks (di-ureasils) designated as d-U(2000) and d-U(600) and incorporating polyether chains with ca. 40.5 and 8.5 oxyethylene repeat units, respectively. Samples with {infinity} > n {>=} 2.5 (where n, composition, is the molar ratio of CH{sub 2}CH{sub 2}O units per Li{sup +} ion) were analyzed. In both di-ureasil systems over the whole range of salt content examined the Li{sup +} ions bond to the ether oxygen atoms of amorphous POE chains and to BF{sub 4}{sup -} ions forming ion contact pairs. Spectroscopic evidences and SEM images confirm the presence of a crystalline POE/LiBF{sub 4} complex of unknown stoichiometry at n < 20 and 25, respectively. Ionic association is particularly important in the case of the d-U(600)-based materials, as a result of the presence of strong hydrogen-bonded aggregates that prevent the establishment of Li{sup +}/urea carbonyl oxygen atom interactions.

  4. Nuclear inelastic scattering and density functional theory studies of a one-dimensional spin crossover [Fe(1,2,4-triazole)2(1,2,4-triazolato)](BF4) molecular chain.

    Science.gov (United States)

    Jenni, Kevin; Scherthan, Lena; Faus, Isabelle; Marx, Jennifer; Strohm, Cornelius; Herlitschke, Marcus; Wille, Hans-Christian; Würtz, Peter; Schünemann, Volker; Wolny, Juliusz A

    2017-07-26

    Nuclear inelastic scattering (NIS) experiments have been performed in order to study the vibrational dynamics of the low- and high-spin states of the polynuclear 1D spin crossover compound [Fe(1,2,4-triazole) 2 (1,2,4-triazolato)](BF 4 ) (1). Density functional theory (DFT) calculations using the functional B3LYP* and the basis set CEP-31G for heptameric and nonameric models of the compound yielded the normal vibrations and electronic energies for high-spin and low-spin isomers of three models differing in the distribution of anionic trz - ligands and BF 4 - anions. On the basis of the obtained energies a structural model with a centrosymmetric Fe(trzH) 4 (trz - ) 2 coordination core of the mononuclear unit of the chain is proposed. The obtained distribution of the BF 4 - counteranions in the proposed structure is similar to that obtained on the basis of X-ray powder diffraction studies by Grossjean et al. (Eur. J. Inorg. Chem., 2013, 796). The NIS data of the system diluted to 10% Fe(ii) content in a 90% Zn(ii) matrix (compound (2)) show a characteristic change of the spectral pattern of the low-spin centres, compared to the low-spin phase of the parent Fe(ii) complex (1). DFT calculations reveal that this is caused by a change of the structure of the neighbours of the low-spin centres. The spectral pattern of the high-spin centres in (2) is within a good approximation identical to that of the high-spin Fe(ii) isomer of (1). The inspection of the molecular orbitals of the monomeric model systems of [Fe(trzH) 4 (trz - ) 2 ] and [Fe(trzH) 6 ], together with calculations of spin transition energies, point towards the importance of an electrostatic effect caused by the negatively charged ligands. This results in the stabilisation of the low-spin state of the complex containing the anionic ligand and shortening of the Fe-N(trz - ) compared to the Fe-N(trzH) bond in high-spin, but not in low-spin [Fe(trzH) 4 (trz - ) 2 ].

  5. Synthesis of the compound tetrakis (2- methoxy isobutyl isonitrile) copper (I) tetrafluoroborate -(Cu[MIBI]4BF4): substance used in the production of the radiopharmaceutical sestamibi 99m Tc

    International Nuclear Information System (INIS)

    Silva, Katia Suzi da Silveira

    2005-01-01

    The radiopharmaceutical SESTAMIBI- 99m Tc presents interest and application in the clinical routine in Nuclear Medicine, especially for evaluation of the myocardium function and in the diagnosis of some tumors types, and the Center of Radiopharmacy of the IPEN has interest in the development of this radiopharmaceutical for attendance of the nuclear medicine class necessities. In this work it was demonstrated the synthesis and characterization of the active compound tetrakis (2- methoxy isobutyl isonitrile) copper (I) tetrafluoroborate - Cu[MIBI] 4 BF 4 - to be used in the preparation of lyophilized reagents for labeling with technetium- 99m as well as labeling studies and biological distribution. The synthesis of the reagent Cu[MIBI] 4 BF 4 was carried out in accordance with previously described procedures, in 5 steps and the compounds were characterized for infra-red, magnetic nuclear resonance, melting point and thin layer chromatography. The characterization of the chelate of MIBI -Cu[MIBI] 4 BF 4 - was carried out using high performance liquid chromatography, compared with a standard sample of the product and presented similar results, as described in literature. The lyophilized reagent was prepared and labeled with technetium- 99m , showing high radiochemical purity, higher than 97%, with high stability. Biological distribution in different animals showed good uptake in the heart, in time compatible with the acquisition of scintigraphy images, demonstrating the applicability of the reagent synthesized in the attainment of cardiac scintigraphy images. (author)

  6. Electrochemical fabrication of TiO2 nanoparticles/[BMIM]BF4 ionic liquid hybrid film electrode and its application in determination of p-acetaminophen

    International Nuclear Information System (INIS)

    Wang, Bin; Li, Yuan; Qin, Xianjing; Zhan, Guoqing; Ma, Ming; Li, Chunya

    2012-01-01

    A water soluble ionic liquid, 1‐butyl‐3‐methylimidazolium tetrafluoroborate ([BMIM]BF 4 ), was incorporated into TiO 2 nanoparticles to fabricate a hybrid film modified glassy carbon electrode (nano‐TiO 2 /[BMIM]BF 4 /GCE) through electrochemical deposition in a tetrabutyltitanate sol solution containing [BMIM]BF 4 . The obtained nano‐TiO 2 /[BMIM]BF 4 /GCEs were characterized scanning electronic microscopy (SEM) and X‐ray photoelectron spectroscopy (XPS). Electrochemical behaviors of p‐acetaminophen at the nano‐TiO 2 /[BMIM]BF 4 /GCEs were thoroughly investigated. Compared to the redox reaction of p‐acetaminophen using an unmodified electrode under the same conditions, a new reduction peak was observed clearly at 0.26 V with the modified electrode. In addition, the peak potential for the oxidation of p‐acetaminophen was found to shift negatively about 90 mV and the current response increased significantly. These changes indicate that the nano‐TiO 2 /[BMIM]BF 4 hybrid film can improve the redox reactions of p‐acetaminophen in aqueous medium. Under optimum conditions, a linear relationship was obtained for the p‐acetaminophen solutions with concentration in the range from 5.0 × 10 −8 to 5.0 × 10 −5 M. The estimated detection limit was 1.0 × 10 −8 M (S/N = 3). The newly developed method was applied for the determination of p-acetaminophen in urine samples. - Highlights: ► Nano-TiO 2 /[BMIM]BF 4 hybrid film electrode was fabricated with electrodeposition. ► Voltammetric behavior of p-acetaminophen at the obtained electrode was investigated. ► The hybrid film electrode shows good electrocatalytic response to p-acetaminophen. ► p-acetaminophen in urine samples was successfully determined.

  7. Characterization of BF4− in terms of its effect on water by the 1-propanol probing methodology

    DEFF Research Database (Denmark)

    Morita, Takeshi; Ayako, Nitta; Nishikawa, Keilo

    2014-01-01

    One of the most common constituent anions for room temperature ionic liquids (RTILs), BF4−, was characterized in terms of its effect on H2O using the so-called 1-propanol (1P) probing methodology developed by us earlier [PCCP, 15(2013) 14548-14565]. The results indicated that BF4− is quantitatively...

  8. Systematic study of spin crossover and structure in [Co(terpyRX)2](Y)2 systems (terpyRX = 4'-alkoxy-2,2':6',2''-terpyridine, X = 4, 8, 12, Y = BF4(-), ClO4(-), PF6(-), BPh4(-))

    DEFF Research Database (Denmark)

    Nielsen, Pia; Nielsen, Hans Toftlund; Bond, Andrew

    2009-01-01

    A family of spin crossover cobalt(II) complexes of the type [Co(terpyRX)(2)](Y)(2) x nH(2)O (X = 4, 8, 12 and Y = BF(4)(-), ClO(4)(-), PF(6)(-), BPh(4)(-)) has been synthesized, whereby the alkyl chain length, RX, and counteranion, Y, have been systematically varied. The structural (single crystal...

  9. TLR4 activates NF-{kappa}B in human ovarian granulosa tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Woods, Dori C., E-mail: dwoods2@partners.org [Vincent Center for Reproductive Biology, Vincent Obstetrics and Gynecology Service, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02114 (United States); White, Yvonne A.R. [Vincent Center for Reproductive Biology, Vincent Obstetrics and Gynecology Service, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02114 (United States); Dau, Caroline [University of California, San Francisco, School of Dentistry, San Francisco, CA 94143 (United States); Johnson, A.L. [Center for Reproductive Biology and Health, The Pennsylvania State University, University Park, PA 16802 (United States)

    2011-06-17

    Highlights: {yields} TLR4 is expressed in human ovarian granulosa tumor cells. {yields} Acting through TLR4, LPS and HSP60 induce a NF{kappa}B signaling cascade in human ovarian granulosa tumor cells. {yields} NF{kappa}B activation or inhibition did not alter chemosensitivity to TRAIL or cisplatin. -- Abstract: Previous studies have demonstrated expression of Toll-like receptors (TLRs) in the surface epithelium of normal ovaries (OSE) and in epithelial ovarian tumors. Most notably, OSE-derived cancers express TLR4, which activates the nuclear factor-kappa B (NF-{kappa}B) signaling cascade as a mediator of inflammatory response. Currently, there is considerable interest in elucidating the role of TLR-mediated signaling in cancers. Nevertheless, the expression of TLRs in granulosa cell tumors (GCTs) of the ovary, and the extent to which GCT expression of TLRs may influence cell-signaling pathways and/or modulate the efficacy of chemotherapeutics, has yet to be determined. In the present study, human GCT lines (COV434 and KGN) were utilized to evaluate expression of functional TLR4. TLR4 is expressed in GCT cell lines and ligation of TLR4 with bacterial lipopolysaccharide (LPS) led to I{kappa}B degradation and activation of NF-{kappa}B. NF-{kappa}B activation was confirmed by nuclear localization of NF-{kappa}B p65 following treatment with LPS and the naturally occurring ligand, HSP60. Notably, immunoneutralization of TLR4 blocked nuclear localization, and inhibition of NF-{kappa}B signaling attenuated LPS-induced TNF{alpha} plus increased doubling time in both cell lines. Contradictory to reports using human OSE cell lines, inhibition of NF-{kappa}B signaling failed to sensitize GCT lines to TRAIL or cisplatin. In summary, findings herein are the first to demonstrate a functional TLR-signaling pathway specifically in GCTs, and indicate that in contrast to OSE-derived cancers, inhibition of NF-{kappa}B does not sensitize GCTs to TRAIL or cisplatin.

  10. Comparison of the local binding motifs in the imidazolium-based ionic liquids [EMIM][BF{sub 4}] and [EMMIM][BF{sub 4}] through cryogenic ion vibrational predissociation spectroscopy: Unraveling the roles of anharmonicity and intermolecular interactions

    Energy Technology Data Exchange (ETDEWEB)

    Fournier, Joseph A.; Wolke, Conrad T.; Johnson, Christopher J.; Johnson, Mark A., E-mail: mark.johnson@yale.edu, E-mail: mccoy@chemistry.ohio-state.edu [Sterling Chemistry Laboratory, Yale University, New Haven, Connecticut 06520 (United States); McCoy, Anne B., E-mail: mark.johnson@yale.edu, E-mail: mccoy@chemistry.ohio-state.edu [Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio 43210 (United States)

    2015-02-14

    We clarify the role of the critical imidazolium C{sub (2)}H position (the central C between N atoms in the heterocycle) in the assembly motif of the [EMIM][BF{sub 4}] ionic liquid by analyzing the vibrational spectra of the bare EMIM{sup +} ion as well as that of the cationic [EMIM]{sub 2}[BF{sub 4}]{sup +} (EMIM{sup +} = 1-ethyl-3-methylimidazolium, C{sub 6}H{sub 11}N{sub 2}{sup +}) cluster. Vibrational spectra of the cold, mass-selected ions are obtained using cryogenic ion vibrational predissociation of weakly bound D{sub 2} molecules formed in a 10 K ion trap. The C{sub (2)}H behavior is isolated by following the evolution of key vibrational features when the C{sub (2)} hydrogen, the proposed binding location of the anion to the imidazolium ring, is replaced by either deuterium or a methyl group (i.e., in the EMMIM{sup +} analogue). Strong features in the ring CH stretching region of the bare ion are traced to Fermi resonances with overtones of lower frequency modes. Upon incorporation into the EMIM{sup +} ⋅ ⋅ ⋅ BF{sub 4}{sup −} ⋅ ⋅ ⋅ EMIM{sup +} ternary complex, the C{sub (2)}H oscillator strength is dramatically increased, accounting for the much more complicated patterns derived from the EMIM{sup +} ring CH stretches in the light isotopomer, which are strongly suppressed in the deuterated analogue. Further changes in the spectra that occur when the C{sub (2)}H is replaced by a methyl group are consistent with BF{sub 4}{sup −} attachment directly to the imidazolium ring in an arrangement that maximizes the electrostatic interaction between the molecular ions.

  11. Exposure to 4-tert-octylphenol, an environmentally persistent alkylphenol, enhances interleukin-4 production in T cells via NF-AT activation

    International Nuclear Information System (INIS)

    Lee, Mi H.; Kim, Eugene; Kim, Tae S.

    2004-01-01

    4-tert-Octylphenol (OP) is a representative endocrine disruptor that may have adverse effects on human health. The influence of this compound on allergic immune responses remains unclear. In this study, we have examined the effects of OP on production of interleukin-4 (IL-4), a pro-inflammatory cytokine closely associated with allergic immune responses. OP significantly enhanced IL-4 production in antigen-primed T cells in a dose-dependent manner. Treatment with OP in vivo resulted in significant increase of IL-4 production in T cells and of IgE levels in sera of antigen-primed mice. Furthermore, OP enhanced the activation of IL-4 gene promoter in EL4 T cells transiently transfected with IL-4 promoter/reporter constructs, and the enhancing effect mapped to a region in the IL-4 promoter containing binding sites for nuclear factor of activated T cell (NF-AT). Activation of T cells by phorbol-12-myristate-13-acetate (PMA) resulted in markedly enhanced binding activities to the NF-AT site, which significantly increased upon addition of OP, indicating that the transcription factor NF-AT was involved in the enhancing effect of OP on IL-4 production. The enhancement of IL-4 production by OP was blocked by FK506, a calcineurin inhibitor, but not by the estrogen receptor (ER) antagonist ICI 182 780. FK506 inhibited the NF-AT-DNA binding activity and IL-4 gene promoter activity enhanced by OP in a dose-dependent manner. These findings demonstrate that OP enhances IL-4 production in T cells via the stimulation of calcineurin-dependent NF-AT activation

  12. The reaction of Cs{sub 2}[Tc(NO)F{sub 5}] with BF{sub 3} in acetonitrile. Formation and structure of [{Tc(NO)(CH_3CN)_4}{sub 2}(μ-F)](BF{sub 4}){sub 3}

    Energy Technology Data Exchange (ETDEWEB)

    Balasekaran, Samundeeswari Mariappan [Institute of Chemistry and Biochemistry, Freie Universitaet Berlin (Germany); Department of Chemistry, University of Nevada, Las Vegas, NV (United States); Hagenbach, Adelheid; Spandl, Johann; Abram, Ulrich [Institute of Chemistry and Biochemistry, Freie Universitaet Berlin (Germany)

    2017-10-04

    The deep blue, paramagnetic Cs{sub 2}[Tc{sup II}(NO)F{sub 5}] is formed during reactions of pertechnetate, acetohydroxamic acid, and CsF in aqueous HF. A reaction of Cs{sub 2}[Tc(NO)F{sub 5}] with BF{sub 3}.MeOH in acetonitrile gives yellow blocks of the fluorido-bridged dimer [{Tc"I(NO)(CH_3CN)_4}{sub 2}F](BF{sub 4}){sub 3}. The compound is stable as solid and in acetonitrile solutions. The complex cation contains a bent μ-F{sup -} ligand and two linear nitrosyl groups. (copyright 2017 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  13. Synthesis and characterization of ionic liquid (EMImBF{sub 4})/Li{sup +} - chitosan membranes for ion battery

    Energy Technology Data Exchange (ETDEWEB)

    Pasaribu, Marvin H., E-mail: marvin-shady88@yahoo.com; Arcana, I Made, E-mail: arcana@chem.itb.ac.id; Wahyuningrum, Deana, E-mail: deana@chem.itb.ac.id [Department of Chemistry, Faculty of Mathematics and Natural Sciences, InstitutTeknologi Bandung, Jl. Ganesha No. 10, Bandung 40132 (Indonesia)

    2015-09-30

    Lithium ion battery has been currently developed and produced because it has a longer life time, high energycapacity, and the efficient use of lithium ion battery that is suitable for storing electrical energy. However, this battery has some drawbacks such as use liquid electrolytes that are prone to leakage and flammability during the battery charging process in high temperature. In this study, an ionic liquid 1-ethyl-3-methylimidazolium tetrafluoroborate (EMImBF4) containing Li{sup +} ions was synthesized and combined with chitosan polymer host as a polymer electrolyte membrane for lithium-ion batteries to solve this problems. This ionic liquid was obtained from the anion metathesis reaction between EMImBr and LiBF4 salt, while EMImBr was synthesized from the reaction between 1-methylimidazole and ethyl bromide utilizing Microwave Assisted Organic Synthesis (MAOS) method. The ionic liquid obtained was characterized by microstructure analysis with using NMR and FTIR spectroscopy. The polymer electrolyte membrane was characterized by analysis functional groups (FTIR), ionic conductivity (EIS), and surface morphology (SEM). The analysis results of ion conductivity by the EIS method showed the increase the ionic conductivity value of membranes from 1.30 × 10{sup −2} S cm{sup −1} for chitosan to 1.30 × 10{sup −2} S cm{sup −1} for chitosan with EMImBF4/Li{sup +}, and this result was supported by analysis the surface morphology (SEM)

  14. TLR4 activates NF-κB in human ovarian granulosa tumor cells

    International Nuclear Information System (INIS)

    Woods, Dori C.; White, Yvonne A.R.; Dau, Caroline; Johnson, A.L.

    2011-01-01

    Highlights: → TLR4 is expressed in human ovarian granulosa tumor cells. → Acting through TLR4, LPS and HSP60 induce a NFκB signaling cascade in human ovarian granulosa tumor cells. → NFκB activation or inhibition did not alter chemosensitivity to TRAIL or cisplatin. -- Abstract: Previous studies have demonstrated expression of Toll-like receptors (TLRs) in the surface epithelium of normal ovaries (OSE) and in epithelial ovarian tumors. Most notably, OSE-derived cancers express TLR4, which activates the nuclear factor-kappa B (NF-κB) signaling cascade as a mediator of inflammatory response. Currently, there is considerable interest in elucidating the role of TLR-mediated signaling in cancers. Nevertheless, the expression of TLRs in granulosa cell tumors (GCTs) of the ovary, and the extent to which GCT expression of TLRs may influence cell-signaling pathways and/or modulate the efficacy of chemotherapeutics, has yet to be determined. In the present study, human GCT lines (COV434 and KGN) were utilized to evaluate expression of functional TLR4. TLR4 is expressed in GCT cell lines and ligation of TLR4 with bacterial lipopolysaccharide (LPS) led to IκB degradation and activation of NF-κB. NF-κB activation was confirmed by nuclear localization of NF-κB p65 following treatment with LPS and the naturally occurring ligand, HSP60. Notably, immunoneutralization of TLR4 blocked nuclear localization, and inhibition of NF-κB signaling attenuated LPS-induced TNFα plus increased doubling time in both cell lines. Contradictory to reports using human OSE cell lines, inhibition of NF-κB signaling failed to sensitize GCT lines to TRAIL or cisplatin. In summary, findings herein are the first to demonstrate a functional TLR-signaling pathway specifically in GCTs, and indicate that in contrast to OSE-derived cancers, inhibition of NF-κB does not sensitize GCTs to TRAIL or cisplatin.

  15. Dexmedetomidine reduces ventilator-induced lung injury (VILI by inhibiting Toll-like receptor 4 (TLR4/nuclear factor (NF-κB signaling pathway

    Directory of Open Access Journals (Sweden)

    Hongli Chen

    2018-02-01

    Full Text Available Mechanical ventilation (MV may lead to ventilator-induced lung injury (VILI. Previous research has shown that dexmedetomidine attenuates pulmonary inflammation caused by MV, but the underlying mechanisms remain unclear. Our study aims to test whether dexmedetomidine has a protective effect against VILI and to explore the possible molecular mechanisms using the rat model. Thirty adult male Wistar rats weighing 200-250 g were randomly assigned to 5 groups (n = 6: control, low tidal volume MV (LMV, high tidal volume (HVT MV (HMV, HVT MV + dexmedetomidine (DEX, HVT MV + dexmedetomidine + yohimbine (DEX+Y. Rats were euthanized after being ventilated for 4 hours. Pathological changes, lung wet/dry (W/D weight ratio, lung myeloperoxidase (MPO activity, levels of inflammatory cytokines (i.e., interleukin [IL]-1β, tumor necrosis factor alpha [TNF-α], and IL-6 in the bronchoalveolar lavage fluid (BALF and lung tissues, expression of Toll-like receptor 4 (TLR4 and nuclear factor (NF-κB, and activation of NF-κB in lung tissues were measured. Compared with HMV, DEX group showed fewer pathological changes, lower W/D ratios and decreased MPO activity of the lung tissues and lower concentrations of the inflammatory cytokines in the BALF and lung tissues. Dexmedetomidine significantly inhibited the expression of TLR4 and NF-κB and activation of NF-κB. Yohimbine partly alleviated the effects of dexmedetomidine. Dexmedetomidine reduced the inflammatory response to HVT-MV and had a protective effect against VILI, with the inhibition of the TLR4/NF-κB signaling pathway, at least partly via α2-adrenoceptors.

  16. Design, synthesis and photoelectrochemical properties of hexagonal metallomacrocycles based on triphenylamine: [M6(4,4'-bis(2,2':6',2''-terpyridinyl)triphenylamine)6(X)12]; [M = Fe(II), PF6- and Zn(II), BF4-].

    Science.gov (United States)

    Hwang, Seok-Ho; Moorefield, Charles N; Wang, Pingshan; Fronczek, Frank R; Courtney, Brandy H; Newkome, George R

    2006-08-07

    Synthesis of a novel bis(terpyridine) ligand, 4,4'-bis(2,2':6',2''-terpyridinyl)triphenylamine, utilizing triphenylamine, as a specific angle controller, has led to the self-assembly of a unique hexagonal metallomacrocycle family, [Fe6(2)6(PF6)12] and [Zn6(2)6(BF4)12], utilizing terpyridine-metal(II)-terpyridine connectivity. The crystal structure of the novel ligand shows that the angle between the two terpyridinyl moieties is 119.69 degrees , which enabled the formation of the hexagonal-shaped macrocycles. The crystal packing architectures of this starting ligand revealed channels induced by solvent encapsulation. Following complexation of this ligand with transition metals [Fe(II) or Zn(II)] in a one-pot reaction, the resultant structures were characterized by (1)H and (13)C NMR, UV/Vis and mass spectroscopies. The expected metal-to-ligand charge transfer (MLCT; lambda(max) = 582 nm) and emission (lambda(em) = 575 nm) characteristics were exhibited by both [Fe6(2)6(PF6)12] and[Zn6(2)6(BF4)12]. The photoelectrochemical characteristics of these hexagonal metallomacrocycles demonstrate that they can be used as sensitizers in dye-sensitized solar cells.

  17. Electrodes for the hydrogen through water electrolysis using BMI.BF{sub 4} as electrolyte; Eletrodos para a producao de hidrogenio via eletrolise da agua utilizando BMI.BF{sub 4} como eletrolito

    Energy Technology Data Exchange (ETDEWEB)

    Botton, Janine Padilha; Martini, Emilse M.A.; Souza, Michele Oberson de; Souza, Roberto Fernando de [Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS (Brazil). Inst. de Quimica. Lab. de Eletroquimica e Catalise]. E-mail: janine@iq.ufrgs.br; Loget, Gabriel [Universite de Rennes 1, Rennes (France). Lab. de Eletroquimica Molecular e Macromolecular. UMR CNRS 6510

    2008-07-01

    The hydrogen production by water electrolysis was tested with different electrocatalysts (nickel, iron alloys containing nickel, chromium and manganese, and molybdenum) in the ionic liquid electrolyte, 1-butyl-3-methylimidazolium tetrafluoroborate (BMI.BF{sub 4}), 10 vol.% in water. The hydrogen evolution reaction (HER) worked at room temperature with a platinum quasi-reference electrode (PtQRE) applying a -1.7 V potential. The experimental conditions used were determined in previous work and such parameters of operation were confirmed with the electrocatalysts employed in this work. A Hoffman cell apparatus was used to perform the water electrolysis. The current density values, j, obtained were between 3.0 mA cm{sup -2} and 77.5 mA cm{sup -2}. The system efficiency was very high for all electrocatalysts tested, between 97.0% and 99.2%. The molybdenum (Mo) electrode was better than others showing the highest current density value in HER. This behavior has been explained by the lower value of activation energy for the electrolysis reaction when Mo is employed comparing with Pt electrode. The energy activation of the HER using platinum (Pt) as electrocatalyst in an aqueous solution of BMI.BF{sub 4} 10 vol.% was 23.40 kJ mol{sup -1}, whereas with electrode of Mo in the same conditions , was 9.22 kJ mol{sup -1}. In an alkaline aqueous electrolyte (usual medium for such reaction), Mo is less efficient than Pt explaining the lack of published citation using pure Mo as cathode for the HER. The excellent results obtained with a Mo electrode employing ionic liquid as electrolyte show that the hydrogen production can be carried out with cheap electrode material at room temperature, which makes this method economically attractive. (author)

  18. Characteristics of ZnO nanostructures produced with [DMIm]BF{sub 4} using ultrasonic radiation

    Energy Technology Data Exchange (ETDEWEB)

    Rahman, I. B. Abdul; Ayob, M. T. M.; Ishak, I. S.; Mohd Lawi, R. L.; Isahak, W. N. R. W.; Hamid, M. H. N. Abd; Othman, N. K.; Radiman, S. [School of Applied Physics, Faculty of Science and Technology (FST), Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor Darul Ehsan (Malaysia); School of Chemistry and Food Technology, Faculty of Science and Technology (FST), Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor Darul Ehsan (Malaysia); School of Applied Physics, Faculty of Science and Technology (FST), Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor Darul Ehsan (Malaysia)

    2012-11-27

    Great interests in metallic oxides have emerged because of the promising properties of these materials for various applications such as solar cells and sensors. ZnO nanostructures with different morphologies were successfully synthesized from Zn(CH{sub 3}COO){sub 2} Bullet 2H{sub 2}O, NaOH and room temperature ionic liquid (RTIL) 1-decyl-3-methylimidazolium tetrafluoroborate, [DMIm][BF{sub 4}] with ultrasound irradiation. Parameters such as the effect of sonication time (30, 60 and 90 minutes) and Zn(Ac){sub 2} precursor to [DMIm][BF{sub 4}] ratios of 3:5, 5:5 and 5:3 were investigated. X-ray diffraction patterns revealed that the ZnO nanocrystals were hexagonal zincite crystalline in structure. The band gap energies (E{sub g}) were estimated to be 3.35-3.55 eV from the UV-Visible spectrum. The solution with the highest ratio of Zn was analysed with photoluminescence spectroscopy, which exhibited peaks at 362, 403, 468 and 539 nm, at room temperature. The micrographs of field emission scanning electron microscopy and transmission electron microscopy showed that the synthesis products were spherical (30-60 nm), spindle ({approx}10 Multiplication-Sign 70 nm for width Multiplication-Sign length) and whisker-like (100-200 nm), with their dimensions decreasing systematically with increased sonication time. Chemical compositions were approximated at 1:1 for Zn and O, estimated by electron dispersive x-ray spectrum.

  19. Eukaryotic Initiation Factor 4H Is under Transcriptional Control of p65/NF-κB

    Science.gov (United States)

    Fiume, Giuseppe; Rossi, Annalisa; de Laurentiis, Annamaria; Falcone, Cristina; Pisano, Antonio; Vecchio, Eleonora; Pontoriero, Marilena; Scala, Iris; Scialdone, Annarita; Masci, Francesca Fasanella; Mimmi, Selena; Palmieri, Camillo; Scala, Giuseppe; Quinto, Ileana

    2013-01-01

    Protein synthesis is mainly regulated at the initiation step, allowing the fast, reversible and spatial control of gene expression. Initiation of protein synthesis requires at least 13 translation initiation factors to assemble the 80S ribosomal initiation complex. Loss of translation control may result in cell malignant transformation. Here, we asked whether translational initiation factors could be regulated by NF-κB transcription factor, a major regulator of genes involved in cell proliferation, survival, and inflammatory response. We show that the p65 subunit of NF-κB activates the transcription of eIF4H gene, which is the regulatory subunit of eIF4A, the most relevant RNA helicase in translation initiation. The p65-dependent transcriptional activation of eIF4H increased the eIF4H protein content augmenting the rate of global protein synthesis. In this context, our results provide novel insights into protein synthesis regulation in response to NF-κB activation signalling, suggesting a transcription-translation coupled mechanism of control. PMID:23776612

  20. Constitutive overexpression of the TaNF-YB4 gene in transgenic wheat significantly improves grain yield.

    Science.gov (United States)

    Yadav, Dinesh; Shavrukov, Yuri; Bazanova, Natalia; Chirkova, Larissa; Borisjuk, Nikolai; Kovalchuk, Nataliya; Ismagul, Ainur; Parent, Boris; Langridge, Peter; Hrmova, Maria; Lopato, Sergiy

    2015-11-01

    Heterotrimeric nuclear factors Y (NF-Ys) are involved in regulation of various vital functions in all eukaryotic organisms. Although a number of NF-Y subunits have been characterized in model plants, only a few have been functionally evaluated in crops. In this work, a number of genes encoding NF-YB and NF-YC subunits were isolated from drought-tolerant wheat (Triticum aestivum L. cv. RAC875), and the impact of the overexpression of TaNF-YB4 in the Australian wheat cultivar Gladius was investigated. TaNF-YB4 was isolated as a result of two consecutive yeast two-hybrid (Y2H) screens, where ZmNF-YB2a was used as a starting bait. A new NF-YC subunit, designated TaNF-YC15, was isolated in the first Y2H screen and used as bait in a second screen, which identified two wheat NF-YB subunits, TaNF-YB2 and TaNF-YB4. Three-dimensional modelling of a TaNF-YB2/TaNF-YC15 dimer revealed structural determinants that may underlie interaction selectivity. The TaNF-YB4 gene was placed under the control of the strong constitutive polyubiquitin promoter from maize and introduced into wheat by biolistic bombardment. The growth and yield components of several independent transgenic lines with up-regulated levels of TaNF-YB4 were evaluated under well-watered conditions (T1-T3 generations) and under mild drought (T2 generation). Analysis of T2 plants was performed in large deep containers in conditions close to field trials. Under optimal watering conditions, transgenic wheat plants produced significantly more spikes but other yield components did not change. This resulted in a 20-30% increased grain yield compared with untransformed control plants. Under water-limited conditions transgenic lines maintained parity in yield performance. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  1. SMAD4 and NF1 mutations as potential biomarkers for poor prognosis to cetuximab-based therapy in Chinese metastatic colorectal cancer patients.

    Science.gov (United States)

    Mei, Zhu; Shao, Yang W; Lin, Peinan; Cai, Xiaomin; Wang, Biao; Ding, Yan; Ma, Xiangyuan; Wu, Xue; Xia, Yewei; Zhu, Dongqin; Shu, Yongqian; Fu, Zan; Gu, Yanhong

    2018-04-27

    Cetuximab, an anti-EGFR monoclonal antibody, is used in combination with chemotherapy in clinic to enhance the outcome in metastatic colorectal cancer (mCRC) patients with only ~ 20% response rate. To date only activating mutations in KRAS and NRAS have been identified as poor prognosis biomarkers in cetuximab-based treatment, which makes an urgent need for identification of novel prognosis biomarkers to precisely predict patients' response in order to maximize the benefit. In this study, we analysed the mutation profiles of 33 Chinese mCRC patients using comprehensive next-generation sequencing (NGS) targeting 416 cancer-relevant genes before cetuximab treatment. Upon receiving cetuximab-based therapy, patients were evaluated for drug response, and the progression-free survival (PFS) was monitored. The association of specific genetic alterations and cetuximab efficacy was analyzed. Patients carrying SMAD4 mutations (SMAD4 mut , n = 8) or NF1 mutations (NF1 mut , n = 4) had significantly shorter PFS comparing to those carrying wildtype SMAD4 (SMAD4 wt , n = 25) (P = 0.0081) or wildtype NF1 (NF1 wt , n = 29) (P = 0.0028), respectively. None of the SMAD4 mut or NF1 mut patients showed response to cetuximab when assessed at 12-week post-treatment. Interestingly, two patients carrying both SMAD4 mut and NF1 mut showed the shortest PFS among all the patients. Our results demonstrated that SMAD4 and NF1 mutations can serve as potential biomarkers for poor prognosis to cetuximab-based therapy in Chinese mCRC patients.

  2. Resveratrol (trans-3,5,4'-trihydroxystilbene) suppresses EL4 tumor growth by induction of apoptosis involving reciprocal regulation of SIRT1 and NF-κB.

    Science.gov (United States)

    Singh, Narendra P; Singh, Udai P; Hegde, Venkatesh L; Guan, Hongbing; Hofseth, Lorne; Nagarkatti, Mitzi; Nagarkatti, Prakash S

    2011-08-01

    Understanding the molecular mechanisms through which natural products and dietary supplements exhibit anticancer properties is crucial and can lead to drug discovery and chemoprevention. The current study sheds new light on the mode of action of resveratrol (RES), a plant-derived polyphenolic compound, against EL-4 lymphoma growth. Immuno-compromised NOD/SCID mice injected with EL-4 tumor cells and treated with RES (100 mg/kg body weight) showed delayed development and progression of tumor growth and increased mean survival time. RES caused apoptosis in EL4 cells through activation of aryl hydrocarbon receptor (AhR) and upregulation of Fas and FasL expression in vitro. Blocking of RES-induced apoptosis in EL4 cells by FasL mAb, cleavage of caspases and PARP, and release of cytochorme c, demonstrated the participation of both extrinsic and intrinsic pathways of apoptosis. RES also induced upregulation of silent mating type information regulation 2 homolog, 1 (SIRT1) and downregulation of nuclear factor kappa B (NF-κB) in EL4 cells. siRNA-mediated downregulation of SIRT1 in EL4 cells increased the activation of NF-κB but decreased RES-mediated apoptosis, indicating the critical role of SIRT1 in apoptosis via blocking activation of NF-κB. These data suggest that RES-induced SIRT1 upregulation promotes tumor cell apoptosis through negative regulation of NF-κB, leading to suppression of tumor growth. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. PSMB4 promotes multiple myeloma cell growth by activating NF-κB-miR-21 signaling

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Peihao; Guo, Honggang [Department of Hematology, Navy General Hospital, Beijing 100048 (China); Li, Guangchao [School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006 (China); Han, Siqi [Department of Medical Oncology, Jinling Hospital, Nanjing 210002 (China); Luo, Fei [Department of Stomatology, Jinling Hospital, Nanjing 210002 (China); Liu, Yi, E-mail: liuyi2033@163.com [Department of Hematology, Navy General Hospital, Beijing 100048 (China)

    2015-03-06

    Proteasomal subunit PSMB4, was recently identified as potential cancer driver genes in several tumors. However, the regulatory mechanism of PSMB4 on carcinogenesis process remains unclear. In this study, we investigated the expression and roles of PSMB4 in multiple myeloma (MM). We found a significant up-regulation of PSMB4 in MM plasma and cell lines. Ectopic overexpression of PSMB4 promoted cell growth and colony forming ability of MM cells, whereas inhibition of PSMB4 led to a decrease of such events. Furthermore, our results demonstrated the up-regulation of miR-21 and a positive correlation between the levels of miR-21 and PSMB4 in MM. Re-expression of miR-21 markedly rescued PSMB4 knockdown-mediated suppression of cell proliferation and clone-formation. Additionally, while enforced expression of PSMB4 profoundly increased NF-κB activity and the level of miR-21, PSMB4 knockdown or NF-κB inhibition suppressed miR-21 expression in MM cells. Taken together, our results demonstrated that PSMB4 regulated MM cell growth in part by activating NF-κB-miR-21 signaling, which may represent promising targets for novel specific therapies. - Highlights: • First reported upregulation of PSMB4 in MM plasma and cell lines. • PSMB4 promoted MM cell growth and colony forming ability. • Further found miR-21 was up-regulated by PSMB4 in MM plasma and cell lines. • PSMB4-induced miR-21 expression was modulated by NF-κB. • PSMB4-NF-κB-miR-21 axis may be potential therapeutic targets of MM.

  4. Study of thermal spin crossover in [Fe(II)(isoxazole)(6)](BF4)(2) with Mossbauer spectroscopy

    NARCIS (Netherlands)

    Bhattacharjee, A.; van Koningsbruggen, P. J.; Hibbs, W.; Miller, Joel S.; Guetlich, P.

    2007-01-01

    Fe-57 Mossbauer spectroscopy of the mononuclear [Fe( II)( isoxazole)(6)]( BF4)(2) compound has been studied to reveal the thermal spin crossover of Fe( II) between low- spin ( S = 0) and high- spin ( S = 2) states. A temperature-dependent spin transition curve has been constructed with the least-

  5. Andrographolide inhibits multiple myeloma cells by inhibiting the TLR4/NF-κB signaling pathway.

    Science.gov (United States)

    Gao, Hui; Wang, Jianrong

    2016-02-01

    Andrographolide is an active component from the extract of Andrographis paniculata [(Burm.f) Nees], a medicinal plant from the Acanthaceae family. Pharmacological studies have revealed that andrographolide possesses anti-bacterial, anti-inflammatory, anti-viral, immune regulatory and hepatoprotective properties, and is efficacious in the treatment of cardiovascular diseases, while exhibiting low toxicity and low cost. The present study aimed to determine the inhibitory effects of andrographolide on the growth of multiple myeloma (MM) cells and its possible impact on the Toll-like receptor (TLR)4/nuclear factor (NF)-κB signaling pathway. Cell proliferation was detected using an MTT assay, cellular apoptosis was measured using flow cytometry, and caspase-9/3 activation were assessed using colorimetric assay kits. Furthermore, TLR4 and NF-κB protein expression was determined by western blot analysis. The results revealed that andrographolide reduced the proliferation, while increasing cellular apoptosis and caspase-9/3 activation of MM cells, in addition to downregulating the expression of TLR4 and NF-κB protein. Of note, TLR4- or NF-κB-targeting small-interfering (si)RNA enhanced the andrographolide-induced inhibition of cell proliferation and induction of apoptosis of MM cells. The results of the present study therefore suggested that andrographolide inhibited multiple myeloma cells via the TLR4/NF-κB signaling pathway.

  6. Rate theory of solvent exchange and kinetics of Li(+) - BF4 (-)/PF6 (-) ion pairs in acetonitrile.

    Science.gov (United States)

    Dang, Liem X; Chang, Tsun-Mei

    2016-09-07

    In this paper, we describe our efforts to apply rate theories in studies of solvent exchange around Li(+) and the kinetics of ion pairings in lithium-ion batteries (LIBs). We report one of the first computer simulations of the exchange dynamics around solvated Li(+) in acetonitrile (ACN), which is a common solvent used in LIBs. We also provide details of the ion-pairing kinetics of Li(+)-[BF4] and Li(+)-[PF6] in ACN. Using our polarizable force-field models and employing classical rate theories of chemical reactions, we examine the ACN exchange process between the first and second solvation shells around Li(+). We calculate exchange rates using transition state theory and weighted them with the transmission coefficients determined by the reactive flux, Impey, Madden, and McDonald approaches, and Grote-Hynes theory. We found the relaxation times changed from 180 ps to 4600 ps and from 30 ps to 280 ps for Li(+)-[BF4] and Li(+)-[PF6] ion pairs, respectively. These results confirm that the solvent response to the kinetics of ion pairing is significant. Our results also show that, in addition to affecting the free energy of solvation into ACN, the anion type also should significantly influence the kinetics of ion pairing. These results will increase our understanding of the thermodynamic and kinetic properties of LIB systems.

  7. Fe4 cluster and a buckled macrocycle complex from the reduction of [(dmgBF2)2Fe(L)2] (L = MeCN, (t)Bu(i)NC).

    Science.gov (United States)

    Rose, Michael J; Winkler, Jay R; Gray, Harry B

    2012-02-20

    We report the syntheses, X-ray structures, and reductive electrochemistry of the Fe(II) complexes [(dmgBF(2))(2)Fe(MeCN)(2)] (1; dmg = dimethylglyoxime, MeCN = acetonitrile) and [(dmgBF(2))Fe((t)Bu(i)NC)(2)] (2; (t)Bu(i)NC = tert-butylisocyanide). The reaction of 1 with Na/Hg amalgam led to isolation and the X-ray structure of [(dmgBF(2))(2)Fe(glyIm)] (3; glyIm = glyimine), wherein the (dmgBF(2))(2) macrocyclic frame is bent to accommodate the binding of a bidentate apical ligand. We also report the X-ray structure of a rare mixed-valence Fe(4) cluster with supporting dmg-type ligands. In the structure of [(dmg(2)BF(2))(3)Fe(3)((1)/(2)dmg)(3)Fe(O)(6)] (4), the (dmgBF(2))(2) macrocycle has been cleaved, eliminating BF(2) groups. Density functional theory calculations and electron paramagnetic resonance data are in accordance with a central Fe(III) ion surrounded by three formally Fe(II)dmg(2)BF(2) units.

  8. Electroreduction Property and MD Simulation of Nitrobenzene in Ionic Liquid [BMim][Tf2N]/[BMim][BF4

    International Nuclear Information System (INIS)

    Zeng, Jianping; Zhang, Yinxu; Sun, Ruyao; Chen, Song

    2014-01-01

    Highlights: • The two different common accessible ionic liquids are mixed in a simple and economic way. • In some compound ratios, the dynamic performance of nitrobenzene is superior to either of ionic liquids. • Modification and functionalization of ionic liquids in electrochemical field is feasible. • The mass transfer of diffusion of nitrobenzene in ionic liquids can be simulated with molecular dynamics. • Molecular dynamics explains the improvement of nitrobenzene in composite ionic liquids. - Abstract: The two different common accessible ionic liquids [BMim][BF 4 ] and [BMim][Tf 2 N] were mixed each other in a simple and economic way. In some compound ratios, the dynamic performance of nitrobenzene in electric reduction was superior to that of any single kind of ionic liquid has been appeared. The interaction and mass transfer of diffusion of nitrobenzene in composite ionic liquids with different volume ratios were studied with molecular dynamics (MD) simulation. The improvement of the electroreduction performance of nitrobenzene in composite ionic liquids was verified and was tried to explain. This provides a new idea for the modification and functionalization of ionic liquids in electrochemical field. The experimental results showed that kinematic viscosity and electroconductibility of different ionic liquid systems display a regular change. And the change law has been basically unchanged after adding water. The two different functional ionic liquids were complemented each other in a simple and economic way, which has compensated for the disadvantage of mono-component ionic liquids. At 25 °C, electroreduction property of V [BMim][BF4] :V [BMim][Tf2N] = 1:1 is the best in cyclic voltammetry experiments of nitrobenzene in different composite ionic liquids. Its electrochemical behavior is significantly affected by scan rate, temperature, concentration of nitrobenzene and concentration of water. The MD simulation results showed most of interaction

  9. Effect of bone marrow-derived CD11b(+)F4/80 (+) immature dendritic cells on the balance between pro-inflammatory and anti-inflammatory cytokines in DBA/1 mice with collagen-induced arthritis.

    Science.gov (United States)

    Fu, Jingjing; Zhang, Lingling; Song, Shanshan; Sheng, Kangliang; Li, Ying; Li, Peipei; Song, Shasha; Wang, Qingtong; Chu, Jianhong; Wei, Wei

    2014-05-01

    To explore the effect of bone marrow-derived CD11b(+)F4/80(+) immature dendritic cells (BM CD11b(+)F4/80(+)iDC) on the balance between pro-inflammatory and anti-inflammatory cytokines in DBA/1 mice with collagen-induced arthritis (CIA). BM CD11b(+)F4/80(+)iDC were induced with rmGM-CSF and rmIL-4, and were identified by the expressions of toll-like receptor 2 (TLR-2), indoleamine 2,3-deoxygenase (IDO), interleukin (IL)-10, transforming growth factor (TGF)-β1 and mixed leukocyte reaction (MLR). CIA was established in DBA/1 mice by immunization with type II collagen. CIA mice were injected intravenously with BM CD11b(+)F4/80(+)iDC three times after immunization. The effect of BM CD11b(+)F4/80(+)iDC on CIA was evaluated by the arthritis index, joint histopathology, body weight, thymus index, thymocytes proliferation, IL-1β, tumor necrosis factor (TNF)-α, IL-17, IL-10 and TGF-β1 levels. BM CD11b(+)F4/80(+)iDC induced with rmGM-CSF and rmIL-4 expressed high levels of TLR-2, IDO, IL-10 and TGF-β1. Infusion of BM CD11b(+)F4/80(+)iDC in CIA mice significantly reduced the arthritis index and pathological scores of joints, recovered the weight, decreased the thymus index and inhibited thymocyte proliferation. Levels of IL-1β, TNF-α and IL-17 were decreased in BM CD11b(+)F4/80(+)iDC-treated mice. BM CD11b(+)F4/80(+)iDC can be induced successfully with rmGM-CSF and rmIL-4. BM CD11b(+)F4/80(+)iDC treatment can ameliorate the development and severity of CIA by regulating the balance between pro-inflammatory cytokines and anti-inflammatory cytokines.

  10. Effect of the Total Extract of Averrhoacarambola (Oxalidaceae Root on the Expression Levels of TLR4 and NF-κB in Streptozotocin-Induced Diabetic Mice

    Directory of Open Access Journals (Sweden)

    Xiaohui Xu

    2015-07-01

    Full Text Available Background: Averrhoacarambola L., which is a folk medicine used in diabetes mellitus (DM in ancient China, has been reported to have anti-diabetic efficacy. Aims: The aim of this study was to evaluate the hypoglycemic effect of the extract of Averrhoacarambola L. root (EACR on the regulation of the Toll-like receptor 4 (TLR4-Nuclear-factor kappa B (NF-κB pathway in B pathway in streptozotocin (STZ-induced diabetic mice. Methods: the mice were injected with STZ (120 mg/kg body weight via a tail vein. After 72 h, the mice with FBG = 11.1 mmol/L were confirmed as having diabetes. Subsequently, the mice were treated intragastrically with EACR (300, 600, 1200 mg/kg body weight/d and metformin (320 mg/kg body weight/d for 14 days. Results: As a result the serum fasting blood glucose (FBG, interleukin-6 (IL-6 and tumor necrosis factor-a (TNF-a levels were decreased following EACR administration. Immunohistochemical analysis revealed that the pancreatic tissue expression levels of TLR4 and NF-κB were downregulated after EACR administration. EACR suppressed pancreatic mRNA expression level of TLR4 and blocked the downstream NF-κB pathway in the pancreas. According to Western blot analysis EACR suppressed pancreatic TLR4 and NF-κB protein expression levels. Histopathological examination of the pancreas showed that STZ-induced pancreas lesions were alleviated by the EACR treatment. Conclusion: These findings suggest that the modulation of the IL-6 and TNF-a inflammatory cytokines and the suppression of the TLR4-NF-κB pathway are most likely involved in the anti-hyperglycemic effect of EACR in STZ-induced diabetic mice.

  11. [Gallic acid inhibits inflammatory response of RAW264.7 macrophages by blocking the activation of TLR4/NF-κB induced by LPS].

    Science.gov (United States)

    Huang, Lihua; Hou, Lin; Xue, Hainan; Wang, Chunjie

    2016-12-01

    Objective To observe the influence of gallic acid on Toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) pathway in the RAW264.7 macrophages stimulated by lipopolysaccharide (LPS). Methods RAW264.7 macrophages were divided into the following groups: control group, LPS group, LPS combined with gallic acid group, LPS combined with pyrrolidine dithiocarbamate (PDTC) group and LPS combined with dexamethasone (DM) group. RAW264.7 cells were cultured for 24 hours after corresponding treatments. The levels of tumor necrosis factor α (TNF-α), interleukin-1 (IL-1) and IL-6 were detected by ELISA. The levels of TLR4 and NF-κB mRNAs were tested by real-time PCR. The levels of p-IκBα, p65, p-p65 and TLR4 proteins were examined by Western blotting. Results The expression levels of TNF-α, IL-1 and IL-6 were up-regulated in the RAW264.7 macrophages after stimulated by LPS. Gallic acid could reduce the elevated expression levels of TNF-α, IL-1 and IL-6 induced by LPS. The expression of TLR4 significantly increased after stimulated by LPS and NF-κB was activated. Gallic acid could reverse the above changes and prevent the activation of NF-κB. Conclusion Gallic acid could inhibit LPS-induced inflammatory response in RAW264.7 macrophages via TLR4/NF-κB pathway.

  12. Lipopolysaccharide promotes lipid accumulation in human adventitial fibroblasts via TLR4-NF-κB pathway

    Directory of Open Access Journals (Sweden)

    Wang Jun

    2012-10-01

    Full Text Available Abstract Background Atherosclerosis is a chronic degenerative disease of the arteries and is thought to be one of the most common causes of death globally. In recent years, the functions of adventitial fibroblasts in the development of atherosclerosis and tissue repair have gained increased interests. LPS can increase the morbidity and mortality of atherosclerosis-associated cardiovascular disease. Although LPS increases neointimal via TLR4 activation has been reported, how LPS augments atherogenesis through acting on adventitial fibroblasts is still unknown. Here we explored lipid deposition within adventitial fibroblasts mediated by lipopolysaccharide (LPS to imitate inflammatory conditions. Results In our study, LPS enhanced lipid deposition by the up-regulated expression of adipose differentiation-related protein (ADRP as the silencing of ADRP abrogated lipid deposition in LPS-activated adventitial fibroblasts. In addition, pre-treatment with anti-Toll-like receptor 4 (TLR4 antibody diminished the LPS-induced lipid deposition and ADRP expression. Moreover, LPS induced translocation of nuclear factor-κB (NF-κB, which could markedly up-regulate lipid deposition as pre-treatment with the NF-κB inhibitor, PDTC, significantly reduced lipid droplets. In addition, the lowering lipid accumulation was accompanied with the decreased ADRP expression. Furthermore, LPS-induced adventitial fibroblasts secreted more monocyte chemoattractant protein (MCP-1, compared with transforming growth factor-β1 (TGF-β1. Conclusions Taken together, these results suggest that LPS promotes lipid accumulation via the up-regulation of ADRP expression through TLR4 activated downstream of NF-κB in adventitial fibroblasts. Increased levels of MCP-1 released from LPS-activated adventitial fibroblasts and lipid accumulation may accelerate monocytes recruitment and lipid-laden macrophage foam cells formation. Here, our study provides a new explanation as to how bacterial

  13. [Fisetin alleviates hypoxia/reoxygenation injury in rat hepatocytes via modulation of TLR4/NF-κB signaling pathway].

    Science.gov (United States)

    Pu, Junliang; Wan, Lei; Zheng, Daofeng; Wei, Xufu; Wu, Zhongjun; Tang, Chengyong

    2017-07-01

    Objective To investigate the protective effect of fisetin (FIS) against hypoxia/reoxygenation (H/R) injury in rat hepatocytes and its mechanism. Methods H/R injury model of BRL-3A cells was established and the cells were pretreated with FIS. Survival rate was detected by CCK-8 assay. Cell apoptosis was measured by flow cytometry. The levels of ALT and AST were determined by microplate assay. The production of TNF-α and IL-1β were detected by ELISA. The mRNA and protein levels of TLR4 and NF-κBp65 were analyzed by quantitative real-time PCR and Western blotting, respectively. Results After subjected to H/R, cell survival rate decreased and the apoptosis level increased. The levels of ALT and AST in cell supernatant were elevated, so were the production of TNF-α and IL-1β. FIS pretreatment increased the cell survival rate and inhibited apoptosis. The levels of ALT, AST and the production of TNF-α and IL-1β were reduced significantly. Moreover, FIS inhibited the increasing expression levels of TLR4 and NF-κBp65 induced by H/R. Conclusion FIS alleviates the hepatocyte injury induced by H/R via modulation of TLR4/NF-κB signaling pathway.

  14. Effect of the structure of imidazolium cations in [BF4](-)-type ionic liquids on direct electrochemistry and electrocatalysis of horseradish peroxidase in Nafion films.

    Science.gov (United States)

    Lu, Lu; Huang, Xirong; Qu, Yinbo

    2011-10-01

    The direct electrochemistry and bioelectrocatalysis of horseradish peroxidase (HRP) in Nafion films at glassy carbon electrode (GCE) was investigated in three [BF(4)](-)-type room-temperature ionic liquids (ILs) to understand the structural effect of imidazolium cations. The three ILs are 1-ethyl-3-methylimidazolium tetrafluoroborate ([Emim][BF(4)]), 1-butyl-3-methylimidazolium tetrafluoroborate ([Bmim][BF(4)]) and 1-hexyl-3-methylimidazolium tetrafluoroborate ([Hmim][BF(4)]). A small amount of water in the three ILs is indispensable for maintaining the electrochemical activity of HRP in Nafion films, and the optimum water contents decrease with the increase of alkyl chain length on imidazole ring. Analysis shows that the optimum water contents are primarily determined by the hydrophilicity of ILs used. In contrast to aqueous medium, ILs media facilitate the direct electron transfer of HRP, and the electrochemical parameters obtained in different ILs are obviously related to the nature of ILs. The direct electron transfer between HRP and GCE is a surface-confined quasi-reversible single electron transfer process. The apparent heterogeneous electron transfer rate constant decreases gradually with the increase of alkyl chain length on imidazole ring, but the changing extent is relatively small. The electrocatalytic reduction current of H(2)O(2) at the present electrode decreases obviously with the increase of alkyl chain length, and the mass transfer of H(2)O(2) via diffusion in ILs should be responsible for the change. In addition, the modified electrode has good stability and reproducibility; the ability to tolerate high levels of F(-) has been greatly enhanced due to the use of Nafion film. When an appropriate mediator is included in the sensing layer, a sensitive nonaqueous biosensor could be fabricated. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Highly precise (liquid + liquid) equilibrium and heat capacity measurements near the critical point for [Bmim][BF4] + 1H, 1H, 2H, 2H perfluoroctanol

    International Nuclear Information System (INIS)

    Pérez-Sánchez, G.; Troncoso, J.; Losada-Pérez, P.; Méndez-Castro, P.; Romaní, L.

    2013-01-01

    Highlights: • Highly precise liquid–liquid curves for [Bmim][BF 4 ] + perfluoroctanol are reported. • Critical behavior of heat capacity for the same system was also characterized. • In contrast to previous results, no coulombic/solvophobic crossover for coexistence curve diameter was found. • The system criticality shows characteristics both solvophobic and coulombic. -- Abstract: Liquid + liquid equilibrium of the system [Bmim][BF 4 ] + 1H, 1H, 2H, 2H perfluoroctanol using a highly precise methodology based on refractive index measurements was experimentally determined. In addition, isobaric heat capacity near the critical point was obtained. The performance of the new refractive index set-up was successfully checked against the coexistence curve of the system dimethyl carbonate + decane, since highly accurate data are available in the literature. The choice of [Bmim][BF 4 ] + 1H, 1H, 2H, 2H perfluoroctanol was motivated by a previous experimental work, whose results suggest that this system could present characteristics of both solvophobic and coulombic behavior, which are the two categories to which an ionic system can belong. Although this was previously observed for other ionic systems, this mixture presented a very striking feature: the diameter of the coexistence curve seemed to change its criticality in the studied temperature range, from solvophobic far away to coulombic close to the critical point. The results of this work reveal that, in fact, [Bmim][BF 4 ] + 1H, 1H, 2H, 2H perfluoroctanol presents characteristics of both solvophobic and coulombic criticality, but no evidence of the observed crossover over the experimental temperature range has been found

  16. Li+ solvation and kinetics of Li+-BF4-/PF6- ion pairs in ethylene carbonate. A molecular dynamics study with classical rate theories

    Science.gov (United States)

    Chang, Tsun-Mei; Dang, Liem X.

    2017-10-01

    Using our polarizable force-field models and employing classical rate theories of chemical reactions, we examine the ethylene carbonate (EC) exchange process between the first and second solvation shells around Li+ and the dissociation kinetics of ion pairs Li+-[BF4] and Li+-[PF6] in this solvent. We calculate the exchange rates using transition state theory and correct them with transmission coefficients computed by the reactive flux, Impey, Madden, and McDonald approaches, and Grote-Hynes theory. We found that the residence times of EC around Li+ ions varied from 60 to 450 ps, depending on the correction method used. We found that the relaxation times changed significantly from Li+-[BF4] to Li+-[PF6] ion pairs in EC. Our results also show that, in addition to affecting the free energy of dissociation in EC, the anion type also significantly influences the dissociation kinetics of ion pairing.

  17. Transforming growth factor-beta 1 (TGF-beta1) promotes IL-2 mRNA expression through the up-regulation of NF-kappaB, AP-1 and NF-AT in EL4 cells.

    Science.gov (United States)

    Han, S H; Yea, S S; Jeon, Y J; Yang, K H; Kaminski, N E

    1998-12-01

    Transforming growth factor beta1 (TGF-beta1) has been previously shown to modulate interleukin 2 (IL-2) secretion by activated T-cells. In the present studies, we determined that TGF-beta1 induced IL-2 mRNA expression in the murine T-cell line EL4, in the absence of other stimuli. IL-2 mRNA expression was significantly induced by TGF-beta1 (0.1-1 ng/ml) over a relatively narrow concentration range, which led to the induction of IL-2 secretion. Under identical condition, we examined the effect of TGF-beta1 on the activity of nuclear factor AT (NF-AT), nuclear factor kappaB (NF-kappaB), activator protein-1 (AP-1) and octamer, all of which contribute to the regulation of IL-2 gene expression. Electrophoretic mobility shift assays showed that TGF-beta1 markedly increased NF-AT, NF-kappaB and AP-1 binding to their respective cognate DNA binding sites, whereas octamer binding remained constant, as compared with untreated cells. Employing a reporter gene expression system with p(NF-kappaB)3-CAT, p(NF-AT)3-CAT and p(AP-1)3-CAT, TGF-beta1 treatment of transfected EL4 cells induced a dose-related increase in chloramphenicol acetyltransferase activity that correlated well with the DNA binding profile found in the electrophoretic mobility shift assay studies. These results show that TGF-beta1, in the absence of any additional stimuli, up-regulates the activity of key transcription factors involved in IL-2 gene expression, including NF-AT, NF-kappaB and AP-1, to help promote IL-2 mRNA expression by EL4 cells.

  18. Lactobacillus rhamnosus GR-1 enhances NF-kappaB activation in Escherichia coli-stimulated urinary bladder cells through TLR4

    Directory of Open Access Journals (Sweden)

    Karlsson Mattias

    2012-01-01

    Full Text Available Abstract Background Epithelial cells of the urinary tract recognize pathogenic bacteria through pattern recognition receptors on their surface, such as toll-like receptors (TLRs, and mount an immune response through the activation of the NF-kappaB pathway. Some uropathogenic bacteria can subvert these cellular responses, creating problems with how the host eliminates pathogens. Lactobacillus is a genus of lactic acid bacteria that are part of the microbiota and consist of many probiotic strains, some specifically for urogenital infections. Immunomodulation has emerged as an important mode of action of probiotic and commensal lactobacilli and given the importance of epithelial cells, we evaluated the effect of the urogenital probiotic Lactobacillus rhamnosus GR-1 on epithelial immune activation. Results Immune activation through the NF-kappaB pathway was initiated by stimulation of T24 urothelial cells with heat-killed Escherichia coli and this was further potentiated when cells were co-cultured with live L. rhamnosus GR-1. Heat-killed lactobacilli were poor activators of NF-kappaB. Concomitant stimulation of bladder cells with E. coli and L. rhamnosus GR-1 increased the levels of the pro-inflammatory cytokine TNF, whereas IL-6 and CXCL8 levels were reduced. Another probiotic, L. rhamnosus GG, was also able to potentiate NF-kappaB in these cells although at a significantly reduced level compared to the GR-1 strain. The transcript numbers and protein levels of the lipopolysaccharide receptor TLR4 were significantly increased after co-stimulation with E. coli and lactobacilli compared to controls. Furthermore, inhibition of TLR4 activation by polymixin B completely blocked the lactobacilli potentiation of NF-kappaB. Conclusions The immunological outcome of E. coli challenge of bladder cells was influenced by probiotic L. rhamnosus GR-1, by enhancing the activation of NF-kappaB and TNF release. Thus the urogenital probiotic L. rhamnosus GR-1

  19. Anti-influenza A virus activity of rhein through regulating oxidative stress, TLR4, Akt, MAPK, and NF-κB signal pathways.

    Directory of Open Access Journals (Sweden)

    Qian-Wen Wang

    Full Text Available Rhein, an anthraquinone compound existing in many traditional herbal medicines, has anti-inflammatory, antioxidant, antitumor, antiviral, hepatoprotective, and nephroprotective activities, but its anti-influenza A virus (IAV activity is ambiguous. In the present study, through plaque inhibition assay, time-of-addition assay, antioxidant assay, qRT-PCR, ELISA, and western blotting assays, we investigated the anti-IAV effect and mechanism of action of rhein in vitro and in vivo. The results showed that rhein could significantly inhibit IAV adsorption and replication, decrease IAV-induced oxidative stress, activations of TLR4, Akt, p38, JNK MAPK, and NF-κB pathways, and production of inflammatory cytokines and matrix metalloproteinases in vitro. Oxidant H2O2 and agonists of TLR4, Akt, p38/JNK and IKK/NF-κB could significantly antagonize the inhibitory effects of rhein on IAV-induced cytopathic effect (CPE and IAV replication. Through an in vivo test in mice, we also found that rhein could significantly improve the survival rate, lung index, pulmonary cytokines, and pulmonary histopathological changes. Rhein also significantly decreased pulmonary viral load at a high dose. In conclusion, rhein can inhibit IAV adsorption and replication, and the mechanism of action to inhibit IAV replication may be due to its ability to suppress IAV-induced oxidative stress and activations of TLR4, Akt, p38, JNK MAPK, and NF-κB signal pathways.

  20. Volumetric and viscosity properties of 1-butyl-3-methylimidazolium tetrafluoroborate ionic liquid in methanol%[Bmim]BF4离子液体在甲醇中的体积和黏度性质

    Institute of Scientific and Technical Information of China (English)

    李诗琴; 周贤丰; 许映杰

    2013-01-01

    在298.15 K和常压下,测定了1-丁基-3-甲基咪唑四氟硼酸([Bmim] BF4)离子液体+甲醇体系的密度和黏度.由密度计算了体系的表观摩尔体积,并采用Redlich-Mayer方程关联了体系的表观摩尔体积与组成的关系,得到了[Bmim]BF4在甲醇中的标准偏摩尔体积.由Jones-Dole方程对体系的黏度随组成的变化进行了拟合,获得了[Bmim] BF4在甲醇中的黏度B系数.结果表明:[Bmim] BF4+甲醇体系的表观摩尔体积和黏度均随[Bmim] BF4浓度的增加而增加,[Bmim] BF4在甲醇中的标准偏摩尔体积和黏度B系数分别为155.72×10-6m3/mol和0.282 9.%Densities and viscosities of l-butyl-3-methylimi-dazolium tetrafluoroborate ionic liquid ( [ Bmim ] BF4 ) with methanol were measured at 298. 15 K and atmospheric pressure. Apparent molar volumes, Vf of the above-mentioned mixture were determined from the experimental densities. Standard partial molar volume , Vo/f of [ Bmim] BF4 in methanol was estimated by the Redlich-Mayer equation. The achieved viscosities were used to calculate the viscosity B-coefficient of [ Bmim ] BF4 in methanol through Jones-Dole equation. The results indicate that the apparent molar volumes and viscosities increase with increasing of ionic liquid concentration. Standard partial molar volume and viscosity B-coefficient of [Bmim] BF4 in methanol is 155.72 ?10-6 m3 穖ol-1 and 0.282 9,respectively.

  1. The PP4R1 sub-unit of protein phosphatase PP4 is essential for inhibition of NF-κB by merkel polyomavirus small tumour antigen.

    Science.gov (United States)

    Abdul-Sada, Hussein; Müller, Marietta; Mehta, Rajni; Toth, Rachel; Arthur, J Simon C; Whitehouse, Adrian; Macdonald, Andrew

    2017-04-11

    Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with a high metastatic potential. The majority of MCC cases are caused by the Merkel cell polyomavirus (MCPyV), through expression of the virus-encoded tumour antigens. Whilst mechanisms attributing tumour antigen expression to transformation are being uncovered, little is known of the mechanisms by which MCPyV persists in the host. We previously identified the MCPyV small T antigen (tAg) as a novel inhibitor of nuclear factor kappa B (NF-kB) signalling and a modulator of the host anti-viral response. Here we demonstrate that regulation of NF-kB activation involves a previously undocumented interaction between tAg and regulatory sub-unit 1 of protein phosphatase 4 (PP4R1). Formation of a complex with PP4R1 and PP4c is required to bridge MCPyV tAg to the NEMO adaptor protein, allowing deactivation of the NF-kB pathway. Mutations in MCPyV tAg that fail to interact with components of this complex, or siRNA depletion of PP4R1, prevents tAg-mediated inhibition of NF-kB and pro-inflammatory cytokine production. Comparison of tAg binding partners from other human polyomavirus demonstrates that interactions with NEMO and PP4R1 are unique to MCPyV. Collectively, these data identify PP4R1 as a novel target for virus subversion of the host anti-viral response.

  2. Expression of the tumor suppressor genes NF2, 4.1B, and TSLC1 in canine meningiomas.

    Science.gov (United States)

    Dickinson, P J; Surace, E I; Cambell, M; Higgins, R J; Leutenegger, C M; Bollen, A W; LeCouteur, R A; Gutmann, D H

    2009-09-01

    Meningiomas are common primary brain tumors in dogs; however, little is known about the molecular genetic mechanisms involved in their tumorigenesis. Several tumor suppressor genes have been implicated in meningioma pathogenesis in humans, including the neurofibromatosis 2 (NF2), protein 4.1B (4.1 B), and tumor suppressor in lung cancer-1 (TSLC1) genes. We investigated the expression of these tumor suppressor genes in a series of spontaneous canine meningiomas using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) (NF2; n = 25) and western blotting (NF2/merlin, 4.1B, TSLC1; n = 30). Decreased expression of 4.1B and TSLC1 expression on western blotting was seen in 6/30 (20%) and in 15/30 (50%) tumors, respectively, with 18/30 (60%) of meningiomas having decreased or absent expression of one or both proteins. NF2 gene expression assessed by western blotting and RT-PCR varied considerably between individual tumors. Complete loss of NF2 protein on western blotting was not seen, unlike 4.1B and TSLC1. Incidence of TSLC1 abnormalities was similar to that seen in human meningiomas, while perturbation of NF2 and 4.1B appeared to be less common than reported for human tumors. No association was observed between tumor grade, subtype, or location and tumor suppressor gene expression based on western blot or RT-PCR. These results suggest that loss of these tumor suppressor genes is a frequent occurrence in canine meningiomas and may be an early event in tumorigenesis in some cases. In addition, it is likely that other, as yet unidentified, genes play an important role in canine meningioma formation and growth.

  3. Curcumin attenuates acute inflammatory injury by inhibiting the TLR4/MyD88/NF-κB signaling pathway in experimental traumatic brain injury

    Science.gov (United States)

    2014-01-01

    Background Traumatic brain injury (TBI) initiates a neuroinflammatory cascade that contributes to substantial neuronal damage and behavioral impairment, and Toll-like receptor 4 (TLR4) is an important mediator of thiscascade. In the current study, we tested the hypothesis that curcumin, a phytochemical compound with potent anti-inflammatory properties that is extracted from the rhizome Curcuma longa, alleviates acute inflammatory injury mediated by TLR4 following TBI. Methods Neurological function, brain water content and cytokine levels were tested in TLR4-/- mice subjected to weight-drop contusion injury. Wild-type (WT) mice were injected intraperitoneally with different concentrations of curcumin or vehicle 15 minutes after TBI. At 24 hours post-injury, the activation of microglia/macrophages and TLR4 was detected by immunohistochemistry; neuronal apoptosis was measured by FJB and TUNEL staining; cytokines were assayed by ELISA; and TLR4, MyD88 and NF-κB levels were measured by Western blotting. In vitro, a co-culture system comprised of microglia and neurons was treated with curcumin following lipopolysaccharide (LPS) stimulation. TLR4 expression and morphological activation in microglia and morphological damage to neurons were detected by immunohistochemistry 24 hours post-stimulation. Results The protein expression of TLR4 in pericontusional tissue reached a maximum at 24 hours post-TBI. Compared with WT mice, TLR4-/- mice showed attenuated functional impairment, brain edema and cytokine release post-TBI. In addition to improvement in the above aspects, 100 mg/kg curcumin treatment post-TBI significantly reduced the number of TLR4-positive microglia/macrophages as well as inflammatory mediator release and neuronal apoptosis in WT mice. Furthermore, Western blot analysis indicated that the levels of TLR4 and its known downstream effectors (MyD88, and NF-κB) were also decreased after curcumin treatment. Similar outcomes were observed in the microglia and

  4. Dicty_cDB: FC-BF01 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC (Link to library) FC-BF01 (Link to dictyBase) - - - Contig-U15105-1 FC-BF01Z (Li...nk to Original site) - - FC-BF01Z 674 - - - - Show FC-BF01 Library FC (Link to library) Clone ID FC-BF01 (Link to dict...yBase) Atlas ID - NBRP ID - dictyBase ID - Link to Contig Contig-U15105-1 Original site URL http://dict...402813_1( AF402813 |pid:none) Ictalurus punctatus 40S ribosomal ... 260 3e-68 AJ783868_1( AJ783868 |pid:none...lasmic 8.0 %: mitochondrial 4.0 %: nuclear >> prediction for FC-BF01 is cyt 5' end seq. ID - 5' end seq. - L

  5. Heat transfer measurements in a forced convection loop with two molten-fluoride salts: LiF--BeF2--ThF2--UF4 and eutectic NaBF4--NaF

    International Nuclear Information System (INIS)

    Silverman, M.D.; Huntley, W.R.; Robertson, H.E.

    1976-10-01

    Heat transfer coefficients were determined experimentally for two molten-fluoride salts [LiF-BeF 2 -ThF 2 -UF 4 (72-16-12-0.3 mole %) and NaBF 4 -NaF (92-8 mole %] proposed as the fuel salt and coolant salt, respectively, for molten-salt breeder reactors. Information was obtained over a wide range of variables, with salt flowing through 12.7-mm-OD (0.5-in.) Hastelloy N tubing in a forced convection loop (FCL-2b). Satisfactory agreement with the empirical Sieder-Tate correlation was obtained in the fully developed turbulent region at Reynolds moduli above 15,000 and with a modified Hausen equation in the extended transition region (Re approx.2100-15,000). Insufficient data were obtained in the laminar region to allow any conclusions to be drawn. These results indicate that the proposed salts behave as normal heat transfer fluids with an extended transition region

  6. Increased expression of NF-AT3 and NF-AT4 in the atria correlates with procollagen I carboxyl terminal peptide and TGF-β1 levels in serum of patients with atrial fibrillation.

    Science.gov (United States)

    Zhao, Fei; Zhang, ShiJiang; Chen, YiJiang; Gu, WeiDong; Ni, BuQing; Shao, YongFeng; Wu, YanHu; Qin, JianWei

    2014-11-25

    Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice. Unfortunately, the precise mechanisms and sensitive serum biomarkers of atrial remodeling in AF remain unclear. The aim of this study was to determine whether the expression of the transcription factors NF-AT3 and NF-AT4 correlate with atrial structural remodeling of atrial fibrillation and serum markers for collagen I and III synthesis. Right and left atrial specimens were obtained from 90 patients undergoing valve replacement surgery. The patients were divided into sinus rhythm (n = 30), paroxysmal atrial fibrillation (n = 30), and persistent atrial fibrillation (n = 30) groups. NF-AT3, NF-AT4, and collagen I and III mRNA and protein expression in atria were measured. We also tested the levels of the carboxyl-terminal peptide from pro-collagen I, the N-terminal type I procollagen propeptides, the N-terminal type III procollagen propeptides, and TGF-β1 in serum using an enzyme immunosorbent assay. NF-AT3 and NF-AT4 mRNA and protein expression were increased in the AF groups, especially in the left atrium. NF-AT3 and NF-AT4 expression in the right atrium was increased in the persistent atrial fibrillation group compared the sinus rhythm group with similar valvular disease. In patients with AF, the expression levels of nuclear NF-AT3 and NF-AT4 correlated with those of collagens I and III in the atria and with PICP and TGF-β1 in blood. These data support the hypothesis that nuclear NF-AT3 and NF-AT4 participates in atrial structural remodeling, and that PICP and TGF-β1 levels may be sensitive serum biomarkers to estimate atrial structural remodeling with atrial fibrillation.

  7. Pysico-chemical properties of hydrophobic ionic liquids containing1-octylpyridinium, 1-octyl-2-methylpyridinium or1-octyl-4-methylpyridinium cations

    Energy Technology Data Exchange (ETDEWEB)

    Papaiconomou, Nicolas; Salminen, Justin; Lee, Jong-Min; Prausnitz, John M.

    2006-09-15

    This paper reports synthesis of some ionic liquids based on cations 1-octylpyridinium, 1-octyl-2-methylpyridinium or 1-octyl-4-methylpyridinium and anions dicyanamide [N(CN)2]-, bis(trifluoromethylsulfonyl)imide [Tf2N]-, bis(pentafluoroethylsulfonyl)imide [BETI]-, trifluoromethyl sulfonate [TfO]-, nonafluorobutyl sulfonate [NfO]-, tetrafluoroborate [BF4]-, trifluorophenylborate [BF3Ph]- or hexafluoroarsenate [AsF6]-. Melting points, decomposition temperatures, densities, mutual solubilities with water, and viscosities have been measured. Unlike similar ionic liquids containing imidazolium cations, pyridinium ionic liquids studied here are nearly immiscible in water. Viscosities are similar and water content is slightly lower than those for ionic liquids containing imidazolium cations.

  8. Renoprotective effect of paricalcitol via a modulation of the TLR4-NF-κB pathway in ischemia/reperfusion-induced acute kidney injury

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jae-Won, E-mail: maestro97@hanmail.net; Kim, Sun Chul, E-mail: linefe99@hanmail.net; Ko, Yoon Sook, E-mail: rainboweyes@hanmail.net; Lee, Hee Young, E-mail: cell1023@hanmail.net; Cho, Eunjung, E-mail: icdej@naver.com; Kim, Myung-Gyu, E-mail: gyu219@hanmail.net; Jo, Sang-Kyung, E-mail: sang-kyung@korea.ac.kr; Cho, Won Yong, E-mail: wonyong@korea.ac.kr; Kim, Hyoung Kyu, E-mail: hyoung@korea.ac.kr

    2014-02-07

    Highlights: • Paricalcitol. • Attenuation of renal inflammation. • Modulation of TLR4-NF-κB signaling. - Abstract: Background: The pathophysiology of ischemic acute kidney injury (AKI) is thought to include a complex interplay between vascular endothelial cell dysfunction, inflammation, and tubular cell damage. Several lines of evidence suggest a potential anti-inflammatory effect of vitamin D in various kidney injury models. In this study, we investigated the effect of paricalcitol, a synthetic vitamin D analog, on renal inflammation in a mouse model of ischemia/reperfusion (I/R) induced acute kidney injury (AKI). Methods: Paricalcitol was administered via intraperitoneal (IP) injection at 24 h before ischemia, and then I/R was performed through bilateral clamping of the renal pedicles. Twenty-four hours after I/R, mice were sacrificed for the evaluation of injury and inflammation. Additionally, an in vitro experiment using HK-2 cells was also performed to examine the direct effect of paricalcitol on tubular cells. Results: Pre-treatment with paricalcitol attenuated functional deterioration and histological damage in I/R induced AKI, and significantly decreased tissue neutrophil and macrophage infiltration and the levels of chemokines, the pro-inflammatory cytokine interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1). It also decreased IR-induced upregulation of Toll-like receptor 4 (TLR4), and nuclear translocation of p65 subunit of NF-κB. Results from the in vitro study showed pre-treatment with paricalcitol suppressed the TNF-α-induced depletion of cytosolic IκB in HK-2 cells. Conclusion: These results demonstrate that pre-treatment with paricalcitol has a renoprotective effect in ischemic AKI, possibly by suppressing TLR4-NF-κB mediated inflammation.

  9. Wogonin improves histological and functional outcomes, and reduces activation of TLR4/NF-κB signaling after experimental traumatic brain injury.

    Directory of Open Access Journals (Sweden)

    Chien-Cheng Chen

    Full Text Available Traumatic brain injury (TBI initiates a neuroinflammatory cascade that contributes to neuronal damage and behavioral impairment. This study was undertaken to investigate the effects of wogonin, a flavonoid with potent anti-inflammatory properties, on functional and histological outcomes, brain edema, and toll-like receptor 4 (TLR4- and nuclear factor kappa B (NF-κB-related signaling pathways in mice following TBI.Mice subjected to controlled cortical impact injury were injected with wogonin (20, 40, or 50 mg·kg(-1 or vehicle 10 min after injury. Behavioral studies, histology analysis, and measurement of blood-brain barrier (BBB permeability and brain water content were carried out to assess the effects of wogonin. Levels of TLR4/NF-κB-related inflammatory mediators were also examined. Treatment with 40 mg·kg(-1 wogonin significantly improved functional recovery and reduced contusion volumes up to post-injury day 28. Wogonin also significantly reduced neuronal death, BBB permeability, and brain edema beginning at day 1. These changes were associated with a marked reduction in leukocyte infiltration, microglial activation, TLR4 expression, NF-κB translocation to nucleus and its DNA binding activity, matrix metalloproteinase-9 activity, and expression of inflammatory mediators, including interleukin-1β, interleukin-6, macrophage inflammatory protein-2, and cyclooxygenase-2.Our results show that post-injury wogonin treatment improved long-term functional and histological outcomes, reduced brain edema, and attenuated the TLR4/NF-κB-mediated inflammatory response in mouse TBI. The neuroprotective effects of wogonin may be related to modulation of the TLR4/NF-κB signaling pathway.

