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    Inhibitory effect of quercetin on tryptase and MCP-1 chemokine release, and histidine decarboxylase mRNA transcription by human mast cell-1 cell line

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    Mast cells are important in reactions of allergic disease and are also involved in a variety of neuroinflammatory diseases. Mast cells can be immunologically activated by IgE through their Fc receptors, as well as by neuropeptides and cytokines to secrete mediators. Here we used a human mast cell-1 (HMC-1) cell line cultured and treated with a physiological activator, anti-IgE, and a nonphysiological activator, calcium ionophore A23187, for tryptase and MCP-1 generation and transcription of histidine decarboxylase. We used quercetin, a potent antioxidant, cytoprotective and anti-inflammatory compound capable of inhibiting histamine and some cytokines released from several cell types, as an inhibitor of immunological and nonimmunological stimulus for mast cells. In this study quercetin inhibits, in a dose-response manner, tryptase and MCP-1. Moreover, using RT-PCR quercetin inhibited the transcription of histidine decarboxylase, the rate-limiting enzyme responsible for the generation of histamine from histidine, and MCP-1. Our data suggest that quercetin is an important and good candidate for reducing the release of pro-inflammatory mast cell mediators activated by physiological and nonphysiological stimulato

    Inhibitory effect of quercetin on tryptase and interleukin-6 release, and histidine decarboxylase mRNA transcription by human mast cell-1 cell line

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    Mast cells are involved in inflammatory processes and in allergic reactions where immunologic stimulation leads to degranulation and generation of numerous cytokines and inflammatory mediators. Mast cells have been proposed as an immune gate to the brain, as well as sensors of environmental and emotional stress, and are likely involved in neuropathologic processes such as multiple sclerosis. Among mast cell products, the protease tryptase could be associated with neurodegenerative processes through the activation of specific receptors (PARs) expressed in the brain, while interleukin (IL)-6 likely causes neurodegeneration and exacerbates dysfunction induced by other cytokines; or it could have a protective effect against demyelinisation. In this report we show that quercetin, a natural compound able to act as an inhibitor of mast cell secretion, causes a decrease in the release of tryptase and IL-6 and the down-regulation of histidine decarboxylase (HDC) mRNA from human mast cell (HMC)-1 cells. As quercetin dramatically inhibits mast cell tryptase and IL-6 release and HDC mRNA transcription by HMC-1 cell line, these results nominate quercetin as a therapeutical compound in association with other therapeutical molecules for neurological diseases mediated by mast cell degranulation

    Modulation of multidrug resistance p-glycoprotein activity by flavonoids and honokiol in human doxorubicin- resistant sarcoma cells (MES-SA/DX-5): implications for natural sedatives as chemosensitizing agents in cancer therapy.

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    Multidrug resistance (MDR) in cancer cells is often caused by the high expression of the plasma membrane drug transporter P-glycoprotein (Pgp) associated with an elevated intracellular glutathione (GSH) content in various human tumors. Several chemosensitizers reverse MDR but have significant toxicities. Sedatives are often used to control anxiety and depression in cancer patients. In this in vitro study we investigated the effects of three plant derived sedatives such as apigenin (Api), fisetin (Fis), flavonoids and honokiol (Hnk) on Pgp activity and cellular GSH content in order to evaluate their potential use as chemosensitizing agents in anticancer chemotherapy. Human doxorubicin (doxo) resistant uterine sarcoma cells (MES-SA/Dx5) that overexpress Pgp, were treated with each sedative alone (10 microM) or in combination with different doxo concentrations (2-8 microM). We measured the intracellular accumulation and cytotoxicity of doxo (MTT assay), the cellular GSH content (GSH assay) and ROS production (DFC-DA assay), in comparison with verapamil (Ver), a specific inhibitor for Pgp, used as reference molecule. We found that exposure at 2 and 8 microM doxo concentrations in the presence of Api, Fis and Hnk enhanced significantly doxo accumulation by 29+/-3.3, 20+/-4.8, 24+/-6.6 percent and 14+/-1.7, 8.3+/-4.2, 10.7+/-3.1 percent, respectively, when compared with doxo alone. These results were consistent with the increase of sensitivity towards doxo in MES-SA/Dx5, resulting in 1.7, 1.2, 1.4-fold and 1.2, 1.0 and 1.1-fold increases, respectively. Moreover, treatment with Api decreased markedly cellular GSH content (18 percent) and increased ROS production (greater than 20 percent) on MES-SA/Dx5 cells, while a significant reduction in ROS levels was observed in Hnk and Fis treated cells, when compared to untreated control. Our in vitro findings provide a rationale for innovative clinical trials to assess the use of natural sedatives or their derivatives as potential adjuvants to anticancer treatment for overcoming multidrug resistance Pgp-mediated in cancer patients

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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