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10.1177/1535370217707731 http://scihub22266oqcxt.onion/10.1177/1535370217707731 C5661767!5661767!28467181     free     free     free Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Exp+Biol+Med+(Maywood) 2017 ; 242 (16): 1605-16 Nephropedia Template TP {{tp|p=28467181|t=2017. Pre-clinical and clinical investigations of metabolic zonation in liver diseases: The potential of microphysiology systems |pdf=|usr=}}{{28467181}} gab.com Text Pre-clinical and clinical investigations of metabolic zonation in liver diseases: The potential of microphysiology systems JO: Exp Biol Med (Maywood) http://www.kidney.de/pget.php?&tw=1&pmid=28467181 #FOAvip The establishment of metabolic zonation within a hepatic lobule ascribes specific functions to hepatocytes based on unique, location-dependent gene expression patterns. Recently, there have been significant developments in the field of metabolic liver zonation. A little over a decade ago, the role of ?-catenin signaling was identified as a key regulator of gene expression and function in pericentral hepatocytes. Since then, additional molecules have been identified that regulate the pattern of Wnt/?-catenin signaling within a lobule and determine gene expression and function in other hepatic zones. Currently, the molecular basis of metabolic zonation in the liver appears to be a ?push and pull? between signaling pathways. Such compartmentalization not only provides an efficient assembly line for hepatocyte functions but also can account for restricting the initial hepatic damage and pathology from some hepatotoxic drugs to specific zones, possibly enabling effective regeneration and restitution responses from unaffected cells. Careful analysis and experimentation have also revealed that many pathological conditions in the liver lobule are spatially heterogeneous. We will review current research efforts that have focused on examination of the role and regulation of such mechanisms of hepatocyte adaptation and repair. We will discuss how the pathological organ-specific microenvironment affects cell signaling and metabolic liver zonation, especially in steatosis, viral hepatitis, and hepatocellular carcinoma. We will discuss how the use of new human microphysiological platforms will lead to a better understanding of liver disease progression, diagnosis, and therapies. In conclusion, we aim to provide insights into the role and regulation of metabolic zonation and function using traditional and innovative approaches.Impact statement: Liver zonation of oxygen tension along the liver sinusoids has been identified as a critical liver microenvironment that impacts specific liver functions such as intermediary metabolism of amino acids, lipids, and carbohydrates, detoxification of xenobiotics and as sites for initiation of liver diseases. To date, most information on the role of zonation in liver disease including, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma (HCC) have been obtained from animal models. It is now possible to complement animal studies with human liver, microphysiology systems (MPS) containing induced pluripotent stem cells engineered to create disease models where it is also possible to control the in vitro liver oxygen microenvironment to define the role of zonation on the mechanism(s) of disease progression. The field now has the tools to investigate human liver disease progression, diagnosis, and therapeutic development. Twit Text FOAVip Pre-clinical and clinical investigations of metabolic zonation in liver diseases: The potential of microphysiology systems ????Exp Biol Med (Maywood) http://www.kidney.de/pget.php?&tw=1&pmid=28467181 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28467181 #FOAvip English Wikipedia <ref>{{Cite pmid|28467181}}</ref> Pre-clinical and clinical investigations of metabolic zonation in liver diseases: The potential of microphysiology systems #MMPMID28467181 Soto-Gutierrez A; Gough A; Vernetti LA; Taylor D; Monga SP Exp Biol Med (Maywood) 2017[Oct]; 242 (16): 1605-16 PMID28467181show ga The establishment of metabolic zonation within a hepatic lobule ascribes specific functions to hepatocytes based on unique, location-dependent gene expression patterns. Recently, there have been significant developments in the field of metabolic liver zonation. A little over a decade ago, the role of ?-catenin signaling was identified as a key regulator of gene expression and function in pericentral hepatocytes. Since then, additional molecules have been identified that regulate the pattern of Wnt/?-catenin signaling within a lobule and determine gene expression and function in other hepatic zones. Currently, the molecular basis of metabolic zonation in the liver appears to be a ?push and pull? between signaling pathways. Such compartmentalization not only provides an efficient assembly line for hepatocyte functions but also can account for restricting the initial hepatic damage and pathology from some hepatotoxic drugs to specific zones, possibly enabling effective regeneration and restitution responses from unaffected cells. Careful analysis and experimentation have also revealed that many pathological conditions in the liver lobule are spatially heterogeneous. We will review current research efforts that have focused on examination of the role and regulation of such mechanisms of hepatocyte adaptation and repair. We will discuss how the pathological organ-specific microenvironment affects cell signaling and metabolic liver zonation, especially in steatosis, viral hepatitis, and hepatocellular carcinoma. We will discuss how the use of new human microphysiological platforms will lead to a better understanding of liver disease progression, diagnosis, and therapies. In conclusion, we aim to provide insights into the role and regulation of metabolic zonation and function using traditional and innovative approaches.Impact statement: Liver zonation of oxygen tension along the liver sinusoids has been identified as a critical liver microenvironment that impacts specific liver functions such as intermediary metabolism of amino acids, lipids, and carbohydrates, detoxification of xenobiotics and as sites for initiation of liver diseases. To date, most information on the role of zonation in liver disease including, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma (HCC) have been obtained from animal models. It is now possible to complement animal studies with human liver, microphysiology systems (MPS) containing induced pluripotent stem cells engineered to create disease models where it is also possible to control the in vitro liver oxygen microenvironment to define the role of zonation on the mechanism(s) of disease progression. The field now has the tools to investigate human liver disease progression, diagnosis, and therapeutic development. äPre-clinical and clinical investigations of metabolic zonation in live(epmc).pdf DeepDyve Pubget Overpricing