  10. Pressure-induced change in the Raman spectra of ionic liquid [DEME][BF4]-H2O mixtures

    International Nuclear Information System (INIS)

    Imai, Y; Abe, H; Goto, T; Miyashita, T; Yoshimura, Y

    2010-01-01

    We have measured Raman spectral changes of N,N,diethyl-N-methyl-N-(2-methoxyethyl) ammonium tetrafluoroborate, [DEME][BF 4 ]-H 2 O mixtures under high pressure. All the Raman spectra of mixtures of water concentrations below 50.0 mol% H 2 O changed at around 1 GPa at room temperature. The spectrum at high pressure is completely different from that obtained by cooling the sample at a normal pressure.

  11. Splenectomy following MCAO inhibits the TLR4-NF-κB signaling pathway and protects the brain from neurodegeneration in rats.

    Science.gov (United States)

    Belinga, Victor Fabrice; Wu, Guan-Jin; Yan, Fu-Ling; Limbenga, Erica Audrey

    2016-04-15

    The Toll-like receptor 4(TLR4)/nuclear factor kappa B NF-κB inflammatory pathway contributes to secondary inflammation in many diseases including stroke. Moreover, the neuroprotective effect of splenectomy in stroke is supported by a vast body of experimental evidence. Nevertheless, the underlying mechanism(s) by which splenectomy enhance neuroprotection in stroke is still poorly understood. Our study aimed to investigate whether post-ischemic splenectomy modulate the TLR4/NF-κB inflammatory pathway in stroke. Immunohistochemistry was used to evaluate the levels of TLR4 and NF-κB expression in brain areas (parietal lobe, hippocampus and striatum) of rats that underwent: MCAO-splenectomy surgery (MS ); MCAO surgery without splenectomy (MCAO control or MC); Sham MCAO and splenectomy surgery (sham control group or SC group respectively. Apoptosis in these areas was assessed by TUNEL detection technique. The levels of TLR4 and NF-κB expression were significantly reduced in splenectomized rats relative to the MS group (Psplenectomy in ischemic stroke. Our results suggest that such an effect might be due to the inhibition of theTLR4/NF-κB inflammatory pathway. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Thermodynamic study of binary mixture of x1[C6mim][BF4] + x21-propanol: Measurements and molecular modeling

    International Nuclear Information System (INIS)

    Kermanpour, F.; Sharifi, T.

    2012-01-01

    Highlights: ► Densities and viscosities for binary mixture of {x 1 [C 6 mim][BF 4 ] + x 2 1-propanol} were measured at different temperatures. ► The excess molar functions were calculated from the obtained experimental data. ► These data were correlated with the Redlich–Kister equation and PFP model to obtain the coefficients and standard deviations. - Abstract: Densities, ρ, and viscosities, η, of pure 1-hexyl-3-methylimidazoliumtetrafluoro borate ([C 6 mim][BF 4 ]) and 1-propanol, and their binary mixture {x 1 [C 6 mim][BF 4 ] + x 2 1-propanol} were measured at atmospheric pressure and in the temperature range of 293.15–333.15 K. The excess molar volumes, V m E , thermal expansion coefficients, α, and their excess values, α E , isothermal coefficient of excess molar enthalpy, (∂H m E /∂p) T,x and excess viscosities, η E , were calculated from the experimental values of densities and viscosities. The excess molar volumes of the binary mixture are negative over the entire mole fraction range and increase with increasing temperature. Excess viscosities are negative over the entire mole fraction range of the mixture and decrease with increasing temperature. The obtained excess molar volumes and excess viscosities were correlated with the Redlich–Kister equation. The experimental results have also been used to examine the applicability of Prigogine–Flory–Patterson (PFP) theory in predicting the excess molar volume of the binary mixture. It is indicated that agreement between excess molar volumes calculated via PFP theory and the experimental results is good in all temperatures.

  13. BAY61-3606 potentiates the anti-tumor effects of TRAIL against colon cancer through up-regulating DR4 and down-regulating NF-κB.

    Science.gov (United States)

    Du, Jipei; Wang, Yufang; Chen, Degao; Ji, Guangyu; Ma, Qizhao; Liao, Shiping; Zheng, Yanjiang; Zhang, Ji; Hou, Yiping

    2016-12-28

    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is well known for its ability to preferentially induce apoptosis in malignant cells without causing damage to most normal cells. However, inherent and acquired resistance of tumor to TRAIL-induced apoptosis limits its therapeutic applicability. Here we show that the orally available tyrosine kinase inhibitor, BAY61-3606, enhances the sensitivity of human colon cancer cells, especially those harboring active mutations in Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) gene, to TRAIL-induced apoptosis in vitro and in vivo. The sensitization was achieved by up-regulating death receptor 4 (DR4) and the tumor suppressor p53. BAY61-3606-induced the up-regulation of DR4 is p53-dependent. Knockout of p53 decreased BAY61-3606-induced DR4 expression and inhibited the effect of BAY61-3606 on TRAIL-induced apoptosis. In addition, BAY61-3606 suppressed activity of NF-κB and regulated its gene products, which might also contribute to TRAIL-induced apoptosis. In conclusion, our results showed that BAY61-3606 sensitizes colon cancer cells to TRAIL-induced apoptosis via up-regulating DR4 expression in p53-dependent manner and inhibiting NF-κB activity, suggesting that the combination of TRAIL and BAY61-3606 may be a promising therapeutic approach in the treatment of colon cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Rate theory of solvent exchange and kinetics of Li+ − BF4−/PF6− ion pairs in acetonitrile

    International Nuclear Information System (INIS)

    Dang, Liem X.; Chang, Tsun-Mei

    2016-01-01

    In this paper, we describe our efforts to apply rate theories in studies of solvent exchange around Li + and the kinetics of ion pairings in lithium-ion batteries (LIBs). We report one of the first computer simulations of the exchange dynamics around solvated Li + in acetonitrile (ACN), which is a common solvent used in LIBs. We also provide details of the ion-pairing kinetics of Li + -[BF 4 ] and Li + -[PF 6 ] in ACN. Using our polarizable force-field models and employing classical rate theories of chemical reactions, we examine the ACN exchange process between the first and second solvation shells around Li + . We calculate exchange rates using transition state theory and weighted them with the transmission coefficients determined by the reactive flux, Impey, Madden, and McDonald approaches, and Grote-Hynes theory. We found the relaxation times changed from 180 ps to 4600 ps and from 30 ps to 280 ps for Li + -[BF 4 ] and Li + -[PF 6 ] ion pairs, respectively. These results confirm that the solvent response to the kinetics of ion pairing is significant. Our results also show that, in addition to affecting the free energy of solvation into ACN, the anion type also should significantly influence the kinetics of ion pairing. These results will increase our understanding of the thermodynamic and kinetic properties of LIB systems.

  15. Stereoisomerization of the P(OCH2CH2)3N+BF4– radical: a single-crystal e.s.r. study

    NARCIS (Netherlands)

    Hamerlinck, J.H.H.; Schipper, P.; Buck, H.M.

    1981-01-01

    The [graphic omitted]+BF4– radical with the unpaired electron in an apical position of the trigonal-bipyramidal (TBP) structure is generated by X-irradiation via an intermediate TBP structure in which the unpaired electron is located in an equatorial position.

  16. Dexmedetomidine Inhibits Inflammatory Reaction in Lung Tissues of Septic Rats by Suppressing TLR4/NF-κB Pathway

    Directory of Open Access Journals (Sweden)

    Yuqing Wu

    2013-01-01

    and 20 μg/kg significantly decreased mortality and pulmonary inflammation of septic rats, as well as suppressed CLP-induced elevation of TNF-α and IL-6 and inhibited TLR4/MyD88 expression and NF-κB activation. These results suggest that dexmedetomidine may decrease mortality and inhibit inflammatory reaction in lung tissues of septic rats by suppressing TLR4/MyD88/NF-κB pathway.

  17. MicroRNA-129-5p inhibits the development of autoimmune encephalomyelitis-related epilepsy by targeting HMGB1 through the TLR4/NF-kB signaling pathway.

    Science.gov (United States)

    Liu, Ai-Hua; Wu, Ya-Ting; Wang, Yu-Ping

    2017-06-01

    The study aimed to explore the effects of microRNA-129-5p (miR-129-5p) on the development of autoimmune encephalomyelitis (AE)-related epilepsy by targeting HMGB1 through the TLR4/NF-kB signaling pathway in a rat model. AE-related epilepsy models were established. Sprague-Dawley (SD) rats were randomly divided into control, model, miR-129-5p mimics, miR-129-5p inhibitor, HMGB1 shRNA, TLR4/NF-kB (TLR4/NF-kB signaling pathway was inhibited) and miR-129-5p mimics+HMGB1 shRNA groups respectively. Latency to a first epilepsy seizure attack was recorded. Neuronal injuries in the hippocampus regions were detected using HE, Nissl and FJB staining methods 24h following model establishment. Microglial cells were detected by OX-42 immunohistochemistry. Expressions of miR-129-5p, HMGB1 and TLR4/NF-kB signaling pathway-related proteins were detected by qRT-PCR. Protein expressions of HMGB1 and TLR4/NF-kB signaling pathway-related proteins were detected by Western blotting. Dual luciferase reporter gene assay showed that miR-129-5p was negatively targeting HMGB1. Neurons of hippocampal tissues in rats were heavily injured by an injection of lithium chloride. Compared with the model and control groups, neuronal injury of the hippocampus and AE-related epilepsy decreased and microglial cells increased in the miR-129-5p mimics, HMGB1 shRNA and TLR4/NF-kB groups; however, in the miR-129-5p inhibitor group, miR-129-5p expression decreased, HMGB1 expression increased, TLR4/NF-kB signaling pathway was activated, latency to a first epilepsy seizure attack was shortened, and neuronal injury increased. This study provides evidence that miR-129-5p inhibits the development of AE-related epilepsy by suppressing HMGB1 expression and inhibiting TLR4/NF-kB signaling pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Bioadhesive floating microsponges of cinnarizine as novel gastroretentive delivery: Capmul GMO bioadhesive coating versus acconon MC 8-2 EP/NF with intrinsic bioadhesive property.

    Science.gov (United States)

    Raghuvanshi, Smita; Pathak, Kamla

    2016-01-01

    The study was aimed at the development of low-density gastroretentive bioadhesive microsponges of cinnarizine by two-pronged approach (i) coating with bioadhesive material and (ii) exploration of acconon MC 8-2 EP/NF as bioadhesive raw material for fabrication. Microsponges were prepared by quasi-emulsion solvent diffusion method using 3 2 factorial design. Capmul GMO was employed for bioadhesive coating. In parallel, potential of acconon for the fabrication of bioadhesive floating microsponges (A8) was assessed. Formulation with entrapment efficiency = 82.4 ± 3.4%, buoyancy = 82.3 ± 2.5%, and correlation of drug release (CDR 8h ) = 88.7% ± 2.9% was selected as optimized formulation (F8) and subjected to bioadhesive coating (BF8). The %CDR 8h for A8 was similar to BF8 (87.2% ± 3.5%). Dynamic in vitro bioadhesion test revealed comparable bioadhesivity with BF8. The ex vivo permeation across gastric mucin displayed 63.16% for BF8 against 56.74% from A8; affirmed the bioadhesivity of both approaches. The study concluded with the development of novel bioadhesive floating microsponges of cinnarizine employing capmul GMO as bioadhesive coating material and confirmed the viability of acconon MC 8-2EP/NF as bioadhesive raw material for sustained targeted delivery of drug.

  19. Highly efficient extraction and oxidative desulfurization system using Na7H2LaW10O36⋅32 H2O in [bmim]BF4 at room temperature.

    Science.gov (United States)

    Xu, Junhua; Zhao, Shen; Chen, Wei; Wang, Miao; Song, Yu-Fei

    2012-04-10

    Highly efficient, deep desulfurization of model oil containing dibenzothiophene (DBT), benzothiophene (BT), or 4,6-dimethyldibenzothiophene (4,6-DMDBT) has been achieved under mild conditions by using an extraction and catalytic oxidative desulfurization system (ECODS) in which a lanthanide-containing polyoxometalate Na(7)H(2)LnW(10)O(36)⋅32 H(2)O (LnW(10); Ln = Eu, La) acts as catalyst, [bmim]BF(4) (bmim = 1-butyl-3-methylimidazolium) as extractant, and H(2)O(2) as oxidant. Sulfur removal follows the order DBT>4,6-DMDBT>BT at 30 °C. DBT can be completely oxidized to the corresponding sulfone in 25 min under mild conditions, and the LaW(10)/[bmim]BF(4) system could be recycled for ten times with only slight decrease in activity. Thus, LaW(10) in [bmim]BF(4) is one of the most efficient systems for desulfurization using ionic liquids as extractant reported so far. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. EGCG Maintains Th1/Th2 Balance and Mitigates Ulcerative Colitis Induced by Dextran Sulfate Sodium through TLR4/MyD88/NF-κB Signaling Pathway in Rats

    Directory of Open Access Journals (Sweden)

    Xue Bing

    2017-01-01

    Full Text Available Objective. To observe the protective effect of epigallocatechin gallate (EGCG on dextran sulfate sodium- (DSS- induced ulcerative colitis in rats and to explore the roles of TLR4/MyD88/NF-κB signaling pathway. Methods. Rat models of ulcerative colitis were established by giving DSS. EGCG (50 mg/kg/d was given to assess disease activity index. HE staining was applied to observe histological changes. ELISA and qPCR detected the expression of inflammatory factors. Flow cytometry was used to measure the percentage of CD4+IFN-γ+ and CD4+IL-4+ in the spleen and colon. TLR4 antagonist E5564 was given in each group. Flow cytometry was utilized to detect CD4+IFN-γ+ and CD4+IL-4+ cells. Immunohistochemistry, qPCR, and western blot assay were applied to measure the expression of TLR4, MyD88, and NF-κB. Results. EGCG improved the intestinal mucosal injury in rats, inhibited production of inflammatory factors, maintained the balance of Th1/Th2, and reduced the expression of TLR4, MyD88, and NF-κB. After TLR4 antagonism, the protective effect of EGCG on intestinal mucosal injury was weakened in rats with ulcerative colitis, and the expressions of inflammatory factors were upregulated. Conclusion. EGCG can inhibit the intestinal inflammatory response by reducing the severity of ulcerative colitis and maintaining the Th1/Th2 balance through the TLR4/MyD88/NF-κB signaling pathway.

  1. Lycium barbarum polysaccharides improve CCl4-induced liver fibrosis, inflammatory response and TLRs/NF-kB signaling pathway expression in wistar rats.

    Science.gov (United States)

    Gan, Fang; Liu, Qing; Liu, Yunhuan; Huang, Da; Pan, Cuiling; Song, Suquan; Huang, Kehe

    2018-01-01

    Lycium barbarum polysaccharides (LBPs) have multiple biological and pharmacological functions, including antioxidant, anti-inflammatory and anticancer activities. This research was conducted to evaluate whether LBPs could alleviate carbon tetrachloride (CCl 4 )-induced liver fibrosis and the underlying signaling pathway mechanism. Fifty male wistar rats were randomly allocated to five groups (n=10): control, CCl 4 and CCl 4 with 400, 800 or 1600mg/kg LBPs, respectively. Each wistar rat from each group was used for blood and tissue collections at the end of experiment. The results showed that CCl 4 induced liver fibrosis as demonstrated by increasing histopathological damage, α-smooth muscle actin expression, aspartate transaminase activities, alkaline phosphatase activities and alanine aminotransferase activities. LBPs supplementation alleviated CCl 4 -induced liver fibrosis as demonstrated by reversing the above parameters. In addition, CCl 4 treatment induced the oxidative injury, increased the mRNA levels of tumor necrosis factor-α, monocyte chemoattractant protein-1 and interleukin-1β, and up-regulated the protein expressions of toll-like receptor 4 (TLR4), TLR2, myeloid differentiation factor 88, nuclear factor-kappa B (NF-kB) and p-p65. LBPs supplementation alleviated CCl 4 -induced oxidative injury, inflammatory response and TLRs/NF-kB signaling pathway expression by reversing the above some parameters. These results suggest that the alleviating effects of LBPs on CCl 4 -induced liver fibrosis in wistar rats may be through inhibiting the TLRs/NF-kB signaling pathway expression. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Expression of TLR-2, TLR-4, NOD2 and pNF-kappaB in a neonatal rat model of necrotizing enterocolitis.

    Directory of Open Access Journals (Sweden)

    Aurelie Le Mandat Schultz

    Full Text Available BACKGROUND: The etiology of necrotizing enterocolitis (NEC results from a combination of several risk factors that act synergistically and occurs in the same circumstances as those which lead to innate immunity activation. Pattern recognition molecules could be an important player in the initiation of an exaggerated inflammatory response leading to intestinal injury in NEC. METHODOLOGY/PRINCIPAL FINDINGS: We specifically evaluated intestinal epithelial cell (IEC expression of Toll-like receptor 2 (TLR-2, TLR-4, NOD2 and phosphorylated NF-kappaB (pNF-kappaB after mucosal injury in a rat model of NEC induced by prematurity, systemic hypoxia, and a rich protein formula. In the control group (group 1, neonatal rats were full-term and breast-fed; in the experimental groups, rat pups were preterm at day 21 of gestation and rat-milk fed (group 2 or hand-gavaged with a protein rich formula after a hypoxia-reoxygenation procedure (group 3. Morphological mucosal changes in the small bowel were scored on hematoxylin- and eosin-stained sections. Immunohistochemistry was performed on frozen tissue sections using anti TLR-2 and active pNF-kappaB p65 antibodies. Real-time RT-PCR was performed to assess mRNA expression of NOD2, TLR-2 and TLR-4. Proliferation and apoptosis were studied in paraffin sections using anti Ki-67 and caspase-3 antibodies, respectively. The combination of immaturity, protein rich formula and a hypoxia-reoxygenation procedure induces pathological mucosal damage consistent with NEC. There was an overexpression of TLR-2, and pNF-kappaB in IECs that was correlated with the severity of mucosal damage, together with an increase of apoptotic IECs and markedly impaired proliferation. In addition, these immunological alterations appeared before severe mucosal damage. TLR-2 mRNA were also increased in NEC together with TLR-4 mRNA using real-time RT-PCR whereas NOD2 expression was unchanged. CONCLUSIONS/SIGNIFICANCE: These results show that this

  3. From lattice BF gauge theory to area-angle Regge calculus

    International Nuclear Information System (INIS)

    Bonzom, Valentin

    2009-01-01

    We consider Riemannian 4D BF lattice gauge theory, on a triangulation of spacetime. Introducing the simplicity constraints which turn BF theory into simplicial gravity, some geometric quantities of Regge calculus, areas, and 3D and 4D dihedral angles, are identified. The parallel transport conditions are taken care of to ensure a consistent gluing of simplices. We show that these gluing relations, together with the simplicity constraints, contain the constraints of area-angle Regge calculus in a simple way, via the group structure of the underlying BF gauge theory. This provides a precise road from constrained BF theory to area-angle Regge calculus. Doing so, a framework combining variables of lattice BF theory and Regge calculus is built. The action takes a form a la Regge and includes the contribution of the Immirzi parameter. In the absence of simplicity constraints, the standard spin foam model for BF theory is recovered. Insertions of local observables are investigated, leading to Casimir insertions for areas and reproducing for 3D angles known results obtained through angle operators on spin networks. The present formulation is argued to be suitable for deriving spin foam models from discrete path integrals and to unravel their geometric content.

  4. Protective Effect of Zingiber Officinale against CCl4-Induced Liver Fibrosis Is Mediated through Downregulating the TGF-β1/Smad3 and NF-ĸB/IĸB Pathways.

    Science.gov (United States)

    Hasan, Iman H; El-Desouky, M A; Hozayen, Walaa G; Abd el Aziz, Ghada M

    2016-01-01

    No ideal hepatoprotective agents are available in modern medicine to effectively prevent liver disorders. In this study, we aimed at evaluating the potential of Zingiber officinale in the regression of liver fibrosis and its underlining mechanism of action. To induce liver fibrosis, male Wistar rats received CCl4 (2 ml/kg/2 times/week; i.p.), with and without 300 or 600 mg/kg Z. officinale extract daily through oral gavage. To assess the protective effect of Z. officinale, liver function parameters, histopathology, inflammatory markers and gene expression of transforming growth factor-beta 1 (TGF-β1)/Smad3 and nuclear factor-kappa B (NF-ĸB)/IĸB pathways were analyzed. Results demonstrate that Z. officinale extract markedly prevented liver injury as evident by the decreased liver marker enzymes. Concurrent administration of Z. officinale significantly protected against the CCl4-induced inflammation as showed by the decreased pro-inflammatory cytokine levels as well as the downregulation of the NF-ĸB)/IĸB and TGF-β1/Smad3 pathways in CCl4-administered rats. In conclusion, our study provides evidence that the protective effect of Z. officinale against rat liver fibrosis could be explained through its ability to modulate the TGF-β1/Smad3 and NF-ĸB)/IĸB signaling pathways. © 2015 S. Karger AG, Basel.

  5. Investigation of electric conductivity, viscosity and density of LiBF4-1,3-dioxolane system in homogeneity region

    International Nuclear Information System (INIS)

    Plakhotnik, V.N.; Tovmash, N.F.; Mishustin, A.N.; Dam'e, V.N.

    1987-01-01

    Solutions of lithium tetrafluoborate in 1,3-dioxolane (DOL) in temperature range and concentrations limiting the homogeneity region from the side of salt crystallization and formation of polymer structures from -30 deg to +25 deg and from 10 -6 to 1.4 mol/l. are investigated using methods of conductometry, densimetry, viscosimetry and by measuring time of spinlattice 7 Li nuclei relaxation. The dissociation constant of LiBF 4 in DOL (pK D =4.9±0.2 at 25 deg) is determined. Comparison with systems based on 1,2-dimethoxyethane and tetrahydrofurane studied earlier is carried out. Suppositions concerning considerable contribution of ion molecular structures with participation of salt ions and solvent molecules to electric conductivity are stated, and it agrees with the data on measurements of velocities of spin-lattice relaxation of 7 Li nuclei

  6. Capillary evaporation of the ionic liquid [EMIM][BF4] in nanoscale solvophobic confinement

    Science.gov (United States)

    Shrivastav, Gourav; Remsing, Richard C.; Kashyap, Hemant K.

    2018-05-01

    Solvent density fluctuations play a crucial role in liquid-vapor transitions in solvophobic confinement and can also be important for understanding solvation of polar and apolar solutes. In the case of ionic liquids (ILs), density fluctuations can be used to understand important processes in the context of nanoscale aggregation and colloidal self-assemblies. In this article, we explore the nature of density fluctuations associated with capillary evaporation of the IL 1-ethyl-3-methylimidazolium tetrafluoroborate ([EMIM][BF4]) in the confined region of model solvophobic nanoscale sheets by using molecular dynamics simulations combined with non-Boltzmann sampling techniques. We demonstrate that density fluctuations of the confined IL play an important role in capillary evaporation, suggesting analogies to dewetting transitions involving water. Significant changes in the interfacial structure of the IL are also detailed and suggested to underlie a non-classical (non-parabolic) dependence of the free energy barrier to evaporation on the degree of confinement.

  7. Fisetin Alleviates Lipopolysaccharide-Induced Acute Lung Injury via TLR4-Mediated NF-κB Signaling Pathway in Rats.

    Science.gov (United States)

    Feng, Guang; Jiang, Ze-Yu; Sun, Bo; Fu, Jie; Li, Tian-Zuo

    2016-02-01

    Acute lung injury (ALI), a common component of systemic inflammatory disease, is a life-threatening condition without many effective treatments. Fisetin, a natural flavonoid from fruits and vegetables, was reported to have wide pharmacological properties such as anti-inflammatory, antioxidant, and anticancer activities. The aim of this study was to detect the effects of fisetin on lipopolysaccharide (LPS)-induced acute lung injury and investigate the potential mechanism. Fisetin was injected (1, 2, and 4 mg/kg, i.v.) 30 min before LPS administration (5 mg/kg, i.v.). Our results showed that fisetin effectively reduced the inflammatory cytokine release and total protein in bronchoalveolar lavage fluids (BALF), decreased the lung wet/dry ratios, and obviously improved the pulmonary histology in LPS-induced ALI. Furthermore, fisetin inhibited LPS-induced increases of neutrophils and macrophage infiltration and attenuated MPO activity in lung tissues. Additionally, fisetin could significantly inhibit the Toll-like receptor 4 (TLR4) expression and the activation of NF-κB in lung tissues. Our data indicates that fisetin has a protective effect against LPS-induced ALI via suppression of TLR4-mediated NF-κB signaling pathways, and fisetin may be a promising candidate for LPS-induced ALI treatment.

  8. Oligonol Ameliorates CCl4-Induced Liver Injury in Rats via the NF-Kappa B and MAPK Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Jeonghyeon Bak

    2016-01-01

    Full Text Available Oxidative stress is thought to be a key risk factor in the development of hepatic diseases. Blocking or retarding the reactions of oxidation and the inflammatory process by antioxidants could be a promising therapeutic intervention for prevention or treatment of liver injuries. Oligonol is a low molecular weight polyphenol containing catechin-type monomers and oligomers derived from lychee fruit. In this study, we investigated the anti-inflammatory effect of oligonol on carbon tetrachloride- (CCl4- induced acute hepatic injury in rats. Oral administration of oligonol (10 or 50 mg/kg reduced CCl4-induced abnormalities in liver histology and serum AST and serum ALT levels. Oligonol treatment attenuated the CCl4-induced production of inflammatory mediators, including TNF-α, IL-1β, cyclooxygenase-2 (COX-2, and inducible nitric oxide synthase (iNOS mRNA levels. Western blot analysis showed that oligonol suppressed proinflammatory nuclear factor-kappa B (NF-κB p65 activation, phosphorylation of extracellular signal-regulated kinase (ERK, c-Jun NH2-terminal kinase (JNK, and p38 mitogen-activated protein kinases (MAPKs as well as Akt. Oligonol exhibited strong antioxidative activity in vitro and in vivo, and hepatoprotective activity against t-butyl hydroperoxide-induced HepG2 cells. Taken together, oligonol showed antioxidative and anti-inflammatory effects in CCl4-intoxicated rats by inhibiting oxidative stress and NF-κB activation via blockade of the activation of upstream kinases including MAPKs and Akt.

  9. Expression and significance of HMGB1, TLR4 and NF-κB p65 in human epidermal tumors

    International Nuclear Information System (INIS)

    Weng, Hui; Deng, Yunhua; Xie, Yuyan; Liu, Hongbo; Gong, Feili

    2013-01-01

    High mobility group protein box 1 (HMGB1) is a DNA binding protein located in nucleus. It is released into extracellular fluid where it acts as a novel proinflammatory cytokine which interacts with Toll like receptor 4 (TLR4) to activate nuclear factor-κB (NF-κB). This sequence of events is involved in tumor growth and progression. However, the effects of HMGB1, TLR4 and NF-κB on epidermal tumors remain unclear. Human epidermal tumor specimens were obtained from 96 patients. Immunohistochemistry was used to detect expression of HMGB1, TLR4 and NF-κB p65 in human epidermal tumor and normal skin specimens. Western blot analysis was used to detect the expression of NF-κB p65 in epithelial cell nuclei in human epidermal tumor and normal tissues. Immunohistochemistry and western blot analysis indicated a progressive but statistically significant increase in p65 expression in epithelial nuclei in benign seborrheic keratosis (SK), precancerous lesions (PCL), low malignancy basal cell carcinoma (BCC) and high malignancy squamous cell carcinoma (SCC) (P <0.01). The level of extracellular HMGB1 in SK was significantly higher than in normal skin (NS) (P <0.01), and was higher than in SCC but without statistical significance. The level of TLR4 on epithelial membranes of SCC cells was significantly higher than in SK, PCL, BCC and NS (P <0.01). There was a significant positive correlation between p65 expression in the epithelial nuclei and TLR4 expression on the epithelial cell membranes (r = 0.3212, P <0.01). These findings indicate that inflammation is intensified in parallel with increasing malignancy. They also indicate that the TLR4 signaling pathway, rather than HMGB1, may be the principal mediator of inflammation in high-grade malignant epidermal tumors. Combined detection of p65 in the epithelial nuclei and TLR4 on the epithelial membranes may assist the accurate diagnosis of malignant epidermal tumors

  10. Annexin A4 fucosylation enhances its interaction with the NF-kB p50 and promotes tumor progression of ovarian clear cell carcinoma.

    Science.gov (United States)

    Wang, Huimin; Deng, Lu; Cai, Mingbo; Zhuang, Huiyu; Zhu, Liancheng; Hao, Yingying; Gao, Jian; Liu, Juanjuan; Li, Xiao; Lin, Bei

    2017-12-08

    To study the structural relationship between annexin A4 and the Lewis y antigen and compare their expression and significance in ovarian clear cell carcinoma, and to explore how annexin A4 fucose glycosylation effects the interaction between annexin A4 and NF-kB p50, and how it promotes tumour progression of ovarian clear cell carcinoma. Structural relationships between annexin A4 and Lewis y antigen were detected using immunoprecipitation. Annexin A4 and Lewis y antigen expression in various subtypes of ovarian cancer tissues was detected by immunohistochemistry, and the relation between their expression was examined. Any interactions between annexin A4 and NF-kB p50 in ovarian clear cell carcinoma were detected by co-immunoprecipitation. Then looked for changes in expression of Lewis y antigen, annexin A4, NF-kB p50 and a number of downstream related molecules before and after transfection annexin A4 or FUT1, and also analyzed changes in biological processes. Lewis y antigen is a part of annexin A4 structure. The expression rate of both annexin A4 and Lewis y antigen was significantly higher in ovarian clear cell carcinoma than in other subtypes of epithelial ovarian cancer, and are associated with the clinical stages, chemotherapy resistance and poor prognostic. The interaction between annexin A4 and NF-kB p50 promoted cell proliferation, adhesion, invasion, metastasis ability and autophagy, and inhibits apoptosis, Lewis y enhanced this interaction. Annexin A4 contains Lewis y structure, Lewis y antigen modification of annexin A4 enhances its interaction with NF-kB p50, which promotes ovarian clear cell carcinoma malignancy progression.

  11. Spin-crossover in [Fe(3-bpp)2][BF4]2 in different solvents--a dramatic stabilisation of the low-spin state in water.

    Science.gov (United States)

    Barrett, Simon A; Kilner, Colin A; Halcrow, Malcolm A

    2011-12-07

    The temperature of spin-crossover in [Fe(3-bpp)(2)][BF(4)](2) (3-bpp = 2,6-di{pyrazol-3-yl}pyridine) tends to increase in associating solvents. In particular, T(½) shifts to 60-70 K higher temperature in water compared to organic solvents.

  12. Up-regulation of interleukin-4 production via NF-AT/AP-1 activation in T cells by biochanin A, a phytoestrogen and its metabolites

    International Nuclear Information System (INIS)

    Park, Jin; Chung, Su Wol; Kim, Seung Hyun; Kim, Tae Sung

    2006-01-01

    Phytoestrogens are naturally occurring compounds derived from plants. Although phytoestrogens exhibit many biological functions including estrogen agonist/antagonist properties, the effect on allergic responses remains unclear. In this study, we investigated whether biochanin A, a phytoestrogen and its metabolites, genistein, p-ethylphenol and phenolic acid, affect production of IL-4, a pro-inflammatory cytokine closely associated with allergic immune responses, in primary CD4 + T cells and EL4 T lymphoma cells. Biochanin A, genistein and p-ethylphenol significantly enhanced IL-4 production from both CD4 + T cells and EL4 cells in a dose-dependent manner, while phenolic acid did not. Biochanin A, genistein and p-ethylphenol also enhanced IL-4 gene promoter activity in EL4 cells transiently transfected with IL-4 promoter constructs, but this effect was impaired in EL4 cells transfected with an IL-4 promoter construct deleted of a P4 site carrying NF-AT and AP-1 binding sites. In addition, biochanin A, genistein and p-ethylphenol increased both NF-AT and AP-1 DNA binding activities, indicating that they might enhance IL-4 production via NF-AT/AP-1 activation. Furthermore, biochanin A, genistein and p-ethylphenol increased p38 MAPK phosphorylation and PKC activity, while they did not affect ERK phosphorylation. The enhanced NF-AT DNA binding activities were suppressed by inhibitors for PI3-K and PKC, but not by p38 MAPK inhibitors. In contrast, the enhanced AP-1 DNA binding activities and p38 MAPK phosphorylation were significantly suppressed by specific inhibitors for PKC and p38 MAPK, but not by PI3-K inhibitors. These results demonstrate, for the first time, that biochanin A, genistein and p-ethylphenol enhance IL-4 production in activated T cells by two independent pathways, PI3-K/PKC/NF-AT and PKC/p38 MAPK/AP-1

  13. Molecular Interactions between NR4A Orphan Nuclear Receptors and NF-κB Are Required for Appropriate Inflammatory Responses and Immune Cell Homeostasis.

    Science.gov (United States)

    Murphy, Evelyn P; Crean, Daniel

    2015-06-29

    Appropriate innate and adaptive immune responses are essential for protection and resolution against chemical, physical or biological insults. Immune cell polarization is fundamental in orchestrating distinct phases of inflammation, specifically acute phase responses followed by resolution and tissue repair. Dysregulation of immune cell and inflammatory responses is a hallmark of multiple diseases encompassing atherosclerosis, rheumatoid arthritis, psoriasis and metabolic syndromes. A master transcriptional mediator of diverse inflammatory signaling and immune cell function is NF-κB, and altered control of this key regulator can lead to an effective switch from acute to chronic inflammatory responses. Members of the nuclear receptor (NR) superfamily of ligand-dependent transcription factors crosstalk with NF-κB to regulate immune cell function(s). Within the NR superfamily the NR4A1-3 orphan receptors have emerged as important regulators of immune cell polarization and NF-κB signaling. NR4A receptors modulate NF-κB activity in a dynamic fashion, either repressing or enhancing target gene expression leading to altered inflammatory outcome. Here we will discuss the pivotal role NR4A's receptors play in orchestrating immune cell homeostasis through molecular crosstalk with NF-κB. Specifically, we will examine such NR4A/NF-κB interactions within the context of distinct cell phenotypes, including monocyte, macrophage, T cells, endothelial, and mesenchymal cells, which play a role in inflammation-associated disease. Finally, we review the therapeutic potential of altering NR4A/NF-κB interactions to limit hyper-inflammatory responses in vivo.

  14. Positive Correlation between Enhanced Expression of TLR4/MyD88/NF-κB with Insulin Resistance in Placentae of Gestational Diabetes Mellitus.

    Directory of Open Access Journals (Sweden)

    Hui Feng

    Full Text Available Insulin resistance (IR is a critical factor of the pathophysiology of Gestational diabetes mellitus (GDM. Studies on key organs involved in IR, such as livers and adipose tissues, showed that Toll-like receptor 4 (TLR4 can regulate insulin sensitivity. As a maternal-fetal interface with multi-functions, placentae could contribute to the development of IR for GDM. Thus, we investigated the expressions of TLR4/Myeloid Differentiation factor 88 (MyD88/Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-kB in term placentae from 33 GDM women and 36 healthy pregnant women with normal glucose tolerance, evaluated local and systemic IR and furthermore identified the association between placental TLR4 and IR. TLR4 protein was expressed in various cells of term placenta, particularly in syncytiotrophoblast of villi. Compared with normal pregnancy, the expression of TLR4/MyD88/NF-kB pathway increased in the placenta of GDM (p<0.05, and these differences were more pronounced in the maternal section of the placenta and the syncytiotrophoblast of villi. In addition, more severe IR was observed in the placenta of GDM patients than the control group, evidenced with higher pIRS-1(ser312 (p<0.001 and lower IRS-1 (p<0.05 as well as pAkt proteins (p<0.01. The expression of TLR4 in placentae is positively correlated with local IR (pIRS-1: r = 0.76, p <0.001 and pAkt: r = -0.47, p <0.001 and maternal fasting (r = 0.42, p <0.01, one-hour (r = 0.52, p <0.01 and two-hour glucose (r = 0.54, p <0.01 at OGTT. We found an that enhanced expression of the TLR4-MyD88-NF-kB pathway occurs in GDM placentae, which positively correlates with heightened local IR in placentae and higher maternal hyperglycemia. The TLR4/MyD88/NF-kB pathway may play a potential role in the development of IR in placentae of GDM.

  15. Investigation of electric conductivity, viscosity and density of LiBF/sub 4/-1,3-dioxolane system in homogeneity region

    Energy Technology Data Exchange (ETDEWEB)

    Plakhotnik, V N; Tovmash, N F; Mishustin, A N; Dam' e, V N

    1987-01-01

    Solutions of lithium tetrafluoborate in 1,3-dioxolane (DOL) in temperature range and concentrations limiting the homogeneity region from the side of salt crystallization and formation of polymer structures from -30 deg to +25 deg and from 10/sup -6/ to 1.4 mol/l. are investigated using methods of conductometry, densimetry, viscosimetry and by measuring time of spinlattice /sup 7/Li nuclei relaxation. The dissociation constant of LiBF/sub 4/ in DOL (pK/sub D/=4.9+-0.2 at 25 deg) is determined. Comparison with systems based on 1,2-dimethoxyethane and tetrahydrofurane studied earlier is carried out. Suppositions concerning considerable contribution of ion molecular structures with participation of salt ions and solvent molecules to electric conductivity are stated, and it agrees with the data on measurements of velocities of spin-lattice relaxation of /sup 7/Li nuclei.

  16. Lipopolysaccharide promotes lipid accumulation in human adventitial fibroblasts via TLR4-NF-κB pathway.

    Science.gov (United States)

    Wang, Jun; Si, Yanfang; Wu, Chen; Sun, Lu; Ma, Yudong; Ge, Aili; Li, Baomin

    2012-10-17

    Atherosclerosis is a chronic degenerative disease of the arteries and is thought to be one of the most common causes of death globally. In recent years, the functions of adventitial fibroblasts in the development of atherosclerosis and tissue repair have gained increased interests. LPS can increase the morbidity and mortality of atherosclerosis-associated cardiovascular disease. Although LPS increases neointimal via TLR4 activation has been reported, how LPS augments atherogenesis through acting on adventitial fibroblasts is still unknown. Here we explored lipid deposition within adventitial fibroblasts mediated by lipopolysaccharide (LPS) to imitate inflammatory conditions. In our study, LPS enhanced lipid deposition by the up-regulated expression of adipose differentiation-related protein (ADRP) as the silencing of ADRP abrogated lipid deposition in LPS-activated adventitial fibroblasts. In addition, pre-treatment with anti-Toll-like receptor 4 (TLR4) antibody diminished the LPS-induced lipid deposition and ADRP expression. Moreover, LPS induced translocation of nuclear factor-κB (NF-κB), which could markedly up-regulate lipid deposition as pre-treatment with the NF-κB inhibitor, PDTC, significantly reduced lipid droplets. In addition, the lowering lipid accumulation was accompanied with the decreased ADRP expression. Furthermore, LPS-induced adventitial fibroblasts secreted more monocyte chemoattractant protein (MCP-1), compared with transforming growth factor-β1 (TGF-β1). Taken together, these results suggest that LPS promotes lipid accumulation via the up-regulation of ADRP expression through TLR4 activated downstream of NF-κB in adventitial fibroblasts. Increased levels of MCP-1 released from LPS-activated adventitial fibroblasts and lipid accumulation may accelerate monocytes recruitment and lipid-laden macrophage foam cells formation. Here, our study provides a new explanation as to how bacterial infection contributes to the pathological process of

  17. Novel 1,3,4-Oxadiazole Induces Anticancer Activity by Targeting NF-κB in Hepatocellular Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Chakrabhavi Dhananjaya Mohan

    2018-03-01

    Full Text Available Aberrant activation of NF-κB is linked with the progression of human malignancies including hepatocellular carcinoma (HCC, and blockade of NF-κB signaling could be a potential target in the treatment of several cancers. Therefore, designing of novel small molecule inhibitors that target NF-κB activation is of prime importance in the treatment of several cancers. In the present work, we report the synthesis of series of 1,3,4-oxadiazoles, investigated their anticancer potential against HCC cells, and identified 2-(3-chlorobenzo[b]thiophen-2-yl-5-(3-methoxyphenyl-1,3,4-oxadiazole (CMO as the lead compound. Further, we examined the effect of CMO on cell cycle distribution (flow cytometry, apoptosis (annexin V-propidium iodide-FITC staining, and phosphorylation of NF-κB signaling pathway proteins (IκB and p65 in HCC cells. We found that CMO induced antiproliferative effect in dose- and time-dependent manner. Also, CMO significantly increased the percentage of sub-G1 cell population and induced apoptosis. Furthermore, CMO found to decrease the phosphorylation of IκB (Ser 32 in the cytoplasmic extract and p65 (Ser 536 in the nuclear extract of HCC cells. It also abrogated the DNA binding ability and transcriptional activity of NF-κB. CMO induced the cleavage of PARP and caspase-3 in a time-dependent manner. In addition, transfection with p65 small interfering RNA blocks CMO-induced caspase-3/7 activation. Molecular docking analysis revealed that CMO interacts with the hydrophobic region of p65 protein. Thus, we are reporting CMO as an inhibitor of NF-κB signaling pathway.

  18. Dinamics of BF3 sorption on activated carbons

    International Nuclear Information System (INIS)

    Polevoj, A.S.; Petrenko, A.E.

    1989-01-01

    The dynamics of BF 3 sorption on BAUAG-3 and SKT-4A carbons is studied by recording the curve of BF 3 concentration change in time at the outlet from the column filled with activated carbon when blowing it with a current of BF 3 and helium mixture. The effect of sorbent type, temperature and pressure of the gaseous mixture, BF 3 content in it and its partial pressure, BF 3 consumption on the width of sorption zone is studied. The results of studies can be used to calculate and optimize the conditions of sorption processes connected with the absorption of BF 3 by carbons from the gaseous flows in the dynamic mode

  19. Early induction of cytokines/cytokine receptors and Cox2, and activation of NF-κB in 4-nitroquinoline 1-oxide-induced murine oral cancer model

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yu-Ching [Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan (China); Department of Veterinary Medicine, National Chung Hsing University, Taichung 402, Taiwan (China); Ho, Heng-Chien; Lee, Miau-Rong [Department of Biochemistry, China Medical University, Taichung 404, Taiwan (China); Lai, Kuang-Chi [Department of Surgery, China Medical University Beigang Hospital, Yunlin 651, Taiwan (China); School of Medicine, China Medical University, Taichung 404, Taiwan (China); Yeh, Chung-Min; Lin, Yueh-Min [Department of Pathology, Changhua Christian Hospital, Changhua 500, Taiwan (China); Ho, Tin-Yun [School of Chinese Medicine, China Medical University, Taichung 404, Taiwan (China); Hsiang, Chien-Yun, E-mail: cyhsiang@mail.cmu.edu.tw [Department of Microbiology, China Medical University, Taichung 404, Taiwan (China); Chung, Jing-Gung, E-mail: jgchung@mail.cmu.edu.tw [Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan (China); Department of Biotechnology, Asia University, Taichung 413, Taiwan (China)

    2012-07-15

    The purpose of this study was to identify the genes induced early in murine oral carcinogenesis. Murine tongue tumors induced by the carcinogen, 4-nitroquinoline 1-oxide (4-NQO), and paired non-tumor tissues were subjected to microarray analysis. Hierarchical clustering of upregulated genes in the tumor tissues revealed an association of induced genes with inflammation. Cytokines/cytokine receptors induced early were subsequently identified, clearly indicating their involvement in oral carcinogenesis. Hierarchical clustering also showed that cytokine-mediated inflammation was possibly linked with Mapk6. Cox2 exhibited the greatest extent (9–18 fold) of induction in the microarray data, and its early induction was observed in a 2 h painting experiment by RT-PCR. MetaCore analysis showed that overexpressed Cox2 may interact with p53 and transcriptionally inhibit expression of several downstream genes. A painting experiment in transgenic mice also demonstrated that NF-κB activates early independently of Cox2 induction. MetaCore analysis revealed the most striking metabolic alterations in tumor tissues, especially in lipid metabolism resulting from the reduction of Pparα and Rxrg. Reduced expression of Mapk12 was noted, and MetaCore analysis established its relationship with decreased efficiency of Pparα phosphorylation. In conclusion, in addition to cytokines/cytokine receptors, the early induction of Cox2 and NF-κB activation is involved in murine oral carcinogenesis.

  20. Early induction of cytokines/cytokine receptors and Cox2, and activation of NF-κB in 4-nitroquinoline 1-oxide-induced murine oral cancer model

    International Nuclear Information System (INIS)

    Liu, Yu-Ching; Ho, Heng-Chien; Lee, Miau-Rong; Lai, Kuang-Chi; Yeh, Chung-Min; Lin, Yueh-Min; Ho, Tin-Yun; Hsiang, Chien-Yun; Chung, Jing-Gung

    2012-01-01

    The purpose of this study was to identify the genes induced early in murine oral carcinogenesis. Murine tongue tumors induced by the carcinogen, 4-nitroquinoline 1-oxide (4-NQO), and paired non-tumor tissues were subjected to microarray analysis. Hierarchical clustering of upregulated genes in the tumor tissues revealed an association of induced genes with inflammation. Cytokines/cytokine receptors induced early were subsequently identified, clearly indicating their involvement in oral carcinogenesis. Hierarchical clustering also showed that cytokine-mediated inflammation was possibly linked with Mapk6. Cox2 exhibited the greatest extent (9–18 fold) of induction in the microarray data, and its early induction was observed in a 2 h painting experiment by RT-PCR. MetaCore analysis showed that overexpressed Cox2 may interact with p53 and transcriptionally inhibit expression of several downstream genes. A painting experiment in transgenic mice also demonstrated that NF-κB activates early independently of Cox2 induction. MetaCore analysis revealed the most striking metabolic alterations in tumor tissues, especially in lipid metabolism resulting from the reduction of Pparα and Rxrg. Reduced expression of Mapk12 was noted, and MetaCore analysis established its relationship with decreased efficiency of Pparα phosphorylation. In conclusion, in addition to cytokines/cytokine receptors, the early induction of Cox2 and NF-κB activation is involved in murine oral carcinogenesis.

  1. Effect of X-irradiation on DNA binding activity of NF-kB in EL-4 cells

    International Nuclear Information System (INIS)

    He Shujie; Jin Shunzi; Liu Shuzheng

    2002-01-01

    Changes in time course of the DNA-binding activity of NF-κB as well as the subcellular localization of p65 subunit and expression of IκBα in EL-4 cells after irradiation with 2 Gy and 0.075 Gy X-rays were examined using electrophoresis mobility shift assay (EMSA) and immunohistochemistry (IHC), respectively. Results showed that the increases in DNA-binding activity of NF-κB p50/p50 and p50/p65 were induced by both 0.075 Gy and 2 Gy X-rays. However, the amplitude of the increase in activity of the two dimers was different after irradiation with the two doses of X-rays. After irradiation with 0.075 Gy, the increase in p50/p65 activity was higher than that of p50/p50 activity. After irradiation with 2 Gy, the situation was reversed. Irradiation with both 2 Gy and 0.075 Gy induced an increase in the rate of p65 nuclear translocation and the degradation of IκBα before the increase of its expression, but the degree of these changes after different dose irradiation was different. These results suggest that the transcriptional regulation of NF-κB changes with irradiation dose, resulted in the difference in responses of cells

  2. Bacterial endotoxin enhances colorectal cancer cell adhesion and invasion through TLR-4 and NF-kappaB-dependent activation of the urokinase plasminogen activator system.

    LENUS (Irish Health Repository)

    Killeen, S D

    2009-05-19

    Perioperative exposure to lipopolysaccharide (LPS) is associated with accelerated metastatic colorectal tumour growth. LPS directly affects cells through Toll-like receptor 4 (TLR-4) and the transcription factor NF-kappaB. The urokinase plasminogen activator (u-PA) system is intimately implicated in tumour cell extracellular matrix (ECM) interactions fundamental to tumour progression. Thus we sought to determine if LPS directly induces accelerated tumour cell ECM adhesion and invasion through activation of the u-PA system and to elucidate the cellular pathways involved. Human colorectal tumour cell lines were stimulated with LPS. u-PA concentration, u-PA activity, active u-PA, surface urokinase plasminogen activator receptor (u-PAR) and TLR-4 expression were assessed by ELISA, colorimetric assay, western blot analysis and flow cytometry respectively. In vitro tumour cell vitronectin adhesion and ECM invasion were analysed by vitronectin adhesion assay and ECM invasion chambers. u-PA and u-PAR function was inhibited with anti u-PA antibodies or the selective u-PA inhibitors amiloride or WXC-340, TLR-4 by TLR-4-blocking antibodies and NF-kappaB by the selective NF-kappaB inhibitor SN-50. LPS upregulates u-PA and u-PAR in a dose-dependent manner, enhancing in vitro tumour cell vitronectin adhesion and ECM invasion by >40% (P<0.01). These effects were ameliorated by u-PA and u-PAR inhibition. LPS activates NF-kappaB through TLR-4. TLR-4 and NF-kappaB inhibition ameliorated LPS-enhanced u-PA and u-PAR expression, tumour cell vitronectin adhesion and ECM invasion. LPS promotes tumour cell ECM adhesion and invasion through activation of the u-PA system in a TLR-4- and NF-kappaB-dependent manner.

  3. Hexaaquacopper(II bis(tetrafluoridoborate–pyrazine 1,4-dioxide (1/3

    Directory of Open Access Journals (Sweden)

    Jan L. Wikaira

    2013-04-01

    Full Text Available The crystal structure of the title compound, [Cu(H2O6](BF42·3C4H4N2O2, comprises discrete [Cu(H2O6]2+ cations and BF4− anions along with three equivalents of pyrazine 1,4-dioxide (pzdo. The hexaaquacopper(II ion and all three pzdo molecules lie about crystallographic inversion centers. The lattice is supported by an extensive hydrogen-bonding network. O—H...O hydrogen bonding between the [Cu(H2O6]2+ and pzdo units creates a pseudo-hexagonal lattice parallel to the bc plane. The BF4− anions lie in the voids of that lattice, held in place by O—H...F hydrogen bonds, and also generate BF4−–pzdo–BF4−–pzdo stacks via short F...N contacts [2.866 (3–3.283 (4 Å].

  4. Gastrodin stimulates anticancer immune response and represses transplanted H22 hepatic ascitic tumor cell growth: Involvement of NF-κB signaling activation in CD4 + T cells

    Energy Technology Data Exchange (ETDEWEB)

    Shu, Guangwen; Yang, Tianming [College of Pharmacy, South-Central University for Nationalities, Wuhan (China); Wang, Chaoyuan [College of Life Science, South-Central University for Nationalities, Wuhan (China); Su, Hanwen, E-mail: suhanwen-1@163.com [Renmin Hospital of Wuhan University, Wuhan (China); Xiang, Meixian, E-mail: xiangmeixian99@163.com [College of Pharmacy, South-Central University for Nationalities, Wuhan (China)

    2013-06-15

    Gastrodia elata Blume (G. elata) is a famous restorative food in East Asia. It can be used as an auxiliary reagent in hepatocellular carcinoma (HCC) treatment. Previous studies unveiled that G. elata exhibited immunomodulatory activities. To explore the active ingredients contributing to its immunomodulatory activities, gastrodin, vanillin, and parishin B were purified from G. elata and their anti-HCC effects were assessed in vivo. Among these compounds, only gastrodin was capable of repressing transplanted H22 ascitic hepatic tumor cell growth in vivo with low toxicity. Further investigations were designed to explore the effects of gastrodin on the immune system of tumor-bearing mice and potential molecular mechanisms underlying these effects. Our data showed that gastrodin ameliorated tumor cell transplantation-induced activation of endogenous pro-apoptotic pathway in CD4 + T cells and abnormalities in serum cytokine profiles in host animals. These events enhanced cytotoxic activities of natural killer and CD8 + T cells against H22 hepatic cancer cells. Gastrodin administration specifically upregulated mRNA levels of several nuclear factor κB (NF-κB) responsive genes in CD4 + T cells but not in CD8 + T cells. Chromatin immunoprecipitation assay showed that gastrodin increased the association of NF-κB p65 subunit to the promoter regions of IL-2 and Bcl-2 encoding genes in CD4 + T cells. Our investigations demonstrated that gastrodin is the main active ingredient contributing to the anticancer immunomodulatory properties of G. elata. Promoting NF-κB-mediated gene transcription in CD4 + T cells is implicated in its immunomodulatory activity. - Highlights: • Gastrodin stimulates anticancer immune response. • Gastrodin represses tumor transplantation-induced CD4 + T cell apoptosis. • Gastrodin activates NF-κB activity in CD4 + T cells.

  5. Gastrodin stimulates anticancer immune response and represses transplanted H22 hepatic ascitic tumor cell growth: Involvement of NF-κB signaling activation in CD4 + T cells

    International Nuclear Information System (INIS)

    Shu, Guangwen; Yang, Tianming; Wang, Chaoyuan; Su, Hanwen; Xiang, Meixian

    2013-01-01

    Gastrodia elata Blume (G. elata) is a famous restorative food in East Asia. It can be used as an auxiliary reagent in hepatocellular carcinoma (HCC) treatment. Previous studies unveiled that G. elata exhibited immunomodulatory activities. To explore the active ingredients contributing to its immunomodulatory activities, gastrodin, vanillin, and parishin B were purified from G. elata and their anti-HCC effects were assessed in vivo. Among these compounds, only gastrodin was capable of repressing transplanted H22 ascitic hepatic tumor cell growth in vivo with low toxicity. Further investigations were designed to explore the effects of gastrodin on the immune system of tumor-bearing mice and potential molecular mechanisms underlying these effects. Our data showed that gastrodin ameliorated tumor cell transplantation-induced activation of endogenous pro-apoptotic pathway in CD4 + T cells and abnormalities in serum cytokine profiles in host animals. These events enhanced cytotoxic activities of natural killer and CD8 + T cells against H22 hepatic cancer cells. Gastrodin administration specifically upregulated mRNA levels of several nuclear factor κB (NF-κB) responsive genes in CD4 + T cells but not in CD8 + T cells. Chromatin immunoprecipitation assay showed that gastrodin increased the association of NF-κB p65 subunit to the promoter regions of IL-2 and Bcl-2 encoding genes in CD4 + T cells. Our investigations demonstrated that gastrodin is the main active ingredient contributing to the anticancer immunomodulatory properties of G. elata. Promoting NF-κB-mediated gene transcription in CD4 + T cells is implicated in its immunomodulatory activity. - Highlights: • Gastrodin stimulates anticancer immune response. • Gastrodin represses tumor transplantation-induced CD4 + T cell apoptosis. • Gastrodin activates NF-κB activity in CD4 + T cells

  6. Andrographolide Suppress Tumor Growth by Inhibiting TLR4/NF-κB Signaling Activation in Insulinoma

    Science.gov (United States)

    Zhang, Qian-Qian; Ding, Yi; Lei, Yan; Qi, Cui-Ling; He, Xiao-Dong; Lan, Tian; Li, Jiang-Chao; Gong, Ping; Yang, Xuesong; Geng, Jian-Guo; Wang, Li-Jing

    2014-01-01

    Insulinomas are rare tumors, and approximately 10% of insulinomas are malignant. Accumulating evidence has implicated that we still lack effective therapy to treat the patients who are diagnosed with rare malignant insulinoma. Previous studies have reported that Andrographolide (Andro) could inhibit cell cycle progression, reduce cell invasion and induce cell apoptosis in many common cancer cells. However, the effects of andro are cell type-dependent. So we emplored the β-TC-6 cells and the RIP1-Tag2 transgenic mouse model of endogenously growing insulinoma model to elucidate the possible anti-cancer effect of Andro on insulinoma, an uncommon type of malignant cancers in this study. Our experiments revealed that Andro significantly inhibited tumor growth at both the early-stage and the advanced-stage of insulinoma through targeting the TLR4/NF-κB signaling pathway. This work initially provides the evidence that the TLR4/NF-κB signaling pathway might be vital as a potential therapeutic target, and also indispensable in Andro-mediated anti-cancer effect in insulinoma. PMID:24719558

  7. URG4/URGCP enhances the angiogenic capacity of human hepatocellular carcinoma cells in vitro via activation of the NF-κB signaling pathway

    International Nuclear Information System (INIS)

    Xing, Sizhong; Zhang, Bing; Hua, Ruixi; Tai, William Chi-shing; Zeng, Zhirong; Xie, Binhui; Huang, Chenghui; Xue, Jisu; Xiong, Shiqiu; Yang, Jianyong; Liu, Side; Li, Heping

    2015-01-01

    Angiogenesis is essential for tumor growth. Hepatocellular carcinoma (HCC) is characterized by hypervascularity; high levels of angiogenesis are associated with poor prognosis and a highly invasive phenotype in HCC. Up-regulated gene-4 (URG4), also known as upregulator of cell proliferation (URGCP), is overexpressed in multiple tumor types and has been suggested to act as an oncogene. This study aimed to elucidate the effect of URG4/URGCP on the angiogenic capacity of HCC cells in vitro. Expression of URG4/URGCP in HCC cell lines and normal liver epithelial cell lines was examined by Western blotting and quantitative real-time PCR. URG4/URGCP was stably overexpressed or transiently knocked down using a shRNA in two HCC cell lines. The human umbilical vein endothelial cell (HUVEC) tubule formation and Transwell migration assays and chicken chorioallantoic membrane (CAM) assay were used to examine the angiogenic capacity of conditioned media from URG4/URGCP-overexpressing and knockdown cells. A luciferase reporter assay was used to examine the transcriptional activity of nuclear factor kappa – light – chain - enhancer of activated B cells (NF-κB). NF-κB was inhibited by overexpressing degradation-resistant mutant inhibitor of κB (IκB)-α. Expression of vascular endothelial growth factor C (VEGFC), tumor necrosis factor-α (TNFα), interleukin (IL)-6, IL-8 and v-myc avian myelocytomatosis viral oncogene homolog (MYC) were examined by quantitative real-time PCR; VEGFC protein expression was analyzed using an ELISA. URG4/URGCP protein and mRNA expression were significantly upregulated in HCC cell lines. Overexpressing URG4/URGCP enhanced - while silencing URG4/URGCP decreased - the capacity of HCC cell conditioned media to induce HUVEC tubule formation and migration and neovascularization in the CAM assay. Furthermore, overexpressing URG4/URGCP increased - whereas knockdown of URG4/URGCP decreased - VEGFC expression, NF-κB transcriptional activity, the levels

  8. 2,2',4,4'-Tetrachlorobiphenyl upregulates cyclooxygenase-2 in HL-60 cells via p38 mitogen-activated protein kinase and NF-κB

    International Nuclear Information System (INIS)

    Bezdecny, Steven A.; Karmaus, Peer; Roth, Robert A.; Ganey, Patricia E.

    2007-01-01

    Polychlorinated biphenyls (PCBs) are ubiquitous, persistent environmental contaminants that affect a number of cellular systems, including neutrophils. Among the effects caused by the noncoplanar PCB 2,2',4,4'-tetrachlorobiphenyl (2244-TCB) in granulocytic HL-60 cells are increases in superoxide anion production, activation of phospholipase A 2 with subsequent release of arachidonic acid (AA) and upregulation of the inflammatory gene cyclooxygenase-2 (COX-2). The objective of this study was to determine the signal transduction pathways involved in the upregulation of COX-2 by 2244-TCB. Treatment of HL-60 cells with 2244-TCB led to increased expression of COX-2 mRNA. This increase was prevented by the transcriptional inhibitor actinomycin D in cells pretreated with 2244-TCB for 10 min. The increase in COX-2 mRNA was associated with release of 3 H-AA, phosphorylation of p38 and extracellular signal-regulated kinase (ERK) mitogen-activated protein (MAP) kinases, increased levels of nuclear NF-κB and increased superoxide anion production. Bromoenol lactone, an inhibitor of the calcium-independent phospholipase A 2 , reduced 3 H-AA release but had no effect on COX-2 mRNA, protein or activity. Pretreatment with SB-202190 or SB-203580, inhibitors of the p38 MAP kinase pathway, prevented the 2244-TCB-mediated induction of COX-2 and phosphorylation of p38 and ERK MAP kinases. These inhibitors did not alter 3 H-AA release. Treatment with PD 98059 or U 0126, inhibitors of the MAP/ERK (MEK) pathway, prevented the 2244-TCB-mediated activation of ERK but had no effect on COX-2 induction or p38 phosphorylation. 2244-TCB treatment did not affect c-Jun N-terminal kinase (JNK) phosphorylation. 2244-TCB exposure increased the amount of nuclear NF-κB. This increase was prevented by pretreatment with p38 MAP kinase inhibitors, but not by pretreatment with MEK inhibitors. Pretreatment with inhibitors of NF-κB prevented the 2244-TCB-mediated induction of COX-2 mRNA. 2244-TCB

  9. A mathematical method to calculate efficiency of BF3 detectors

    International Nuclear Information System (INIS)

    Si Fenni; Hu Qingyuan; Peng Taiping

    2009-01-01

    In order to calculate absolute efficiency of the BF 3 detector, MCNP/4C code is applied to calculate relative efficiency of the BF 3 detector first, and then absolute efficiency is figured out through mathematical techniques. Finally an energy response curve of the BF 3 detector for 1-20 MeV neutrons is derived. It turns out that efficiency of BF 3 detector are relatively uniform for 2-16 MeV neutrons. (authors)

  10. Photomagnetic studies on spin-crossover solid solutions containing two different metal complexes, [Fe(1-bpp)(2)](x)[M(terpy)2](1-x)[BF4]2 (M = Ru or Co).

    Science.gov (United States)

    Chastanet, Guillaume; Tovee, Clare A; Hyett, Geoffrey; Halcrow, Malcolm A; Létard, Jean-François

    2012-04-28

    The photomagnetic properties of two series of spin-crossover solid solutions, [Fe(1-bpp)(2)](x)[Ru(terpy)(2)](1-x)(BF(4))(2) and [Fe(1-bpp)(2)](x)[Co(terpy)(2)](1-x)(BF(4))(2) (1-bpp = 2,6-bis[pyrazol-1-yl]pyridine), have been investigated. For all the materials, the evolution of the T(LIESST) value, the high-spin → low-spin relaxation parameters and the LITH loops were thoroughly studied. Interestingly in the Fe:Co series, along the photo-excitation, cobalt ions are concomitantly converted from low-spin to high-spin states with the iron centres, and also fully relax after light excitation. This journal is © The Royal Society of Chemistry 2012

  11. Andrographolide suppresses proliferation of human colon cancer SW620 cells through the TLR4/NF-κB/MMP-9 signaling pathway.

    Science.gov (United States)

    Zhang, Rui; Zhao, Jian; Xu, Jian; Jiao, De-Xin; Wang, Jian; Gong, Zhi-Qiang; Jia, Jian-Hui

    2017-10-01

    Modern pharmacological research has revealed that andrographolide has various functions, including anti-bacterial, anti-inflammatory and anti-viral effects, immunoregulation, treating cardiovascular and cerebrovascular diseases, and prevention and treatment of alcoholic liver injury. The present study investigated whether andrographolide suppresses the proliferation of human colon cancer cell through the Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB/matrix metalloproteinase-9 (MMP-9) signaling pathway. The MTT assay and lactate dehydrogenase assay were used to evaluate the anticancer effects of andrographolide on cell proliferation and cytotoxicity in human colon cancer SW620 cells. Flow cytometry was used to analyze the anticancer effects of andrographolide on apoptosis by Annexin V-fluorescein isothiocyanate/propidium iodide kit. The effects of andrographolide on the activity of caspase-3/9 were measured using ELISA. Western blot analysis was also used to analyze the protein expression of TLR4, myeloid differentiation primary response gene 88 (MyD88), NF-κB-p65 and MMP-9. In the present study, it was found that andrographolide suppressed the cell proliferation, augmented cytotoxicity, evoked cell apoptosis and activated caspase-3/9 activities in human colon cancer SW620 cells. The results revealed that the anti-proliferation effects of andrographolide on the SW620 cells was associated with the inhibition of TLR4, MyD88, NF-κB-p65 and MMP-9 signaling activation. The results suggest that andrographolide is a promising drug for treatment of human colon cancer via suppression of the TLR4/NF-κB/MMP-9 signaling pathway.

  12. A dual-channel gas chromatography method for the quantitation of low and high concentrations of NF3 and CF4 to study membrane separation of the two compounds.

    Science.gov (United States)

    Branken, D J; le Roux, J P; Krieg, H M; Lachmann, G

    2013-09-13

    A dual-channel gas chromatographic method is described in this paper that can be conveniently used for quantitation of NF3/CF4 mixtures with a thermal conductivity detector (TCD) on one channel for the quantitation of high-concentrations, and a pulsed discharge helium ionization detector (PDHID) on a second channel for the quantitation of low concentrations. It is shown that adequate separation is achieved on both channels with this dual single-column setup in which column switching as used for NF3/CF4 analysis in industrial chromatographic methods are not required, thus yielding an effective analysis method for laboratory-scale investigations. In addition, the use of packed columns with purified divinylbenzene-styrene co-polymers as the sole stationary phase yields satisfactory resolution between NF3 and CF4 at isothermal conditions of 30°C, with elution times of less than 8min on the TCD channel and less than 4min on the PDHID channel. Consequently, this method allows for reliable, straight-forward quantitation of NF3/CF4 mixtures, which is necessary when studying the commercially important problem of NF3 and CF4 separation by different methods. Therefore, the applicability of the method to studying membrane separation of NF3 and CF4 is briefly discussed and illustrated, for which the dual-channel setup is especially beneficial. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Synthesis and Characterization of Pyridino(1,4-Η-cyclohexa-1,3-dieneDerivatives of Iron Tricarbonyl Complexes

    Directory of Open Access Journals (Sweden)

    T. I. Odiaka

    2011-01-01

    Full Text Available In this synthesis, we have been able to show that, the addition of x- substituted pyridines, (X = H, 2- Me, 3- Me 4- Me, 4-NH2 and 4-N(CH32 to the dienyl ring of the organometallic cation, [(Fe(CO3 (1-5- η-2-Me0C3H6]BF4 and [(Fe(CO3(1-5-η-C6H7]BF4 gives ionic substituted diene products, (X C5H4-C6H6Y (Fe(CO3] BF4,Y=H or 2-MeO. The reaction takes place at ordinary room temperature. The resulting products were isolated and characterized.

  14. Thermophysical properties of 1-butyl-4-methylpyridinium tetrafluoroborate

    International Nuclear Information System (INIS)

    Safarov, Javid; Kul, Ismail; El-Awady, Waleed A.; Nocke, Jürgen; Shahverdiyev, Astan; Hassel, Egon

    2012-01-01

    Highlights: ► (p, ρ, T) data of 1-butyl-4-methylpyridinium tetrafluoroborate are estimated. ► The measurements were carried out with a vibration-tube densimeter. ► The thermomechanical coefficients were calculated. - Abstract: Thermophysical properties, {(p, ρ, T) at T = (283.15 to 393.15) K, pressures up to p = 100 MPa, and viscosity at T = (283.15 to 373.15) K and p = 0.101 MPa}, of 1-butyl-4-methylpyridinium tetrafluoroborate [b4mpy][BF 4 ] are reported. The measurements were carried out with a recently constructed Anton-Paar DMA HPM vibration-tube densimeter and a fully automated SVM 3000 Anton-Paar rotational Stabinger viscometer. The vibration-tube densimeter was calibrated using double-distilled water, methanol, toluene, and aqueous NaCl solutions. An empirical equation of state for fitting of the (p, ρ, T) data of [b4mpy][BF 4 ] has been developed as a function of pressure and temperature to calculate the thermal properties of the ionic liquid (IL), such as isothermal compressibility, isobaric thermal expansibility, differences in isobaric and isochoric heat capacities, thermal pressure coefficient, and internal pressure. Internal pressure and the temperature coefficient of internal pressure data were used to make conclusions on the molecular characteristics of the IL.

  15. Maraviroc is associated with latent HIV-1 reactivation through NF-κB activation in resting CD4+ T cells from HIV-Infected Individuals on Suppressive Antiretroviral Therapy.

    Science.gov (United States)

    Madrid-Elena, Nadia; García-Bermejo, María Laura; Serrano-Villar, Sergio; Díaz-de Santiago, Alberto; Sastre, Beatriz; Gutiérrez, Carolina; Dronda, Fernando; Coronel Díaz, María; Domínguez, Ester; López-Huertas, María Rosa; Hernández-Novoa, Beatriz; Moreno, Santiago

    2018-02-14

    Maraviroc is a CCR5 antagonist used in the treatment of HIV-1 infection. We and others have suggested that maraviroc could reactivate latent HIV-1. To test the latency reversing potential of maraviroc and the mechanisms involved, we performed a phase-II, single-center, open-label study in which maraviroc was administered for 10 days to 20 HIV-1-infected individuals on suppressive antiretroviral therapy (Eudra CT: 2012-003215-66). All patients completed full maraviroc dosing and follow up. The primary endpoint was to study whether maraviroc may reactivate HIV-1 latency, eliciting signalling pathways involved in the viral reactivation. An increase in HIV-1 transcription in resting CD4 + T-cells, estimated by HIV-1 unspliced RNA, was observed. Moreover, activation of the NF-κB transcription factor was observed in these cells. In contrast, AP-1 and NFAT activity was not detected. To elucidate the mechanism of NF-κB activation by maraviroc, we have evaluated in HeLa P4 C5 cells, which stably express CCR5, if maraviroc could be acting as a partial CCR5-agonist, with no other mechanisms or pathways involved. Our results show that maraviroc can induce NF-κB activity and NF-κB target genes expression by CCR5 binding, since the use of TAK779, a CCR5 inhibitor, blocked NF-κB activation and functionality. Taken together, we show that maraviroc may have a role in the activation of latent virus transcription through the activation of NF-κB as a result of binding CCR5. Our results strongly support a novel use of maraviroc as a potential latency reversal agent in HIV-1-infected patients. IMPORTANCE HIV-1 persistence in a small pool of long-lived latently infected resting CD4 + T-cells is a major barrier to viral eradication in HIV-1-infected patients on antiretroviral therapy. A potential strategy to cure HIV-1-infection is the use of latency reversing agents to eliminate the reservoirs established in resting CD4 + T-cells. As no drug has been shown to be completely

  16. The Cytoprotective Effects of E-α-(4-Methoxyphenyl-2',3,4,4'-Tetramethoxychalcone (E-α-p-OMe-C6H4-TMC--A Novel and Non-Cytotoxic HO-1 Inducer.

    Directory of Open Access Journals (Sweden)

    Kai B Kaufmann

    Full Text Available Cell protection against different noxious stimuli like oxidative stress or chemical toxins plays a central role in the treatment of many diseases. The inducible heme oxygenase isoform, heme oxygenase-1 (HO-1, is known to protect cells against a variety of harmful conditions including apoptosis. Because a number of medium strong electrophiles from a series of α-X-substituted 2',3,4,4'-tetramethoxychalcones (α-X-TMCs, X = H, F, Cl, Br, I, CN, Me, p-NO2-C6H4, Ph, p-OMe-C6H4, NO2, CF3, COOEt, COOH had proven to activate Nrf2 resulting in HO-1 induction and inhibit NF-κB downstream target genes, their protective effect against staurosporine induced apoptosis and reactive oxygen species (ROS production was investigated. RAW264.7 macrophages treated with 19 different chalcones (15 α-X-TMCs, chalcone, 2'-hydroxychalcone, calythropsin and 2'-hydroxy-3,4,4'-trimethoxychalcone prior to staurosporine treatment were analyzed for apoptosis and ROS production, as well as HO-1 protein expression and enzyme activity. Additionally, Nrf2 and NF-κB activity was assessed. We found that amongst all tested chalcones only E-α-(4-methoxyphenyl-2',3,4,4'-tetramethoxychalcone (E-α-p-OMe-C6H4-TMC demonstrated a distinct, statistically significant antiapoptotic effect in a dose dependent manner, showing no toxic effects, while its double bond isomer Z-α-p-OMe-C6H4-TMC displayed no significant activity. Also, E-α-p-OMe-C6H4-TMC induced HO-1 protein expression and increased HO-1 activity, whilst inhibition of HO-1 by SnPP-IX abolished its antiapoptotic effect. The only weakly electrophilic chalcone E-α-p-OMe-C6H4-TMC reduced the staurosporine triggered formation of ROS, while inducing the translocation of Nrf2 into the nucleus. Furthermore, staurosporine induced NF-κB activity was attenuated following E-α-p-OMe-C6H4-TMC treatment. Overall, E-α-p-OMe-C6H4-TMC demonstrated its effective cytoprotective potential via a non-toxic induction of HO-1 in RAW264

  17. pVT-Second Virial Coefficients B(T ), Viscosity η(T ), and Self-Diffusion ρD(T) of the Gases: BF3, CF4, SiF4, CCl4, SiCl4, SF6, MoF6, WF6, UF6, C(CH3)4, and Si(CH3)4 Determined by Means of an Isotropic Temperature-Dependent Potential

    Science.gov (United States)

    Zarkova, L.; Hohm, U.

    2002-03-01

    We present results on self-consistent calculations of second pVT-virial coefficients B(T), viscosity data η(T), and diffusion coefficients ρD(T) for eleven heavy globular gases: boron trifluoride (BF3), carbon tetrafluoride (CF4), silicon tetrafluoride (SiF4), carbon tetrachloride (CCl4), silicon tetrachloride (SiCl4), sulfur hexafluoride (SF6), molybdenum hexafluoride (MoF6), tungsten hexafluoride (WF6), uranium hexafluoride (UF6), tetramethyl methane (C(CH3)4, TMM), and tetramethyl silane (Si(CH3)4, TMS). The calculations are performed mainly in the temperature range between 200 and 900 K by means of isotropic n-6 potentials with temperature-dependent separation rm(T) and potential well depth ɛ(T). The potential parameters at T=0 K (ɛ, rm, n) and the enlargement of the first level radii δ are obtained solving an ill-posed problem of minimizing the squared deviations between experimental and calculated values normalized to their relative experimental error. The temperature dependence of the potential is obtained as a result of the influence of vibrational excitation on binary interactions. This concept of the isotropic temperature-dependent potential (ITDP) is presented in detail where gaseous SF6 will serve as an example. The ITDP is subsequently applied to all other gases. This approach and the main part of the results presented here have already been published during 1996-2000. However, in some cases the data are upgraded due to the recently improved software (CF4, SF6) and newly found experimental data (CF4, SiF4, CCl4, SF6).

  18. 2',4-Dihydroxy-3',4',6'-trimethoxychalcone from Chromolaena odorata possesses anti-inflammatory effects via inhibition of NF-κB and p38 MAPK in lipopolysaccharide-activated RAW 264.7 macrophages.

    Science.gov (United States)

    Dhar, Rana; Kimseng, Rungruedee; Chokchaisiri, Ratchanaporn; Hiransai, Poonsit; Utaipan, Tanyarath; Suksamrarn, Apichart; Chunglok, Warangkana

    2018-02-01

    Immune dysregulation has been implicated in the pathogenesis of many diseases. Macrophages play a crucial role contributing to the onset, progression, and resolution of inflammation. Macrophage inflammatory mediators are of considerable interest as potential targets to treat inflammatory diseases. The present study was conducted to elucidate the anti-inflammatory mechanism of 2',4-dihydroxy-3',4',6'-trimethoxychalcone (1), the major chalcone isolated from Chromolaena odorata (L.) R.M.King & H.Rob, against lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophages. Cell viability, nitric oxide (NO), and proinflammatory cytokines of LPS-activated RAW 264.7 cells were measured by MTT, Griess, and ELISA assays, respectively. Cell lysates were subjected to Western blotting for investigation of protein expression. Treatment with the major chalcone 1 significantly attenuated the production of NO and proinflammatory cytokines, tumor necrosis factor-α, interleukin-1β, and interleukin-6 in a dose-dependent manner. The chalcone suppressed nuclear factor-κB (NF-κB) stimulation by preventing activation of inhibitor κB kinase (IKK) α/β, degradation of inhibitor κB (IκB) α, and translocation of p65 NF-κB into the nucleus. Additionally, the chalcone markedly repressed the phosphorylation of p38 mitogen-activated protein kinase (MAPK), but no further inhibition was detected for c-Jun N-terminal activated kinases or extracellular regulated kinases. Thus, suppression of NF-κB and p38 MAPK activation may be the core mechanism underlying the anti-inflammatory activity of 2',4-dihydroxy-3',4',6'-trimethoxychalcone (1). These findings provide evidence that 2',4-dihydroxy-3',4',6'-trimethoxychalcone (1) possesses anti-inflammatory activity via targeting proinflammatory macrophages. This anti-inflammatory chalcone is a promising compound for reducing inflammation.

  19. Andrographolide Ameliorates Liver Fibrosis in Mice: Involvement of TLR4/NF-κB and TGF-β1/Smad2 Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Liteng Lin

    2018-01-01

    Full Text Available Liver fibrosis is characterized by activated hepatic stellate cells (HSC and extracellular matrix accumulation. Blocking the activation of HSC and the inflammation response are two major effective therapeutic strategies for liver fibrosis. In addition to the long history of using andrographolide (Andro for inflammatory disorders, we aimed at elucidating the pharmacological effects and potential mechanism of Andro on liver fibrosis. In this study, liver fibrosis was induced by carbon tetrachloride (CCl4 and the mice were intraperitoneally injected with Andro for 6 weeks. HSC cell line (LX-2 and primary HSC were also treated with Andro in vitro. Treatment of CCl4-induced mice with Andro decreased the levels of alanine aminotransferase (ALT and aspartate aminotransferase (AST, Sirius red staining as well as the expression of α smooth muscle actin (α-SMA and transforming growth factor- (TGF- β1. Furthermore, the expression of Toll-like receptor (TLR4 and NF-κB p50 was also inhibited by Andro. Additionally, in vitro data confirmed that Andro treatment not only attenuated the expression of profibrotic and proinflammatory factors but also blocked the TGF-β1/Smad2 and TLR4/NF-κB p50 pathways. These results demonstrate that Andro prevents liver inflammation and fibrosis, which is in correlation with the inhibition of the TGF-β1/Smad2 and TLR4/NF-κB p50 pathways, highlighting Andro as a potential therapeutic strategy for liver fibrosis.

