1,720,982 research outputs found

    Nicotinamide N-Methyltransferase Inhibition in Endothelium: Effect on Cell Viability and Respiration

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    An impairment of the vascular endothelium plays a role, either as a primary cause or as a result of organ damage, in most of human diseases. Despite intensive research, molecular mechanisms underlying endothelial dysfunction remain unclear. Potential factors affecting normal endothelial functions could be nicotinamide N-methyltransferase (NNMT) and 1-Methylnicotinamide (MNA). The aim of this work was to explore the role of NNMT in endothelial cells subjected to different types (models) of stressors. Experiments were performed with the use of endothelial cells EA.hy926 in which the NNMT expression was silenced. For EA.hy926 stable transfection, it was used a set of pLKO.1 vectors containing stem-loop cassettes encoding short hairpin RNA (shRNA) targeted to human NNMT. NNMT silenced cells were incubated with increasing concentrations of menadione, ONOO- and H2O2 for 24h and data obtained showed a significant decrease of cell viability in NNMT silenced cell lines compared to controls. Subsequently, metabolic function was evaluated through the Seahorse technology. Surprisingly, NNMT silenced lines showed reduced levels of mitochondrial respiration parameters compared to control line EAhy.926. In the second part of the work, results obtained were confirmed by using Human Aortic Endothelial Cells (HAEC) primary line, in which the MNA production was repressed by novel NNMT inhibitors 5-Amino-1-methylquinoline and 6-Methoxynicotinamide N-methylated. Consistently with data obtained on NNMT silenced EAhy.926 cells, menadione-treated HAECs incubated with NNMT inhibitors showed a significant decrease of cell viability compared to controls. Experiments of Seahorse technology revealed reduced levels of mitochondrial respiration parameters in HAECs treated with NNMT inhibitors compared to control. Taken together, data obtained suggest a possible involvement of NNMT in the bioenergetic regulation of endothelial cells and confirm the protective role of the enzyme in the endothelium

    The Multifaceted Role of the Polyphenol Curcumin: A Focus on Type 2 Diabetes Mellitus

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    Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disorder characterized by chronic hyperglycemia, which often co-exists with other metabolic impairments. This condition can damage various tissues and organs, resulting in the development of severe complications, both microvascular, such as retinopathy, nephropathy, and neuropathy, and macrovascular, responsible for an increased risk of cardiovascular diseases. Curcumin is the main bioactive molecule found in the rhizomes of turmeric. Many studies have reported curcumin to exhibit antioxidant, anti-inflammatory, anti-infectious, and anti-cancer properties; thus, there is an increasing interest in exploiting these properties in order to prevent the rise or the progression of T2DM, as well as its possible associated conditions. In this review, we have presented the current state-ofart regarding the clinical trials that have involved curcumin administration and analyzed the possible mechanisms by which curcumin might exert the beneficial effects observed in literature

    The Role of Xenobiotic Caffeine on Cardiovascular Health: Promises and Challenges

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    Cardiovascular diseases (CVDs) represent a leading cause of premature mortality and disability worldwide, with their incidence expected to rise, potentially reaching 24 million deaths per year by 2030. These multifactorial diseases, including hypertension, coronary artery disease, arrhythmia, and heart failure, are often linked to metabolic disturbances such as diabetes, oxidative stress, endothelial dysfunction, and inflammation. Natural compounds, such as caffeine, have been explored for their potential therapeutic effects on CVDs. Caffeine, found in coffee, tea, cocoa, and various energy drinks, is a widely consumed psychoactive compound with noted analgesic and anti-inflammatory properties. Despite its long history of use, caffeine’s impact on cardiovascular health remains controversial, with both beneficial and harmful effects reported. This review examines the current literature on the effects of caffeine on cardiovascular diseases (CVDs), with an emphasis on preclinical and clinical studies, its pharmacokinetic properties, and the molecular mechanisms it modulates. There is evidence that moderate caffeine intake can be beneficial for some CVDs, such as hypertension, while for other CVDs, such as dyslipidemia, the evidence collected so far suggests that caffeine intake could be detrimental since it increases total cholesterol levels. But variability in dosage, intake patterns, and individual factors (such as genetics and diet) complicates the reliability of results. Additionally, challenges related to dose standardization and the absence of consistent clinical trial designs hinder the full utilization of caffeine in CVD treatment. Nonetheless, caffeine appears to be safe for individuals without significant cardiovascular conditions. Future research should aim for well-designed studies with precise patient cohorts and standardized methodologies to better assess caffeine’s role in CVD management

    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

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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