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https://www.readbyqxmd.com/read/28102638/farnesoid-x-receptor-ablation-sensitizes-mice-to-hepatitis-b-virus-x-protein-induced-hepatocarcinogenesis
#1
Yongdong Niu, Meishu Xu, Betty L Slagle, Haihua Huang, Song Li, Grace L Guo, Ganggang Shi, Wenxin Qin, Wen Xie
: Chronic hepatitis B virus infection is a major risk factor for hepatocellular carcinoma (HCC). Hepatitis B virus X protein (HBx) is a hepatitis B virus protein that has multiple cellular functions, but its role in HCC pathogenesis has been controversial. Farnesoid X receptor (FXR) is a nuclear receptor with activities in anti-inflammation and inhibition of hepatocarcinogenesis. However, whether or how FXR can impact hepatitis B virus/HBx-induced hepatocarcinogenesis remains unclear...
November 5, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28096543/therapy-experimental-portal-hypertension-pinning-hopes-on-fxr-agonists
#2
Katrina Ray
No abstract text is available yet for this article.
January 18, 2017: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28086800/relevance-of-fxr-p62-sqstm1-pathway-for-survival-and-protection-of-mouse-hepatocytes-and-liver-especially-with-steatosis
#3
Sanae Haga, Yimin, Michitaka Ozaki
BACKGROUND: Liver injury and regeneration involve complicated processes and are affected by various physio-pathological conditions. Surgically, severe liver injury after surgical resection often leads to fatal liver failure, especially with some underlying pathological conditions such as steatosis. Therefore, protection from the injury of hepatocytes and liver is a serious concern in various clinical settings. METHODS: We studied the effects of the farnesoid X receptor (FXR) on cell survival and steatosis in mouse hepatocytes (AML12 mouse liver cells) and investigated their molecular mechanisms...
January 13, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28077388/the-na-taurocholate-cotransporting-polypeptide-ntcp-slc10a1-ortholog-in-the-marine-skate-leucoraja-erinacea-is-not-a-physiological-bile-salt-transporter
#4
Dongke Yu, Han Zhang, Daniel A Lionarons, James L Boyer, Shi-Ying Cai
The Na(+)-dependent taurocholate co-transporting polypeptide (NTCP/SLC10A1) is a hepatocyte specific solute carrier, which plays an important role in maintaining bile salt homeostasis in mammals. The absence of an hepatic Na(+)-dependent bile salt transport system in marine skate and rainbow trout raises a question regarding the function of the Slc10a1 gene in these species. Here we have characterized the Slc10a1 gene in the marine skate, Leucoraja erinacea. The transcript of skate Slc10a1 (skSlc10a1) encodes 319 amino acids and shares 46% identity to human NTCP (hNTCP) with similar topology to mammalian NTCP...
January 11, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28066584/overexpression-of-farnesoid-x-receptor-in-small-airways-contributes-to-epithelial-to-mesenchymal-transition-and-cox-2-expression-in-chronic-obstructive-pulmonary-disease
#5
Bi Chen, Wen-Jie You, Shan Xue, Hui Qin, Xu-Ji Zhao, Miao Zhang, Xue-Qing Liu, Shu-Yang Zhu, Han-Dong Jiang
BACKGROUND: Epithelial-mesenchymal transition (EMT) and cyclooxygenase-2 (COX-2) contribute to airway remodelling and inflammation in chronic obstructive pulmonary disease (COPD). Recent data suggest that the farnesoid X receptor (FXR), a nuclear receptor traditionally considered as bile acid-activated receptor, is also expressed in non-classical bile acids target tissues with novel functions beyond regulating bile acid homeostasis. This study aimed to investigate the potential role of FXR in the development of COPD, as well as factors that affect FXR expression...