  20. Inhibition of HMGB1 reduces rat spinal cord astrocytic swelling and AQP4 expression after oxygen-glucose deprivation and reoxygenation via TLR4 and NF-κB signaling in an IL-6-dependent manner.

    Science.gov (United States)

    Sun, Lin; Li, Man; Ma, Xun; Feng, Haoyu; Song, Junlai; Lv, Cong; He, Yajun

    2017-11-25

    Spinal cord astrocyte swelling is an important component to spinal cord edema and is associated with poor functional recovery as well as therapeutic resistance after spinal cord injury (SCI). High mobility group box-1 (HMGB1) is a mediator of inflammatory responses in the central nervous system and plays a critical role after SCI. Given this, we sought to identify both the role and underlying mechanisms of HMGB1 in cellular swelling and aquaporin 4 (AQP4) expression in cultured rat spinal cord astrocytes after oxygen-glucose deprivation/reoxygenation (OGD/R). The post-natal day 1-2 Sprague-Dawley rat spinal cord astrocytes were cultured in vitro, and the OGD/R model was induced. We first investigated the effects of OGD/R on spinal cord astrocytic swelling and HMGB1 and AQP4 expression, as well as HMGB1 release. We then studied the effects of HMGB1 inhibition on cellular swelling, HMGB1 and AQP4 expression, and HMGB1 release. The roles of both toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway and interleukin-6 (IL-6) in reducing cellular swelling resulting from HMGB1 inhibition in spinal cord astrocytes after OGD/R were studied. Intergroup data were compared using one-way analysis of variance (ANOVA) followed by Dunnett's test. The OGD/R increased spinal cord astrocytic swelling and HMGB1 and AQP4 expression, as well as HMGB1 release. Inhibition of HMGB1 using either HMGB1 shRNA or ethyl pyruvate resulted in reduced cellular volume, mitochondrial and endoplasmic reticulum swelling, and lysosome number and decreased upregulation of both HMGB1 and AQP4 in spinal cord astrocytes, as well as HMGB1 release. The HMGB1 effects on spinal cord astrocytic swelling and AQP4 upregulation after OGD/R were mediated-at least in part-via activation of TLR4, myeloid differentiation primary response gene 88 (MyD88), and NF-κB. These activation effects can be repressed by TLR4 inhibition using CLI-095 or C34, or by NF-κB inhibition using BAY 11

  1. Effects of returning NF concentrate on the MBR-NF process treating antibiotic production wastewater.

    Science.gov (United States)

    Li, Kun; Cheng, Yutao; Wang, Jianxing; Zhang, Junya; Liu, Jibao; Yu, Dawei; Li, Mingyue; Wei, Yuansong

    2016-07-01

    The optimization of the nanofiltration (NF) concentrate backflow ratio (R cb) and the influence of the NF concentrate on the performance of membrane bioreactor-nanofiltration (MBR-NF) process treating antibiotic production wastewater were investigated on a laboratory scale. The R cb was optimized at 60 % based on the removal rates of chemical oxygen demand (COD) and NH4 (+)-N by MBR. Data analyses indicated that salinity brought by NF concentrate is the major driver leading to the decrease of sludge activity, especially at a high R cb. EPS analysis showed that electric conductivity (EC), proteins in soluble microbial products (SMP), and SMP brought by NF concentrate are the dominant factors causing the severe membrane fouling in MBR. Furthermore, undegradable substances including fulvic acid-like and humic acid-like compounds accumulated in NF concentrate showed significant influence on fouling of NF. MBR could well degrade small MW compounds in NF concentrate, which confirmed the enhancement of organic removal efficiency by recycling the NF concentrate to MBR. The MBR-NF process showed a relatively stable performance at the R cb of 60 % (volume reduction factor (VRF) = 5), and the NF permeate could satisfy the water quality standard for fermentation process with a water recovery rate of 90.9 %.

  2. Atmospheric observations for quantifying emissions of point-source synthetic greenhouse gases (CF4, NF3 and HFC-23)

    Science.gov (United States)

    Arnold, Tim; Manning, Alistair J.; Li, Shanlan; Kim, Jooil; Park, Sunyoung; Fraser, Paul J.; Mitrevski, Blagoj; Steele, L. Paul; Krummel, Paul B.; Mühle, Jens; Weiss, Ray F.

    2016-04-01

    The fluorinated species carbon tetrafluoride (CF4; PFC-14), nitrogen trifluoride (NF3) and trifluoromethane (CHF3; HFC-23) are potent greenhouse gases with 100-year global warming potentials of 6,630, 16,100 and 12,400, respectively. Unlike the majority of CFC-replacement compounds that are emitted from fugitive and mobile emission sources, these gases are largely emitted from large single point sources - semiconductor manufacturing facilities (all three), aluminium smelting plants (CF4) and chlorodifluoromethane factories (HFC-23). In this work we show the potential for atmospheric measurements to understand regional sources of these gases and to highlight emission 'hotspots'. We target our analysis on measurements from two Advanced Global Atmospheric Gases Experiment (AGAGE) long term monitoring sites that are particularly sensitive to regional emissions of these gases: Gosan on Jeju Island in the Republic of Korea and Cape Grim on Tasmania in Australia. These sites measure CF4, NF3 and HFC-23 alongside a suite of greenhouse and stratospheric ozone depleting gases every two hours using automated in situ gas-chromatography mass-spectrometry instrumentation. We couple each measurement to an analysis of air history using the regional atmospheric transport model NAME (Numerical Atmospheric dispersion Modelling Environment) driven by 3D meteorology from the Met Office's Unified Model, and use a Bayesian inverse method (InTEM - Inversion Technique for Emission Modelling) to calculate yearly emission changes over a decade (2005-2015) at high spatial resolution. At present these gases make a small contribution to global radiative forcing, however, given that their impact could rise significantly and that point sources of such gases can be mitigated, atmospheric monitoring could be an important tool for aiding emissions reduction policy.

  3. Functional conservation of rice OsNF-YB/YC and Arabidopsis AtNF-YB/YC proteins in the regulation of flowering time

    KAUST Repository

    Hwang, Yoon-Hyung; Kim, SoonKap; Lee, Keh Chien; Chung, Young Soo; Lee, Jeong Hwan; Kim, Jeong-Kook

    2016-01-01

    Plant NUCLEAR FACTOR Y (NF-Y) transcription factors play important roles in plant development and abiotic stress. In Arabidopsis thaliana, two NF-YB (AtNF-YB2 and AtNF-YB3) and five NF-YC (AtNF-YC1, AtNF-YC2, AtNF-YC3, AtNF-YC4, and AtNF-YC9) genes regulate photoperiodic flowering by interacting with other AtNF-Y subunit proteins. Three rice NF-YB (OsNF-YB8, OsNF-YB10, and OsNF-YB11) and five rice OsNF-YC (OsNF-YC1, OsNF-YC2, OsNF-YC4, OsNF-YC6, and OsNF-YC7) genes are clustered with two AtNF-YB and five AtNF-YC genes, respectively. To investigate the functional conservation of these NF-YB and NF-YC genes in rice and Arabidopsis, we analyzed the flowering phenotypes of transgenic plants overexpressing the respective OsNF-YB and OsNF-YC genes in Arabidopsis mutants. Overexpression of OsNF-YB8/10/11 and OsNF-YC2 complemented the late flowering phenotype of Arabidopsis nf-yb2 nf-yb3 and nf-yc3 nf-yc4 nf-yc9 mutants, respectively. The rescued phenotype of 35S::OsNF-YC2 nf-yc3 nf-yc4 nf-yc9 plants was attributed to the upregulation of FLOWERING LOCUS T (FT) and SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1). In vitro and in planta protein–protein analyses revealed that OsNF-YB8/10/11 and OsNF-YC1/2/4/6/7 interact with AtNF-YC3/4/9 and AtNF-YB2/3, respectively. Our data indicate that some OsNF-YB and OsNF-YC genes are functional equivalents of AtNF-YB2/3 and AtNF-YC3/4/9 genes, respectively, and suggest functional conservation of Arabidopsis and rice NF-Y genes in the control of flowering time.

  4. Functional conservation of rice OsNF-YB/YC and Arabidopsis AtNF-YB/YC proteins in the regulation of flowering time

    KAUST Repository

    Hwang, Yoon-Hyung

    2016-01-11

    Plant NUCLEAR FACTOR Y (NF-Y) transcription factors play important roles in plant development and abiotic stress. In Arabidopsis thaliana, two NF-YB (AtNF-YB2 and AtNF-YB3) and five NF-YC (AtNF-YC1, AtNF-YC2, AtNF-YC3, AtNF-YC4, and AtNF-YC9) genes regulate photoperiodic flowering by interacting with other AtNF-Y subunit proteins. Three rice NF-YB (OsNF-YB8, OsNF-YB10, and OsNF-YB11) and five rice OsNF-YC (OsNF-YC1, OsNF-YC2, OsNF-YC4, OsNF-YC6, and OsNF-YC7) genes are clustered with two AtNF-YB and five AtNF-YC genes, respectively. To investigate the functional conservation of these NF-YB and NF-YC genes in rice and Arabidopsis, we analyzed the flowering phenotypes of transgenic plants overexpressing the respective OsNF-YB and OsNF-YC genes in Arabidopsis mutants. Overexpression of OsNF-YB8/10/11 and OsNF-YC2 complemented the late flowering phenotype of Arabidopsis nf-yb2 nf-yb3 and nf-yc3 nf-yc4 nf-yc9 mutants, respectively. The rescued phenotype of 35S::OsNF-YC2 nf-yc3 nf-yc4 nf-yc9 plants was attributed to the upregulation of FLOWERING LOCUS T (FT) and SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1). In vitro and in planta protein–protein analyses revealed that OsNF-YB8/10/11 and OsNF-YC1/2/4/6/7 interact with AtNF-YC3/4/9 and AtNF-YB2/3, respectively. Our data indicate that some OsNF-YB and OsNF-YC genes are functional equivalents of AtNF-YB2/3 and AtNF-YC3/4/9 genes, respectively, and suggest functional conservation of Arabidopsis and rice NF-Y genes in the control of flowering time.

  5. Diclofenac pretreatment modulates exercise-induced inflammation in skeletal muscle of rats through the TLR4/NF-κB pathway.

    Science.gov (United States)

    Barcelos, Rômulo Pillon; Bresciani, Guilherme; Cuevas, Maria José; Martínez-Flórez, Susana; Soares, Félix Alexandre Antunes; González-Gallego, Javier

    2017-07-01

    Nonsteroidal anti-inflammatory drugs, such as diclofenac, are widely used to treat inflammation and pain in several conditions, including sports injuries. This study analyzes the influence of diclofenac on the toll-like receptor-nuclear factor kappa B (TLR-NF-κB) pathway in skeletal muscle of rats submitted to acute eccentric exercise. Twenty male Wistar rats were divided into 4 groups: control-saline, control-diclofenac, exercise-saline, and exercise-diclofenac. Diclofenac or saline were administered for 7 days prior to an acute eccentric exercise bout. The inflammatory status was evaluated through mRNA levels of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), IL-1β, and tumor necrosis factor alpha (TNF-α), and protein content of COX-2, IL-6, and TNF-α in vastus lateralis muscle. Data obtained showed that a single bout of eccentric exercise significantly increased COX-2 gene expression. Similarly, mRNA expression and protein content of other inflammation-related genes also increased after the acute exercise. However, these effects were attenuated in the exercise + diclofenac group. TLR4, myeloid differentiation primary response gene 88 (MyD88), and p65 were also upregulated after the acute eccentric bout and the effect was blunted by the anti-inflammatory drug. These findings suggest that pretreatment with diclofenac may represent an effective tool to ameliorate the pro-inflammatory status induced by acute exercise in rat skeletal muscle possibly through an attenuation of the TLR4-NF-κB signaling pathway.

  6. 1H, 19F and 11B nuclear magnetic resonance characterization of BF3:amine catalysts used in the cure of C fiber-epoxy prepregs

    International Nuclear Information System (INIS)

    Happe, J.A.; Morgan, R.J.; Walkup, C.M.

    1983-12-01

    The chemical composition of commercial BF 3 :amine complexes are variable and contain BF 4 - and BF 3 (OH) - salts together with other unidentified highly reactive species. The BF 3 :amine complexes, which are susceptible to hydrolysis, also partially convert to the BF 4 - salt (i.e. BF 4 - NH 3 + C 2 H 5 ) upon heating. This salt formation is accelerated in dimethyl sulfoxide solution and in the presence of the epoxides that are present in commercial prepregs. Commercial C fiber-epoxy prepregs are shown to contain either BF 3 :NH 2 C 2 H 5 or BF 3 :NHC 5 H 10 species together with their BF 4 - salts and a variety of boron-fluorine or carbon-fluorine prepreg species. Considerable variation in the relative quantities of BF 3 :amine to its BF 4 - salt was observed from prepreg lot to lot, which will cause variable viscosity-time-temperature prepreg cure profiles. It is concluded that the chemically stable and mobile BF 4 - salt is the pre-dominant catalytic species, acting as a cationic catalyst for the prepreg cure reactions. During the early stages of cure the BF 3 :amine catalyst converts to the BF 4 - salt in the presence of epoxides, whereas the BF 3 -prepreg species are susceptible to catalytic deactivation and immobilization

  7. Cold-inducible RNA-binding protein mediates cold air inducible airway mucin production through TLR4/NF-κB signaling pathway.

    Science.gov (United States)

    Chen, Lingxiu; Ran, Danhua; Xie, Wenyue; Xu, Qing; Zhou, Xiangdong

    2016-10-01

    Mucus overproduction is an important feature in patients with chronic inflammatory airway diseases and cold air stimulation has been shown to be associated with the severity of these diseases. However, the regulatory mechanisms that mediate excessive mucin production under cold stress remain elusive. Recently, the cold-inducible RNA-binding protein (CIRP) has been shown to be markedly induced after exposure to cold air. In this study, we sought to explore the expression of CIRP within bronchial biopsy specimens, the effect on mucin5AC (MUC5AC) production in chronic inflammatory airway diseases and the potential signaling pathways involved in cold air stimulation process. We found that CIRP protein expression was significantly increased in patients with COPD and in mice treated with cold air. Moreover, cold air stimulation induced MUC5AC expression in wild-type mice but not in CIRP(-/-) mice. In vitro, cold air stress significantly elevated the transcriptional and protein expression levels of MUC5AC in human bronchial epithelial cells. CIRP, toll-like receptor 4 (TLR4) and phosphorylated NF-κB p65 (p-p65) increased significantly in response to cold stress and CIRP siRNA, TLR4 - neutralizing Ab and a specific inhibitor of NF-κB could attenuated cold stress inducible MUC5AC expression. In addition, CIRP siRNA could hindered the expression levels of TLR4 and p-p65 both induced by cold stress. Taken together, these results suggest that airway epithelial cells constitutively express CIRP in vitro and in vivo. CIRP is responsible for cold-inducible MUC5AC expression by activating TLR4/NF-κB signaling pathway. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Epstein-Barr virus EBNA2 directs doxorubicin resistance of B cell lymphoma through CCL3 and CCL4-mediated activation of NF-κB and Btk.

    Science.gov (United States)

    Kim, Joo Hyun; Kim, Won Seog; Hong, Jung Yong; Ryu, Kung Ju; Kim, Seok Jin; Park, Chaehwa

    2017-01-17

    Epstein-Barr virus (EBV)-encoded nuclear antigen, EBNA2, expressed in EBV-infected B lymphocytes is critical for lymphoblastoid cell growth. Microarray profiling and cytokine array screening revealed that EBNA2 is associated with upregulation of the chemokines CCL3 and CCL4 in lymphoma cells. Depletion or inactivation of CCL3 or CCL4 sensitized DLBCL cells to doxorubicin. Our results indicate that EBV influences cell survival via an autocrine mechanism whereby EBNA2 increases CCL3 and CCL4, which in turn activate the Btk and NF-κB pathways, contributing to doxorubicin resistance of B lymphoma cells. Western blot data further confirmed that CCL3 and CCL4 direct activation of Btk and NF-κB. Based on these findings, we propose that a pathway involving EBNA2/Btk/NF-κB/CCL3/CCL4 plays a key role in doxorubicin resistance, and therefore, inhibition of specific components of this pathway may sensitize lymphoma cells to doxorubicin. Evaluation of the relationship between CCL3 expression and EBV infection revealed high CCL3 levels in EBV-positive patients. Our data collectively suggest that doxorubicin treatment for EBNA2-positive DLBCL cells may be effectively complemented with a NF-κB or Btk inhibitor. Moreover, evaluation of the CCL3 and CCL4 levels may be helpful for selecting DLBCL patients likely to benefit from doxorubicin treatment in combination with the velcade or ibrutinib.

  9. Stacking reactions of the borole complex Cp*Rh(η5-C4H4BPh) with the dicationic fragments [Cp*M]2+ (M = Rh or Ir)

    International Nuclear Information System (INIS)

    Loginov, D.A.; Muratov, D.V.; Starikova, Z.A.; Petrovskij, P.V.; Kudinov, A.R.

    2006-01-01

    The reaction of the (borole)rhodium iodide complex [(η-C 4 H 4 BPh)RhI] 4 with Cp*Li afforded the sandwich compound Cp*Rh(η-C 4 H 4 BPh) (1). The reactions of compound 1 with the solvated complexes [Cp*M(MeNO 2 ) 3 ] 2+ (BF 4 - ) 2 gave triple-decker cationic complexes with the central borole ligand [Cp*Rh(μ-η 5 :η 5 -C 4 H 4 BPh)MCp*] 2+ (BF 4 - ) 2 (M = Rh or Ir). The structure of complex 1 was established by X-ray diffraction [ru

  10. Synthesis, characterization, structure and properties of heterobimetallic complexes [CuNi(μ-OAc) (μ-OH) (μ-OH2) (bpy)2] (BF4)2 and [CuNi(bz)3(bpy)2] ClO4 from 2,2‧ bipyridine

    Science.gov (United States)

    Kurbah, Sunshine D.; Kumar, A.; Syiemlieh, I.; Dey, A. K.; Lal, R. A.

    2018-02-01

    Heterobimetallic complexes of the composition [CuNi(bpy)2 (μ-OAc) (μ-OH) (μ-OH2)](BF4)2 (1) and [CuNi(bz)3 (bpy)2]ClO4 (2) were synthesized in moderate yield through solid state reaction and have been characterized by elemental analyses, molar conductance, mass spectra, magnetic moment, EPR, UV-Vis, IR spectroscopies and cyclic voltammetry. The ground state in complex (1) is doublet while that in complex (2), the ground state is a mixture of doublet and quartet, respectively. The structure of the complexes has been established by X-ray crystallography. The electron transfer reactions of the complexes have been investigated by cyclic voltammetry.

  11. Sinomenine inhibits breast cancer cell invasion and migration by suppressing NF-κB activation mediated by IL-4/miR-324-5p/CUEDC2 axis

    Energy Technology Data Exchange (ETDEWEB)

    Song, Lingqin, E-mail: qinlingsongxa@163.com [Department of Oncology, The Second Affiliated Hospital, Medical School of Xi' an Jiaotong University, Xi' an 710004 (China); Liu, Di; Zhao, Yang [Department of Oncology, The Second Affiliated Hospital, Medical School of Xi' an Jiaotong University, Xi' an 710004 (China); He, Jianjun [Department of Surgical Oncology, The First Affiliated Hospital, Medical School of Xi' an Jiaotong University, Xi' an 710061 (China); Kang, Huafeng; Dai, Zhijun; Wang, Xijing; Zhang, Shuqun; Zan, Ying [Department of Oncology, The Second Affiliated Hospital, Medical School of Xi' an Jiaotong University, Xi' an 710004 (China)

    2015-08-28

    Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a vital transcription factor that regulates multiple important biological processes, including the epithelial–mesenchymal transition (EMT) and metastasis of breast cancer. Sinomenine is an isoquinoline well known for its remarkable curative effect on rheumatic and arthritic diseases and can induce apoptosis of several cancer cell types. Recently, sinomenine was reported as a tumor suppressor via inhibiting cell proliferation and inducing apoptosis. However, the role and mechanism of sinomenine in invasion and metastasis of breast cancer are largely unknown. Here, we report that sinomenine suppressed the invasion and migration of MDA-MB-231 and 4T1 breast cancer cells in a dose-dependent manner. We detected binding of NF-κB to the inhibitor of NF-κB (IκB) after the MDA-MB-231 cells were treated with 0.25, 0.5, and 1 mM sinomenine. Co-IP analysis revealed that sinomenine enhanced the binding of NF-κB and IκB in a dose-dependent manner, suggesting that sinomenine had an effect on inactivation of NF-κB. Western blotting and ELISA approaches indicated that the suppression effect was closely associated with the phosphorylation of IκB kinase (IKK) and its negative regulator CUEDC2. Sinomenine treatment decreased miR-324-5p expression, thus increased the level of its target gene CUEDC2, and then blocked the phosphorylation of IKK through altering the upstream axis. Finally, transfection of a miR-324-5p mimic inhibited the suppression of invasion and metastasis of MDA-MB-231 and 4T1 cell by sinomenine, providing evidence that sinomenine treatment suppressed breast cancer cell invasion and metastasis via regulation of the IL4/miR-324-5p/CUEDC2 axis. Our findings reveal a novel mechanism by which sinomenine suppresses cancer cell invasion and metastasis, i.e., blocking NF-κB activation. - Highlights: • Sinomenine reduced invasion and migration of MDA-MB-231 and 4T1 breast cancer cells.

  12. Sinomenine inhibits breast cancer cell invasion and migration by suppressing NF-κB activation mediated by IL-4/miR-324-5p/CUEDC2 axis

    International Nuclear Information System (INIS)

    Song, Lingqin; Liu, Di; Zhao, Yang; He, Jianjun; Kang, Huafeng; Dai, Zhijun; Wang, Xijing; Zhang, Shuqun; Zan, Ying

    2015-01-01

    Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a vital transcription factor that regulates multiple important biological processes, including the epithelial–mesenchymal transition (EMT) and metastasis of breast cancer. Sinomenine is an isoquinoline well known for its remarkable curative effect on rheumatic and arthritic diseases and can induce apoptosis of several cancer cell types. Recently, sinomenine was reported as a tumor suppressor via inhibiting cell proliferation and inducing apoptosis. However, the role and mechanism of sinomenine in invasion and metastasis of breast cancer are largely unknown. Here, we report that sinomenine suppressed the invasion and migration of MDA-MB-231 and 4T1 breast cancer cells in a dose-dependent manner. We detected binding of NF-κB to the inhibitor of NF-κB (IκB) after the MDA-MB-231 cells were treated with 0.25, 0.5, and 1 mM sinomenine. Co-IP analysis revealed that sinomenine enhanced the binding of NF-κB and IκB in a dose-dependent manner, suggesting that sinomenine had an effect on inactivation of NF-κB. Western blotting and ELISA approaches indicated that the suppression effect was closely associated with the phosphorylation of IκB kinase (IKK) and its negative regulator CUEDC2. Sinomenine treatment decreased miR-324-5p expression, thus increased the level of its target gene CUEDC2, and then blocked the phosphorylation of IKK through altering the upstream axis. Finally, transfection of a miR-324-5p mimic inhibited the suppression of invasion and metastasis of MDA-MB-231 and 4T1 cell by sinomenine, providing evidence that sinomenine treatment suppressed breast cancer cell invasion and metastasis via regulation of the IL4/miR-324-5p/CUEDC2 axis. Our findings reveal a novel mechanism by which sinomenine suppresses cancer cell invasion and metastasis, i.e., blocking NF-κB activation. - Highlights: • Sinomenine reduced invasion and migration of MDA-MB-231 and 4T1 breast cancer cells.

  13. Heme activates TLR4-mediated inflammatory injury via MyD88/TRIF signaling pathway in intracerebral hemorrhage

    Directory of Open Access Journals (Sweden)

    Lin Sen

    2012-03-01

    Full Text Available Abstract Background Inflammatory injury plays a critical role in intracerebral hemorrhage (ICH-induced neurological deficits; however, the signaling pathways are not apparent by which the upstream cellular events trigger innate immune and inflammatory responses that contribute to neurological impairments. Toll-like receptor 4 (TLR4 plays a role in inflammatory damage caused by brain disorders. Methods In this study, we investigate the role of TLR4 signaling in ICH-induced inflammation. In the ICH model, a significant upregulation of TLR4 expression in reactive microglia has been demonstrated using real-time RT-PCR. Activation of microglia was detected by immunohistochemistry, cytokines were measured by ELISA, MyD88, TRIF and NF-κB were measured by Western blot and EMSA, animal behavior was evaluated by animal behavioristics. Results Compared to WT mice, TLR4−/− mice had restrained ICH-induced brain damage showing in reduced cerebral edema and lower neurological deficit scores. Quantification of cytokines including IL-6, TNF-α and IL-1β and assessment of macrophage infiltration in perihematoma tissues from TLR4−/−, MyD88−/− and TRIF−/− mice showed attenuated inflammatory damage after ICH. TLR4−/− mice also exhibited reduced MyD88 and TRIF expression which was accompanied by decreased NF-κB activity. This suggests that after ICH both MyD88 and TRIF pathways might be involved in TLR4-mediated inflammatory injury possibly via NF-κB activation. Exogenous hemin administration significantly increased TLR4 expression and microglial activation in cultures and also exacerbated brain injury in WT mice but not in TLR4−/− mice. Anti-TLR4 antibody administration suppressed hemin-induced microglial activation in cultures and in the mice model of ICH. Conclusions Our findings suggest that heme potentiates microglial activation via TLR4, in turn inducing NF-κB activation via the MyD88/TRIF signaling pathway, and ultimately

  14. BF-30 effectively inhibits ciprofloxacin-resistant bacteria in vitro and in a rat model of vaginosis.

    Science.gov (United States)

    Wang, Jing; Li, Bing; Li, Yang; Dou, Jie; Hao, Qingru; Tian, Yuwei; Wang, Hui; Zhou, Changlin

    2014-07-01

    Bacterial infections are becoming increasingly difficult to treat due to the increasing number of multidrug-resistant strains. Cathelicidin-BF (BF-30) is a cathelicidin-like antimicrobial peptide and exhibits broad antimicrobial activity against bacteria. In the present study, the antibacterial activity of BF-30 against ciprofloxacin-resistant Escherichia coli and Staphylococcus aureus was examined, and the protective effects of this peptide against these bacteria in rats with bacterial vaginosis were identified for the first time. The data showed that BF-30 had effective antimicrobial activities against ciprofloxacin-resistant E. coli and S. aureus. The minimal inhibitory concentrations for both bacterial strains were 16 μg/ml, and the minimal bactericidal concentrations were 64 and 128 μg/ml, respectively. A time course experiment showed that the CFU counts rapidly decreased after BF-30 treatment, and the bacteria were nearly eliminated within 4 h. BF-30 could reduce the fold change (CFU/ml) in local colonization by drug-resistant E. coli and S. aureus to 0.01 at a dose of 0.8 mg/kg/day in the rats' vaginal secretions. In addition, BF-30 induced membrane permeabilization and bound to the genomic DNA, interrupting protein synthesis. Taken together, our data demonstrate that BF-30 has potential therapeutic value for the prevention and treatment of bacterial vaginosis.

  15. Gold-quercetin nanoparticles prevent metabolic endotoxemia-induced kidney injury by regulating TLR4/NF-kB signaling and Nrf2 pathway in high fat diet fed mice

    Directory of Open Access Journals (Sweden)

    Xu MX

    2017-01-01

    Full Text Available Min-Xuan Xu,1,2,* Ming Wang,3,* Wei-Wei Yang4 1Chongqing Key Laboratory of Medicinal Resources in the Three Gorges Reservoir Region, School of Biological and Chemical Engineering, Chongqing University of Education, Chongqing, 2College of Engineering and Applied Sciences, Nanjing University, Nanjing, 3Department of Urology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 4Department of Nephrology, Huai’an First People’s Hospital, Nanjing Medical University, Jiangsu, People’s Republic of China *These authors contributed equally to this work Abstract: High-fat diet-induced metabolic syndrome followed by chronic kidney disease caused by intestinal endotoxemia have received extensive attention. Toll-like receptor 4 (TLR4/nuclear factor-kappa B (NF-κB and oxidative stress-related Nrf2/Keap1 were regarded as the key target points involved in metabolic inflammation and kidney injury. However, the molecular mechanism of interaction between TLR4/NF-κB and Nrf2 activation in high-fat diet-induced renal injury is not absolutely understood. Quercetin, a natural product, has been reported to possess antitumor and anti-inflammatory effects. In this regard, this study attempted to prepare poly(d,l-lactide-co-glycolide-loaded gold nanoparticles precipitated with quercetin (GQ to investigate the anti-inflammatory and anti-oxidative stress effects in high-fat diet-induced kidney failure. For this study, C57BL/6 mice fed fat-rich fodder were used as the metabolic syndrome model to evaluate the protective effects of GQ on kidney injury and to determine whether TLR4/NF-κB and Nrf2 pathways were associated with the process. Moreover, histological examinations, enzyme-linked immunosorbent assay, Western blot, and basic blood tests and systemic inflammation-related indicators were used to investigate the inhibitory effects of GQ and underlying molecular mechanism by which it may reduce renal injury. Of note, podocyte

  16. Electronic and structural aspects of spin transitions observed by optical microscopy. The case of [Fe(ptz)6](BF4)2.

    Science.gov (United States)

    Chong, Christian; Mishra, Haritosh; Boukheddaden, Kamel; Denise, Stéphane; Bouchez, Guillaume; Collet, Eric; Ameline, Jean-Claude; Naik, Anil D; Garcia, Yann; Varret, François

    2010-02-11

    The colorimetric analysis of images recorded with an optical microscope during the onset of the spin crossover transformation allows monitoring separately the involved electronic and structural aspects, through the separation of resonant absorption and scattering effects. Complementary information can also be obtained by using the polarized modes of the microscope. These potentialities are illustrated by the observation of [Fe(ptz)(6)](BF(4))(2) single crystals during the onset of the thermal transitions in the 110-140 K range. We characterized the interplay between the electronic (HS LS) and structural (order disorder) transformations. Elastic stresses and mechanical effects (hopping, self-cleavage) generated by the volume change upon electronic transition are also illustrated, with their impact on the photoswitching properties of the crystals.

  17. Gold-quercetin nanoparticles prevent metabolic endotoxemia-induced kidney injury by regulating TLR4/NF-κB signaling and Nrf2 pathway in high fat diet fed mice.

    Science.gov (United States)

    Xu, Min-Xuan; Wang, Ming; Yang, Wei-Wei

    2017-01-01

    High-fat diet-induced metabolic syndrome followed by chronic kidney disease caused by intestinal endotoxemia have received extensive attention. Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) and oxidative stress-related Nrf2/Keap1 were regarded as the key target points involved in metabolic inflammation and kidney injury. However, the molecular mechanism of interaction between TLR4/NF-κB and Nrf2 activation in high-fat diet-induced renal injury is not absolutely understood. Quercetin, a natural product, has been reported to possess antitumor and anti-inflammatory effects. In this regard, this study attempted to prepare poly(d,l-lactide- co -glycolide)-loaded gold nanoparticles precipitated with quercetin (GQ) to investigate the anti-inflammatory and anti-oxidative stress effects in high-fat diet-induced kidney failure. For this study, C57BL/6 mice fed fat-rich fodder were used as the metabolic syndrome model to evaluate the protective effects of GQ on kidney injury and to determine whether TLR4/NF-κB and Nrf2 pathways were associated with the process. Moreover, histological examinations, enzyme-linked immunosorbent assay, Western blot, and basic blood tests and systemic inflammation-related indicators were used to investigate the inhibitory effects of GQ and underlying molecular mechanism by which it may reduce renal injury. Of note, podocyte injury was found to participate in endotoxin-stimulated inflammatory response. TLR4/NF-κB and Nrf2 pathways were upregulated with high-fat diet intake in mice, resulting in reduction of superoxide dismutase activity and increase in superoxide radical, H 2 O 2 , malondialdehyde, XO, XDH, and XO/XDH ratio. In addition, upregulation of TLR4/NF-κB and oxidative stress by endotoxin were observed in vitro, which were suppressed by GQ administration, ultimately alleviating podocyte injury. These findings indicated that GQ could restore the metabolic disorders caused by high-fat diet, which suppresses insulin

  18. Synthesis and characterization of organically modified silica gel with 4-amino-5-(4-pyridyl)-4h-1 ,2,4-triazole-3-thiol (APTT); Sintese e caracterizacao da silica gel organofuncionalizada com 4-amino-5-(4-piridil)-4h-1,2,4-triazol-3-tiol (APTT)

    Energy Technology Data Exchange (ETDEWEB)

    Magossi, M.S.; Carmo, D.R. do, E-mail: maiaramagossi@gmail.com [Universidade Estadual Paulista Julio de Mesquita Filho (UNESP), Ilha Solteira, SP (Brazil). Faculdade de Engenharia

    2014-07-01

    This work object the preparation and characterization of a silica gel (SG) organically with a triazole compound, 4-amino-5-(4-pyridyl)-4H-1,2,4-triazole-3- thiol (APTT). The prepared organofunctionalized material (SGAPTT) was preliminarily characterized by spectroscopic techniques such as: Spectroscopy in the Region of Infrared (FTIR), Scanning Electron Microscopy (SEM) and Energy Dispersive Spectroscopy X-ray (EDX). The vibrational spectrum (FTIR) showed characteristic bands of the starting materials, such as bands at ∼ 1120cm{sup -1} related to the asymmetric stretching Si-O-Si (νSi-O-Si) as well as the bands between 1350 and 1650 cm{sup -1} assigned vibrations and deformations of the ring APTT. The SGAPTT material was tested as support for adsorption of cupric ions in aqueous solution, ethanol and 42% ethanol. The maximum amount of copper (II) adsorbed (Nf {sup max.}) was 22.0 × 10{sup -5} mol g{sup -1}, 31.4 × 10-5 mol g-1 and 47.17 × 10{sup -5} mol g{sup -1} to aqueous media, 42% ethanol and 99% ethanol respectively. (author)

  19. An intronic polymorphism of IRF4 gene influences gene transcription in vitro and shows a risk association with childhood acute lymphoblastic leukemia in males.

    Science.gov (United States)

    Do, Thuy N; Ucisik-Akkaya, Esma; Davis, Charronne F; Morrison, Brittany A; Dorak, M Tevfik

    2010-02-01

    The interferon regulatory factor (IRF) family of DNA-binding proteins regulates expression of interferon-inducible genes with roles in the immune response and carcinogenesis. IRF4 is involved in the differentiation of B and T cells and is overexpressed in B-cell malignancies as a result of c-REL (NF-kappaB) hyperactivation. IRF4 polymorphisms are associated with susceptibility to chronic lymphoid leukemia (CLL) and non-Hodgkin lymphoma (NHL). We examined 13 IRF4 SNPs in 114 cases of childhood acute lymphoblastic leukemia (ALL) and 388 newborn controls from Wales (U.K.) using TaqMan assays. IRF4 intron 4 SNP rs12203592 showed a male-specific risk association (OR=4.4, 95% CI=1.5 to 12.6, P=0.007). Functional consequences of the C>T substitution at this SNP were assessed by cell-based reporter assays using three different cell lines. We found a repressive effect of the rs12203592 wildtype allele C on IRF4 promoter activity (Pcell line tested. Thus, homozygosity for the rs12203592 variant allele would result in increased IRF4 expression. This increase would be compounded by high levels of NF-kappaB activity in males due to the absence of estrogen. IRF4 differs from other IRFs in its anti-interferon activity which interferes with immune surveillance. We propose that a detailed study of IRF4 can provide information on the mechanism of the sex effect and the role of immune surveillance in childhood ALL development. Copyright 2009 Elsevier B.V. All rights reserved.

  20. The HIV-1 epidemic in Bolivia is dominated by subtype B and CRF12_BF "family" strains

    Directory of Open Access Journals (Sweden)

    Guimarães Monick L

    2012-01-01

    Full Text Available Abstract Background Molecular epidemiological studies of HIV-1 in South America have revealed the occurrence of subtypes B, F1 and BF1 recombinants. Even so, little information concerning the HIV-1 molecular epidemiology in Bolivia is available. In this study we performed phylogenetic analyses from samples collected in Bolivia at two different points in time over a 10 year span. We analyzed these samples to estimate the trends in the HIV subtype and recombinant forms over time. Materials and methods Fifty one HIV-1 positive samples were collected in Bolivia over two distinct periods (1996 and 2005. These samples were genetically characterized based on partial pol protease/reverse transcriptase (pr/rt and env regions. Alignment and neighbor-joining (NJ phylogenetic analyses were established from partial env (n = 37 and all pol sequences using Mega 4. The remaining 14 env sequences from 1996 were previously characterized based on HMA-env (Heteroduplex mobility assay. The Simplot v.3.5.1 program was used to verify intragenic recombination, and SplitsTree 4.0 was employed to confirm the phylogenetic relationship of the BF1 recombinant samples. Results Phylogenetic analysis of both env and pol regions confirmed the predominance of "pure" subtype B (72.5% samples circulating in Bolivia and revealed a high prevalence of BF1 genotypes (27.5%. Eleven out of 14 BF1 recombinants displayed a mosaic structure identical or similar to that described for the CRF12_BF variant, one sample was classified as CRF17_BF, and two others were F1pol/Benv. No "pure" HIV-1 subtype F1 or B" variant of subtype B was detected in the present study. Of note, samples characterized as CRF12_BF-related were depicted only in 2005. Conclusion HIV-1 genetic diversity in Bolivia is mostly driven by subtype B followed by BF1 recombinant strains from the CRF12_BF "family". No significant temporal changes were detected between the mid-1990s and the mid-2000s for subtype B (76.2% vs 70

  1. Role of S100A1 in hypoxia-induced inflammatory response in cardiomyocytes via TLR4/ROS/NF-κB pathway.

    Science.gov (United States)

    Yu, Jiangkun; Lu, Yanyu; Li, Yapeng; Xiao, Lili; Xing, Yu; Li, Yanshen; Wu, Leiming

    2015-09-01

    S100A1 plays a crucial role in hypoxia-induced inflammatory response in cardiomyocytes. However, the role of S100A1 in hypoxia-induced inflammatory response in cardiomyocytes is still unknown. enzyme-linked immunosorbent assay (ELISA) was performed for the determination of inflammatory cytokines. Immunocytochemistry and immunofluorescence, Western blot analysis and Real-time polymerase chain reaction (RT-PCR) were conducted to assess protein or mRNA expressions. Fluorogenic probe dihydroethidium (DHE) was used to evaluate the generation of reactive oxygen species (ROS) while Hoechst 33342 staining for apoptosis. Small interfering RNA (siRNA) for S100A1 was used to evaluate the role of S100A1. The levels of ROS and inflammatory cytokine including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-8 in H9c2 cells were increased remarkably by hypoxia. However, IL-37 protein or mRNA levels were decreased significantly. Both Toll-like receptor 4 (TLR4) inhibitor Ethyl (6R)-6-[N-(2-Chloro-4fluorophenyl)sulfamoyl]cyclohex-1-ene-1-carboxylate (TAK-242) treatment or siRNA S100A1 downregulated TLR4 expression and inflammatory cytokine level and mRNA in H9c2 cells, as well as weakening ROS and phospho-p65 Nuclear factor (NF)-κB levels. Further, S100A1 treatment significantly reduced TNF-α protein or mRNA level whereas enhanced IL-37 protein or mRNA level, and could attenuate ROS and phospho-p65 NF-κB levels. Our results demonstrate that S100A1 can regulate the inflammatory response and oxidative stress in H9C2 cells via TLR4/ROS/NF-κB pathway. These findings provide an interesting strategy for protecting cardiomyocytes from hypoxia-induced inflammatory response. © 2015 Royal Pharmaceutical Society.

  2. RNA interference suppression of A100A4 reduces the growth and metastatic phenotype of human renal cancer cells via NF-kB-dependent MMP-2 and bcl-2 pathway.

    Science.gov (United States)

    Yang, X-C; Wang, X; Luo, L; Dong, D-H; Yu, Q-C; Wang, X-S; Zhao, K

    2013-06-01

    S100A4 is a well established marker and mediator of metastatic disease, but the exact mechanisms responsible for the metastasis promoting effects are less well defined. We tested a hypothesis that the S100A4 gene plays a role in the proliferation and invasiveness of human renal cancer cells (RCC) and may be associated with its metastatic spread. The small interference RNA vector pcDNA3.1-S100A4 siRNA was transfected in to the human renal cancer cell lines ACHN, Ketr-3, OS-RC-2, CaKi-2 and HTB-47, then treated with ABT-737 or BB94. Cell apoptosis and cell viability was detected by flow cytometry and MTT assay. Matrigel was used for cell motility and invasion assay. MMP-2, bcl-2 and S100A4 was detected by RT-PCR and western blot assay. NF-kB subunit p65 activity was detected by confocal microscopy assay. We then determine the effect S100A4 sliencing on tumor growth, lung metastasis development in vivo. Immunohistochemistry was used to detected the expression of S100A4, bcl-2, MMP-2, p65 and CD31. S100A4 silencing in ACHN cells by RNA interference significantly inhibited NF-kB and NF-kB-mediated MMP-2 and bcl-2 activation and cellular migration, proliferation, and promoted apoptosis. Furthermore, re-expression of S100A4 in S100A4-siRNA-transfected ACHN cells by transient S100A4 cDNA transfection restored the NF-kB and NF-kB-mediated MMP-2 and bcl-2 activation and their high migratory and cellular proliferative ability. An inhibitor ABT-737 (the Bcl-2 antagonist targets Bcl-2) against Bcl-2 suppressed cellular proliferation and promoted apoptosis induced by S100A4 re-expression in S100A4-siRNA-transfected ACHN cells. A inhibitor BB94 against MMPs to neutralize MMP-2 protein suppressed cellular invasion and migration induced by S100A4 re-expression in S100A4-siRNA-transfected ACHN cells. In the prevention model, S100A4 silencing inhibited primary tumor growth by (tumor weight) (76 ± 8%) and (tumor volum) (78 ± 4%) respectively and promoted apoptosis and the formation

  3. TEffect of nf-kappa B on diabetic retinopathy%NF-κB对糖尿病视网膜病变的影响

    Institute of Scientific and Technical Information of China (English)

    王爽; 宋子宣

    2015-01-01

    normal rats and was (74.4300 ± 4.4900) in the model-building-with-water group.The results of the apoptosis experiment showed that the number of apoptotic signals was (32.2 ± 3.1) in the normal rats and was (7.4 ± 4.2) in the model-building-with-water group.Conclusions Nf-kappa B reduces the proliferation of retinal blood vessels in patients with diabetic retinopathy mainly causing cell apoptosis.

  4. Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21.

    LENUS (Irish Health Repository)

    Sheedy, FJ

    2009-11-29

    The tumor suppressor PDCD4 is a proinflammatory protein that promotes activation of the transcription factor NF-kappaB and suppresses interleukin 10 (IL-10). Here we found that mice deficient in PDCD4 were protected from lipopolysaccharide (LPS)-induced death. The induction of NF-kappaB and IL-6 by LPS required PDCD4, whereas LPS enhanced IL-10 induction in cells lacking PDCD4. Treatment of human peripheral blood mononuclear cells with LPS resulted in lower PDCD4 expression, which was due to induction of the microRNA miR-21 via the adaptor MyD88 and NF-kappaB. Transfection of cells with a miR-21 precursor blocked NF-kappaB activity and promoted IL-10 production in response to LPS, whereas transfection with antisense oligonucleotides to miR-21 or targeted protection of the miR-21 site in Pdcd4 mRNA had the opposite effect. Thus, miR-21 regulates PDCD4 expression after LPS stimulation.

  5. TLR4/MyD88/NF-κB signaling and PPAR-γ within the paraventricular nucleus are involved in the effects of telmisartan in hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Li, Hong-Bao; Li, Xiang; Huo, Chan-Juan; Su, Qing; Guo, Jing [Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases, Xi' an Jiaotong University School of Basic Medical Sciences, Xi' an Jiaotong University Health Science Center, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an 710061 (China); Yuan, Zu-Yi [Department of Cardiovascular Medicine, First Affiliated Hospital of Medical College of Xi' an Jiaotong University, Xi' an 710061 (China); Zhu, Guo-Qing [Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029 (China); Shi, Xiao-Lian, E-mail: shxl@mail.xjtu.edu.cn [Department of Pharmacology, School of Basic Medical Sciences, Xi' an Jiaotong University Health Science Center, Xi' an 710061 (China); Liu, Jin-Jun, E-mail: jupet@163.com [Department of Physiology and Pathophysiology, Xi' an Jiaotong University School of Basic Medical Sciences, Xi' an Jiaotong University Health Science Center, Xi' an 710061 (China); Kang, Yu-Ming, E-mail: ykang@mail.xjtu.edu.cn [Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases, Xi' an Jiaotong University School of Basic Medical Sciences, Xi' an Jiaotong University Health Science Center, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an 710061 (China)

    2016-08-15

    Previous findings from our laboratory and others indicate that the main therapeutic effect of angiotensin II type 1 receptor (AT1-R) antagonists is to decrease blood pressure and exert anti-inflammatory effects in the cardiovascular system. In this study, we determined whether AT1-R antagonist telmisartan within the hypothalamic paraventricular nucleus (PVN) attenuates hypertension and hypothalamic inflammation via both the TLR4/MyD88/NF-κB signaling pathway and peroxisome proliferator-activated receptor-γ (PPAR-γ) in the PVN in hypertensive rats. Spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats were treated for 4 weeks through bilateral PVN infusion with the AT1-R antagonist telmisartan (TEL, 10 μg/h), or losartan (LOS, 20 μg/h), or the PPAR-γ antagonist GW9662 (GW, 100 μg/h), or vehicle via osmotic minipump. Mean arterial pressure (MAP) was recorded by a tail-cuff occlusion method. PVN tissue and blood were collected for the measurement of AT1-R, PPAR-γ, pro-inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6), inducible nitric oxide synthase (iNOS), TLR4, MyD88, nuclear factor-kappa B (NF-κB) activity and plasma norepinephrine (NE), respectively. Hypertensive rats exhibited significantly higher level of AT1-R and lower level of PPAR-γ in the PVN. PVN treatment with TEL attenuated MAP, improved cardiac hypertrophy, reduced TNF-α, IL-1β, IL-6, iNOS levels, and plasma NE in SHR but not in WKY rats. These results were associated with reduced TLR4, MyD88 and NF-κB levels and increased PPAR-γ level in the PVN of hypertensive rats. Our findings suggest that TLR4/MyD88/NF-κB signaling and PPAR-γ within the PVN are involved in the beneficial effects of telmisartan in hypertension. - Highlights: • PVN infusion of TEL in spontaneously hypertensive rats is reported. • PVN infusion of TEL attenuates hypertension and proinflammatory cytokines in PVN. • PVN blockade of AT1-R attenuates

  6. 4-(4,4-Difluoro-1,3,5,7-tetramethyl-3a-aza-4a-azonia-4-borata-s-indacen-8-ylbenzonitrile

    Directory of Open Access Journals (Sweden)

    Yuting Chen

    2011-04-01

    Full Text Available The title compound, C20H18BF2N3, contains one C9BN2 (Bodipy framework and one cyanobenzyl group. The Bodipy framework is essentially planar with a maximum deviation of 0.041 (2 Å. The introduction of two methyl groups at positions 1 and 7 of s-indacene in the Bodipy unit results in almost orthogonal configuration between the mean plane of the Bodipy unit and the cyanobenzyl group [dihedral angle = 89.78 (4°].

  7. BF2.649 [1-{3-[3-(4-Chlorophenyl)propoxy]propyl}piperidine, hydrochloride], a nonimidazole inverse agonist/antagonist at the human histamine H3 receptor: Preclinical pharmacology.

    Science.gov (United States)

    Ligneau, X; Perrin, D; Landais, L; Camelin, J-C; Calmels, T P G; Berrebi-Bertrand, I; Lecomte, J-M; Parmentier, R; Anaclet, C; Lin, J-S; Bertaina-Anglade, V; la Rochelle, C Drieu; d'Aniello, F; Rouleau, A; Gbahou, F; Arrang, J-M; Ganellin, C R; Stark, H; Schunack, W; Schwartz, J-C

    2007-01-01

    Histamine H3 receptor inverse agonists are known to enhance the activity of histaminergic neurons in brain and thereby promote vigilance and cognition. 1-{3-[3-(4-Chlorophenyl)propoxy]propyl}piperidine, hydrochloride (BF2.649) is a novel, potent, and selective nonimidazole inverse agonist at the recombinant human H3 receptor. On the stimulation of guanosine 5'-O-(3-[35S]thio)triphosphate binding to this receptor, BF2.649 behaved as a competitive antagonist with a Ki value of 0.16 nM and as an inverse agonist with an EC50 value of 1.5 nM and an intrinsic activity approximately 50% higher than that of ciproxifan. Its in vitro potency was approximately 6 times lower at the rodent receptor. In mice, the oral bioavailability coefficient, i.e., the ratio of plasma areas under the curve after oral and i.v. administrations, respectively, was 84%. BF2.649 dose dependently enhanced tele-methylhistamine levels in mouse brain, an index of histaminergic neuron activity, with an ED50 value of 1.6 mg/kg p.o., a response that persisted after repeated administrations for 17 days. In rats, the drug enhanced dopamine and acetylcholine levels in microdialysates of the prefrontal cortex. In cats, it markedly enhanced wakefulness at the expense of sleep states and also enhanced fast cortical rhythms of the electroencephalogram, known to be associated with improved vigilance. On the two-trial object recognition test in mice, a promnesiant effect was shown regarding either scopolamine-induced or natural forgetting. These preclinical data suggest that BF2.649 is a valuable drug candidate to be developed in wakefulness or memory deficits and other cognitive disorders.

  8. The ROS/NF-κB/NR4A2 pathway is involved in H2O2 induced apoptosis of resident cardiac stem cells via autophagy.

    Science.gov (United States)

    Shi, Xingxing; Li, Wenjing; Liu, Honghong; Yin, Deling; Zhao, Jing

    2017-09-29

    Cardiac stem cells (CSCs)-based therapy provides a promising avenue for the management of ischemic heart diseases. However, engrafted CSCs are subjected to acute cell apoptosis in the ischemic microenvironment. Here, stem cell antigen 1 positive (Sca-1 + ) CSCs proved to own therapy potential were cultured and treated with H 2 O 2 to mimic the ischemia situation. As autophagy inhibitor, 3-methyladenine (3MA), inhibited H 2 O 2 -induced CSCs apoptosis, thus we demonstrated that H 2 O 2 induced autophagy-dependent apoptosis in CSCs, and continued to find key proteins responsible for the crosstalk between autophagy and apoptosis. Nuclear Receptor Subfamily 4 Group A Member 2 (NR4A2), increased upon cardiomyocyte injury with unknown functions in CSCs, was increased by H 2 O 2 . NR4A2 siRNA attenuated H 2 O 2 induced autophagy and apoptosis in CSCs, which suggested an important role of NR4A2 in CSCs survival in ischemia conditions. Reactive oxygen species (ROS) and NF-κB (P65) subunit were both increased by H 2 O 2 . Either the ROS scavenger, N-acetyl-l-cysteine (NAC) or NF-κB signaling inhibitor, bay11-7082 could attenuate H 2 O 2 -induced autophagy and apoptosis in CSCs, which suggested they were involved in this process. Furthermore, NAC inhibited NF-κB activities, while bay11-7082 inhibited NR4A2 expression, which revealed a ROS/NF-κB/NR4A2 pathway responsible for H 2 O 2 -induced autophagy and apoptosis in CSCs. Our study supports a new clue enhancing the survival rate of CSCs in the infarcted myocardium for cell therapy in ischemic cardiomyopathy.

  9. Differential protection by cell wall components of Lactobacillus amylovorus DSM 16698Tagainst alterations of membrane barrier and NF-kB activation induced by enterotoxigenic F4+ Escherichia coli on intestinal cells.

    Science.gov (United States)

    Roselli, Marianna; Finamore, Alberto; Hynönen, Ulla; Palva, Airi; Mengheri, Elena

    2016-09-29

    The role of Lactobacillus cell wall components in the protection against pathogen infection in the gut is still largely unexplored. We have previously shown that L. amylovorus DSM 16698 T is able to reduce the enterotoxigenic F4 + Escherichia coli (ETEC) adhesion and prevent the pathogen-induced membrane barrier disruption through the regulation of IL-10 and IL-8 expression in intestinal cells. We have also demonstrated that L. amylovorus DSM 16698 T protects host cells through the inhibition of NF-kB signaling. In the present study, we investigated the role of L. amylovorus DSM 16698 T cell wall components in the protection against F4 + ETEC infection using the intestinal Caco-2 cell line. Purified cell wall fragments (CWF) from L. amylovorus DSM 16698 T were used either as such (uncoated, U-CWF) or coated with S-layer proteins (S-CWF). Differentiated Caco-2/TC7 cells on Transwell filters were infected with F4 + ETEC, treated with S-CWF or U-CWF, co-treated with S-CWF or U-CWF and F4 + ETEC for 2.5 h, or pre-treated with S-CWF or U-CWF for 1 h before F4 + ETEC addition. Tight junction (TJ) and adherens junction (AJ) proteins were analyzed by immunofluorescence and Western blot. Membrane permeability was determined by phenol red passage. Phosphorylated p65-NF-kB was measured by Western blot. We showed that both the pre-treatment with S-CWF and the co- treatment of S-CWF with the pathogen protected the cells from F4 + ETEC induced TJ and AJ injury, increased membrane permeability and activation of NF-kB expression. Moreover, the U-CWF pre-treatment, but not the co-treatment with F4 + ETEC, inhibited membrane damage and prevented NF-kB activation. The results indicate that the various components of L. amylovorus DSM 16698 T cell wall may counteract the damage caused by F4 + ETEC through different mechanisms. S-layer proteins are essential for maintaining membrane barrier function and for mounting an anti-inflammatory response against F4 + ETEC infection. U-CWF are

  10. Fluoride substitution in LiBH4; destabilization and decomposition

    DEFF Research Database (Denmark)

    Richter, Bo; Ravnsbaek, Dorthe B.; Sharma, Manish

    2017-01-01

    Fluoride substitution in LiBH4 is studied by investigation of LiBH4-LiBF4 mixtures (9:1 and 3:1). Decomposition was followed by in situ synchrotron radiation X-ray diffraction (in situ SR-PXD), thermogravimetric analysis and differential scanning calorimetry with gas analysis (TGA/DSC-MS) and in ......Fluoride substitution in LiBH4 is studied by investigation of LiBH4-LiBF4 mixtures (9:1 and 3:1). Decomposition was followed by in situ synchrotron radiation X-ray diffraction (in situ SR-PXD), thermogravimetric analysis and differential scanning calorimetry with gas analysis (TGA...

  11. An NF-Y-dependent switch of positive and negative histone methyl marks on CCAAT promoters.

    Directory of Open Access Journals (Sweden)

    Giacomo Donati

    Full Text Available BACKGROUND: Histone tails have a plethora of different post-translational modifications, which are located differently in "open" and "closed" parts of genomes. H3K4me3/H3K79me2 and H4K20me3 are among the histone marks associated with the early establishment of active and inactive chromatin, respectively. One of the most widespread promoter elements is the CCAAT box, bound by the NF-Y trimer. Two of NF-Y subunits have an H2A-H2B-like structure. PRINCIPAL FINDINGS: We established the causal relationship between NF-Y binding and positioning of methyl marks, by ChIP analysis of mouse and human cells infected with a dominant negative NF-YA: a parallel decrease in NF-Y binding, H3K4me3, H3K79me2 and transcription was observed in promoters that are dependent upon NF-Y. On the contrary, changes in the levels of H3K9-14ac were more subtle. Components of the H3K4 methylating MLL complex are not recruited in the absence of NF-Y. As for repressed promoters, NF-Y removal leads to a decrease in the H4K20me3 mark and deposition of H3K4me3. CONCLUSIONS: Two relevant findings are reported: (i NF-Y gains access to its genomic locations independently from the presence of methyl histone marks, either positive or negative; (ii NF-Y binding has profound positive or negative consequences on the deposition of histone methyl marks. Therefore NF-Y is a fundamental switch at the heart of decision between gene activation and repression in CCAAT regulated genes.

  12. Fentanyl Suppresses the Survival of CD4+ T Cells Isolated from Human Umbilical Cord Blood through Inhibition of IKKs-mediated NF-κB Activation.

    Science.gov (United States)

    Ma, K; Ma, P; Lu, H; Liu, S; Cao, Q

    2017-05-01

    The aim of this study was to investigate the effects and the underlying mechanisms of fentanyl anaesthetic on T lymphocytes isolated from human umbilical cord blood in vitro. The percentages of CD4 + , CD8 + and regulatory T (Treg) cells in human umbilical cord blood mononuclear cells (UBMC) treated with fentanyl in vitro were analysed by flow cytometry. The levels of cytokines IFN-γ, IL-2, IL-4 and IL-17 secreted by activated CD4 + T cells were measured by ELISA assays. Expressions of MAPK and NF-κB signalling pathway proteins were determined by Western blotting. Effects of fentanyl on IKK and p65 expression promoter activities were analysed by luciferase assay. Fentanyl decreased the percentages and amounts of CD4 + , CD8 + and Foxp3 + Treg T lymphocyte subsets in UBMCs in a dose-dependent manner. Fentanyl inhibited the proliferation and induced apoptosis of activated CD4 + T cells dose dependently. Fentanyl could not reverse the increase of cell proliferation in activated groups to be equivalent with those in inactivated group. Secretions of IFN-γ, IL-2 and IL-4 cytokines were significantly decreased by moderate to high dose of fentanyl compared with controls. No significant differences were observed in protein expressions of MAPK pathway. In addition, fentanyl suppressed the IKKs-mediated activation of NF-κB. This study demonstrates that fentanyl exerts immunosuppressive effects on T lymphocytes obtained from UBMCs. Thus, the clinical application of fentanyl would not only relieve pain caused by surgery but regulate immune responses post-operation possibly through inhibition of IKKs-mediated NF-κB activation. © 2017 The Foundation for the Scandinavian Journal of Immunology.

  13. Synthesis and characterization of organically modified silica gel with 4-amino-5-(4-pyridyl)-4h-1 ,2,4-triazole-3-thiol (APTT)

    International Nuclear Information System (INIS)

    Magossi, M.S.; Carmo, D.R. do

    2014-01-01

    This work object the preparation and characterization of a silica gel (SG) organically with a triazole compound, 4-amino-5-(4-pyridyl)-4H-1,2,4-triazole-3- thiol (APTT). The prepared organofunctionalized material (SGAPTT) was preliminarily characterized by spectroscopic techniques such as: Spectroscopy in the Region of Infrared (FTIR), Scanning Electron Microscopy (SEM) and Energy Dispersive Spectroscopy X-ray (EDX). The vibrational spectrum (FTIR) showed characteristic bands of the starting materials, such as bands at ∼ 1120cm"-"1 related to the asymmetric stretching Si-O-Si (νSi-O-Si) as well as the bands between 1350 and 1650 cm"-"1 assigned vibrations and deformations of the ring APTT. The SGAPTT material was tested as support for adsorption of cupric ions in aqueous solution, ethanol and 42% ethanol. The maximum amount of copper (II) adsorbed (Nf "m"a"x".) was 22.0 × 10"-"5 mol g"-"1, 31.4 × 10-5 mol g-1 and 47.17 × 10"-"5 mol g"-"1 to aqueous media, 42% ethanol and 99% ethanol respectively. (author)

  14. Li + solvation and kinetics of Li+BF4-/PF 6 - ion pairs in ethylene carbonate. A molecular dynamics study with classical rate theories

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Tsun-Mei [Department of Chemistry, University of Wisconsin–Parkside, Kenosha, Wisconsin 53141, USA; Dang, Liem X. [Physical Sciences Division, Pacific Northwest National Laboratory, Richland, Washington 93352, USA

    2017-10-28

    Using our polarizable force-field models and employing classical rate theories of chemical reactions, we examine the ethylene carbonate (EC) exchange process between the first and second solvation shells around Li+ and the dissociation kinetics of ion pairs Li+-[BF4] and Li+-[PF6] in this solvent. We calculate the exchange rates using transition state theory and correct them with transmission coefficients computed by the reactive flux; Impey, Madden, and McDonald approaches; and Grote-Hynes theory. We found the residence times of EC around Li+ ions varied from 70 to 450 ps, depending on the correction method used. We found the relaxation times changed significantly from Li+-[BF4] to Li+-[PF6] ion pairs in EC. Our results also show that, in addition to affecting the free energy of dissociation in EC, the anion type also significantly influence the dissociation kinetics of ion pairing. This work was supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences, and Biosciences. The calculations were carried out using computer resources provided by the Office of Basic Energy Sciences.

  15. Reverting antibiotic tolerance of Pseudomonas aeruginosa PAO1 persister cells by (Z-4-bromo-5-(bromomethylene-3-methylfuran-2(5H-one.

    Directory of Open Access Journals (Sweden)

    Jiachuan Pan

    Full Text Available BACKGROUND: Bacteria are well known to form dormant persister cells that are tolerant to most antibiotics. Such intrinsic tolerance also facilitates the development of multidrug resistance through acquired mechanisms. Thus persister cells are a promising target for developing more effective methods to control chronic infections and help prevent the development of multidrug-resistant bacteria. However, control of persister cells is still an unmet challenge. METHODOLOGY/PRINCIPAL FINDINGS: We show in this report that (Z-4-bromo-5-(bromomethylene-3-methylfuran-2(5H-one (BF8 can restore the antibiotic susceptibility of Pseudomonas aeruginosa PAO1 persister cells at growth non-inhibitory concentrations. Persister control by BF8 was found to be effective against both planktonic and biofilm cells of P. aeruginosa PAO1. Interestingly, although BF8 is an inhibitor of quorum sensing (QS in Gram-negative bacteria, the data in this study suggest that the activities of BF8 to revert antibiotic tolerance of P. aeruginosa PAO1 persister cells is not through QS inhibition and may involve other targets. CONCLUSION: BF8 can sensitize P. aeruginosa persister cells to antibiotics.

  16. Repeated stimulation by LPS promotes the senescence of DPSCs via TLR4/MyD88-NF-κB-p53/p21 signaling.

    Science.gov (United States)

    Feng, Guijuan; Zheng, Ke; Cao, Tong; Zhang, Jinlong; Lian, Min; Huang, Dan; Wei, Changbo; Gu, Zhifeng; Feng, Xingmei

    2018-02-26

    Dental pulp stem cells (DPSCs), one type of mesenchymal stem cells, are considered to be a type of tool cells for regenerative medicine and tissue engineering. Our previous studies found that the stimulation with lipopolysaccharide (LPS) might introduce senescence of DPSCs, and this senescence would have a positive correlation with the concentration of LPS. The β-galactosidase (SA-β-gal) staining was used to evaluate the senescence of DPSCs and immunofluorescence to show the morphology of DPSCs. Our findings suggested that the activity of SA-β-gal has increased after repeated stimulation with LPS and the morphology of DPSCs has changed with the stimulation with LPS. We also found that LPS bound to the Toll-like receptor 4 (TLR4)/myeloid differentiation factor (MyD) 88 signaling pathway. Protein and mRNA expression of TLR4, MyD88 were enhanced in DPSCs with LPS stimulation, resulting in the activation of nuclear factor-κB (NF-κB) signaling, which exhibited the expression of p65 improved in the nucleus while the decreasing of IκB-α. Simultaneously, the expression of p53 and p21, the downstream proteins of the NF-κB signaling, has increased. In summary, DPSCs tend to undergo senescence after repeated stimulation in an inflammatory microenvironment. Ultimately, these findings may lead to a new direction for cell-based therapy in oral diseases and other regenerative medicines.

  17. Electrochemistry of TiF4 in 1-butyl-2,3-dimethylimidazolium tetrafluoroborate

    International Nuclear Information System (INIS)

    Andriyko, Yuriy; Andriiko, Alexander; Babushkina, Olga B.; Nauer, Gerhard E.

    2010-01-01

    Electrochemical behaviour of Ti(IV) species in the ionic liquid (IL) 1-butyl-2,3-dimethylimidazolium tetrafluoroborate (BMMImBF 4 ) was studied by means of chronopotentiometry (CP) and cyclic voltammetry (CV) in melts with different concentrations of TiF 4 (2-35 mol%) within a temperature range of 65-180 deg. C. The electrochemical reduction of Ti(IV) was suggested to proceed via the sequence of one-electron steps with the formation of poorly soluble low valence intermediates (LVI). LVIs undergo further solid-state electrochemical reduction to Ti metal. Thin Ti coatings on a Pt substrate were thus obtained and characterized by ESEM method. FTIR spectroscopy was used for identification of the electrochemical active species of Ti(IV). The reaction 2BF 4 - + TiF 4 ↔ TiF 6 2- + 2BF 3 ↑ takes place in the concentrated solutions of TiF 4 at elevated temperatures.

  18. (S-(−-1-Phenylethanaminium 4-(4,4-difluoro-1,3,5,7-tetramethyl-3a,4a-diaza-4-borata-s-indacen-8-ylbenzoate

    Directory of Open Access Journals (Sweden)

    Lindsay M. Hinkle

    2011-09-01

    Full Text Available The title compound, C8H12N+·C20H18BF2N2O2−, crystallizes with a significant amount of void space [4.0 (5%] in the unit cell. The structure displays N—H...O hydrogen bonding between the components. The plane formed by the benzoic acid moiety of the BODIPY-CO2− is twisted by 80.71 (6° relative to the plane formed by the ring C and N atoms of the tetramethyldipyrrin portion of the molecule.

  19. Chlamydia abortus Pmp18.1 Induces IL-1β Secretion by TLR4 Activation through the MyD88, NF-κB, and Caspase-1 Signaling Pathways.

    Science.gov (United States)

    Pan, Qing; Zhang, Qiang; Chu, Jun; Pais, Roshan; Liu, Shanshan; He, Cheng; Eko, Francis O

    2017-01-01

    The polymorphic membrane protein D (Pmp18D) is a 160-kDa outer membrane protein that is conserved and plays an important role in Chlamydia abortus pathogenesis. We have identified an N-terminal fragment of Pmp18D (designated Pmp18.1) as a possible subunit vaccine antigen. In this study, we evaluated the vaccine potential of Pmp18.1 by investigating its ability to induce innate immune responses in dendritic cells and the signaling pathway(s) involved in rPmp18.1-induced IL-1β secretion. We next investigated the immunomodulatory impact of VCG, in comparison with the more established Th1-promoting adjuvants, CpG and FL, on rPmp18.1-mediated innate immune activation. Finally, the effect of siRNA targeting TLR4, MyD88, NF-κB p50, and Caspase-1 mRNA in DCs on IL-1β cytokine secretion was also investigated. Bone marrow-derived dendritic cells (BMDCs) were stimulated with rPmp18.1 in the presence or absence of VCG or CpG or FL and the magnitude of cytokines produced was assessed using a multiplex cytokine ELISA assay. Expression of costimulatory molecules and Toll-like receptors (TLRs) was analyzed by flow cytometry. Quantitation of intracellular levels of myeloid differentiation factor 88 (MyD88), nuclear factor kappa beta (NF-κB p50/p65), and Caspase-1 was evaluated by Western immunoblotting analysis while NF-κB p65 nuclear translocation was assessed by confocal microscopy. The results showed DC stimulation with rPmp18.1 provoked the secretion of proinflammatory cytokines and upregulated expression of TLRs and co-stimulatory molecules associated with DC maturation. These responses were significantly ( p ≤ 0.001) enhanced by VCG but not CpG or FL. In addition, rPmp18.1 activated the expression of MyD88, NF-κB p50, and Caspase-1 as well as the nuclear expression of NF-κB p65 in treated DCs. Furthermore, targeting TLR4, MyD88, NF-κB p50, and Caspase-1 mRNA in BMDCs with siRNA significantly reduced their expression levels, resulting in decreased IL-1β cytokine

  20. Chlamydia abortus Pmp18.1 Induces IL-1β Secretion by TLR4 Activation through the MyD88, NF-κB, and Caspase-1 Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Qing Pan

    2017-12-01

    Full Text Available The polymorphic membrane protein D (Pmp18D is a 160-kDa outer membrane protein that is conserved and plays an important role in Chlamydia abortus pathogenesis. We have identified an N-terminal fragment of Pmp18D (designated Pmp18.1 as a possible subunit vaccine antigen. In this study, we evaluated the vaccine potential of Pmp18.1 by investigating its ability to induce innate immune responses in dendritic cells and the signaling pathway(s involved in rPmp18.1-induced IL-1β secretion. We next investigated the immunomodulatory impact of VCG, in comparison with the more established Th1-promoting adjuvants, CpG and FL, on rPmp18.1-mediated innate immune activation. Finally, the effect of siRNA targeting TLR4, MyD88, NF-κB p50, and Caspase-1 mRNA in DCs on IL-1β cytokine secretion was also investigated. Bone marrow-derived dendritic cells (BMDCs were stimulated with rPmp18.1 in the presence or absence of VCG or CpG or FL and the magnitude of cytokines produced was assessed using a multiplex cytokine ELISA assay. Expression of costimulatory molecules and Toll-like receptors (TLRs was analyzed by flow cytometry. Quantitation of intracellular levels of myeloid differentiation factor 88 (MyD88, nuclear factor kappa beta (NF-κB p50/p65, and Caspase-1 was evaluated by Western immunoblotting analysis while NF-κB p65 nuclear translocation was assessed by confocal microscopy. The results showed DC stimulation with rPmp18.1 provoked the secretion of proinflammatory cytokines and upregulated expression of TLRs and co-stimulatory molecules associated with DC maturation. These responses were significantly (p ≤ 0.001 enhanced by VCG but not CpG or FL. In addition, rPmp18.1 activated the expression of MyD88, NF-κB p50, and Caspase-1 as well as the nuclear expression of NF-κB p65 in treated DCs. Furthermore, targeting TLR4, MyD88, NF-κB p50, and Caspase-1 mRNA in BMDCs with siRNA significantly reduced their expression levels, resulting in decreased IL-1

  1. Cloning and functional characterization of IRAK4 in large yellow croaker (Larimichthys crocea) that associates with MyD88 but impairs NF-κB activation.

    Science.gov (United States)

    Zou, Peng Fei; Huang, Xue Na; Yao, Cui Luan; Sun, Qing Xue; Li, Ying; Zhu, Qian; Yu, Zhen Xing; Fan, Ze Jun

    2017-04-01

    As crucial signaling transducer in Toll-like receptor (TLR) and interleukin (IL)-1 receptor (IL-1R) signaling pathway, IL-1R-associated kinase 4 (IRAK4) mediates downstream signaling cascades and plays important roles in innate and adaptive immune responses. In the present study, an IRAK4 orthologue was characterized from large yellow croaker (Larimichthys crocea), named Lc-IRAK4, with a conservative N-terminal death domain and a C-terminal protein kinase domain. The genome of Lc-IRAK4 is structured into eleven exons and ten introns. Expression analysis indicated that Lc-IRAK4 was widely expressed in tested tissues, with the highest level in liver and weakest in muscle. Additionally, in the spleen, liver tissues and blood, it could be induced by poly I:C and LPS stimulation, but not be induced by Vibrio parahemolyticus infection. Fluorescence microscopy assays revealed that Lc-IRAK4 localized in the cytoplasm in HEK 293T cells. It was also determined that Lc-IRAK4 could interact with MyD88, whereas MyD88-mediated NF-κB activation was significantly impaired when co-transfected the two in HEK 293T cells. These findings collectively indicated that although Lc-IRAK4 was evolutionarily conserved in vertebrates, the exact function especially the signaling transduction mediated by IRAK4 in fish immune response was different from that in mammals, which impaired MyD88-mediated NF-κB activation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. An apple oligogalactan prevents against inflammation and carcinogenesis by targeting LPS/TLR4/NF-κB pathway in a mouse model of colitis-associated colon cancer.

    Science.gov (United States)

    Liu, Li; Li, Yu H; Niu, Yin B; Sun, Yang; Guo, Zhen J; Li, Qian; Li, Chen; Feng, Juan; Cao, Shou S; Mei, Qi B

    2010-10-01

    Evidence strongly supported a link between inflammation and cancer. Patients with colitis have high risk for development of colon cancer. Nuclear factor-kappa B (NF-κB), partially induced by lipopolysaccharide (LPS) binding to Toll-like receptor (TLR) 4, is a vital molecule in supervising the transformation of colitis to colon cancer. It could be a good strategy to prevent colitis carcinogenesis for targeting LPS/TLR4/NF-κB pathway. In the present study, we obtained an oligogalactan composed of five galacturonic acids from apple pectin and evaluated its protective efficacy on intestinal toxicities and carcinogenesis in a mouse model of colitis-associated colon cancer induced by 1,2-dimethylhydrazine and dextran sodium sulfate (DSS). The apple oligogalactan (AOG) was highly effective against intestinal toxicities and carcinogenesis and decreased the elevated levels of TLR4 and tumor necrosis factor-α (TNF-α) induced by inflammation in vivo in this model system. In vitro studies, AOG alone only slightly increased the levels of protein expression and messenger RNA of TLR4, phosphorylation of IκBα and production of TNF-α in HT-29 cells. However, AOG significantly decreased the elevation of all the biomarkers induced by LPS when it was combined with LPS. The effect of AOG may be related to membrane internalization and redistribution of TLR4 from cell membrane to cytoplasm. AOG is active against inflammation and carcinogenesis through targeting LPS/TLR4/NF-κB pathway. Both AOG and LPS are agonists of TLR4 for sharing the same ligand but AOG has a much lower intrinsic activity than that of LPS. AOG may be useful for treatment of colitis and prevention of carcinogenesis in the clinics.

  3. Thermal reactions of uranium metal, UO 2, U 3O 8, UF 4, and UO 2F 2 with NF 3 to produce UF 6

    Science.gov (United States)

    McNamara, Bruce; Scheele, Randall; Kozelisky, Anne; Edwards, Matthew

    2009-11-01

    This paper demonstrates that NF 3 fluorinates uranium metal, UO 2, UF 4, UO 3, U 3O 8, and UO 2F 2·2H 2O to produce the volatile UF 6 at temperatures between 100 and 550 °C. Thermogravimetric and differential thermal analysis reaction profiles are described that reflect changes in the uranium fluorination/oxidation state, physiochemical effects, and instances of discrete chemical speciation. Large differences in the onset temperatures for each system investigated implicate changes in mode of the NF 3 gas-solid surface interaction. These studies also demonstrate that NF 3 is a potential replacement fluorinating agent in the existing nuclear fuel cycle and in actinide volatility reprocessing.

  4. Post-test analysis of PANDA test P4

    International Nuclear Information System (INIS)

    Hart, J.; Woudstra, A.; Koning, H.

    1999-01-01

    The results of a post-test analysis of the integral system test P4, which has been executed in the PANDA facility at PSI in Switzerland within the framework of Work Package 2 of the TEPSS project are presented. The post-test analysis comprises an evaluation of the PANDA test P4 and a comparison of the test results with the results of simulations using the RELAPS/MOD3.2, TRAC-BF1, and MELCOR 1.8.4 codes. The PANDA test P4 has provided data about how trapped air released from the drywell later in the transient affects PCCS performance in an adequate manner. The well-defined measurements can serve as an important database for the assessment of thermal hydraulic system analysis codes, especially for conditions that could be met in passively operated advanced reactors, i.e. low pressure and small driving forces. Based on the analysis of the test data, the test acceptance criteria have been met. The test P4 has been successfully completed and the instrument readings were with the permitted ranges. The PCCs showed a favorable and robust performance and a wide margin for decay heat removal from the containment. The PANDA P4 test demonstrated that trapped air, released from the drywell later in the transient, only temporarily and only slightly affected the performance of the passive containment cooling system. The analysis of the results of the RELAPS code showed that the overall behaviour of the test has been calculated quite well with regards to pressure, mass flow rates, and pool boil-down. This accounts both for the pre-test and the post-test simulations. However, due to the one-dimensional, stacked-volume modeling of the PANDA DW, WW, and GDCS vessels, 3D-effects such as in-vessel mixing and recirculation could not be calculated. The post-test MELCOR simulation showed an overall behaviour that is comparable to RELAPS. However, MELCOR calculated almost no air trapping in the PCC tubes that could hinder the steam condensation rate. This resulted in lower calculated

  5. Exact partition functions for deformed N=2 theories with N_f=4 flavours

    International Nuclear Information System (INIS)

    Beccaria, Matteo; Fachechi, Alberto; Macorini, Guido; Martina, Luigi

    2016-01-01

    We consider the Ω-deformed N=2SU(2) gauge theory in four dimensions with N_f=4 massive fundamental hypermultiplets. The low energy effective action depends on the deformation parameters ε_1,ε_2, the scalar field expectation value a, and the hypermultiplet masses m=(m_1,m_2,m_3,m_4). Motivated by recent findings in the N=2"∗ theory, we explore the theories that are characterized by special fixed ratios ε_2/ε_1 and m/ε_1 and propose a simple condition on the structure of the multi-instanton contributions to the prepotential determining the effective action. This condition determines a finite set Π_N of special points such that the prepotential has N poles at fixed positions independent on the instanton number. In analogy with what happens in the N=2"∗ gauge theory, the full prepotential of the Π_N theories may be given in closed form as an explicit function of a and the modular parameter q appearing in special combinations of Eisenstein series and Jacobi theta functions with well defined modular properties. The resulting finite pole partition functions are related by AGT correspondence to special 4-point spherical conformal blocks of the Virasoro algebra. We examine in full details special cases where the closed expression of the block is known and confirms our Ansatz. We systematically study the special features of Zamolodchikov’s recursion for the Π_N conformal blocks. As a result, we provide a novel effective recursion relation that can be exactly solved and allows to prove the conjectured closed expressions analytically in the case of the Π_1 and Π_2 conformal blocks.

  6. Chronic intermittent hypoxia induces liver fibrosis in mice with diet-induced obesity via TLR4/MyD88/MAPK/NF-kB signaling pathways.

