1,720,958 research outputs found
Lipoxins and aspirin-triggered lipoxins in resolution of inflammation
No full textThe resolution of the inflammatory response is highly regulated by the timely biosynthesis of a number of endogenous lipid mediators. Among these, lipoxins (LX) and their 15-epimers, aspirin triggered lipoxins (ATL) derived by the lipoxygenase (LO) route of arachidonic acid metabolism. In particular, they are formed and released by cells expressing 5-,12- and 15-LO such as leukocytes, platelets, vascular endothelium and epithelium, alone or during transcellular interactions. ATL biosynthesis requires cyclooxygenase-2 acetylation by aspirin. LX and ATL exert potent bioactions on leukocytes, vascular and epithelial cells to stop inflammation and promote resolution. They have shown to be beneficial in a broad spectrum of preclinical models of disease as well as in some clinical trials. Counter-regulatory signaling by LXA4 and 15-epi-LXA4 follows the activation of a G protein-coupled receptor, termed ALX/FPR2, which is emerging as a key anti-inflammatory receptor
Epigenetic regulation of the formyl peptide receptor 2 gene
No full textpoxin (LX) A4, a main stop signal of inflammation, exerts potent bioactions by activating a specific G proteincoupled
receptor, termed formyl peptide receptor 2 and recently renamed ALX/FPR2. Knowledge of the regulatory
mechanisms that drive ALX/FPR2 gene expression is key for the development of innovative antiinflammatory
pharmacology. Here, we examined chromatin patterns of the ALX/FPR2 gene. We report that in
MDA-MB231 breast cancer cells, the ALX/FPR2 gene undergoes epigenetic silencing characterized by low acetylation
at lysine 27 and trimethylation at lysine 4, associated with high methylation at lysine 27 of histone 3. This
pattern, which is consistent with transcriptionally inaccessible chromatin leading to low ALX/FPR2 mRNA and
protein expression, is reversed in polymorphonuclear leukocytes that express high ALX/FPR2 levels. Activation
of p300 histone acetyltransferase and inhibition of DNA methyltransferase restored chromatin accessibility and
significantly increased ALX/FPR2 mRNA transcription and protein levels in MDA-MB231 cells, as well as in pulmonary
artery endothelial cells. In both cells types, changes in the histone acetylation/methylation status enhanced
ALX/FPR2 signaling in response to LXA4. Collectively, these results uncover unappreciated epigenetic
regulation of ALX/FPR2 expression that can be exploited for innovative approaches to inflammatory disorders
MicroRNA-181b regulates ALX/FPR2 expression and proresolution signaling in human macrophages.
No full textRegulatory mechanisms of ALX/FPR2, the lipoxin A4 receptor, expression have considerable relevance in inflammation resolution. Because microRNAs (miRs) are emerging as key players in inflammation resolution, here we examined microRNA-mediated regulation of ALX/FPR2 (lipoxin A4 receptor/formyl peptide receptor 2) expression. By matching data from bioinformatic algorithms, we found 27 miRs predicted to bind the 3'-UTR of ALX/FPR2. Among these, we selected miR-181b because of its link with inflammation. Using a luciferase reporter system, we assessed miR-181b binding to ALX/FPR2 3'-UTR. Consistent with this, miR-181b overexpression in human macrophages significantly down-regulated ALX/FPR2 protein levels (-25%), whereas miR-181b knockdown gave a significant increase in ALX/FPR2 (+60%). miR-181b levels decreased during monocyte to macrophage differentiation (-50%), whereas ALX/FPR2 expression increased significantly (+60%). miR-181b overexpression blunted lipoxin A4 (0.1-10 nm)- and resolvin D1 (0.01-10 nm)-stimulated phagocytic activity of macrophages. These results unravel novel regulatory mechanisms of ALX/FPR2 expression and ligand-evoked macrophages proresolution responses mediated by miR-181b, thus uncovering novel components of the endogenous inflammation resolution circuits
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
Persistence and adherence to androgen deprivation therapy in men with prostate cancer: an administrative database study
No full textBACKGROUND: The aim of this study was to assess adherence to and persistence with androgen deprivation therapy (ADT) in a large cohort of prostate cancer (PCa) patients selected from an administrative database, with special attention to elderly patients.
METHODS: Patients treated with LHRH analogues, LHRH antagonists, the novel androgen antagonist enzalutamide, and the CYP17 inhibitor abiraterone were included spanning the years 2011-2017. Descriptive statistics were used to analyze persistence and adherence in older patients stratified by age (46-55.56-65, 66-75. 76-85, and >85 years). The effect of persistence duration on overall survival in super-elderly patients was analyzed by the Kaplan-Meier method, together with the influence of multiple prescriptions on overall survival.
RESULTS: A total of 1160 male patients were treated with ADT. Of these, 1075 were given LHRH analogues. 80 LHRH antagonists, 14 novel androgen antagonists, and 109 the CYP17 inhibitor. Median adherence values were 0.93, 0.97, 0.95, and 0.99 respectively. The highest persistence was recorded for LHRH analogues/antagonists (24 months), followed enzalutamide and abiraterone (8 months). A total of 107 patients (9.2%) were classified as super-elderly (age range 85-97 years). Median persistence and OS in this group were 13 months and 29 months, respectively. The adherence was 0.92. Overall survival was significantly associated with additional prescriptions for other conditions-indications (P=0.0047) but not with differences in adherence rates (P=0.98).
CONCLUSIONS: Our data showed high adherence and persistence rates in men on ADT. The overall survival in the super-elderly is not influenced by persistence and/or adherence but rather by coprescriptions
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