Suchergebnisse

This research was funded by the Ministerio de Ciencia, Innovacion y Universidades (Project Grant RTI2018-095114-B-I00) Madrid, Spain; European Union (Fondos FEDER, "una manera de hacer Europa"); CERCA Program/Generalitat de Catalunya; the Secretaria d' Universitats I Recerca del Departament d' Economia I Coneixement (Project Grant 2017_SGR_551) Barcelona, Spain, by the COST action Programs CA17103 (DARTER), CA17112 (PRO-EURO-DILI-NET), CA17121 (COMULIS) and CA17126 (TUMIEE), and by the Consejo Nacional de Ciencia y Tecnologia (CONACYT), Fondo Sectorial de Investigacion para la Educacion (Project grant 257743), Mexico. Marc Mico-Carnero is the recipient of a fellowship from FCT (Fundacio Catalana de Trasplantament), Spain. ; Hepatocellular carcinoma has become a leading cause of cancer-associated mortality throughout the world, and is of great concern. Currently used chemotherapeutic drugs in the treatment of hepatocellular carcinoma lead to severe side effects, thus underscoring the need for further research to develop novel and safer therapies. Liver resection in cancer patients is routinely performed. After partial resection, liver regeneration is a perfectly calibrated response apparently sensed by the body's required liver function. This process hinges on the effect of several growth factors, among other molecules. However, dysregulation of growth factor signals also leads to growth signaling autonomy and tumor progression, so control of growth factor expression may prevent tumor progression. This review describes the role of some of the main growth factors whose dysregulation promotes liver tumor progression, and are also key in regenerating the remaining liver following resection. We herein summarize and discuss studies focused on partial hepatectomy and liver carcinogenesis, referring to hepatocyte growth factor, insulin-like growth factor, and epidermal growth factor, as well as their suitability as targets in the treatment of hepatocellular carcinoma. Finally, and given that drugs remain one of the mainstay treatment options in liver carcinogenesis, we have reviewed the current pharmacological approaches approved for clinical use or research targeting these factors. ; Ministerio de Ciencia, Innovacion y Universidades Madrid, Spain RTI2018-095114-B-I00 ; European Union (Fondos FEDER, "una manera de hacer Europa") ; General Electric ; Secretaria d' Universitats I Recerca del Departament d' Economia I Coneixement Barcelona, Spain 2017_SGR_551 ; COST action Programs CA17103 CA17112 CA17121 CA17126 ; Consejo Nacional de Ciencia y Tecnologia (CONACyT) ; Fondo Sectorial de Investigacion para la Educacion, Mexico 257743 ; FCT (Fundacio Catalana de Trasplantament), Spain

This research was supported by the "Ministerio de Ciencia, Innovacion y Universidades (MCIU)" (RTI2018-095114-B-I00) Madrid, Spain, by the European Union (Fondos Feder, "Una manera de hacer Europa"), by "CERCA Program/Generalitat de Catalunya", and by the "Secretaria d'Universitats i Recerca" (2017SGR-551) Barcelona, Spain, and by the COST action Programs CA17103 (DARTER), CA17121 (COMULIS), CA17112 (PROEURO-DILI-NETWORK) and CA17126 (TUMIEE). Marc Mico-Carnero is a recipient of a fellowship from "Fundacio Catalana de trasplantament" (FCT). ; The pro-tumorigenic activity of fibroblast growth factor (FGF) 19 (FGF15 in its rodent orthologue) in hepatocellular carcinoma (HCC), as well as the unsolved problem that ischemia-reperfusion (IR) injury supposes in liver surgeries, are well known. However, it has been shown that FGF15 administration protects against liver damage and regenerative failure in liver transplantation (LT) from brain-dead donors without tumor signals, providing a benefit in avoiding IR injury. The protection provided by FGF15/19 is due to its anti-apoptotic and pro-regenerative properties, which make this molecule a potentially beneficial or harmful factor, depending on the disease. In the present review, we describe the preclinical models currently available to understand the signaling pathways responsible for the apparent controversial effects of FGF15/19 in the liver (to repair a damaged liver or to promote tumorigenesis). As well, we study the potential pharmacological use that has the activation or inhibition of FGF15/19 pathways depending on the disease to be treated. We also discuss whether FGF15/19 non-pro-tumorigenic variants, which have been developed for the treatment of liver diseases, might be promising approaches in the surgery of hepatic resections and LT using healthy livers and livers from extended-criteria donors. ; "Ministerio de Ciencia, Innovacion y Universidades (MCIU)", Madrid, Spain RTI2018-095114-B-I00 ; European Union (Fondos Feder, "Una manera de hacer Europa") ; CERCA Program/Generalitat de Catalunya ; "Secretaria d'Universitats i Recerca", Barcelona, Spain 2017SGR-551 ; European Cooperation in Science and Technology (COST) CA17103 CA17121 CA17112 CA17126 ; "Fundacio Catalana de trasplantament" (FCT)

Ischemia-reperfusion (I/R) injury is an unresolved problem in liver resection and transplantation. The preexisting nutritional status related to the gut microbial profile might contribute to primary non-function after surgery. Clinical studies evaluating artificial nutrition in liver resection are limited. The optimal nutritional regimen to support regeneration has not yet been exactly defined. However, overnutrition and specific diet factors are crucial for the nonalcoholic or nonalcoholic steatohepatitis liver diseases. Gut-derived microbial products and the activation of innate immunity system and inflammatory response, leading to exacerbation of I/R injury or impaired regeneration after resection. This review summarizes the role of starvation, supplemented nutrition diet, nutritional status, and alterations in microbiota on hepatic I/R and regeneration. We discuss the most updated effects of nutritional interventions, their ability to alter microbiota, some of the controversies, and the suitability of these interventions as potential therapeutic strategies in hepatic resection and transplantation, overall highlighting the relevance of considering the extended criteria liver grafts in the translational liver surgery. ; This research was supported by the Ministerio de Ciencia, Innovacion y Universidades (RTI2018-095114-B-I00) Madrid, Spain; European Union (Fondos Feder, "una manera de hacer Europa"); CERCA Program/Generalitat de Catalunya and Secretaria d'Universitats I Recerca del Departament d'Economia I Coneixement (2017 SGR-551) Barcelona, Spain.