    Science.gov (United States)

    Kang, Hyeon Hui; Kim, In Kyoung; Lee, Hye In; Joo, Hyonsoo; Lim, Jeong Uk; Lee, Jongmin; Lee, Sang Haak; Moon, Hwa Sik

    2017-08-19

    Obstructive sleep apnea (OSA) is associated with nonalcoholic fatty liver disease (NAFLD), and causes chronic intermittent hypoxia (CIH) during sleep. Inflammation is associated with the development of metabolic complications induced by CIH. Research suggests that innate immune mechanisms are involved in the pro-inflammatory pathways of liver fibrosis. The purpose of this study was to investigate whether innate immune responses induce liver fibrosis, and to evaluate mechanisms underlying hepatic inflammation related to CIH in a murine diet-induced obesity (DIO) model. Inflammatory and oxidative stress markers, TLR4, MyD88, Toll/interleukin-1-receptor-domain-containing adaptor-inducing interferon-β (TRIF), I-κB, NF-κB, p38 MAPK, c-JNK, and ERK activation, were measured in the serum and liver. As a result, α1(I)-collagen mRNA was significantly higher in DIO mice exposed to CIH than in the control groups. CIH mice exhibited liver fibrosis and significantly higher protein expression of TLR4, MyD88, phosphorylated (phospho-) I-κB, and phospho-ERK1/2 activation in the liver, and higher expression of NF-κB than that in the controls. TRIF, p38 MAPK, and JNK activation did not differ significantly between groups. We conclude that CIH in DIO mice leads to liver fibrosis via TLR4/MyD88/MAPK/NF-kB signaling pathways. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Fisetin alleviates early brain injury following experimental subarachnoid hemorrhage in rats possibly by suppressing TLR 4/NF-κB signaling pathway.

    Science.gov (United States)

    Zhou, Chen-hui; Wang, Chun-xi; Xie, Guang-bin; Wu, Ling-yun; Wei, Yong-xiang; Wang, Qiang; Zhang, Hua-sheng; Hang, Chun-hua; Zhou, Meng-liang; Shi, Ji-xin

    2015-12-10

    Early brain injury (EBI) determines the unfavorable outcomes after subarachnoid hemorrhage (SAH). Fisetin, a natural flavonoid, has anti-inflammatory and neuroprotection properties in several brain injury models, but the role of fisetin on EBI following SAH remains unknown. Our study aimed to explore the effects of fisetin on EBI after SAH in rats. Adult male Sprague-Dawley rats were randomly divided into the sham and SAH groups, fisetin (25mg/kg or 50mg/kg) or equal volume of vehicle was given at 30min after SAH. Neurological scores and brain edema were assayed. The protein expression of toll-like receptor 4 (TLR 4), p65, ZO-1 and bcl-2 was examined by Western blot. TLR 4 and p65 were also assessed by immunohistochemistry (IHC). Enzyme-linked immunosorbent assay (ELISA) was performed to detect the production of pro-inflammatory cytokines. Terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling (TUNEL) was perform to assess neural cell apoptosis. High-dose (50mg/kg) fisetin significantly improved neurological function and reduced brain edema at both 24h and 72h after SAH. Remarkable reductions of TLR 4 expression and nuclear factor κB (NF-κB) translocation to nucleus were detected after fisetin treatment. In addition, fisetin significantly reduced the productions of pro-inflammatory cytokines, decreased neural cell apoptosis and increased the protein expression of ZO-1 and bcl-2. Our data provides the evidence for the first time that fisetin plays a protective role in EBI following SAH possibly by suppressing TLR 4/NF-κB mediated inflammatory pathway. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Electrochemistry of TiF{sub 4} in 1-butyl-2,3-dimethylimidazolium tetrafluoroborate

    Energy Technology Data Exchange (ETDEWEB)

    Andriyko, Yuriy, E-mail: yuriy.andriyko@cest.a [Centre of Electrochemical Surface Technology (CEST), Viktor Kaplan-Strasse 2, A-2700 Wiener Neustadt (Austria); Andriiko, Alexander [National Technical University of Ukraine ' Kyiv Polytechnic Institute' , Prospect Peremogy 37, 03057 Kyiv (Ukraine); Babushkina, Olga B. [Centre of Electrochemical Surface Technology (CEST), Viktor Kaplan-Strasse 2, A-2700 Wiener Neustadt (Austria); Nauer, Gerhard E. [Centre of Electrochemical Surface Technology (CEST), Viktor Kaplan-Strasse 2, A-2700 Wiener Neustadt (Austria); Vienna University, Faculty of Chemistry, Waehringer Strasse 42, A-1090 Wien (Austria)

    2010-01-01

    Electrochemical behaviour of Ti(IV) species in the ionic liquid (IL) 1-butyl-2,3-dimethylimidazolium tetrafluoroborate (BMMImBF{sub 4}) was studied by means of chronopotentiometry (CP) and cyclic voltammetry (CV) in melts with different concentrations of TiF{sub 4} (2-35 mol%) within a temperature range of 65-180 deg. C. The electrochemical reduction of Ti(IV) was suggested to proceed via the sequence of one-electron steps with the formation of poorly soluble low valence intermediates (LVI). LVIs undergo further solid-state electrochemical reduction to Ti metal. Thin Ti coatings on a Pt substrate were thus obtained and characterized by ESEM method. FTIR spectroscopy was used for identification of the electrochemical active species of Ti(IV). The reaction 2BF{sub 4}{sup -} + TiF{sub 4} reversible TiF{sub 6}{sup 2-} + 2BF{sub 3}arrow up takes place in the concentrated solutions of TiF{sub 4} at elevated temperatures.

  9. Hyperin protects against LPS-induced acute kidney injury by inhibiting TLR4 and NLRP3 signaling pathways

    Science.gov (United States)

    Chunzhi, Gong; Zunfeng, Li; Chengwei, Qin; Xiangmei, Bu; Jingui, Yu

    2016-01-01

    Hyperin is a flavonoid compound derived from Ericaceae, Guttifera, and Celastraceae that has been shown to have various biological effects, such as anti-inflammatory and anti-oxidant effects. However, there is no evidence to show the protective effects of hyperin on lipopolysaccharide (LPS)-induced acute kidney injury (AKI). Therefore, we investigated the protective effects and mechanism of hyperin on LPS-induced AKI in mice. The levels of TNF-α, IL-6, and IL-1β were tested by ELISA. The effects of hyperin on blood urea nitrogen (BUN) and serum creatinine were also detected. In addition, the expression of TLR4, NF-κB, and NLRP3 were detected by western blot analysis. The results showed that hyperin significantly inhibited LPS-induced TNF-α, IL-6, and IL-1β production. The levels of BUN and creatinine were also suppressed by hyperin. Furthermore, LPS-induced TLR4 expression and NF-κB activation were also inhibited by hyperin. In addition, treatment of hyperin dose-dependently inhibited LPS-induced NLRP3 signaling pathway. In conclusion, the results showed that hyperin inhibited LPS-induced inflammatory response by inhibiting TLR4 and NLRP3 signaling pathways. Hyperin has potential application prospects in the treatment of sepsis-induced AKI. PMID:27813491

  10. Omega-3 polyunsaturated fatty acid supplementation attenuates microglial-induced inflammation by inhibiting the HMGB1/TLR4/NF-κB pathway following experimental traumatic brain injury.

    Science.gov (United States)

    Chen, Xiangrong; Wu, Shukai; Chen, Chunnuan; Xie, Baoyuan; Fang, Zhongning; Hu, Weipeng; Chen, Junyan; Fu, Huangde; He, Hefan

    2017-07-24

    Microglial activation and the subsequent inflammatory response in the central nervous system play important roles in secondary damage after traumatic brain injury (TBI). High-mobility group box 1 (HMGB1) protein, an important mediator in late inflammatory responses, interacts with transmembrane receptor for advanced glycation end products (RAGE) and toll-like receptors (TLRs) to activate downstream signaling pathways, such as the nuclear factor (NF)-κB signaling pathway, leading to a cascade amplification of inflammatory responses, which are related to neuronal damage after TBI. Omega-3 polyunsaturated fatty acid (ω-3 PUFA) is a commonly used clinical immunonutrient, which has antioxidative and anti-inflammatory effects. However, the effects of ω-3 PUFA on HMGB1 expression and HMGB1-mediated activation of the TLR4/NF-κB signaling pathway are not clear. The Feeney DM TBI model was adopted to induce brain injury in rats. Modified neurological severity scores, brain water content, and Nissl staining were employed to determine the neuroprotective effects of ω-3 PUFA supplementation. Assessment of microglial activation in lesioned sites and protein markers for proinflammatory, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, interferon (IFN)-γ, and HMGB1 were used to evaluate neuroinflammatory responses and anti-inflammation effects of ω-3 PUFA supplementation. Immunofluorescent staining and western blot analysis were used to detect HMGB1 nuclear translocation, secretion, and HMGB1-mediated activation of the TLR4/NF-κB signaling pathway to evaluate the effects of ω-3 PUFA supplementation and gain further insight into the mechanisms underlying the development of the neuroinflammatory response after TBI. It was found that ω-3 PUFA supplementation inhibited TBI-induced microglial activation and expression of inflammatory factors (TNF-α, IL-1β, IL-6, and IFN-γ), reduced brain edema, decreased neuronal apoptosis, and improved neurological

  11. MCNP to study the BF3 detection efficiency

    International Nuclear Information System (INIS)

    Castro, Vinicius A.; Cavalieri, Tassio A.; Siqueira, Paulo T.D.; Fedorenko, Giuliana G.; Coelho, Paulo R.P.; Madi Filho, Tufic

    2011-01-01

    One of the main parameters to monitor on the employment of the Boron Neutron Capture Therapy (BNCT) is the thermal neutron flux. It can be performed by different techniques such as the activation analysis and the detection by a Boron Trifluoride detector (BF 3 ). BF 3 detector is a real time neutron flux detector which retrieves results in real time. It is however necessary to study the efficiency of the BF 3 detectors when they are exposed to fields of different neutron energy spectra. BF 3 is known to have high efficiency for thermal neutrons (with energy up to 0.5 eV) due the presence of 10 B atoms in the detector. However, one must also understand how this detector interacts with other neutron energy ranges (epithermal and fast). This work shows the experiment and a set of associated simulations carried out in order to evaluate the BF 3 detector efficiency dependence on neutron energy spectra. A set of experiments was conducted in which a BF 3 detector was submitted to different mixed fields (field containing gamma rays and neutrons). These fields were generated by the interposition of paraffin layers with distinct thicknesses between the Am-Be source and the BF 3 detector. The BF 3 detector responses were recorded according to the number of paraffin planes used. MCNP simulations were also performed to study the detector responses on such experimental conditions. It has been possible to achieve the intended goal of evaluating the BF 3 detector response to different mixed irradiation fields. (author)

  12. Inhibitory effect of a tyrosine-fructose Maillard reaction product, 2,4-bis(p-hydroxyphenyl-2-butenal on amyloid-β generation and inflammatory reactions via inhibition of NF-κB and STAT3 activation in cultured astrocytes and microglial BV-2 cells

    Directory of Open Access Journals (Sweden)

    Choi Im Seup

    2011-10-01

    Full Text Available Abstract Background Amyloidogenesis is linked to neuroinflammation. The tyrosine-fructose Maillard reaction product, 2,4-bis(p-hydroxyphenyl-2-butenal, possesses anti-inflammatory properties in cultured macrophages, and in an arthritis animal model. Because astrocytes and microglia are responsible for amyloidogenesis and inflammatory reactions in the brain, we investigated the anti-inflammatory and anti-amyloidogenic effects of 2,4-bis(p-hydroxyphenyl-2-butenal in lipopolysaccharide (LPS-stimulated astrocytes and microglial BV-2 cells. Methods Cultured astrocytes and microglial BV-2 cells were treated with LPS (1 μg/ml for 24 h, in the presence (1, 2, 5 μM or absence of 2,4-bis(p-hydroxyphenyl-2-butenal, and harvested. We performed molecular biological analyses to determine the levels of inflammatory and amyloid-related proteins and molecules, cytokines, Aβ, and secretases activity. Nuclear factor-kappa B (NF-κB DNA binding activity was determined using gel mobility shift assays. Results We found that 2,4-bis(p-hydroxyphenyl-2-butenal (1, 2, 5 μM suppresses the expression of inducible nitric oxide synthase (iNOS and cyclooxygenase-2 (COX-2 as well as the production of nitric oxide (NO, reactive oxygen species (ROS, tumor necrosis factor-α (TNF-α, and interleukin-1β (IL-1β in LPS (1 μg/ml-stimulated astrocytes and microglial BV-2 cells. Further, 2,4-bis(p-hydroxyphenyl-2-butenal inhibited the transcriptional and DNA binding activity of NF-κB--a transcription factor that regulates genes involved in neuroinflammation and amyloidogenesis via inhibition of IκB degradation as well as nuclear translocation of p50 and p65. Consistent with the inhibitory effect on inflammatory reactions, 2,4-bis(p-hydroxyphenyl-2-butenal inhibited LPS-elevated Aβ42 levels through attenuation of β- and γ-secretase activities. Moreover, studies using signal transducer and activator of transcription 3 (STAT3 siRNA and a pharmacological inhibitor showed that 2,4

  13. Oxidative Damage, Inflammation, and Toll-Like Receptor 4 Pathway Are Increased in Preeclamptic Patients: A Case-Control Study

    Directory of Open Access Journals (Sweden)

    Fabiana C. B. Bernardi

    2012-01-01

    Full Text Available Problem. There was no direct correlation between plasma and placental oxidative damage parameters and inflammation and evidence of TLR4 pathway activation in the placenta in preeclamptic (PE patients. Method of Study. 33 PE patients and 33 normotensive pregnant women were included. The maternal section of the placenta and blood were collected to the determination of oxidative damage markers (thiobarbituric acid reactive species and protein carbonyls, inflammatory response (interleukin-6 and myeloperoxidase activity, and activation of the TLR-4-NF-kB pathway. Results. An increase of IL-6 levels in both plasma and placenta was observed, but myeloperoxidase activity was not significantly different comparing the groups. Oxidative damage parameters were increased in plasma and placenta in PE patients. A significant increase of the protein levels of TLR-4 and NF-kB was observed in the placenta. Conclusion. The TLR4-NF-kB pathway is upregulated in PE, probably generating local and systemic inflammatory response that is followed by local and systemic oxidative damage.

  14. Stabilization and reactivity of a terminal phosphidounit on Pt(II). Synthesis and X-ray structure of cationic diphelylphosphine [Pt{C6H3(CH2NMe2)2-2,6}(PHPh2)][CF3SO3] and Diphenyl-phosphido Bridged Pt(II)-Pd(II) Complex [Pt{C6H3(CH2NMe2)2-2,6} (µ-PPh2) Pd(C6H4CH2NMe2-2)(H2O)][BF4] CH2Cl2

    NARCIS (Netherlands)

    Koten, G. van; Maassarani, F.; Davidson, M.F.; Wehman-Ooyevaar, ICM; Grove, D.M.; Koten, M.A. van; Smeets, W.J.J.; Spek, A.L.

    1995-01-01

    Reaction of diphenylphosphine with the complexes [Pt(NCN)(H{2}O)]X (NCN = C{6}H{3}(CH{2}NMe{2}){2}-2, 6; X = BF{4} (1a), OSO{2}CF{3} (1b)) leads to substitution of the H{2}O ligand to afford the ionic Pt(II) complexes [Pt(NCN)(PHPh{2})]X (X = BF{4} (2a), OSO{2}CF{3} (2b)). The X-ray structure of the

  15. Immunomodulatory effect of APS and PSP is mediated by Ca2+-cAMP and TLR4/NF-κB signaling pathway in macrophage.

    Science.gov (United States)

    Wang, Zhixue; Liu, Zijing; Zhou, Lijng; Long, Tingting; Zhou, Xing; Bao, Yixi

    2017-01-01

    This study is to investigate the role of second messengers and TLR4/NF-κB signaling pathway in the immunomodulatory activities of Astragalus polysaccharide (APS) and Polysaccharopeptide (PSP) in macrophages. RAW 264.7 macrophage cells were treated with APS, PSP, lipopolysaccharide (LPS), or NiCl 2 . Power-spectral method was used to detect protein kinase C (PKC) and Griess reaction to detect nitric oxide (NO). ELISA was conducted to detect cyclic adenosine monophosphate (cAMP), diglycerides (DAG), inositol 1, 4, 5-triphosphate (IP3), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Confocal laser scanning microscopy was performed to detect calcium level. qRT-PCR and Western blot was used to detect mRNA and protein expression of NF-κB. APS and PSP significantly increased the concentrations of intracellular second messengers (NO, cAMP, DAG, IP3, Ca 2+ ) and the activity of PKC in macrophages (pAPS and PSP (pAPS and PSP mediated immunomodulatory activities in macrophages. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Pomegranate protects liver against cecal ligation and puncture-induced oxidative stress and inflammation in rats through TLR4/NF-κB pathway inhibition.

    Science.gov (United States)

    Makled, Mirhan N; El-Awady, Mohammed S; Abdelaziz, Rania R; Atwan, Nadia; Guns, Emma T; Gameil, Nariman M; Shehab El-Din, Ahmed B; Ammar, Elsayed M

    2016-04-01

    Acute liver injury secondary to sepsis is a major challenge in intensive care unit. This study was designed to investigate potential protective effects of pomegranate against sepsis-induced acute liver injury in rats and possible underlying mechanisms. Pomegranate was orally given (800mg/kg/day) for two weeks before sepsis induction by cecal ligation and puncture (CLP). Pomegranate improved survival and attenuated liver inflammatory response, likely related to downregulation of mRNA expression of toll like recptor-4, reduced nuclear translocation and DNA binding activity of proinflammatory transcription factor NF-κB subunit p65, decreased mRNA and protein expression of tumor necrosis factor-alpha and reduction in myeloperoxidase activity and mRNA expression. Pomegranate also decreased CLP-induced oxidative stress as reflected by decreased malondialdehyde content, and increased reduced glutathione level and superoxide dismutase activity. These results confirm the antiinflammatory and antioxidant effects of pomegranate in CLP-induced acute liver injury mediated through inhibiting TLR4/NF-κB pathway, lipid peroxidation and neutrophil infiltration. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Anti-oxidative stress regulator NF-E2-related factor 2 mediates the adaptive induction of antioxidant and detoxifying enzymes by lipid peroxidation metabolite 4-hydroxynonenal

    Directory of Open Access Journals (Sweden)

    Huang Ying

    2012-11-01

    Full Text Available Abstract Background NF-E2-related factor 2 (NRF2 regulates a battery of antioxidative and phase II drug metabolizing/detoxifying genes through binding to the antioxidant response elements (ARE. NRF2-ARE signaling plays a central role in protecting cells from a wide spectrum of reactive toxic species including reactive oxygen/nitrogen species (RONS. 4-hydroxylnonenal (4-HNE is a major end product from lipid peroxidation of omega-6 polyunsaturated fatty acids (PUFA induced by oxidative stress, and it is highly reactive to nucleophilic sites in DNA and proteins, causing cytotoxicity and genotoxicity. In this study, we examined the role of NRF2 in regulating the 4-HNE induced gene expression of antioxidant and detoxifying enzymes. Results When HeLa cells were treated with 4-HNE, NRF2 rapidly transloated into the nucleus, as determined by the distribution of NRF2 tagged with the enhanced green fluorescent protein (EGFP and increased NRF2 protein in the nuclear fraction. Transcriptional activity of ARE-luciferase was significantly induced by 0.01-10 μM of 4-HNE in a dose-dependent manner, and the induction could be blocked by pretreatment with glutathione (GSH. 4-HNE induced transcriptional expression of glutathione S-transferase (GST A4, aldoketone reductase (AKR 1C1 and heme oxygenase-1 (HO-1, and the induction was attenuated by knocking down NRF2 using small interfering RNA. Conclusions NRF2 is critical in mediating 4-HNE induced expression of antioxidant and detoxifying genes. This may account for one of the major cellular defense mechanisms against reactive metabolites of lipids peroxidation induced by oxidative stress and protect cells from cytotoxicity.

  18. Tungsten phosphanylarylthiolato complexes [W{PhP(2-SC6H4)2-kappa3S,S',P} 2] and [W{P(2-SC6H4)3-kappa4S,S',S",P}2]: synthesis, structures and redox chemistry.

    Science.gov (United States)

    Hildebrand, Alexandra; Lönnecke, Peter; Silaghi-Dumitrescu, Luminita; Hey-Hawkins, Evamarie

    2008-09-14

    PhP(2-SHC6H4)2 (PS2H2) reacts with WCl6 with reduction of tungsten to give the air-sensitive tungsten(IV) complex [W{PhP(2-SC6H4)2-kappa(3)S,S',P}2] (1). 1 is oxidised in air to [WO{PhPO(2-SC6H4)2-kappa(3)S,S',O}{PhP(2-SC6H4)2-kappa(3)S,S',P}] (2). The attempted synthesis of 2 by reaction of 1 with iodosobenzene as oxidising agent was unsuccessful. [W{P(2-SC6H4)3-kappa(4)S,S',S",P}2] (3) was formed in the reaction of P(2-SHC6H4)3 (PS3H3) with WCl6. The W(VI) complex 3 contains two PS3(3-) ligands, each coordinated in a tetradentate fashion resulting in a tungsten coordination number of eight. The reaction of 3 with AgBF4 yields the dinuclear tungsten complex [W2{P(2-SC6H4)3-kappa(4)S,S',S",P}3]BF4 (4). Complexes 1-4 were characterised by spectral methods and X-ray structure determination.

  19. Investigations of 1-(4-propylamino-3-ethyl imidazolium tetrafluoroborate ionic liquid capturing CO2

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    Yang Lijuan

    2013-01-01

    Full Text Available 1-(4-propylamino-3-ethyl imidazolium ([Paeim]+ Tetrafluoroborate([BF4]- Ionic liquid (IL, capturing CO2, was explored systematically at B3LYP/6-311++G** and mp2/6-311++G** level. The stable geometries of ILs and capture products were optimized, the energies of these geometries were obtained and corrected by Zero-point-vibration-energy and basis set superposition error correction. The results show that the interactions between [Paeim]+and [BF4]-are mainly displayed as hydrogen bonds, but the interaction energies exceeds -328 kJ/mol. Further analysis found that the interactions are reinforced by charge dispersion and charge redistribution of ion-pair, and that electrostatic attraction contributes much to the interaction energies. This IL system capturing CO2belongs to the class of physical sorption with 1:1 molar absorption ratio, the absorption energy is nearly -18kJ/moland thus this IL may have low energy consumption when regenerated from IL-CO2.

  20. Protective Effect of 2-Dodecyl-6-Methoxycyclohexa-2, 5-Diene-1, 4-Dione, Isolated from Averrhoa Carambola L., Against Palmitic Acid-Induced Inflammation and Apoptosis in Min6 Cells by Inhibiting the TLR4-MyD88-NF-κB Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Qiuqiao Xie

    2016-09-01

    Full Text Available Background/Aims: Studies have demonstrated that 2-dodecyl-6-methoxycyclohexa-2, 5-diene-1, 4-dione (DMDD, isolated from the roots of Averrhoa carambola L., has significant therapeutic potential for the treatment of diabetes. However, the protective effect of DMDD against pancreatic beta cell dysfunction has never been reported. We investigated whether DMDD protected against palmitic acid-induced dysfunction in pancreatic β-cell line Min6 cells by attenuating the inflammatory response and apoptosis and to shed light on its possible mechanism. Methods: Cell viability was assessed by CCK-8. Glucose-stimulated insulin secretion levels and inflammatory cytokines levels were examined by ELISA. Apoptosis was assessed by Annexin V-FITC/PI Flow cytometry assay, Hoechst 33342/PI double-staining assay, and Transmission electron microscopy assay. Relative quantitative real-time PCR and western blot were used to determine the expressions of genes and proteins. Results: Cell viability and glucose-stimulated insulin secretion levels were increased in DMDD-pretreated Min6 cells. DMDD inhibited inflammatory cytokines IL-6, TNF-α and MCP-1 generations in palmitic acid (PA-induced Min6 cells. Moreover, DMDD protected against PA-induced Min6 cells apoptosis and the expression of Cleaved-Caspase-3, -8 and -9 were down-regulated and the Bcl-2/Bax ratio was increased in DMDD-pretreated Min6 cells. In addition, the expression of TLR4, MyD88 and NF-κB were down-regulated in DMDD-pretreated Min6 cells and TAK-242-pretreated group cells. Conclusions: DMDD protected Min6 cells against PA-induced dysfunction by attenuating the inflammatory response and apoptosis, and its mechanism of this protection was associated with inhibiting the TLR4-MyD88-NF-κB signaling pathway.

  1. 2-Methylsulfanyl-5,6-dihydro-2H-1,3-dithiolo[4,5-b][1,4]dioxin-2-ium tetrafluoroborate

    Directory of Open Access Journals (Sweden)

    Guoquan Zhou

    2012-04-01

    Full Text Available The title compound, C6H7O2S3+·BF4−, consists of a planar 2-thioxo-1,3-dithiol-4,5-yl unit [maximum deviation from the ring plane = 0.020 (3 Å], with an ethylenedioxy group fused at the 4,5-positions; the ethylenedioxy C atoms are disordered over two positions with site-occupancy factors of 0.5. The 1,4-dioxine ring has a twist-chair conformation. Weak cation–anion S...F interactions [3.022 (4–3.095 (4 Å] and an S...O [3.247 (4 Å] interaction are present.

  2. Cardiac and renal upregulation of Nox2 and NF-κB and repression of Nox4 and Nrf2 in season- and diabetes-mediated models of vascular oxidative stress in guinea-pig and rat.

    Science.gov (United States)

    Gajos-Draus, Anna; Duda, Monika; Beręsewicz, Andrzej

    2017-11-01

    The superoxide-forming NADPH oxidase homologues, Nox1, Nox2, and Nox5, seem to mediate the pro-atherosclerotic vascular phenotype. The hydrogen peroxide-forming Nox4 afforded vascular protection, likely via NF-E2-related factor-2 (Nrf2) activation and/or Nox2 downregulation in transgenic mice. We hypothesized that oxidative stress in the intact vasculature involves, aside from the upregulation of the superoxide-forming Noxs, the downregulation of the Nox4/Nrf2 pathway. Guinea-pigs and rats were studied either in winter or in summer, and the streptozotocin diabetic rats in winter. Plasma nitrite, and superoxide production by isolated hearts were measured, while frozen tissues served in biochemical analyses. Summer in both species and diabetes in rats downregulated myocardial Nox4 while reciprocally upregulating Nox2 and Nox5 in guinea-pigs, and Nox2 in rats. Simultaneously, myocardial Nrf2 activity and the expression of the Nrf2-directed heme oxygenase-1 and endothelial NO synthase were reduced while activity of the nuclear factor κ B (NF- κ B) and the expression of NF- κ B-directed inducible NO synthase and the vascular cell adhesion molecule-1 were increased. Cardiac superoxide production was increased while plasma nitrite was decreased reciprocally. Analogous disregulation of Noxs, Nrf2, and NF- κ B, occurred in diabetic rat kidneys. Given the diversity of the experimental settings and the uniform pattern of the responses, we speculate that: (1) chronic vascular oxidative stress is a nonspecific (model-, species-, organ-independent) response involving the induction of Nox2 (and Nox5 in guinea-pigs) and the NF- κ B pathway, and the repression of Nox4 and the Nrf2 pathway; and (2) the systems Nox2-NF- κ B and Nox4-Nrf2 regulate each other negatively. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  3. Kaempferol ameliorates H9N2 swine influenza virus-induced acute lung injury by inactivation of TLR4/MyD88-mediated NF-κB and MAPK signaling pathways.

    Science.gov (United States)

    Zhang, Ruihua; Ai, Xia; Duan, Yongjie; Xue, Man; He, Wenxiao; Wang, Cunlian; Xu, Tong; Xu, Mingju; Liu, Baojian; Li, Chunhong; Wang, Zhijun; Zhang, Ruihong; Wang, Guohua; Tian, Shufei; Liu, Huifeng

    2017-05-01

    Kaempferol, a very common type of dietary flavonoids, has been found to exert antioxidative and anti-inflammatory properties. The purpose of our investigation was designed to reveal the effect of kaempferol on H9N2 influenza virus-induced inflammation in vivo and in vitro. In vivo, BALB/C mice were infected intranasally with H9N2 influenza virus with or without kaempferol treatment to induce acute lung injury (ALI) model. In vitro, MH-S cells were infected with H9N2 influenza virus with or without kaempferol treatment. In vivo, kaempferol treatment attenuated pulmonary edema, the W/D mass ratio, pulmonary capillary permeability, myeloperoxidase (MPO) activity, and the numbers of inflammatory cells. Kaempferol reduced ROS and Malondialdehyde (MDA) production, and increased the superoxide dismutase (SOD) activity. Kaempferol also reduced overproduction of TNF-α, IL-1β and IL-6. In addition, kaempferol decreased the H9N2 viral titre. In vitro, ROS, MDA, TNF-α, IL-1β and IL-6 was also reduced by kaempferol. Moreover, our data showed that kaempferol significantly inhibited the upregulation of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), phosphorylation level of IκBα and nuclear factor-κB (NF-κB) p65, NF-κB p65 DNA binding activity, and phosphorylation level of MAPKs, both in vivo and in vitro. These results suggest that kaempferol exhibits a protective effect on H9N2 virus-induced inflammation via suppression of TLR4/MyD88-mediated NF-κB and MAPKs pathways, and kaempferol may be considered as an effective drug for the potential treatment of influenza virus-induced ALI. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. Low nuclear body formation and tax SUMOylation do not prevent NF-kappaB promoter activation

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    Bonnet Amandine

    2012-09-01

    Full Text Available Abstract Background The Tax protein encoded by Human T-lymphotropic virus type 1 (HTLV-1 is a powerful activator of the NF-κB pathway, a property critical for HTLV-1-induced immortalization of CD4+ T lymphocytes. Tax permanently stimulates this pathway at a cytoplasmic level by activating the IκB kinase (IKK complex and at a nuclear level by enhancing the binding of the NF-κB factor RelA to its cognate promoters and by forming nuclear bodies, believed to represent transcriptionally active structures. In previous studies, we reported that Tax ubiquitination and SUMOylation play a critical role in Tax localization and NF-κB activation. Indeed, analysis of lysine Tax mutants fused or not to ubiquitin or SUMO led us to propose a two-step model in which Tax ubiquitination first intervenes to activate IKK while Tax SUMOylation is subsequently required for promoter activation within Tax nuclear bodies. However, recent studies showing that ubiquitin or SUMO can modulate Tax activities in either the nucleus or the cytoplasm and that SUMOylated Tax can serve as substrate for ubiquitination suggested that Tax ubiquitination and SUMOylation may mediate redundant rather than successive functions. Results In this study, we analyzed the properties of a new Tax mutant that is properly ubiquitinated, but defective for both nuclear body formation and SUMOylation. We report that reducing Tax SUMOylation and nuclear body formation do not alter the ability of Tax to activate IKK, induce RelA nuclear translocation, and trigger gene expression from a NF-κB promoter. Importantly, potent NF-κB promoter activation by Tax despite low SUMOylation and nuclear body formation is also observed in T cells, including CD4+ primary T lymphocytes. Moreover, we show that Tax nuclear bodies are hardly observed in HTLV-1-infected T cells. Finally, we provide direct evidence that the degree of NF-κB activation by Tax correlates with the level of Tax ubiquitination, but not

  5. BF2 complex of fluorinated dipyrrolyldiketone: a new class of efficient receptor for acetate anions.

    Science.gov (United States)

    Maeda, Hiromitsu; Ito, Yoshihiro

    2006-10-02

    The beta-fluorinated derivative (2b) of the 1,3-dipyrrolyl-1,3-propanedione BF2 complex has been prepared from 3,4-difluoropyrrole and malonyl chloride, followed by treatment with BF3.OEt2. Despite the simple, acyclic, and neutral structure, 2b exhibits efficient 1:1 binding for anions in CH2Cl2 using the bridging CH and pyrrole NH as interaction sites. The binding constant (Ka) of 2b for acetate (CH3CO(2-)), associating more effectively than anions such as F-, Cl-, Br-, H2PO(4-), and HSO(4-), is estimated to be 9.6 x 10(5) M(-1), approximately 9 times larger than that of the beta-H derivative 2a (1.1 x 10(5) M(-1)). The UV-vis and fluorescence spectral changes of 2b elucidate the effective recognition of an amino acid, such as phenylalanine, in the anionic form; this is also supported by CD spectral changes with mirror images by L- and D-isomers. Furthermore, in the solid state, BF2 complex 2b provides Cl- -bridged supramolecular networks and, in sharp contrast, deprotonated "anionic" self-assembled structures by F- binding.

  6. A reciprocity formula from abelian BF and Turaev–Viro theories

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    P. Mathieu

    2016-11-01

    Full Text Available In this article we show that the use of Deligne–Beilinson cohomology in the context of the U(1 BF theory on a closed 3-manifold M yields a discrete ZN BF theory whose partition function is an abelian TV invariant of M. By comparing the expectation values of the U(1 and ZN holonomies in both BF theories we obtain a reciprocity formula.

  7. The HIV-1 epidemic in Bolivia is dominated by subtype B and CRF12_BF "family" strains.

    Science.gov (United States)

    Guimarães, Monick L; Velarde-Dunois, Ketty G; Segurondo, David; Morgado, Mariza G

    2012-01-16

    Molecular epidemiological studies of HIV-1 in South America have revealed the occurrence of subtypes B, F1 and BF1 recombinants. Even so, little information concerning the HIV-1 molecular epidemiology in Bolivia is available. In this study we performed phylogenetic analyses from samples collected in Bolivia at two different points in time over a 10 year span. We analyzed these samples to estimate the trends in the HIV subtype and recombinant forms over time. Fifty one HIV-1 positive samples were collected in Bolivia over two distinct periods (1996 and 2005). These samples were genetically characterized based on partial pol protease/reverse transcriptase (pr/rt) and env regions. Alignment and neighbor-joining (NJ) phylogenetic analyses were established from partial env (n = 37) and all pol sequences using Mega 4. The remaining 14 env sequences from 1996 were previously characterized based on HMA-env (Heteroduplex mobility assay). The Simplot v.3.5.1 program was used to verify intragenic recombination, and SplitsTree 4.0 was employed to confirm the phylogenetic relationship of the BF1 recombinant samples. Phylogenetic analysis of both env and pol regions confirmed the predominance of "pure" subtype B (72.5%) samples circulating in Bolivia and revealed a high prevalence of BF1 genotypes (27.5%). Eleven out of 14 BF1 recombinants displayed a mosaic structure identical or similar to that described for the CRF12_BF variant, one sample was classified as CRF17_BF, and two others were F1pol/Benv. No "pure" HIV-1 subtype F1 or B" variant of subtype B was detected in the present study. Of note, samples characterized as CRF12_BF-related were depicted only in 2005. HIV-1 genetic diversity in Bolivia is mostly driven by subtype B followed by BF1 recombinant strains from the CRF12_BF "family". No significant temporal changes were detected between the mid-1990s and the mid-2000s for subtype B (76.2% vs 70.0%) or BF1 recombinant (23.8% vs 30.0%) samples from Bolivia.

  8. Down-regulation of NF-κB DNA binding activity by Angelica Sinensis to ameliorate radiation-induced pulmonary injury in mouse model

    International Nuclear Information System (INIS)

    Cao Zhen; Xie Conghua; Zhou Fuxiang; Luo Zhiguo; Zhou Yunfeng; Hang Guang

    2008-01-01

    Objective: To study the trend of NF-kB binding activity during the course of radiation-induced pulmonary injury (RPI), and to evaluate the intervention effect of Angelica Sinensis on it. Methods: Adult female C57BL/6J mice were randomly divided into 4 groups: blank control group (N group), Angelica Sinensis control group (A group), irradiation group (NX group) and irradiation group with Angelica Sinensis intervention (AX group). All mice from the NX and AX groups underwent single fraction of 12 Gy γ-ray delivered to the whole thorax. All mice were intraperitoneally injected 25% Angelica Sinensis injection (20 ml/kg) or identical volume Normal Sodiumdaily injection initiated 1 week before irradiation, lasted till 2 weeks after irradiation. Mice were sacrificed at designated time points (1, 24, 72 h, 1, 2, 4, 8, 16 and 24 weeks), and the whole lungs were removed freshly. HE and Masson staining were performed to provide histopathologic evidence and to evaluate the collagen deposit situation respectively. The immunohistochemical staining of NF-κB P65 protein was performed to identify the location as well as the relative content of P65 protein. The DNA binding activity of NF-κB was detected by TransAM TM ELISA assay. Results: HE and Masson staining manifested that visible pathological alterations began at 2 weeks, typical interstitial pneumonitis were showed at 4 and 8 weeks, collagen deposition was visible from 16 weeks. The NF-κB binding activity detection and the immunohistochemical half-quantity analysis showed two-phase elevation, at 24 h and 8 weeks. Preventive application of Angelica Sinensis revealed prominently ameliorative effect for RPI, with pathological improvement, decreased immunohistochemical staining and lower NF-κB binding activity in both peaks. Conclusions: During the development process of RPI, NF-κB binding activity shows two-phase elevation. Chinese medicine Angelica Sinensis can down-regulate the elevation, showing noted ameliorative effect

  9. Inhibitory effects of glucocorticoid on apoptosis and activation of NF-κB in P388 cells induced by radiation

    International Nuclear Information System (INIS)

    Shi Jianhui; Niu Yuhong; Ge Junbo; Xu Xiaoping; Cheng Wenying; Feng Xiao; Zhang Zongliang

    2002-01-01

    Objective: To explore effects of glucocorticoid on apoptosis and activation of NF-κB in P388 cells induced by radiation. Methods: Apoptosis in P388 cells induced by radiation treatment was detected by TUNEL assay. EMSA was used to detect the activation of NF-κB . Results: The apoptosis and activation of NF-κB in P388 cells could be induced by radiation. Dexamethasone (DXM) which could suppress activation of NF-κB of P388 cells increased significantly the apoptosis induced by radiation. Apoptosis rates in DXM-treated P388 cells after 2, 4, 6 and 8 Gy exposure increased by 60%, 100%, 129% and 67%, respectively. Activation rates of NF-κB in DXM-treated P388 cells after 2, 4, 6 and 8 Gy exposure decreased by 25%, 45%, 52% and 40%, respectively. Conclusion: Radiation induces apoptosis and activation of NF-κB in P388 cells simultaneously. Glucocorticoid enhances apoptosis in leukemic cells, which may be by means of suppressing activation of NF-κB

  10. Paeoniflorin Suppressed High Glucose-Induced Retinal Microglia MMP-9 Expression and Inflammatory Response via Inhibition of TLR4/NF-κB Pathway Through Upregulation of SOCS3 in Diabetic Retinopathy.

    Science.gov (United States)

    Zhu, Su-Hua; Liu, Bing-Qian; Hao, Mao-Juan; Fan, Yi-Xin; Qian, Cheng; Teng, Peng; Zhou, Xiao-Wei; Hu, Liang; Liu, Wen-Tao; Yuan, Zhi-Lan; Li, Qing-Ping

    2017-10-01

    Diabetic retinopathy (DR) is a serious-threatening complication of diabetes and urgently needed to be treated. Evidence has accumulated indicating that microglia inflammation within the retina plays a critical role in DR. Microglial matrix metalloproteinase 9 (MMP-9) has an important role in the destruction of the integrity of the blood-retinal barrier (BRB) associated with the development of DR. MMP-9 was also considered important for regulating inflammatory responses. Paeoniflorin, a monoterpene glucoside, has a potent immunomodulatory effect on microglia. We hypothesized that paeoniflorin could significantly suppress microglial MMP-9 activation induced by high glucose and further relieve DR. BV2 cells were used to investigate the effects and mechanism of paeoniflorin. The activation of MMP-9 was measured by gelatin zymography. Cell signaling was measured by western blot assay and immunofluorescence assay. High glucose increased the activation of MMP-9 in BV2 cells, which was abolished by HMGB1, TLR4, p38 MAPK, and NF-κB inhibition. Phosphorylation of p38 MAPK induced by high glucose was decreased by TLR4 inhibition in BV2 cells. Paeoniflorin induced suppressor of cytokine signaling 3 (SOCS3) expression and reduced MMP-9 activation in BV2 cells. The effect of paeoniflorin on SOCS3 was abolished by the TLR4 inhibitor. In streptozotocin (STZ)-induced diabetes mice, paeoniflorin induced SOCS3 expression and reduced MMP-9 activation. Paeoniflorin suppressed STZ-induced IBA-1 and IL-1β expression and decreased STZ-induced high blood glucose level. In conclusion, paeoniflorin suppressed high glucose-induced retinal microglia MMP-9 expression and inflammatory response via inhibition of the TLR4/NF-κB pathway through upregulation of SOCS3 in diabetic retinopathy.

  11. Nitrosonium complexation by the tetraphosphonate cavitand 5,11,17,23-tetramethyl-6,10:12,16:18,22:24,4-tetrakis(phenylphosphonato-κ2O,Oresorcin(4arene

    Directory of Open Access Journals (Sweden)

    Roberta Pinalli

    2017-12-01

    Full Text Available The crystal structure of a new supramolecular complex between the tetraphosphonate cavitand 5,11,17,23-tetramethyl-6,10:12,16:18,22:24,4-tetrakis(phenylphosphonato-κ2O,O′resorcin(4arene and the nitrosyl cation NO+, as the BF4− salt, is reported. The complex, of general formula [(C56H44P4O12(NO]BF4·CH2Cl2 or NO@Tiiii[H, CH3, C6H5] BF4·CH2Cl2, crystallizes in the space group P-1. The nitrosyl cation is disordered over two equivalent positions, with occupancies of 0.503 (2 and 0.497 (2, and interacts with two adjacent P=O groups at the upper rim of the cavitand through dipole–charge interactions. In the lattice, the cavitands are connected through a series of C—H...π interactions involving the methyl and methylenic H atoms and the aromatic rings of the macrocycle. The structure is further stabilized by the presence of C—H...F interactions between the hydrogen atoms of the cavitands and the F atoms of the tetrafluoridoborate anion. As a result of the disorder, the lattice dichloromethane molecules could not be modelled in terms of atomic sites, and were treated using the PLATON SQUEEZE procedure [Spek (2015. Acta Cryst. C71, 9–18]. The complexation process has also been studied in solution through NMR titrations.

  12. The proportion of prostate biopsy tissue with Gleason pattern 4 or 5 predicts for biochemical and clinical outcome after radiotherapy for prostate cancer

    International Nuclear Information System (INIS)

    D'Ambrosio, David J.; Hanlon, Alexandra L.; Al-Saleem, Tahseen; Feigenberg, Steven J.; Horwitz, Eric M.; Uzzo, Robert G.; Pollack, Alan; Buyyounouski, Mark K.

    2007-01-01

    Purpose: To investigate the prognostic utility of the proportion of prostate biopsy tissue containing Gleason pattern 4 or 5 (GP4/5) after definitive radiotherapy (RT) for prostate cancer. Methods and Materials: A total of 568 patients with T1c-3 Nx/0 prostate cancer who received three-dimensional conformal RT alone between May 1989 and August 2001 were studied. There were 161 men with Gleason score 7-10 disease. The GP4/5 was defined as the percentage of biopsy tissue containing Gleason pattern 4 or 5. A Cox proportional hazards model was used for univariate and multivariate analyses (MVA) for biochemical failure (BF) (American Society of Therapeutic Radiology and Oncology definition) and distant metastasis (DM). A recursive partitioning analysis was done using the results of the MVA to identify a cutpoint for GP4/5. Results: The median follow-up was 46 (range, 13-114) months and median RT dose was 76 (range, 65-82) Gy. On MVA, increasing initial prostate-specific antigen (p = 0.0248) decreasing RT dose (continuous, p = 0.0022), T stage (T1/2 vs. T3) (p = 0.0136) and GP4/5 (continuous, p < 0.0001) were significant predictors of BF in a model also containing GS. GP4/5 was the only significant predictor of DM in the same model (p < 0.0001). Conclusion: The GP4/5 in prostate biopsy specimens is a predictor of BF and DM after RT independent of Gleason score. This parameter should be reported by the pathologist when reviewing prostatic biopsy specimens

  13. Dicty_cDB: Contig-U01505-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available y1 Gm-c1004 Glycine max cDNA clone GENOME... 32 3.7 2 ( DV211690 ) 0089P0160Z_H09_T7 Mimulus guttatus library 2 Mimu...38TG Tetrahymena thermophila EST library str... 38 2.5 2 ( AC177658 ) Strongylocentrotus purpuratus clone R3...6 1.4 1 ( BG041778 ) saa41a04.y1 Gm-c1059 Glycine soja cDNA clone GENO... 46 1.4 1 ( BF645094 ) NF034E10EC1F1082 Elicited cell cultur...e Medicago t... 46 1.4 1 ( BF644741 ) NF014E01EC1F1005 Elicited cell culture Medica...a oleracea var. alboglabra EST, clone AAF... 44 5.4 1 ( CN828044 ) EL2662R Brassica embryo library (EL) Brassic

  14. Nuclear factor 1 regulates adipose tissue-specific expression in the mouse GLUT4 gene

    International Nuclear Information System (INIS)

    Miura, Shinji; Tsunoda, Nobuyo; Ikeda, Shinobu; Kai, Yuko; Cooke, David W.; Lane, M. Daniel; Ezaki, Osamu

    2004-01-01

    Previous studies demonstrated that an adipose tissue-specific element(s) (ASE) of the murine GLUT4 gene is located between -551 and -506 in the 5'-flanking sequence and that a high-fat responsive element(s) for down-regulation of the GLUT4 gene is located between bases -701 and -552. A binding site for nuclear factor 1 (NF1), that mediates insulin and cAMP-induced repression of GLUT4 in 3T3-L1 adipocytes is located between bases -700 and -688. To examine the role of NF1 in the regulation of GLUT4 gene expression in white adipose tissues (WAT) in vivo, we created two types of transgenic mice harboring mutated either 5' or 3' half-site of NF1-binding sites in GLUT4 minigene constructs. In both cases, the GLUT4 minigene was not expressed in WAT, while expression was maintained in brown adipose tissue, skeletal muscle, and heart. This was an unexpected finding, since a -551 GLUT4 minigene that did not have the NF1-binding site was expressed in WAT. We propose a model that explains the requirement for both the ASE and the NF1-binding site for expression of GLUT4 in WAT

  15. Antioxidant and anti-inflammatory properties of 1,2,4-oxadiazole analogs of resveratrol.

    Science.gov (United States)

    Gobec, Martina; Tomašič, Tihomir; Markovič, Tijana; Mlinarič-Raščan, Irena; Dolenc, Marija Sollner; Jakopin, Žiga

    2015-10-05

    The chemopreventive properties of resveratrol are ascribed mostly to its antioxidant activity, in particular its scavenging ability for reactive oxygen species (ROS), and to the inhibition of NF-κB pathway which has also been suggested as an important underlying mechanism of its reported properties. In present study, a small library of nine 1,2,4-oxadiazole-based structural analogs of resveratrol were assayed for their antioxidant and anti-inflammatory activities. Several compounds showed significant inhibitory activities against NF-κB and/or ROS production. Compound 2, incorporating two para-hydroxyphenyl moieties connected by the 1,2,4-oxadiazole ring, was the most active, its potency in inhibiting activation of NF-κB and ROS scavenging abilities surpassing that of resveratrol. Additionally, we elucidated the mechanisms underlying the NF-κB inhibitory activity of compound 2. Finally, in contrast to resveratrol, compound 2 significantly reduced the LPS-induced release of pro-inflammatory cytokines, indicating its prominent anti-inflammatory potential. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Hypoxia attenuates inflammatory mediators production induced by Acanthamoeba via Toll-like receptor 4 signaling in human corneal epithelial cells

    International Nuclear Information System (INIS)

    Pan, Hong; Wu, Xinyi

    2012-01-01

    Highlights: ► Hypoxia attenuates Acanthamoeba-induced the production of IL-8 and IFN-β. ► Hypoxia inhibits TLR4 expression in a time-dependent manner in HCECs. ► Hypoxia inhibits Acanthamoeba-induced the activation of NF-κB and ERK1/2 in HCECs. ► Hypoxia decreases Acanthamoeba-induced inflammatory response via TLR4 signaling. ► LPS-induced the secretion of IL-6 and IL-8 is abated by hypoxia via TLR4 signaling. -- Abstract: Acanthamoeba keratitis (AK) is a vision-threatening corneal infection that is intimately associated with contact lens use which leads to hypoxic conditions on the corneal surface. However, the effect of hypoxia on the Acanthamoeba-induced host inflammatory response of corneal epithelial cells has not been studied. In the present study, we investigated the effect of hypoxia on the Acanthamoeba-induced production of inflammatory mediators interleukin-8 (IL-8) and interferon-β (IFN-β) in human corneal epithelial cells and then evaluated its effects on the Toll-like receptor 4 (TLR4) signaling, including TLR4 and myeloid differentiation primary response gene (88) (MyD88) expression as well as the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and extracellular signal-regulated kinases 1/2 (ERK1/2). We then studied the effect of hypoxia on a TLR4-specific inflammatory response triggered by the TLR4 ligand lipopolysaccharide (LPS). Our data showed that hypoxia significantly decreased the production of IL-8 and IFN-β. Furthermore, hypoxia attenuated Acanthamoeba-triggered TLR4 expression as well as the activation of NF-κB and ERK1/2, indicating that hypoxia abated Acanthamoeba-induced inflammatory responses by affecting TLR4 signaling. Hypoxia also inhibited LPS-induced IL-6 and IL-8 secretion, myeloid differentiation primary response gene (88) MyD88 expression and NF-κB activation, confirming that hypoxia suppressed the LPS-induced inflammatory response by affecting TLR4 signaling. In conclusion

  17. Let-7b is involved in the inflammation and immune responses associated with Helicobacter pylori infection by targeting Toll-like receptor 4.

    Directory of Open Access Journals (Sweden)

    Gui-gen Teng

    Full Text Available OBJECTIVES: Toll-like receptors (TLRs are important initiators in native immune responses to microbial infections. TLR4 is up-regulated in response to H.pylori infection in gastric epithelial cells. However, the regulatory mechanisms for the expression of TLR4 in H.pylori infection have not been clearly defined. The aims of this study are to present the evidence that microRNA let-7b directly regulates TLR4 expression in human gastric epithelial cells, and subsequently influences the activation of NF-κB and the expression of the downstream genes in H.pylori infection. METHODS: The expression of let-7b was determined in gastric mucosa specimens and in two gastric epithelial cell lines using quantitative RT-PCR. The expression of TLR4 was determined by immunohistochemistry staining and RT-PCR. The potential target of let-7b was identified by luciferase reporter assay and Western blot. Let-7b mimics and inhibitors were used to examine the effects of let-7b on NF-κB activity. The expression of the downstream genes of NF-κB was also determined in cells infected with H.pylori 26695. RESULTS: Let-7b was significantly decreased in gastric mucosa specimens and in gastric epithelial cell lines (AGS, GES-1 infected with H.pylori 26695 (cagA+. Let-7b was complementary to the 3'-UTR of TLR4 mRNA and regulated TLR4 expression via post-transcriptional suppression in gastric epithelium. Infection of H.pylori induced the expression of TLR4 and activated NF-κB in AGS and GES-1 cells. Overexpression of let-7b by mimics downregulated TLR4, and subsequently attenuated NF-κB, MyD88, NF-κB1/p50, RelA/p65. The expression of IL-8, COX-2 and CyclinD1 was inhibited in H.pylori infected cells with let-7b overexpression. Both TAK-242 (TLR4 inhibitor and SN50 (NF-κB inhibitor significantly inhibited the H.pylori induced downregulation of let-7b. CONCLUSIONS: Let-7b targets at TLR4 mRNA, and regulates the activation of NF-κB and the expression of the downstream genes

  18. Pharmacological Inhibition of Macrophage Toll-like Receptor 4/Nuclear Factor-kappa B Alleviates Rhabdomyolysis-induced Acute Kidney Injury.

    Science.gov (United States)

    Huang, Rong-Shuang; Zhou, Jiao-Jiao; Feng, Yu-Ying; Shi, Min; Guo, Fan; Gou, Shen-Ju; Salerno, Stephen; Ma, Liang; Fu, Ping

    2017-09-20

    Acute kidney injury (AKI) is the most common and life-threatening systemic complication of rhabdomyolysis. Inflammation plays an important role in the development of rhabdomyolysis-induced AKI. This study aimed to investigate the kidney model of AKI caused by rhabdomyolysis to verify the role of macrophage Toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) signaling pathway. C57BL/6 mice were injected with a 50% glycerin solution at bilateral back limbs to induce rhabdomyolysis, and CLI-095 or pyrrolidine dithiocarbamate (PDTC) was intraperitoneally injected at 0.5 h before molding. Serum creatinine levels, creatine kinase, the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6, and hematoxylin and eosin stainings of kidney tissues were tested. The infiltration of macrophage, mRNA levels, and protein expression of TLR4 and NF-κB were investigated by immunofluorescence double-staining techniques, reverse transcriptase-quantitative polymerase chain reaction, and Western blotting, respectively. In vitro, macrophage RAW264.7 was stimulated by ferrous myoglobin; the cytokines, TLR4 and NF-κB expressions were also detected. In an in vivo study, using CLI-095 or PDTC to block TLR4/NF-κB, functional and histologic results showed that the inhibition of TLR4 or NF-κB alleviated glycerol-induced renal damages (P rhabdomyolysis-induced AKI by the regulation of proinflammatory cytokine production and macrophage infiltration.

  19. Anti-proliferative, Cytotoxic and NF-ĸB Inhibitory Properties of Spiro(Lactone-Cyclohexanone) Compounds in Human Leukemia.

    Science.gov (United States)

    Bouhenna, Mustapha M; Orlikova, Barbora; Talhi, Oualid; Schram, Ben; Pinto, Diana C G A; Taibi, Nadia; Bachari, Khaldoun; Diederich, Marc; Silva, Artur M S; Mameri, Nabil

    2017-09-01

    NF-ĸB affects most aspects of cellular physiology. Deregulation of NF-ĸB signaling is associated with inflammatory diseases and cancer. In this study, we evaluated the cytotoxic and NF-ĸB inhibition potential of new spiro(lactone-cyclohexanone) compounds in two different human leukemia cell lines (U937 and K562). The anti-proliferative effects of the spiro(lactone-cyclohexanone) compounds on human K562 and U937 cell lines was evaluated by trypan blue staining, as well as their involvement in NF-kB regulation were analyzed by luciferase reporter gene assay, Caspase-3/7 activities were evaluated to analyze apoptosis induction. Both spiro(coumarin-cyclohexanone) 4 and spiro(6- methyllactone-cyclohexanone) 9 down-regulated cancer cell viability and proliferation. Compound 4 inhibited TNF-α-induced NF-ĸB activation in a dose-dependent manner and induced caspase-dependent apoptosis in both leukemia cell lines. Results show that compound 4 and compound 9 have potential as anti-cancer agents. In addition, compound 4 exerted NF-kB inhibition activity in leukemia cancer cells. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  20. Toll-like receptor 4 mediates microglial activation and production of inflammatory mediators in neonatal rat brain following hypoxia: role of TLR4 in hypoxic microglia

    Science.gov (United States)

    2013-01-01

    downregulation-mediated inhibition of inflammatory cytokines in primary microglia and BV-2 cells was accompanied by the suppression of NF-κB activation. Furthermore, HIF-1α antibody neutralization attenuated the increase of TLR4 expression in hypoxic BV-2 cells. TLR4 inhibition in vivo attenuated the immunoexpression of TNF-α, IL-1β and iNOS on microglia post-hypoxia. Conclusion Activated microglia TLR4 expression mediated neuroinflammation via a NF-κB signaling pathway in response to hypoxia. Hence, microglia TLR4 presents as a potential therapeutic target for neonatal hypoxia brain injuries. PMID:23388509

  1. Synthesis of some (eta-arene)dihydridorhenium cations and their reactions with LiAlH4 and LiAlD4

    International Nuclear Information System (INIS)

    Baudrey, D.; Boydell, P.; Ephritikhine, M.

    1986-01-01

    A series of cations [Re(eta-arene)H 2 (PPh 3 ) 2 ] + (arene benzene, toluene, p-xylene, or mesitylene) was prepared from the corresponding neutral dihydridocyclohexadienyl complexes by treatment with CPh 3 BF 4 . These cations reacted with LiAlH 4 and LiAlD 4 to form dihydridocyclohexadienyl complexes. The unusual selectivity of the hydride attack is explained by steric interactions between the ring methyl groups and the bulky phosphine ligands. The initial product of the reaction of the eta-mesitylene cation with LiAlD 4 allows the isomerisation mechanism for the cyclohexadienyl complexes to be clarified. (author)

  2. Anesthetic propofol reduces endotoxic inflammation by inhibiting reactive oxygen species-regulated Akt/IKKβ/NF-κB signaling.

    Directory of Open Access Journals (Sweden)

    Chung-Hsi Hsing

    Full Text Available BACKGROUND: Anesthetic propofol has immunomodulatory effects, particularly in the area of anti-inflammation. Bacterial endotoxin lipopolysaccharide (LPS induces inflammation through toll-like receptor (TLR 4 signaling. We investigated the molecular actions of propofol against LPS/TLR4-induced inflammatory activation in murine RAW264.7 macrophages. METHODOLOGY/PRINCIPAL FINDINGS: Non-cytotoxic levels of propofol reduced LPS-induced inducible nitric oxide synthase (iNOS and NO as determined by western blotting and the Griess reaction, respectively. Propofol also reduced the production of tumor necrosis factor-α (TNF-α, interleukin (IL-6, and IL-10 as detected by enzyme-linked immunosorbent assays. Western blot analysis showed propofol inhibited LPS-induced activation and phosphorylation of IKKβ (Ser180 and nuclear factor (NF-κB (Ser536; the subsequent nuclear translocation of NF-κB p65 was also reduced. Additionally, propofol inhibited LPS-induced Akt activation and phosphorylation (Ser473 partly by reducing reactive oxygen species (ROS generation; inter-regulation that ROS regulated Akt followed by NF-κB activation was found to be crucial for LPS-induced inflammatory responses in macrophages. An in vivo study using C57BL/6 mice also demonstrated the anti-inflammatory properties against LPS in peritoneal macrophages. CONCLUSIONS/SIGNIFICANCE: These results suggest that propofol reduces LPS-induced inflammatory responses in macrophages by inhibiting the interconnected ROS/Akt/IKKβ/NF-κB signaling pathways.

  3. Anesthetic Propofol Reduces Endotoxic Inflammation by Inhibiting Reactive Oxygen Species-regulated Akt/IKKβ/NF-κB Signaling

    Science.gov (United States)

    Hsing, Chung-Hsi; Lin, Ming-Chung; Choi, Pui-Ching; Huang, Wei-Ching; Kai, Jui-In; Tsai, Cheng-Chieh; Cheng, Yi-Lin; Hsieh, Chia-Yuan; Wang, Chi-Yun; Chang, Yu-Ping; Chen, Yu-Hong; Chen, Chia-Ling; Lin, Chiou-Feng

    2011-01-01

    Background Anesthetic propofol has immunomodulatory effects, particularly in the area of anti-inflammation. Bacterial endotoxin lipopolysaccharide (LPS) induces inflammation through toll-like receptor (TLR) 4 signaling. We investigated the molecular actions of propofol against LPS/TLR4-induced inflammatory activation in murine RAW264.7 macrophages. Methodology/Principal Findings Non-cytotoxic levels of propofol reduced LPS-induced inducible nitric oxide synthase (iNOS) and NO as determined by western blotting and the Griess reaction, respectively. Propofol also reduced the production of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-10 as detected by enzyme-linked immunosorbent assays. Western blot analysis showed propofol inhibited LPS-induced activation and phosphorylation of IKKβ (Ser180) and nuclear factor (NF)-κB (Ser536); the subsequent nuclear translocation of NF-κB p65 was also reduced. Additionally, propofol inhibited LPS-induced Akt activation and phosphorylation (Ser473) partly by reducing reactive oxygen species (ROS) generation; inter-regulation that ROS regulated Akt followed by NF-κB activation was found to be crucial for LPS-induced inflammatory responses in macrophages. An in vivo study using C57BL/6 mice also demonstrated the anti-inflammatory properties against LPS in peritoneal macrophages. Conclusions/Significance These results suggest that propofol reduces LPS-induced inflammatory responses in macrophages by inhibiting the interconnected ROS/Akt/IKKβ/NF-κB signaling pathways. PMID:21408125

  4. Identification and functional characterization of a solute carrier family 15, member 4 gene in Litopenaeus vannamei.

    Science.gov (United States)

    Chen, Yong-Gui; Yuan, Kai; Zhang, Ze-Zhi; Yuan, Feng-Hua; Weng, Shao-Ping; Yue, Hai-Tao; He, Jian-Guo; Chen, Yi-Hong

    2016-04-01

    Innate immunity in shrimp is important in resisting bacterial infection. The NF-κB pathway is pivotal in such an immune response. This study cloned and functionally characterized the solute carrier family (SLC) 15 member A 4 (LvSLC15A4) gene in Litopenaeus vannamei. The open reading frame of LvSLC15A4 is 1, 902 bp long and encodes a putative 633-amino acid protein, which is localized in the plasma membrane and intracellular vesicular compartments. Results of the reporter gene assay showed that LvSLC15A4 upregulated NF-κB target genes, including the immediate-early gene 1 of white spot syndrome virus, as well as several antimicrobial peptide genes, such as pen4, CecA, AttA, and Mtk in S2 cells. Moreover, knocked-down expression of LvSLC15A4 reduced pen4 expression in L. vannamei. LvSLC15A4 down-regulation also increased the cumulative mortality of Vibrio parahemolyticus-infected L. vannamei. Furthermore, LvSLC15A4 expression was induced by unfolded protein response (UPR) in L. vannamei hematocytes. These results suggest that LvSLC15A4 participates in L. vannamei innate immunity via the NF-κB pathway and thus may be related to UPR. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Loss of BMI-1 dampens migration and EMT of colorectal cancer in inflammatory microenvironment through TLR4/MD-2/MyD88-mediated NF-κB signaling.

    Science.gov (United States)

    Ye, Kai; Chen, Qi-Wei; Sun, Ya-Feng; Lin, Jian-An; Xu, Jian-Hua

    2018-02-01

    Increasing evidence from various clinical and experimental studies has demonstrated that the inflammatory microenvironment created by immune cells facilitates tumor migration. Epithelial-mesenchymal transition (EMT) is involved in the progression of cancer invasion and metastasis in an inflammatory microenvironment. B-lymphoma Moloney murine leukemia virus insertion region 1 (BMI-1) acts as an oncogene in various tumors. Ectopic expression of Bmi-1 have an effect on EMT and invasiveness. The purpose of this study was to investigate the efficacy of BMI-1 on inflammation-induced tumor migration and EMT and the underlying mechanism. We observed that the expression of BMI-1, TNF-α, and IL-1β was significantly increased in HT29 and HCT116 cells after THP-1 Conditioned-Medium (THP-1-CM) stimulation. Additionally, inhibition of BMI-1 impeded cell invasion induced by THP-1-CM-stimulation in both HT29 and HCT116 cells. BMI-1 knockdown remarkably repressed THP-1-CM-induced EMT by regulating the expression of EMT biomarkers with an increase in E-cadherin accompanied by decrease in N-cadherin and vimentin. Furthermore, downregulation of BMI-1 dramatically impeded THP-1-CM-triggered Toll-like receptor 4(TLR4)/myeloid differentiation protein 2(MD-2)/myeloid differentiation factor 88(MyD88) activity by repressing the expression of the TLR4/MD-2 complex and MyD88. Further data demonstrated that knockout of BMI-1 also dampened NF-κB THP-1-CM-triggered activity. Taken all data together, our findings established that BMI-1 modulated TLR4/MD-2/MyD88 complex-mediated NF-κB signaling involved in inflammation-induced cancer cells invasion and EMT, and therefore, could be a potential chemopreventive agent against inflammation-associated colorectal cancer. Establishment of an inflammatory microenvironment. Suppression of BMI-1 reverses THP-1-CM-induced inflammatory cytokine production in CRC. Loss of BMI-1 suppressed TLR4/MD-2/MyD88 complex-mediated NF-κB signaling. © 2017 Wiley

  6. KIR2DL4 differentially signals downstream functions in human NK cells through distinct structural modules.

    Science.gov (United States)

    Miah, S M Shahjahan; Hughes, Tracey L; Campbell, Kerry S

    2008-03-01

    KIR2DL4 (2DL4) is a member of the killer cell Ig-like receptor (KIR) family in human NK cells. It can stimulate potent cytokine production and weak cytolytic activity in resting NK cells, but the mechanism for 2DL4-mediated signaling remains unclear. In this study we characterized the signaling pathways stimulated by 2DL4 engagement. In a human NK-like cell line, KHYG-1, cross-linking of 2DL4 activated MAPKs including JNK, ERK, and p38. Furthermore, 2DL4 cross-linking resulted in phosphorylation of IkappaB kinase beta (IKKbeta) and the phosphorylation and degradation of IkappaBalpha, which indicate activation of the classical NF-kappaB pathway. Engagement of 2DL4 was also shown to activate the transcription and translation of a variety of cytokine genes, including TNF-alpha, IFN-gamma, MIP1alpha, MIP1beta, and IL-8. Pharmacological inhibitors of JNK, MEK1/2 and p38, blocked IFN-gamma, IL-8, and MIP1alpha production, suggesting that MAPKs are regulating 2DL4-mediated cytokine production in a nonredundant manner. Activation of both p38 and ERK appear to be upstream of the stimulation of NF-kappaB. Mutation of a transmembrane arginine in 2DL4 to glycine (R/G mutant) abrogated FcepsilonRI-gamma association, as well as receptor-mediated cytolytic activity and calcium responses. Surprisingly, the R/G mutant still activated MAPKs and the NF-kappaB pathway and selectively stimulated the production of MIP1alpha, but not that of IFN-gamma or IL-8. In conclusion, we provide evidence that the activating functions of 2DL4 can be compartmentalized into two distinct structural modules: 1) through transmembrane association with FcepsilonRI-gamma; and 2) through another receptor domain independent of the transmembrane arginine.

  7. The entropic boundary law in BF theory

    Science.gov (United States)

    Livine, Etera R.; Terno, Daniel R.

    2009-01-01

    We compute the entropy of a closed bounded region of space for pure 3d Riemannian gravity formulated as a topological BF theory for the gauge group SU(2) and show its holographic behavior. More precisely, we consider a fixed graph embedded in space and study the flat connection spin network state without and with particle-like topological defects. We regularize and compute exactly the entanglement for a bipartite splitting of the graph and show it scales at leading order with the number of vertices on the boundary (or equivalently with the number of loops crossing the boundary). More generally these results apply to BF theory with any compact gauge group in any space-time dimension.

  8. Antitumor Activity of Portulaca Oleracea L. Polysaccharide on HeLa Cells Through Inducing TLR4/NF-κB Signaling.

    Science.gov (United States)

    Zhao, Rui; Zhang, Tao; Ma, Baoling; Li, Xing

    2017-01-01

    Abstarct We have previously shown that Portulaca oleracea L. polysaccharide (POL-P3b) possesses the ability to inhibit cervical cancer cell growth in vitro and in vivo. In this study, we explored how toll-like receptor 4 (TLR4) signaling correlated with the antitumor mechanism of POL-P3b. Western blotting was utilized to detect the expression of TLR4 and the downstream signaling pathway. The level of inflammatory mediator was quantified using enzyme-linked immunosorbent assay (ELISA) kits. The effects of POL-P3b on the proliferation and apoptosis in HeLa cells were determined by WST-8 assay and Hoechst 33342/propidium iodide (PI) assay. Our results demonstrated that lipopolysaccharide (LPS) binding to TLR4 on tumor cells could enhance HeLa cell proliferation and increase the expression of TLR4 and the downstream molecules. Treating HeLa cells with POL-P3b could decrease the proliferation of HeLa cells, and upregulate Bax level and downregulate Bcl-2 level in a concentration-dependent manner. In addition, POL-P3b inhibited the protein expression levels of TLR4, MyD88, TRAF6, Activator Protein-1 (AP-1) and nuclear factor-κB (NF-κB) subunit P65 in HeLa cells. Furthermore, POL-P3b also reduced the production of cytokine/chemokine. Taken together, the present work suggested the antitumor mechanism of POL-P3b by downregulating TLR4 downstream signaling pathway and inducing cell apoptosis. Our results may provide direct evidence to suggest that POL-P3b should be considered as a potent nutrient supplement for oncotherapy.

  9. Environmental and economic assessment of hybrid FO-RO/NF system with selected inorganic draw solutes for the treatment of mine impaired water

    KAUST Repository

    Kim, Jung Eun

    2018-01-01

    A hybrid forward osmosis (FO) and reverse osmosis (RO)/nanofiltration (NF) system in a closed-loop operation with selected draw solutes was evaluated to treat coal mine impaired water. This study provides an insight of selecting the most suitable draw solution (DS) by conducting environmental and economic life cycle assessment (LCA). Baseline environmental LCA showed that the dominant components to energy use and global warming are the DS recovery processes (i.e. RO or NF processes) and FO membrane materials, respectively. When considering the DS replenishment in FO, the contribution of chemical use to the overall global warming impact was significant for all hybrid systems. Furthermore, from an environmental perspective, the FO-NF hybrid system with Na2SO4 shows the lowest energy consumption and global warming with additional considerations of final product water quality and FO brine disposal. From an economic perspective, the FO-NF with Na2SO4 showed the lowest total operating cost due to its lower DS loss and relatively low solute cost. In a closed-loop system, FO-NF with NaCl and Na2SO4 had the lowest total water cost at optimum NF recovery rates of 90 and 95%, respectively. FO-NF with Na2SO4 had the lowest environmental and economic impacts. Overall, draw solute performances and cost in FO and recovery rate in RO/NF play a crucial role in determining the total water cost and environmental impact of FO hybrid systems in a closed-loop operation.

  10. Nitrative DNA damage and Oct3/4 expression in urinary bladder cancer with Schistosomahaematobium infection

    International Nuclear Information System (INIS)

    Ma, Ning; Thanan, Raynoo; Kobayashi, Hatasu; Hammam, Olfat; Wishahi, Mohamed; Leithy, Tarek El; Hiraku, Yusuke; Amro, EL-Karef; Oikawa, Shinji; Ohnishi, Shiho; Murata, Mariko; Kawanishi, Shosuke

    2011-01-01

    Highlights: → Oct3/4-positive cells increase in Schistosoma haematobium (SH)-associated bladder cancer. → iNOS-dependent DNA lesion, 8-nitroguanine, was formed in Oct3/4-positive cells. → 8-Nitroguanine formed in stem-like cells plays a role in SH-induced carcinogenesis. → Mutant stem cells may participate in inflammation-related carcinogenesis. -- Abstract: To investigate whether mutant stem cells participate in inflammation-related carcinogenesis, we performed immunohistochemical analysis to examine nitrative and oxidative DNA lesions (8-nitroguanine and 8-oxodG) and a stem cell marker Oct3/4 in bladder tissues obtained from cystitis and bladder cancer patients infected with Schistosomahaematobium (S. haematobium). We also detected the expression of nuclear factor-κB (NF-κB) and inducible nitric oxide synthase (iNOS), which lead to 8-nitroguanine formation. The staining intensity of 8-nitroguanine and 8-oxodG was significantly higher in bladder cancer and cystitis tissues than in normal tissues. iNOS expression was colocalized with NF-κB in 8-nitroguanine-positive tumor cells from bladder cancer patients. Oct3/4 expression was significantly increased in cells from S. haematobium-associated bladder cancer tissues in comparison to normal bladder and cancer tissues without infection. Oct3/4 was also expressed in epithelial cells of cystitis patients. Moreover, 8-nitroguanine was formed in Oct3/4-positive stem cells in S. haematobium-associated cystitis and cancer tissues. In conclusion, inflammation by S.haematobium infection may increase the number of mutant stem cells, in which iNOS-dependent DNA damage occurs via NF-κB activation, leading to tumor development.

  11. Nanostructured Co3O4 grown on nickel foam: An efficient and readily recyclable 3D catalyst for heterogeneous peroxymonosulfate activation.

    Science.gov (United States)

    Yuan, Ruixia; Hu, Lin; Yu, Peng; Wang, Huaiyuan; Wang, Zhaohui; Fang, Jingyun

    2018-05-01

    Cobalt-based heterogeneous catalyst has been recognized as one of most efficient activators for peroxymonosulfate (PMS) decomposition, but usually suffers from the poor stability and difficulty to recover and reuse. Here easily recyclable cobalt oxide (Co 3 O 4 ) nanowires and nanoflowers grown on nickel foam (NF) are fabricated by a hydrothermal and calcination method. The prepared 3D Co 3 O 4 /NF catalyst is characterized and applied as a heterogeneous catalyst for PMS activation to generate sulfate radicals for decomposition of Acid Orange 7 (AO7). The results show that the AO7 degradation rate increases with cobalt loading and PMS dosage, but decreases with the increase of solution pH. The Co 3 O 4 /NF catalyst using 2 mM Co(NO 3 ) 2 ·6H 2 O as cobalt source exhibits highest activity, and almost complete decolorization could be achieved within 30 min. The diverse effects of coexisting anions (SO 4 2- , HCO 3 - , NO 3 - and Cl - ) on AO7 degradation are observed and explained. After 10 consecutive runs, excellent catalytic reactivity of the catalyst remains while the level of leached cobalt during the catalyst usage is much lower than the maximum allowable concentration in drinking and natural water. More importantly, the macroscopic Co 3 O 4 /NF catalyst shows advantage of easy recycling after application compared to traditional catalysts. It is believed that the as-prepared Co 3 O 4 /NF is promising to be an effective and green heterogeneous catalyst for PMS activation to degrade organic pollutants for environmental application. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Baicalin inhibits toll-like receptor 2/4 expression and downstream signaling in rat experimental periodontitis.

    Science.gov (United States)

    Sun, Jun-Yi; Li, Dong-Ling; Dong, Yan; Zhu, Chun-Hui; Liu, Jin; Li, Jue-Dan; Zhou, Tao; Gou, Jian-Zhong; Li, Ang; Zang, Wei-Jin

    2016-07-01

    Periodontitis is a severe inflammatory response, leading to characteristic periodontal soft tissue destruction and alveolar bone resorption. Baicalin possesses potent anti-inflammatory activity; however, it is still unclear whether baicalin regulates toll-like receptor (TLR) 2/4 expression and downstream signaling during the process of periodontitis. In this study, the cervical area of the maxillary second molars of rats was ligated and inoculated with Porphyromonas gingivalis (P. gingivalis) for 4weeks to induce periodontitis. Some rats with periodontitis were treated intragastrically with baicalin (50, 100 or 200mg/kg/day) or vehicle for 4weeks. Compared with the sham group, the levels of TLR2, TLR4 and MyD88 expression and the p38 MAPK and NF-κB activation were up-regulated in the experimental periodontitis group (EPG), accompanied by marked alveolar bone loss and severe inflammation. Treatment with 100 or 200mg/kg/day baicalin dramatically reduced the alveolar bone loss, the levels of HMGB1, TNF-α, IL-1β, and MPO expression, and the numbers of inflammatory infiltrates in the gingival tissues. Importantly, treatment with 100 or 200mg/kg/day baicalin mitigated the periodontitis-up-regulated TLR2, TLR4 and MyD88 expression, and the p38 MAPK and NF-κB activation. Hence, the blockage of the TLR2 and TLR4/MyD88/p38 MAPK/NF-κB signaling by baicalin may contribute to its anti-inflammatory effects in rat model of periodontitis. In conclusion, these novel findings indicate that baicalin inhibits the TLR2 and TLR4 expression and the downstream signaling and mitigates inflammatory responses and the alveolar bone loss in rat experimental periodontitis. Therefore, baicalin may be a potential therapeutic agent for treatment of periodontitis. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Intracellular expression of toll-like receptor 4 in neuroblastoma cells and their unresponsiveness to lipopolysaccharide

    Directory of Open Access Journals (Sweden)

    Mori Isamu

    2006-12-01

    Full Text Available Abstract Background Recently it has been reported that, toll-like receptors (TLRs are expressed on a series of tumor cells, such as colon cancer, breast cancer, prostate cancer, melanoma and lung cancer. Although some cancer cells like melanoma cells are known to respond to lipopolysaccharide (LPS via TLR4, not all cancer cells are positive for TLR4. There is little information on the expression and function of TLR4 in neuroblastoma cells. In this study, we investigated the expression of TLR4 in human neuroblastoma NB-1 cell line. Methods Expression and localization of TLR4 were detected by reverse transcription-polymerase chain reaction (RT-PCR and flow cytometric analysis, respectively. Activation of nuclear factor (NF-κB by LPS was detected by degradation of IκB-α and NF-κB luciferase assay. Activation and expression of mitogen-activated protein (MAP kinase and interferon regulatory factor (IRF-3 was detected by immunoblot analysis. Results Human NB-1 neuroblastoma cells expressed intracellular form of TLR4, but not the cell surface form. Further, NB-1 cells express CD14, MD2 and MyD88, which are required for LPS response. However, LPS did not significantly induce NF-κB activation in NB-1 cells although it slightly degraded IκB-α. NB-1 cells expressed no IRF-3, which plays a pivotal role on the MyD88-independent pathway of LPS signaling. Collectively, NB-1 cells are capable to avoid their response to LPS. Conclusion Although human NB-1 neuroblastoma cells possessed all the molecules required for LPS response, they did not respond to LPS. It might be responsible for intracellular expression of TLR4 or lack of IRF-3.

