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Farnesoid x receptor

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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/28091894/mechanisms-of-action-of-surgical-interventions-on-weight-related-diseases-the-potential-role-of-bile-acids
#2
REVIEW
Mohsen Mazidi, Pedro Paulo P de Caravatto, John R Speakman, Ricardo V Cohen
Surgical interventions for weight-related diseases (SWRD) may have substantial and sustainable effect on weight reduction, also leading to a higher remission rate of type 2 diabetes (T2D) mellitus than any other medical treatment or lifestyle intervention. The resolution of T2D after Roux-en-Y gastric bypass (RYGB) typically occurs too quickly to be accounted for by weight loss alone, suggesting that these operations have a direct impact on glucose homeostasis. The mechanisms underlying these beneficial effects however remain unclear...
January 14, 2017: Obesity Surgery
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/28066584/overexpression-of-farnesoid-x-receptor-in-small-airways-contributes-to-epithelial-to-mesenchymal-transition-and-cox-2-expression-in-chronic-obstructive-pulmonary-disease
#4
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
#5
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/28063004/tubulin-alpha-8-is-expressed-in-hepatic-stellate-cells-and-is-induced-in-transformed-hepatocytes
#6
Lisa Rein-Fischboeck, Rebekka Pohl, Elisabeth M Haberl, Sebastian Zimny, Maximilian Neumann, Kristina Eisinger, Thomas S Weiss, Sabrina Krautbauer, Christa Buechler
Tubulin alpha 8 (TUBA8) is highly abundant in murine liver tumors suggesting a role in hepatocellular carcinoma (HCC). Non-alcoholic steatohepatitis (NASH) is a risk factor for HCC. In mice that are fed with a methionine-choline deficient diet for two weeks to induce advanced murine NASH, we do see increased hepatic levels of TUBA8 protein. In animals given a high-fat diet for 14 weeks or an atherogenic diet for 12 weeks, hepatic TUBA8 is unchanged. TUBA8 is highly expressed in human hepatic stellate cells (HSC) and co-localizes with the HSC marker desmin in the murine liver...
January 7, 2017: Molecular and Cellular Biochemistry
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/28045080/transforming-growth-factor-%C3%AE-activated-kinase-1-transcriptionally-suppresses-hepatitis-b-virus-replication
#9
Jinke Pang, Geng Zhang, Yong Lin, Zhanglian Xie, Hongyan Liu, Libo Tang, Mengji Lu, Ran Yan, Haitao Guo, Jian Sun, Jinlin Hou, Xiaoyong Zhang
Hepatitis B Virus (HBV) replication in hepatocytes is restricted by the host innate immune system and related intracellular signaling pathways. Transforming growth factor β-activated kinase 1 (TAK1) is a key mediator of toll-like receptors and pro-inflammatory cytokine signaling pathways. Here, we report that silencing or inhibition of endogenous TAK1 in hepatoma cell lines leads to an upregulation of HBV replication, transcription, and antigen expression. In contrast, overexpression of TAK1 significantly suppresses HBV replication, while an enzymatically inactive form of TAK1 exerts no effect...
January 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28043194/differential-regulation-of-intestinal-efflux-transporters-by-pregnancy-in-mice
#10
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/28041731/analysis-of-bull-bos-taurus-seminal-vesicle-fluid-proteome-in-relation-to-seminal-plasma-proteome
#11
B Westfalewicz, M A Dietrich, A Mostek, A Partyka, W Bielas, W Niżański, A Ciereszko
The existing knowledge on the bull seminal vesicle proteome, a major seminal plasma constituent, and its relationship with seminal plasma is limited. This knowledge is prerequisite for a better understanding of seminal plasma variability, which is linked to semen quality. The objective of this study was to characterize the proteomes of seminal vesicle fluid and seminal plasma and to compare them to better understand the origin of seminal plasma proteins. We collected ejaculates and seminal vesicle fluid postmortem from 6 mature Holstein Friesian bulls...
