1,720,975 research outputs found
Dipotassium glycyrrhizate via HMGB1 or AMPK signaling suppresses oxidative stress during intestinal inflammation
No full textAims: Oxidative stress and inflammation are always associated. Appropriate management of oxidative
mediators may represent a therapeutic strategy to reduce inflammation, and use of antioxidant can be
protective against inflammatory diseases. Glycyrrhizin (GL) plays an anti-inflammatory and antioxidant
effect by inhibiting high mobility group box 1 (HMGB1) or 11-b-hydroxysteroid dehydrogenase type II
(11bHSD2) enzyme. In this study, the potential role of dipotassium glycyrrhizate (DPG), a salt of GL, to
reduce oxidative stress in intestinal inflammatory condition was investigated in vivo and the mechanism
of action of DPG was studied in vitro.
Results: In a colitis mouse model DPG affected oxidative stress reducing iNOS and COX-2 expression, as
well as NO and PGE2 levels. By means of LPS-stimulated macrophages we found that DPG inhibited the
expression of pro-inflammatory cytokines and reduced iNOS and COX-2 expression in a time dependent
manner, through two different ways of signal. DPG reduced, at a later time, both iNOS and COX-2, through
a mechanism HMGB1-dependent, and at an earlier time only COX-2, through a mechanism AMP-
activated kinase (AMPK)-phosphorylation-mediated.
Conclusion: DPG has a protective effect on colitis and inflammation through the inhibition of oxidative
stress. This study clarifies the two-ways mechanism by which DPG inhibits iNOS and COX-2 during
inflammation and demonstrates for the first time that AMPK is a target of DPG. Uncovering this
mechanism is significant to clarify the relationship between energy homeostasis and anti-oxidative
responses and suggests that DPG could play a relevant role in the development of new therapy against
inflammatory diseases associated to oxidative stress.Aims: Oxidative stress and inflammation are always associated. Appropriate management of oxidative
mediators may represent a therapeutic strategy to reduce inflammation, and use of antioxidant can be
protective against inflammatory diseases. Glycyrrhizin (GL) plays an anti-inflammatory and antioxidant
effect by inhibiting high mobility group box 1 (HMGB1) or 11-b-hydroxysteroid dehydrogenase type II
(11bHSD2) enzyme. In this study, the potential role of dipotassium glycyrrhizate (DPG), a salt of GL, to
reduce oxidative stress in intestinal inflammatory condition was investigated in vivo and the mechanism
of action of DPG was studied in vitro.
Results: In a colitis mouse model DPG affected oxidative stress reducing iNOS and COX-2 expression, as
well as NO and PGE2 levels. By means of LPS-stimulated macrophages we found that DPG inhibited the
expression of pro-inflammatory cytokines and reduced iNOS and COX-2 expression in a time dependent
manner, through two different ways of signal. DPG reduced, at a later time, both iNOS and COX-2, through
a mechanism HMGB1-dependent, and at an earlier time only COX-2, through a mechanism AMP-
activated kinase (AMPK)-phosphorylation-mediated.
Conclusion: DPG has a protective effect on colitis and inflammation through the inhibition of oxidative
stress. This study clarifies the two-ways mechanism by which DPG inhibits iNOS and COX-2 during
inflammation and demonstrates for the first time that AMPK is a target of DPG. Uncovering this
mechanism is significant to clarify the relationship between energy homeostasis and anti-oxidative
responses and suggests that DPG could play a relevant role in the development of new therapy against
inflammatory diseases associated to oxidative stress
PARP1 inactivation increases regulatory T / Th17 cell proportion in intestinal inflammation. Role of HMGB1
No full text: Inflammatory bowel diseases (IBD) are chronic relapsing disorders with increasing prevalence. Knowledge gaps still limit the possibility to develop more specific and effective therapies. Using a dextran sodium sulfate colitis mouse model, we found that inflammation increased the total number and altered the frequencies of leukocytes within colon mesenteric lymph nodes (cMLNs). Although the inflammation reduced the frequency of regulatory T (Treg) cells, their absolute numbers were increased. Increased frequency of colitogenic Th17 cells was also observed. Noteworthy, untreated mice lacking Poly(ADP-ribose)-Polimerase-1 functional gene (PARP-1KO) displayed higher frequency of Treg cells and lower percentage of Th17 cells in cMLNs. In colitic PARP-1KO mice the inflammation driven expansion of the Foxp3 Treg population was more pronounced than in WT mice. Conversely, colitis increased Th17 cells to a lower extent in PARP-1KO mice compared with WT mice, resulting in a more protective Treg/Th17 cell ratio. Consequently PARP-1KO mice developed less severe colitis with reduced expression of inflammatory cytokines. In ex vivo experiments PARP-1KO and WT CD11c dendritic cells (DCs) promoted naïve CD4 T cell differentiation differently, the former sustaining more efficiently the generation of Treg cells, the latter that of Th17 cells. Addition of HMGB1 B box or of dipotassium glycyrrhizate, which sequesters extracellular HMGB1, revealed a role for this alarmin in the regulation exerted by PARP-1 on the stimulating vs. tolerogenic function of DCs during colitis. Moreover, a higher percentage of CD11c DC from PARP-1KO mice expressed CD103, a marker associated with the ability of DC to induce Treg cells, compared with WT DC. Conversely, PARP-1KO DC were including a reduced percentage of CX3CR1+ DC, described to induce Th17 cells. These findings were observed in both splenic and colon lamina propria DC
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
Glycyrrhizin Decreases HMGB1 Release and Is Effective for the Treatment of Chemical-Induced Murine Colitis
No full textNOD2 induces autophagy to control AIEC bacteria infectiveness in intestinal epithelial cells
No full textOBJECTIVE:
The importance of autophagy in mechanisms underlying inflammation has been highlighted. Downstream effects of the bacterial sensor NOD2 include autophagy induction. Recently, a relationship between defects in autophagy and adherent/invasive Escherichia coli (AIEC) persistence has emerged. The present study aims at investigating the interplay between autophagy, NOD2 and AIEC bacteria and assessing the expression level of autophagic proteins in intestinal biopsies of pediatric patients with inflammatory bowel disease (IBD).
METHODS:
A human epithelial colorectal adenocarcinoma (Caco2) cell line stably over-expressing NOD2 was produced (Caco2NOD2). ATG16L1, LC3 and NOD2 levels were analysed in the Caco2 cell line and Caco2NOD2 after exposure to AIEC strains, by western blot and immunofluorescence. AIEC survival inside cells and TNFα, IL-8 and IL-1βmRNA expression were analysed by gentamicin protection assay and real time PCR. ATG16L1 and LC3 expression was analyzed in the inflamed ileum and colon of 28 patients with Crohn's disease (CD), 14 with ulcerative colitis (UC) and 23 controls by western blot.
RESULTS:
AIEC infection increased ATG16L1 and LC3 in Caco2 cells. Exposure to AIEC strains increased LC3 and ATG16L1 in Caco2 overexpressing NOD2, more than in Caco2 wild type, while a decrease of AIEC survival rate and cytokine expression was observed in the same cell line. LC3 expression was increased in the inflamed colon of CD and UC children.
CONCLUSIONS:
The NOD2-mediated autophagy induction is crucial to hold the intramucosal bacterial burden, especially towards AIEC, and to limit the resulting inflammatory response. Autophagy is active in inflamed colonic tissues of IBD pediatric patients
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