  14. Dicty_cDB: Contig-U11911-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available 15738 ) EST1224699 MTY Medicago truncatula cDNA clone MTY... 46 0.077 2 ( BF643524 ) NF021F09EC1F1079 Elicited cell culture Medic...6 0.079 2 ( BF647644 ) NF078B01EC1F1011 Elicited cell culture Medicago t... 46 0....ited cell culture Medicago t... 46 0.086 2 ( BQ136068 ) NF032G12EC1F1099 Elicited cell culture Medic...tyostelium discoideum cDNA clone:ddc53b21, 3' ... 188 2e-47 2 ( CK249786 ) EST733423 potato callus cDNA library..., normalized ... 46 4e-04 3 ( CK249616 ) EST733253 potato callus cDNA library

  15. No Amelioration of Uromodulin Maturation and Trafficking Defect by Sodium 4-Phenylbutyrate in Vivo

    Science.gov (United States)

    Kemter, Elisabeth; Sklenak, Stefanie; Rathkolb, Birgit; Hrabě de Angelis, Martin; Wolf, Eckhard; Aigner, Bernhard; Wanke, Ruediger

    2014-01-01

    Uromodulin (UMOD)-associated kidney disease (UAKD) belongs to the hereditary progressive ER storage diseases caused by maturation defects of mutant UMOD protein. Current treatments of UAKD patients are symptomatic and cannot prevent disease progression. Two in vitro studies reported a positive effect of the chemical chaperone sodium 4-phenylbutyrate (4-PBA) on mutant UMOD maturation. Thus, 4-PBA was suggested as a potential treatment for UAKD. This study evaluated the effects of 4-PBA in two mouse models of UAKD. In contrast to previous in vitro studies, treatment with 4-PBA did not increase HSP70 expression or improve maturation and trafficking of mutant UMOD in vivo. Kidney function of UAKD mice was actually deteriorated by 4-PBA treatment. In transfected tubular epithelial cells, 4-PBA did not improve maturation but increased the expression level of both mutant and wild-type UMOD protein. Activation of NF-κB pathway in thick ascending limb of Henle's loop cells of UAKD mice was detected by increased abundance of RelB and phospho-IκB kinase α/β, an indirect activator of NF-κB. Furthermore, the abundance of NF-κB1 p105/p50, NF-κB2 p100/p52, and TRAF2 was increased in UAKD. NF-κB activation was identified as a novel disease mechanism of UAKD and might be a target for therapeutic intervention. PMID:24567330

  16. Krüppel-like factor 4, a novel transcription factor regulates microglial activation and subsequent neuroinflammation

    Directory of Open Access Journals (Sweden)

    Das Sulagna

    2010-10-01

    . We found that Klf4 can potentially interact with pNF-κB and is important for iNOS and Cox-2 promoter activity in vitro. Conclusions These studies demonstrate the role of Klf4 in microglia in mediating neuroinflammation in response to the bacterial endotoxin LPS.

  17. On chirality transfer in electron donor-acceptor complexes. A prediction for the sulfinimine···BF3 system.

    Science.gov (United States)

    Rode, Joanna E; Dobrowolski, Jan Cz

    2012-01-01

    Stabilization energies of the electron donor-acceptor sulfinimine···BF(3) complexes calculated at either the B3LYP/aug-cc-pVTZ or the MP2/aug-cc-pVTZ level do not allow to judge, whether the N- or O-atom in sulfinimine is stronger electron-donor to BF(3) . The problem seems to be solvable because chirality transfer phenomenon between chiral sulfinimine and achiral BF(3) is expected to be vibrational circular dichroism (VCD) active. Moreover, the bands associated with the achiral BF(3) molecule are predicted to be the most intense in the entire spectrum. However, the VCD band robustness analyses show that most of the chirality transfer modes of BF(3) are unreliable. Conversely, variation of VCD intensity with change of intermolecular distance, angle, and selected dihedrals between the complex partners shows that to establish the robustness of chirality transfer mode. It is also necessary to determine the influence of the potential energy surface (PES) shape on the VCD intensity. At the moment, there is still no universal criterion for the chirality transfer mode robustness and the conclusions formulated based on one system cannot be directly transferred even to a quite similar one. However, it is certain that more attention should be focused on relation of PES shape and the VCD mode robustness problem. Copyright © 2011 Wiley Periodicals, Inc.

  18. The role of NF-κB signaling in the maintenance of pluripotency of human induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Osamu Takase

    Full Text Available NF-κB signaling plays an essential role in maintaining the undifferentiated state of embryonic stem (ES cells. However, opposing roles of NF-κB have been reported in mouse and human ES cells, and the role of NF-κB in human induced pluripotent stem (iPS cells has not yet been clarified. Here, we report the role of NF-κB signaling in maintaining the undifferentiated state of human iPS cells. Compared with differentiated cells, undifferentiated human iPS cells showed an augmentation of NF-κB activity. During differentiation induced by the removal of feeder cells and FGF2, we observed a reduction in NF-κB activity, the expression of the undifferentiation markers Oct3/4 and Nanog, and the up-regulation of the differentiated markers WT-1 and Pax-2. The specific knockdown of NF-κB signaling using p65 siRNA also reduced the expression of Oct3/4 and Nanog and up-regulated WT-1 and Pax-2 but did not change the ES-like colony formation. Our results show that the augmentation of NF-κB signaling maintains the undifferentiated state of human iPS and suggest the importance of this signaling pathway in maintenance of human iPS cells.

  19. Profile of NF-κBp(65/NFκBp50) among prostate specific antigen sera levels in prostatic pathologies.

    Science.gov (United States)

    Bouraoui, Y; Ben Jemaa, A; Rodriguez, G; Ben Rais, N; Fraile, B; Paniagua, R; Sellemi, S; Royuela, M; Oueslati, R

    2012-10-01

    The aim of this work was to characterise the immunoexpression of NF-κB (p50/p65) in human prostatic pathologies and to study its profiles of activation among sera prostate specific antigen antigen (PSA) according the three groups: 0-4ng/mL, 4-20ng/mL and >20ng/mL. Twenty-four men with benign prostate hyperplasia (BPH); 19 men with prostate cancer (PC) and five men with normal prostates (NP). Immunohistochemical and western blot analysis was performed. Serum levels of PSA were assayed by immulite autoanalyser. In BPH and PC samples, immunoexpressions were observed for NF-κBp65 and NF-κBp50; while in NP samples, only were detected NF-κBp50. PC samples showed immunoreactions to NF-κBp65 and NF-κBp50 more intense (respectively 24.18±0.67 and 28.23±2.01) than that observed in BPH samples (respectively18.46±2.04 and 18.66±1.59) with special localisation in the nucleus. Different profiles of NF-κBp65 immunoexpressions were observed and BPH patients with sera PSA levels between 0-4ng/mL presented a significant weak percentage compared to BPH patients with sera PSA levels between 4-20ng/mL and >20ng/mL. No immunoreactions to NF-κBp65 were observed in PC patients with sera PSA levels between 4-20ng/mL. The sensibility of both NF-κB and PSA to inflammation allowed confirming the relationship between these two molecules and its involvement in prostatic diseases progression (inflammatory and neoplasic). Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  20. Phase space descriptions for simplicial 4D geometries

    International Nuclear Information System (INIS)

    Dittrich, Bianca; Ryan, James P

    2011-01-01

    Starting from the canonical phase space for discretized (4D) BF theory, we implement a canonical version of the simplicity constraints and construct phase spaces for simplicial geometries. Our construction allows us to study the connection between different versions of Regge calculus and approaches using connection variables, such as loop quantum gravity. We find that on a fixed triangulation the (gauge invariant) phase space associated with loop quantum gravity is genuinely larger than the one for length and even area Regge calculus. Rather, it corresponds to the phase space of area-angle Regge calculus, as defined in [1] (prior to the imposition of gluing constraints, which ensure the metricity of the triangulation). Finally, we show that for a subclass of triangulations one can construct first-class Hamiltonian and diffeomorphism constraints leading to flat 4D spacetimes.

  1. Induction of oncogene addiction shift to NF-κB by camptothecin in solid tumor cells

    International Nuclear Information System (INIS)

    Togano, Tomiteru; Sasaki, Masataka; Watanabe, Mariko; Nakashima, Makoto; Tsuruo, Takashi; Umezawa, Kazuo; Higashihara, Masaaki; Watanabe, Toshiki; Horie, Ryouichi

    2009-01-01

    The biological basis of the resistance of solid tumor cells to chemotherapy is not well understood. While addressing this problem, we found that gastric cancer cell line St-4/CPT, lung cancer cell line A549/CPT, and colon cancer cell line HT-29/CPT, all of which are resistant to camptothecin (CPT), showed strong and constitutive nuclear factor (NF)-κB activity driven by IκB kinase compared with their parental cell lines St-4, A549, and HT-29. A new NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), reduced viability and induced apoptosis in St-4/CPT, A549/CPT, and HT-29/CPT cell lines, while their parental cell lines were resistant to DHMEQ. The results in this study present an example of the shift in signals that support the survival of solid tumor cells to NF-κB during the acquisition of resistance to CPT. The results also indicate that solid tumor cells that become resistant to chemotherapy may be more easily treated by NF-κB inhibitors.

  2. Induction of oncogene addiction shift to NF-{kappa}B by camptothecin in solid tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Togano, Tomiteru; Sasaki, Masataka; Watanabe, Mariko; Nakashima, Makoto [Department of Hematology, School of Medicine, Kitasato University, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555 (Japan); Tsuruo, Takashi [Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-10-6 Ariake, Koto-ku, Tokyo 135-8550 (Japan); Umezawa, Kazuo [Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-0061 (Japan); Higashihara, Masaaki [Department of Hematology, School of Medicine, Kitasato University, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555 (Japan); Watanabe, Toshiki [Laboratory of Tumor Cell Biology, Department of Medical Genome Sciences, Graduate School of Frontier Sciences, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Horie, Ryouichi, E-mail: rhorie@med.kitasato-u.ac.jp [Department of Hematology, School of Medicine, Kitasato University, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555 (Japan)

    2009-12-04

    The biological basis of the resistance of solid tumor cells to chemotherapy is not well understood. While addressing this problem, we found that gastric cancer cell line St-4/CPT, lung cancer cell line A549/CPT, and colon cancer cell line HT-29/CPT, all of which are resistant to camptothecin (CPT), showed strong and constitutive nuclear factor (NF)-{kappa}B activity driven by I{kappa}B kinase compared with their parental cell lines St-4, A549, and HT-29. A new NF-{kappa}B inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), reduced viability and induced apoptosis in St-4/CPT, A549/CPT, and HT-29/CPT cell lines, while their parental cell lines were resistant to DHMEQ. The results in this study present an example of the shift in signals that support the survival of solid tumor cells to NF-{kappa}B during the acquisition of resistance to CPT. The results also indicate that solid tumor cells that become resistant to chemotherapy may be more easily treated by NF-{kappa}B inhibitors.

  3. A new synthetic chalcone derivative, 2-hydroxy-3',5,5'-trimethoxychalcone (DK-139), suppresses the Toll-like receptor 4-mediated inflammatory response through inhibition of the Akt/NF-κB pathway in BV2 microglial cells.

    Science.gov (United States)

    Lee, Young Han; Jeon, Seung-Hyun; Kim, Se Hyun; Kim, Changyoun; Lee, Seung-Jae; Koh, Dongsoo; Lim, Yoongho; Ha, Kyooseob; Shin, Soon Young

    2012-06-30

    Microglial cells are the resident innate immune cells that sense pathogens and tissue injury in the central nervous system (CNS). Microglial activation is critical for neuroinflammatory responses. The synthetic compound 2-hydroxy-3',5,5'-trimethoxychalcone (DK-139) is a novel chalcone-derived compound. In this study, we investigated the effects of DK-139 on Toll-like receptor 4 (TLR4)-mediated inflammatory responses in BV2 microglial cells. DK-139 inhibited lipopolysaccharide (LPS)-induced TLR4 activity, as determined using a cell-based assay. DK-139 blocked LPS-induced phosphorylation of IκB and p65/RelA NF-κB, resulting in inhibition of the nuclear translocation and trans-acting activity of NF-κB in BV2 microglial cells. We also found that DK-139 reduced the expression of NF-κB target genes, such as those for COX-2, iNOS, and IL-1β, in LPS-stimulated BV2 microglial cells. Interestingly, DK-139 blocked LPS-induced Akt phosphorylation. Inhibition of Akt abrogated LPS-induced phosphorylation of p65/RelA, while overexpression of dominant- active p110CAAX enhanced p65/RelA phosphorylation as well as iNOS and COX2 expression. These results suggest that DK-139 exerts an anti-inflammatory effect on microglial cells by inhibiting the Akt/IκB kinase (IKK)/NF-κB signaling pathway.

  4. Conclusion. Chapter 4

    International Nuclear Information System (INIS)

    1999-01-01

    Beginning 1992, January 1 Semipalatinsk test site was transforming into large research scientific center. The National Nuclear Center (NNC) was formed on the base of site's research enterprises. The principal problems of NNC are as follows: liquidation of nuclear tests consequences; liquidation of technological infrastructure for preparation and conducting of nuclear tests, creation of technology for radioactive wastes store; implementation of atomic energy development conception in Kazakhstan, etc. Program of site conversion constantly is expanding. In this chapter measures by rehabilitation of injured population are revealed. Taking into account radioecological situation, dose loadings, demographic indexes, sick rate and mortality of population on territories exposed to site's influence Government of Kazakhstan adopted Decree on declaration of these lands of zone of ecological catastrophe. Measures on improvement of radioecological situation are reduce to following ones: determination of irradiation doses received by population during testing period; study of existing radiation contamination; study of all possible sources for dose increasing and taking into account other ones; information of population about radioecological situation and about all consequences of nuclear tests. In 1992 Supreme Soviet of Republic of Kazakhstan worked out and adopted law On social defence of citizens suffered from consequences of nuclear tests on Semipalatinsk test site. It was distinguished four zones of radiation risk. The first zone is zone of extreme risk. It is part of territory subjected to radiation contamination with dose of influence on population above 100 rem during of total period of tests conducting. To this zone belong following inhabited settlements: Budene, Dolon', Cheremushki, Mostik, Sarzhal, Isa, Sarpan, Karakoryk, Zagotskot-2. Second zone is zone of maximal radiation risk. To this zone belong inhabited settlements of following districts: Abaj, Abraly, Beskargaj and Zana-Semej. Population of these districts have been exposed to ionizing radiation influence in doses from 35 up to 100 rem. Third zone is zone of increased risk. To this zone belong inhabited settlements of following districts of Semipalatinsk region: Chybartau, Novo-Shul'ba, Borodulikha, Charsk, Zharmy, Ayaguz. Effective equivalent doses for population during all these years made up from 7 to 35 rem. Forth zone is zone of minimal radiation risk. To this zone the inhabited settlements of Makanchi, Urdzhary, Taskesken, Kokpekty, Aksuat districts belongs. Effective equivalent doses of population irradiation made up from 0.1 to 7 rem. Measures on compensation payment for caused harm to suffered peoples health in result of nuclear weapon test have been carried out with taking into consideration of living duration in different zones

  5. Synthesis of some (eta-arene)dihydridorhenium cations and their reactions with LiAlH/sub 4/ and LiAlD/sub 4/

    Energy Technology Data Exchange (ETDEWEB)

    Baudrey, D.; Boydell, P.; Ephritikhine, M.

    1986-03-01

    A series of cations (Re(eta-arene)H/sub 2/(PPh/sub 3/)/sub 2/)/sup +/ (arene benzene, toluene, p-xylene, or mesitylene) was prepared from the corresponding neutral dihydridocyclohexadienyl complexes by treatment with CPh/sub 3/BF/sub 4/. These cations reacted with LiAlH/sub 4/ and LiAlD/sub 4/ to form dihydridocyclohexadienyl complexes. The unusual selectivity of the hydride attack is explained by steric interactions between the ring methyl groups and the bulky phosphine ligands. The initial product of the reaction of the eta-mesitylene cation with LiAlD/sub 4/ allows the isomerisation mechanism for the cyclohexadienyl complexes to be clarified.

  6. TLR2 ligands induce NF-κB activation from endosomal compartments of human monocytes.

    Directory of Open Access Journals (Sweden)

    Karim J Brandt

    Full Text Available Localization of Toll-like receptors (TLR in subcellular organelles is a major strategy to regulate innate immune responses. While TLR4, a cell-surface receptor, signals from both the plasma membrane and endosomal compartments, less is known about the functional role of endosomal trafficking upon TLR2 signaling. Here we show that the bacterial TLR2 ligands Pam3CSK4 and LTA activate NF-κB-dependent signaling from endosomal compartments in human monocytes and in a NF-κB sensitive reporter cell line, despite the expression of TLR2 at the cell surface. Further analyses indicate that TLR2-induced NF-κB activation is controlled by a clathrin/dynamin-dependent endocytosis mechanism, in which CD14 serves as an important upstream regulator. These findings establish that internalization of cell-surface TLR2 into endosomal compartments is required for NF-κB activation. These observations further demonstrate the need of endocytosis in the activation and regulation of TLR2-dependent signaling pathways.

  7. Prevalence of bortezomib-resistant constitutive NF-kappaB activity in mantle cell lymphoma

    Directory of Open Access Journals (Sweden)

    Kahl Brad S

    2008-05-01

    Full Text Available Abstract Background The proteasome inhibitor bortezomib can inhibit activation of the transcription factor NF-κB, a mechanism implicated in its anti-neoplastic effects observed in mantle cell lymphoma (MCL. However, NF-κB can be activated through many distinct mechanisms, including proteasome independent pathways. While MCL cells have been shown to harbor constitutive NF-κB activity, what fraction of this activity in primary MCL samples is sensitive or resistant to inhibition by bortezomib remains unclear. Results Proteasome activity in the EBV-negative MCL cell lines Jeko-1 and Rec-1 is inhibited by greater than 80% after exposure to 20 nM bortezomib for 4 hours. This treatment decreased NF-κB activity in Jeko-1 cells, but failed to do so in Rec-1 cells when assessed by electrophoretic mobility shift assay (EMSA. Concurrently, Rec-1 cells were more resistant to the cytotoxic effects of bortezomib than Jeko-1 cells. Consistent with a proteasome inhibitor resistant pathway of activation described in mouse B-lymphoma cells (WEHI231 and a breast carcinoma cell line (MDA-MB-468, the bortezomib-resistant NF-κB activity in Rec-1 cells is inhibited by calcium chelators, calmodulin inhibitors, and perillyl alcohol, a monoterpene capable of blocking L-type calcium channels. Importantly, the combination of perillyl alcohol and bortezomib is synergistic in eliciting Rec-1 cell cytotoxicity. The relevance of these results is illuminated by the additional finding that a considerable fraction of primary MCL samples (8 out of 10 displayed bortezomib-resistant constitutive NF-κB activity. Conclusion Our findings show that bortezomib-resistant NF-κB activity is frequently observed in MCL samples and suggest that this activity may be relevant to MCL biology as well as serve as a potential therapeutic target.

  8. Respiratory Syncytial Virus Fusion Protein-Induced Toll-Like Receptor 4 (TLR4) Signaling Is Inhibited by the TLR4 Antagonists Rhodobacter sphaeroides Lipopolysaccharide and Eritoran (E5564) and Requires Direct Interaction with MD-2

    Science.gov (United States)

    Rallabhandi, Prasad; Phillips, Rachel L.; Boukhvalova, Marina S.; Pletneva, Lioubov M.; Shirey, Kari Ann; Gioannini, Theresa L.; Weiss, Jerrold P.; Chow, Jesse C.; Hawkins, Lynn D.; Vogel, Stefanie N.; Blanco, Jorge C. G.

    2012-01-01

    ABSTRACT Respiratory syncytial virus (RSV) is a leading cause of infant mortality worldwide. Toll-like receptor 4 (TLR4), a signaling receptor for structurally diverse microbe-associated molecular patterns, is activated by the RSV fusion (F) protein and by bacterial lipopolysaccharide (LPS) in a CD14-dependent manner. TLR4 signaling by LPS also requires the presence of an additional protein, MD-2. Thus, it is possible that F protein-mediated TLR4 activation relies on MD-2 as well, although this hypothesis has not been formally tested. LPS-free RSV F protein was found to activate NF-κB in HEK293T transfectants that express wild-type (WT) TLR4 and CD14, but only when MD-2 was coexpressed. These findings were confirmed by measuring F-protein-induced interleukin 1β (IL-1β) mRNA in WT versus MD-2−/− macrophages, where MD-2−/− macrophages failed to show IL-1β expression upon F-protein treatment, in contrast to the WT. Both Rhodobacter sphaeroides LPS and synthetic E5564 (eritoran), LPS antagonists that inhibit TLR4 signaling by binding a hydrophobic pocket in MD-2, significantly reduced RSV F-protein-mediated TLR4 activity in HEK293T-TLR4–CD14–MD-2 transfectants in a dose-dependent manner, while TLR4-independent NF-κB activation by tumor necrosis factor alpha (TNF-α) was unaffected. In vitro coimmunoprecipitation studies confirmed a physical interaction between native RSV F protein and MD-2. Further, we demonstrated that the N-terminal domain of the F1 segment of RSV F protein interacts with MD-2. These data provide new insights into the importance of MD-2 in RSV F-protein-mediated TLR4 activation. Thus, targeting the interaction between MD-2 and RSV F protein may potentially lead to novel therapeutic approaches to help control RSV-induced inflammation and pathology. PMID:22872782

  9. Comparison of Body Fat Results from 4 Bioelectrical Impedance Analysis Devices vs. Air Displacement Plethysmography in American Adolescent Wrestlers

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    Melissa M. Montgomery

    2017-10-01

    Full Text Available Background: Accurate and accessible methods of body composition are necessary to ensure health and safety of wrestlers during competition. The most valid and reliable instruments are expensive and relatively inaccessible to high school wrestlers; therefore, more practical technology is needed. Objective: To compare body fat percentage (BF% results from 4 bioelectrical impedance analysis (BIA devices to those from air displacement plethysmography (ADP in adolescent wrestlers. Methodology: 134 adolescent male and female wrestlers (1.72±0.9 m, 66.8±14.3 kg, 15.6±1.1 yrs. were tested for hydration and then completed 4 body composition tests with different BIA devices and one with Bod Pod. Relative and absolute agreement were assessed between each BIA device and ADP on a single day. Results: When compared with ADP, all devices demonstrated excellent reliability (ICC (2,1 range: 0.88-0.94, but questionable measurement error (SEM range: 2.3-3.6 %BF. Bland-Altman plots revealed that each bioelectrical impedance device we tested over-estimated body fat percent in high school wrestlers (range: 0.8-3.6 %BF and demonstrated wide 95% limits of agreement (range: 15.0-20.8 %BF compared to ADP. Conclusions: The devices investigated demonstrated reasonable measurement accuracy. However, wide margins of error of each device were noted. Caution should be taken when assessing adolescent wrestlers with lower amounts of body fat, as it may result in failing to identify those who do not meet the minimum body fat percentage for competition. The governing bodies should use the research data in the decision-making process regarding appropriate devices for use in their weight management programs.

  10. Hubungan Imunoekspresi NF-kB dengan Sinus Rokitansky Aschoff pada Kolesistitis Kronik

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    Herry Yulianti

    2014-06-01

    Full Text Available Carcinoma of the gallbladder is relatively uncommon but it is a very lethal disease. Gallbladder cancer constitutes 3−4% of all malignant lesions and ranks 5th among the digestive system tumors. Gallblader carcinoma is difficult to detect and diagnose in early stage because it usually has very slight symptoms or asymptomatic. It becomes increasingly necessary to make early diagnosis and identification of high-risk patient,as well as gallstone and history of chronic cholecystitis. Chronic cholecystitis is a chronic inflammation of gallbladder associated with cholelithiasis in more than 90% of cases. Cholelithiasis is one of the important etiological factors in carcinoma of the gallbladder. The histological examination of chronical cholecystitis shows the presence of Rokitansky Aschoff sinuses. Genetic approaches have proven that the components of inflammation such as primary inflammatory cytokines, interleukin-1 (IL-1, tumor necrosis factor (TNF, IL-6 and nuclear factor-kB (NF-kB play the key roles in carcinogenesis. The purpose of this study was to understand the correlation between the immunoexpression of NF-kB and Rokitansky Aschoff sinuses in chronic cholecystitis. The method was cross sectional of 30 cases of chronic cholecystitis from Department of Pathology Anatomy of Dr. Hasan Sadikin General Hospital Bandung/Faculty of Medicine Universitas Padjadjaran in 2010−2011. A section from 4 µm-thick paraffin embedded tissue of chronic cholecystitis was stained with hematoxylin eosin for histopatological evaluation and immunohistochemical using polyclonal NF-kB antibody. Immunoreactive cells was counted in five tumor areas of 400x field by light microscopy. The result showed a significant correlation between the immunoexpression of NFkB and Rokitansky Aschoff sinuses (p=0.000. In conclusion, there is a correlation between immunoexpression of NFkB and Rokitansky Aschoff sinuses because as the immunoexpression of NFkB increase, more Rokitansky

  11. QQS orphan gene regulates carbon and nitrogen partitioning across species via NF-YC interactions.

    Science.gov (United States)

    Li, Ling; Zheng, Wenguang; Zhu, Yanbing; Ye, Huaxun; Tang, Buyun; Arendsee, Zebulun W; Jones, Dallas; Li, Ruoran; Ortiz, Diego; Zhao, Xuefeng; Du, Chuanlong; Nettleton, Dan; Scott, M Paul; Salas-Fernandez, Maria G; Yin, Yanhai; Wurtele, Eve Syrkin

    2015-11-24

    The allocation of carbon and nitrogen resources to the synthesis of plant proteins, carbohydrates, and lipids is complex and under the control of many genes; much remains to be understood about this process. QQS (Qua-Quine Starch; At3g30720), an orphan gene unique to Arabidopsis thaliana, regulates metabolic processes affecting carbon and nitrogen partitioning among proteins and carbohydrates, modulating leaf and seed composition in Arabidopsis and soybean. Here the universality of QQS function in modulating carbon and nitrogen allocation is exemplified by a series of transgenic experiments. We show that ectopic expression of QQS increases soybean protein independent of the genetic background and original protein content of the cultivar. Furthermore, transgenic QQS expression increases the protein content of maize, a C4 species (a species that uses 4-carbon photosynthesis), and rice, a protein-poor agronomic crop, both highly divergent from Arabidopsis. We determine that QQS protein binds to the transcriptional regulator AtNF-YC4 (Arabidopsis nuclear factor Y, subunit C4). Overexpression of AtNF-YC4 in Arabidopsis mimics the QQS-overexpression phenotype, increasing protein and decreasing starch levels. NF-YC, a component of the NF-Y complex, is conserved across eukaryotes. The NF-YC4 homologs of soybean, rice, and maize also bind to QQS, which provides an explanation of how QQS can act in species where it does not occur endogenously. These findings are, to our knowledge, the first insight into the mechanism of action of QQS in modulating carbon and nitrogen allocation across species. They have major implications for the emergence and function of orphan genes, and identify a nontransgenic strategy for modulating protein levels in crop species, a trait of great agronomic significance.

  12. Ankyrin repeat and SOCS box containing protein 4 (Asb-4 colocalizes with insulin receptor substrate 4 (IRS4 in the hypothalamic neurons and mediates IRS4 degradation

    Directory of Open Access Journals (Sweden)

    Xia Zefeng

    2011-09-01

    Full Text Available Abstract Background The arcuate nucleus of the hypothalamus regulates food intake. Ankyrin repeat and SOCS box containing protein 4 (Asb-4 is expressed in neuropeptide Y and proopiomelanocortin (POMC neurons in the arcuate nucleus, target neurons in the regulation of food intake and metabolism by insulin and leptin. However, the target protein(s of Asb-4 in these neurons remains unknown. Insulin receptor substrate 4 (IRS4 is an adaptor molecule involved in the signal transduction by both insulin and leptin. In the present study we examined the colocalization and interaction of Asb-4 with IRS4 and the involvement of Asb-4 in insulin signaling. Results In situ hybridization showed that the expression pattern of Asb-4 was consistent with that of IRS4 in the rat brain. Double in situ hybridization showed that IRS4 colocalized with Asb-4, and both Asb-4 and IRS4 mRNA were expressed in proopiomelanocortin (POMC and neuropeptide Y (NPY neurons within the arcuate nucleus of the hypothalamus. In HEK293 cells co-transfected with Myc-tagged Asb-4 and Flag-tagged IRS4, Asb-4 co-immunoprecipitated with IRS4; In these cells endogenous IRS4 also co-immunoprecipitated with transfected Myc-Asb-4; Furthermore, Asb-4 co-immunoprecipitated with IRS4 in rat hypothalamic extracts. In HEK293 cells over expression of Asb-4 decreased IRS4 protein levels and deletion of the SOCS box abolished this effect. Asb-4 increased the ubiquitination of IRS4; Deletion of SOCS box abolished this effect. Expression of Asb-4 decreased both basal and insulin-stimulated phosphorylation of AKT at Thr308. Conclusions These data demonstrated that Asb-4 co-localizes and interacts with IRS4 in hypothalamic neurons. The interaction of Asb-4 with IRS4 in cell lines mediates the degradation of IRS4 and decreases insulin signaling.

  13. Electroacupuncture Improved Hippocampal Neurogenesis following Traumatic Brain Injury in Mice through Inhibition of TLR4 Signaling Pathway

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    Yuqin Ye

    2017-01-01

    Full Text Available The protective role of electroacupuncture (EA treatment in diverse neurological diseases such as ischemic stroke is well acknowledged. However, whether and how EA act on hippocampal neurogenesis following traumatic brain injury (TBI remains poorly understood. This study aims to investigate the effect of EA on hippocampal neurogenesis and neurological functions, as well as its underlying association with toll-like receptor 4 (TLR4 signaling in TBI mice. BrdU/NeuN immunofluorescence was performed to label newborn neurons in the hippocampus after EA treatment. Water maze test and neurological severity score were used to evaluate neurological function posttrauma. The hippocampal level of TLR4 and downstream molecules and inflammatory cytokines were, respectively, detected by Western blot and enzyme-linked immunosorbent assay. EA enhanced hippocampal neurogenesis and inhibited TLR4 expression at 21, 28, and 35 days after TBI, but the beneficial effects of EA on posttraumatic neurogenesis and neurological functions were attenuated by lipopolysaccharide-induced TLR4 activation. In addition, EA exerted an inhibitory effect on both TLR4/Myd88/NF-κB and TLR4/TRIF/NF-κB pathways, as well as the inflammatory cytokine expression in the hippocampus following TBI. In conclusion, EA promoted hippocampal neurogenesis and neurological recovery through inhibition of TLR4 signaling pathway posttrauma, which may be a potential approach to improve the outcome of TBI.

  14. Aquaporin-4 mediates communication between astrocyte and microglia: Implications of neuroinflammation in experimental Parkinson's disease.

    Science.gov (United States)

    Sun, H; Liang, R; Yang, B; Zhou, Y; Liu, M; Fang, F; Ding, J; Fan, Y; Hu, G

    2016-03-11

    Aquaporin-4 (AQP4), a water-selective membrane transport protein, is up-regulated in astrocytes in various inflammatory lesions, including Parkinson disease (PD). However, the exact functional roles of AQP4 in neuroinflammation remain unknown. In the present study, we investigated how AQP4 participates in the neuroinflammation of PD using AQP4 knockout (KO) mice and astrocyte-microglial co-cultures. We found that AQP4 KO mice exhibited increased basal and inducible canonical NF-κB activity, and showed significantly enhanced gliosis (astrocytosis and microgliosis) in chronic MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)/probenecid PD models, companying with the increase in the production of IL-1β and TNF-α in the midbrain. Similarly, AQP4 deficiency augmented the activation of the NF-κB pathway and the production of IL-1β and TNF-α in midbrain astrocyte cultures treated with MPP(+) (1-methyl-4-phenylpyridinium). Furthermore, AQP4 deficiency promoted activation of microglial cells in the co-cultured system. Our data provide the first evidence that AQP4 modulates astrocyte-to-microglia communication in neuroinflammation, although its effect on astrocyte inflammatory activation remains to be explored. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. Characterization of solvated electrons in hydrogen cyanide clusters: (HCN)n- (n=3, 4)

    Science.gov (United States)

    Wu, Di; Li, Ying; Li, Zhuo; Chen, Wei; Li, Zhi-Ru; Sun, Chia-Chung

    2006-02-01

    Theoretical studies of the solvated electrons (HCN)n- (n =3, 4) reveal a variety of electron trapping possibilities in the (HCN)n (n =3, 4) clusters. Two isomers for (HCN)3- and four isomers for (HCN)4- are obtained at the MP2/aug -cc-pVDZ+dBF (diffusive bond functions) level of theory. In view of vertical electron detachment energies (VDEs) at the CCSD(T) level, the excess electron always "prefers" locating in the center of the system, i.e., the isomer with higher coordination number shows larger VDE value. However, the most stable isomers of the solvated electron state (HCN)3- and (HCN)4- are found to be the linear C∞ν and D∞h structures, respectively, but not the fullyl symmetric structures which have the largest VDE values.

  16. In vivo detection of prion amyloid plaques using [11C]BF-227 PET

    International Nuclear Information System (INIS)

    Okamura, Nobuyuki; Yanai, Kazuhiko; Shiga, Yusei; Itoyama, Yasuhito; Furumoto, Shozo; Tashiro, Manabu; Tsuboi, Yoshio; Furukawa, Katsutoshi; Arai, Hiroyuki; Iwata, Ren; Kudo, Yukitsuka; Doh-ura, Katsumi

    2010-01-01

    In vivo detection of pathological prion protein (PrP) in the brain is potentially useful for the diagnosis of transmissible spongiform encephalopathies (TSEs). However, there are no non-invasive ante-mortem means for detection of pathological PrP deposition in the brain. The purpose of this study is to evaluate the amyloid imaging tracer BF-227 with positron emission tomography (PET) for the non-invasive detection of PrP amyloid in the brain. The binding ability of BF-227 to PrP amyloid was investigated using autoradiography and fluorescence microscopy. Five patients with TSEs, including three patients with Gerstmann-Straeussler-Scheinker disease (GSS) and two patients with sporadic Creutzfeldt-Jakob disease (CJD), underwent [ 11 C]BF-227 PET scans. Results were compared with data from 10 normal controls and 17 patients with Alzheimer's disease (AD). The regional to pons standardized uptake value ratio was calculated as an index of BF-227 retention. Binding of BF-227 to PrP plaques was confirmed using brain samples from autopsy-confirmed GSS cases. In clinical PET study, significantly higher retention of BF-227 was detected in the cerebellum, thalamus and lateral temporal cortex of GSS patients compared to that in the corresponding tissues of normal controls. GSS patients also showed higher retention of BF-227 in the cerebellum, thalamus and medial temporal cortex compared to AD patients. In contrast, the two CJD patients showed no obvious retention of BF-227 in the brain. Although [ 11 C]BF-227 is a non-specific imaging marker of cerebral amyloidosis, it is useful for in vivo detection of PrP plaques in the human brain in GSS, based on the regional distribution of the tracer. PET amyloid imaging might provide a means for both early diagnosis and non-invasive disease monitoring of certain forms of TSEs. (orig.)

  17. A Study of the Spin-State Transition and Phase Transformation in [Fe(bpp)(2)][CF(3)SO(3)](2).H(2)O and [Fe(bpp)(2)][BF(4)](2) Using Mn(2+) Electron Spin Resonance.

    Science.gov (United States)

    Sung, Raymond C. W.; McGarvey, Bruce R.

    1999-08-09

    X-band ESR powder studies have been done on the spin transition in Mn(2+)-doped [Fe(bpp)(2)][CF(3)SO(3)](2).H(2)O and [Fe(bpp)(2)][BF(4)](2) (bpp = 2,6-bis(pyrazol-3-yl) pyridine). The change in D value of Mn(2+) during the thermally induced high-spin (HS) low-spin (LS) transition shows that the spin transition is accompanied by a phase transformation involving a domain mechanism. Irradiation experiments at 77 K have shown that a LS --> HS spin change occurs without a change in the crystalline phase. The rate of the change from the HS phase to the LS phase in the vicinity of 100 K has been measured and is found to be the same as that measured for the corresponding spin change obtained from Mössbauer spectroscopy and magnetic susceptibility studies.

  18. Identification of a novel TIF-IA-NF-κB nucleolar stress response pathway.

    Science.gov (United States)

    Chen, Jingyu; Lobb, Ian T; Morin, Pierre; Novo, Sonia M; Simpson, James; Kennerknecht, Kathrin; von Kriegsheim, Alex; Batchelor, Emily E; Oakley, Fiona; Stark, Lesley A

    2018-06-05

    p53 as an effector of nucleolar stress is well defined, but p53 independent mechanisms are largely unknown. Like p53, the NF-κB transcription factor plays a critical role in maintaining cellular homeostasis under stress. Many stresses that stimulate NF-κB also disrupt nucleoli. However, the link between nucleolar function and activation of the NF-κB pathway is as yet unknown. Here we demonstrate that artificial disruption of the PolI complex stimulates NF-κB signalling. Unlike p53 nucleolar stress response, this effect does not appear to be linked to inhibition of rDNA transcription. We show that specific stress stimuli of NF-κB induce degradation of a critical component of the PolI complex, TIF-IA. This degradation precedes activation of NF-κB and is associated with increased nucleolar size. It is mimicked by CDK4 inhibition and is dependent upon a novel pathway involving UBF/p14ARF and S44 of the protein. We show that blocking TIF-IA degradation blocks stress effects on nucleolar size and NF-κB signalling. Finally, using ex vivo culture, we show a strong correlation between degradation of TIF-IA and activation of NF-κB in freshly resected, human colorectal tumours exposed to the chemopreventative agent, aspirin. Together, our study provides compelling evidence for a new, TIF-IA-NF-κB nucleolar stress response pathway that has in vivo relevance and therapeutic implications.

  19. MicroRNA-4443 Causes CD4+ T Cells Dysfunction by Targeting TNFR-Associated Factor 4 in Graves’ Disease

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    Yicheng Qi

    2017-11-01

    Full Text Available ContextAberrant CD4+ T cell function plays a critical role in the process of Graves’ disease (GD. MicroRNAs (miRNAs are important regulators of T cell activation, proliferation, and cytokine production. However, the contribution of miRNAs to CD4+ T cell dysfunction in GD remains unclear.ObjectiveTo investigate how certain miRNA causes aberrant CD4+ T cell function in GD patients.MethodsWe compared the expression pattern of miRNAs in CD4+ T cells from untreated GD (UGD patients with those from healthy controls. The most significantly dysregulated miRNAs were selected and their correlations with clinical parameters were analyzed. The effect of miR-4443 on CD4+ T cells cytokines production and proliferation was assessed. The potential gene target was identified and validated.ResultsGD patients had unique pattern of miRNA expression profile in CD4+ T cells comparing to healthy subjects. miR-10a, miR-125b, and miR-4443 were the three most significantly dysregulated miRNAs. The elevated miR-4443 levels were strongly correlated with clinical parameters in an independent dataset of UGD patients (N = 40, while miR-4443 was normally expressed in GD patients with euthyroidism and negative TRAb level. We found that miR-4443 directly inhibited TNFR-associated factor (TRAF 4 expression to increase CD4+ T cells cytokines secretion as well as proliferation through the NF-κB pathway. Furthermore, the TRAF4 levels in GD patients were inversely correlated with miR-4443, and knocking down TRAF4 had a similar effect with miR-4443 overexpression.ConclusionThe increased expression of miR-4443 induced CD4+ T cells dysfunction by targeting TRAF4, which may cause GD.

  20. Paricalcitol attenuates lipopolysaccharide-induced inflammation and apoptosis in proximal tubular cells through the prostaglandin E₂ receptor EP4

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    Yu Ah Hong

    2017-06-01

    Full Text Available Background: Vitamin D is considered to exert a protective effect on various renal diseases but its underlying molecular mechanism remains poorly understood. This study aimed to determine whether paricalcitol attenuates inflammation and apoptosis during lipopolysaccharide (LPS-induced renal proximal tubular cell injury through the prostaglandin E₂ (PGE₂ receptor EP4. Methods: Human renal tubular epithelial (HK-2 cells were pretreated with paricalcitol (2 ng/mL for 1 hour and exposed to LPS (1 μg/mL. The effects of paricalcitol pretreatment in relation to an EP4 blockade using AH-23848 or EP4 small interfering RNA (siRNA were investigated. Results: The expression of cyclooxygenase-2, PGE₂, and EP4 were significantly increased in LPS-exposed HK-2 cells treated with paricalcitol compared with cells exposed to LPS only. Paricalcitol prevented cell death induced by LPS exposure, and the cotreatment of AH-23848 or EP4 siRNA offset these cell-protective effects. The phosphorylation and nuclear translocation of p65 nuclear factor-kappaB (NF-κB were decreased and the phosphorylation of Akt was increased in LPS-exposed cells with paricalcitol treatment. AH-23848 or EP4 siRNA inhibited the suppressive effects of paricalcitol on p65 NF-κB nuclear translocation and the activation of Akt. The production of proinflammatory cytokines and the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells were attenuated by paricalcitol in LPS exposed HK-2 cells. The cotreatment with an EP4 antagonist abolished these anti-inflammatory and antiapoptotic effects. Conclusion: EP4 plays a pivotal role in anti-inflammatory and antiapoptotic effects through Akt and NF-κB signaling after paricalcitol pretreatment in LPS-induced renal proximal tubule cell injury.

  1. Plumbagin exerts an immunosuppressive effect on human T-cell acute lymphoblastic leukemia MOLT-4 cells

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Kyoung Jun; Lee, Yura [Department of Biomedical Laboratory Science, Daejeon 34824 (Korea, Republic of); Kim, Soon Ae [Department of Pharmacology, School of Medicine, Daejeon 34824 (Korea, Republic of); Kim, Jiyeon, E-mail: yeon@eulji.ac.kr [Department of Biomedical Laboratory Science, Daejeon 34824 (Korea, Republic of)

    2016-04-22

    Of the hematological disorders typified by poor prognoses and survival rates, T-cell acute lymphoblastic leukemia (T-ALL) is one of the most commonly diagnosed. Despite the development of new therapeutic agents, the treatment options for this cancer remain limited. In this manuscript, we investigated the anti-proliferative effects of plumbagin, mediated by the activation of mitogen-activated protein kinase (MAPK) pathways, and inhibition of NF-κB signaling; the human T-ALL MOLT-4 cell line was used as our experimental system. Plumbagin is a natural, plant derived compound, which exerts an anti-proliferative activity against many types of human cancer. Our experiments confirm that plumbagin induces a caspase-dependent apoptosis of MOLT-4 cells, with no significant cytotoxicity seen for normal peripheral blood mononuclear cells (PBMCs). Plumbagin also inhibited LPS-induced phosphorylation of p65, and the transcription of NF-κB target genes. Our results now show that plumbagin is a potent inhibitor of the NF-κB signaling pathway, and suppressor of T-ALL cell proliferation. - Highlights: • Plumbagin induces caspase-dependent apoptosis in T-ALL MOLT-4 cells. • Plumbagin activates phosphorylation of stress-activated protein kinase (SAPK) JNK and p38. • Plumbagin inhibits LPS-mediated NF-κB signaling cascade. • Plumbagin inhibits LPS-mediated transcriptional activity of pro-inflammatory cytokines.

  2. Late-phase synthesis of I��B�� insulates the TLR4-activated canonical NF-��B pathway from noncanonical NF-��B signaling in macrophages

    OpenAIRE

    Chatterjee, Budhaditya; Banoth, Balaji; Mukherjee, Tapas; Taye, Nandaraj; Vijayaragavan, Bharath; Chattopadhyay, Samit; Gomes, James; Basak, Soumen

    2016-01-01

    The nuclear factor ��B (NF-��B) transcription factors coordinate the inflammatory immune response during microbial infection. Pathogenic substances engage canonical NF-��B signaling through the heterodimer RelA:p50, which is subjected to rapid negative feedback by inhibitor of ��B�� (I��B��). The noncanonical NF-��B pathway is required for the differentiation of immune cells; however, crosstalk between both pathways can occur. Concomitantly activated noncanonical signaling generates p52 from ...

  3. Protective effect of Rabdosia amethystoides (Benth Hara extract on acute liver injury induced by Concanavalin A in mice through inhibition of TLR4-NF-κB signaling pathway

    Directory of Open Access Journals (Sweden)

    Ke-Feng Zhai

    2016-02-01

    Full Text Available Extract of Rabdosia amethystoides (Benth Hara (ERA, a traditional Chinese medicine has antibacterial, antiviral, anti-tumor, anti-hepatitis and anti-inflammatory properties. However, the hepatoprotective effects and molecular mechanisms of ERA on acute liver injury have not been fully elucidated. This study aims to investigate the anti-inflammatory effect and liver protection of ERA against the acute liver injury induced by Concanavalin A (Con A and its underlying molecular mechanisms in mice. Mice received ERA (50, 100, 150 mg/kg body weight by gavage before Con A intravenous administration. We found that ERA pretreatment was able to significantly reduce the elevated serum alanine and aspartate aminotransferase levels and liver necrosis in Con A-induced hepatitis. In addition, ERA treatment significantly decreased the myeloperoxidase, malondialdehyde levels and augmented superoxide dismutase level in the liver tissue, and also suppressed the secretion of proinflammatory cytokines in the serum, compared with Con A group by enzyme linked immunosorbent assay. Furthermore, we observed that ERA pretreatment can significantly decrease the expression level of Toll-like receptor (TLR 4 mRNA or protein in liver tissues. Further results showed that ERA pretreatment was capable of attenuating the activation of the NF-κB pathway by inhibiting IκBα kinase and p65 phosphorylation in Con A-induced liver injury. Our results demonstrate that ERA pretreatment has hepatoprotective property against Con A-induced liver injury through inhibition of inflammatory mediators in mice. The beneficial effect of ERA may be mediated by the downregulation of TLR4 expression and the inhibition of NF-κB activation.

  4. 4,4-Difluoro-2,3;5,6-bis(tetramethylene-4-bora-3a,4a-diaza-s-indacene (LD540

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    Kirsi Salorinne

    2014-01-01

    Full Text Available The title compound, C18H21BF2N2, is a lipophilic dye based on a BODIPY fluorophore backbone, which was developed for microscopic imaging of lipid droplets; the molecule has a planar BODIPY core [dihedral angle between the pyrrole rings = 2.3 (3°] and two tetramethylene substituents at the 2,3- and 5,6-positions in a half-chair conformation. One of the tetramethylene substituents is disordered over two two sets of sites with site occupancies of 0.5. In the crystal, pairs of C—H...F interactions link the molecules into inversion dimers. Neighbouring dimers are linked by further C—H...F interactions, forming an infinite array. C—H...π and π–π [centroid–centroid distance = 4.360 (3 Å] interactions are observed between the BODIPY core and the tetramethylene substituents of neighbouring dimer pairs.

  5. Topological BF field theory description of topological insulators

    International Nuclear Information System (INIS)

    Cho, Gil Young; Moore, Joel E.

    2011-01-01

    Research highlights: → We show that a BF theory is the effective theory of 2D and 3D topological insulators. → The non-gauge-invariance of the bulk theory yields surface terms for a bosonized Dirac fermion. → The 'axion' term in electromagnetism is correctly obtained from gapped surfaces. → Generalizations to possible fractional phases are discussed in closing. - Abstract: Topological phases of matter are described universally by topological field theories in the same way that symmetry-breaking phases of matter are described by Landau-Ginzburg field theories. We propose that topological insulators in two and three dimensions are described by a version of abelian BF theory. For the two-dimensional topological insulator or quantum spin Hall state, this description is essentially equivalent to a pair of Chern-Simons theories, consistent with the realization of this phase as paired integer quantum Hall effect states. The BF description can be motivated from the local excitations produced when a π flux is threaded through this state. For the three-dimensional topological insulator, the BF description is less obvious but quite versatile: it contains a gapless surface Dirac fermion when time-reversal-symmetry is preserved and yields 'axion electrodynamics', i.e., an electromagnetic E . B term, when time-reversal symmetry is broken and the surfaces are gapped. Just as changing the coefficients and charges of 2D Chern-Simons theory allows one to obtain fractional quantum Hall states starting from integer states, BF theory could also describe (at a macroscopic level) fractional 3D topological insulators with fractional statistics of point-like and line-like objects.

  6. Anti-proliferative effect of RCE-4 from Reineckia carnea on human cervical cancer HeLa cells by inhibiting the PI3K/Akt/mTOR signaling pathway and NF-κB activation.

    Science.gov (United States)

    Bai, Caihong; Yang, Xiaojiao; Zou, Kun; He, Haibo; Wang, Junzhi; Qin, Huilin; Yu, Xiaoqin; Liu, Chengxiong; Zheng, Juyan; Cheng, Fan; Chen, Jianfeng

    2016-06-01

    Cervical cancer is the second leading cause of cancer deaths in women worldwide. In recent years, the studies find that inflammation is a critical component of tumor progression, and the ideal therapeutic methods should be aimed at the inflammation reaction triggers. (1β,3β,5β,25S)-spirostan-1,3-diol1-[α-L-rhamnopyranosyl-(1 → 2)-β-D-xylopyranoside] (RCE-4) was the main active composition of Reineckia carnea (Andr.) Kunth. It significantly induced apoptosis in cervical cancer Caski cells through the mitochondrial pathway in our previous studies; however, its underlying mechanism remains poorly understood. This study aimed to further evaluate the effect of RCE-4 on human cervical cancer HeLa cells. Based on this observation, we investigated the anti-cervical cancer effect of RCE-4 by modulating phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway, nuclear factor-kappa B (NF-κB) activation, and inflammation-related key factors in HeLa cells. The results indicated that the HeLa cell was the most sensitive with an IC50 of 7.01 μM; RCE-4 significantly promoted the release of cellular lactate dehydrogenase (LDH); increased DNA fragmentation and apoptosis; reduced PI3K, Akt, mTOR, and NF-κBp65 phosphorylation levels; increased the Bax and cleaved poly (ADP-ribose) polymerase (PARP) protein levels; suppressed Bcl-2 protein expression; elevated the Bax/Bcl-2 expression ratio; and decreased the interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) mRNA expressions in HeLa cells in a concentration-dependent manner. These findings suggest that RCE-4 exerted beneficially anti-cervical cancer effect on HeLa cells, mainly inhibiting PI3K/Akt/mTOR signaling pathway phosphorylation and NF-κB activation, promoting HeLa cell apoptosis. Graphical abstract Anti-tumor effect of RCE-4 on HeLa cells.

  7. Exogenous oxidants activate nuclear factor kappa B through Toll-like receptor 4 stimulation to maintain inflammatory phenotype in macrophage.

    Science.gov (United States)

    Zhang, Yan; Igwe, Orisa J

    2018-01-01

    Disturbances in redox equilibrium in tissue can lead to inflammatory state, which is a mediatory factor in many human diseases. The mechanism(s) by which exogenous oxidants may activate an inflammatory response is not fully understood. Emerging evidence suggests that oxidant-induced Toll-like receptor 4 (TLR4) activation plays a major role in "sterile" inflammation. In the present study, we used murine macrophage RAW-Blue cells, which are chromosomally integrated with secreted embryonic alkaline phosphatase (SEAP) inducible by NF-κB. We confirmed the expression of TLR4 mRNA and protein in RAW-Blue cells by RT-PCR and Western blot, respectively. We showed that oxidants increased intracellular reactive oxygen species production and lipid peroxidation, which resulted in decreased intracellular total antioxidant capacity. Consistent with the actions of TLR4-specific agonist LPS-EK, exogenous oxidants increased transcriptional activity of NF-κB p65 with subsequent release of NF-κB reporter gene SEAP. These effects were blocked by pretreatment with TLR4 neutralizing pAb and TLR4 signaling inhibitor CLI-095. In addition, oxidants decreased the expression of IκBα with enhanced phosphorylation at the Tyr42 residue. Finally, oxidants and LPS-EK increased TNFα production, but did not affect IL-10 production, which may cause imbalance between pro- and anti-inflammatory processes, which CLI-095 inhibited. For biological relevance, we confirmed that oxidants increased release of TNFα and IL-6 in primary macrophages derived from TLR4-WT and TLR4-KO mice. Our results support the involvement of TLR4 mediated oxidant-induced inflammatory phenotype through NF-κB activation in macrophages. Thus exogenous oxidants may play a role in activating inflammatory phenotypes that propagate and maintain chronic disease states. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Multicomponent Reaction in Ionic Liquid: A Novel and Green Synthesis of 1, 4-Dihydropyridine Derivatives

    Institute of Scientific and Technical Information of China (English)

    Xin Ying ZHANG; Yan Zhen LI; Xue Sen FAN; Gui Rong QU; Xue Yuan HU; Jian Ji WANG

    2006-01-01

    An efficient and green method for the synthesis of 1, 4-dihydropyridine derivatives mediated in an ionic liquid, [bmim][BF4], through a four-component condensation process of aldehydes, 1, 3-dione, Meldrum's acid and ammonium acetate is disclosed in this paper.

  9. SCFJFK is a bona fide E3 ligase for ING4 and a potent promoter of the angiogenesis and metastasis of breast cancer

    Science.gov (United States)

    Yan, Ruorong; He, Lin; Li, Zhongwu; Han, Xiao; Liang, Jing; Si, Wenzhe; Chen, Zhe; Li, Lei; Xie, Guojia; Li, Wanjin; Wang, Peiyan; Lei, Liandi; Zhang, Hongquan; Pei, Fei; Cao, Dengfeng

    2015-01-01

    Loss of function/dysregulation of inhibitor of growth 4 (ING4) and hyperactivation of NF-κB are frequent events in many types of human malignancies. However, the molecular mechanisms underlying these remarkable aberrations are not understood. Here, we report that ING4 is physically associated with JFK. We demonstrated that JFK targets ING4 for ubiquitination and degradation through assembly of an Skp1–Cul1–F-box (SCF) complex. We showed that JFK-mediated ING4 destabilization leads to the hyperactivation of the canonical NF-κB pathway and promotes angiogenesis and metastasis of breast cancer. Significantly, the expression of JFK is markedly up-regulated in breast cancer, and the level of JFK is negatively correlated with that of ING4 and positively correlated with an aggressive clinical behavior of breast carcinomas. Our study identified SCFJFK as a bona fide E3 ligase for ING4 and unraveled the JFK–ING4NF-κB axis as an important player in the development and progression of breast cancer, supporting the pursuit of JFK as a potential target for breast cancer intervention. PMID:25792601

  10. The Fps/Fes kinase regulates the inflammatory response to endotoxin through down-regulation of TLR4, NF-kappaB activation, and TNF-alpha secretion in macrophages.

    Science.gov (United States)

    Parsons, Sean A; Greer, Peter A

    2006-12-01

    Fps/Fes and Fer are members of a distinct subfamily of cytoplasmic protein tyrosine kinases that have recently been implicated in the regulation of innate immunity. Previous studies showed that mice lacking Fps/Fes are hypersensitive to systemic LPS challenge, and Fer-deficient mice displayed enhanced recruitment of leukocytes in response to local LPS challenge. This study identifies physiological, cellular, and molecular defects that contribute to the hyperinflammatory phenotype in Fps/Fes null mice. Plasma TNF-alpha levels were elevated in LPS challenged Fps/Fes null mice as compared with wild-type mice and cultured Fps/Fes null peritoneal macrophages treated with LPS showed increased TNF-alpha production. Cultured Fps/Fes null macrophages also displayed prolonged LPS-induced degradation of IkappaB-alpha, increased phosphorylation of the p65 subunit of NF-kappaB, and defective TLR4 internalization, compared with wild-type macrophages. Together, these observations provide a likely mechanistic basis for elevated proinflammatory cytokine secretion by Fps/Fes null macrophages and the increased sensitivity of Fps/Fes null mice to endotoxin. We posit that Fps/Fes modulates the innate immune response of macrophages to LPS, in part, by regulating internalization and down-regulation of the TLR4 receptor complex.

  11. Sensitization of interferon-γ induced apoptosis in human osteosarcoma cells by extracellular S100A4

    International Nuclear Information System (INIS)

    Pedersen, Kjetil Boye; Andersen, Kristin; Fodstad, Øystein; Mælandsmo, Gunhild Mari

    2004-01-01

    S100A4 is a small Ca 2+ -binding protein of the S100 family with metastasis-promoting properties. Recently, secreted S100A4 protein has been shown to possess a number of functions, including induction of angiogenesis, stimulation of cell motility and neurite extension. Cell cultures from two human osteosarcoma cell lines, OHS and its anti-S100A4 ribozyme transfected counterpart II-11b, was treated with IFN-γ and recombinant S100A4 in order to study the sensitizing effects of extracellular S100A4 on IFN-γ mediated apoptosis. Induction of apoptosis was demonstrated by DNA fragmentation, cleavage of poly (ADP-ribose) polymerase and Lamin B. In the present work, we found that the S100A4-expressing human osteosarcoma cell line OHS was more sensitive to IFN-γ-mediated apoptosis than the II-11b cells. S100A4 protein was detected in conditioned medium from OHS cells, but not from II-11b cells, and addition of recombinant S100A4 to the cell medium sensitized II-11b cells to apoptosis induced by IFN-γ. The S100A4/IFN-γ-mediated induction of apoptosis was shown to be independent of caspase activation, but dependent on the formation of reactive oxygen species. Furthermore, addition of extracellular S100A4 was demonstrated to activate nuclear factor-κB (NF-κB). In conclusion, we have shown that S100A4 sensitizes osteosarcoma cells to IFN-γ-mediated induction of apoptosis. Additionally, extracellular S100A4 activates NF-κB, but whether these events are causally related remains unknown

  12. Body fat throughout childhood in 2647 healthy Danish children

    DEFF Research Database (Denmark)

    Wohlfahrt-Veje, Christine; Tinggaard, Jeanette; Winther, K.

    2014-01-01

    stage and social class. SF %BF correlated strongly with DXA %BF (r=0.86). BMI and WC also correlated positively with DXA %BF (Z-scores; r= 0.78 and 0.69). Sensitivity and specificity were 79.5 and 93.8 for SF %BF, 75.9 and 90.3 for BMI and 59.2 and 95.4 for WC. CONCLUSIONS: SF %BF showed the highest...

  13. Co3O4 nanoneedle@electroactive nickel boride membrane core/shell arrays: A novel hybrid for enhanced capacity

    International Nuclear Information System (INIS)

    Li, Tingting; Zhu, Congxu; Yang, Xiaogang; Gao, Yuanhao; He, Weiwei; Yue, Hongwei; Zhao, Hongxiao

    2017-01-01

    Graphical abstract: Active nickel boride membrane anchored Co 3 O 4 nanoneedle arrays hybrid is synthesized via rapid interface reaction. The optimized core/shell nanostructure demonstrates greatly enhanced electrochemical properties. Display Omitted -- Highlights: •Active nickel boride membrane anchored Co 3 O 4 nanoneedle arrays core-shell hybrid architectures was fabricated via rapid interface reaction. •Specific capacity was improved by synergy between highly active components and optimized electron transfer microstructure. •The assembled asymmetric supercapacitor device exhibited excellent electrochemical performance. -- Abstract: Exploring novel hybrid materials with efficient microstructure using facile approaches is highly urgent in designing supercapacitor electrodes. Here, the Ni-B membrane was used for coating the porous Co 3 O 4 nanoneedle arrays which supported on the nickel foam (NF) frameworks through a rapid chemical reduction process (denoted as NF/Co 3 O 4 @NiB). The Ni-B membrane both provided sufficient active sites for redox reactions and inhibited the aggregation of formed hybrid architectures. Benefiting from the unique structural design and strongly coupled effects between porous Co 3 O 4 arrays and Ni-B membrane, the resulted NF/Co 3 O 4 @NiB electrode exhibited high areal capacitance of 3.47 F cm −2 (0.48 mAh cm −2 ) at a current density of 2.5 mA cm −2 , an excellent rate capability while maintaining 95.5% capacity retention after 2000 cycles. The asymmetric supercapacitor constructed with the NF/Co 3 O 4 @NiB as positive electrode and hierarchical porous carbon (HPC) as negative electrode also showed ideal capacitive behavior, and simultaneously delivered high energy and power densities. The easily decoration of Ni-B membrane on various active nanoarrays may arouse more novel design about hybrid architectures for large-scale applications.

  14. In vivo detection of prion amyloid plaques using [{sup 11}C]BF-227 PET

    Energy Technology Data Exchange (ETDEWEB)

    Okamura, Nobuyuki; Yanai, Kazuhiko [Tohoku University School of Medicine, Department of Pharmacology, Sendai (Japan); Shiga, Yusei; Itoyama, Yasuhito [Tohoku University School of Medicine, Department of Neurology, Sendai (Japan); Furumoto, Shozo [Tohoku University School of Medicine, Department of Pharmacology, Sendai (Japan); Tohoku University, Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Sendai (Japan); Tashiro, Manabu [Tohoku University, Division of Cyclotron Nuclear Medicine, Cyclotron and Radioisotope Center, Sendai (Japan); Tsuboi, Yoshio [Fukuoka University School of Medicine, Department of Neurology, Fukuoka (Japan); Furukawa, Katsutoshi; Arai, Hiroyuki [Institute of Development, Aging, and Cancer, Tohoku University, Department of Geriatrics and Gerontology, Division of Brain Sciences, Sendai (Japan); Iwata, Ren [Tohoku University, Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Sendai (Japan); Kudo, Yukitsuka [Tohoku University, Innovation of New Biomedical Engineering Center, Sendai (Japan); Doh-ura, Katsumi [Tohoku University School of Medicine, Department of Prion Research, 2-1 Seiryo-machi, Aoba-ku, Sendai (Japan)

    2010-05-15

    In vivo detection of pathological prion protein (PrP) in the brain is potentially useful for the diagnosis of transmissible spongiform encephalopathies (TSEs). However, there are no non-invasive ante-mortem means for detection of pathological PrP deposition in the brain. The purpose of this study is to evaluate the amyloid imaging tracer BF-227 with positron emission tomography (PET) for the non-invasive detection of PrP amyloid in the brain. The binding ability of BF-227 to PrP amyloid was investigated using autoradiography and fluorescence microscopy. Five patients with TSEs, including three patients with Gerstmann-Straeussler-Scheinker disease (GSS) and two patients with sporadic Creutzfeldt-Jakob disease (CJD), underwent [{sup 11}C]BF-227 PET scans. Results were compared with data from 10 normal controls and 17 patients with Alzheimer's disease (AD). The regional to pons standardized uptake value ratio was calculated as an index of BF-227 retention. Binding of BF-227 to PrP plaques was confirmed using brain samples from autopsy-confirmed GSS cases. In clinical PET study, significantly higher retention of BF-227 was detected in the cerebellum, thalamus and lateral temporal cortex of GSS patients compared to that in the corresponding tissues of normal controls. GSS patients also showed higher retention of BF-227 in the cerebellum, thalamus and medial temporal cortex compared to AD patients. In contrast, the two CJD patients showed no obvious retention of BF-227 in the brain. Although [{sup 11}C]BF-227 is a non-specific imaging marker of cerebral amyloidosis, it is useful for in vivo detection of PrP plaques in the human brain in GSS, based on the regional distribution of the tracer. PET amyloid imaging might provide a means for both early diagnosis and non-invasive disease monitoring of certain forms of TSEs. (orig.)

  15. Reduced RAC1 activity inhibits cell proliferation and induces apoptosis in neurofibromatosis type 2(NF2)-associated schwannoma.

    Science.gov (United States)

    Wang, Ying; Wang, Bo; Li, Peng; Zhang, Qi; Liu, Pinan

    2017-12-01

    Objective To study the function and potential mechanism of RAC1 inhibitors in NF2-associated schwannoma. Methods In this study, we the downregulation of RAC1 activity and tumor cell phenotypes by RAC1 inhibitor NSC23766 in vitro. And we further validated the anti-proliferation effect by this RAC1 inhibitor in subcutaneous xenograft tumor model and sciatic nerve model. Results Pharmacological inhibition of RAC1 could significantly inhibit the proliferation of both RT4 cells and human NF2-associated primary schwannoma cells by inducing apoptosis. Pharmacological inhibition of RAC1 effectively reduced Rac1 activity and down-regulated the pathway downstream of Rac. Moreover, pharmacological inhibition of RAC1 showed a potential antitumor effect, with low toxicity in vivo. Conclusion RAC1 inhibitors may play a therapeutic role in patients with schwannoma.

  16. SCF(JFK) is a bona fide E3 ligase for ING4 and a potent promoter of the angiogenesis and metastasis of breast cancer.

    Science.gov (United States)

    Yan, Ruorong; He, Lin; Li, Zhongwu; Han, Xiao; Liang, Jing; Si, Wenzhe; Chen, Zhe; Li, Lei; Xie, Guojia; Li, Wanjin; Wang, Peiyan; Lei, Liandi; Zhang, Hongquan; Pei, Fei; Cao, Dengfeng; Sun, Luyang; Shang, Yongfeng

    2015-03-15

    Loss of function/dysregulation of inhibitor of growth 4 (ING4) and hyperactivation of NF-κB are frequent events in many types of human malignancies. However, the molecular mechanisms underlying these remarkable aberrations are not understood. Here, we report that ING4 is physically associated with JFK. We demonstrated that JFK targets ING4 for ubiquitination and degradation through assembly of an Skp1-Cul1-F-box (SCF) complex. We showed that JFK-mediated ING4 destabilization leads to the hyperactivation of the canonical NF-κB pathway and promotes angiogenesis and metastasis of breast cancer. Significantly, the expression of JFK is markedly up-regulated in breast cancer, and the level of JFK is negatively correlated with that of ING4 and positively correlated with an aggressive clinical behavior of breast carcinomas. Our study identified SCF(JFK) as a bona fide E3 ligase for ING4 and unraveled the JFK-ING4-NF-κB axis as an important player in the development and progression of breast cancer, supporting the pursuit of JFK as a potential target for breast cancer intervention. © 2015 Yan et al.; Published by Cold Spring Harbor Laboratory Press.

  17. Downregulation of NF-ΚB1 enhances the radiosensitivity of renal cell carcinoma

    International Nuclear Information System (INIS)

    Ikegami, Amanda; Silva, Luiz Felipe Teixeira da; Bellini, Maria Helena

    2017-01-01

    significantly more radiosensitive than controls - Renca-WT and Renca-Mock, (P<0.001 vs Renca-Mock). The ratio α/β was increased in Renca-shRNA-NF-kB1: -0.177±0.677 compared with 7.368±1.833 and 11.960±5.240 of the Renca- WT and Renca-Mock, respectively. There was no significant difference in the survival fraction between Renca-WT and Renca-Mock groups. The lethal dose 50% (LD50) of Renca-WT was 3.33 Gy and Renca-Mock was 3.288 Gy whereas for the Renca-shRNA-NF-kB1 group it was 2.08 Gy. Corroborating these data, the Renca-shRNA-NF-kB1 showed reduction of 16.75±0.06% in the viability when compared to the Renca-Mock (P<0.001). Conclusion: The knockdown of NF-kB1 gene mediated by shRNA on Renca cells led to a decrease in the radioresistance. Therefore, this gene can be a therapeutic target for CCR treatment. (author)

  18. Downregulation of NF-ΚB1 enhances the radiosensitivity of renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Ikegami, Amanda; Silva, Luiz Felipe Teixeira da; Bellini, Maria Helena [Instituto De Pesquisas Energéticas e Nucleares (IPEN/CNEN-SP), São Paulo, SP (Brazil)

    2017-07-01

    to be significantly more radiosensitive than controls - Renca-WT and Renca-Mock, (P<0.001 vs Renca-Mock). The ratio α/β was increased in Renca-shRNA-NF-kB1: -0.177±0.677 compared with 7.368±1.833 and 11.960±5.240 of the Renca- WT and Renca-Mock, respectively. There was no significant difference in the survival fraction between Renca-WT and Renca-Mock groups. The lethal dose 50% (LD50) of Renca-WT was 3.33 Gy and Renca-Mock was 3.288 Gy whereas for the Renca-shRNA-NF-kB1 group it was 2.08 Gy. Corroborating these data, the Renca-shRNA-NF-kB1 showed reduction of 16.75±0.06% in the viability when compared to the Renca-Mock (P<0.001). Conclusion: The knockdown of NF-kB1 gene mediated by shRNA on Renca cells led to a decrease in the radioresistance. Therefore, this gene can be a therapeutic target for CCR treatment. (author)

  19. D-Saccharic acid 1,4-lactone protects diabetic rat kidney by ameliorating hyperglycemia-mediated oxidative stress and renal inflammatory cytokines via NF-κB and PKC signaling

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharya, Semantee [Department of Life Sciences and Biotechnology, Jadavpur University, 188, Raja S C Mullick Road, Kolkata 700 032 (India); Manna, Prasenjit [Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata-700054 (India); Gachhui, Ratan [Department of Life Sciences and Biotechnology, Jadavpur University, 188, Raja S C Mullick Road, Kolkata 700 032 (India); Sil, Parames C., E-mail: parames@bosemain.boseinst.ac.in [Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata-700054 (India)

    2013-02-15

    Increasing evidence suggests that oxidative stress is involved in the pathogenesis of diabetic nephropathy (DN) and this can be attenuated by antioxidants. D-Saccharic acid 1,4-lactone (DSL) is known for its detoxifying and antioxidant properties. Our early investigation showed that DSL can ameliorate alloxan (ALX) induced diabetes mellitus and oxidative stress in rats by inhibiting pancreatic β-cell apoptosis. In the present study we, therefore, investigated the protective role of DSL against renal injury in ALX induced diabetic rats. ALX exposure (at a dose of 120 mg/kg body weight, i. p., once) elevated the blood glucose level, serum markers related to renal injury, the production of reactive oxygen species (ROS), and disturbed the intra-cellular antioxidant machineries. Oral administration of DSL (80 mg/kg body weight) restored all these alterations close to normal. In addition, DSL could also normalize the aldose reductase activity which was found to increase in the diabetic rats. Investigating the mechanism of its protective activity, we observed the activation of different isoforms of PKC along with the accumulation of matrix proteins like collagen and fibronectin. The diabetic rats also showed nuclear translocation of NF-κB and increase in the concentration of inflammatory cytokines in the renal tissue. The activation of mitochondria dependent apoptotic pathway was observed in the diabetic rat kidneys. However, treatment of diabetic rats with DSL counteracted all these changes. These findings, for the first time, demonstrated that DSL could ameliorate renal dysfunction in diabetic rats by suppressing the oxidative stress related signalling pathways. - Highlights: ► Sustained hyperglycemia and oxidative stress lead to diabetic renal injury. ► D-saccharic acid 1,4-lactone prevents renal damage in alloxan-induced diabetes. ► It restores intra-cellular antioxidant machineries and kidney apoptosis. ► DSL reduces hyperglycemia-mediated oxidative stress

  20. NF-kappaB mediates FGF signal regulation of msx-1 expression.

    Science.gov (United States)

    Bushdid, P B; Chen, C L; Brantley, D M; Yull, F; Raghow, R; Kerr, L D; Barnett, J V

    2001-09-01

    The nuclear factor-kappaB (NF-kappaB) family of transcription factors is involved in proliferation, differentiation, and apoptosis in a stage- and cell-dependent manner. Recent evidence has shown that NF-kappaB activity is necessary for both chicken and mouse limb development. We report here that the NF-kappaB family member c-rel and the homeodomain gene msx-1 have partially overlapping expression patterns in the developing chick limb. In addition, inhibition of NF-kappaB activity resulted in a decrease in msx-1 mRNA expression. Sequence analysis of the msx-1 promoter revealed three potential kappaB-binding sites similar to the interferon-gamma (IFN-gamma) kappaB-binding site. These sites bound to c-Rel, as shown by electrophoretic mobility shift assay (EMSA). Furthermore, inhibition of NF-kappaB activity significantly reduced transactivation of the msx-1 promoter in response to FGF-2/-4, known stimulators of msx-1 expression. These results suggest that NF-kappaB mediates the FGF-2/-4 signal regulation of msx-1 gene expression. Copyright 2001 Academic Press.

  1. Beneficial Effects of Ethyl Pyruvate through Inhibiting High-Mobility Group Box 1 Expression and TLR4/NF-κB Pathway after Traumatic Brain Injury in the Rat

    Directory of Open Access Journals (Sweden)

    Xingfen Su

    2011-01-01

    Full Text Available Ethyl pyruvate (EP has demonstrated neuroprotective effects against acute brain injury through its anti-inflammatory action. The nuclear protein high-mobility group box 1 (HMGB1 can activate inflammatory pathways when released from dying cells. This study was designed to investigate the protective effects of EP against secondary brain injury in rats after Traumatic Brain Injury (TBI. Adult male rats were randomly divided into three groups: (1 Sham + vehicle group, (2 TBI + vehicle group, and (3 TBI + EP group (n=30 per group. Right parietal cortical contusion was made by using a weight-dropping TBI method. In TBI + EP group, EP was administered intraperitoneally at a dosage of 75 mg/kg at 5 min, 1 and 6 h after TBI. Brain samples were harvested at 24 h after TBI. We found that EP treatment markedly inhibited the expressions of HMGB1 and TLR4, NF-κB DNA binding activity and inflammatory mediators, such as IL-1β, TNF-α and IL-6. Also, EP treatment significantly ameliorated beam walking performance, brain edema, and cortical apoptotic cell death. These results suggest that the protective effects of EP may be mediated by the reduction of HMGB1/TLR4/NF-κB-mediated inflammatory response in the injured rat brain.

  2. Extension of the Th-232 burnup chain in the WIMSD/4 program library

    International Nuclear Information System (INIS)

    Caldeira, A.D.

    1991-07-01

    The Th-232 burnup chain was extended through U-236, in the WIMSD/4 program library. The evolution of the values of k i nf and U-235 number density, as function of time, for the modified TRX1 problem, calculated with the new library, shows an improvement in the results when compared with LEOPARD program. (author)

  3. Synthesis, characterization and crystal structure determination of a new Zn(II Schiff base complex derived from condensation of a new asymmetrical tripodal amine, 3-((4-aminobutyl(pyridin-2-ylmethylaminopropan-1-ol and 2-hydroxy-3-methoxybenzaldehyde

    Directory of Open Access Journals (Sweden)

    Majid Rezaeivala

    2017-05-01

    Full Text Available A new tripodal amine, 3-((4-aminobutyl(pyridin-2-ylmethylaminopropan-1-ol (HL has been prepared. This has been used to synthesize a new Schiff base complex by template condensation with 2-hydroxy-3-methoxybenzaldehyde in the presence of Zn(II metal ion in methanol. The complex has been characterized using spectroscopic methods and the crystal structure of [ZnL]BF4, L:3-((4-aminobutyl(pyridin-2-ylmethylaminopropan-1-ol was confirmed by single crystal X-ray diffraction studies. Single crystal X-ray structure analysis showed that in the mononuclear Zn(II complex, [ZnL]BF4 the Zn(II ion is in a distorted square pyramidal environment.

  4. Thymosin beta-4 promotes mesenchymal stem cell proliferation via an interleukin-8-dependent mechanism

    International Nuclear Information System (INIS)

    Jeon, Byung-Joon; Yang, Yoolhee; Kyung Shim, Su; Yang, Heung-Mo; Cho, Daeho; Ik Bang, Sa

    2013-01-01

    Mesenchymal stem cells (MSCs) hold great promise for the field of tissue regeneration. Because only a limited number of MSCs can be obtained from each donor site, it is important to establish standard methods for MSC expansion using growth and trophic factors. Thymosin β4 (Tβ4) is a novel trophic factor that has antimicrobial effects and the potential to promote tissue repair. Tβ4 is a ubiquitous, naturally-occurring peptide in the wound bed. Therefore, the relationship between Tβ4 and MSCs, especially adjacent adipose tissue-derived stem cells (ASCs), merits consideration. Exogenous Tβ4 treatment enhanced the proliferation of human ASCs, resulting in prominent nuclear localization of PCNA immunoreactivity. In addition, exogenous Tβ4 also increased IL-8 secretion and blocking of IL-8 with neutralizing antibodies decreased Tβ4-induced ASC proliferation, suggesting that IL-8 is a critical mediator of Tβ4-enhanced proliferation. Moreover, Tβ4 activated phosphorylation of ERK1/2 and increased the nuclear translocation of NF-κB. These observation provide that Tβ4 promotes the expansion of human ASCs via an IL-8-dependent mechanism that involves the ERK and NF-κB pathways. Therefore, Tβ4 could be used as a tool for MSC expansion in cell therapeutics. - Highlights: • This is fundamental information required to correlate Tβ4 with MSC expansion. • MSC expansion by Tβ4 is involved in enhancement of IL-8 and ERK/NF-κB pathway. • Tβ4 could be used as a tool for MSC expansion in cell therapeutics

  5. Thymosin beta-4 promotes mesenchymal stem cell proliferation via an interleukin-8-dependent mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Jeon, Byung-Joon [Department of Plastic and Reconstructive Surgery, Korea University Medical Center, Gojan 1-dong, Danwon-gu, Ansan-si, Gyeonggi-do 425-707 (Korea, Republic of); Yang, Yoolhee; Kyung Shim, Su [Department of Plastic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul 135-710 (Korea, Republic of); Yang, Heung-Mo [Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul 135-710 (Korea, Republic of); Cho, Daeho, E-mail: cdhkor@sookmyung.ac.kr [Department of Life Science, Sookmyung Women' s University, Hyochangwon-gil 52, Yongsan-gu, Seoul 140-742 (Korea, Republic of); Ik Bang, Sa, E-mail: si55.bang@samsung.com [Department of Plastic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul 135-710 (Korea, Republic of)

    2013-10-15

    Mesenchymal stem cells (MSCs) hold great promise for the field of tissue regeneration. Because only a limited number of MSCs can be obtained from each donor site, it is important to establish standard methods for MSC expansion using growth and trophic factors. Thymosin β4 (Tβ4) is a novel trophic factor that has antimicrobial effects and the potential to promote tissue repair. Tβ4 is a ubiquitous, naturally-occurring peptide in the wound bed. Therefore, the relationship between Tβ4 and MSCs, especially adjacent adipose tissue-derived stem cells (ASCs), merits consideration. Exogenous Tβ4 treatment enhanced the proliferation of human ASCs, resulting in prominent nuclear localization of PCNA immunoreactivity. In addition, exogenous Tβ4 also increased IL-8 secretion and blocking of IL-8 with neutralizing antibodies decreased Tβ4-induced ASC proliferation, suggesting that IL-8 is a critical mediator of Tβ4-enhanced proliferation. Moreover, Tβ4 activated phosphorylation of ERK1/2 and increased the nuclear translocation of NF-κB. These observation provide that Tβ4 promotes the expansion of human ASCs via an IL-8-dependent mechanism that involves the ERK and NF-κB pathways. Therefore, Tβ4 could be used as a tool for MSC expansion in cell therapeutics. - Highlights: • This is fundamental information required to correlate Tβ4 with MSC expansion. • MSC expansion by Tβ4 is involved in enhancement of IL-8 and ERK/NF-κB pathway. • Tβ4 could be used as a tool for MSC expansion in cell therapeutics.

