1,720,957 research outputs found
Cyanidin-3-O-glucoside exhibits anti-inflammatory properties and improves intestinal epithelial barrier integrity in Caco-2 cells exposed to TNF-alpha
No full textThe intestinal mucosal barrier plays an important role in the body’s protection against luminal pathogens and antigenic molecules; intercellular tight junctions (TJs), mainly composed of cytoplasmic proteins, including zona occludens (ZO) proteins, and two distinct transmembrane proteins, occludin and claudin, are the key structures responsible for intestinal epithelial barrier integrity (Turner, 2009). A dysregulation of one of this components, resulting in a paracellular permeability alteration, can lead to severe intestinal disorders, including inflammatory bowel disease (IBDs), the collective name for Crohn’s disease and ulcerative colitis, characterized by symptoms such as weight loss, diarrhoea, rectal bleeding, abdominal pain, fever and anemia (Cao et
al, 2013). TNF-α-induced increase in intestinal epithelial tight junction permeability has been proposed to be an important proinflammatory mechanism contributing to intestinal inflammation in IBD, as demonstrated by the presence of markedly elevated levels of this cytokine in the intestinal tissue and serum of patients suffering from Crohn's disease (Ye et al, 2006). Although the molecular mechanism involved in intestinal barrier dysfunction caused by proinflammatory cytokines is still unclear and it represents a research focus in pathogenesis of IBD, it has been believed that NF-kB plays a very important role in the proinflammatory cytokines induced intestinal barrier disruption and in a downregulation of tight junction proteins expression. Recent studies
support beneficial effects of anthocyanins, a class of flavonoid compounds that are widely
distributed in mediterranean diet, in various chronic inflammatory diseases, such as IBDs. The aim of this work was to determine some of the intracellular mechanisms involved in TNF-α modulation of intestinal epithelial permeability by using an in vitro intestinal epithelial system consisting of filter grown Caco-2 monolayers and the effects exerted by Cyanidin-3-O-glucoside (C3G) pretreatment. Caco-2 cells exposure to TNF-α for 6 h activated IKK/NF-kB proinflammatory pathway, and induced COX-2 and IL6 expression. Interestingly, cells pretreatment for 24h with C3G (20 and 40 μM) was effective in preventing TNF-α-induced changes. Furthermore, C3G was able to improve intracellular redox status altered by TNF-α by increasing GSH levels and cellular antioxidant power. Furthermore, TNF-α exposure for 6h altered Caco-2 cells barrier permeability and integrity. C3G pretreatment prevented the increase in Caco-2 TJ permeability and epithelial barrier integrity. In conclusion, C3G showed anti-inflammatory properties through the modulation of NF-kB pathway and improved intestinal epithelial barrier integrity altered by TNF-α in Caco-2 cells. These data suggest that anthocyanins could contribute, as complementary approaches to the conventional already existing therapeutic approaches (i.e. non-steroidal anti-inflammatory drugs), to the management of IBDs (Romier et al, 2008)
Uso dell’acido lipoico nella poliabortività: studio in vitro dei meccanismi molecolari dell’effetto protettivo nella disfunzione endoteliale
No full textL’incidenza della poliabortività è fortemente aumentata nel corso degli ultimi anni. Essa è definita come la manifestazione di tre o più aborti consecutivi entro la ventesima settimana di gestazione e può essere causata da molteplici fattori tra cui anomalie genetiche, stress ossidativo, processi infiammatori e disordini del sistema immunitario. Lo stress ossidativo e l’infiammazione svolgono un ruolo fondamentale nella disfunzione endoteliale, e quest’ultima sembra essere correlata alla fisiopatologia della poliabortività. Elevati livelli di citochine pro-infiammatorie, come IL-1β, IFN-ɣ e TNF-α, e di molecole di adesione endoteliale sono stati riscontrati in casi di poliabortività. L’aumento delle molecole di adesione a causa di citochine infiammatorie come il TNF-α dipende dall’attivazione del fattore nucleare NF-kB. L’acido α-lipoico (ALA) è un composto organo-solforico e un essenziale co-fattore mitocondriale. Per le sue proprietà antiossidanti e anti-infiammatorie