November 2016: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28065787/intestinal-farnesoid-x-receptor-controls-transintestinal-cholesterol-excretion-in-mice
#6
Jan Freark de Boer, Marleen Schonewille, Marije Boesjes, Henk Wolters, Vincent W Bloks, Trijnie Bos, Theo H van Dijk, Angelika Jurdzinski, Renze Boverhof, Justina C Wolters, Jan A Kuivenhoven, Jan M van Deursen, Ronald P J Oude Elferink, Antonio Moschetta, Claus Kremoser, Henkjan J Verkade, Folkert Kuipers, Albert K Groen
BACKGROUND & AIMS: The role of the intestine in the maintenance of cholesterol homeostasis is increasingly recognized. Fecal excretion of cholesterol is the last step in the atheroprotective reverse cholesterol transport pathway, to which biliary and transintestinal cholesterol excretion (TICE) contribute. The mechanisms controlling the flux of cholesterol through the TICE pathway are, however, poorly understood. We aimed to identify mechanisms that regulate and stimulate TICE. METHODS: We performed studies with C57Bl/6J mice, as well as mice with intestine-specific knockout of the farnesoid X receptor (FXR), mice that express an FXR transgene specifically in the intestine, and ABCG8-knockout mice...
January 5, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28060943/farnesoid-x-receptor-activation-attenuates-intestinal-ischemia-reperfusion-injury-in-rats
#7
Laurens J Ceulemans, Len Verbeke, Jean-Paul Decuypere, Ricard Farré, Gert De Hertogh, Kaatje Lenaerts, Ina Jochmans, Diethard Monbaliu, Frederik Nevens, Jan Tack, Wim Laleman, Jacques Pirenne
INTRODUCTION: The farnesoid X receptor (FXR) is abundantly expressed in the ileum, where it exerts an enteroprotective role as a key regulator of intestinal innate immunity and homeostasis, as shown in pre-clinical models of inflammatory bowel disease. Since intestinal ischemia reperfusion injury (IRI) is characterized by hyperpermeability, bacterial translocation and inflammation, we aimed to investigate, for the first time, if the FXR-agonist obeticholic acid (OCA) could attenuate intestinal ischemia reperfusion injury...
2017: PloS One
https://www.readbyqxmd.com/read/28051334/glutamine-attenuates-obstructive-cholestasis-in-rats-via-farnesoid-x-receptor-mediated-regulation-of-bsep-and-mrp2
#8
Bingli Liu, Yiming Li, Hong Ji, Hongwei Lu, Hua Li, Yakun Shi
To investigate the protective effect of glutamine (Gln) against obstructive cholestasis in association with farnesoid X receptor (FXR) activation, an obstructive cholestasis model was established in male Sprague-Dawley rats by bile duct ligation (BDL). Serum biomarkers and hematoxylin plus eosin staining were used to identify the degree of hepatic injury in the rats with obstructive cholestasis after Gln treatment. Immunohistochemistry, real-time PCR, Western blot, cultured primary rat hepatocytes with FXR knockdown, and dual-luciferase reporter assay were performed to elucidate the mechanisms underlying Gln hepatoprotection...
October 5, 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28043194/differential-regulation-of-intestinal-efflux-transporters-by-pregnancy-in-mice
#9
Jamie E Moscovitz, Gabriel Yarmush, Guadalupe Herrera-Garcia, Grace L Guo, Lauren M Aleksunes
1. In the intestines, the nuclear receptors farnesoid X receptor (Fxr) and pregnane X receptor (Pxr) regulate the transcription of metabolizing enzymes and transporters that dictate the absorption of nutrients and xenobiotics. 2. Here, we sought to determine whether Fxr and Pxr signaling pathways are disrupted in response to high-circulating concentrations of steroid hormones late in pregnancy leading to altered transporter expression. To test this, ileum were collected from virgin and pregnant C57BL/6 mice on gestation days 14, 17 and 19...
January 3, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28036031/drug-transporter-expression-and-activity-in-human-hepatoma-huh-7-cells
#10
Elodie Jouan, Marc Le Vée, Claire Denizot, Yannick Parmentier, Olivier Fardel
Human hepatoma cells may represent a valuable alternative to the use of human hepatocytes for studying hepatic drug transporters, which is now a regulatory issue during drug development. In the present work, we have characterized hepatic drug transporter expression, activity and regulation in human hepatoma HuH-7 cells, in order to determine the potential relevance of these cells for drug transport assays. HuH-7 cells displayed notable multidrug resistance-associated protein (MRP) activity, presumed to reflect expression of various hepatic MRPs, including MRP2...