  6. Total body fat, abdominal fat, body fat distribution and surrogate markers for health related to adipocyte fatty acid-binding protein (FABP4) in children.

    Science.gov (United States)

    Dencker, Magnus; Danielson, Anton; Karlsson, Magnus K; Wollmer, Per; Andersen, Lars B; Thorsson, Ola

    2017-04-01

    The aim of the study was to assess possible relationships between adipocyte fatty acid-binding protein (FABP4) and total body fat (TBF), abdominal fat, body fat distribution, aerobic fitness, blood pressure, cardiac dimensions and the increase in body fat over 2 years in a community sample of children. A cross-sectional study was used in a community sample of 170 (92 boys and 78 girls) children aged 8-11 years. TBF and abdominal fat (AFM) were measured by dual-energy X-ray absorptiometry (DXA). TBF was also expressed as percentage of total body mass (BF%), and body fat distribution was calculated as AFM/TBF. Maximal oxygen uptake (VO2PEAK) was assessed by indirect calorimetry during a maximal exercise test and scaled to body mass. Systolic and diastolic blood pressure (SBP and DBP) and pulse pressure (PP) were measured. Echocardiography was performed. Left atrial (LA) size was measured, and left ventricular mass (LVM) was calculated. A follow-up DXA scan was available in 152 children (84 boys and 68 girls). Frozen serum samples were analyzed for FABP4. Partial correlations, with adjustment for sex, between FABP4 vs. ln TBF, ln BF%, ln AFM, AFM/TBF and VO2PEAK were (r=0.69, 0.68, 0.69, 0.49 and -0.39, pfat or change in fat distribution were not correlated.) Conclusions: Findings from this community-based cohort of young children show that increased body fat and abdominal fat, more abdominal body fat distribution, low fitness, more LVM and increased LA, increased SBP and PP were all associated with increased levels of FABP4. Increase in TBF and abdominal fat over 2 years were also associated with increased levels of FABP4.

  7. Telomere-mediated chromosomal instability triggers TLR4 induced inflammation and death in mice.

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    Rabindra N Bhattacharjee

    Full Text Available BACKGROUND: Telomeres are essential to maintain chromosomal stability. Cells derived from mice lacking telomerase RNA component (mTERC-/- mice display elevated telomere-mediated chromosome instability. Age-dependent telomere shortening and associated chromosome instability reduce the capacity to respond to cellular stress occurring during inflammation and cancer. Inflammation is one of the important risk factors in cancer progression. Controlled innate immune responses mediated by Toll-like receptors (TLR are required for host defense against infection. Our aim was to understand the role of chromosome/genome instability in the initiation and maintenance of inflammation. METHODOLOGY/PRINCIPAL FINDINGS: We examined the function of TLR4 in telomerase deficient mTERC-/- mice harbouring chromosome instability which did not develop any overt immunological disorder in pathogen-free condition or any form of cancers at this stage. Chromosome instability was measured in metaphase spreads prepared from wildtype (mTERC+/+, mTERC+/- and mTERC-/- mouse splenocytes. Peritoneal and/or bone marrow-derived macrophages were used to examine the responses of TLR4 by their ability to produce inflammatory mediators TNFalpha and IL6. Our results demonstrate that TLR4 is highly up-regulated in the immune cells derived from telomerase-null (mTERC-/- mice and lipopolysaccharide, a natural ligand for TLR4 stabilises NF-kappaB binding to its promoter by down-regulating ATF-3 in mTERC-/- macrophages. CONCLUSIONS/SIGNIFICANCE: Our findings implied that background chromosome instability in the cellular level stabilises the action of TLR4-induced NF-kappaB action and sensitises cells to produce excess pro-inflammatory mediators. Chromosome/genomic instability data raises optimism for controlling inflammation by non-toxic TLR antagonists among high-risk groups.

  8. Complete genomic sequences for hepatitis C virus subtypes 4b, 4c, 4d, 4g, 4k, 4l, 4m, 4n, 4o, 4p, 4q, 4r and 4t.

    Science.gov (United States)

    Li, Chunhua; Lu, Ling; Wu, Xianghong; Wang, Chuanxi; Bennett, Phil; Lu, Teng; Murphy, Donald

    2009-08-01

    In this study, we characterized the full-length genomic sequences of 13 distinct hepatitis C virus (HCV) genotype 4 isolates/subtypes: QC264/4b, QC381/4c, QC382/4d, QC193/4g, QC383/4k, QC274/4l, QC249/4m, QC97/4n, QC93/4o, QC139/4p, QC262/4q, QC384/4r and QC155/4t. These were amplified, using RT-PCR, from the sera of patients now residing in Canada, 11 of which were African immigrants. The resulting genomes varied between 9421 and 9475 nt in length and each contains a single ORF of 9018-9069 nt. The sequences showed nucleotide similarities of 77.3-84.3 % in comparison with subtypes 4a (GenBank accession no. Y11604) and 4f (EF589160) and 70.6-72.8 % in comparison with genotype 1 (M62321/1a, M58335/1b, D14853/1c, and 1?/AJ851228) reference sequences. These similarities were often higher than those currently defined by HCV classification criteria for subtype (75.0-80.0 %) and genotype (67.0-70.0 %) division, respectively. Further analyses of the complete and partial E1 and partial NS5B sequences confirmed these 13 'provisionally assigned subtypes'.

  9. LiFePO4/polymer/natural graphite: low cost Li-ion batteries

    International Nuclear Information System (INIS)

    Zaghib, K.; Striebel, K.; Guerfi, A.; Shim, J.; Armand, M.; Gauthier, M

    2004-01-01

    The aging and performance of natural graphite/PEO-based gel electrolyte/LiFePO 4 cells are reported. The gel polymer electrolytes were produced by electron-beam irradiation and then soaked in a liquid electrolyte. The natural graphite anode in gel electrolyte containing LiBF4-EC/GBL exhibited high reversible capacity (345 mAh/g) and high coulombic efficiency (91%). The LiFePO 4 cathode in the same gel-polymer exhibited a reversible capacity of 160 mAh/g and 93% coulombic efficiency. Better performance was obtained at high-rate discharge with 6% carbon additive in the cathode, however the graphite anode performance suffers at high rate. The Li-ion gel polymer battery shows a capacity fade of 13% after 180 cycles and has poor performance at low temperature due to low diffusion of the lithium to the graphite in the GBL system. The LiFePO 4 /gel/Li system has an excellent rate capacity. LiFePO 4 cathode material is suitable for HEV application

  10. Moderate voluntary exercise attenuates the metabolic syndrome in melanocortin-4 receptor-deficient rats showing central dopaminergic dysregulation

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    Silvana Obici

    2015-10-01

    Conclusions: Central dopamine dysregulation during VWR reinforces the link between MC4R function and molecular and behavioral responding to rewards. The data also suggest that exercise can be a successful lifestyle intervention in MC4R-haploinsufficient individuals despite reduced positive reinforcement during exercise training.

  11. κ-Carrageenan Enhances Lipopolysaccharide-Induced Interleukin-8 Secretion by Stimulating the Bcl10-NF-κB Pathway in HT-29 Cells and Aggravates C. freundii-Induced Inflammation in Mice

    Directory of Open Access Journals (Sweden)

    Wei Wu

    2017-01-01

    Full Text Available Background. The dietary usage of carrageenan as common food additive has increased observably over the last 50 years. But there is substantial controversy about its safety. Methods. We investigated whether the κ-carrageenan could enhance lipopolysaccharide-induced IL-8 expression by studying its actions on the TLR4-NF-κB pathway. The aggravating effect of κ-carrageenan on Citrobacter freundii DBS100-induced intestinal inflammation was also investigated in a mouse model. Results. Our data show that κ-carrageenan pretreatment promoted LPS-induced IL-8 expression in HT-29 cells. Although CD14, MD-2, and TLR4 were upregulated, the binding of LPS was not enhanced. However, the pathway of Bcl10-NF-κB was triggered. Interestingly, κ-carrageenan competitively blocked the binding of FITC-LPS. Furthermore, pretreatment with κ-carrageenan for one week previous to gavage with C. freundii DBS100 markedly aggravated weight loss, mortality, and colonic damage. The secretion of cytokines was unbalanced and the ratio of Tregs was decreased significantly. In addition, κ-carrageenan, together with C. freundii DBS100, enhanced the transcription and secretion of TLR4 and NF-κB. Conclusions. κ-Carrageenan can synergistically activate LPS-induced inflammatory through the Bcl10-NF-κB pathway, as indicated by its aggravation of C. freundii DBS100-induced colitis in mice. General Significance. Our results suggest that κ-carrageenan serves as a potential inflammatory agent that magnifies existing intestinal inflammation.

  12. TNF{alpha} and IL-1{beta} are mediated by both TLR4 and Nod1 pathways in the cultured HAPI cells stimulated by LPS

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Wenwen; Zheng, Xuexing [College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, Jilin Province (China); Department of Anesthesiology, University of Miami Miller School of Medicine, Miami, FL 33136 (United States); Liu, Shue [Department of Anesthesiology, University of Miami Miller School of Medicine, Miami, FL 33136 (United States); Ouyang, Hongsheng [College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, Jilin Province (China); Levitt, Roy C.; Candiotti, Keith A. [Department of Anesthesiology, University of Miami Miller School of Medicine, Miami, FL 33136 (United States); Hao, Shuanglin, E-mail: shao@med.miami.edu [Department of Anesthesiology, University of Miami Miller School of Medicine, Miami, FL 33136 (United States)

    2012-04-20

    Highlights: Black-Right-Pointing-Pointer LPS induces proinflammatory cytokine release in HAPI cells. Black-Right-Pointing-Pointer JNK pathway is dependent on TLR4 signaling to release cytokines. Black-Right-Pointing-Pointer NF-{kappa}B pathway is dependent on Nod1 signaling to release cytokines. -- Abstract: A growing body of evidence recently suggests that glial cell activation plays an important role in several neurodegenerative diseases and neuropathic pain. Microglia in the central nervous system express toll-like receptor 4 (TLR4) that is traditionally accepted as the primary receptor of lipopolysaccharide (LPS). LPS activates TLR4 signaling pathways to induce the production of proinflammatory molecules. In the present studies, we verified the LPS signaling pathways using cultured highly aggressively proliferating immortalized (HAPI) microglial cells. We found that HAPI cells treated with LPS upregulated the expression of TLR4, phospho-JNK (pJNK) and phospho-NF-{kappa}B (pNF-{kappa}B), TNF{alpha} and IL-1{beta}. Silencing TLR4 with siRNA reduced the expression of pJNK, TNF{alpha} and IL-1{beta}, but not pNF-{kappa}B in the cells. Inhibition of JNK with SP600125 (a JNK inhibitor) decreased the expression of TNF{alpha} and IL-1{beta}. Unexpectedly, we found that inhibition of Nod1 with ML130 significantly reduced the expression of pNF-{kappa}B. Inhibition of NF-{kappa}B also reduced the expression of TNF{alpha} and IL-1{beta}. Nod1 ligand, DAP induced the upregulation of pNF-{kappa}B which was blocked by Nod1 inhibitor. These data indicate that LPS-induced pJNK is TLR4-dependent, and that pNF-{kappa}B is Nod1-dependent in HAPI cells treated with LPS. Either TLR4-JNK or Nod1-NF-{kappa}B pathways is involved in the expression of TNF{alpha} and IL-1{beta}.

  13. Bovine TLR2 and TLR4 mediate Cryptosporidium parvum recognition in bovine intestinal epithelial cells.

    Science.gov (United States)

    Yang, Zhengtao; Fu, Yunhe; Gong, Pengtao; Zheng, Jingtong; Liu, Li; Yu, Yuqiang; Li, Jianhua; Li, He; Yang, Ju; Zhang, Xichen

    2015-08-01

    Cryptosporidium parvum (C. parvum) is an intestinal parasite that causes diarrhea in neonatal calves. It results in significant morbidity of neonatal calves and economic losses for producers worldwide. Innate resistance against C. parvum is thought to depend on engagement of pattern recognition receptors. However, the role of innate responses to C. parvum has not been elucidated in bovine. The aim of this study was to evaluate the role of TLRs in host-cell responses during C. parvum infection of cultured bovine intestinal epithelial cells. The expressions of TLRs in bovine intestinal epithelial cells were detected by qRT-PCR. To determine which, if any, TLRs may play a role in the response of bovine intestinal epithelial cells to C. parvum, the cells were stimulated with C. parvum and the expression of TLRs were tested by qRT-PCR. The expression of NF-κB was detected by western blotting. Further analyses were carried out in bovine TLRs transfected HEK293 cells and by TLRs-DN transfected bovine intestinal epithelial cells. The results showed that bovine intestinal epithelial cells expressed all known TLRs. The expression of TLR2 and TLR4 were up-regulated when bovine intestinal epithelial cells were treated with C. parvum. Meanwhile, C. parvum induced IL-8 production in TLR2 or TLR4/MD-2 transfected HEK293 cells. Moreover, C. parvum induced NF-κB activation and cytokine expression in bovine intestinal epithelial cells. The induction of NF-κB activation and cytokine expression by C. parvum were reduced in TLR2-DN and TLR4-DN transfected cells. The results showed that bovine intestinal epithelial cells expressed all known TLRs, and bovine intestinal epithelial cells recognized and responded to C. parvum via TLR2 and TLR4. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Trichomonas vaginalis Induces SiHa Cell Apoptosis by NF-κB Inactivation via Reactive Oxygen Species

    Science.gov (United States)

    Quan, Juan-Hua; Kang, Byung-Hun; Yang, Jung-Bo; Rhee, Yun-Ee; Noh, Heung-Tae; Choi, In-Wook; Cha, Guang-Ho; Yuk, Jae-Min

    2017-01-01

    Trichomonas vaginalis induces apoptosis in host cells through various mechanisms; however, little is known about the relationship between apoptosis, reactive oxygen species (ROS), and NF-κB signaling pathways in the cervical mucosal epithelium. Here, we evaluated apoptotic events, ROS production, and NF-κB activity in T. vaginalis-treated cervical mucosal epithelial SiHa cells, with or without specific inhibitors, using fluorescence microscopy, DNA fragmentation assays, subcellular fractionation, western blotting, and luciferase reporter assay. SiHa cells treated with live T. vaginalis at a multiplicity of infection of 5 (MOI 5) for 4 h produced intracellular and mitochondrial ROS in a parasite-load-dependent manner. Incubation with T. vaginalis caused DNA fragmentation, cleavage of caspase 3 and PARP, and release of cytochrome c into the cytoplasm. T. vaginalis-treated SiHa cells showed transient early NF-κB p65 nuclear translocation, which dramatically dropped at 4 h after treatment. Suppression of NF-κB activity was dependent on parasite burden. However, treatment with the ROS scavenger, N-acetyl-C-cysteine (NAC), reversed the effect of T. vaginalis on apoptosis and NF-κB inactivation in SiHa cells. Taken together, T. vaginalis induces apoptosis in human cervical mucosal epithelial cells by parasite-dose-dependent ROS production through an NF-κB-regulated, mitochondria-mediated pathway. PMID:29410962

  15. Trichomonas vaginalis Induces SiHa Cell Apoptosis by NF-κB Inactivation via Reactive Oxygen Species

    Directory of Open Access Journals (Sweden)

    Juan-Hua Quan

    2017-01-01

    Full Text Available Trichomonas vaginalis induces apoptosis in host cells through various mechanisms; however, little is known about the relationship between apoptosis, reactive oxygen species (ROS, and NF-κB signaling pathways in the cervical mucosal epithelium. Here, we evaluated apoptotic events, ROS production, and NF-κB activity in T. vaginalis-treated cervical mucosal epithelial SiHa cells, with or without specific inhibitors, using fluorescence microscopy, DNA fragmentation assays, subcellular fractionation, western blotting, and luciferase reporter assay. SiHa cells treated with live T. vaginalis at a multiplicity of infection of 5 (MOI 5 for 4 h produced intracellular and mitochondrial ROS in a parasite-load-dependent manner. Incubation with T. vaginalis caused DNA fragmentation, cleavage of caspase 3 and PARP, and release of cytochrome c into the cytoplasm. T. vaginalis-treated SiHa cells showed transient early NF-κB p65 nuclear translocation, which dramatically dropped at 4 h after treatment. Suppression of NF-κB activity was dependent on parasite burden. However, treatment with the ROS scavenger, N-acetyl-C-cysteine (NAC, reversed the effect of T. vaginalis on apoptosis and NF-κB inactivation in SiHa cells. Taken together, T. vaginalis induces apoptosis in human cervical mucosal epithelial cells by parasite-dose-dependent ROS production through an NF-κB-regulated, mitochondria-mediated pathway.

  16. Low nuclear body formation and tax SUMOylation do not prevent NF-kappaB promoter activation.

    Science.gov (United States)

    Bonnet, Amandine; Randrianarison-Huetz, Voahangy; Nzounza, Patrycja; Nedelec, Martine; Chazal, Maxime; Waast, Laetitia; Pene, Sabrina; Bazarbachi, Ali; Mahieux, Renaud; Bénit, Laurence; Pique, Claudine

    2012-09-25

    The Tax protein encoded by Human T-lymphotropic virus type 1 (HTLV-1) is a powerful activator of the NF-κB pathway, a property critical for HTLV-1-induced immortalization of CD4⁺ T lymphocytes. Tax permanently stimulates this pathway at a cytoplasmic level by activating the IκB kinase (IKK) complex and at a nuclear level by enhancing the binding of the NF-κB factor RelA to its cognate promoters and by forming nuclear bodies, believed to represent transcriptionally active structures. In previous studies, we reported that Tax ubiquitination and SUMOylation play a critical role in Tax localization and NF-κB activation. Indeed, analysis of lysine Tax mutants fused or not to ubiquitin or SUMO led us to propose a two-step model in which Tax ubiquitination first intervenes to activate IKK while Tax SUMOylation is subsequently required for promoter activation within Tax nuclear bodies. However, recent studies showing that ubiquitin or SUMO can modulate Tax activities in either the nucleus or the cytoplasm and that SUMOylated Tax can serve as substrate for ubiquitination suggested that Tax ubiquitination and SUMOylation may mediate redundant rather than successive functions. In this study, we analyzed the properties of a new Tax mutant that is properly ubiquitinated, but defective for both nuclear body formation and SUMOylation. We report that reducing Tax SUMOylation and nuclear body formation do not alter the ability of Tax to activate IKK, induce RelA nuclear translocation, and trigger gene expression from a NF-κB promoter. Importantly, potent NF-κB promoter activation by Tax despite low SUMOylation and nuclear body formation is also observed in T cells, including CD4⁺ primary T lymphocytes. Moreover, we show that Tax nuclear bodies are hardly observed in HTLV-1-infected T cells. Finally, we provide direct evidence that the degree of NF-κB activation by Tax correlates with the level of Tax ubiquitination, but not SUMOylation. These data reveal that the

  17. Dynamic activity of NF-κB in multiple trauma patients and protective effects of ulinastain

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    LI Jun

    2012-02-01

    Full Text Available 【Abstract】Objective: To investigate the dynamic activity of NF-κB at the early stage of injury in multiple trauma patients and the protective effects of ulinastain. Methods: From January 2008 to May 2010, patients with multiple traumas admitted to our emergency department were enrolled in this study. Their age varied from 20-55 years. All enrolled patients were assigned randomly into control group (26 cases of multiple injury without ulinastain treatment, ulinastain group (25 cases of multiple injury with ulinastain treatment, and mild injury group (20 cases for basic control. The inclusion criteria for mild injury group were AIS-2005≤3, single wound, previously healthy inhospital patients without the history of surgical intervention. In addition to routine treatment, patients in ulinastain group were intravenously injected 200 000 IU of ulinastain dissolved in 100 ml of normal saline within 12 hours after injury and subsequently injected at the interval of every 8 hours for 7 days. NF-κB activity in monocytes and the level of TNF? IL-1, IL? in serum on admission (day 0, day 1, 2, 3, 4, and 7 were measured. Data were compared and analyzed between different groups. Results: NF-κB activity in monocytes and TNF? IL-1 and IL? of these patients reached peak levels at 24 hour after trauma, with gradual decrease to normal at 72 hour after trauma. NF-κB activity and levels of TNF? IL-1 and IL? were lower in ulinastain group than control one, without any significant difference between the two groups. The mean duration for systemic inflammatory response syndrome and multiple organ dysfunction syndrome was 7 d?.1 d and 10 d?.5 d in ulinastain group and control group respectively, and showed a significant difference. Conclusions: NF-κB activity in monocytes and the levels of inflammatory cytokines in multiply injured patients increased transiently at the early stage of trauma. Ulinastain may shorten the duration of systemic inflammatory

  18. Molecular beam electric deflection of the tetrahalides CF4, CCl4, SiF4, SiCl4, GeCl4, TiF4, TiCl4, VF4, and VCl4

    International Nuclear Information System (INIS)

    Muenter, A.A.; Dyke, T.R.; Falconer, W.E.; Klemperer, W.

    1975-01-01

    Using molecular beam electric deflection, the temperature dependence of polar behavior has been studied for the molecules CF 4 , CCl 4 , SiF 4 , SiCl 4 , GeCl 4 , TiF 4 TiCl 4 , VF 4 , VF 4 , and VCl 4 . A number of these molecules show polar behavior consistent with a vibrationally induced dipole moment for states with one or both of the triply degenerate vibrations excited. In four of the tetrachloride species, the presence of a vibrationally induced dipole moment was confirmed by the change in polar behavior with isotopic substituion of the Cl atoms. The deflection behavior of the transition metal tetrahalides varied from nonpolar in VCl 4 to very polar in TiF 4

  19. Recruitment of Gr1(+)CD11b (+)F4/80 (+) population in the bone marrow and spleen by irradiation-induced pulmonary damage.

    Science.gov (United States)

    Thanasegaran, Suganya; Ito, Sachiko; Nishio, Naomi; Uddin, Mohammad Nizam; Sun, Yang; Isobe, Ken-ichi

    2015-04-01

    Radiation-induced lung injury is a kind of sterile inflammation, which may lead to morbidity and mortality. The mechanism by which ionizing radiation activate the immune system is not well understood. In the present study, we have investigated the immunological responses induced by local irradiation-induced damage in mouse lung. The left lungs of C57BL/6 mice were irradiated at a high dose of 100 Gy. The histology of the lungs and spleen showed evidences of alveolar inflammation and congestion at 2 weeks after X-ray treatment. Also, prominent increase in cells expressing the cell surface markers, Gr(+)CD11b(+)F4/80(+) and Ly6C(+) Ly6G(+) were observed 2 weeks after X-ray treatment (100 Gy). Gr1(+)CD11b(+)F4/80(+) cell depletion by clodronate treatment reversed the histological effects and also failed to recruit Gr(+)CD11b(+) cells or F4/80(+) cells caused by irradiation. The origin of recruited Gr1(+)CD11b(+) cells was found to be a mixed resident and recruited phenotype.

  20. Zn(II) coordination polymer of an in situ generated 4-pyridyl (4Py) attached bis(amido)phosphate ligand, [PO2(NH4Py)2]- showing preferential water uptake over aliphatic alcohols.

    Science.gov (United States)

    Gupta, Arvind K; Nagarkar, Sanjog S; Boomishankar, Ramamoorthy

    2013-08-14

    Two polymorphic 2D-coordination polymers of composition [ZnL(HCO2)]∞ were synthesized from an in situ generated ligand [PO2(NH(4)Py)2](-) (L(-)). The ligand L(-) was generated by a facile metal-assisted P-N bond hydrolysis reaction from the corresponding phosphonium salt 1, [P(NH(4)Py)4]Cl, or from the neutral phosphoric triamide 2, [PO(NH(4)Py)3]. The de-solvated sample of the polymer [ZnL(HCO2)]∞ features polar micropores and shows a type I isotherm for CO2 sorption whereas a type II behaviour was observed for N2. The vapour sorption isotherm of the de-solvated sample of [ZnL(HCO2)]∞ shows preferential adsorption of water vapour over aliphatic alcohols.

  1. Inhibition of the promotion of hepatocarcinogenesis by 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153) by the deletion of the p50 subunit of NF-κB in mice

    International Nuclear Information System (INIS)

    Glauert, Howard P.; Tharappel, Job C.; Banerjee, Subhashis; Chan, Nelson L.S.; Kania-Korwel, Izabela; Lehmler, Hans-Joachim; Lee, Eun Y.; Robertson, Larry W.; Spear, Brett T.

    2008-01-01

    Polychlorinated biphenyls (PCBs) are persistent and ubiquitous environmental chemicals that bioaccumulate and have hepatic tumor promoting activity in rodents. The present study examined the effect of deleting the p50 subunit of NF-κB on the hepatic tumor promoting activity of 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153) in mice. Both wild-type and p50-/- male mice were injected i.p. with diethylnitrosamine (DEN, 90 mg/kg) and then subsequently injected biweekly with 20 i.p. injections of PCB-153 (300 μmol/kg/injection). p50 deletion decreased the tumor incidence in both PCB- and vehicle-treated mice, whereas PCB-153 slightly (P = 0.09) increased the tumor incidence in wild-type and p50-/- mice. PCB-153 increased the total tumor volume in both wild-type and p50-/- mice, but the total tumor volume was not affected by p50 deletion in either PCB- or vehicle-treated mice. The volume of tumors that were positive for glutamine synthetase (GS), which is indicative of mutations in the beta-catenin gene, was increased in both wild-type and p50-/- mice administered PCB-153 compared to vehicle controls, and inhibited in p50-/- mice compared to wild-type mice (in both PCB- and vehicle-treated mice). The volume of tumors that were negative for GS was increased in p50-/- mice compared to wild-type mice but was not affected by PCB-153. PCB-153 increased cell proliferation in normal hepatocytes in wild-type but not p50-/- mice; this increase was inhibited in p50-/- mice. In hepatic tumors, the rate of cell proliferation was much higher than in normal hepatocytes, but was not affected by PCB treatment or p50 deletion. The rate of apoptosis, as measured by the TUNEL assay, was not affected by PCB-153 or p50 deletion in normal hepatocytes. In hepatic tumors, the rate of apoptosis was lower than in normal hepatocytes; PCB-153 slightly (P = 0.10) increased apoptosis in p50-/- but not wild-type mice; p50 deletion had no effect. Taken together, these data indicate that the absence of

  2. Lipopolysaccharide induces proliferation and osteogenic differentiation of adipose-derived mesenchymal stromal cells in vitro via TLR4 activation

    Energy Technology Data Exchange (ETDEWEB)

    Herzmann, Nicole; Salamon, Achim [Department of Cell Biology, University Medicine Rostock, Schillingallee 69, D-18057 Rostock (Germany); Fiedler, Tomas [Institute for Medical Microbiology, Virology and Hygiene, University Medicine Rostock, Schillingallee 70, D-18057 Rostock (Germany); Peters, Kirsten, E-mail: kirsten.peters@med.uni-rostock.de [Department of Cell Biology, University Medicine Rostock, Schillingallee 69, D-18057 Rostock (Germany)

    2017-01-01

    Multipotent mesenchymal stromal cells (MSC) are capable of multi-lineage differentiation and support regenerative processes. In bacterial infections, resident MSC can come intocontact with and need to react to bacterial components. Lipopolysaccharide (LPS), a typical structure of Gram-negative bacteria, increases the proliferation and osteogenic differentiation of MSC. LPS is usually recognized by the toll-like receptor (TLR) 4 and induces pro-inflammatory reactions in numerous cell types. In this study, we quantified the protein expression of TLR4 and CD14 on adipose-derived MSC (adMSC) in osteogenic differentiation and investigated the effect of TLR4 activation by LPS on NF-κB activation, proliferation and osteogenic differentiation of adMSC. We found that TLR4 is expressed on adMSC whereas CD14 is not, and that osteogenic differentiation induced an increase of the amount of TLR4 protein whereas LPS stimulation did not. Moreover, we could show that NF-κB activation via TLR4 occurs upon LPS treatment. Furthermore, we were able to show that competitive inhibition of TLR4 completely abolished the stimulatory effect of LPS on the proliferation and osteogenic differentiation of adMSC. In addition, the inhibition of TLR4 leads to the complete absence of osteogenic differentiation of adMSC, even when osteogenically stimulated. Thus, we conclude that LPS induces proliferation and osteogenic differentiation of adMSC in vitro through the activation of TLR4 and that the TLR4 receptor seems to play a role during osteogenic differentiation of adMSC.

  3. Dissipation of pyraclostrobin and its metabolite BF-500-3 in maize under field conditions.

    Science.gov (United States)

    You, Xiangwei; Liu, Congyun; Liu, Fengmao; Liu, Yanping; Dong, Jiannan

    2012-06-01

    The dissipation and residue of pyraclostrobin and its metabolite BF-500-3 in maize under field conditions were investigated. A sensitive, simple and fast method for simultaneous determination of pyraclostrobin and BF-500-3 in maize matrix was established by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The average recoveries of pyraclostrobin and BF-500-3 were found in the range of 83.6-104.9% with relative standard deviations (RSDs) of 2.3-10.0%. The results showed that pyraclostrobin dissipated quickly in maize plant with half-lives of 1.6-1.7 days. Its metabolite BF-500-3 showed a tendency of rapid increasing initially and decreasing afterwards. At harvest time, the terminal residues of pyraclostrobin were below the maximum residue limit (MRL) set by USA and Canada in maize grain when measured 7 days after the final application, which suggested that the use of this fungicide was safe for humans. The results could provide guidance to safe and reasonable use of pyraclostrobin in agriculture. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. A dual-channel gas chromatography method for the quantitation of low and high concentrations of NF3 and CF4 to study membrane separation of the two compounds

    OpenAIRE

    Branken, D.J.; Le Roux, J.P.; Krieg, H.M.; Lachmann, G.

    2013-01-01

    A dual-channel gas chromatographic method is described in this paper that can be conveniently used for quantitation of NF3/CF4 mixtures with a thermal conductivity detector (TCD) on one channel for the quantitation of high-concentrations, and a pulsed discharge helium ionization detector (PDHID) on a second channel for the quantitation of low concentrations. It is shown that adequate separation is achieved on both channels with this dual single-column setup in which column switchi...

  5. Conclusions

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Conclusions. Be it 2G or 4G, networks are vulnerable to unwanted access and thus should be protected. 4G networks would be more sensitive as its core network will be TCP/IP based. Accordingly, resource and security management schemes with seamless ...

  6. Interleukin-4 (IL4 and Interleukin-4 receptor (IL4RA polymorphisms in asthma: a case control study

    Directory of Open Access Journals (Sweden)

    Lorente Félix

    2005-11-01

    simulations = 0.0016, OR:3.39; 95% CI:1.50–7.66]. Conclusion Our results show a trend of association between the genetic combination of the T allele of -33C>TIL4 and the A allele of 576Q>RIL4RA with asthma. This genetic variant was more frequently observed in patients with persistent asthma. As long as this study was performed in a small population, further studies in other populations are needed to confirm these results.

  7. Influence of 17β-estradiol treatment on the expression of NF-κB in complete hydatidiform mole culture

    Directory of Open Access Journals (Sweden)

    Tatit Nurseta

    2013-12-01

    Full Text Available Background:  Genetic evidence has established a role of nuclear factor kappa B (NF-κB signaling in oncogenesis. However, activity of NF-κB in complete hydatidiform mole (CHM cell culture under 17β-estradiol (E2 treatment is not yet known. Recently, a positive cross-talk between estrogen receptor (ER and NF-κB to promote survival and progress of cancer cells to a more aggressive phenotype was established. In the present study, we examined the influence of E2 treatment on the NF-κB expression in CHM’s culture.Methods:  This experimental study measured the expression of NF-κB in CHM culture treated with E2: 10, 100, 300, 600, and 1000 pg/mL and without E2. Imunohistochemistry staining was used to assess the expression of NF-κB. Microphotographs were taken using 400x magnification. Adobe photoshop CS2 was used to assess the NF-κB expression in cell nucleus. The lower the color intensity of cell RGBbv, is the higher the expression of NF-κB in cells. ANOVA test was performed to compare the expression of NF-κB.Results: NF-κB expression as indicated by color intensity in control group was 114.84 ± 9.02. NF-κB expression in E2 treatment groups were respectively: E2 10 pg/mL: 106.30 ± 13.95; E2 100 pg/mL: 82.47 ± 4.72; E2 300 pg/mL: 82.24 ± 2.67; E2 600 pg/mL: 69.05 ± 6.47; E2 1000 pg/mL: 68.49 ± 2.37. There was progressive decline in color intensity of cells with E2 treatment indicating the increase expression of NF-κB. Significant differences with the control group occurred in doses of E2 100, 300, 600, dan 1000 pg/mL.Conclusion: Treatment of CHM trophoblast culture with escalating doses of E2 was associated with the increase of NF-κB expression in a dose dependent manner. (Med J Indones. 2013;22:197-201. doi: 10.13181/mji.v22i4.599Keywords: 17-β Estradiol, Hydatidiform mole, NF-κB

  8. Regorafenib induces extrinsic and intrinsic apoptosis through inhibition of ERK/NF-κB activation in hepatocellular carcinoma cells.

    Science.gov (United States)

    Tsai, Jai-Jen; Pan, Po-Jung; Hsu, Fei-Ting

    2017-02-01

    The aim of the present study was to investigate the role of NF-κB inactivation in regorafenib-induced apoptosis in human hepatocellular carcinoma SK-HEP-1 cells. SK-HEP-1 cells were treated with different concentrations of the NF-κB inhibitor 4-N-[2-(4-phenoxyphenyl)ethyl]quinazoline-4,6-diamine (QNZ) or regorafenib for different periods. The effects of QNZ and regorafenib on cell viability, expression of NF-κB-modulated anti-apoptotic proteins and apoptotic pathways were analyzed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, western blotting, DNA gel electrophoresis, flow cytometry and NF-κB reporter gene assay. Inhibitors of various kinases including AKT, c-Jun N-terminal kinase (JNK), P38 and extracellular signal-regulated kinase (ERK) were used to evaluate the mechanism of regorafenib-induced NF-κB inactivation. The results demonstrated that both QNZ and regorafenib significantly inhibited the expression of anti-apoptotic proteins and triggered extrinsic and intrinsic apoptosis. We also demonstrated that regorafenib inhibited NF-κB activation through ERK dephosphorylation. Taken all together, our findings indicate that regorafenib triggers extrinsic and intrinsic apoptosis through suppression of ERK/NF-κB activation in SK-HEP-1 cells.

  9. Towards continuous global measurements and optimal emission estimates of NF3

    Science.gov (United States)

    Arnold, T.; Muhle, J.; Salameh, P.; Harth, C.; Ivy, D. J.; Weiss, R. F.

    2011-12-01

    We present an analytical method for the continuous in situ measurement of nitrogen trifluoride (NF3) - an anthropogenic gas with a global warming potential of ~16800 over a 100 year time horizon. NF3 is not included in national reporting emissions inventories under the United Nations Framework Convention on Climate Change (UNFCCC). However, it is a rapidly emerging greenhouse gas due to emission from a growing number of manufacturing facilities with increasing output and modern end-use applications, namely in microcircuit etching, and in production of flat panel displays and thin-film photovoltaic cells. Despite success in measuring the most volatile long lived halogenated species such as CF4, the Medusa preconcentration GC/MS system of Miller et al. (2008) is unable to detect NF3 under remote operation. Using altered techniques of gas separation and chromatography after initial preconcentration, we are now able to make continuous atmospheric measurements of NF3 with average precisions NF3 produced. Emission factors are shown to have reduced over the last decade; however, rising production and end-use have caused the average global atmospheric concentration to double between 2005 and 2011 i.e. half the atmospheric NF3 present today originates from emissions after 2005. Finally we show the first continuous in situ measurements from La Jolla, California, illustrating how global deployment of our technique could improve the temporal and spatial scale of NF3 'top-down' emission estimates over the coming years. These measurements will be important for independent verification of emissions should NF3 be regulated under a new climate treaty.

  10. Troxerutin protects against 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47)-induced liver inflammation by attenuating oxidative stress-mediated NAD+-depletion

    International Nuclear Information System (INIS)

    Zhang, Zi-Feng; Zhang, Yan-qiu; Fan, Shao-Hua; Zhuang, Juan; Zheng, Yuan-Lin; Lu, Jun; Wu, Dong-Mei; Shan, Qun; Hu, Bin

    2015-01-01

    Highlights: • BDE-47 promotes liver inflammation by triggering oxidative stress-induced NAD + depletion. • Troxerutin inhibits BDE-47-induced liver inflammation via its antioxidant properties. • Troxerutin restores NAD + level and consequently abates SirT1 loss. • Troxerutin represses acetylation of NF-κB p65 (K310) and H3K9. • Troxerutin is a candidate for prevention and therapy of BDE-47-induced hepatotoxicity. - Abstract: Emerging evidence indicates that 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) induces liver injury through enhanced ROS production and lymphocytic infiltration, which may promote a liver inflammatory response. Antioxidants have been reported to attenuate the cellular toxicity associated with polybrominated diphenyl ethers (PBDEs). In this study, we investigated the effect of troxerutin, a trihydroxyethylated derivative of the natural bioflavonoid rutin, on BDE-47-induced liver inflammation and explored the potential mechanisms underlying this effect. Our results showed that NAD + -depletion was involved in the oxidative stress-mediated liver injury in a BDE-47 treated mouse model, which was confirmed by Vitamin E treatment. Furthermore, our data revealed that troxerutin effectively alleviated liver inflammation by mitigating oxidative stress-mediated NAD + -depletion in BDE-47 treated mice. Consequently, troxerutin remarkably restored SirT1 protein expression and activity in the livers of BDE-47-treated mice. Mechanistically, troxerutin dramatically repressed the nuclear translocation of NF-κB p65 and the acetylation of NF-κB p65 (Lys 310) and Histone H3 (Lys9) to abate the transcription of inflammatory genes in BDE-47-treated mouse livers. These inhibitory effects of troxerutin were markedly blunted by EX527 (SirT1 inhibitor) treatment. This study provides novel mechanistic insights into the toxicity of BDE-47 and indicates that troxerutin might be used in the prevention and therapy of BDE-47-induced hepatotoxicity

  11. Separation of toluene and heptane by liquid-liquid extraction using z-methyl-N-butylpyridinium tetrafluoroborate isomers (z = 2, 3, or 4) at T = 313.2 K

    International Nuclear Information System (INIS)

    Garcia, Julian; Garcia, Silvia; Torrecilla, Jose S.; Oliet, Mercedes; Rodriguez, Francisco

    2010-01-01

    The (liquid + liquid) equilibrium (LLE) data for three ternary systems containing heptane, toluene, and a z-methyl-N-butylpyridinium tetrafluoroborate ionic liquid ([zbmpy][BF 4 ] IL, where z = 2, 3, or 4) were determined at T = 313.2 K and atmospheric pressure. The effect of IL cation isomers on the LLE data was evaluated for the first time. The selectivity and extractive capacity from these LLE data were calculated and compared to those previously reported in the literature for the systems (heptane + toluene + [4bmpy][BF 4 ]) and (heptane + toluene + sulfolane). The results show that the LLE data for the systems comprising the ILs with the metha- and para-substituted cations do not differ significantly from isomer to isomer. On the other hand, significant differences were observed among the systems with the ortho-substituted cation and the other two cation isomers. The degree of consistency of the experimental LLE data was ascertained by applying the Othmer-Tobias correlation. In addition, the LLE data were satisfactorily correlated by means of the thermodynamic NRTL model.

  12. Role of nuclear factor of activated T-cells and activator protein-1 in the inhibition of interleukin-2 gene transcription by cannabinol in EL4 T-cells.

    Science.gov (United States)

    Yea, S S; Yang, K H; Kaminski, N E

    2000-02-01

    We previously reported that immunosuppressive cannabinoids inhibited interleukin (IL)-2 steady-state mRNA expression and secretion by phorbol-12-myristate-13-acetate plus ionomycin-activated mouse splenocytes and EL4 murine T-cells. Here we show that inhibition of IL-2 production by cannabinol, a modest central nervous system-active cannabinoid, is mediated through the inhibition of IL-2 gene transcription. Moreover, electrophoretic mobility shift assays demonstrated that cannabinol markedly inhibited the DNA binding activity of nuclear factor of activated T-cells (NF-AT) and activator protein-1 (AP-1) in a time- and concentration-dependent manner in activated EL4 cells. The inhibitory effects produced by cannabinol on AP-1 DNA binding were quite transient, showing partial recovery by 240 min after cell activation and no effect on the activity of a reporter gene under the control of AP-1. Conversely, cannabinol-mediated inhibition of NF-AT was robust and sustained as demonstrated by an NF-AT-regulated reporter gene. Collectively, these results suggest that decreased IL-2 production by cannabinol in EL4 cells is due to the inhibition of transcriptional activation of the IL-2 gene and is mediated, at least in part, through a transient inhibition of AP-1 and a sustained inhibition of NF-AT.

  13. Inversion of spin levels in Ni sup 2 sup + : Zn(BF sub 4) sub 2 centre dot 6H sub 2 O at all -round compression and effect of transition coincidence

    CERN Document Server

    Krygin, I M; Nejlo, G N; Prokhorov, A D

    2001-01-01

    The study of the EPR spectrum of the Ni sup 2 sup + ion, replacing Zn sup 2 sup + in the Zn(BF sub 4) centre dot 6H sub 2 O crystals in the wide temperature range by the all-round compression in the X- and Q-ranges is carried out. The basic changes by varying temperature and pressure occur with the D parameter, characterizing the initial splitting by practically unchanged g-factor. The increase in the temperature is accompanied by the D nonlinear growth. The all-round compression linearly changes the initial splitting and leads to the change in the D-sign, signifying the spin levels inversion by 3.5 kbar. Coincidence of EPR lines, relative to different transitions, leads to the crevasse appearance in the outline of this one, that is connected with cross-relaxation inside the spin system

  14. Up-regulation of TLR2 and TLR4 in high mobility group Box1-stimulated macrophages in pulpitis patients

    Science.gov (United States)

    Mahmoudi, Javad; Sabermarouf, Babak; Baradaran, Behzad; Sadat-Hatamnezhad, Leila; Shotorbani, Siamak Sandoghchian

    2017-01-01

    Objective(s): High Mobility Group Box1 (HMGB1) is a nonhistone, DNA-binding protein that serves a crucial role in regulating gene transcription and is involved in a variety of proinflammatory, extracellular activities. The aim of this study was to explore whether HMGB1 stimulation can up-regulate the expression of Toll-like Receptor 2 (TLR2) and Toll-like Receptor 4 (TLR4) on macrophages from pulpitis and to clarify the subsequent events involving Th17 cells and Th17 cell-associated cytokine changes. Materials and Methods: Having prepared dental pulp tissues of pulpitis and healthy controls, macrophage were isolated and cultured. Macrophages were thereafter stimulated by HMGB1 time course. RT-QPCR, flowcytometer, immunofluorescence, Western blotting, and ELISA techniques were used in the present research. Results: Our results showed that the expression of TLR2 and TLR4 on macrophages stimulated with HMGB1 increased in pulpitis compared with controls (macrophages without HMGB1 stimulation) with a statistical significance (Ppulpitis increased, and NF-kB, the downstream target of TLR2 and TLR4, also showed a marked elevation after macrophages’ stimulation by HMGB1. Conclusion: The evidence from the present study suggests that the enhanced TLR2 and TLR4 pathways and Th17 cell polarization may be due to HMGB1 stimulation in pulpitis. PMID:28293399

  15. Predicting the performance of the CMS precision PbWO$_4$ electromagnetic calorimeter in the HL-LHC era from test beam results on irradiated crystals

    CERN Document Server

    Zghiche, Amina

    2017-01-01

    The harsh radiation environment in which detectors will have to operate during the High Luminosity phase of the LHC (HL-LHC) represents a crucial challenge for many calorimeter technologies. In the CMS forward calorimeters, ionizing doses and hadron fluences will reach up to 300 kGy (at a dose rate of 30 Gy/h) and ${\\bf 2\\times 10^{14} cm^{-2}}$, respectively, at the pseudorapidity region of {\\bf $\\vert\\eta\\vert$}= 2.6. To evaluate the evolution of the CMS ECAL performance in such conditions, a set of \\PWO crystals, which had previously been exposed to 24 GeV protons up to integrated fluences between ${\\bf 2.1\\times 10^{13} cm^{-2}}$ and ${\\bf 1.3\\times 10^{14} cm^{-2}}$, has been studied in beam tests. A degradation of the energy resolution and a non-linear response to electron showers are observed in damaged crystals. Direct measurements of the light output from the crystals show the amplitude decreasing and pulse becoming faster as the fluence increases. The evolution of the performance of the PbWO$_4$ cry...

  16. Single-cell and population NF-κB dynamic responses depend on lipopolysaccharide preparation.

    Directory of Open Access Journals (Sweden)

    Miriam V Gutschow

    Full Text Available Lipopolysaccharide (LPS, found in the outer membrane of gram-negative bacteria, elicits a strong response from the transcription factor family Nuclear factor (NF-κB via Toll-like receptor (TLR 4. The cellular response to lipopolysaccharide varies depending on the source and preparation of the ligand, however. Our goal was to compare single-cell NF-κB dynamics across multiple sources and concentrations of LPS.Using live-cell fluorescence microscopy, we determined the NF-κB activation dynamics of hundreds of single cells expressing a p65-dsRed fusion protein. We used computational image analysis to measure the nuclear localization of the fusion protein in the cells over time. The concentration range spanned up to nine orders of magnitude for three E. coli LPS preparations. We find that the LPS preparations induce markedly different responses, even accounting for potency differences. We also find that the ability of soluble TNF receptor to affect NF-κB dynamics varies strikingly across the three preparations.Our work strongly suggests that the cellular response to LPS is highly sensitive to the source and preparation of the ligand. We therefore caution that conclusions drawn from experiments using one preparation may not be applicable to LPS in general.

  17. Gastroesophageal reflux activates the NF-κB pathway and impairs esophageal barrier function in mice

    Science.gov (United States)

    Fang, Yu; Chen, Hao; Hu, Yuhui; Djukic, Zorka; Tevebaugh, Whitney; Shaheen, Nicholas J.; Orlando, Roy C.; Hu, Jianguo

    2013-01-01

    The barrier function of the esophageal epithelium is a major defense against gastroesophageal reflux disease. Previous studies have shown that reflux damage is reflected in a decrease in transepithelial electrical resistance associated with tight junction alterations in the esophageal epithelium. To develop novel therapies, it is critical to understand the molecular mechanisms whereby contact with a refluxate impairs esophageal barrier function. In this study, surgical models of duodenal and mixed reflux were developed in mice. Mouse esophageal epithelium was analyzed by gene microarray. Gene set enrichment analysis showed upregulation of inflammation-related gene sets and the NF-κB pathway due to reflux. Significance analysis of microarrays revealed upregulation of NF-κB target genes. Overexpression of NF-κB subunits (p50 and p65) and NF-κB target genes (matrix metalloproteinases-3 and -9, IL-1β, IL-6, and IL-8) confirmed activation of the NF-κB pathway in the esophageal epithelium. In addition, real-time PCR, Western blotting, and immunohistochemical staining also showed downregulation and mislocalization of claudins-1 and -4. In a second animal experiment, treatment with an NF-κB inhibitor, BAY 11-7085 (20 mg·kg−1·day−1 ip for 10 days), counteracted the effects of duodenal and mixed reflux on epithelial resistance and NF-κB-regulated cytokines. We conclude that gastroesophageal reflux activates the NF-κB pathway and impairs esophageal barrier function in mice and that targeting the NF-κB pathway may strengthen esophageal barrier function against reflux. PMID:23639809

  18. 1,2,3,3-Tetramethyl-7-nitro-3,4-dihydroisoquinolinium tetrafluoroborate

    Directory of Open Access Journals (Sweden)

    Mouna Bouzid

    2016-04-01

    Full Text Available The title salt, C13H17N2O2+·BF4−, was prepared by the methylation of the imine with Meerwein salt in dichloromethane. The asymmetric unit comprises a 1,3,3-trimethyl-7-nitro-3,4-dihydroisoquinolinium cation and a tetrafluoroborate anion. The coordination around the boron atom in the tetrafluoroborate anion is tetrahedral. The heterocyclic ring adopts a half-chair conformation. The crystal packing is governed by means of C—H...F contacts, which lead to the formation of a three-dimensional network.

  19. Protective Effect of 2-Dodecyl-6-Methoxycyclohexa-2, 5-Diene-1, 4-Dione, Isolated from Averrhoa Carambola L., Against Palmitic Acid-Induced Inflammation and Apoptosis in Min6 Cells by Inhibiting the TLR4-MyD88-NF-κB Signaling Pathway.

    Science.gov (United States)

    Xie, Qiuqiao; Zhang, Shijun; Chen, Chunxia; Li, Juman; Wei, Xiaojie; Xu, Xiaohui; Xuan, Feifei; Chen, Ning; Pham, Thithaihoa; Qin, Ni; He, Junhui; Ye, Fangxing; Huang, Wansu; Huang, Renbin; Wen, Qingwei

    2016-01-01

    Studies have demonstrated that 2-dodecyl-6-methoxycyclohexa-2, 5-diene-1, 4-dione (DMDD), isolated from the roots of Averrhoa carambola L., has significant therapeutic potential for the treatment of diabetes. However, the protective effect of DMDD against pancreatic beta cell dysfunction has never been reported. We investigated whether DMDD protected against palmitic acid-induced dysfunction in pancreatic β-cell line Min6 cells by attenuating the inflammatory response and apoptosis and to shed light on its possible mechanism. Cell viability was assessed by CCK-8. Glucose-stimulated insulin secretion levels and inflammatory cytokines levels were examined by ELISA. Apoptosis was assessed by Annexin V-FITC/PI Flow cytometry assay, Hoechst 33342/PI double-staining assay, and Transmission electron microscopy assay. Relative quantitative real-time PCR and western blot were used to determine the expressions of genes and proteins. Cell viability and glucose-stimulated insulin secretion levels were increased in DMDD-pretreated Min6 cells. DMDD inhibited inflammatory cytokines IL-6, TNF-α and MCP-1 generations in palmitic acid (PA)-induced Min6 cells. Moreover, DMDD protected against PA-induced Min6 cells apoptosis and the expression of Cleaved-Caspase-3, -8 and -9 were down-regulated and the Bcl-2/Bax ratio was increased in DMDD-pretreated Min6 cells. In addition, the expression of TLR4, MyD88 and NF-κB were down-regulated in DMDD-pretreated Min6 cells and TAK-242-pretreated group cells. DMDD protected Min6 cells against PA-induced dysfunction by attenuating the inflammatory response and apoptosis, and its mechanism of this protection was associated with inhibiting the TLR4-MyD88-NF-κB signaling pathway. © 2016 The Author(s) Published by S. Karger AG, Basel.

  20. Functional Toll-like receptor 4 expressed in lactotrophs mediates LPS-induced proliferation in experimental pituitary hyperplasia

    International Nuclear Information System (INIS)

    Sabatino, María Eugenia; Sosa, Liliana del Valle; Petiti, Juan Pablo; Mukdsi, Jorge Humberto; Mascanfroni, Iván Darío; Pellizas, Claudia Gabriela; Gutiérrez, Silvina; Torres, Alicia Inés; De Paul, Ana Lucía

    2013-01-01

    Toll like receptor 4 (TLR4) has been characterized for its ability to recognize bacterial endotoxin lipopolysaccharide (LPS). Considering that infections or inflammatory processes might contribute to the progression of pituitary tumors, we analyzed the TLR4 functional role by evaluating the LPS effect on lactotroph proliferation in primary cultures from experimental pituitary tumors, and examined the involvement of PI3K-Akt and NF-κB activation in this effect. In addition, the role of 17β-estradiol as a possible modulator of LPS-induced PRL cell proliferation was further investigated. In estrogen-induced hyperplasic pituitaries, LPS triggered lactotroph cell proliferation. However, endotoxin failed to increase the number of lactotrophs taking up BrdU in normal pituitaries. Moreover, incubation with anti-TLR4 antibody significantly reduced LPS-induced lactotroph proliferation, suggesting a functional role of this receptor. As a sign of TLR4 activation, an LPS challenge increased IL-6 release in normal and tumoral cells. By flow cytometry, TLR4 baseline expression was revealed at the plasma membrane of tumoral lactotrophs, without changes noted in the percentage of double PRL/TLR4 positive cells after LPS stimulus. Increases in TLR4 intracellular expression were detected as well as rises in CD14, p-Akt and NF-κB after an LPS challenge, as assessed by western blotting. The TLR4/PRL and PRL/NF-κB co-localization was also corroborated by immunofluorescence and the involvement of PI3K/Akt signaling in lactotroph proliferation and IL-6 release was revealed through the PI3K inhibitor Ly-294002. In addition, 17β-estradiol attenuated the LPS-evoked increase in tumoral lactotroph proliferation and IL-6 release. Collectively these results demonstrate the presence of functional TLR4 in lactotrophs from estrogen-induced hyperplasic pituitaries, which responded to the proliferative stimulation and IL-6 release induced by LPS through TLR4/CD14, with a contribution of the PI3K

  1. Functional Toll-like receptor 4 expressed in lactotrophs mediates LPS-induced proliferation in experimental pituitary hyperplasia

    Energy Technology Data Exchange (ETDEWEB)

    Sabatino, María Eugenia; Sosa, Liliana del Valle; Petiti, Juan Pablo; Mukdsi, Jorge Humberto [Centro de Microscopía Electrónica, Instituto de Investigaciones en Ciencias de la Salud (INICSA-CONICET), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Av. Enrique Barros y Enfermera Gordillo, Ciudad Universitaria, CP 5000, Córdoba (Argentina); Mascanfroni, Iván Darío; Pellizas, Claudia Gabriela [Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Av. Haya de la Torre y Medina Allende, Ciudad Universitaria, CP 5000, Córdoba (Argentina); Gutiérrez, Silvina; Torres, Alicia Inés [Centro de Microscopía Electrónica, Instituto de Investigaciones en Ciencias de la Salud (INICSA-CONICET), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Av. Enrique Barros y Enfermera Gordillo, Ciudad Universitaria, CP 5000, Córdoba (Argentina); De Paul, Ana Lucía, E-mail: adepaul@cmefcm.uncor.edu [Centro de Microscopía Electrónica, Instituto de Investigaciones en Ciencias de la Salud (INICSA-CONICET), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Av. Enrique Barros y Enfermera Gordillo, Ciudad Universitaria, CP 5000, Córdoba (Argentina)

    2013-11-15

    Toll like receptor 4 (TLR4) has been characterized for its ability to recognize bacterial endotoxin lipopolysaccharide (LPS). Considering that infections or inflammatory processes might contribute to the progression of pituitary tumors, we analyzed the TLR4 functional role by evaluating the LPS effect on lactotroph proliferation in primary cultures from experimental pituitary tumors, and examined the involvement of PI3K-Akt and NF-κB activation in this effect. In addition, the role of 17β-estradiol as a possible modulator of LPS-induced PRL cell proliferation was further investigated. In estrogen-induced hyperplasic pituitaries, LPS triggered lactotroph cell proliferation. However, endotoxin failed to increase the number of lactotrophs taking up BrdU in normal pituitaries. Moreover, incubation with anti-TLR4 antibody significantly reduced LPS-induced lactotroph proliferation, suggesting a functional role of this receptor. As a sign of TLR4 activation, an LPS challenge increased IL-6 release in normal and tumoral cells. By flow cytometry, TLR4 baseline expression was revealed at the plasma membrane of tumoral lactotrophs, without changes noted in the percentage of double PRL/TLR4 positive cells after LPS stimulus. Increases in TLR4 intracellular expression were detected as well as rises in CD14, p-Akt and NF-κB after an LPS challenge, as assessed by western blotting. The TLR4/PRL and PRL/NF-κB co-localization was also corroborated by immunofluorescence and the involvement of PI3K/Akt signaling in lactotroph proliferation and IL-6 release was revealed through the PI3K inhibitor Ly-294002. In addition, 17β-estradiol attenuated the LPS-evoked increase in tumoral lactotroph proliferation and IL-6 release. Collectively these results demonstrate the presence of functional TLR4 in lactotrophs from estrogen-induced hyperplasic pituitaries, which responded to the proliferative stimulation and IL-6 release induced by LPS through TLR4/CD14, with a contribution of the PI3K

  2. Curcumin improves prostanoid ratio in diabetic mesenteric arteries associated with cyclooxygenase-2 and NF-κB suppression

    Directory of Open Access Journals (Sweden)

    Patumraj S

    2010-12-01

    Full Text Available Sirada Rungseesantivanon1, Naris Thengchaisri4, Preecha Ruangvejvorachai2, Suthiluk Patumraj31Interdepartment of Physiology, Graduate School, 2Department of Pathology, 3Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; 4Department of Companion Animal Clinical Sciences, Faculty of Veterinary Medicine, Kasetsart University, Bangkok, ThailandBackground: Curcumin, the active ingredient from turmeric rhizomes, has been shown to have a wide range of pharmacological properties including antioxidant and anti-inflammatory effects. Curcumin has been reviewed for its multiple molecular action on inhibiting tumor angiogenesis via its mechanisms of cyclooxygenase (COX-2, and vascular endothelial growth factor (VEGF inhibition. In this present study, we aimed to assess the effects of curcumin on preventing diabetes-induced vascular dysfunction in association with COX-2, nuclear factor-κB (NF-κB expression, and prostanoid production.Methods: Twelve-week-old male Wistar rats were separated into five groups: 1 diabetes with 0.9% normal saline (DM-NSS; n = 10, 2 diabetes treated with curcumin 30 mg/kg (n = 10, 3 diabetes treated with curcumin 300 mg/kg (n = 10, 4 the control with 0.9% normal saline (n = 10, and 5 the control treated with 300 mg/kg (n = 10. Daily oral feeding of curcumin was started at 6 weeks after the streptozotocin injection. Levels of 6-keto prostaglandin (PG F1α and thromboxane (TX B2 were determined from mesenteric perfusates using enzyme immunoassay kits. Protein kinase C (PKC-ßII and COX-2 with NF-κB levels were analyzed in the mesenteric arteries by immunofluorescent staining and immunohistochemistry, respectively.Results: The ratio of 6-keto-PGF1α and TXB2 was significantly decreased in DM-NSS compared with the control (P < 0.05. Double-immunofluorescent staining with specific antibodies for PKC-βII and a-smooth muscle actins showed that the diabetic mesenteric arteries contained increased

  3. Young's modulus of BF wood material by longitudinal vibration

    International Nuclear Information System (INIS)

    Phadke, Sushil; Shrivastava, Bhakt Darshan; Mishra, Ashutosh; Dagaonkar, N

    2014-01-01

    All engineered structures are designed and built with consideration of resisting the same fundamental forces of tension, compression, shear, bending and torsion. Structural design is a balance of these internal and external forces. So, it is interesting to calculate the Young's moduli of Borassus Flabellifier BF wood are quite important from the application point of view. The ultrasonic waves are closely related with the elastic and inelastic properties of the materials. In the present study, we measured longitudinal wave ultrasonic velocities in BF wood material by longitudinal vibration method. After measuring ultrasonic velocity in BF wood material, we calculated Young's modulus of Borassus Flabellifier BF wood material. We used ultrasonic interferometer for measuring longitudinal wave ultrasonic velocity in BF wood material made by Mittal Enterprises, New Delhi, India in our laboratory. Borassus Flabellifier BF wood material was collected from Dhar district of Madhya Pradesh, India.

  4. Troxerutin protects against 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47)-induced liver inflammation by attenuating oxidative stress-mediated NAD{sup +}-depletion

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Zi-Feng [School of Environment Science and Spatial Informatics, China University of Mining and Technology, Xuzhou 221008, Jiangsu Province (China); Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, 101 Shanghai Road, Xuzhou 221116, Jiangsu Province (China); Zhang, Yan-qiu [School of Environment Science and Spatial Informatics, China University of Mining and Technology, Xuzhou 221008, Jiangsu Province (China); Fan, Shao-Hua [Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, 101 Shanghai Road, Xuzhou 221116, Jiangsu Province (China); Zhuang, Juan [School of Environment Science and Spatial Informatics, China University of Mining and Technology, Xuzhou 221008, Jiangsu Province (China); Zheng, Yuan-Lin, E-mail: ylzheng@jsnu.edu.cn [Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, 101 Shanghai Road, Xuzhou 221116, Jiangsu Province (China); Lu, Jun; Wu, Dong-Mei; Shan, Qun; Hu, Bin [Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, 101 Shanghai Road, Xuzhou 221116, Jiangsu Province (China)

    2015-02-11

    Highlights: • BDE-47 promotes liver inflammation by triggering oxidative stress-induced NAD{sup +} depletion. • Troxerutin inhibits BDE-47-induced liver inflammation via its antioxidant properties. • Troxerutin restores NAD{sup +} level and consequently abates SirT1 loss. • Troxerutin represses acetylation of NF-κB p65 (K310) and H3K9. • Troxerutin is a candidate for prevention and therapy of BDE-47-induced hepatotoxicity. - Abstract: Emerging evidence indicates that 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) induces liver injury through enhanced ROS production and lymphocytic infiltration, which may promote a liver inflammatory response. Antioxidants have been reported to attenuate the cellular toxicity associated with polybrominated diphenyl ethers (PBDEs). In this study, we investigated the effect of troxerutin, a trihydroxyethylated derivative of the natural bioflavonoid rutin, on BDE-47-induced liver inflammation and explored the potential mechanisms underlying this effect. Our results showed that NAD{sup +}-depletion was involved in the oxidative stress-mediated liver injury in a BDE-47 treated mouse model, which was confirmed by Vitamin E treatment. Furthermore, our data revealed that troxerutin effectively alleviated liver inflammation by mitigating oxidative stress-mediated NAD{sup +}-depletion in BDE-47 treated mice. Consequently, troxerutin remarkably restored SirT1 protein expression and activity in the livers of BDE-47-treated mice. Mechanistically, troxerutin dramatically repressed the nuclear translocation of NF-κB p65 and the acetylation of NF-κB p65 (Lys 310) and Histone H3 (Lys9) to abate the transcription of inflammatory genes in BDE-47-treated mouse livers. These inhibitory effects of troxerutin were markedly blunted by EX527 (SirT1 inhibitor) treatment. This study provides novel mechanistic insights into the toxicity of BDE-47 and indicates that troxerutin might be used in the prevention and therapy of BDE-47-induced

  5. Scaffold protein JLP mediates TCR-initiated CD4+T cell activation and CD154 expression.

    Science.gov (United States)

    Yan, Qi; Yang, Cheng; Fu, Qiang; Chen, Zhaowei; Liu, Shan; Fu, Dou; Rahman, Rahmat N; Nakazato, Ryota; Yoshioka, Katsuji; Kung, Sam K P; Ding, Guohua; Wang, Huiming

    2017-07-01

    CD4 + T-cell activation and its subsequent induction of CD154 (CD40 ligand, CD40L) expression are pivotal in shaping both the humoral and cellular immune responses. Scaffold protein JLP regulates signal transduction pathways and molecular trafficking inside cells, thus represents a critical component in maintaining cellular functions. Its role in regulating CD4 + T-cell activation and CD154 expression, however, is unclear. Here, we demonstrated expression of JLP in mouse tissues of lymph nodes, thymus, spleen, and also CD4 + T cells. Using CD4+ T cells from jlp-deficient and jlp-wild-type mice, we demonstrated that JLP-deficiency impaired T-cell proliferation, IL-2 production, and CD154 induction upon TCR stimulations, but had no impacts on the expression of other surface molecules such as CD25, CD69, and TCR. These observed impaired T-cell functions in the jlp-/- CD4 + T cells were associated with defective NF-AT activation and Ca 2 + influx, but not the MAPK, NF-κB, as well as AP-1 signaling pathways. Our findings indicated that, for the first time, JLP plays a critical role in regulating CD4 + T cells response to TCR stimulation partly by mediating the activation of TCR-initiated Ca 2+ /NF-AT. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. The Arabidopsis NF-YA3 and NF-YA8 genes are functionally redundant and are required in early embryogenesis.

    Directory of Open Access Journals (Sweden)

    Monica Fornari

    Full Text Available Nuclear factor Y (NF-Y is a trimeric transcription factor composed of three distinct subunits called NF-YA, NF-YB and NF-YC. In Arabidopsis thaliana, NF-Y subunits are known to play roles in many processes, such as gametogenesis, embryogenesis, seed development, drought resistance, ABA signaling, flowering time, primary root elongation, Endoplasmic Reticulum (ER stress response and blue light responses. Here, we report that the closely related NF-YA3 and NF-YA8 genes control early embryogenesis. Detailed GUS and in situ analyses showed that NF-YA3 and NF-YA8 are expressed in vegetative and reproductive tissues with the highest expression being during embryo development from the globular to the torpedo embryo stage. Plants from the nf-ya3 and nf-ya8 single mutants do not display any obvious phenotypic alteration, whereas nf-ya3 nf-ya8 double mutants are embryo lethal. Morphological analyses showed that the nf-ya3 nf-ya8 embryos fail to undergo to the heart stage and develop into abnormal globular embryos with both proembryo and suspensor characterized by a disordered cell cluster with an irregular shape, suggesting defects in embryo development. The suppression of both NF-YA3 and NF-YA8 gene expression by RNAi experiments resulted in defective embryos that phenocopied the nf-ya3 nf-ya8 double mutants, whereas complementation experiments partially rescued the abnormal globular nf-ya3 nf-ya8 embryos, confirming that NF-YA3 and NF-YA8 are required in early embryogenesis. Finally, the lack of GFP expression of the auxin responsive DR5rev::GFP marker line in double mutant embryos suggested that mutations in both NF-YA3 and NF-YA8 affect auxin response in early developing embryos. Our findings indicate that NF-YA3 and NF-YA8 are functionally redundant genes required in early embryogenesis of Arabidopsis thaliana.

  7. No amelioration of uromodulin maturation and trafficking defect by sodium 4-phenylbutyrate in vivo: studies in mouse models of uromodulin-associated kidney disease.

    Science.gov (United States)

    Kemter, Elisabeth; Sklenak, Stefanie; Rathkolb, Birgit; Hrabě de Angelis, Martin; Wolf, Eckhard; Aigner, Bernhard; Wanke, Ruediger

    2014-04-11

    Uromodulin (UMOD)-associated kidney disease (UAKD) belongs to the hereditary progressive ER storage diseases caused by maturation defects of mutant UMOD protein. Current treatments of UAKD patients are symptomatic and cannot prevent disease progression. Two in vitro studies reported a positive effect of the chemical chaperone sodium 4-phenylbutyrate (4-PBA) on mutant UMOD maturation. Thus, 4-PBA was suggested as a potential treatment for UAKD. This study evaluated the effects of 4-PBA in two mouse models of UAKD. In contrast to previous in vitro studies, treatment with 4-PBA did not increase HSP70 expression or improve maturation and trafficking of mutant UMOD in vivo. Kidney function of UAKD mice was actually deteriorated by 4-PBA treatment. In transfected tubular epithelial cells, 4-PBA did not improve maturation but increased the expression level of both mutant and wild-type UMOD protein. Activation of NF-κB pathway in thick ascending limb of Henle's loop cells of UAKD mice was detected by increased abundance of RelB and phospho-IκB kinase α/β, an indirect activator of NF-κB. Furthermore, the abundance of NF-κB1 p105/p50, NF-κB2 p100/p52, and TRAF2 was increased in UAKD. NF-κB activation was identified as a novel disease mechanism of UAKD and might be a target for therapeutic intervention.

  8. Troxerutin protects against 2,2',4,4'-tetrabromodiphenyl ether (BDE-47)-induced liver inflammation by attenuating oxidative stress-mediated NAD⁺-depletion.

    Science.gov (United States)

    Zhang, Zi-Feng; Zhang, Yan-Qiu; Fan, Shao-Hua; Zhuang, Juan; Zheng, Yuan-Lin; Lu, Jun; Wu, Dong-Mei; Shan, Qun; Hu, Bin

    2015-01-01

    Emerging evidence indicates that 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) induces liver injury through enhanced ROS production and lymphocytic infiltration, which may promote a liver inflammatory response. Antioxidants have been reported to attenuate the cellular toxicity associated with polybrominated diphenyl ethers (PBDEs). In this study, we investigated the effect of troxerutin, a trihydroxyethylated derivative of the natural bioflavonoid rutin, on BDE-47-induced liver inflammation and explored the potential mechanisms underlying this effect. Our results showed that NAD(+)-depletion was involved in the oxidative stress-mediated liver injury in a BDE-47 treated mouse model, which was confirmed by Vitamin E treatment. Furthermore, our data revealed that troxerutin effectively alleviated liver inflammation by mitigating oxidative stress-mediated NAD(+)-depletion in BDE-47 treated mice. Consequently, troxerutin remarkably restored SirT1 protein expression and activity in the livers of BDE-47-treated mice. Mechanistically, troxerutin dramatically repressed the nuclear translocation of NF-κB p65 and the acetylation of NF-κB p65 (Lys 310) and Histone H3 (Lys9) to abate the transcription of inflammatory genes in BDE-47-treated mouse livers. These inhibitory effects of troxerutin were markedly blunted by EX527 (SirT1 inhibitor) treatment. This study provides novel mechanistic insights into the toxicity of BDE-47 and indicates that troxerutin might be used in the prevention and therapy of BDE-47-induced hepatotoxicity. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Suppression of TLR4-mediated inflammatory response by macrophage class A scavenger receptor (CD204)

    Energy Technology Data Exchange (ETDEWEB)

    Ohnishi, Koji; Komohara, Yoshihiro; Fujiwara, Yukio; Takemura, Kenichi [Department of Cell Pathology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan); Lei, XiaoFeng [Department of Cell Pathology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan); Department of Biochemistry, Showa University School of Medicine, Tokyo (Japan); Nakagawa, Takenobu [Department of Cell Pathology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan); Sakashita, Naomi [Department of Cell Pathology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan); Department of Human Pathology, Institute of Health Biosciences, The University of Tokushima, Tokushima (Japan); Takeya, Motohiro, E-mail: takeya@kumamoto-u.ac.jp [Department of Cell Pathology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan)

    2011-08-05

    Highlights: {yields} We focused on the interaction between SR-A and TLR4 signaling in this study. {yields} SR-A deletion promoted NF{kappa}B activation in macrophages in septic model mouse. {yields} SR-A suppresses both MyD88-dependent and -independent TLR4 signaling in vitro. {yields} SR-A clears LPS binding to TLR4 which resulting in the suppression of TLR4 signals. -- Abstract: The class A scavenger receptor (SR-A, CD204), one of the principal receptors expressed on macrophages, has been found to regulate inflammatory response and attenuate septic endotoxemia. However, the detailed mechanism of this process has not yet been well characterized. To clarify the regulative mechanisms of lipopolysaccharide (LPS)-induced macrophage activation by SR-A, we evaluated the activation of Toll-like receptor 4 (TLR4)-mediated signaling molecules in SR-A-deficient (SR-A{sup -/-}) macrophages. In a septic shock model, the blood levels of tumor necrosis factor (TNF)-{alpha}, interleukin (IL)-6 and interferon (IFN)-{beta} were significantly increased in SR-A{sup -/-} mice compared to wild-type mice, and elevated nuclear factor kappa B (NF{kappa}B) activation was detected in SR-A{sup -/-} macrophages. SR-A deletion increased the production of pro-inflammatory cytokines, and the phosphorylation of mitogen-activated protein kinase (MAPK) and NF{kappa}B in vitro. SR-A deletion also promoted the nuclear translocation of NF{kappa}B and IFN regulatory factor (IRF)-3. In addition, a competitive binding assay with acetylated low-density lipoprotein, an SR-A-specific ligand, and anti-SR-A antibody induced significant activation of TLR4-mediated signaling molecules in wild-type macrophages but not in SR-A{sup -/-} macrophages. These results suggest that SR-A suppresses the macrophage activation by inhibiting the binding of LPS to TLR4 in a competitive manner and it plays a pivotal role in the regulation of the LPS-induced inflammatory response.

  10. AMT1;1 transgenic rice plants with enhanced NH4(+) permeability show superior growth and higher yield under optimal and suboptimal NH4(+) conditions.

    Science.gov (United States)

    Ranathunge, Kosala; El-Kereamy, Ashraf; Gidda, Satinder; Bi, Yong-Mei; Rothstein, Steven J

    2014-03-01

    The major source of nitrogen for rice (Oryza sativa L.) is ammonium (NH4(+)). The NH4(+) uptake of roots is mainly governed by membrane transporters, with OsAMT1;1 being a prominent member of the OsAMT1 gene family that is known to be involved in NH4(+) transport in rice plants. However, little is known about its involvement in NH4(+) uptake in rice roots and subsequent effects on NH4(+) assimilation. This study shows that OsAMT1;1 is a constitutively expressed, nitrogen-responsive gene, and its protein product is localized in the plasma membrane. Its expression level is under the control of circadian rhythm. Transgenic rice lines (L-2 and L-3) overexpressing the OsAMT1;1 gene had the same root structure as the wild type (WT). However, they had 2-fold greater NH4(+) permeability than the WT, whereas OsAMT1;1 gene expression was 20-fold higher than in the WT. Analogous to the expression, transgenic lines had a higher NH4(+) content in the shoots and roots than the WT. Direct NH4(+) fluxes in the xylem showed that the transgenic lines had significantly greater uptake rates than the WT. Higher NH4(+) contents also promoted higher expression levels of genes in the nitrogen assimilation pathway, resulting in greater nitrogen assimilates, chlorophyll, starch, sugars, and grain yield in transgenic lines than in the WT under suboptimal and optimal nitrogen conditions. OsAMT1;1 also enhanced overall plant growth, especially under suboptimal NH4(+) levels. These results suggest that OsAMT1;1 has the potential for improving nitrogen use efficiency, plant growth, and grain yield under both suboptimal and optimal nitrogen fertilizer conditions.

  11. AMT1;1 transgenic rice plants with enhanced NH4 + permeability show superior growth and higher yield under optimal and suboptimal NH4 + conditions

    Science.gov (United States)

    Rothstein, Steven J.

    2014-01-01

    The major source of nitrogen for rice (Oryza sativa L.) is ammonium (NH4 +). The NH4 + uptake of roots is mainly governed by membrane transporters, with OsAMT1;1 being a prominent member of the OsAMT1 gene family that is known to be involved in NH4 + transport in rice plants. However, little is known about its involvement in NH4 + uptake in rice roots and subsequent effects on NH4 + assimilation. This study shows that OsAMT1;1 is a constitutively expressed, nitrogen-responsive gene, and its protein product is localized in the plasma membrane. Its expression level is under the control of circadian rhythm. Transgenic rice lines (L-2 and L-3) overexpressing the OsAMT1;1 gene had the same root structure as the wild type (WT). However, they had 2-fold greater NH4 + permeability than the WT, whereas OsAMT1;1 gene expression was 20-fold higher than in the WT. Analogous to the expression, transgenic lines had a higher NH4 + content in the shoots and roots than the WT. Direct NH4 + fluxes in the xylem showed that the transgenic lines had significantly greater uptake rates than the WT. Higher NH4 + contents also promoted higher expression levels of genes in the nitrogen assimilation pathway, resulting in greater nitrogen assimilates, chlorophyll, starch, sugars, and grain yield in transgenic lines than in the WT under suboptimal and optimal nitrogen conditions. OsAMT1;1 also enhanced overall plant growth, especially under suboptimal NH4 + levels. These results suggest that OsAMT1;1 has the potential for improving nitrogen use efficiency, plant growth, and grain yield under both suboptimal and optimal nitrogen fertilizer conditions. PMID:24420570

  12. Molecular cloning, structural analysis and expression of complement component Bf/C2 genes in the nurse shark, Ginglymostoma cirratum.

    Science.gov (United States)

    Shin, Dong-Ho; Webb, Barbara; Nakao, Miki; Smith, Sylvia L

    2007-01-01

    Factor B and C2 are serine proteases that provide the catalytic subunits of C3 and C5 convertases of the alternative (AP) and classical (CP) complement pathways. Two Bf/C2 cDNAs, GcBf/C2-1 and -2 (previously referred to as nsBf/C2-A and nsBf/C2-B), were isolated from the nurse shark, Ginglymostoma cirratum. GcBf/C2-1 and -2 are 3364 and 3082bp in length and encode a leader peptide, three CCPs, one VWFA, the serine protease domain and have a putative factor D/C1s/MASP cleavage site. Southern blots show that there might be up to two Bf/C2-like genes for each of the two GcBf/C2 isoforms. GcBf/C2-1 and -2 are constitutively expressed, albeit at different levels, in all nine tissues examined. Expression in erythrocytes is a novel finding. Structural analysis has revealed that the localization of glycosylation sites in the SP domain of both putative proteins indicates that the molecular organization of the shark molecules is more like C2 than factor B. Phylogenetic analysis indicates that GcBf/C2-1 and -2 and TrscBf of Triakis scyllia (another shark species) originated from a common ancestor and share a remote ancestor with Bf and C2 of mammals and bony fish.

  13. Superacid Catalyzed Depolymerization and Conversion of Coals. Final Technical Report. [HF:BF{sub 2}/H{sub 2}

    Science.gov (United States)

    Olah, G.

    1980-01-01

    We were interested in applying superacid catalyzed cleavage-depolymerization and ionic hydrogenation low temperature conversion of coal to liquid hydrocarbon, as well as obtaining information about the reactions involved and the structure of intermediates of the coal liquefaction process. In order to show the feasibility of our proposed research we have carried out preliminary investigation in these areas. Preceding our work there was no practical application of a superacid system to coal liquefaction. We carried out an extensive study of the potential of the HF:BF{sub 3}/H{sub 2} system for coal hydroliquefaction. Under varying conditions of reactant ratio, reaction time and temperature, we were able to obtain over 95% pyridine extractible product by treating coal in HF:BF{sub 3}:H{sub 2} system at approx. 100 degrees C for 4 hours. The coal to acid ratio was 1:5 and FB{sub 3} at 900 psi and H{sub 2} at 500 psi were used. These are extremely encouraging results in that the conditions used are drastically milder than those used in any known process, such as Exxon donor solvent and related processes. The cyclohexane extractibility of the treated coal was as high as 27% and the yield of liquid distillate at 400 degrees C/5 x 10{sup -3}/sup torr/ was approx. 30%. The infrared spectrum of product coal, extracts and distillates were distinctly different from the starting coal and show a significant increase in the amount of saturates. The {sup 1}H NMR spectrum of cyclohexane extract of the treated coal shows essentially all aliphatic photons. The spectra of other treated coal extracts show increased amounts and types of aliphatic protons as well as significant amounts of protons bound to unsaturated sites. This again indicates that the HF-BF{sub 3} system is depolymerizing the coal to small fragments which are soluble in non-polar solvents.

