1,721,061 research outputs found
Biomarkers in nonalcoholic fatty liver disease. a new era in diagnosis and staging of disease in children
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Deciphering the Role of Gasdermin D in Liver Inflammation and Fibrosis: A Potential Therapeutic Target in Metabolic Dysfunction-Associated Steatohepatitis
No full textPyroptosis is a form of programmed cell death initiated by inflammasomes and characterized by Caspase-1 activation and gasdermin D (GSDMD)-dependent pore formation, fueling liver inflammation and fibrosis. The activation of the NLRP3 inflammasome plays a pivotal role in driving these processes in Metabolic Dysfunction-Associated Steatohepatitis (MASH).Here, we tested the hypothesis that global deletion of GSDMD (GSDMDKO) provides protection against diet-induced MASH by attenuating inflammasome activation. This protective effect may reduce fibrogenesis through attenuated inflammasome activation and diminished bidirectional activation of resident liver cells within the inflammatory environment. Our work showed that GSDMD deletion protected the liver from pro-inflammatory cytokine expression and immune cell infiltration in response to a choline-deficient, amino acid-defined high-fat diet (CDAA-HF), thereby alleviating both steatosis and inflammation in MASH. Additionally, GSDMDKO mice exhibited reduced hepatic fibrosis, revealing a critical role for GSDMD in regulating lipid metabolism, immune response, and fibrogenesis through modulation of HSC and myeloid cell activity. Notably, close interactions between monocytes, Kupffer cells (KCs), HSCs, and hepatocytes fostered a distinctive inflammatory microenvironment, characterized by the expulsion of monocyte extracellular traps (METs). The deletion of GSDMD shifted Kupffer cells from inflammatory mediators to central niche regulators, establishing a bidirectional crosstalk with HSCs and modulating their fibrogenic activity. Our findings highlight GSDMD as a central orchestrator of liver inflammation and fibrogenesis in MASH. These results underscore GSDMD's potential as a therapeutic target to disrupt the inflammatory cascade and fibrosis in liver disease
Circulating Soluble Fas and Fas Ligand Levels Are Elevated in Children with Nonalcoholic Steatohepatitis
No full textBACKGROUND: There is an urgent need to develop alternatives to liver biopsy in children to diagnose nonalcoholic steatohepatitis (NASH), the aggressive form of nonalcoholic fatty liver disease (NAFLD). Increased hepatocyte apoptosis plays a central role in the development of NASH.
AIMS: To evaluate the plasma levels of two markers of apoptosis, soluble Fas (sFas) and soluble Fas ligand (sFasL), in children with NAFLD and assess their utility as biomarkers of disease severity.
METHODS: Children with biopsy-proven NAFLD were included, and blood samples were collected. Patients were divided into NASH and "not NASH." We measured plasma sFas and sFasL using specific ELISA immunoassays. RESULTS: One hundred and seventeen children with NAFLD were recruited. Average age was 12.2 ± 2.9 years, 67 % were male, and 58 % had NASH. Patients with NASH had significantly higher levels of sFas and sFasL than patients in the "not NASH" group (686.0 ± 186.5 pg/mL versus 594.2 ± 244.9, p = 0.023 for sFas and 324.9 ± 146.5 pg/mL versus 221.4 ± 134.0, p < 0.001 for sFasL). sFasL was found to have higher accuracy for predicting the presence of NASH on liver biopsy with an AUC (95 % CI) of 0.714 (0.618, 0.810). A prediction model, the NASH apoptosis score, was generated consisting of plasma sFasL, age, ferritin, transferrin, and triglyceride levels. The area under receiver operating characteristic curve was 0.78 (95 % CI 0.0.69, 0.87).
CONCLUSIONS: Markers of the extrinsic pathway of hepatocyte apoptosis are elevated in children with NASH. sFasL and the NASH apoptosis score are potential novel biomarkers for NASH
A low n‐6 to n‐3 polyunsaturated fatty acid ratio diet improves hyperinsulinaemia by restoring insulin clearance in obese youth
No full textAim: A low n-6 to n-3 polyunsaturated fatty acid (PUFA) ratio diet reduces hyperinsulinemia in insulin-resistant adolescents even in the absence of change in body weight and glucose metabolism. The aim of this study was to examine the determinants and metabolic impact of the dietary-induced reduction in fasting and post-load insulin levels in obese youths. Materials and methods: Insulin secretion and clearance were assessed by measuring and modeling plasma insulin and C-peptide in 17 obese youth who underwent a 9-point, 180-min oral glucose tolerance test (OGTT) before and after a 12-week, eucaloric low n-6:n-3 PUFA ratio diet. Hepatic fat content was assessed by repeated abdominal magnetic resonance imaging (MRI). Results: Insulin clearance at fasting and during the OGTT was significantly increased after the diet, while absolute and glucose-dependent insulin secretion and model-derived parameters of β cell function were not affected. Dietary-induced changes in insulin clearance positively correlated with changes in whole-body insulin sensitivity and β cell glucose sensitivity, but not with changes in hepatic fat. Subjects with greater increases in insulin clearance showed a worse metabolic profile at enrollment, characterized by impaired insulin clearance, β cell glucose sensitivity, and glucose tolerance, and benefited the most from the diet, achieving greater improvements in glucose-stimulated hyperinsulinemia, insulin resistance, and β cell function. Conclusions: We demonstrated that a 12-week low n-6:n-3 PUFA ratio diet improves hyperinsulinemia by increasing fasting and post-load insulin clearance in obese youth, independently of weight loss, glucose concentrations and insulin secretion. This article is protected by copyright. All rights reserved
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
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