December 29, 2016: Journal of Dairy Science
https://www.readbyqxmd.com/read/28036031/drug-transporter-expression-and-activity-in-human-hepatoma-huh-7-cells
#12
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/28029021/bile-acid-nuclear-receptor-farnesoid-x-receptor-therapeutic-target-for-nonalcoholic-fatty-liver-disease
#13
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/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/28003721/primary-biliary-cholangitis-disease-pathogenesis-and-implications-for-established-and-novel-therapeutics
#15
REVIEW
Amitkumar Patel, Anil Seetharam
Primary Biliary Cholangitis is a progressive, autoimmune cholestatic liver disorder. Cholestasis with disease progression may lead to dyslipidemia, osteodystrophy and fat-soluble vitamin deficiency. Portal hypertension may develop prior to advanced stages of fibrosis. Untreated disease may lead to cirrhosis, hepatocellular cancer and need for orthotopic liver transplantation. Classically, diagnosis is made with elevation of alkaline phosphatase, demonstration of circulating antimitochondrial antibody, and if performed: asymmetric destruction/nonsupperative cholangitis of intralobular bile ducts on biopsy...
December 2016: Journal of Clinical and Experimental Hepatology
https://www.readbyqxmd.com/read/27993043/mechanisms-of-action-of-compounds-that-enhance-storage-lipid-accumulation-in-daphnia-magna
#16
Rita Jordão, Bruno Campos, Benjamín Piña, Romà Tauler, Amadeu M V M Soares, Carlos Barata
Accumulation of storage lipids in the crustacean Daphnia magna can be altered by a number of exogenous and endogenous compounds, like 20-hydroxyecdysone (natural ligand of the ecdysone receptor, EcR), methyl farnesoate, pyrirproxyfen (agonists of the methyl farnesoate receptor, MfR), and tributyltin (agonist of the retinoid X acid receptor, RXR). This effect, analogous to the obesogenic disruption in mammals, alters Daphnia's growth and reproductive investment. Here we propose that storage lipid accumulation in droplets is regulated in Daphnia by the interaction between the nuclear receptor heterodimer EcR:RXR and MfR...
December 20, 2016: Environmental Science & Technology
https://www.readbyqxmd.com/read/27976737/altered-systemic-bile-acid-homeostasis-contributes-to-liver-disease-in-pediatric-patients-with-intestinal-failure
#17
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
https://www.readbyqxmd.com/read/27956475/induction-of-fxr-signaling-in-germ-free-mice-colonized-with-a-human-microbiota
#18
Annika Wahlström, Petia Kovatcheva-Datchary, Marcus Ståhlman, Muhammad-Tanweer Khan, Fredrik Bäckhed, Hanns-Ulrich Marschall
: The gut microbiota influences the development and progression of metabolic diseases partly by metabolism of bile acids (BAs) and modified signaling through the farnesoid X receptor (FXR). In this study we aimed to determine how the human gut microbiota metabolizes murine BAs and affects FXR signaling in colonized mice. We colonized germ-free (GF) mice with caecal content from a mouse donor or faeces from a human donor and killed the mice after short term (2 weeks) or long term (15 weeks) colonization...
December 12, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27940481/regulation-of-lipid-metabolism-by-obeticholic-acid-in-hyperlipidemic-hamsters
#19
Bin Dong, Mark Young, Xueqing Liu, Amar Bahadur Singh, Jingwen Liu
The farnesoid X receptor (FXR) plays critical roles in plasma cholesterol metabolism, in particular HDL-C homeostasis. Obeticholic acid (OCA) is a FXR agonist being developed for treating various chronic liver diseases. Previous studies reported inconsistent effects of OCA on regulating plasma cholesterol levels in different animal models and in different patient populations. The mechanisms underlying its divergent effects yet have not been thoroughly investigated. The scavenger receptor class B type I (SR-BI) is a FXR modulated gene and the major receptor for HDL-C...
December 9, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27939985/dihydroartemisinin-protects-against-alcoholic-liver-injury-through-alleviating-hepatocyte-steatosis-in-a-farnesoid-x-receptor-dependent-manner
#20
Wenxuan Xu, Chunfeng Lu, Lu Yao, Feng Zhang, Jiangjuan Shao, Shizhong Zheng
Alcoholic liver disease (ALD) is a common etiology of liver diseases, characterized by hepatic steatosis. We previously identified farnesoid X receptor (FXR) as a potential therapeutic target for ALD. Dihydroartemisinin (DHA) has been recently identified to possess potent pharmacological activities on liver diseases. This study was aimed to explore the impact of DHA on ALD and further elaborate the underlying mechanisms. Gain- or loss-of-function analyses of FXR were applied in both in vivo and in vitro studies...
December 6, 2016: Toxicology and Applied Pharmacology
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