  14. Polydatin Protects Rat Liver against Ethanol-Induced Injury: Involvement of CYP2E1/ROS/Nrf2 and TLR4/NF-κB p65 Pathway

    Directory of Open Access Journals (Sweden)

    Qiong-Hui Huang

    2017-01-01

    Full Text Available Excessive alcohol consumption leads to serious liver injury, associating with oxidative stress and inflammatory response. Previous study has demonstrated that polydatin (PD exerted antioxidant and anti-inflammatory effects and attenuated ethanol-induced liver damage, but the research remained insufficient. Hence, this experiment aimed to evaluate the hepatoprotective effect and potential mechanisms of PD on ethanol-induced hepatotoxicity. Our results showed that PD pretreatment dramatically decreased the levels of alanine aminotransferase (ALT, aspartate aminotransferase (AST, alkaline phosphatase (ALP, and lactate dehydrogenase (LDH in the serum, suppressed the malonaldehyde (MDA and triglyceride (TG content and the production of reactive oxygen species (ROS, and enhanced the activities of superoxide dismutase (SOD, glutathione peroxidase (GSH-Px, catalase (CAT, andalcohol dehydrogenase (ADH, and aldehyde dehydrogenase (ALDH, paralleled by an improvement of histopathology alterations. The protective effect of PD against oxidative stress was probably associated with downregulation of cytochrome P450 2E1 (CYP2E1 and upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2 and its target gene haem oxygenase-1 (HO-1. Moreover, PD inhibited the release of proinflammatory cytokines (TNF-α, IL-1β, and IL-6 via downregulating toll-like receptor 4 (TLR4 and nuclear factor kappa B (NF-κB p65. To conclude, PD pretreatment protects against ethanol-induced liver injury via suppressing oxidative stress and inflammation.

  15. Relationship between child epilepsy and MRI findings in von Recklinghausen Neurofibromatosis (NF 1)

    International Nuclear Information System (INIS)

    Yasujima, Hidehiro; Komatsu, Mikio; Sakurai, Takashi; Kodama, Soichi

    1994-01-01

    Fourteen children meeting the NIH consensus diagnostic criteria for NF 1 were evaluated at the Department of Pediatrics, Himeji Red Cross Hospital. MRI and EEG were examined in all patients, respectively. Four of 14 patients had a history of epilepsy, two had suffered West syndrome, one had complex partial seizures and one had secondary generalized partial epilepsy. Seven (50%) of 14 patients showed abnormal MRI; three (75%) of 4 patients with epilepsy and four (40%) of 10 patients with epilepsy showed low intensity on T 1 -weighted images and hyperintensity on T 2 -weighted images in the globus pallidus and brain stem. These results suggest that children with NF 1 have a spectrum of MRI abnormalities, irrespective of existence of epilepsy. (author)

  16. Dicty_cDB: Contig-U01510-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available .4 1 ( BE248608 ) NF021H01DT1F1013 Drought Medicago truncatula cDNA... 42 6.4 1 ( BE205651 ) AOB130 Onion seedling leaf cDNA library...-41B2_Sp6.1 CH216 Xenopus (Silurana) tropica... 42 6.4 1 ( CG770475 ) TcB41.2_F05_SP6 Tribolium BAC library ...ed ... 44 1.6 1 ( CK424003 ) AUF_IpSto_10_c04 Stomach cDNA library Ictalurus p........ 42 6.4 1 ( EI465423 ) PV_GBa0071A02.f PV_GBa Phaseolus vulgaris genomic... 42 6.4 1 ( ED568449 ) SBA034_G14.f Sugar beet BAC libra...ago trunca... 42 6.4 1 ( BF650883 ) NF097E12EC1F1097 Elicited cell culture Medicago t... 42 6.4 1 (

  17. Effects of curcumin on antioxidative activities and cytokine production in Jian carp (Cyprinus carpio var. Jian) with CCl4-induced liver damage.

    Science.gov (United States)

    Cao, Liping; Ding, Weidong; Du, Jingliang; Jia, Rui; Liu, Yingjuan; Zhao, Caiyuan; Shen, Yujin; Yin, Guojun

    2015-03-01

    We investigated the protective effects of curcumin on liver-damaged Cyprinus carpio var. Jian (Jian carp). The carp were fed 0.1%, 0.5%, or 1.0% curcumin for 60 days, then injected intraperitoneally with 30% carbon tetrachloride solution. Liver and blood samples were collected to measure the liver index, serum- and liver-associated enzymes, liver histology, nuclear factor-κB (NF-κB)/c-Rel, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and IL-12 mRNA expression, and the level of NF-κB/c-Rel protein in the liver, and for a comet assay. We found that 0.5% and 1.0% curcumin significantly reduced the CCl(4)-induced increase in the liver index. The comet assay showed that the tail moment, olive tail moment, tail length, and tail DNA% improved in fish pretreated with 0.5 or 1.0% curcumin. CCl(4)-induced histological changes, including extensive hepatocyte degeneration, indistinct cell borders, nuclear condensation, and karyolysis were clearly reduced after treatment with 0.5% and 1.0% curcumin. Moreover, 0.5% and 1.0% curcumin significantly inhibited the CCl(4)-induced increase in serum glutamic oxaloacetic transaminase and promoted the restoration of superoxide dismutase in the liver; 1.0% curcumin significantly reduced serum glutamic pyruvic transaminase and lactate dehydrogenase and hepatic malondialdehyde, but significantly increased the total antioxidant capacity and glutathione levels in the liver. The CCl(4)-induced upregulation of NF-κB/c-Rel, IL-1β, and TNF-α mRNAs and NF-κB/c-Rel protein levels was inhibited by 0.5% and 1.0% curcumin, and IL-12 mRNA was reduced by all three doses of curcumin. The effects of curcumin on the liver index, enzymes, histological changes, and cytokines were dose-dependent. Our results indicate that curcumin reduces CCl(4)-induced liver damage in Jian carp by upregulating antioxidative activities and inhibiting NF-κB, IL-1β, TNF-α, and IL-12 expression. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Pepsin Digest of Wheat Gliadin Fraction Increases Production of IL-1β via TLR4/MyD88/TRIF/MAPK/NF-κB Signaling Pathway and an NLRP3 Inflammasome Activation

    Science.gov (United States)

    Palová-Jelínková, Lenka; Dáňová, Klára; Drašarová, Hana; Dvořák, Miloš; Funda, David P.; Fundová, Petra; Kotrbová-Kozak, Anna; Černá, Marie; Kamanová, Jana; Martin, Stefan F.; Freudenberg, Marina; Tučková, Ludmila

    2013-01-01

    Celiac disease (CD) is a gluten-responsive, chronic inflammatory enteropathy. IL-1 cytokine family members IL-1β and IL-18 have been associated with the inflammatory conditions in CD patients. However, the mechanisms of IL-1 molecule activation in CD have not yet been elucidated. We show in this study that peripheral blood mononuclear cells (PBMC) and monocytes from celiac patients responded to pepsin digest of wheat gliadin fraction (PDWGF) by a robust secretion of IL-1β and IL-1α and a slightly elevated production of IL-18. The analysis of the upstream mechanisms underlying PDWGF-induced IL-1β production in celiac PBMC show that PDWGF-induced de novo pro-IL-1β synthesis, followed by a caspase-1 dependent processing and the secretion of mature IL-1β. This was promoted by K+ efflux and oxidative stress, and was independent of P2X7 receptor signaling. The PDWGF-induced IL-1β release was dependent on Nod-like receptor family containing pyrin domain 3 (NLRP3) and apoptosis-associated speck like protein (ASC) as shown by stimulation of bone marrow derived dendritic cells (BMDC) from NLRP3−/− and ASC−/− knockout mice. Moreover, treatment of human PBMC as well as MyD88−/− and Toll-interleukin-1 receptor domain-containing adaptor-inducing interferon-β (TRIF)−/− BMDC illustrated that prior to the activation of caspase-1, the PDWGF-triggered signal constitutes the activation of the MyD88/TRIF/MAPK/NF-κB pathway. Moreover, our results indicate that the combined action of TLR2 and TLR4 may be required for optimal induction of IL-1β in response to PDWGF. Thus, innate immune pathways, such as TLR2/4/MyD88/TRIF/MAPK/NF-κB and an NLRP3 inflammasome activation are involved in wheat proteins signaling and may play an important role in the pathogenesis of CD. PMID:23658628

  19. Neuronal RING finger protein 11 (RNF11 regulates canonical NF-κB signaling

    Directory of Open Access Journals (Sweden)

    Pranski Elaine L

    2012-04-01

    Full Text Available Abstract Background The RING domain-containing protein RING finger protein 11 (RNF11 is a member of the A20 ubiquitin-editing protein complex and modulates peripheral NF-κB signaling. RNF11 is robustly expressed in neurons and colocalizes with a population of α-synuclein-positive Lewy bodies and neurites in Parkinson disease patients. The NF-κB pathway has an important role in the vertebrate nervous system, where the absence of NF-κB activity during development can result in learning and memory deficits, whereas chronic NF-κB activation is associated with persistent neuroinflammation. We examined the functional role of RNF11 with respect to canonical NF-κB signaling in neurons to gain understanding of the tight association of inflammatory pathways, including NF-κB, with the pathogenesis of neurodegenerative diseases. Methods and results Luciferase assays were employed to assess NF-κB activity under targeted short hairpin RNA (shRNA knockdown of RNF11 in human neuroblastoma cells and murine primary neurons, which suggested that RNF11 acts as a negative regulator of canonical neuronal NF-κB signaling. These results were further supported by analyses of p65 translocation to the nucleus following depletion of RNF11. Coimmunoprecipitation experiments indicated that RNF11 associates with members of the A20 ubiquitin-editing protein complex in neurons. Site-directed mutagenesis of the myristoylation domain, which is necessary for endosomal targeting of RNF11, altered the impact of RNF11 on NF-κB signaling and abrogated RNF11’s association with the A20 ubiquitin-editing protein complex. A partial effect on canonical NF-κB signaling and an association with the A20 ubiquitin-editing protein complex was observed with mutagenesis of the PPxY motif, a proline-rich region involved in Nedd4-like protein interactions. Last, shRNA-mediated reduction of RNF11 in neurons and neuronal cell lines elevated levels of monocyte chemoattractant protein 1 and

  20. Toll-like receptor 4 signaling in neurons of trigeminal ganglion contributes to nociception induced by acute pulpitis in rats.

    Science.gov (United States)

    Lin, Jia-Ji; Du, Yi; Cai, Wen-Ke; Kuang, Rong; Chang, Ting; Zhang, Zhuo; Yang, Yong-Xiang; Sun, Chao; Li, Zhu-Yi; Kuang, Fang

    2015-07-30

    Pain caused by acute pulpitis (AP) is a common symptom in clinical settings. However, its underlying mechanisms have largely remained unknown. Using AP model, we demonstrated that dental injury caused severe pulp inflammation with up-regulated serum IL-1β. Assessment from head-withdrawal reflex thresholds (HWTs) and open-field test demonstrated nociceptive response at 1 day post injury. A consistent up-regulation of Toll-like receptor 4 (TLR4) in the trigeminal ganglion (TG) ipsilateral to the injured pulp was found; and downstream signaling components of TLR4, including MyD88, TRIF and NF-κB, and cytokines such as TNF-α and IL-1β, were also increased. Retrograde labeling indicated that most TLR4 positve neuron in the TG innnervated the pulp and TLR4 immunoreactivity was mainly in the medium and small neurons. Double labeling showed that the TLR4 expressing neurons in the ipsilateral TG were TRPV1 and CGRP positive, but IB4 negative. Furthermore, blocking TLR4 by eritoran (TLR4 antagonist) in TGs of the AP model significantly down-regulated MyD88, TRIF, NF-κB, TNF-α and IL-1β production and behavior of nociceptive response. Our findings suggest that TLR4 signaling in TG cells, particularly the peptidergic TRPV1 neurons, plays a key role in AP-induced nociception, and indicate that TLR4 signaling could be a potential therapeutic target for orofacial pain.

  1. Emodin Protects Against Concanavalin A-Induced Hepatitis in Mice Through Inhibiting Activation of the p38 MAPK-NF-κB Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Jihua Xue

    2015-03-01

    Full Text Available Background/Aims: To investigate the effects of emodin on concanavalin A (Con A-induced hepatitis in mice and to elucidate its underlying molecular mechanisms. Methods: A fulminant hepatitis model was established successfully by the intravenous administration of Con A (20 mg/kg to male Balb/c mice. Emodin was administered to the mice by gavage before and after Con A injection. The levels of pro-inflammatory cytokines and chemokines, numbers of CD4+ and F4/80+ cells infiltrated into the liver, and amounts of phosphorylated p38 MAPK and NF-γB in mouse livers and RAW264.7 and EL4 cells were measured. Results: Pretreatment with emodin significantly protected the animals from T cell-mediated hepatitis, as shown by the decreased elevations of serum alanine aminotransferase (ALT and aspartate aminotransferase (AST, as well as reduced hepatic necrosis. In addition, emodin pretreatment markedly reduced the intrahepatic expression of pro-inflammatory cytokines and chemokines, including tumor necrosis factor (TNF-a, interferon (IFN-γ, interleukin (IL-1ß, IL-6, IL-12, inducible nitric oxide synthase (iNOS, integrin alpha M (ITGAM, chemokine (C-C motif ligand 2 (CCL2, macrophage inflammatory protein 2 (MIP-2 and chemokine (CXC motif receptor 2 (CXCR2. Furthermore, emodin pretreatment dramatically suppressed the numbers of CD4+ and F4/80+ cells infiltrating into the liver as well as the activation of p38 MAPK and NF-γB in Con A-treated mouse livers and RAW264.7 and EL4 cells. Conclusion: The results indicate that emodin pretreatment protects against Con A-induced liver injury in mice; these beneficial effects may occur partially through inhibition of both the infiltration of CD4+ and F4/80+ cells and the activation of the p38 MAPK-NF-γB pathway in CD4+ T cells and macrophages.

  2. Plant-derived SAC domain of PAR-4 (Prostate Apoptosis Response 4 exhibits growth inhibitory effects in prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Shayan eSarkar

    2015-10-01

    Full Text Available The gene Par-4 (Prostate Apoptosis Response 4 was originally identified in prostate cancer cells undergoing apoptosis and its product Par-4 showed cancer specific pro-apoptotic activity. Particularly, the SAC domain of Par-4 (SAC-Par-4 selectively kills cancer cells leaving normal cells unaffected. The therapeutic significance of bioactive SAC-Par-4 is enormous in cancer biology; however, its large scale production is still a matter of concern. Here we report the production of SAC-Par-4-GFP fusion protein coupled to translational enhancer sequence (5′ AMV and apoplast signal peptide (aTP in transgenic Nicotiana tabacum cv. Samsun NN plants under the control of a unique recombinant promoter M24. Transgene integration was confirmed by genomic DNA PCR, Southern and Northern blotting, Real-time PCR and Nuclear run-on assays. Results of Western blot analysis and ELISA confirmed expression of recombinant SAC-Par-4-GFP protein and it was as high as 0.15% of total soluble protein. In addition, we found that targeting of plant recombinant SAC-Par-4-GFP to the apoplast and endoplasmic reticulum (ER was essential for the stability of plant recombinant protein in comparison to the bacterial derived SAC-Par-4. Deglycosylation analysis demonstrated that ER-targeted SAC-Par-4-GFP-SEKDEL undergoes O-linked glycosylation unlike apoplast-targeted SAC-Par-4-GFP. Furthermore, various in vitro studies like mammalian cells proliferation assay (MTT, apoptosis induction assays, and NF-κB suppression suggested the cytotoxic and apoptotic properties of plant-derived SAC-Par-4-GFP against multiple prostate cancer cell lines. Additionally, pre-treatment of MAT-LyLu prostate cancer cells with purified SAC-Par-4-GFP significantly delayed the onset of tumor in a syngeneic rat prostate cancer model. Taken altogether, we proclaim that plant made SAC-Par-4 may become a useful alternate therapy for effectively alleviating cancer in the new era.

  3. Performance enhancement of Ge-on-Insulator tunneling FETs with source junctions formed by low-energy BF2 ion implantation

    Science.gov (United States)

    Katoh, Takumi; Matsumura, Ryo; Takaguchi, Ryotaro; Takenaka, Mitsuru; Takagi, Shinichi

    2018-04-01

    To clarify the process of formation of source regions of high-performance Ge n-channel tunneling field-effect transistors (TFETs), p+-n junctions formed by low-energy ion implantation (I/I) of BF2 atoms are characterized. Here, the formation of p+-n junctions with steep B profiles and low junction leakage is a key issue. The steepness of 5.7 nm/dec in profiles of B implanted into Ge is obtained for BF2 I/I at 3 keV with a dose of 4 × 1014 cm-2. Ge-on-insulator (GOI) n-TFETs with the source tunnel junctions formed by low-energy B and BF2 I/I are fabricated on GOI substrates and the device operation is confirmed. Although the performance at room temperature is significantly degraded by the source junction leakage current, an I on/I off ratio of 105 and the minimum sub-threshold swing (S.S.) of 130 mV/dec are obtained at 10 K. It is found that GOI n-TFETs with steeper B profiles formed by BF2 I/I have led to higher on current and a lower sub-threshold slope, demonstrating the effectiveness of steep B profiles in enhancing the GOI TFET performance.

  4. Protease-Activated Receptor 4 (PAR4): A Promising Target for Antiplatelet Therapy.

    Science.gov (United States)

    Rwibasira Rudinga, Gamariel; Khan, Ghulam Jilany; Kong, Yi

    2018-02-14

    Cardiovascular diseases (CVDs) are currently among the leading causes of death worldwide. Platelet aggregation is a key cellular component of arterial thrombi and major cause of CVDs. Protease-activated receptors (PARs), including PAR1, PAR2, PAR3 and PAR4, fall within a subfamily of seven-transmembrane G-protein-coupled receptors (GPCR). Human platelets express PAR1 and PAR4, which contribute to the signaling transduction processes. In association with CVDs, PAR4 not only contributes to platelet activation but also is a modulator of cellular responses that serve as hallmarks of inflammation. Although several antiplatelet drugs are available on the market, they have many side effects that limit their use. Emerging evidence shows that PAR4 targeting is a safer strategy for preventing thrombosis and consequently may improve the overall cardiac safety profile. Our present review summarizes the PAR4 structural characteristics, activation mechanism, role in the pathophysiology of diseases and understanding the association of PAR4 targeting for improved cardiac protection. Conclusively, this review highlights the importance of PAR4 antagonists and its potential utility in different CVDs.

  5. Testis-expressed profilins 3 and 4 show distinct functional characteristics and localize in the acroplaxome-manchette complex in spermatids

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    Rothkegel Martin

    2009-05-01

    Full Text Available Abstract Background Multiple profilin isoforms exist in mammals; at least four are expressed in the mammalian testis. The testis-specific isoforms profilin-3 (PFN3 and profilin-4 (PFN4 may have specialized roles in spermatogenic cells which are distinct from known functions fulfilled by the "somatic" profilins, profilin-1 (PFN1 and profilin-2 (PFN2. Results Ligand interactions and spatial distributions of PFN3 and PFN4 were compared by biochemical, molecular and immunological methods; PFN1 and PFN2 were employed as controls. β-actin, phosphoinositides, poly-L-proline and mDia3, but not VASP, were confirmed as in vitro interaction partners of PFN3. In parallel experiments, PFN4 bound to selected phosphoinositides but not to poly-L-proline, proline-rich proteins, or actin. Immunofluorescence microscopy of PFN3 and PFN4 revealed distinct subcellular locations in differentiating spermatids. Both were associated first with the acroplaxome and later with the transient manchette. Predicted 3D structures indicated that PFN3 has the actin-binding site conserved, but retains only approximately half of the common poly-L-proline binding site. PFN4, in comparison, has lost both, polyproline and actin binding sites completely, which is well in line with the experimental data. Conclusion The testis-specific isoform PFN3 showed major hallmarks of the well characterized "somatic" profilin isoforms, albeit with distinct binding affinities. PFN4, on the other hand, did not interact with actin or polyproline in vitro. Rather, it seemed to be specialized for phospholipid binding, possibly providing cellular functions which are distinct from actin dynamics regulation.

  6. Compact 4-kHz XeF-laser with multisectional discharge gap

    Science.gov (United States)

    Andramanov, A. V.; Kabaev, S. A.; Lazhintsev, Boris V.; Nor-Arevyan, Vladimir A.; Selemir, V. D.

    2005-03-01

    An electric-discharge XeF-laser with a pulse repetition rate up to 4 kHz was developed. The laser electrode unit was made on the basis of plate-like electrodes with inductive-capacity discharge stabilization. The narrow discharge width laser energy was 3 mJ by using He/Xe/NF3 and Ne/Xe/NF3 mixtures at the total pressure of 0.8 atm and 1.2 atm, respectively. The maximum laser efficiency was ~ 0.73% The gas flow was formed with the help of a diametrical fan rotated by the direct-current motor with 80 W power. The gas velocity of 20 m/s in the interelectrode gap was achieved. The laser pulse energy for a pulse repetition rate up to 3.5...4 kHz was virtually equal to the laser pulse energy in the infrequently-repeating-pulse regime. The average output power of 12 W at the pulse repetition rate of 4 kHz was achieved. The relative root-mean-square pulse-to-pulse variation of the output energy σ = 2.5% was reached.

  7. 1D and 2D assembly structures by imidazole···chloride hydrogen bonds of iron(II) complexes [Fe(II)(HL(n-Pr))3]Cl·Y (HL(n-Pr) = 2-methylimidazol-4-yl-methylideneamino-n-propyl; Y = AsF6, BF4) and their spin states.

    Science.gov (United States)

    Fujinami, Takeshi; Nishi, Koshiro; Matsumoto, Naohide; Iijima, Seiichiro; Halcrow, Malcolm A; Sunatsuki, Yukinari; Kojima, Masaaki

    2011-12-07

    Two Fe(II) complexes fac-[Fe(II)(HL(n-Pr))(3)]Cl·Y (Y = AsF(6) (1) and BF(4) (2)) were synthesized, where HL(n-Pr) is 2-methylimidazole-4-yl-methylideneamino-n-propyl. Each complex-cation has the same octahedral N(6) geometry coordinated by three bidentate ligands and assumes facial-isomerism, fac-[Fe(II)(HL(n-Pr))(3)](2+) with Δ- and Λ-enantiomorphs. Three imidazole groups per Δ- or Λ-fac-[Fe(II)(HL(n-Pr))(3)](2+) are hydrogen-bonded to three Cl(-) ions or, from the viewpoint of the Cl(-) ion, one Cl(-) ion is hydrogen-bonded to three neighbouring fac-[Fe(II)(HL(n-Pr))(3)](2+) cations. The 3 : 3 NH···Cl(-) hydrogen bonds between Δ- or Λ-fac-[Fe(II)(HL(n-Pr))(3)](2+) and Cl(-) generate two kinds of assembly structures. The directions of the 3 : 3 NH···Cl(-) hydrogen bonds and hence the resulting assembly structures are determined by the size of the anion Y, though Y is not involved into the network structure and just accommodated in the cavity. Compound 1 has a 1D ladder structure giving a larger cavity, in which the Δ- and Λ-fac-[Fe(II)(HL(n-Pr))(3)](2+) enantiomorphs are bridged by two NH···Cl(-) hydrogen bonds. Compound 2 has a 2D network structure with a net unit of a cyclic trimer of {fac-[Fe(II)(HL(n-Pr))(3)](2+)···Cl(-)}(3) giving a smaller cavity, in which Δ- or Λ-fac-[Fe(II)(HL(n-Pr))(3)](2+) species with the same chirality are linked by NH···Cl(-) hydrogen bonds to give a homochiral 2D network structure. Magnetic susceptibility and Mössbauer spectral measurements demonstrated that compound 1 showed an abrupt one-step spin crossover with 4.0 K thermal hysteresis of T(c↓) = 125.5 K and T(c↑) = 129.5 K and compound 2 showed no spin transition and stayed in the high-spin state over the 5-300 K temperature range.

  8. Two dimensional untwisted (4,4), twisted (4,4-bar) and chiral supersymmetric non linear σ-models

    International Nuclear Information System (INIS)

    Lhallabi, T.; Saidi, E.H.

    1987-09-01

    D=2 N=(4,4) harmonic superspace analysis is developed. The underlying untwisted (4,4) non linear σ-models are studied. A method of deriving chiral (4,0) and (0,4) models is presented. The Lagrange superparameter leading to the constraint specifying the hyperkahler manifold structure is predicted and its relation to the matter superfield is stated in a covariant way. A known construction is recovered. We show also that (4,4) model is not a direct sum of the chiral ones. Finally a twisted (4,4-bar) model is obtained. (author). 28 refs

  9. Regulation of IFN regulatory factor 4 expression in human T cell leukemia virus-I-transformed T cells.

    Science.gov (United States)

    Sharma, Sonia; Grandvaux, Nathalie; Mamane, Yael; Genin, Pierre; Azimi, Nazli; Waldmann, Thomas; Hiscott, John

    2002-09-15

    IFN regulatory factor (IRF)-4 is a lymphoid/myeloid-restricted member of the IRF transcription factor family that plays an essential role in the homeostasis and function of mature lymphocytes. IRF-4 expression is tightly regulated in resting primary T cells and is transiently induced at the mRNA and protein levels after activation by Ag-mimetic stimuli such as TCR cross-linking or treatment with phorbol ester and calcium ionophore (PMA/ionomycin). However, IRF-4 is constitutively upregulated in human T cell leukemia virus type I (HTLV-I) infected T cells as a direct gene target for the HTLV-I Tax oncoprotein. In this study we demonstrate that chronic IRF-4 expression in HTLV-I-infected T lymphocytes is associated with a leukemic phenotype, and we examine the mechanisms by which continuous production of IRF-4 is achieved in HTLV-I-transformed T cells. IRF-4 expression in HTLV-1-infected cells is driven through activation of the NF-kappaB and NF-AT pathways, resulting in the binding of p50, p65, and c-Rel to the kappaB1 element and p50, c-Rel, and NF-ATp to the CD28RE element within the -617 to -209 region of the IRF-4 promoter. Furthermore, mutation of either the kappaB1 or CD28RE sites blocks Tax-mediated transactivation of the human IRF-4 promoter in T cells. These experiments constitute the first detailed analysis of human IRF-4 transcriptional regulation within the context of HTLV-I infection and transformation of CD4(+) T lymphocytes.

  10. Leonurine (SCM-198) attenuates myocardial fibrotic response via inhibition of NADPH oxidase 4.

    Science.gov (United States)

    Liu, Xin-Hua; Pan, Li-Long; Deng, Hai-Yan; Xiong, Qing-Hui; Wu, Dan; Huang, Guo-Ying; Gong, Qi-Hai; Zhu, Yi-Zhun

    2013-01-01

    In our previous studies, we have reported that leonurine, a plant phenolic alkaloid in Herba leonuri, exerted cardioprotective properties in a number of preclinical experiments. Herein, we investigated the roles and the possible mechanisms of leonurine for reducing fibrotic responses in angiotensin II (Ang II)-stimulated primary neonatal rat cardiac fibroblasts and post-myocardial infarction (MI) rats. In in vitro experiments performed in neonatal rat cardiac fibroblasts, leonurine (10-20 μM) pretreatment attenuated Ang II-induced activation of extracellular signal-regulated kinase 1/2, production of intracellular reactive oxygen species (ROS), expression and activity of matrix metalloproteinase (MMP)-2/9, and expression of α-smooth muscle actin and types I and III collagen. A small interfering RNA-mediated knockdown strategy for NADPH oxidase 4 (Nox4) revealed that Nox4 was required for Ang II-induced activation of cardiac fibroblasts. In vivo studies using a post-MI model in rats indicated that administration of leonurine inhibited myocardial fibrosis while reducing cardiac Nox4 expression, ROS production, NF-κB activation, and plasma MMP-2 activity. In conclusion, our results provide the first evidence that leonurine could prevent cardiac fibrosis and the activation of cardiac fibroblasts partly through modulation of a Nox4-ROS pathway. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. The Quantum Description of BF Model in Superspace

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    Manoj Kumar Dwivedi

    2018-01-01

    Full Text Available We consider the BRST symmetric four-dimensional BF theory, a topological theory, containing antisymmetric tensor fields in Landau gauge and extend the BRST symmetry by introducing a shift symmetry to it. Within this formulation, the antighost fields corresponding to shift symmetry coincide with antifields of standard field/antifield formulation. Furthermore, we provide a superspace description for the BF model possessing extended BRST and extended anti-BRST transformations.

  12. 3-Hydroxy-4,7-megastigmadien-9-one, isolated from Ulva pertusa, attenuates TLR9-mediated inflammatory response by down-regulating mitogen-activated protein kinase and NF-κB pathways.

    Science.gov (United States)

    Ali, Irshad; Manzoor, Zahid; Koo, Jung-Eun; Kim, Jung-Eun; Byeon, Sang-Hee; Yoo, Eun-Sook; Kang, Hee-Kyoung; Hyun, Jin-Won; Lee, Nam-Ho; Koh, Young-Sang

    2017-12-01

    Seaweeds are rich in bioactive compounds in the form of vitamins, phycobilins, polyphenols, carotenoids, phycocyanins and polysaccharides; many of these are known to have advantageous applications in human health. 3-Hydroxy-4,7-megastigmadien-9-one (comp) was isolated from Ulva pertusa (U. pertusa) Kjellman (Ulvaceae), which is a familiar edible green seaweed. This study evaluates the anti-inflammatory activity of comp in CpG DNA-stimulated bone marrow-derived dendritic cells (BMDCs). For evaluating the effect of comp on cytokines production, BMDCs were treated with doses of comp (0, 0.5, 1, 2, 5, 10, 25 and 50 μM) for 1 h before stimulation with CpG DNA (1 μM). Cytokine production was measured by ELISA. Western blotting was conducted for evaluating effect of comp (50 μM) on MAPKs and NF-κB pathways. Luciferase reporter gene assay was conducted for effect of comp (0, 5, 10 and 25 μM) on transcriptional activity of AP-1 and NF-κB. Comp exhibited strong inhibition of interleukin (IL)-12 p40, IL-6 and TNF-α cytokine production with IC 50 values of 6.02 ± 0.35, 27.14 ± 0.73, and 7.56 ± 0.21 μM, respectively. It blocked MAPKs and NF-κB pathways by inhibiting the phosphorylation of ERK1/2, JNK1/2, p38 and IκBα. In addition, it strongly inhibited the transcriptional activity of AP-1 and NF-κB with IC 50 values of 8.74 ± 0.31 and 12.08 ± 0.24 μM, respectively. Taken together, these data suggest that comp has a significant anti-inflammatory property and warrants further studies concerning the potential of comp for medicinal use.

  13. Corneal NF-kappaB activity is necessary for the retention of transparency in the cornea of UV-B-exposed transgenic reporter mice.

    Science.gov (United States)

    Alexander, George; Carlsen, Harald; Blomhoff, Rune

    2006-04-01

    To determine the dynamics of Nuclear Factor-kappaB (NF-kappaB) in murine corneal pathology and the role of NF-kappaB in maintaining corneal clarity after ultraviolet B radiation insult, transgenic mice containing NF-kappaB-luciferase reporter were exposed to LPS (bacterial lipopolysaccharide), TNF-alpha (Tumor Necrosis Factor-alpha) or 4 kJ m(-2) UV-B radiation. NF-kappaB decoy oligonucleotides were also administered in some of the UV-B experiments. Following various exposure times, the mice were sacrificed and whole eyes or corneal tissues were obtained. Whole eyes were examined for scattering using a point-source optical imaging technique. Tissue homogenates were examined for luciferase activity using a luminometer. TNF-alpha and LPS-injected NF-kappaB-luciferase transgenic mice demonstrated 3-10-fold increases in cornea NF-kappaB with peak activities at 4 and 6 hr post-injection, respectively. Mice exposed to 4 kJ m(-2) UV-B exhibited a 3-fold increase in NF-kappaB activity 4 hr post-exposure. The administration of NF-kappaB-decoy oligonucleotides to mice had the effect of reducing UV-B-induced NF-kappaB activity in the cornea and significantly increasing the amount of light scattering in UV-B exposed corneas 7 days post-UV-B exposure when compared to sham injected mice. These results indicate that NF-kappaB is activated in cornea in pathologies that involves increased plasma levels of LPS and TNF-alpha, as well as direct UV-B exposure, and suggest that NF-kappaB activation play an essential part in the corneal healing process.

  14. Study of multiplet structures of Mn4+ activated in fluoride crystals

    International Nuclear Information System (INIS)

    Novita, Mega; Honma, Tetsuo; Hong, Byungchul; Ohishi, Atsushi; Ogasawara, Kazuyoshi

    2016-01-01

    We investigated the optical properties of Mn 4+ in some fluoride crystals such as Cs 2 MnF 6 , Cs 2 GeF 6 , Rb 2 GeF 6 , Cs 2 SiF 6 , K 2 SiF 6 , Rb 2 MnF 6 , Rb 2 SiF 6 , K 2 GeF 6 , K 2 TiF 6 , Li 2 MnF 6 , Na 2 GeF 6 , Na 2 SiF 6 , and Na 2 TiF 6 based on the first-principle calculation using the discrete-variational multi-electron method. In order to estimate the lattice relaxation, we performed EXAFS measurement of Mn 4+ doped in K 2 SiF 6 , K 2 TiF 6 , and K 2 GeF 6 . The relaxation rates of A 2 BF 6 :Mn 4+ were fixed to be the above estimated values, 102.24%, 107.37% or 96.80% for crystal having Si, Ge, or Ti at the B cation site, respectively. In this work, we also considered some corrections such as configuration dependent correction and correlation correction to improve the theoretical energies. It has been shown that to reproduce multiplet energy levels quantitatively, the lattice relaxation is very important. On the other hand, for a qualitative prediction of the tendencies of the multiplet energies, the combination of lattice relaxation effect, configuration dependent correction, and correlation correction is effective. - Highlights: • Multiplet structures of A 2 BF 6 :Mn 4+ were calculated from first-principles. • Lattice relaxation was estimated based on EXAFS experiment. • Lattice relaxation is important to reproduce multiplet energies quantitatively. • CDC and CC are important to reproduce tendencies of multiplet energies.

  15. An additional memory effect in mass spectrometry for BF3

    International Nuclear Information System (INIS)

    Hoshino, Kiichi; Satooka, Sakae

    1978-01-01

    It is considered that the memory effect appears in a metallic gas inlet of a mass spectrometer for measurement with samples of BF 3 is classified into two kinds, one is essential memory effect which is caused by an action between the surface of metal and BF 3 , and the other is additional memory effect which is caused by viscous liquid produced by reaction among water, BF 3 and metals. The additional memory effect is caused by stain on the inner surface of the gas inlet. Air is introduced into the sample bottle joint at each time for change of sample bottle. Moisture in the air is adsorbed on inner surfaces of the joint and piping made of metal, and combined with BF 3 which is introduced, and then viscous compound is produced by dissolution of the metal into the compound made from H 2 O and BF 3 . The vapour pressure of the viscous compound is not sufficient low, and so the compound propagates from the sample bottle joint to the whole of the gas inlet at each time of opening and closing of valves of the gas inlet. The coated film of the viscous compound with adsorption and release of Bf 3 is a cause of the additional memory effect. If the stain of the inner surface of the gas inlet grows up, the additional memory effect becomes more intense compared with the essential memory effect, and the measured values are not converged. To remove the additional memory effect, it is desirable to introduce the sample BF 3 after the moisture intruded into the piping by the exchange of sample bottles is removed sufficiently by introduction of F 2 or ClF 3 . (auth.)

  16. AAV-based shRNA silencing of NF-κB ameliorates muscle pathologies in mdx mice.

    Science.gov (United States)

    Yang, Q; Tang, Y; Imbrogno, K; Lu, A; Proto, J D; Chen, A; Guo, F; Fu, F H; Huard, J; Wang, B

    2012-12-01

    Chronic inflammation, promoted by an upregulated NF-kappa B (NF-κB) pathway, has a key role in Duchenne muscular dystrophy (DMD) patients' pathogenesis. Blocking the NF-κB pathway has been shown to be a viable approach to diminish chronic inflammation and necrosis in the dystrophin-defective mdx mouse, a murine DMD model. In this study, we used the recombinant adeno-associated virus serotype 9 (AAV9) carrying an short hairpin RNA (shRNA) specifically targeting the messenger RNA of NF-κB/p65 (p65-shRNA), the major subunit of NF-κB associated with chronic inflammation in mdx mice. We examined whether i.m. AAV9-mediated delivery of p65-shRNA could decrease NF-κB activation, allowing for amelioration of muscle pathologies in 1- and 4-month-old mdx mice. At 1 month after treatment, NF-κB/p65 levels were significantly decreased by AAV gene transfer of p65-shRNA in the two ages of treatment groups, with necrosis significantly decreased compared with controls. Quantitative analysis revealed that central nucleation (CN) of the myofibers of p65-shRNA-treated 1-month-old mdx muscles was reduced from 67 to 34%, but the level of CN was not significantly decreased in treated 4-month-old mdx mice. Moreover, delivery of the p65-shRNA enhanced the capacity of myofiber regeneration in old mdx mice treated at 4 months of age when the dystrophic myofibers were most exhausted; however, such p65 silencing diminished the myofiber regeneration in young mdx mice treated at 1 month of age. Taken together, these findings demonstrate that the AAV-mediated delivery of p65-shRNA has the capacity to ameliorate muscle pathologies in mdx mice by selectively reducing NF-κB/p65 activity.

  17. Fusion proteins of HIV-1 envelope glycoprotein gp120 with CD4-induced antibodies showed enhanced binding to CD4 and CD4 binding site antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Weizao, E-mail: chenw3@mail.nih.gov [Protein Interactions Group, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); Feng, Yang [Protein Interactions Group, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); Wang, Yanping [Protein Interactions Group, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); The Basic Research Program, Science Applications International Corporation-Frederick, Inc., National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); Zhu, Zhongyu; Dimitrov, Dimiter S. [Protein Interactions Group, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States)

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer Some recombinant HIV-1 gp120s do not preserve their conformations on gp140s. Black-Right-Pointing-Pointer We hypothesize that CD4i antibodies could induce conformational changes in gp120. Black-Right-Pointing-Pointer CD4i antibodies enhance binding of CD4 and CD4bs antibodies to gp120. Black-Right-Pointing-Pointer CD4i antibody-gp120 fusion proteins could have potential as vaccine immunogens. -- Abstract: Development of successful AIDS vaccine immunogens continues to be a major challenge. One of the mechanisms by which HIV-1 evades antibody-mediated neutralizing responses is the remarkable conformational flexibility of its envelope glycoprotein (Env) gp120. Some recombinant gp120s do not preserve their conformations on gp140s and functional viral spikes, and exhibit decreased recognition by CD4 and neutralizing antibodies. CD4 binding induces conformational changes in gp120 leading to exposure of the coreceptor-binding site (CoRbs). In this study, we test our hypothesis that CD4-induced (CD4i) antibodies, which target the CoRbs, could also induce conformational changes in gp120 leading to better exposed conserved neutralizing antibody epitopes including the CD4-binding site (CD4bs). We found that a mixture of CD4i antibodies with gp120 only weakly enhanced CD4 binding. However, such interactions in single-chain fusion proteins resulted in gp120 conformations which bound to CD4 and CD4bs antibodies better than the original or mutagenically stabilized gp120s. Moreover, the two molecules in the fusion proteins synergized with each other in neutralizing HIV-1. Therefore, fusion proteins of gp120 with CD4i antibodies could have potential as components of HIV-1 vaccines and inhibitors of HIV-1 entry, and could be used as reagents to explore the conformational flexibility of gp120 and mechanisms of entry and immune evasion.

  18. DESAIN DAN SINTESIS SENYAWA ACES (ANALOG CURCUMIN SERIES DENGAN METODE SOLID PHASE REACTION SEBAGAI SENYAWA ANTIKANKER POTEN DENGAN MEKANISME MENGHAMBAT PROTEIN NF-kB

    Directory of Open Access Journals (Sweden)

    Monica Sabrina Widiapranolo

    2016-04-01

    Full Text Available Abstract: Analog of curcumin in forms of enone and dienone aromatic is known for their activity as an NF-κB inhibitor. In this study, will be synthesize 2-(4'-N, N-dimethylamino benzilidine cyclohexane-1,3-dione as an analog that predicted has an activity as an NF-κB inhibitor. This research was conducted based on the crossed aldol condensation reaction by reacting 3 mmole pN,N-dimethylamino benzaldehide and 6 mmole cyclohexane-1,3-dione with hydrochloric acid as the catalyst using solid phase reaction method. Based on computational analysis, 2-(4'-N,Ndimethylamino benzilidine cyclohexane-1,3-dione showed a better interaction with NF-κB protein with PLANTSPLP score was -69,7895. The outcome of the reaction was yellow colored powder, no odor and soluble in hydrochloric acid 3N. The yield value was 78.8%. Liquid chromatography showed 100% purity. The melting point range was 237.5-240.3°C. The results of structure elucidation by 1H-NMR, infrared and mass spectroscopy tests indicated the compound was 2-(4-(dimetilaminobenzilidena-4-(3-oksosiklohex-1-enil sikloheksana-1,3-dion. Key words: 2-(4'-N, N-dimethylamino benzilidine cyclohexane-1,3-dione, crossed aldol condensation, solid phase reaction.

  19. A non-canonical Flt3ITD/NF-κB signaling pathway represses DAPK1 in acute myeloid leukemia (AML)

    Science.gov (United States)

    Shanmugam, Rajasubramaniam; Sayar, Hamid; Suvannasankha, Attaya; Goswami, Chirayu; Li, Lang; Gupta, Sushil; Cardoso, Angelo A.; Baghdadi, Tareq Al; Sargent, Katie J.; Cripe, Larry D.; Kalvakolanu, Dhananjaya V.; Boswell, H. Scott

    2014-01-01

    Purpose DAPK1, a tumor suppressor, is a rate-limiting effector in an ER stress-dependent apoptotic pathway. Its expression is epigenetically suppressed in several tumors. A mechanistic basis for epigenetic/transcriptional repression of DAPK1 was investigated in certain forms of AML with poor prognosis, which lacked ER stress-induced apoptosis. Experimental Design Heterogeneous primary AMLs were screened to identify a subgroup with Flt3ITD in which repression of DAPK1, among NF-κB- and c- jun-responsive genes, was studied. RNAi knockdown studies were performed in Flt3ITD+ve cell line, MV-4-11, to establish genetic epistasis in the pathway Flt3ITD-TAK1-DAPK1 repression, and chromatin immunoprecipitations were performed to identify proximate effector proteins, including TAK1-activated p52NF-κB, at the DAPK1 locus. Results AMLs characterized by normal karyotype with Flt3ITD were found to have 10-100-fold lower DAPK1 transcripts normalized to the expression of c-jun, a transcriptional activator of DAPK1, as compared to a heterogeneous cytogenetic category. Meis1, a c-jun-responsive adverse AML prognostic gene signature was also measured as control. These Flt3ITD+ve AMLs over-express relB, a transcriptional repressor, which forms active heterodimers with p52NF-κB. Chromatin immunoprecipitation assays identified p52NF-κB binding to the DAPK1 promoter along with HDAC2 and HDAC6 in the Flt3ITD+ve human AML cell line MV-4-11. Knockdown of p52NF-κB or its upstream regulator, NIK, de-repressed DAPK1. DAPK1-repressed primary Flt3ITD+ve AMLs had selective nuclear activation of p52NF-κB. Conclusions Flt3ITD promotes a non-canonical pathway via TAK1 and p52NF-κB to suppress DAPK1 in association with HDACs, which explains DAPK1 repression in Flt3ITD+ve AML. PMID:22096027

  20. Advancing Venus Geophysics with the NF4 VOX Gravity Investigation.

    Science.gov (United States)

    Iess, L.; Mazarico, E.; Andrews-Hanna, J. C.; De Marchi, F.; Di Achille, G.; Di Benedetto, M.; Smrekar, S. E.

    2017-12-01

    The Venus Origins Explorer is a JPL-led New Frontiers 4 mission proposal to Venus to answer critical questions about the origin and evolution of Venus. Venus stands out among other planets as Earth's twin planet, and is a natural target to better understand our own planet's place, in our own Solar System but also among the ever-increasing number of exoplanetary systems. The VOX radio science investigation will make use of an innovative Ka-band transponder provided by the Italian Space Agency (ASI) to map the global gravity field of Venus to much finer resolution and accuracy than the current knowledge, based on the NASA Magellan mission. We will present the results of comprehensive simulations performed with the NASA GSFC orbit determination and geodetic parameter estimation software `GEODYN', based on a realistic mission scenario, tracking schedule, and high-fidelity Doppler tracking noise model. We will show how the achieved resolution and accuracy help fulfill the geophysical goals of the VOX mission, in particular through the mapping of subsurface crustal density or thickness variations that will inform the composition and origin of the tesserae and help ascertain the heat loss and importance of tectonism and subduction.

  1. An activating mutation of interferon regulatory factor 4 (IRF4) in adult T cell leukemia.

    Science.gov (United States)

    Cherian, Mathew A; Olson, Sydney; Sundaramoorthi, Hemalatha; Cates, Kitra; Cheng, Xiaogang; Harding, John; Martens, Andrew; Challen, Grant A; Tyagi, Manoj; Ratner, Lee; Rauch, Daniel

    2018-03-14

    The human T cell leukemia virus-1 (HTLV-1) oncoprotein Tax drives cell proliferation and resistance to apoptosis early in the pathogenesis of adult T-cell leukemia (ATL). Subsequently, likely as a result of specific immuno-editing, Tax expression is downregulated and functionally replaced by somatic driver mutations of the host genome. Both amplification and point mutations of interferon regulatory factor 4 (IRF4) have been previously detected in ATL, and the K59R mutation is the most common single-nucleotide variation in IRF4 and is found exclusively in ATL. Here high throughput whole-exome sequencing revealed recurrent activating genetic alterations in the T cell receptor, CD28, and NF-kB pathways. Moreover, we found that IRF4, which is transcriptionally activated downstream of these pathways, is frequently mutated in ATL. IRF4 RNA, protein, and IRF4 transcriptional targets are uniformly elevated in HTLV transformed cells and ATL cell lines, and IRF4 was bound to genomic regulatory DNA of many of these transcriptional targets in HTLV-1 transformed cell lines. We further noted that the K59R IRF4 mutant is expressed at higher levels in the nucleus than is wild-type IRF4, and is transcriptionally more active. Expression of both wild-type and the K59R mutant of IRF4 from a constitutive promoter in retrovirally transduced murine bone marrow cells increased the abundance of T lymphocytes but not myeloid cells or B lymphocytes in mice. IRF4 may represent a therapeutic target in ATL since ATL cells select for a mutant of IRF4 with higher nuclear expression and transcriptional activity, and over-expression of IRF4 induces the expansion of T lymphocytes in vivo. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

  2. N = 4 Superconformal Chern-Simons theories with hyper and twisted hyper multiplets

    International Nuclear Information System (INIS)

    Hosomichi, Kazuo; Lee, Ki-Myeong; Lee, Sungjay; Lee, Sangmin; Park, Jaemo

    2008-01-01

    We extend the N = 4 superconformal Chern-Simons theories of Gaiotto and Witten to those with additional twisted hyper-multiplets. The new theories are generically linear quiver gauge theories with the two types of hyper-multiplets alternating between gauge groups. Our construction includes the Bagger-Lambert model of SO(4) gauge group. A family of abelian theories are identified with those proposed earlier in the context of the M-crystal model for M2-branes probing (C 2 /Z n ) 2 orbifolds. Possible extension with non-abelian BF couplings and string/M-theory realization are briefly discussed.

  3. Intracellular expression of toll-like receptor 4 in neuroblastoma cells and their unresponsiveness to lipopolysaccharide

    International Nuclear Information System (INIS)

    Hassan, Ferdaus; Islam, Shamima; Tumurkhuu, Gantsetseg; Naiki, Yoshikazu; Koide, Naoki; Mori, Isamu; Yoshida, Tomoaki; Yokochi, Takashi

    2006-01-01

    Recently it has been reported that, toll-like receptors (TLRs) are expressed on a series of tumor cells, such as colon cancer, breast cancer, prostate cancer, melanoma and lung cancer. Although some cancer cells like melanoma cells are known to respond to lipopolysaccharide (LPS) via TLR4, not all cancer cells are positive for TLR4. There is little information on the expression and function of TLR4 in neuroblastoma cells. In this study, we investigated the expression of TLR4 in human neuroblastoma NB-1 cell line. Expression and localization of TLR4 were detected by reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometric analysis, respectively. Activation of nuclear factor (NF)-κB by LPS was detected by degradation of IκB-α and NF-κB luciferase assay. Activation and expression of mitogen-activated protein (MAP) kinase and interferon regulatory factor (IRF)-3 was detected by immunoblot analysis. Human NB-1 neuroblastoma cells expressed intracellular form of TLR4, but not the cell surface form. Further, NB-1 cells express CD14, MD2 and MyD88, which are required for LPS response. However, LPS did not significantly induce NF-κB activation in NB-1 cells although it slightly degraded IκB-α. NB-1 cells expressed no IRF-3, which plays a pivotal role on the MyD88-independent pathway of LPS signaling. Collectively, NB-1 cells are capable to avoid their response to LPS. Although human NB-1 neuroblastoma cells possessed all the molecules required for LPS response, they did not respond to LPS. It might be responsible for intracellular expression of TLR4 or lack of IRF-3

  4. Protease-Activated Receptor 4 (PAR4: A Promising Target for Antiplatelet Therapy

    Directory of Open Access Journals (Sweden)

    Gamariel Rwibasira Rudinga

    2018-02-01

    Full Text Available Cardiovascular diseases (CVDs are currently among the leading causes of death worldwide. Platelet aggregation is a key cellular component of arterial thrombi and major cause of CVDs. Protease-activated receptors (PARs, including PAR1, PAR2, PAR3 and PAR4, fall within a subfamily of seven-transmembrane G-protein-coupled receptors (GPCR. Human platelets express PAR1 and PAR4, which contribute to the signaling transduction processes. In association with CVDs, PAR4 not only contributes to platelet activation but also is a modulator of cellular responses that serve as hallmarks of inflammation. Although several antiplatelet drugs are available on the market, they have many side effects that limit their use. Emerging evidence shows that PAR4 targeting is a safer strategy for preventing thrombosis and consequently may improve the overall cardiac safety profile. Our present review summarizes the PAR4 structural characteristics, activation mechanism, role in the pathophysiology of diseases and understanding the association of PAR4 targeting for improved cardiac protection. Conclusively, this review highlights the importance of PAR4 antagonists and its potential utility in different CVDs.

  5. Zn(3)(4-OOCC(6)H(4)PO(3))(2): A polar metal phosphonate with pillared layered structure showing SHG-activity and large dielectric anisotropy.

    Science.gov (United States)

    Li, Jin-Tang; Cao, Deng-Ke; Akutagawa, Tomoyuki; Zheng, Li-Min

    2010-10-07

    A new metal phosphonate Zn(3)(4-OOCC(6)H(4)PO(3))(2) (1) is reported which crystallizes in orthorhombic space group Pca2(1). It shows a pillared layered structure in which the {ZnO(4)}, {ZnO(5)} and {PO(3)C} polyhedra are connected through corner- or edge-sharing to form an inorganic layer in the ab plane which contains 4- and 5-member rings. These layers are pillared by the uni-oriented 4-carboxylatephenylphosphonate ligands, thus leading to a polar 3D architecture. The dielectric anisotropy measurements of a single crystal of 1 reveal that dielectric constant along the inter-layer is larger than that along the intra-layer with a ratio of about 2.3. Second harmonic generation (SHG) activity is observed.

  6. Recombinant production and characterisation of two related GH5 endo-β-1,4-mannanases from Aspergillus nidulans FGSC A4 showing distinctly different transglycosylation capacity

    DEFF Research Database (Denmark)

    Dilokpimol, Adiphol; Nakai, Hiroyuki; Gotfredsen, Charlotte Held

    2011-01-01

    The glycoside hydrolase family 5 (GH5) endo-β-1,4-mannanases ManA and ManC from Aspergillus nidulans FGSC A4 were produced in Pichia pastoris X33 and purified in high yields of 120 and 145mg/L, respectively, from the culture supernatants. Both enzymes showed increasing catalytic efficiency (kcat...

  7. Rationally Designed TLR4 Ligands for Vaccine Adjuvant Discovery

    Directory of Open Access Journals (Sweden)

    Kelsey A. Gregg

    2017-05-01

    Full Text Available Adjuvant properties of bacterial cell wall components like MPLA (monophosphoryl lipid A are well described and have gained FDA approval for use in vaccines such as Cervarix. MPLA is the product of chemically modified lipooligosaccharide (LOS, altered to diminish toxic proinflammatory effects while retaining adequate immunogenicity. Despite the virtually unlimited number of potential sources among bacterial strains, the number of useable compounds within this promising class of adjuvants are few. We have developed bacterial enzymatic combinatorial chemistry (BECC as a method to generate rationally designed, functionally diverse lipid A. BECC removes endogenous or introduces exogenous lipid A-modifying enzymes to bacteria, effectively reprogramming the lipid A biosynthetic pathway. In this study, BECC is applied within an avirulent strain of Yersinia pestis to develop structurally distinct LOS molecules that elicit differential Toll-like receptor 4 (TLR4 activation. Using reporter cell lines that measure NF-κB activation, BECC-derived molecules were screened for the ability to induce a lower proinflammatory response than Escherichia coli LOS. Their structures exhibit varied, dose-dependent, TLR4-driven NF-κB activation with both human and mouse TLR4 complexes. Additional cytokine secretion screening identified molecules that induce levels of tumor necrosis factor alpha (TNF-α and interleukin-8 (IL-8 comparable to the levels induced by phosphorylated hexa-acyl disaccharide (PHAD. The lead candidates demonstrated potent immunostimulation in mouse splenocytes, human primary blood mononuclear cells (PBMCs, and human monocyte-derived dendritic cells (DCs. This newly described system allows directed programming of lipid A synthesis and has the potential to generate a diverse array of TLR4 agonist candidates.

  8. Identification of a third protein 4.1 tumor suppressor, protein 4.1R, in meningioma pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Robb, Victoria A.; Li, Wen; Gascard, Philippe; Perry, Arie; Mohandas, Narla; Gutmann, David H.

    2003-06-11

    Meningiomas are common tumors of the central nervous system, however, the mechanisms under lying their pathogenesis are largely undefined. Two members of the Protein 4.1 super family, the neuro fibromatosis 2 (NF2) gene product (merlin/schwannomin) and Protein 4.1B have been implicated as meningioma tumor suppressors. In this report, we demonstrate that another Protein 4.1 family member, Protein 4.1R, also functions as a meningioma tumor suppressor. Based on the assignment of the Protein 4.1R gene to chromosome 1p32-36, a common region of deletion observed in meningiomas, we analyzed Protein 4.1R expression in meningioma cell lines and surgical tumor specimens. We observed loss of Protein 4.1R protein expression in two meningioma cell lines (IOMM-Lee, CH157-MN) by Western blotting as well as in 6 of 15 sporadic meningioma as by immuno histo chemistry (IHC). Analysis of a subset of these sporadic meningiomas by fluorescent in situ hybridization (FISH) with a Protein 4.1R specific probe demonstrated 100 percent concordance with the IHC results. In support of a meningioma tumor suppressor function, over expression of Protein 4.1R resulted in suppression of IOMM-Lee and CH157MN cell proliferation. Similar to the Protein 4.1B and merlin meningioma tumor suppressors, Protein 4.1R localization in the membrane fraction increased significantly under conditions of growth arrest in vitro. Lastly, Protein 4.1R interacted with some known merlin/Protein 4.1B interactors such as CD44 and bII-spectrin, but did not associate with the Protein 4.1B interactors 14-3-3 and PRMT3 or the merlin binding proteins SCHIP-1 and HRS. Collectively, these results suggest that Protein 4.1R functions as an important tumor suppressor important in the molecular pathogenesis of meningioma.

  9. Lipoxin A4 suppresses osteoclastogenesis in RAW264.7 cells and prevents ovariectomy-induced bone loss

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Changyu; Guan, Hanfeng; Cai, Cong; Li, Feng, E-mail: lifengmd@hust.edu.cn; Xiao, Jun, E-mail: jun_xiao@hust.edu.cn

    2017-03-15

    Lipoxin A4 (LXA4; 5S, 6R, 15Strihydroxy- 7,9,13-trans-11-eicosatetraenoic acid) is a metabolic product of arachidonic acid under the action of lipoxidase. This lipid molecule plays important roles in several biological functions, especially inflammatory processes. In vivo, LXA4 regulates the inflammatory response through several signaling pathways. Its mechanism suggests that it might have an effect on osteoclastogenesis and bone loss. Using both in vitro and in vivo studies, it was here observed that LXA4 could significantly inhibit the formation and function of osteoclasts and these effects could be blocked by Boc-2, the specific inhibitor of FPR2/ALX (the receptor of LXA4). Meanwhile, LXA4 reduce the amount of ovariectomy-induced bone loss. These protective effects was found to be associated with inhibition of nuclear factor-κB (NF-κB), activator protein-1 (AP-1), PI3K-AKT, and p-38, ERK, and JNK in MAPKs. The expression of the receptor activator of the NF-κB ligand RANKL:osteoprotegerin ratio and serum levels of TNF-α, IL-1β, and IL-6 were decreased by LXA4. Moreover, LXA4 prevented the production of reactive oxygen species (ROS), the expression of osteoclast-specific genes, including tartrate-resistant acid phosphatase (TRAP), cathepsin K (CK), matrix metalloproteinase (MMP)-9, RANK, and osteoclastic related transcription factors of c-Fos, NFATc1 could also be significantly inhibited by LXA4 in a dose-dependent manner. Studies have demonstrated that LXA4 can inhibit the formation and function of osteoclasts through modulation of several pathways both upstream and downstream of RANKL signaling and FPR2/ALX was involved in the procedures. This shows that LXA4 may be used as a new strategy for the treatment of osteoclast-related diseases. - Highlights: • Lipoxin A4 can significantly inhibit the formation and function of osteoclasts. • Several pathways both upstream and downstream of RANKL signaling can be inhibit by Lipoxin A4. • Lipoxin A4 can

  10. Bundesamt fuer Strahlenschutz (BfS). Annual report 1991

    International Nuclear Information System (INIS)

    1992-08-01

    The progress report submitted by Bundesamt fuer Strahlenschutz reveals that this federal radiation protection agency is not only entrusted with the fulfillment of the federal administrative tasks imposed by law but engages in applications-oriented research regarding the operational, metrological and health-related aspects of radiation protection, regarding nuclear safety and radioactive waste management. In addition, BfS takes care of public-relations tasks. The reports submitted by the BfS departments are completed by summaries of the main research results. (DG) [de

  11. Higgsless superconductivity from topological defects in compact BF terms

    Directory of Open Access Journals (Sweden)

    M. Cristina Diamantini

    2015-02-01

    Full Text Available We present a new Higgsless model of superconductivity, inspired from anyon superconductivity but P- and T-invariant and generalisable to any dimension. While the original anyon superconductivity mechanism was based on incompressible quantum Hall fluids as average field states, our mechanism involves topological insulators as average field states. In D space dimensions it involves a (D−1-form fictitious pseudovector gauge field which originates from the condensation of topological defects in compact low-energy effective BF theories. In the average field approximation, the corresponding uniform emergent charge creates a gap for the (D−2-dimensional branes via the Magnus force, the dual of the Lorentz force. One particular combination of intrinsic and emergent charge fluctuations that leaves the total charge distribution invariant constitutes an isolated gapless mode leading to superfluidity. The remaining massive modes organise themselves into a D-dimensional charged, massive vector. There is no massive Higgs scalar as there is no local order parameter. When electromagnetism is switched on, the photon acquires mass by the topological BF mechanism. Although the charge of the gapless mode (2 and the topological order (4 are the same as those of the standard Higgs model, the two models of superconductivity are clearly different since the origins of the gap, reflected in the high-energy sectors are totally different. In 2D this type of superconductivity is explicitly realised as global superconductivity in Josephson junction arrays. In 3D this model predicts a possible phase transition from topological insulators to Higgsless superconductors.

  12. Turmeric (Curcuma longa) inhibits inflammatory nuclear factor (NF)-κB and NF-κB-regulated gene products and induces death receptors leading to suppressed proliferation, induced chemosensitization, and suppressed osteoclastogenesis.

    Science.gov (United States)

    Kim, Ji H; Gupta, Subash C; Park, Byoungduck; Yadav, Vivek R; Aggarwal, Bharat B

    2012-03-01

    The incidence of cancer is significantly lower in regions where turmeric is heavily consumed. Whether lower cancer incidence is due to turmeric was investigated by examining its effects on tumor cell proliferation, on pro-inflammatory transcription factors NF-κB and STAT3, and on associated gene products. Cell proliferation and cell cytotoxicity were measured by the MTT method, NF-κB activity by EMSA, protein expression by Western blot analysis, ROS generation by FACS analysis, and osteoclastogenesis by TRAP assay. Turmeric inhibited NF-κB activation and down-regulated NF-κB-regulated gene products linked to survival (Bcl-2, cFLIP, XIAP, and cIAP1), proliferation (cyclin D1 and c-Myc), and metastasis (CXCR4) of cancer cells. The spice suppressed the activation of STAT3, and induced the death receptors (DR)4 and DR5. Turmeric enhanced the production of ROS, and suppressed the growth of tumor cell lines. Furthermore, turmeric sensitized the tumor cells to chemotherapeutic agents capecitabine and taxol. Turmeric was found to be more potent than pure curcumin for cell growth inhibition. Turmeric also inhibited NF-κB activation induced by RANKL that correlated with the suppression of osteoclastogenesis. Our results indicate that turmeric can effectively block the proliferation of tumor cells through the suppression of NF-κB and STAT3 pathways. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. U4+ spectroscopic properties in Dsub(2d) with ThCl4, UCl4 and ThSiO4

    International Nuclear Information System (INIS)

    Khan Malek, C.

    1985-01-01

    This thesis is concerned with the study of the electronic structure of the tetravalent actinide ions in solid state. The technique used was high resolution optical spectroscopy. We deal with the U 4+ ion (sf 2 ) in the monocrystals ThCl 4 , UCl 4 , and ThSiO 4 where the U 4+ ion is substituded for the Th 4+ ion by doping. Visible and infrared optical spectra were recorded between 300 and 4.2K. With these three compounds, it is possible to compare the influence of different environments of Dsub(2d) symmetry: real symmetry for U 4+ in UCl 4 and ThSiO 4 ; approximate symmetry in ThCl 4 , whose structure is incommensurate and modulated at low temperature. The fitting of the data was carried out by diagonalizing the hamiltonian which describes the interactions of the U 4+ ion in a crystal field with its environment. This fitting procedure led to a coherent set of spectroscopic parameters. The fluorescence of U 4+ was observed in ThCl 4 and ThSiO 4 and the effect of the incommensurate structure of ThCl 4 on the optical spectra was studied. The symmetry of the U 4+ sites was identified by site selective excitation experiments and a relationship between the incommensurate structure and the lifetime of U 4+ energy levels was found. In conclusion, the U 4+ energy levels in a relatively low crystal field were determined for compounds that have a similar coordination polyhedron about the actinide ion. The values for these energy levels were then compared to those of lanthanide and 3d elements [fr

  14. Quantitative kinetic analysis of PET amyloid imaging agents [11C]BF227 and [18F]FACT in human brain

    International Nuclear Information System (INIS)

    Shidahara, Miho; Watabe, Hiroshi; Tashiro, Manabu; Okamura, Nobuyuki; Furumoto, Shozo; Watanuki, Shoichi; Furukawa, Katsutoshi; Arakawa, Yuma; Funaki, Yoshihito; Iwata, Ren; Gonda, Kohsuke; Kudo, Yukitsuka; Arai, Hiroyuki; Ishiwata, Kiichi; Yanai, Kazuhiko

    2015-01-01

    Introduction: The purpose of this study was to compare two amyloid imaging agents, [ 11 C]BF227 and [ 18 F]FACT (derivative from [ 11 C]BF227) through quantitative pharmacokinetics analysis in human brain. Methods: Positron emission tomography studies were performed on six elderly healthy control (HC) subjects and seven probable Alzheimer’s disease (AD) patients with [ 11 C]BF227 and 10 HC subjects and 10 probable AD patients with [ 18 F]FACT. Data from nine regions of interest were analyzed by several approaches, namely non-linear least-squared fitting methods with arterial input functions (one-tissue compartment model(1TCM), two-tissue compartment model (2TCM)), Logan plot, and linearized methods with reference region (Reference Logan plot (RefLogan), MRTM0, MRTM2). We also evaluated SUV and SUVR for both tracers. The parameters estimated by several approaches were compared between two tracers for detectability of differences between HC and AD patients. Results: For [ 11 C]BF227, there were no significant difference of V T (2TCM, 1TCM) and SUV in all regions (Student t-test; p < 0.05) and significant differences in the DVRs (Logan, RefLogan, and MRTM2) and SUVRs in six neocortical regions (p < 0.05) between the HC and AD groups. For [ 18 F]FACT, significant differences in DVRs (RefLogan, MRTM0, and MRTM2) were observed in more than four neocortical regions between the HC and AD groups (p < 0.05), and the significant differences were found in SUVRs for two neocortical regions (inferior frontal coretex and lateral temporal coretex). Our results showed that both tracers can clearly distinguish between HC and AD groups although the pharmacokinetics and distribution patterns in brain for two tracers were substantially different. Conclusion: This study revealed that although the PET amyloid imaging agents [ 11 C]BF227 and [ 18 F]FACT have similar chemical and biological properties, they have different pharmacokinetics, and caution must be paid for usage of the

  15. Classical and alternative NF-κB signaling cooperate in regulating adipocyte differentiation and function

    DEFF Research Database (Denmark)

    Weidemann, A.; Lovas, A.; Rauch, A.

    2016-01-01

    Background and objective:Inflammation of adipose tissue (AT) is a central mediator of insulin resistance. However, the molecular mechanisms triggered by inflammatory cells are not fully understood. The aim of this study was to analyze the metabolic functions of lymphotoxin-β-receptor (LTβ...... to adipocytes. The molecular mechanism was elucidated by chromatin immunoprecipitation and combinatorial treatment with α-LTβR and tumor necrosis factor (TNF).Results:RelB FatKO mice showed improved insulin sensitivity despite increased adiposity and adipocyte hypertrophy. LTβR-induced activation of p52-Rel.......Conclusions:Our data describe an anti-adipogenic action of LTβR signaling and a novel synergism of alternative and classical NF-κB signaling in the regulation of adipocytes. In conclusion, this strong synergism between the two NF-κB pathways shows a method to inhibit adipocyte differentiation and to improve insulin...

  16. Synthesis, physical and chemical properties, antihypoxic activity of some 5-[((5-(adamantane-1-yl-4-R-4H-1,2,4-triazole-3-ylthiomethyl]-N-R1-1,3,4-thiadiazole-2-amines and 5-[((5-(adamantane-1-yl-4-R-4H-1,2,4-triazole-3-ylthiomethyl]-4-R1-4H-1,2,4-t

    Directory of Open Access Journals (Sweden)

    V. M. Odyntsova

    2018-03-01

    Full Text Available Today, an increase of natural and technogenic situations leads to the disorders of the central nervous system, functional-metabolic processes, vascular diseases, in particular, acute cerebral blood flow disorders. In addition, the changes occurring on the molecular and cellular levels are in the basis of the functional violations of individual systems and the organism as a whole. Hypoxia not only complicates the disease course, but in most cases, determines its outcome. The important role in the fight against hypoxia belongs to antioxidants, which improve the circulating oxygen utilization by the body, reduce its need for the organs and tissues, which is not only expedient but necessary for the treatment of many acute and chronic pathological processes. So, the frequency of the hypoxic states and a wide range of factors causing them determine the relevance of new ways and methods finding to overcome the oxygen deficiency. The aim of this work is the purposeful search of some 5-[((5-(adamantane-1-yl-4-R-4H-1,2,4-triazole-3-ylthiomethyl]-N-R1-1,3,4-thiadiazole-2-amines and 5-[((5-(adamantane-1-yl-4-R-4H-1,2,4-triazole-3-ylthiomethyl]-4-R1-4H-1,2,4-triazole-3-thiols, the study of their physical and chemical properties and pharmacological screening of the antihypoxic activity of the obtained compounds. Materials and methods. The study of physical and chemical properties was conducted on certified and licensed modern equipment. Antihypoxic activity was studied during the modeling process of hypoxia with hypercapnia. Mexidol was used as a comparison drug in studies at a dose of 100 mg/kg. Results. As the result of the study, it was found that the synthesized compounds and the comparison drug influenced on rats’ life span differently. Compounds, the antihypoxic activity of which exceeded control have been discovered, and others’ were at the level of Mexidol. A number of compounds showed a somewhat less activity in comparison with control, and two

  17. Commensal-induced regulatory T cells mediate protection against pathogen-stimulated NF-kappaB activation.

    Directory of Open Access Journals (Sweden)

    Caitlin O'Mahony

    Full Text Available Host defence against infection requires a range of innate and adaptive immune responses that may lead to tissue damage. Such immune-mediated pathologies can be controlled with appropriate T regulatory (Treg activity. The aim of the present study was to determine the influence of gut microbiota composition on Treg cellular activity and NF-kappaB activation associated with infection. Mice consumed the commensal microbe Bifidobacterium infantis 35624 followed by infection with Salmonella typhimurium or injection with LPS. In vivo NF-kappaB activation was quantified using biophotonic imaging. CD4+CD25+Foxp3+ T cell phenotypes and cytokine levels were assessed using flow cytometry while CD4+ T cells were isolated using magnetic beads for adoptive transfer to naïve animals. In vivo imaging revealed profound inhibition of infection and LPS induced NF-kappaB activity that preceded a reduction in S. typhimurium numbers and murine sickness behaviour scores in B. infantis-fed mice. In addition, pro-inflammatory cytokine secretion, T cell proliferation, and dendritic cell co-stimulatory molecule expression were significantly reduced. In contrast, CD4+CD25+Foxp3+ T cell numbers were significantly increased in the mucosa and spleen of mice fed B. infantis. Adoptive transfer of CD4+CD25+ T cells transferred the NF-kappaB inhibitory activity. Consumption of a single commensal micro-organism drives the generation and function of Treg cells which control excessive NF-kappaB activation in vivo. These cellular interactions provide the basis for a more complete understanding of the commensal-host-pathogen trilogue that contribute to host homeostatic mechanisms underpinning protection against aberrant activation of the innate immune system in response to a translocating pathogen or systemic LPS.

  18. A density functional theory study on the interactions between dibenzothiophene and tetrafluoroborate-based ionic liquids.

    Science.gov (United States)

    Lin, Jin; Lü, Renqing; Wu, Chongchong; Xiao, Ye; Liang, Fei; Famakinwa, Temilola

    2017-04-01

    The interactions between dibenzothiophene (DBT) and N-butyl-N-methylimidazolium tetrafluoroborate ([BMIM][BF 4 ]), N-butyl-N-methylmorpholinium tetrafluoroborate ([Bmmorpholinium][BF 4 ]), N-butyl-N-methylpiperdinium tetrafluoroborate ([BMPiper][BF 4 ]), N-butyl-N-methylpyrrolidinium tetrafluoroborate ([BMPyrro][BF 4 ]), and N-butylpyridinium tetrafluoroborate ([BPY][BF 4 ]) were investigated using density functional theory approach. Geometric, electron, and topological properties were analyzed using natural bond orbital, atoms in molecules theory, and noncovalent interaction methods in order to understand intermolecular interactions between DBT and ionic liquids. The result shows that hydrogen bond and van der Waals interactions are widespread in all the ionic liquids-DBT systems. Ion-π interactions between DBT and cation or anion are also observed, while π + -π interactions are only found in the [BMIM][BF 4 ]-DBT and [BPY][BF 4 ]-DBT systems. The order of interaction energy is [BPY][BF4]-DBT > [BMIM][BF 4 ]-DBT > [BMPiper][BF 4 ]-DBT > [BMPyrro][BF 4 ]-DBT > [BMmorpholinum][BF 4 ]-DBT. The energies between DBT and the two ionic liquids containing aromatic cations are significantly higher.

  19. "4 x 4 vasovasostomy": A simplified technique for vasectomy reversal

    Directory of Open Access Journals (Sweden)

    Rajeev Kumar

    2010-01-01

    Conclusions : The "4 × 4" modified two-layer vasovasostomy is a simple technique that can be performed in quick time with excellent results. It may allow a common ground between the complex microdot two-layer technique and the over-simplified single-layer procedure.

  20. Microwave Acoustics Handbook. Volume 4. Bulk Wave Velocities-Numerical Data.

    Science.gov (United States)

    1980-06-01

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  1. Prototype ATLAS IBL modules using the FE-I4A front-end readout chip

    Czech Academy of Sciences Publication Activity Database

    Albert, J.; Alex, M.; Alimonti, G.; Hejtmánek, Martin; Janoška, Zdenko; Korchak, Oleksandr; Popule, Jiří; Šícho, Petr; Sloboda, Michal; Tomášek, Michal; Vrba, Václav

    2012-01-01

    Roč. 7, NOV (2012), 1-45 ISSN 1748-0221 R&D Projects: GA MŠk LA08032 Institutional research plan: CEZ:AV0Z10100502 Keywords : ATLAS * upgrade * tracker * silicon * FE-I4 * planar sensors * test beam Subject RIV: BF - Elementary Particles and High Energy Physics Impact factor: 1.869, year: 2011 http://arxiv.org/abs/arXiv:1209.1906

  2. Targeting the ECM to Enhance Drug Delivery in Nf1-Associated Nerve Sheath Tumors

    Science.gov (United States)

    2016-10-01

    development of the principal discipline(s) of the project? • We have learned that the drug PEGPH20, which degrades a component of connective tissue called...AWARD NUMBER: W81XWH-15-1-0114 TITLE: Targeting the ECM to Enhance Drug Delivery in Nf1-Associated Nerve Sheath Tumors PRINCIPAL INVESTIGATOR...14 Sep 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER NF140089 Targeting the ECM to Enhance Drug Delivery in Nf1-Associated Nerve Sheath Tumors 5b

  3. Targeted Disruption of NF1 in Osteocytes Increases FGF23 and Osteoid With Osteomalacia-like Bone Phenotype.

    Science.gov (United States)

    Kamiya, Nobuhiro; Yamaguchi, Ryosuke; Aruwajoye, Olumide; Kim, Audrey J; Kuroyanagi, Gen; Phipps, Matthew; Adapala, Naga Suresh; Feng, Jian Q; Kim, Harry Kw

    2017-08-01

    Neurofibromatosis type 1 (NF1, OMIM 162200), caused by NF1 gene mutations, exhibits multi-system abnormalities, including skeletal deformities in humans. Osteocytes play critical roles in controlling bone modeling and remodeling. However, the role of neurofibromin, the protein product of the NF1 gene, in osteocytes is largely unknown. This study investigated the role of neurofibromin in osteocytes by disrupting Nf1 under the Dmp1-promoter. The conditional knockout (Nf1 cKO) mice displayed serum profile of a metabolic bone disorder with an osteomalacia-like bone phenotype. Serum FGF23 levels were 4 times increased in cKO mice compared with age-matched controls. In addition, calcium-phosphorus metabolism was significantly altered (calcium reduced; phosphorus reduced; parathyroid hormone [PTH] increased; 1,25(OH) 2 D decreased). Bone histomorphometry showed dramatically increased osteoid parameters, including osteoid volume, surface, and thickness. Dynamic bone histomorphometry revealed reduced bone formation rate and mineral apposition rate in the cKO mice. TRAP staining showed a reduced osteoclast number. Micro-CT demonstrated thinner and porous cortical bones in the cKO mice, in which osteocyte dendrites were disorganized as assessed by electron microscopy. Interestingly, the cKO mice exhibited spontaneous fractures in long bones, as found in NF1 patients. Mechanical testing of femora revealed significantly reduced maximum force and stiffness. Immunohistochemistry showed significantly increased FGF23 protein in the cKO bones. Moreover, primary osteocytes from cKO femora showed about eightfold increase in FGF23 mRNA levels compared with control cells. The upregulation of FGF23 was specifically and significantly inhibited by PI3K inhibitor Ly294002, indicating upregulation of FGF23 through PI3K in Nf1-deficient osteocytes. Taken together, these results indicate that Nf1 deficiency in osteocytes dramatically increases FGF23 production and causes a mineralization

  4. Hierarchical chestnut-like MnCo2O4 nanoneedles grown on nickel foam as binder-free electrode for high energy density asymmetric supercapacitors

    Science.gov (United States)

    Hui, Kwun Nam; Hui, Kwan San; Tang, Zikang; Jadhav, V. V.; Xia, Qi Xun

    2016-10-01

    Hierarchical chestnut-like manganese cobalt oxide (MnCo2O4) nanoneedles (NNs) are successfully grown on nickel foam using a facile and cost-effective hydrothermal method. High resolution TEM image further verifies that the chestnut-like MnCo2O4 structure is assembled by numerous 1D MnCo2O4 nanoneedles, which are formed by numerous interconnected MnCo2O4 nanoparticles with grain diameter of ∼10 nm. The MnCo2O4 electrode exhibits high specific capacitance of 1535 F g-1 at 1 A g-1 and good rate capability (950 F g-1 at 10 A g-1) in a 6 M KOH electrolyte. An asymmetric supercapacitor is fabricated using MnCo2O4 NNs on Ni foam (MnCo2O4 NNs/NF) as the positive electrode and graphene/NF as the negative electrode. The device shows an operation voltage of 1.5 V and delivers a high energy density of ∼60.4 Wh kg-1 at a power density of ∼375 W kg-1. Moreover, the device exhibits an excellent cycling stability of 94.3% capacitance retention after 12000 cycles at 30 A g-1. This work demonstrates that hierarchical chestnut-like MnCo2O4 NNs could be a promising electrode for the high performance energy storage devices.

