1,721,062 research outputs found

    COX-2 inhibition induces autophagic flux and influences extracellular vesicle profile in human glioblastoma U87MG cell line

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    Introduction: Glioblastoma Multiforme (GBM), a lethal primary tumor of the central nervous system, is characterized by a highly infiltrating capacity, striking cellular heterogeneity, relapsing ability, and resistance to therapy. At present, the standard of therapeutic protocol consists of maximum conceivable surgical resection, followed by radiotherapy plus parallel adjuvant chemotherapy with temozolomide. Despite this, resistance to therapy limits its effectiveness, and GBM cannot be effectively controlled, being characterized by an extremely broad set of genetic and epigenetic alterations and high rates of recurrences. Several studies have suggested that gliomas, similar to most established malignant tumors, are characterized by a moderately inflammatory environment. Growing evidence over the past decades indicates the involvement of COX-2 in the progression of a variety of tumors, including GBM. We analyzed the effect of NS398, a COX-2 inhibitor, on the autophagic flux and extracellular vesicle (EV) secretion in the human U87MG glioma cell line. The effects of glioma stem cells (GSC)-derived EVs on adherent U87MG were also evaluated. Methods: After treatments, cell morphology was assessed by optical microscopy and by SEM. Cell proliferation and migration were examined using CCK-8 and scratch wound healing assay. Cell cycle profile and apoptosis were analyzed by flow cytometry. Autophagy-associated acidic vesicular organelles were quantified by acridine orange staining. A nanoparticle tracking analysis was used to assess the number and size of EVs. EV ultrastructure was verified by TEM and protein levels analyzed by WB. Acid sphingomyelinase was determined through ceramide levels. Results: NS398 was able to induce autophagy in both adherent U87MG and GSCs and EV secretion in GSCs. EVs secreted by NS398-treated GSC, but not those from untreated cells, were able to inhibit adherent U87MG cell growth and migration while also inducing a consistent level of autophagy. Conclusions: The hypothesis of COX-2 expression as GBM profile marker or interesting therapeutic target is supported by our findings. Autophagy and EV release following treatment with the COX-2 inhibitor could represent useful elements to better understand the complex biomolecular frame of GBM

    Association between salivary cortisol level and caries in early childhood

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    The present study aimed to evaluate the association between caries and oral health status, age, salivary cortisol levels, and parental education in children with and without prior dental caries experience. Methods An observational case-control study was performed including 122 children aged between 3 and 6 years who were clinically examined for caries experience using the sum of decayed, missing, and filled teeth in the primary (dmft index) and permanent (DMFT index) dentition. Oral health status was also evaluated using the Simplified Oral Hygiene index (OHI-S). Parents filled a questionnaire to provide information on other variables. Salivary cortisol levels were estimated 1 h after routine dental brushing. Results We found that dental caries experience was associated with cortisol level, plaque, age, and high calculus levels. High cortisol levels and age are important risk factors for caries development with odds ratios of 3.05 (95% CI: 1.84-5.06) and 1.59 (95% CI: 1.09-2.58), respectively. Multivariate logistic analysis showed that cortisol level and age were independently associated with caries presence. Caries experience was not associated with education of parents, feedinghygiene habits of child or birth events. Conclusion The present findings support the hypothesis that caries is mainly correlated with high salivary cortisol levels. Dental caries experience in children was also positively associated with tartar, plaque, and age. © 2018, Italian Society of Paediatric Dentistry

    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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