December 28, 2016: Pharmaceutics
https://www.readbyqxmd.com/read/28029505/parenteral-nutrition-dysregulates-bile-salt-homeostasis-in-a-rat-model-of-parenteral-nutrition-associated-liver-disease
#11
Kiran V K Koelfat, Frank G Schaap, Caroline M J M Hodin, Ruben G J Visschers, Björn I Svavarsson, Martin Lenicek, Ronit Shiri-Sverdlov, Kaatje Lenaerts, Steven W M Olde Damink
BACKGROUND & AIMS: Parenteral nutrition (PN), a lifesaving therapy in patients with intestinal failure, has been associated with hepatobiliary complications including steatosis, cholestasis and fibrosis, collectively known as parenteral nutrition-associated liver disease (PNALD). To date, the pathogenesis of PNALD is poorly understood and therapeutic options are limited. Impaired bile salt homeostasis has been proposed to contribute PNALD. The objective of this study was to establish a PNALD model in rats and to evaluate the effects of continuous parenteral nutrition (PN) on bile salt homeostasis...
September 24, 2016: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28029021/bile-acid-nuclear-receptor-farnesoid-x-receptor-therapeutic-target-for-nonalcoholic-fatty-liver-disease
#12
REVIEW
Sun Gi Kim, Byung Kwon Kim, Kyumin Kim, Sungsoon Fang
Nonalcoholic fatty liver disease (NAFLD) is one of the causes of fatty liver, occurring when fat is accumulated in the liver without alcohol consumption. NAFLD is the most common liver disorder in advanced countries. NAFLD is a spectrum of pathology involving hepatic steatosis with/without inflammation and nonalcoholic steatohepatitis with accumulation of hepatocyte damage and hepatic fibrosis. Recent studies have revealed that NAFLD results in the progression of cryptogenic cirrhosis that leads to hepatocarcinoma and cardiovascular diseases such as heart failure...
December 2016: Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28028560/pathophysiology-prevention-treatment-and-outcomes-of-intestinal-failure-associated-liver-disease
#13
REVIEW
Noora H Al-Shahwani, David L Sigalet
BACKGROUND: Intestinal failure-associated liver disease (IFALD) remains a serious problem in the treatment of infants with nutritional problems and short bowel syndrome. METHODS: A review of the recent literature from 2010 to 2016, concentrating on articles related to the pathophysiology of IFALD and to outcomes of novel nutritional and pharmacological therapies for neonatal cholestasis in the post-surgical neonate. RESULTS: The pathophysiology of IFALD relates to an increase sensitivity of the neonatal liver to cholestasis in the non-fed state; prolonged cholestasis almost inevitably results in liver damage which will progress from fibrosis to cirrhosis...
December 27, 2016: Pediatric Surgery International
https://www.readbyqxmd.com/read/28008998/impaired-hepatic-adaptation-to-chronic-cholestasis-induced-by-primary-sclerosing-cholangitis
#14
Malgorzata Milkiewicz, Marta Klak, Agnieszka Kempinska-Podhorodecka, Anna Wiechowska-Kozlowska, Elzbieta Urasinska, Malgorzata Blatkiewicz, Ewa Wunsch, Elwyn Elias, Piotr Milkiewicz
Pathogenesis of primary sclerosing cholangitis (PSC) may involve impaired bile acid (BA) homeostasis. We analyzed expressions of factors mediating enterohepatic circulation of BA using ileal and colonic (ascending and sigmoid) biopsies obtained from patients with PSC with and without ulcerative colitis (UC) and explanted PSC livers. Two-fold increase of BA-activated farnesoid X receptor (FXR) protein levels were seen in ascending and sigmoid colon of PSC patients with correspondingly decreased apical sodium-dependent BA transporter (ASBT) gene expression...
December 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/28006925/bile-acids-nuclear-receptors-and-cytochrome-p450
#15
J Juřica, G Dovrtělová, K Nosková, O Zendulka
This review summarizes the importance of bile acids (BA) as important regulators of various homeostatic mechanisms with detailed focus on cytochrome P450 (CYP) enzymes. In the first part, synthesis, metabolism and circulation of BA is summarized and BA are reviewed as physiological ligands of nuclear receptors which regulate transcription of genes involved in their metabolism, transport and excretion. Notably, PXR, FXR and VDR are the most important nuclear receptors through which BA regulate transcription of CYP genes involved in the metabolism of both BA and xenobiotics...