  5. Expression of programmed cell death protein 4 (PDCD4) and miR-21 in urothelial carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, Nicolas, E-mail: simplissimus@gmx.de [Department of Urology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn (Germany); Goeke, Friederike, E-mail: Friederike.goeke@ukb.uni-bonn.de [Department of Pathology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn (Germany); Splittstoesser, Vera, E-mail: Veri.sp@web.de [Department of Urology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn (Germany); Lankat-Buttgereit, Brigitte, E-mail: Lankatbu@staff.uni-marburg.de [Department of Internal Medicine, Philipps-University of Marburg, Baldingerstrasse, 35043 Marburg (Germany); Mueller, Stefan C., E-mail: Stefan.mueller@ukb.uni-bonn.de [Department of Urology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn (Germany); Ellinger, Joerg, E-mail: Joerg.ellinger@ukb.uni-bonn.de [Department of Urology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn (Germany)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer The tumor suppressor gene PDCD4 is down-regulated in many tumorous entities. Black-Right-Pointing-Pointer We investigate the impact of PDCD4 and its regulating factor miR-21 in urothelial carcinoma. Black-Right-Pointing-Pointer We confirm PDCD4 as a tumor suppressor gene and it could be a diagnostic marker for this tumor. -- Abstract: Background: We investigated the role of the programmed cell death 4 (PDCD4) tumor suppressor gene in specimens of transitional cell carcinoma and of healthy individuals. Methods: PDCD4 immunohistochemical expression was investigated in 294 cases in histologically proven transitional cell carcinoma in different tumorous stages (28 controls, 122 non-muscle invasive urothelial carcinoma, stages Tis-T1, 119 invasive transitional cell carcinoma stages T2-T4 and 25 metastases). MiR-21 expression, an important PDCD4 regulator, was assessed with real-time PCR analysis and showed inverse correlation to tissue PDCD4 expression. Results: Nuclear and cytoplasmatic PDCD4 immunostaining decreased significantly with histopathological progression of the tumor (p < 0001). Controls showed strong nuclear and cytoplasmatic immunohistochemical staining. MiR-21 up regulation in tissue corresponded to PDCD4 suppression. Conclusions: These data support a decisive role for PDCD4 down regulation in transitional cell carcinoma and confirm miR-21 as a negative regulator for PDCD4. Additionally, PDCD4 immunohistochemical staining turns out to be a possible diagnostic marker for transitional cell carcinoma.

  6. Expression of programmed cell death protein 4 (PDCD4) and miR-21 in urothelial carcinoma

    International Nuclear Information System (INIS)

    Fischer, Nicolas; Göke, Friederike; Splittstößer, Vera; Lankat-Buttgereit, Brigitte; Müller, Stefan C.; Ellinger, Jörg

    2012-01-01

    Highlights: ► The tumor suppressor gene PDCD4 is down-regulated in many tumorous entities. ► We investigate the impact of PDCD4 and its regulating factor miR-21 in urothelial carcinoma. ► We confirm PDCD4 as a tumor suppressor gene and it could be a diagnostic marker for this tumor. -- Abstract: Background: We investigated the role of the programmed cell death 4 (PDCD4) tumor suppressor gene in specimens of transitional cell carcinoma and of healthy individuals. Methods: PDCD4 immunohistochemical expression was investigated in 294 cases in histologically proven transitional cell carcinoma in different tumorous stages (28 controls, 122 non-muscle invasive urothelial carcinoma, stages Tis-T1, 119 invasive transitional cell carcinoma stages T2–T4 and 25 metastases). MiR-21 expression, an important PDCD4 regulator, was assessed with real-time PCR analysis and showed inverse correlation to tissue PDCD4 expression. Results: Nuclear and cytoplasmatic PDCD4 immunostaining decreased significantly with histopathological progression of the tumor (p < 0001). Controls showed strong nuclear and cytoplasmatic immunohistochemical staining. MiR-21 up regulation in tissue corresponded to PDCD4 suppression. Conclusions: These data support a decisive role for PDCD4 down regulation in transitional cell carcinoma and confirm miR-21 as a negative regulator for PDCD4. Additionally, PDCD4 immunohistochemical staining turns out to be a possible diagnostic marker for transitional cell carcinoma.

  7. NF-κB and p53 Are the Dominant Apoptosis-inducing Transcription Factors Elicited by the HIV-1 Envelope

    OpenAIRE

    Perfettini, Jean-Luc; Roumier, Thomas; Castedo, Maria; Larochette, Nathanael; Boya, Patricia; Raynal, Brigitte; Lazar, Vladimir; Ciccosanti, Fabiola; Nardacci, Roberta; Penninger, Josef; Piacentini, Mauro; Kroemer, Guido

    2004-01-01

    The coculture of cells expressing the HIV-1 envelope glycoprotein complex (Env) with cells expressing CD4 results into cell fusion, deregulated mitosis, and subsequent cell death. Here, we show that NF-κB, p53, and AP1 are activated in Env-elicited apoptosis. The nuclear factor κB (NF-κB) super repressor had an antimitotic and antiapoptotic effect and prevented the Env-elicited phosphorylation of p53 on serine 15 and 46, as well as the activation of AP1. Transfection with dominant-negative p5...

  8. Synthesis of LiNixFe1−xPO4 solid solution as cathode materials for lithium ion batteries

    International Nuclear Information System (INIS)

    Qing, Rui; Yang, Ming-Che; Meng, Ying Shirley; Sigmund, Wolfgang

    2013-01-01

    Highlights: • Phase pure LiNi x Fe 1−x PO 4 and LiNi x Fe 1−x PO 4 /C nanocomposites were obtained via a solid state reaction method. • Crystallite sizes were around 50 nm. Linear relationship was observed between lattice parameters and chemical composition. • Synthesized materials displayed electronic conductivity similar to reported value of LiFePO 4 . Carbon coating increased the conductivity to ∼10 −3 S/cm. • Chemical delithiation via NO 2 BF 4 extracted more than 90% of lithium from the nanocomposites, proving that Ni 2+ /Ni 3+ redox couple was activated. -- Abstract: Nanosize LiNi x Fe 1−x PO 4 solid solution and LiNi x Fe 1−x PO 4 /C nanocomposites were prepared via a solid state reaction method under argon atmosphere. A single phase olivine-type structure with Pnma space group was determined by X-ray diffraction. Crystallite sizes were found to be around 50 nm. A linear relationship was observed between lattice parameters and chemical composition which follows Vegard's law. Synthesized materials displayed electronic conductivity similar to previous reported values of LiFePO 4 . Carbon coating further increased the overall conductivity of nanocomposites to the order of 10 −3 S/cm. Chemical delithiation via NO 2 BF 4 oxidant extracted more than 95% of lithium from the solid solution material accompanied by a decrease in lattice parameters

  9. Gender- and Gestational Age-Specific Body Fat Percentage at Birth.

    LENUS (Irish Health Repository)

    Hawkes, Colin P

    2011-08-08

    Background: There is increasing evidence that in utero growth has both immediate and far-reaching influence on health. Birth weight and length are used as surrogate measures of in utero growth. However, these measures poorly reflect neonatal adiposity. Air-displacement plethysmography has been validated for the measurement of body fat in the neonatal population. Objective: The goal of this study was to show the normal reference values of percentage body fat (%BF) in infants during the first 4 days of life. Methods: As part of a large population-based birth cohort study, fat mass, fat-free mass, and %BF were measured within the first 4 days of life using air-displacement plethsymography. Infants were grouped into gestational age and gender categories. Results: Of the 786 enrolled infants, fat mass, fat-free mass, and %BF were measured in 743 (94.5%) infants within the first 4 days of life. %BF increased significantly with gestational age. Mean (SD) %BF at 36 to 37 weeks\\' gestation was 8.9% (3.5%); at 38 to 39 weeks\\' gestation, 10.3% (4%); and at 40 to 41 weeks\\' gestation, 11.2% (4.3%) (P < .001). Female infants had significantly increased mean (SD) %BF at 38 to 39(11.1% [3.9%] vs 9.8% [3.9%]; P = .012) and at 40 to 41 (12.5% [4.4%] vs 10% [3.9%]; P < .001) weeks\\' gestation compared with male infants. Gender- and gestational age-specific centiles were calculated, and a normative table was generated for reference. Conclusion: %BF at birth is influenced by gestational age and gender. We generated accurate %BF centiles from a large population-based cohort.

  10. Association of Adipocyte Fatty Acid–Binding Protein (FABP4 Level with Obesity in Women

    Directory of Open Access Journals (Sweden)

    Hussein Jasim AL-Harbi

    2017-02-01

    Full Text Available Adipocyte Fatty Acid–Binding Protein(FABP 4 is produced by mature adipocytes, cytoplasmic lipid protein carrier, 132 amino acid and secretion increases during adipogenesis. Chemerin is adipocytokine anewly discovered novel adipokine that regulates adipocyte metabolism and adipogenesis, is The aim of this study is to investigated the relationship of chemerin and FABP4 level with obesity and identifing the usefulness of waist circumference (WC, hip circumference , waist-to-hip ratio (WHR, body mass index (BMI,, and body fat percentage( BF% in screening obesity . Anthropometric data were collected for 180 healthy women with an age range 35-60 years, divided into four groups due to body mass index: normalweight (18.5-24.9 kg/m2, overweight (25-29.9 kg/m2 , obese (30-39.9 kg/m2 and morbid(≥ 40 kg/m2. The results revealed that FABP4 and Chemerin circulating concentration were significantly increased (P<0.01 in healthy morbid and obese adult women when compared with lean healthy (normal and over weight women also significant increase of A-FABP and Chemerin with the body mass index (BMI, waist hip ratio, hip circumference, waist circumference, and with BF percentage. According to these finding suggest that the circulating chemerin and A-FABP levels can be used as Prediction marker of overall fat mass and obesity in women.

  11. Thermal and x-ray studies on Tl2U(MoO4)3 and Tl4U(MoO4)4

    International Nuclear Information System (INIS)

    Dahale, N.D.; Keskar, Meera; Kulkarni, N.K.; Singh Mudher, K.D.

    2006-01-01

    In the quaternary Tl-U(IV)-Mo-O system, two new compounds namely Tl 2 U(MoO 4 ) 3 and Tl 4 U(MoO 4 ) 4 were prepared and characterized by powder X-ray diffraction and thermal methods. These compounds were prepared by solid state reactions of Tl 2 MoO 4 , UMoO 5 and MoO 3 in the required stoichiometric ratio at 500 deg C in evacuated sealed quartz ampoule. The XRD data of Tl 2 U(MoO 4 ) 3 and Tl 4 U(MoO 4 ) 4 were indexed on orthorhombic cell. TG curves of Tl 2 U(MoO 4 ) 3 and Tl 4 U(MoO 4 ) 4 did not show any weight change up to 700 deg C in an inert atmosphere. During heating in an inert atmosphere, Tl 2 U(MoO 4 ) 3 and Tl 4 U(MoO 4 ) 4 showed endothermic Dta peaks due to melting of the compounds at 519 and 565 deg C, respectively. (author)

  12. Adsorption of tentacled tetragonal star connectors, C4R4-Co-C-5(HgX)(5), on mercury

    Czech Academy of Sciences Publication Activity Database

    Pospíšil, Lubomír; Varaksa, N.; Magnera, T. F.; Brotin, T.; Michl, Josef

    2007-01-01

    Roč. 23, č. 2 (2007), s. 930-935 ISSN 0743-7463 R&D Projects: GA MŠk LC510; GA MŠk OC 140; GA MŠk ME 857; GA AV ČR IAA400400505 Grant - others:USARO(US) W911NF-05-0535; NSF(US) OISE 0532040 Institutional research plan: CEZ:AV0Z40400503 Source of funding: V - iné verejné zdroje ; V - iné verejné zdroje Keywords : air water interface * square-grid polymer * potential sweep voltammetry * electrochemistry Subject RIV: CG - Electrochemistry Impact factor: 4.009, year: 2007

  13. Extensive proteomic screening identifies the obesity-related NYGGF4 protein as a novel LRP1-interactor, showing reduced expression in early Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Taddei Kevin

    2010-01-01

    Full Text Available Abstract Background The low-density lipoprotein receptor related protein 1 (LRP1 has been implicated in Alzheimer's disease (AD but its signalling has not been fully evaluated. There is good evidence that the cytoplasmic domain of LRP1 is involved in protein-protein interactions, important in the cell biology of LRP1. Results We carried out three yeast two-hybrid screens to identify proteins that interact with the cytoplasmic domain of LRP1. The screens included both conventional screens as well as a novel, split-ubiquitin-based screen in which an LRP1 construct was expressed and screened as a transmembrane protein. The split-ubiquitin screen was validated in a screen using full-length amyloid protein precursor (APP, which successfully identified FE65 and FE65L2, as well as novel interactors (Rab3a, Napg, and ubiquitin b. Using both a conventional screen as well as the split-ubiquitin screen, we identified NYGGF4 as a novel LRP1 interactor. The interaction between LRP1 and NYGGF4 was validated using two-hybrid assays, coprecipitation and colocalization in mammalian cells. Mutation analysis demonstrated a specific interaction of NYGGF4 with an NPXY motif that required an intact tyrosine residue. Interestingly, while we confirmed that other LRP1 interactors we identified, including JIP1B and EB-1, were also able to bind to APP, NYGGF4 was unique in that it showed specific binding with LRP1. Expression of NYGGF4 decreased significantly in patients with AD as compared to age-matched controls, and showed decreasing expression with AD disease progression. Examination of Nyggf4 expression in mice with different alleles of the human APOE4 gene showed significant differences in Nyggf4 expression. Conclusions These results implicate NYGGF4 as a novel and specific interactor of LRP1. Decreased expression of LRP1 and NYGGF4 over disease, evident with the presence of even moderate numbers of neuritic plaques, suggests that LRP1-NYGGF4 is a system altered

  14. EBV induces persistent NF-κB activation and contributes to survival of EBV-positive neoplastic T- or NK-cells.

    Directory of Open Access Journals (Sweden)

    Honami Takada

    Full Text Available Epstein-Barr virus (EBV has been detected in several T- and NK-cell neoplasms such as extranodal NK/T-cell lymphoma nasal type, aggressive NK-cell leukemia, EBV-positive peripheral T-cell lymphoma, systemic EBV-positive T-cell lymphoma of childhood, and chronic active EBV infection (CAEBV. However, how this virus contributes to lymphomagenesis in T or NK cells remains largely unknown. Here, we examined NF-κB activation in EBV-positive T or NK cell lines, SNT8, SNT15, SNT16, SNK6, and primary EBV-positive and clonally proliferating T/NK cells obtained from the peripheral blood of patients with CAEBV. Western blotting, electrophoretic mobility shift assays, and immunofluorescent staining revealed persistent NF-κB activation in EBV-infected cell lines and primary cells from patients. Furthermore, we investigated the role of EBV in infected T cells. We performed an in vitro infection assay using MOLT4 cells infected with EBV. The infection directly induced NF-κB activation, promoted survival, and inhibited etoposide-induced apoptosis in MOLT4 cells. The luciferase assay suggested that LMP1 mediated NF-κB activation in MOLT4 cells. IMD-0354, a specific inhibitor of NF-κB that suppresses NF-κB activation in cell lines, inhibited cell survival and induced apoptosis. These results indicate that EBV induces NF-κB-mediated survival signals in T and NK cells, and therefore, may contribute to the lymphomagenesis of these cells.

  15. Synthesis of new low band gap dyes with BF{sub 2}-azopyrrole complex and their use for dye-sensitized solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Mikroyannidis, John A. [Chemical Technology Laboratory, Department of Chemistry, University of Patras, GR-26500 Patras (Greece); Roy, M.S. [Defence Laboratory, Jodhpur (Raj.) (India); Sharma, G.D. [Physics Department, Molecular Electronic and Optoelectronic Device Laboratory, JNV University, Jodhpur (Raj.) 342005 (India); Jaipur Engineering College, Kukas, Jaipur (Raj.) (India)

    2010-08-15

    The diazonium salt derived from 4-aminobenzoic acid, 4-aminophenol or 2-aminophenol reacted with half equivalent of pyrrole to afford symmetrical 2,5-bisazopyrroles. They reacted subsequently with boron trifluoride in the presence of triethylamine to afford the corresponding BF{sub 2}-azopyrrole complexes D1, D2 and D3 respectively. They were soluble and stable in nonprotic solvents such as chloroform, dichloromethane and tetrahydrofuran but unstable in protic solvents such as ethanol. Their absorption spectra were broad with optical band gap of 1.49-1.70 eV. Among these dyes D2 displayed the broader absorption spectrum with low band gap E{sub g}{sup opt} of 1.49 eV. We have utilized these complexes as photosensitizers for quasi solid state dye-sensitized solar cells (DSSCs) and achieved power conversion efficiency in the range of 4.0-6.0%. We have also found that the co-adsorption of citric acid hindered the formation of dye aggregates and might improve the electron injection efficiency leading to an enhancement in short circuit photocurrent. This work suggests that metal-free dyes based on BF{sub 2}-azopyrrole complex are promising candidates for improvement of the DSSC performance. (author)

  16. In situ study of heavy ion induced radiation damage in NF616 (P92) alloy

    International Nuclear Information System (INIS)

    Topbasi, Cem; Motta, Arthur T.; Kirk, Mark A.

    2012-01-01

    Highlights: ► The ferritic–martensitic alloy NF616 was irradiated in situ with 1 MeV Kr ions at 50 K and 473 K. ► The defect cluster density increases with dose and saturates at ∼6 dpa at 50 K and 473 K. ► The defect size distributions do not change with dose at this temperature range. ► Results indicate that defect cluster formation and destruction is governed by cascade impact. - Abstract: NF616 is a nominal 9Cr ferritic–martensitic steel that is amongst the primary candidates for cladding and duct applications in the Sodium-Cooled Fast Reactor, one of the Generation IV nuclear energy systems. In this study, an in situ investigation of the microstructure evolution in NF616 under heavy ion irradiation has been conducted. NF616 was irradiated to 8.4 dpa at 50 K and to 7.6 dpa at 473 K with 1 MeV Kr ions. Nano-sized defects first appeared as white dots in dark-field TEM images and their areal density increased until saturation (∼6 dpa). Dynamic observations at 50 K and 473 K showed appearance and disappearance of TEM-visible defect clusters under irradiation that continued above saturation dose. Quantitative analysis showed no significant change in the average size (∼3–4 nm) and distribution of defect clusters with increasing dose at 50 K and 473 K. These results indicate a cascade-driven process of microstructure evolution under irradiation in these alloys that involves both the formation of TEM-visible defect clusters by various degrees of cascade overlap and cascade induced defect cluster elimination. According to this mechanism, saturation of defect cluster density is reached when the rate of defect cluster formation by overlap is equal to the rate of cluster elimination during irradiation.

  17. Significance of thymosin β4 and implication of PINCH-1-ILK-α-parvin (PIP complex in human dilated cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Nikolai Sopko

    Full Text Available Myocardial remodeling is a major contributor in the development of heart failure (HF after myocardial infarction (MI. Integrin-linked kinase (ILK, LIM-only adaptor PINCH-1, and α-parvin are essential components of focal adhesions (FAs, which are highly expressed in the heart. ILK binds tightly to PINCH-1 and α-parvin, which regulates FA assembly and promotes cell survival via the activation of the kinase Akt. Mice lacking ILK, PINCH or α-parvin have been shown to develop severe defects in the heart, suggesting that these proteins play a critical role in heart function. Utilizing failing human heart tissues (dilated cardiomyopathy, DCM, we found a 2.27-fold (p<0.001 enhanced expression of PINCH, 4 fold for α-parvin, and 10.5 fold (p<0.001 for ILK as compared to non-failing (NF counterparts. No significant enhancements were found for the PINCH isoform PINCH-2 and parvin isoform β-parvin. Using a co-immunoprecipitation method, we also found that the PINCH-1-ILK-α-parvin (PIP complex and Akt activation were significantly up-regulated. These observations were further corroborated with the mouse myocardial infarction (MI and transaortic constriction (TAC model. Thymosin beta4 (Tβ4, an effective cell penetrating peptide for treating MI, was found to further enhance the level of PIP components and Akt activation, while substantially suppressing NF-κB activation and collagen expression--the hallmarks of cardiac fibrosis. In the presence of an Akt inhibitor, wortmannin, we show that Tβ4 had a decreased effect in protecting the heart from MI. These data suggest that the PIP complex and activation of Akt play critical roles in HF development. Tβ4 treatment likely improves cardiac function by enhancing PIP mediated Akt activation and suppressing NF-κB activation and collagen-mediated fibrosis. These data provide significant insight into the role of the PIP-Akt pathway and its regulation by Tβ4 treatment in post-MI.

  18. BRD4 Phosphorylation Regulates HPV E2-Mediated Viral Transcription, Origin Replication, and Cellular MMP-9 Expression

    Directory of Open Access Journals (Sweden)

    Shwu-Yuan Wu

    2016-08-01

    Full Text Available Post-translational modification can modulate protein conformation and alter binding partner recruitment within gene regulatory regions. Here, we report that bromodomain-containing protein 4 (BRD4, a transcription co-factor and chromatin regulator, uses a phosphorylation-induced switch mechanism to recruit E2 protein encoded by cancer-associated human papillomavirus (HPV to viral early gene and cellular matrix metalloproteinase-9 (MMP-9 promoters. Enhanced MMP-9 expression, induced upon keratinocyte differentiation, occurs via BRD4-dependent recruitment of active AP-1 and NF-κB to their target sequences. This is triggered by replacement of AP-1 family members JunB and JunD by c-Jun and by re-localization of NF-κB from the cytoplasm to the nucleus. In addition, BRD4 phosphorylation is critical for E2- and origin-dependent HPV DNA replication. A class of phospho-BRD4-targeting compounds, distinct from the BET bromodomain inhibitors, effectively blocks BRD4 phosphorylation-specific functions in transcription and factor recruitment.

  19. Immunosuppressive effect of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) through the inhibition of T-lymphocyte proliferation and IL-2 production

    International Nuclear Information System (INIS)

    Yun, Cheol-Heui; Son, Chang Gue; Jung, Uhee; Han, Seung Hyun

    2006-01-01

    2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the predominant heterocyclic amine formed in cooked meat and fish and causes cancers in the colon, the mammary glands, and the lymphoid organs. In the present study, we investigated the immunological impact of PhIP using thymocytes isolated from Balb/c mice and a murine thymocyte-derived cell line, EL4. Treatment of the thymocytes with PhIP moderately inhibited T-cell mitogen-induced cell proliferation and interleukin (IL)-2 secretion. Reverse transcription-polymerase chain reaction (RT-PCR) analysis demonstrated that PhIP attenuated IL-2 mRNA expression in the thymocytes and EL4 cells stimulated with phytohemagglutinin (PHA) plus phorbol 12-myristate 13-acetate (PMA). In vitro transient transfection assay using a reporter gene construct containing IL-2 promoter showed that the decrease in the steady-state IL-2 mRNA level by PhIP is partially due to the attenuation of IL-2 mRNA synthesis at the transcriptional level. Furthermore, an electrophoretic mobility shift assay showed that PhIP inhibited DNA binding activity of nuclear factor for immunoglobulin κ chain in B cells (NF-κB), activator protein-1 (AP-1) and nuclear factor of activated T cells (NF-AT), which are known to be responsible for IL-2 transcriptional activation. Concomitantly, PhIP inhibited the PMA/PHA-induced generation of reactive oxygen species (ROS) involved in activation of the transcription factors. These results suggest that PhIP has potential immunosuppressive effects by inhibiting T-cell proliferation and IL-2 expression through down regulation of ROS generation and thereby inhibiting NF-κB, AP-1 and NF-AT activation

  20. Pedilanthus tithymaloides Inhibits HSV Infection by Modulating NF-κB Signaling.

    Directory of Open Access Journals (Sweden)

    Durbadal Ojha

    Full Text Available Pedilanthus tithymaloides (PT, a widely used ethnomedicinal plant, has been employed to treat a number of skin conditions. To extend its utility and to fully exploit its medicinal potential, we have evaluated the in vitro antiviral activity of a methanolic extract of PT leaves and its isolated compounds against Herpes Simplex Virus type 2 (HSV-2. Bioactivity-guided studies revealed that the extract and one of its constituents, luteolin, had potent antiviral activity against wild-type and clinical isolates of HSV-2 (EC50 48.5-52.6 and 22.4-27.5 μg/ml, respectively, with nearly complete inhibition at 86.5-101.8 and 40.2-49.6 μg/ml, respectively. The inhibitory effect was significant (p<0.001 when the drug was added 2 h prior to infection, and was effective up to 4 h post-infection. As viral replication requires NF-κB activation, we examined whether the observed extract-induced inhibition of HSV-2 was related to NF-κB inhibition. Interestingly, we observed that treatment of HSV-2-infected cells with extract or luteolin suppressed NF-κB activation. Although NF-κB, JNK and MAPK activation was compromised during HSV replication, neither the extract nor luteolin affected HSV-2-induced JNK1/2 and MAPK activation. Moreover, the PT leaf extract and luteolin potently down-regulated the expression of tumor necrosis factor (TNF-α, Interleukin (IL-1β, IL-6, NO and iNOS and the production of gamma interferon (IFN-γ, which are directly involved in controlling the NF-κB signaling pathway. Thus, our results indicate that both PT leaf extract and luteolin modulate the NF-κB signaling pathway, resulting in the inhibition of HSV-2 replication.

  1. Effect of baicalin on toll-like receptor 4-mediated ischemia/reperfusion inflammatory responses in alcoholic fatty liver condition

    International Nuclear Information System (INIS)

    Kim, Seok-Joo; Lee, Sun-Mee

    2012-01-01

    Alcoholic fatty liver is susceptible to secondary stresses such as ischemia/reperfusion (I/R). Baicalin is an active component extracted from Scutellaria baicalensis, which is widely used in herbal preparations for treatment of hepatic diseases and inflammatory disorders. This study evaluated the potential beneficial effect of baicalin on I/R injury in alcoholic fatty liver. Rats were fed an alcohol liquid diet or a control isocaloric diet for 5 weeks, and then subjected to 60 min of hepatic ischemia and 5 h of reperfusion. Baicalin (200 mg/kg) was intraperitoneally administered 24 and 1 h before ischemia. After reperfusion, baicalin attenuated the increases in serum alanine aminotransferase activity, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels in alcoholic fatty liver. The increased levels of TNF-α and IL-6 mRNA expression and inducible nitric oxide synthase and cyclooxygenase-2 protein and mRNA expressions increased after reperfusion, which were higher in ethanol-fed animals, were attenuated by baicalin. In ethanol-fed animals, baicalin attenuated the increases in toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 protein expressions and the nuclear translocation of NF-κB after reperfusion. In conclusion, our findings suggest that baicalin ameliorates I/R-induced hepatocellular damage by suppressing TLR4-mediated inflammatory responses in alcoholic fatty liver. -- Highlights: ► Baicalin attenuates hepatic I/R-induced inflammation in alcoholic fatty liver. ► Baicalin downregulates TLR4, MyD88 expression during I/R in alcoholic fatty liver. ► Baicalin attenuates NF-κB nuclear translocation during I/R in alcoholic fatty liver.

  2. Preparation and Characterization of Facilitated Transport Membranes Composed of Chitosan-Styrene and Chitosan-Acrylonitrile Copolymers Modified by Methylimidazolium Based Ionic Liquids for CO2 Separation from CH4 and N2

    Directory of Open Access Journals (Sweden)

    Ksenia V. Otvagina

    2016-06-01

    Full Text Available CO2 separation was found to be facilitated by transport membranes based on novel chitosan (CS–poly(styrene (PS and chitosan (CS–poly(acrylonitrile (PAN copolymer matrices doped with methylimidazolium based ionic liquids: [bmim][BF4], [bmim][PF6], and [bmim][Tf2N] (IL. CS plays the role of biodegradable film former and selectivity promoter. Copolymers were prepared implementing the latest achievements in radical copolymerization with chosen monomers, which enabled the achievement of outstanding mechanical strength values for the CS-based membranes (75–104 MPa for CS-PAN and 69–75 MPa for CS-PS. Ionic liquid (IL doping affected the surface and mechanical properties of the membranes as well as the gas separation properties. The highest CO2 permeability 400 Barrers belongs to CS-b-PS/[bmim][BF4]. The highest selectivity α (CO2/N2 = 15.5 was achieved for CS-b-PAN/[bmim][BF4]. The operational temperature of the membranes is under 220 °C.

  3. A 5.4mW GPS CMOS quadrature front-end based on a single-stage LNA-mixer-VCO

    DEFF Research Database (Denmark)

    Liscidini, Amtonio; Mazzanti, Andrea; Tonietto, Riccardo

    2006-01-01

    A GPS RF front-end combines the LNA, mixer, and VCO in a single stage and can operate from a 1.2V supply. The chip is implemented in a 0.13um CMOS process and occupies 1.5mm2 active area. It consumes 5.4mW with a 4.8dB NF, 36dB gain, and a P1dB of -31dBm.......A GPS RF front-end combines the LNA, mixer, and VCO in a single stage and can operate from a 1.2V supply. The chip is implemented in a 0.13um CMOS process and occupies 1.5mm2 active area. It consumes 5.4mW with a 4.8dB NF, 36dB gain, and a P1dB of -31dBm....

  4. Bundesamt fuer Strahlenschutz (BfS). Annual report 2011; Bundesamt fuer Strahlenschutz (BfS). Jahresbericht 2011

    Energy Technology Data Exchange (ETDEWEB)

    Ebermann, Lutz (comp.)

    2012-07-01

    The annual report 2011 of the Bundesamt fuer Strahlenschutz (BfS) includes the following main articles: Fukushima and the consequences, new power lines across Germany and the management of radioactive wastes in Germany. Further topics of the BfS were reasonable exposure to sun and skin cancer prevention, individual health assessment of lung cancer with low-dose CT, occupational radiation exposure in medicine, radiation protection at setting up digital radio of security authorities and organizations, importance of laboratory ring experiments for incorporation monitoring, defence against nuclear hazards: cooperation and exercises in 2011, new developments with regard to radioactivity in drinking water, reportable events in nuclear facilities in 2011, decommissioning of a permanently shut down NPP. The environmental research program of the Federal Environmental ministry - research for strengthening nuclear safety and radiation protection: German uranium miners biobank: consequences of uranium mining and radiological impacts, German miners cohort study, health effects of strong magnetic fields of NMR imaging, radiation exposure due to nuclear medical examinations, national survey on the radio-cesium contamination of wild boars.

  5. Antifibrotic effects of D-limonene (5(1-methyl-4-[1-methylethenyl]) cyclohexane) in CCl4 induced liver toxicity in Wistar rats.

    Science.gov (United States)

    Ahmad, Sheikh Bilal; Rehman, Muneeb U; Fatima, Bilques; Ahmad, Bilal; Hussain, Ishraq; Ahmad, Sheikh Pervaiz; Farooq, Adil; Muzamil, Showkeen; Razzaq, Rahil; Rashid, Shahzada Mudasir; Ahmad Bhat, Showkat; Mir, Manzoor Ur Rahman

    2018-03-01

    This study was designed to assess the potential antifibrotic effect of D-Limonene-a component of volatile oils extracted from citrus plants. D-limonene is reported to have numerous therapeutic properties. CCl 4 -intduced model of liver fibrosis in Wistar rats is most widely used model to study chemopreventive studies. CCl 4 -intoxication significantly increased serum aminotransferases and total cholesterol these effects were prevented by cotreatment with D-Limonene. Also, CCl 4 -intoxication caused depletion of glutathione and other antioxidant enzymes while D-Limonene preserved them within normal values. Hydroxyproline and malondialdehyde content was increased markedly by CCl 4 treatment while D-Limonene prevented these alterations. Levels of TNF-α, TGF-β, and α-SMA were also assessed; CCl 4 increased the expression of α-SMA, NF-κB and other downstream inflammatory cascade while D-Limonene co-treatment inhibited them. Collectively these findings indicate that D-Limonene possesses potent antifibrotic effect which may be attributed to its antioxidant and anti-inflammatory properties. © 2017 Wiley Periodicals, Inc.

  6. Synthesis and characterization of monomeric and polymeric Cu(II) complexes of 3,4-ethylenedioxythiophene-functionalized with cyclam ligand

    International Nuclear Information System (INIS)

    Velauthamurty, Kuhamoorthy; Higgins, Simon J.; Rajapakse, R.M. Gamini; Bandara, H.M.N.; Shimomura, Masaru

    2010-01-01

    A functionalized EDOT derivative with 1,4,8,11-tetraazacyclotetradecane (cyclam) ligand pendant to the ethylene bridge (4) and its complexes [M(4)(BF 4 ) 2 ], where M(II) = Cu(II), was prepared and characterized. Their electrochemical copolymerization with EDOT was studied. The electro-co-polymerized films were characterized by electrochemical methods, X-ray photoelectron spectroscopy and by X-ray fluorescence spectroscopy. The co-polymerization method was found to afford a good control of the metal concentration in the polymer matrix and represents a good technique for preparing electronically conductive polymers containing redox-active metal complexes.

  7. Verification of Gamma-ray Sensitivity for BF3 Neutron Detection System

    International Nuclear Information System (INIS)

    Choi, Yu Sun; Cho, Jin Bok; Lyou, Seok Jean

    2016-01-01

    The BF3(Boron Tri-Fluorides) gas filled neutron detector(hereafter BF3 Detector) is commonly used for nuclear reactor’s startup channel due to its relatively high neutron efficiency and good discrimination against gamma-ray backgrounds. In order to measure how much this gamma-ray will affect on BF3 neutron detector performance in view of gamma noise discrimination, Multi-Channel Analyzer(MCA) is utilized for spectrum based signal analysis. The pre-test of BF3 Detector should be performed in an area where the ionization does not exceed 2.5 micro Gy/Hr(Ref.1). In this paper, the discrimination level (Voltage Unit) is verified by experimentally measurement if that discrimination level is acceptable within the criteria or not before installation. The maximum discrimination level, so called LLD, is determined by experimentally measurement. This BF3 Detector (LND20372) is insensitive under 540 micro Gy/Hr of gamma ray and 0.3V of LLD could cut off a background and gamma induced signal in a laboratory. MCA could be a convenient tool for spectrum analysis of signals that induced from gamma ray and a time saving tool rather than oscilloscope investigation due to its function to integrate all input signals at a sudden duration

  8. All Chern-Simons invariants of 4D, N=1 gauged superform hierarchies

    Energy Technology Data Exchange (ETDEWEB)

    Becker, Katrin; Becker, Melanie; III, William D. Linch [George P. and Cynthia Woods Mitchell Institute for Fundamental Physics and Astronomy,Texas A& M University,College Station, TX 77843-4242 (United States); Randall, Stephen [Department of Physics, University of California,Berkeley, CA 94720-7300 (United States); Robbins, Daniel [Department of Physics, University at Albany,Albany, NY 12222 (United States)

    2017-04-19

    We give a geometric description of supersymmetric gravity/(non-)abelian p-form hierarchies in superspaces with 4D, N=1 super-Poincaré invariance. These hierarchies give rise to Chern-Simons-like invariants, such as those of the 5D, N=1 graviphoton and the eleven-dimensional 3-form but also generalizations such as Green-Schwarz-like/BF-type couplings. Previous constructions based on prepotential superfields are reinterpreted in terms of p-forms in superspace thereby elucidating the underlying geometry. This vastly simplifies the calculations of superspace field-strengths, Bianchi identities, and Chern-Simons invariants. Using this, we prove the validity of a recursive formula for the conditions defining these actions for any such tensor hierarchy. Solving it at quadratic and cubic orders, we recover the known results for the BF-type and cubic Chern-Simons actions. As an application, we compute the quartic invariant ∼AdAdAdA+… relevant, for example, to seven-dimensional supergravity compactifications.

  9. Identification of NR4A2 as a transcriptional activator of IL-8 expression in human inflammatory arthritis.

    LENUS (Irish Health Repository)

    Aherne, Carol M

    2009-10-01

    Expression of the orphan nuclear receptor NR4A2 is controlled by pro-inflammatory mediators, suggesting that NR4A2 may contribute to pathological processes in the inflammatory lesion. This study identifies the chemoattractant protein, interleukin 8 (IL-8\\/CXCL8), as a molecular target of NR4A2 in human inflammatory arthritis and examines the mechanism through which NR4A2 modulates IL-8 expression. In TNF-alpha-activated human synoviocyte cells, enhanced expression of IL-8 mRNA and protein correspond to temporal changes in NR4A2 transcription and nuclear distribution. Ectopic expression of NR4A2 leads to robust changes in endogenous IL-8 mRNA levels and co-treatment with TNF-alpha results in significant (p<0.001) secretion of IL-8 protein. Transcriptional effects of NR4A2 on the human IL-8 promoter are enhanced in the presence of TNF-alpha, suggesting molecular crosstalk between TNF-alpha signalling and NR4A2. A dominant negative IkappaB kinase antagonizes the combined effects of NR4A2 and TNF-alpha on IL-8 promoter activity. Co-expression of NR4A2 and the p65 subunit of NF-kappaB enhances IL-8 transcription and functional studies indicate that transactivation occurs independently of NR4A2 binding to DNA or heterodimerization with additional nuclear receptors. The IL-8 minimal promoter region is sufficient to support NR4A2 and NF-kappaB\\/p65 co-operative activity and NR4A2 can interact with NF-kappaB\\/p65 on a 39bp sequence within this region. In patients treated with methotrexate for active inflammatory arthritis, a reduction in NR4A2 synovial tissue levels correlate significantly (n=10, r=0.73, p=0.002) with changes in IL-8 expression. Collectively, these data delineate an important role for NR4A2 in modulating IL-8 expression and reveal novel transcriptional responses to TNF-alpha in human inflammatory joint disease.

  10. Curcumin Protects against Atherosclerosis in Apolipoprotein E-Knockout Mice by Inhibiting Toll-like Receptor 4 Expression.

    Science.gov (United States)

    Zhang, Shanshan; Zou, Jun; Li, Peiyang; Zheng, Xiumei; Feng, Dan

    2018-01-17

    Toll-like receptor 4 (TLR4) has been reported to play a critical role in the pathogenesis of atherosclerosis, the current study aimed to investigate whether curcumin suppresses atherosclerosis development in ApoE-knockout (ApoE -/- ) mice by inhibiting TLR4 expression. ApoE -/- mice were fed a high-fat diet supplemented with or without curcumin (0.1% w/w) for 16 weeks. Curcumin supplementation significantly reduced TLR4 expression and macrophage infiltration in atherosclerotic plaques. Curcumin also reduced aortic interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) expression, nuclear factor-κB (NF-κB) activity, and plasma IL-1β, TNF-α, soluble VCAM-1 and ICAM-1 levels. In addition, aortic sinus sections revealed that curcumin treatment reduced the extent of atherosclerotic lesions and inhibited atherosclerosis development. In vitro, curcumin inhibited NF-κB activation in macrophages and reduced TLR4 expression induced by lipopolysaccharide. Our results indicate that curcumin protects against atherosclerosis at least partially by inhibiting TLR4 expression and its related inflammatory reaction.

  11. Synthesis and physical-chemical properties of 3-alkylthio-5-(quinoline-2-yl, 2-hydroxyquinoline-4-yl-4-R-2,4-dihydro-3H-1,2,4-triazoles

    Directory of Open Access Journals (Sweden)

    T. M. Kaplaushenko

    2016-06-01

    Full Text Available The major social and economic problem of pharmaceutical industry is the search for biologically active substances, which may become the basis of new drugs, competitive with expensive imported drugs. Analysis of literature shows that in recent decades the attention is paid to researches of heterocyclic systems as potential biologically active agents of both domestic and foreign scientists. Particular interest in this regard cause 3-thio derivatives of 1,2,4-triazoles. Despite high number of publications relating to synthesis and biological properties of 1,2,4-triazole derivatives, the structure and physical-chemical properties of these compounds are studied insufficiently. In this regard, the study of synthetic, physical-chemical and biological properties of 3-alkylthio-5-(quinoline-2-yl, 2-hydroxyquinoline-4-yl-4-R1-2,4-dihydro-3H-1,2,4-triazoles in our point of view is a new, theoretically and practically significant direction. Purpose - targeted synthesis of new low-toxic and highly effective compounds with potential pharmacological activity in a series of 3-alkylthio-5-(quinoline-2-yl, 2-hydroxyquinoline-4-yl-4-R-2,4-dihydro-3H-1,2,4-triazoles and the study of physical and chemical properties of the synthesized compounds. Materials and methods. As starting compounds 5-(quinoline-2-il- 2-hydroxyquinoline-4-yl-4-R1-3-thio-1,2,4-triazoles have been used. Through further cooperation with halogen alkanes (ethyl bromide, propyl bromide, amyl bromide, octyl bromide, nonyl bromide, decyl bromide, cyclohexyl chloride, benzyl chloride 3-alkylthio-5-(quinoline-2-yl, 2-hydroxyquinoline-4-yl-4-R1-2,4-dyhidro-3H-1,2,4-triazoles have been obtained. Results. 15 New compounds have been received as a result of synthetic transformations, the structure of synthesized compounds has been confirmed by modern complex of physical and chemical methods of analysis (IR-spectrophotometry, 1H NMR-spectroscopy, elemental analysis, and their individuality has been proved by

  12. The novel thiosemicarbazone, di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC, inhibits neuroblastoma growth in vitro and in vivo via multiple mechanisms

    Directory of Open Access Journals (Sweden)

    Zhu-Ling Guo

    2016-09-01

    Full Text Available Abstract Background Neuroblastoma is a relatively common and highly belligerent childhood tumor with poor prognosis by current therapeutic approaches. A novel anti-cancer agent of the di-2-pyridylketone thiosemicarbazone series, namely di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT, demonstrates promising anti-tumor activity. Recently, a second-generation analogue, namely di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC, has entered multi-center clinical trials for the treatment of advanced and resistant tumors. The current aim was to examine if these novel agents were effective against aggressive neuroblastoma in vitro and in vivo and to assess their mechanism of action. Methods Neuroblastoma cancer cells as well as immortalized normal cells were used to assess the efficacy and selectivity of DpC in vitro. An orthotopic SK-N-LP/Luciferase xenograft model was used in nude mice to assess the efficacy of DpC in vivo. Apoptosis in tumors was confirmed by Annexin V/PI flow cytometry and H&E staining. Results DpC demonstrated more potent cytotoxicity than Dp44mT against neuroblastoma cells in a dose- and time-dependent manner. DpC significantly increased levels of phosphorylated JNK, neuroglobin, cytoglobin, and cleaved caspase 3 and 9, while decreasing IkBα levels in vitro. The contribution of JNK, NF-ĸB, and caspase signaling/activity to the anti-tumor activity of DpC was verified by selective inhibitors of these pathways. After 3 weeks of treatment, tumor growth in mice was significantly (p < 0.05 reduced by DpC (4 mg/kg/day given intravenously and the agent was well tolerated. Xenograft tissues showed significantly higher expression of neuroglobin, cytoglobin, caspase 3, and tumor necrosis factor-α (TNFα levels and a slight decrease in interleukin-10 (IL-10. Conclusions DpC was found to be highly potent against neuroblastoma, demonstrating its potential as a novel therapeutic for this disease. The ability

  13. Eggshell membrane hydrolyzates activate NF-κB in vitro: possible implications for in vivo efficacy

    Directory of Open Access Journals (Sweden)

    Ruff KJ

    2015-02-01

    Full Text Available Kevin J Ruff,1 Paul L Durham,2 Austin O’Reilly,2 F Daniel Long1 1ESM Technologies, LLC, Carthage, MO, USA; 2Center for Biomedical and Life Sciences, Missouri State University, Springfield, MO, USA Purpose: Eggshell membrane (ESM has been shown to contain naturally occurring bioactive components, and biological activities such as reducing proinflammatory cytokines, liver fibrosis, and joint pain in osteoarthritis sufferers have also been reported for ESM matrix as a whole. Nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB is a signaling protein found in the cytoplasm of nearly all human and animal cell types and is a primary regulator of immune function. The studies reported herein were designed to investigate the possible role that NF-κB activity might play in the reported biological activities of ESM. Methods: Three ESM hydrolyzates produced via fermentation, enzymatic, or chemical hydrolysis were evaluated in vitro in either human peripheral blood mononuclear cell or THP-1 (human leukemic monocyte cell cultures for NF-κB activity following 4-hour exposure. The hydrolyzates were compared with untreated control cells or cells incubated with lipopolysaccharide or ascorbic acid. The source of ESM activity was also evaluated. Results: NF-κB levels were increased above levels found in untreated cells at all three dilutions (1:100, 1:1,000, and 1:10,000 for the fermentation hydrolyzate of ESM (ESM-FH (P=0.021, P=0.020, P=0.009, respectively in peripheral blood mononuclear cells. The enzymatic hydrolyzate of ESM (ESM-EH also produced statistically significant levels of activated NF-κB at the 1:100 and 1:1,000 dilutions (P=0.004, P=0.006, respectively but fell just shy of significance at the 1:10,000 dilution (P=0.073. Similarly, ESM-FH (P=0.021, P=0.002 and ESM-EH (P=0.007, P=0.007 activated NF-κB in THP-1 cells at 1:1,000 and 1:10,000 dilutions, respectively. The chemical hydrolyzate of ESM (ESM-CH showed statistically

  14. A Kallosh theorem for BF-type topological field theory

    International Nuclear Information System (INIS)

    Birmingham, D.; Gibbs, R.; Mokhtari, S.

    1991-01-01

    A Kallosh theorem is established for the case of BF-type theories in three dimensions, including a coupling to Chern-Simons theory. The phase contribution to the one-loop off-shell effective action is computed for a two-parameter family of local covariant gauges. It is shown that the phase is independent of these parameters, and thus equals the 'no Vilkovisky-DeWitt' gauge result. The field space metric dependence of a corresponding calculation for generalized BF theory is briefly discussed. (orig.)

  15. Dioscorin isolated from Dioscorea alata activates TLR4-signaling pathways and induces cytokine expression in macrophages.

    Science.gov (United States)

    Fu, Shu-Ling; Hsu, Ya-Hui; Lee, Pei-Yeh; Hou, Wen-Chi; Hung, Ling-Chien; Lin, Chao-Hsiung; Chen, Chiu-Ming; Huang, Yu-Jing

    2006-01-06

    The Toll-like receptor 4 (TLR4)-signaling pathway is crucial for activating both innate and adaptive immunity. TLR4 is a promising molecular target for immune-modulating drugs, and TLR4 agonists are of therapeutic potential for treating immune diseases and cancers. Several medicinal herb-derived components have recently been reported to act via TLR4-dependent pathways, suggesting that medicinal plants are potential resources for identifying TLR4 activators. We have applied a screening procedure to systematically identify herbal constituents that activate TLR4. To exclude possible LPS contamination in these plant-derived components, a LPS inhibitor, polymyxin B, was added during screening. One of the plant components we identified from the screening was dioscorin, the glycoprotein isolated from Dioscorea alata. It induced TLR4-downstream cytokine expression in bone marrow cells isolated from TLR4-functional C3H/HeN mice but not from TLR4-defective C3H/HeJ mice. Dioscorin also stimulated multiple signaling molecules (NF-kappaB, ERK, JNK, and p38) and induced the expression of cytokines (TNF-alpha, IL-1beta, and IL-6) in murine RAW 264.7 macrophages. Furthermore, the ERK, p38, JNK, and NF-kappaB-mediated pathways are all involved in dioscorin-mediated TNF-alpha production. In summary, our results demonstrate that dioscorin is a novel TLR4 activator and induces macrophage activation via typical TLR4-signaling pathways.

  16. NCOA4 Deficiency Impairs Systemic Iron Homeostasis

    Directory of Open Access Journals (Sweden)

    Roberto Bellelli

    2016-01-01

    Full Text Available The cargo receptor NCOA4 mediates autophagic ferritin degradation. Here we show that NCOA4 deficiency in a knockout mouse model causes iron accumulation in the liver and spleen, increased levels of transferrin saturation, serum ferritin, and liver hepcidin, and decreased levels of duodenal ferroportin. Despite signs of iron overload, NCOA4-null mice had mild microcytic hypochromic anemia. Under an iron-deprived diet (2–3 mg/kg, mice failed to release iron from ferritin storage and developed severe microcytic hypochromic anemia and ineffective erythropoiesis associated with increased erythropoietin levels. When fed an iron-enriched diet (2 g/kg, mice died prematurely and showed signs of liver damage. Ferritin accumulated in primary embryonic fibroblasts from NCOA4-null mice consequent to impaired autophagic targeting. Adoptive expression of the NCOA4 COOH terminus (aa 239–614 restored this function. In conclusion, NCOA4 prevents iron accumulation and ensures efficient erythropoiesis, playing a central role in balancing iron levels in vivo.

  17. Diclofenac pretreatment effects on the toll-like receptor 4/nuclear factor kappa B-mediated inflammatory response to eccentric exercise in rat liver.

    Science.gov (United States)

    Barcelos, Rômulo Pillon; Bresciani, Guilherme; Rodriguez-Miguelez, Paula; Cuevas, Maria José; Soares, Félix Alexandre Antunes; Barbosa, Nilda Vargas; González-Gallego, Javier

    2016-03-01

    Acute exercise is a stress stimulus that may cause cell damage through the activation of the toll-like receptor (TLR)4 pathway, resulting in the translocation of nuclear factor kappa B (NF-κB) into the cell nucleus and the upregulation of inflammatory genes. Nonsteroidal anti-inflammatory drugs, such as diclofenac, are often prescribed to counteract exercise-induced inflammation. This study analyzed effects of diclofenac pretreatment on the TLR4/NF-κB pathway in rat liver after an acute eccentric exercise. Twenty male Wistar rats were divided in four groups: control-saline, control-diclofenac, exercise-saline and exercise-diclofenac. The rats received saline or diclofenac (10mg/kg) for 7days prior to an eccentric exercise bout. After exercise there was an increase in TLR4, myeloid differentiation primary response gene 88 (MyD88), TIR domain-containing adaptor inducing interferon (TRIF) and p65 NF-κB subunit protein levels. Exercise also resulted in increased mRNA and protein expression of interleukin (IL)-6, inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF)-α. Proinflammatory effects of exercise were prevented by the administration of diclofenac, which blunted the activation of the TLR4/NF-κB pathway and the inflammatory response in the liver of exercised rats. Results from the present study highlight the role of TLR4 as a target for anti-inflammatory interventions. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. The C-terminal domains of NF-H and NF-M subunits maintain axonal neurofilament content by blocking turnover of the stationary neurofilament network.

    Directory of Open Access Journals (Sweden)

    Mala V Rao

    Full Text Available Newly synthesized neurofilaments or protofilaments are incorporated into a highly stable stationary cytoskeleton network as they are transported along axons. Although the heavily phosphorylated carboxyl-terminal tail domains of the heavy and medium neurofilament (NF subunits have been proposed to contribute to this process and particularly to stability of this structure, their function is still obscure. Here we show in NF-H/M tail deletion [NF-(H/M(tailΔ] mice that the deletion of both of these domains selectively lowers NF levels 3-6 fold along optic axons without altering either rates of subunit synthesis or the rate of slow axonal transport of NF. Pulse labeling studies carried out over 90 days revealed a significantly faster rate of disappearance of NF from the stationary NF network of optic axons in NF-(H/M(tailΔ mice. Faster NF disappearance was accompanied by elevated levels of NF-L proteolytic fragments in NF-(H/M(tailΔ axons. We conclude that NF-H and NF-M C-terminal domains do not normally regulate NF transport rates as previously proposed, but instead increase the proteolytic resistance of NF, thereby stabilizing the stationary neurofilament cytoskeleton along axons.

  19. Interactions among oscillatory pathways in NF-kappa B signaling

    Directory of Open Access Journals (Sweden)

    White Michael RH

    2011-02-01

    Full Text Available Abstract Background Sustained stimulation with tumour necrosis factor alpha (TNF-alpha induces substantial oscillations—observed at both the single cell and population levels—in the nuclear factor kappa B (NF-kappa B system. Although the mechanism has not yet been elucidated fully, a core system has been identified consisting of a negative feedback loop involving NF-kappa B (RelA:p50 hetero-dimer and its inhibitor I-kappa B-alpha. Many authors have suggested that this core oscillator should couple to other oscillatory pathways. Results First we analyse single-cell data from experiments in which the NF-kappa B system is forced by short trains of strong pulses of TNF-alpha. Power spectra of the ratio of nuclear-to-cytoplasmic concentration of NF-kappa B suggest that the cells' responses are entrained by the pulsing frequency. Using a recent model of the NF-kappa B system due to Caroline Horton, we carried out extensive numerical simulations to analyze the response frequencies induced by trains of pulses of TNF-alpha stimulation having a wide range of frequencies and amplitudes. These studies suggest that for sufficiently weak stimulation, various nonlinear resonances should be observable. To explore further the possibility of probing alternative feedback mechanisms, we also coupled the model to sinusoidal signals with a wide range of strengths and frequencies. Our results show that, at least in simulation, frequencies other than those of the forcing and the main NF-kappa B oscillator can be excited via sub- and superharmonic resonance, producing quasiperiodic and even chaotic dynamics. Conclusions Our numerical results suggest that the entrainment phenomena observed in pulse-stimulated experiments is a consequence of the high intensity of the stimulation. Computational studies based on current models suggest that resonant interactions between periodic pulsatile forcing and the system's natural frequencies may become evident for sufficiently

  20. Epipolythiodiketopiperazines from the Marine Derived Fungus Dichotomomyces cejpii with NF-κB Inhibitory Potential

    Directory of Open Access Journals (Sweden)

    Henrik Harms

    2015-08-01

    Full Text Available The Ascomycota Dichotomomyces cejpii was isolated from the marine sponge Callyspongia cf. C. flammea. A new gliotoxin derivative, 6-acetylmonodethiogliotoxin (1 was obtained from fungal extracts. Compounds 2 and 3, methylthio-gliotoxin derivatives were formerly only known as semi-synthetic compounds and are here described as natural products. Additionally the polyketide heveadride (4 was isolated. Compounds 1, 2 and 4 dose-dependently down-regulated TNFα-induced NF-κB activity in human chronic myeloid leukemia cells with IC50s of 38.5 ± 1.2 µM, 65.7 ± 2.0 µM and 82.7 ± 11.3 µM, respectively. The molecular mechanism was studied with the most potent compound 1 and results indicate downstream inhibitory effects targeting binding of NF-κB to DNA. Compound 1 thus demonstrates potential of epimonothiodiketopiperazine-derived compounds for the development of NF-κB inhibitors.

  1. The Effect of 4-week Difference Training Methods on Some Fitness Variables in Youth Handball Players

    Directory of Open Access Journals (Sweden)

    Abdolhossein a Parnow

    2016-09-01

    Full Text Available Handball is a team sport in which main activities such as sprinting, arm throwing, hitting, and so on involve. This Olympic team sport requires a standard of preparation in order to complete sixteen minutes of competitive play and to achieve success. This study, therefore, was done to determinate the effect of a 4-week different training on some physical fitness variables in youth Handball players. Thirty high-school students participated in the study and assigned into the Resistance Training (RT (n = 10: 16.75± 0.36 yr; 63.14± 4.19 kg; 174.8 ± 5.41 cm, Plyometric Training (PT (n = 10: 16.57± 0.26 yr; 65.52± 6.79 kg; 173.5 ± 5.44 cm, and Complex Training (CT (n=10, 16.23± 0.50 yr; 58.43± 10.50 kg; 175.2 ± 8.19 cm groups. Subjects were evaluated in anthropometric and physiological characteristics 48 hours before and after of a 4-week protocol. Because of study purposes, statistical analyses consisted of a repeated measure ANVOA and one-way ANOVA were used. In considering with pre to post test variables changes in the groups, data analysis showed BF, strength, speed, agility, and explosive power were affected by training protocols (P0.05. In conclusion, complex training result in advantageous effect on variables such as strength, explosive power, speed and agility in youth handball players compare with resistance and plyometric training although we also reported positive effect of these training methods. Coaches and players, therefore, could consider complex training as alternative method for other training methods.

  2. DRD4 long allele carriers show heightened attention to high-priority items relative to low-priority items.

    Science.gov (United States)

    Gorlick, Marissa A; Worthy, Darrell A; Knopik, Valerie S; McGeary, John E; Beevers, Christopher G; Maddox, W Todd

    2015-03-01

    Humans with seven or more repeats in exon III of the DRD4 gene (long DRD4 carriers) sometimes demonstrate impaired attention, as seen in attention-deficit hyperactivity disorder, and at other times demonstrate heightened attention, as seen in addictive behavior. Although the clinical effects of DRD4 are the focus of much work, this gene may not necessarily serve as a "risk" gene for attentional deficits, but as a plasticity gene where attention is heightened for priority items in the environment and impaired for minor items. Here we examine the role of DRD4 in two tasks that benefit from selective attention to high-priority information. We examine a category learning task where performance is supported by focusing on features and updating verbal rules. Here, selective attention to the most salient features is associated with good performance. In addition, we examine the Operation Span (OSPAN) task, a working memory capacity task that relies on selective attention to update and maintain items in memory while also performing a secondary task. Long DRD4 carriers show superior performance relative to short DRD4 homozygotes (six or less tandem repeats) in both the category learning and OSPAN tasks. These results suggest that DRD4 may serve as a "plasticity" gene where individuals with the long allele show heightened selective attention to high-priority items in the environment, which can be beneficial in the appropriate context.

  3. The TLR4 D299G and T399I SNPs are constitutively active to up-regulate expression of Trif-dependent genes.

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    Georgina L Hold

    Full Text Available Dysregulated Toll-Like Receptor (TLR signalling and genetic polymorphisms in these proteins are linked to many human diseases. We investigated TLR4 functional variants D299G and T399I to assess the impact on LPS-induced responsiveness in comparison to wild-type TLR4. The mechanism by which this occurs in unclear as these SNPs do not lie within the lipid A binding domain or dimerisation sites of the LPS-TLR4/MD2 receptor complexes. Transfection of TLR4D299G, TLR4T399I or TLR4D299G. T399I into HEK cells resulted in constitutive activation of an NF-κB reporter gene and a blunting of the LPS-induced reporter activation compared to WT-TLR4. Unstimulated human monocyte/macrophages, from patients with the D299G and T399I SNPs demonstrated a downregulation of many genes, particularly Tram/Trif signalling pathway constitutents compared to the TLR4 wild-type subjects supporting the concept of basal receptor activity. Monocyte/macrophages from carriers of the TLR4 D299G and T399I polymorphisms stimulated with LPS showed >6 fold lower levels of NF-κB and ∼12 fold higher IFN-β gene expression levels compared to wild-type subjects (P<0.05; MWU test and dramatically altered resultant cytokine profiles. We conclude that these TLR4 SNPs affect constitutive receptor activity which impacts on the hosts ability to respond to LPS challenge leading to a dysregulated sub-optimal immune response to infection.

  4. Endocytosis-independent function of clathrin heavy chain in the control of basal NF-κB activation.

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    Man Lyang Kim

    Full Text Available BACKGROUND: Nuclear factor-κB (NF-κB is a transcription factor that regulates the transcription of genes involved in a variety of biological processes, including innate and adaptive immunity, stress responses and cell proliferation. Constitutive or excessive NF-κB activity has been associated with inflammatory disorders and higher risk of cancer. In contrast to the mechanisms controlling inducible activation, the regulation of basal NF-κB activation is not well understood. Here we test whether clathrin heavy chain (CHC contributes to the regulation of basal NF-κB activity in epithelial cells. METHODOLOGY: Using RNA interference to reduce endogenous CHC expression, we found that CHC is required to prevent constitutive activation of NF-κB and gene expression. Immunofluorescence staining showed constitutive nuclear localization of the NF-κB subunit p65 in absence of stimulation after CHC knockdown. Elevated basal p65 nuclear localization is caused by constitutive phosphorylation and degradation of inhibitor of NF-κB alpha (IκBα through an IκB kinase α (IKKα-dependent mechanism. The role of CHC in NF-κB signaling is functionally relevant as constitutive expression of the proinflammatory chemokine interleukin-8 (IL-8, whose expression is regulated by NF-κB, was found after CHC knockdown. Disruption of clathrin-mediated endocytosis by chemical inhibition or depletion of the μ2-subunit of the endocytosis adaptor protein AP-2, and knockdown of clathrin light chain a (CHLa, failed to induce constitutive NF-κB activation and IL-8 expression, showing that CHC acts on NF-κB independently of endocytosis and CLCa. CONCLUSIONS: We conclude that CHC functions as a built-in molecular brake that ensures a tight control of basal NF-κB activation and gene expression in unstimulated cells. Furthermore, our data suggest a potential link between a defect in CHC expression and chronic inflammation disorder and cancer.

  5. NF2 tumor suppressor gene: a comprehensive and efficient detection of somatic mutations by denaturing HPLC and microarray-CGH.

    Science.gov (United States)

    Szijan, Irene; Rochefort, Daniel; Bruder, Carl; Surace, Ezequiel; Machiavelli, Gloria; Dalamon, Viviana; Cotignola, Javier; Ferreiro, Veronica; Campero, Alvaro; Basso, Armando; Dumanski, Jan P; Rouleau, Guy A

    2003-01-01

    The NF2 tumor suppressor gene, located in chromosome 22q12, is involved in the development of multiple tumors of the nervous system, either associated with neurofibromatosis 2 or sporadic ones, mainly schwannomas and meningiomas. In order to evaluate the role of the NF2 gene in sporadic central nervous system (CNS) tumors, we analyzed NF2 mutations in 26 specimens: 14 meningiomas, 4 schwannomas, 4 metastases, and 4 other histopathological types of neoplasms. Denaturing high performance liquid chromatography (denaturing HPLC) and comparative genomic hybridization on a DNA microarray (microarray- CGH) were used as scanning methods for small mutations and gross rearrangements respectively. Small mutations were identified in six out of seventeen meningiomas and schwannomas, one mutation was novel. Large deletions were detected in six meningiomas. All mutations were predicted to result in truncated protein or in the absence of a large protein domain. No NF2 mutations were found in other histopathological types of CNS tumors. These results provide additional evidence that mutations in the NF2 gene play an important role in the development of sporadic meningiomas and schwannomas. Denaturing HPLC analysis of small mutations and microarray-CGH of large deletions are complementary, fast, and efficient methods for the detection of mutations in tumor tissues.

  6. A Kallosh theorem for BF-type topological field theory

    Energy Technology Data Exchange (ETDEWEB)

    Birmingham, D. (Theory Div., CERN, Geneva (Switzerland)); Gibbs, R.; Mokhtari, S. (Physics Dept., Louisiana Tech. Univ., Ruston, LA (United States))

    1991-12-12

    A Kallosh theorem is established for the case of BF-type theories in three dimensions, including a coupling to Chern-Simons theory. The phase contribution to the one-loop off-shell effective action is computed for a two-parameter family of local covariant gauges. It is shown that the phase is independent of these parameters, and thus equals the 'no Vilkovisky-DeWitt' gauge result. The field space metric dependence of a corresponding calculation for generalized BF theory is briefly discussed. (orig.).

  7. A putative SUMO interacting motif in the B30.2/SPRY domain of rhesus macaque TRIM5α important for NF-κB/AP-1 signaling and HIV-1 restriction

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    Marie-Édith Nepveu-Traversy

    2016-01-01

    Full Text Available TRIM5α from the rhesus macaque (TRIM5αRh is a restriction factor that shows strong activity against HIV-1. TRIM5αRh binds specifically to HIV-1 capsid (CA through its B30.2/PRYSPRY domain shortly after entry of the virus into the cytoplasm. Recently, three putative SUMO interacting motifs (SIMs have been identified in the PRYSPRY domain of human and macaque TRIM5α. However, structural modeling of this domain suggested that two of them were buried in the hydrophobic core of the protein, implying that interaction with SUMO was implausible, while the third one was not relevant to restriction. In light of these results, we re-analyzed the TRIM5αRh PRYSPRY sequence and identified an additional putative SIM (435VIIC438 which we named SIM4. This motif is exposed at the surface of the PRYSPRY domain, allowing potential interactions with SUMO or SUMOylated proteins. Introducing a double mutation in SIM4 (V435K, I436K did not alter stability, unlike mutations in SIM1. SIM4-mutated TRIM5αRh failed to bind HIV-1CA and lost the ability to restrict this virus. Accordingly, SIM4 undergoes significant variation among primates and substituting this motif with naturally occurring SIM4 variants affected HIV-1 restriction by TRIM5αRh, suggesting a direct role in capsid recognition. Interestingly, SIM4-mutated TRIM5αRh also failed to activate NF-κB and AP-1-mediated transcription. Although there is no direct evidence that SIM4 is involved in direct interaction with SUMO or a SUMOylated protein, mutating this motif strongly reduced co-localization of TRIM5αRh with SUMO-1 and with PML, a SUMOylated nuclear protein. In conclusion, this new putative SIM is crucial for both direct interaction with incoming capsids and for NF-κB/AP-1 signaling. We speculate that the latter function is mediated by interactions of SIM4 with a SUMOylated protein involved in the NF-κB/AP-1 signaling pathways.

  8. Thermal expansion studies on Th(MoO4)2, Na2Th(MoO4)3 and Na4Th(MoO4)4

    International Nuclear Information System (INIS)

    Keskar, Meera; Krishnan, K.; Dahale, N.D.

    2008-01-01

    Thermal expansion behavior of Th(MoO 4 ) 2 , Na 2 Th(MoO 4 ) 3 and Na 4 Th(MoO 4 ) 4 was studied under vacuum in the temperature range of 298-1123 K by high temperature X-ray diffractometer. Th(MoO 4 ) 2 was synthesized by reacting ThO 2 with 2 mol of MoO 3 , at 1073 K in air and Na 2 Th(MoO 4 ) 3 and Na 4 Th(MoO 4 ) 4 were prepared by reacting Th(MoO 4 ) 2 with 1 and 2 mol of Na 2 MoO 4 , respectively at 873 K in air. The XRD data of Th(MoO 4 ) 2 was indexed on orthorhombic system where as XRD data of Na 2 Th(MoO 4 ) 3 and Na 4 Th(MoO 4 ) 4 were indexed on tetragonal system. The lattice parameters and cell volume of all the three compounds, fit into polynomial expression with respect to temperature, showed positive thermal expansion (PTE) up to 1123 K. The average value of thermal expansion coefficients for Th(MoO 4 ) 2 , Na 2 Th(MoO 4 ) 3 and Na 4 Th(MoO 4 ) 4 were determined from the high temperature data

  9. A role for NF-κB activity in skin hyperplasia and the development of keratoacanthomata in mice.

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    Brian Poligone

    Full Text Available BACKGROUND: Previous studies have implicated NF-κB signaling in both cutaneous development and oncogenesis. However, these studies have been limited in part by the lethality that results from extreme over- or under-expression of NF-κB in available mouse models. Even cre-driven tissue specific expression of transgenes, or targeted deletion of NF-κB can cause cell death. Therefore, the present study was undertaken to evaluate a novel mouse model of enhanced NF-κB activity in the skin. METHODS: A knock-in homologous recombination technique was utilized to develop a mouse model (referred to as PD mice with increased NF-κB activity. RESULTS: The data show that increased NF-κB activity leads to hyperproliferation and dysplasia of the mouse epidermis. Chemical carcinogenesis in the context of enhanced NF-κB activity promotes the development of keratoacanthomata. CONCLUSION: Our findings support an important role for NF-κB in keratinocyte dysplasia. We have found that enhanced NF-κB activity renders keratinocytes susceptible to hyperproliferation and keratoacanthoma (KA development but is not sufficient for transformation and SCC development. We therefore propose that NF-κB activation in the absence of additional oncogenic events can promote TNF-dependent, actinic keratosis-like dysplasia and TNF-independent, KAs upon chemical carcinogensis. These studies suggest that resolution of KA cannot occur when NF-κB activation is constitutively enforced.

  10. BF integrase genes of HIV-1 circulating in São Paulo, Brazil, with a recurrent recombination region.

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    Atila Iamarino

    Full Text Available Although some studies have shown diversity in HIV integrase (IN genes, none has focused particularly on the gene evolving in epidemics in the context of recombination. The IN gene in 157 HIV-1 integrase inhibitor-naïve patients from the São Paulo State, Brazil, were sequenced tallying 128 of subtype B (23 of which were found in non-B genomes, 17 of subtype F (8 of which were found in recombinant genomes, 11 integrases were BF recombinants, and 1 from subtype C. Crucially, we found that 4 BF recombinant viruses shared a recurrent recombination breakpoint region between positions 4900 and 4924 (relative to the HXB2 that includes 2 gRNA loops, where the RT may stutter. Since these recombinants had independent phylogenetic origin, we argue that these results suggest a possible recombination hotspot not observed so far in BF CRF in particular, or in any other HIV-1 CRF in general. Additionally, 40% of the drug-naïve and 45% of the drug-treated patients had at least 1 raltegravir (RAL or elvitegravir (EVG resistance-associated amino acid change, but no major resistance mutations were found, in line with other studies. Importantly, V151I was the most common minor resistance mutation among B, F, and BF IN genes. Most codon sites of the IN genes had higher rates of synonymous substitutions (dS indicative of a strong negative selection. Nevertheless, several codon sites mainly in the subtype B were found under positive selection. Consequently, we observed a higher genetic diversity in the B portions of the mosaics, possibly due to the more recent introduction of subtype F on top of an ongoing subtype B epidemics and a fast spread of subtype F alleles among the B population.

  11. Inhibition of the aryl hydrocarbon receptor prevents Western diet-induced obesity. Model for AHR activation by kynurenine via oxidized-LDL, TLR2/4, TGFβ, and IDO1

    Energy Technology Data Exchange (ETDEWEB)

    Moyer, Benjamin J. [Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States); Rojas, Itzel Y. [Department of Medicine, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States); Department of Pharmacology & Toxicology, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States); Kerley-Hamilton, Joanna S. [Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States); Hazlett, Haley F. [Department of Pharmacology & Toxicology, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States); Department of Immunology & Microbiology, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States); Nemani, Krishnamurthy V. [Department of Radiology, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States); Trask, Heidi W.; West, Rachel J. [Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States); Lupien, Leslie E. [Department of Medicine, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States); Collins, Alan J. [Department of Immunology & Microbiology, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States); and others

    2016-06-01

    Obesity is an increasingly urgent global problem, yet, little is known about its causes and less is known how obesity can be effectively treated. We showed previously that the aryl hydrocarbon receptor (AHR) plays a role in the regulation of body mass in mice fed Western diet. The AHR is a ligand-activated nuclear receptor that regulates genes involved in a number of biological pathways, including xenobiotic metabolism and T cell polarization. This study was an investigation into whether inhibition of the AHR prevents Western diet-based obesity. Male C57Bl/6J mice were fed control and Western diets with and without the AHR antagonist α-naphthoflavone or CH-223191, and a mouse hepatocyte cell line was used to delineate relevant cellular pathways. Studies are presented showing that the AHR antagonists α-naphthoflavone and CH-223191 significantly reduce obesity and adiposity and ameliorates liver steatosis in male C57Bl/6J mice fed a Western diet. Mice deficient in the tryptophan metabolizing enzyme indoleamine 2,3-dioxygenase 1 (IDO1) were also resistant to obesity. Using an AHR-directed, luciferase-expressing mouse hepatocyte cell line, we show that the transforming growth factor β1 (TGFβ1) signaling pathway via PI3K and NF-κB and the toll-like receptor 2/4 (TLR2/4) signaling pathway stimulated by oxidized low-density lipoproteins via NF-κB, each induce luciferase expression; however, TLR2/4 signaling was significantly reduced by inhibition of IDO1. At physiological levels, kynurenine but not kynurenic acid (both tryptophan metabolites and known AHR agonists) activated AHR-directed luciferase expression. We propose a hepatocyte-based model, in which kynurenine production is increased by enhanced IDO1 activity stimulated by TGFβ1 and TLR2/4 signaling, via PI3K and NF-κB, to perpetuate a cycle of AHR activation to cause obesity; and inhibition of the AHR, in turn, blocks the cycle's output to prevent obesity. The AHR with its broad ligand binding

  12. Inhibition of the aryl hydrocarbon receptor prevents Western diet-induced obesity. Model for AHR activation by kynurenine via oxidized-LDL, TLR2/4, TGFβ, and IDO1

    International Nuclear Information System (INIS)

    Moyer, Benjamin J.; Rojas, Itzel Y.; Kerley-Hamilton, Joanna S.; Hazlett, Haley F.; Nemani, Krishnamurthy V.; Trask, Heidi W.; West, Rachel J.; Lupien, Leslie E.; Collins, Alan J.

    2016-01-01

    Obesity is an increasingly urgent global problem, yet, little is known about its causes and less is known how obesity can be effectively treated. We showed previously that the aryl hydrocarbon receptor (AHR) plays a role in the regulation of body mass in mice fed Western diet. The AHR is a ligand-activated nuclear receptor that regulates genes involved in a number of biological pathways, including xenobiotic metabolism and T cell polarization. This study was an investigation into whether inhibition of the AHR prevents Western diet-based obesity. Male C57Bl/6J mice were fed control and Western diets with and without the AHR antagonist α-naphthoflavone or CH-223191, and a mouse hepatocyte cell line was used to delineate relevant cellular pathways. Studies are presented showing that the AHR antagonists α-naphthoflavone and CH-223191 significantly reduce obesity and adiposity and ameliorates liver steatosis in male C57Bl/6J mice fed a Western diet. Mice deficient in the tryptophan metabolizing enzyme indoleamine 2,3-dioxygenase 1 (IDO1) were also resistant to obesity. Using an AHR-directed, luciferase-expressing mouse hepatocyte cell line, we show that the transforming growth factor β1 (TGFβ1) signaling pathway via PI3K and NF-κB and the toll-like receptor 2/4 (TLR2/4) signaling pathway stimulated by oxidized low-density lipoproteins via NF-κB, each induce luciferase expression; however, TLR2/4 signaling was significantly reduced by inhibition of IDO1. At physiological levels, kynurenine but not kynurenic acid (both tryptophan metabolites and known AHR agonists) activated AHR-directed luciferase expression. We propose a hepatocyte-based model, in which kynurenine production is increased by enhanced IDO1 activity stimulated by TGFβ1 and TLR2/4 signaling, via PI3K and NF-κB, to perpetuate a cycle of AHR activation to cause obesity; and inhibition of the AHR, in turn, blocks the cycle's output to prevent obesity. The AHR with its broad ligand binding

  13. Cartan's equations define a topological field theory of the BF type

    International Nuclear Information System (INIS)

    Cuesta, Vladimir; Montesinos, Merced

    2007-01-01

    Cartan's first and second structure equations together with first and second Bianchi identities can be interpreted as equations of motion for the tetrad, the connection and a set of two-form fields T I and R J I . From this viewpoint, these equations define by themselves a field theory. Restricting the analysis to four-dimensional spacetimes (keeping gravity in mind), it is possible to give an action principle of the BF type from which these equations of motion are obtained. The action turns out to be equivalent to a linear combination of the Nieh-Yan, Pontrjagin, and Euler classes, and so the field theory defined by the action is topological. Once Einstein's equations are added, the resulting theory is general relativity. Therefore, the current results show that the relationship between general relativity and topological field theories of the BF type is also present in the first-order formalism for general relativity

  14. Identification and characterization of NF-YB family genes in tung tree.

    Science.gov (United States)

    Yang, Susu; Wang, Yangdong; Yin, Hengfu; Guo, Haobo; Gao, Ming; Zhu, Huiping; Chen, Yicun

    2015-12-01

    The NF-YB transcription factor gene family encodes a subunit of the CCAAT box-binding factor (CBF), a highly conserved trimeric activator that strongly binds to the CCAAT box promoter element. Studies on model plants have shown that NF-YB proteins participate in important developmental and physiological processes, but little is known about NF-YB proteins in trees. Here, we identified seven NF-YB transcription factor-encoding genes in Vernicia fordii, an important oilseed tree in China. A phylogenetic analysis separated the genes into two groups; non-LEC1 type (VfNF-YB1, 5, 7, 9, 11, 13) and LEC1-type (VfNF-YB 14). A gene structure analysis showed that VfNF-YB 5 has three introns and the other genes have no introns. The seven VfNF-YB sequences contain highly conserved domains, a disordered region at the N terminus, and two long helix structures at the C terminus. Phylogenetic analyses showed that VfNF-YB family genes are highly homologous to GmNF-YB genes, and many of them are closely related to functionally characterized NF-YBs. In expression analyses of various tissues (root, stem, leaf, and kernel) and the root during pathogen infection, VfNF-YB1, 5, and 11 were dominantly expressed in kernels, and VfNF-YB7 and 9 were expressed only in the root. Different VfNF-YB family genes showed different responses to pathogen infection, suggesting that they play different roles in the pathogen response. Together, these findings represent the first extensive evaluation of the NF-YB family in tung tree and provide a foundation for dissecting the functions of VfNF-YB genes in seed development, stress adaption, fatty acid synthesis, and pathogen response.

  15. Aerobic degradation of 4-nitroaniline (4-NA) via novel degradation intermediates by Rhodococcus sp. strain FK48

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    Khan, Fazlurrahman; Pandey, Janmejay; Vikram, Surendra; Pal, Deepika; Cameotra, Swaranjit Singh, E-mail: ssc@imtech.res.in

    2013-06-15

    Highlights: • This study reports isolation of a novel bacterium capable of mineralizing 4-nitroaniline (4-NA). • This bacterium has been identified as Rhodococcus sp. strain FK48. • Strain FK48 degrades 4-NA via a novel aerobic degradation pathway that involves 4-AP and 1,2,4-BT. • Subsequent degradation proceeds via ring fission and formation of maleylacetate. • This is the first report showing elucidation of catabolic pathway for microbial degradation 4-NA. -- Abstract: An aerobic strain, Rhodococcus sp. strain FK48, capable of growing on 4-nitroaniline (4-NA) as the sole source of carbon, nitrogen, and energy has been isolated from enrichment cultures originating from contaminated soil samples. During growth studies with non- induced cells of FK48 catalyzed sequential denitrification (release of NO{sub 2} substituent) and deamination (release of NH{sub 2} substituent) of 4-NA. However, none of the degradation intermediates could be identified with growth studies. During resting cell studies, 4-NA-induced cells of strain FK48 transformed 4-NA via a previously unknown pathway which involved oxidative hydroxylation leading to formation of 4-aminophenol (4-AP). Subsequent degradation involved oxidated deamination of 4-AP and formation of 1,2,4-benzenetriol (BT) as the major identified terminal aromatic intermediate. Identification of these intermediates was ascertained by HPLC, and GC–MS analyses of the culture supernatants. 4-NA-indu