1,720,971 research outputs found
Apoptosis, necrosis, and necroptosis in the gut and intestinal homeostasis
Full text linkIntestinal epithelial cells (IECs) form a physiochemical barrier that separates the intestinal lumen from the host’s internal milieu
and is critical for electrolyte passage, nutrient absorption, and interaction with commensal microbiota.Moreover, IECs are strongly
involved in the intestinal mucosal inflammatory response as well as in mucosal innate and adaptive immune responses. Cell death
in the intestinal barrier is finely controlled, since alterations may lead to severe disorders, including inflammatory diseases. The
emerging picture indicates that intestinal epithelial cell death is strictly related to the maintenance of tissue homeostasis. This
review is focused on previous reports on different forms of cell death in intestinal epitheliumIntestinal epithelial cells (IECs) form a physiochemical barrier that separates the intestinal lumen from the host’s internal milieu
and is critical for electrolyte passage, nutrient absorption, and interaction with commensal microbiota.Moreover, IECs are strongly
involved in the intestinal mucosal inflammatory response as well as in mucosal innate and adaptive immune responses. Cell death
in the intestinal barrier is finely controlled, since alterations may lead to severe disorders, including inflammatory diseases. The
emerging picture indicates that intestinal epithelial cell death is strictly related to the maintenance of tissue homeostasis. This
review is focused on previous reports on different forms of cell death in intestinal epitheliu
NOD2 and inflammation: current insights
Full text linkThe nucleotide-binding oligomerization domain (NOD) protein, NOD2, belonging to the intracellular NOD-like receptor family, detects conserved motifs in bacterial peptidoglycan and promotes their clearance through activation of a proinflammatory transcriptional program and other innate immune pathways, including autophagy and endoplasmic reticulum stress. An inactive form due to mutations or a constitutive high expression of NOD2 is associated with several inflammatory diseases, suggesting that balanced NOD2 signaling is critical for the maintenance of immune homeostasis. In this review, we discuss recent developments about the pathway and mechanisms of regulation of NOD2 and illustrate the principal functions of the gene, with particular emphasis on its central role in maintaining the equilibrium between intestinal microbiota and host immune responses to control inflammation. Furthermore, we survey recent studies illustrating the role of NOD2 in several inflammatory diseases, in particular, inflammatory bowel disease, of which it is the main susceptibility gene
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
Endoplasmic reticulum stress and unfolded protein response are involved in paediatric inflammatory bowel disease
No full textEndoplasmic reticulum stress and unfolded protein response have been recently associated with the development of inflammatory bowel diseases in adults. We aimed at assessing the involvement of these pathways also in paediatric inflammatory bowel disease by analysing the expression of the main genes involved in endoplasmic reticulum stress and correlating them with the degree of intestinal inflammation.
Real-time PCR and Western blot analysis of the expression of the endoplasmic reticulum stress marker HSPA5 and of selected genes representing the three pathways of unfolded protein response (IRE-XBP1, PERK-ATF4, ATF6p90-p50) in inflamed and uninflamed biopsies from 28 inflammatory bowel disease paediatric patients and 10 controls.
HSPA5, PDIA4, as well as unspliced and spliced XBP1 mRNAs were significantly increased in patients' inflamed colonic mucosa compared to uninflamed mucosa and controls. HSPA5, PDIA4, ATF6, and phospho-IRE proteins were also upregulated, indicating the activation of the IRE-XBP1 and ATF6p90-p50 branches of unfolded protein response. A positive significant correlation between interleukin-8 levels, as a marker of inflammation, and upregulated genes was found in the inflamed colonic mucosa.
A deregulation of the genes involved in the endoplasmic reticulum stress and unfolded protein response pathways may be a key component of the inflammatory response in paediatric patients with inflammatory bowel disease
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
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
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