Ischemia-reperfusion (I/R) injury is an unresolved problem in liver resection and transplantation. The preexisting nutritional status related to the gut microbial profile might contribute to primary non-function after surgery. Clinical studies evaluating artificial nutrition in liver resection are limited. The optimal nutritional regimen to support regeneration has not yet been exactly defined. However, overnutrition and specific diet factors are crucial for the nonalcoholic or nonalcoholic steatohepatitis liver diseases. Gut-derived microbial products and the activation of innate immunity system and inflammatory response, leading to exacerbation of I/R injury or impaired regeneration after resection. This review summarizes the role of starvation, supplemented nutrition diet, nutritional status, and alterations in microbiota on hepatic I/R and regeneration. We discuss the most updated effects of nutritional interventions, their ability to alter microbiota, some of the controversies, and the suitability of these interventions as potential therapeutic strategies in hepatic resection and transplantation, overall highlighting the relevance of considering the extended criteria liver grafts in the translational liver surgery. ; This research was supported by the Ministerio de Ciencia, Innovacion y Universidades (RTI2018-095114-B-I00) Madrid, Spain; European Union (Fondos Feder, "una manera de hacer Europa"); CERCA Program/Generalitat de Catalunya and Secretaria d'Universitats I Recerca del Departament d'Economia I Coneixement (2017 SGR-551) Barcelona, Spain. ; Yes

We thank Toffa (Language Advisory Service, University of Barcelona, Barcelona, Spain) for revising the English text ; Microbiota is defined as the collection of microorganisms within the gastrointestinal ecosystem. These microbes are strongly implicated in the stimulation of immune responses. An unbalanced microbiota, termed dysbiosis, is related to the development of several liver diseases. The bidirectional relationship between the gut, its microbiota and the liver is referred to as the gut–liver axis. The translocation of bacterial products from the intestine to the liver induces inflammation in different cell types such as Kupffer cells, and a fibrotic response in hepatic stellate cells, resulting in deleterious effects on hepatocytes. Moreover, ischemia-reperfusion injury, a consequence of liver surgery, alters the microbiota profile, affecting inflammation, the immune response and even liver regeneration. Microbiota also seems to play an important role in post-operative outcomes (i.e., liver transplantation or liver resection). Nonetheless, studies to determine changes in the gut microbial populations produced during and after surgery, and affecting liver function and regeneration are scarce. In the present review we analyze and discuss the preclinical and clinical studies reported in the literature focused on the evaluation of alterations in microbiota and its products as well as their effects on post-operative outcomes in hepatic surgery. ; Ministerio de Ciencia, Innovacion y Universidades (MCIU) Madrid, Spain RTI2018-095114-B-I00 ; European Union (Fondos Feder, "Una manera de hacer Europa") ; CERCA Program/Generalitat de Catalunya ; Secretaria d'Universitats i Recerca Barcelona, Spain 2017SGR-551 ; COST action Programs CA17103 CA17126

Julio Plaza-Diaz is part of the "UGR Plan Propio de Investigación 2016" and the "Excellence actions: Unit of Excellence on Exercise and Health (UCEES), University of Granada". Patricio Solis-Urra was supported by a fellowship from the National Agency for Research and Development (ANID) BECAS Chile/72180543. Julio Plaza-Diaz is supported by a fellowship awarded to postdoctoral researchers at foreign universities and research centers from the "Fundación Ramón Areces", Madrid, Spain. Jerónimo Aragón-Vela was funded by a Postdoctoral fellowship from the 'Fundación Alfonso Martín Escudero' (Spain). Francisco Javier Ruiz-Ojeda is supported by a fellowship from Spanish Government "Agencia Estatal de Investigación-Juan de la Cierva-Incorporación" program (IJC2020-042739-I). We are grateful to Belén Vázquez-González for her assistance with the illustration service. ; Physical activity, exercise, or physical fitness are being studied as helpful nonpharmacological therapies to reduce signaling pathways related to inflammation. Studies describing changes in intestinal microbiota have stated that physical activity could increase the microbial variance and enhance the ratio of Firmicutes/Bacteroidetes, and both actions could neutralize the obesity progression and diminish body weight. The aim of this review is to provide an overview of the literature describing the relationship between physical activity profiles and gut microbiota and in obesity and some associated comorbidities. Promoting physical activity could support as a treatment to maintain the gut microbiota composition or to restore the balance toward an improvement of dysbiosis in obesity; however, these mechanisms need to be studied in more detail. The opportunity to control the microbiota by physical activity to improve health results and decrease obesity and related comorbidities is very attractive. Nevertheless, several incompletely answered questions need to be addressed before this strategy can be implemented. ; ANID BECAS Chile/72180543 ; Agencia Estatal de Investigación-Juan de la Cierva-Incorporación ; National Agency for Research and Development ; University of Granada ; Fundación Alfonso Martín Escudero ; Fundación Ramón Areces ; Agencia Estatal de Investigación IJC2020-042739-I