December 21, 2016: Physiological Research
https://www.readbyqxmd.com/read/27997980/new-therapeutic-concepts-in-bile-acid-transport-and-signaling-for-management-of-cholestasis
#16
REVIEW
Michael Trauner, Claudia Daniela Fuchs, Emina Halilbasic, Gustav Paumgartner
The identification of the key regulators of bile acid synthesis and transport within the enterohepatic circulation has unravelled potential targets for pharmacological therapies of cholestatic liver diseases. Novel drug targets include the bile acid receptors FXR and TGR5, the bile acid-induced gut hormones FGF19 and GLP-1, and the bile acid transport systems ASBT and NTCP within the enterohepatic circulation. Moreover, bile acid derivatives undergoing cholehepatic shunting may allow improved targeting to the bile ducts...
December 20, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27993716/the-fxr-agonist-px20606-ameliorates-portal-hypertension-by-targeting-vascular-remodelling-and-sinusoidal-dysfunction
#17
Philipp Schwabl, Eva Hambruch, Berit A Seeland, Hubert Hayden, Michael Wagner, Lukas Garnys, Bastian Strobel, Tim-Lukas Schubert, Florian Riedl, Dieter Mittereger, Michael Burnet, Patrick Starlinger, Georg Oberhuber, Ulrich Deuschle, Nataliya Rohr-Udilova, Bruno K Podesser, Markus Peck-Radosavljevic, Thomas Reiberger, Claus Kremoser, Michael Trauner
BACKGROUND & AIMS: Steroidal FXR agonists demonstrated potent anti-fibrotic activities and lowered portal hypertension in experimental models. The impact of the novel non-steroidal and selective FXR agonist PX20606 on portal hypertension and fibrosis was explored in this study. METHODS: In experimental models of non-cirrhotic (partial portal vein ligation, PPVL, 7 days) and cirrhotic (carbon-tetrachloride, CCl4, 14 weeks) portal hypertension, PX20606 (PX,10mg/kg) or the steroidal FXR agonist obeticholic acid (OCA,10mg/kg) were gavaged...
December 16, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27988401/geniposide-attenuates-anit-induced-cholestasis-through-regulation-of-transporters-and-enzymes-involved-in-bile-acids-homeostasis-in-rats
#18
Lingling Wang, Guixin Wu, Feihua Wu, Nan Jiang, Yining Lin
ETHNOPHARMACOLOGICAL RELEVANCE: Geniposide (GE) is one of the major iridoid glycosides isolated from the fruit of Gardenia jasminoides Ellis that has been used to treat hepatic disorders including cholestasis. However, the underlying mechanisms for GE ameliorating the reduction in bile acids accumulation by α-naphthylisothiocyanate (ANIT) remain unclear. AIM OF THE STUDY: The purpose of this study is to characterize the efficacy of GE in regulation of bile acids uptake, synthesis, metabolism, and transport in ANIT-induced rats...
January 20, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27981592/the-ascending-pathophysiology-of-cholestatic-liver-disease
#19
REVIEW
Peter L M Jansen, Ahmed Ghallab, Nachiket Vartak, Raymond Reif, Frank G Schaap, Jochen Hampe, Jan G Hengstler
In this review we develop the argument that cholestatic liver diseases, particularly PBC and PSC, evolve over time with anatomically an ascending course of the disease process. The first and early lesions are in 'downstream' bile ducts. This eventually leads to cholestasis and this causes bile salt-mediated toxic injury of the 'upstream' liver parenchyma. Bile salts are toxic in high concentration. These concentrations are present in the canalicular network, bile ducts and gallbladder. Leakage of bile from this network and ducts could be an important driver of toxicity...
December 16, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27976737/altered-systemic-bile-acid-homeostasis-contributes-to-liver-disease-in-pediatric-patients-with-intestinal-failure
#20
Yong-Tao Xiao, Yi Cao, Ke-Jun Zhou, Li-Na Lu, Wei Cai
Intestinal failure (IF)-associated liver disease (IFALD), as a major complication, contributes to significant morbidity in pediatric IF patients. However, the pathogenesis of IFALD is still uncertain. We here investigate the roles of bile acid (BA) dysmetabolism in the unclear pathogenesis of IFALD. It found that the histological evidence of pediatric IF patients exhibited liver injury, which was characterized by liver bile duct proliferation, inflammatory infiltration, hepatocyte apoptosis and different stages of fibrosis...
December 15, 2016: Scientific Reports
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