1,720,995 research outputs found
New insights on the role of vascular endothelial growth factor in biliary pathophysiology
Full text linkThe family of vascular endothelial growth factors (VEGFs) includes 5 members (VEGF-A to -D, and placenta growth factor), which regulate several critical biological processes. VEGF-A exerts a variety of biological effects through high-affinity binding to tyrosine kinase receptors (VEGFR-1, -2 and -3), co-receptors and accessory proteins. In addition to its fundamental function in angiogenesis and endothelial cell biology, VEGF/VEGFR signalling also plays a role in other cell types including epithelial cells. This review provides an overview of VEGF signalling in biliary epithelial cell biology in both normal and pathologic conditions. VEGF/VEGFR-2 signalling stimulates bile duct proliferation in an autocrine and paracrine fashion. VEGF/VEGFR-1/VEGFR-2 and angiopoietins are involved at different stages of biliary development. In certain conditions, cholangiocytes maintain the ability to secrete VEGF-A, and to express a functional VEGFR-2 receptor. For example, in polycystic liver disease, VEGF secreted by cystic cells stimulates cyst growth and vascular remodelling through a PKA/RAS/ERK/HIF1α-dependent mechanism, unveiling a new level of complexity in VEFG/VEGFR-2 regulation in epithelial cells. VEGF/VEGFR-2 signalling is also reactivated during the liver repair process. In this context, pro-angiogenic factors mediate the interactions between epithelial, mesenchymal and inflammatory cells. This process takes place during the wound healing response, however, in chronic biliary diseases, it may lead to pathological neo-angiogenesis, a condition strictly linked with fibrosis progression, the development of cirrhosis and related complications, and cholangiocarcinoma. Novel observations indicate that in cholangiocarcinoma, VEGF is a determinant of lymphangiogenesis and of the immune response to the tumour. Better insights into the role of VEGF signalling in biliary pathophysiology might help in the search for effective therapeutic strategies
Notch signalling beyond liver development: emerging concepts in liver repair and oncogenesis.
No full textNotch signalling is an evolutionarily conserved intercellular pathway involved in many aspects of development and tissue renewal in several organs. The importance of Notch signalling in liver development and morphogenesis is well established. However, the post-natal role of Notch in liver repair/regeneration is only now beginning to be unveiled. Despite the simplicity of the pathway activation, a fine spatial-temporal regulation of Notch signalling is required to avoid pathologic effects. This review highlights recent advances in the field indicating that Notch signalling is involved in the reparative morphogenesis of the biliary tree and in liver carcinogenesis. Defective Notch signalling leads to impaired ability of the liver to repair liver damage, while excessive activation may be involved in liver cancer. Even though much remains to be understood about these mechanisms, including the cross-talk between Notch signalling and other liver morphogens, current evidence suggests that the modulation of the Notch pathway may represent a therapeutic target in chronic liver disease
INAPPROPRIATE STORE-OPERATED CYCLIC-AMP PRODUCTION LINKS ALTERED ENDOPLASMIC RETICULUM (ER) CA2 HOMEOSTASIS TO ERK/VEGF SIGNALING IN TRPP2-DEFECTIVE CHOLANGIOCYTES IN A MOUSE MODEL OF POLYCYSTIC LIVER DISEASE
No full textNotch Signalling Beyond Liver Development: Emerging Concepts in Liver Repair and Oncogenesis
No full textACTIVATION OF STORE-OPERATED CAMP SIGNALING IS RESPONSIBLE FOR ERK 1⁄2 PHOSPHORYLATION IN POLYCYSTIN-2/TRPP2 DEFECTIVE CHOLANGIOCYTES
No full textVenti anni di esperienza nell'uso del metodo dell'ombrello di infilaggi come sostegno per lo scavo di gallerie
No full textCholangiocyte Biology and Pathobiology
No full textCholangiocytes are the epithelial cells that line the intrahepatic and extrahepatic biliary tree. The biliary system is a complex network of tubules coated by epithelial cells, or cholangiocytes, which starts from the canals of Hering in the liver lobules, continues outside the liver, and terminates into the ampulla of Vater. The extra- and intrahepatic branches of the biliary tree originate from different embryological areas, explaining their morphological and biological properties. A fundamental function of epithelial cells, including cholangiocytes, is to selectively control the diffusion of ions and molecules through the epithelial barrier. Biliary epithelial cells are usually quiescent, following a liver insult, cholangiocytes activate and/or proliferate as a part of the so-called "hepatic reparative complex". Proliferation of cholangiocytes is fundamental for the maintenance of the normal homeostasis of the biliary tree, and in response to liver damage. A major role in epithelial..
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
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