ALA è stato recentemente proposto come composto terapeutico in numerose patologie. Si suppone che l’origine di queste attività risieda nell’attivazione o repressione di due fattori trascrizionali essenziali: Nrf2, che svolge un ruolo fondamentale nell’omeostasi dello stato redox cellulare, e NF-kB, il principale fattore trascrizionale coinvolto nei processi
infiammatori. Lo scopo del lavoro è stato quello di valutare l’effetto in vitro di ALA a concentrazioni raggiungibili in vivo mediante integrazione della dieta (0,25 -1μM), contro la disfunzione endoteliale indotta da TNF-α in cellule endoteliali della vena ombelicale umana (HUVEC). Le HUVEC sono state pretrattate per 2 ore con concentrazioni 0,25 – 1 μM di ALA, lavate con PBS, ed esposte per 2 ore a TNF-α 20 ng/ml. Inoltre, per testare l’attività di ALA su un endotelio già attivato, in un’altra serie di esperimenti le HUVEC sono state precedentemente esposte a TNF-α 20 ng/ml per 2 ore e, dopo lavaggi con PBS, trattate con ALA 0,25 – 1 μM per le successive 2 ore. I risultati hanno mostrato la capacità di ALA di inibire l’attivazione del pathway infiammatorio di NF-ĸB indotta da TNF-α in cellule HUVEC, come dimostrato dai ridotti livelli nucleari della subunità p65 di NF-ĸB e dall’aumento dei livelli citoplasmatici della proteina inibitrice pIkB. L’effetto benefico di ALA, nei confronti della disfunzione endoteliale indotta da citochine infiammatorie, è stato avvalorato dalla riduzione dell’espressione genica delle molecole di adesione, E-selectina e ICAM-1, indotta da TNF-α. Elevati livelli nucleari di Nrf2 e citoplasmatici di Keap1 hanno dimostrato la capacità di ALA di innescare una risposta cellulare adattativa attivando il pathway di Nrf2 in cellule HUVEC, il quale agisce come modulatore dell’espressione di geni antiossidanti e citoprotettivi. Inoltre, è di notevole importanza sottolineare che ALA si è mostrato in grado di determinare questi effetti, in modo dose dipendente, sia dopo esposizione con TNF-α, sia su cellule precedentemente stimolate. La capacità di basse concentrazioni di ALA, raggiungibili con l’integrazione, di attivare il pathway di Nrf2 e di inibire quello di NF-ĸB attivato da TNF-α, potrebbero rappresentare i meccanismi alla base dell’effetto protettivo di questa molecola. Questi dati supportano una potenziale azione preventiva e/o terapeutica del ALA nella poliabortività causata da disfunzione endoteliale
Cyanidin-3-O-Glucoside Modulates the In Vitro Inflammatory Crosstalk between Intestinal Epithelial and Endothelial Cells
Full text linkIntestinal epithelium represents a protective physical barrier and actively contributes to the mucosal immune system. Polarized basolateral intestinal secretion of inflammatory mediators, followed by activation of NF-κB signaling and inflammatory pathways in endothelial cells, efficiently triggers extravasation of neutrophils from the vasculature, therefore contributing to the development and maintenance of intestinal inflammation. Proper regulation of NF-κB activation at the epithelial interface is crucial for the maintenance of physiological tissue homeostasis. Many papers reported that anthocyanins, a group of compounds belonging to flavonoids, possess anti-inflammatory effects and modulate NF-κB activity. In this study, by using a coculture in vitro system, we aimed to evaluate the effects of TNF-α-stimulated intestinal cells on endothelial cells activation, as well as the protective effects of cyanidin-3-glucoside (C3G). In this model, TNF-α induced nuclear translocation of NF-κB and TNF-α and IL-8 gene expression in Caco-2 cells, whereas C3G pretreatment dose-dependently reduced these effects. Furthermore, TNF-α-stimulated Caco-2 cells induced endothelial cells activation with increased E-selectin and VCAM-1 mRNA, leukocyte adhesion, and NF-κB levels in HUVECs, which were inhibited by C3G. We demonstrated that selective inhibition of the NF-κB pathway in epithelial cells represents the main mechanism by which C3G exerts these protective effects. Thus, anthocyanins could contribute to the management of chronic gut inflammatory diseases
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Full text linkWe 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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe 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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