1,720,995 research outputs found
Le interazioni tra PDX-1 e Hes-1 determinano la risposta proliferativa dei colangiociti al danno
No full textIntroduzione e scopo: La proliferazione dei colangiociti in corso di danno cronico del fegato
è ritenuta un evento fondamentale nel determinare la progressione delle colangiopatie.
Tuttavia, i meccanismi molecolari responsabili della proliferazione dei colangiociti non sono
ancora completamente definiti. I colangiociti reattivi esprimono il Pancreatic Duodenal
Homeobox protein 1 (PDX-1). Nel pancreas, l’attivazione di PDX-1 guida la risposta
proliferativa al danno delle cellule duttali. Gli effetti di PDX-1 sono contrastati da Hairy and
enhancer of split 1 (Hes-1). L’obiettivo di questo studio è di investigare gli effetti
dell’interazione tra PDX-1 e Hes-1 sulla proliferazione dei colangiociti in risposta al danno.
Metodi: in vitro, la proliferazione cellulare è stata studiata in cellule sottoposte a knockdown
per PDX-1 o in cellule controllo. In vivo, topi eterozigoti per PDX-1 (+/-) o topi di controllo
sono stati sottoposti a dieta con DDC o a legatura del dotto coledoco (BDL). Gli effetti
dell’interazione tra PDX-1 e Hes-1 sono stati studiati, sia in vitro che in vivo, tramite
trattamento con All-trans retinoic acid (At-RA), una molecola capace di indurre l’espressione
di Hes-1. Risultati: In vitro, la proliferazione cellulare è ridotta in colangiociti con
knockdown per PDX-1. In vivo, la proliferazione dei colangiociti e la deposizione di
collagene stimolate dalla dieta con DDC o dalla BDL sono ridotti in topi PDX-1+/-.
L’espressione di Hes-1 è ridotta nei colangiociti proliferanti. At-RA induce un incremento
dose-dipendente dell’espressione Hes-1 e una diminuzione di PDX-1. At-RA neutralizza gli
incrementi dell’espressione di PDX-1 e della proliferazione cellulare, sia in vitro che in vivo.
Nei colangiociti isolati da fegato di pazienti affetti da PSC, l’espressione di PDX-1 è
aumentata e quella di Hes-1 è diminuita. Conclusioni: Hes-1 riduce l’espressione di PDX-1
nei colangiociti. La repressione di Hes-1 permette a PDX-1 di stimolare la proliferazione dei
colangiociti in corso di danno epatico cronico
Reply to "Time to standardize preoperative EUS for lymph node staging in resectable extrahepatic cholangiocarcinoma"
No full text
Gastrointestinal disorders as immune-related adverse events
No full textImmune checkpoint inhibitors, such as cytotoxic T-lymphocyte antigen 4 inhibitors, programmed cell death 1 inhibitors and programmed cell death-ligand 1 inhibitors, have recently emerged as novel drugs in the anti-cancer therapy. Their use in different types of advanced cancer has shown good results and an increase in survival rates. However, immune-related adverse events (irAEs) are frequent and often require special care. IrAEs may affect all the organs, but they are most commonly seen in skin, lungs, endocrine glands and in the gastrointestinal tract where small bowel, colon, the liver and/or the pancreas can be involved. Despite being usually mild and self-resolving, irAEs may present in severe and life-threatening forms, causing the withdrawal of anti-cancer therapy. IrAEs, therefore, represent a challenging condition to manage that often requires the cooperation between the oncologists and the gastroenterologists in order to identify and treat them adequately
Role of cholangiocytes in primary biliary cirrhosis
No full textPrimary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by selective destruction of intrahepatic cholangiocytes. Mechanisms underlying the development and progression of the disease are still controversial and largely undefined. Evidence suggests that PBC results from an articulated immunologic response against an immunodominant mitochondrial autoantigen, the E2 component of the pyruvate dehydrogenase complex (PDC-E2); characteristics of the disease are also the presence of disease-specific antimitochondrial autoantibodies (AMAs) and autoreactive CD4 and CD8 T cells. Recent evidence suggests that cholangiocytes show specific immunobiological features that are responsible for the selective targeting of those cells by the immune system. The immune reaction in PBC selectively targets small sized, intrahepatic bile ducts; although a specific reason for that has not been defined yet, it has been established that the biliary epithelium displays a unique heterogeneity, for which the physiological and pathophysiological features of small and large cholangiocytes significantly differ. In this review article, the authors provide a critical overview of the current evidence on the role of cholangiocytes in the immune-mediated destruction of the biliary tree that characterizes PBC
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
Gut-Liver Axis and Inflammasome Activation in Cholangiocyte Pathophysiology
No full textThe Nlrp3 inflammasome is a multiprotein complex activated by a number of bacterial products or danger signals and is involved in the regulation of inflammatory processes through caspase-1 activation. The Nlrp3 is expressed in immune cells but also in hepatocytes and cholangiocytes, where it appears to be involved in regulation of biliary damage, epithelial barrier integrity and development of fibrosis. Activation of the pathways of innate immunity is crucial in the pathophysiology of hepatobiliary diseases, given the strong link between the gut and the liver. The liver secretes bile acids, which influence the bacterial composition of the gut microbiota and, in turn, are heavily modified by microbial metabolism. Alterations of this balance, as for the development of dysbiosis, may deeply influence the composition of the bacterial products that reach the liver and are able to activate a number of intracellular pathways. This alteration may be particularly important in the pathogenesis of cholangiopathies and, in particular, of primary sclerosing cholangitis, given its strong association with inflammatory bowel disease. In the present review, we summarize current knowledge on the gut-liver axis in cholangiopathies and discuss the role of Nlrp3 inflammasome activation in cholestatic conditions
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