1,721,015 research outputs found
Metabolomic Profiling to Identify Predictors of Response to Vitamin E for Non-Alcoholic Steatohepatitis (NASH)
Full text linkVitamin E was recently shown to improve hepatic histology in a randomized controlled trial of pioglitazone or vitamin E for nonalcoholic steatohepatitis (PIVENS). The current study utilized samples collected in the PIVENS trial to identify: (1) baseline metabolomic profiles that could identify who would respond to vitamin E treatment and (2) end of treatment metabolomic profiles reflective of histologic improvement. A comprehensive analysis of metabolomics profiles (n = 547) quantified by mass spectrometry was performed in vitamin E responders (n = 16), vitamin E non-responders (n = 15), and placebo responders (n = 15). At baseline, phenyl-propionic acid (Odds ratio: 29.4, p\u3c0.01), indole-propionic acid levels (Odds ratio: 16.2, p\u3c0.01) were directly associated with a subsequent histologic response to vitamin E treatment whereas γ-carboxyethylhydroxychroman (CEHC) levels were inversely related to histologic response. Adjusting for baseline values by analysis of covariance, the end of treatment levels of gamma-glutamyl leucine (Fold change: 0.82, p\u3c0.02) and gamma-glutamyl valine (Fold change: 0.8, p\u3c0.03) were significantly lower in vitamin E responders compared to non-responders. The levels of gamma-glutamyl transpeptidase were not significantly different across the two groups. Subjects receiving placebo who demonstrated a histologic improvement also demonstrated lower levels of gamma-glutamylated amino acids (leucine, valine and isoleucine) compared to vitamin E non-responders. These data provide exploratory proof that there are measurable differences in the metabolic profile of subjects who are likely (vs unlikely) to respond to vitamin E treatment for NASH and in those experiencing histologic improvement (vs no improvement) on treatment and support further studies to validate these biomarkers
Hepatokines and adipokines in NASH-related hepatocellular carcinoma
Full text linkThe incidence of hepatocellular carcinoma (HCC) is increasing in industrialised societies; this is likely secondary to the increasing burden of non-alcoholic fatty liver disease (NAFLD), its progressive form non-alcoholic steatohepatitis (NASH), and the metabolic syndrome. Cumulative studies suggest that NAFLD-related HCC may also develop in non-cirrhotic livers. However, prognosis and survival do not differ between NAFLD- or virus-associated HCC. Thus, research has increasingly focused on NAFLD-related risk factors to better understand the biology of hepatocarcinogenesis and to develop new diagnostic, preventive, and therapeutic strategies. One important aspect thereof is the role of hepatokines and adipokines in NAFLD/NASH-related HCC. In this review, we compile current data supporting the use of hepatokines and adipokines as potential markers of disease progression in NAFLD or as early markers of NAFLD-related HCC. While much work must be done to elucidate the mechanisms and interactions underlying alterations to hepatokines and adipokines, current data support the possible utility of these factors – in particular, angiopoietin-like proteins, fibroblast growth factors, and apelin – for detection or even as therapeutic targets in NAFLD-related HCC.Fil: Kucukoglu, Ozlem. Otto-von-Guericke-Universität Magdeburg; AlemaniaFil: Sowa, Jan Peter. Ruhr Universität Bochum; AlemaniaFil: Mazzolini Rizzo, Guillermo Daniel. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Syn, Wing Kin. Universidad del País Vasco; EspañaFil: Canbay, Ali. Otto-von-Guericke-Universität Magdeburg; Alemani
The role of osteopontin in liver fibrosis
Full text link150 p.Osteopontin (OPN) is a cytokine and matrix molecule that is upregulated in human and mouse models of chronic liver injury and directly promotes liver fibrogenesis by activating hepatic stellate cells (HSC) and liver progenitors (LPC). OPN is secreted by multiple cell types including HSC, LPC, as well as recruited immune cells such as natural killer T (NKT) cells, which amplify the fibrogenic response. In vivo, OPN neutralization abrogates the LPC response, inhibits HSC activation, and reduces liver fibrosis, thus demonstrating that targeting OPN is a potentially attractive anti-fibrotic strategy
NASH, Metabolic Syndrome, and Diabetes: How Sugar and Fat Increase the Risk of Developing Advanced Liver Disease
Full text linkOpen Access funding enabled and organized by Projekt DEAL
Significance of Simple Steatosis: An Update on the Clinical and Molecular Evidence
Full text linkNon-alcoholic fatty liver disease (NAFLD) is defined clinicopathologically by the accumulation of lipids in >5% of hepatocytes and the exclusion of secondary causes of fat accumulation. NAFLD encompasses a wide spectrum of liver damage, extending from simple steatosis or non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH)-the latter is characterized by inflammation and hepatocyte ballooning degeneration, in addition to the steatosis, with or without fibrosis. NAFLD is now the most common cause of chronic liver disease in Western countries and affects around one quarter of the general population. It is a multisystem disorder, which is associated with an increased risk of type 2 diabetes mellitus as well as liver- and cardiovascular-related mortality. Although earlier studies had suggested that NAFL is benign (i.e., non-progressive), cumulative evidence challenges this dogma, and recent data suggest that nearly 25% of those with NAFL may develop fibrosis. Importantly, NAFLD patients are more susceptible to the toxic effects of alcohol, drugs, and other insults to the liver. This is likely due to the functional impairment of steatotic hepatocytes, which is virtually undetectable by current clinical tests. This review provides an overview of the current evidence on the clinical significance of NAFL and discusses the molecular basis for NAFL development and progression.Fil: Mazzolini Rizzo, Guillermo Daniel. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Sowa, Jan Peter. Ruhr Universität Bochum; AlemaniaFil: Atorrasagasti, María Catalina. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Kücükoglu, Özlem. Otto-von-Guericke-Universität Magdeburg; AlemaniaFil: Syn, Wing Kin. Universidad del País Vasco; España. Medical University of South Carolina; Estados Unidos. University of the Basque Country; EspañaFil: Canbay, Ali. Ruhr Universität Bochum; Alemani
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
Sulphasalazine-induced hypersensitivity syndrome: A relapsing disorder and the role of human herpes virus-6 [1]
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