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Liver X Receptor

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https://www.readbyqxmd.com/read/28714273/%C3%AE-catenin-regulation-of-farnesoid-x-receptor-signaling-and-bile-acid-metabolism-during-murine-cholestasis
#1
Michael D Thompson, Akshata Moghe, Pamela Cornuet, Rebecca Marino, Jianmin Tian, Pengcheng Wang, Xiaochao Ma, Marc Abrams, Joseph Locker, Satdarshan P S Monga, Kari Nejak-Bowen
Cholestatic liver diseases result from impaired bile flow and are characterized by inflammation, atypical ductular proliferation (ADP), and fibrosis. The Wnt/β-catenin pathway plays a role in bile duct development, yet its role in cholestatic injury remains indeterminate. Liver-specific β-catenin knockout (KO) mice and wild-type (WT) littermates were subjected to cholestatic injury via bile duct ligation or short-term exposure to 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet. Intriguingly, KO exhibit a dramatic protection from liver injury, fibrosis, and ADP, which coincided with significantly decreased total hepatic bile acids (BA)...
July 17, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28711154/western-diet-induced-dysbiosis-in-farnesoid-x-receptor-knockout-mice-causes-persistent-hepatic-inflammation-after-antibiotic-treatment
#2
Prasant K Jena, Lili Sheng, Hui-Xin Liu, Karen M Kalanetra, Annie Mirsoian, William J Murphy, Samuel W French, Viswanathan V Krishnan, David A Mills, Yu-Jui Yvonne Wan
Patients who have liver cirrhosis and liver cancer also have reduced farnesoid X receptor (FXR). The current study analyzes the effect of diet through microbiota that affect hepatic inflammation in FXR knockout (KO) mice. Wild-type and FXR KO mice were on a control (CD) or Western diet (WD) for 10 months. In addition, both CD- and WD-fed FXR KO male mice, which had hepatic lymphocyte and neutrophil infiltration, were treated by vancomycin, polymyxin B, and Abx (ampicillin, neomycin, metronidazole, and vancomycin)...
July 11, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28709961/bile-acids-fgf15-19-and-liver-regeneration-from-mechanisms-to-clinical-applications
#3
REVIEW
Gloria Alvarez-Sola, Iker Uriarte, Maria U Latasa, Maddalen Jimenez, Marina Barcena-Varela, Eva Santamaría, Raquel Urtasun, Carlos Rodriguez-Ortigosa, Jesús Prieto, Pedro Berraondo, Maite G Fernandez-Barrena, Carmen Berasain, Matías A Avila
The liver has an extraordinary regenerative capacity rapidly triggered upon injury or resection. This response is intrinsically adjusted in its initiation and termination, a property termed the "hepatostat". Several molecules have been involved in liver regeneration, and among them bile acids may play a central role. Intrahepatic levels of bile acids rapidly increase after resection. Through the activation of farnesoid X receptor (FXR), bile acids regulate their hepatic metabolism and also promote hepatocellular proliferation...
July 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28705489/the-effects-of-estradiol-valerate-and-remifemin-on-liver-lipid-metabolism
#4
Biao Jin, Wenjuan Wang, Wenpei Bai, Jing Zhang, Ke Wang, Lihua Qin
To investigate the lipid metabolism dysregulation in the liver of ovariectomized (OVX) rats and effects of estradiol valerate (E) and remifemin (ICR) thereon, forty female Sprague-Dawley rats were randomly divided into sham-operated (SHAM), OVX, OVX+E, and OVX+ICR group. After 4 weeks' E or ICR treatment, serum estrogen, cholesterol, and triglyceride levels; lipid droplets in hepatocytes; hepatocyte morphology; and the expression of estrogen receptor α (ERα), liver X receptor (LXR), and sterol regulatory element binding proteins (SREBPs) in the liver of the rats were assessed...
July 11, 2017: Acta Histochemica
https://www.readbyqxmd.com/read/28704236/liver-x-receptors-agonist-t0901317-downregulates-matrix-metalloproteinase-9-expression-in-non-small-cell-lung-cancer-by-repressing-nuclear-factor-%C3%AE%C2%BAb
#5
Qiong-Ju Chen, Ying Shi, Jun-Feng Shi, Zhen-Hua Yuan, Ji-Yong Ma, Su-Rong Fang, Wei Gu
The liver X receptors (LXRs) is an important component of the nuclear receptor (NR) superfamily. Previous studies have shown that the LXRs possessed antitumor activity in various types of tumor cells. However, the complicated mechanisms underlying the antitumor activity remain largely unexplored. In this study, we incubated A549 cells with the compound T0901317, a specific LXRs agonist, for 24 h. The MTT assay was used to assess cell viability. Transwell assays were used to evaluate cell migration and invasion...
July 12, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28702667/microengineered-cultures-containing-human-hepatic-stellate-cells-and-hepatocytes-for-drug-development
#6
Matthew D Davidson, David A Kukla, Salman R Khetani
In non-alcoholic steatohepatitis (NASH), hepatic stellate cells (HSC) differentiate into myofibroblast-like cells that cause fibrosis, which predisposes patients to cirrhosis and hepatocellular carcinoma. Thus, modeling interactions between activated HSCs and hepatocytes in vitro can aid in the development of anti-NASH/fibrosis therapeutics and lead to a better understanding of disease progression. Species-specific differences in drug metabolism and disease pathways now necessitate the supplementation of animal studies with data acquired using human liver models; however, current models do not adequately model the negative effects of primary human activated HSCs on the phenotype of otherwise well-differentiated primary human hepatocytes (PHHs) as in vivo...
July 12, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28694068/jkb-122-is-effective-alone-or-in-combination-with-prednisolone-in-con-a-induced-hepatitis
#7
Mei-Chi Hsu, Sheng-Hung Liu, Chiung-Wen Wang, Nai-Yun Hu, Edwin S C Wu, Ying-Chu Shih, Peter J S Chiu
Con A-induced hepatitis in mice is an established model of autoimmune hepatitis (AIH). JKB-122, a toll-like receptor 4 (TLR4) antagonist, was tested for hepatotprotectant activity. Within several hours of Con A challenge (15mg/kg iv), increased production of proinflammatory cytokines with inflammatory infiltrate occurred in the liver. The severity of tissue necrosis and the amount of circulating liver enzymes peak at 24h post Con A challenge. JKB-122 was given 24 and 16h before, then concurrently, and 4 and 8h (× 5 doses) after challenge with Con A...
July 8, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28692048/increased-expression-of-programmed-cell-death-protein-1-on-nk-cells-inhibits-nk-cell-mediated-anti-tumor-function-and-indicates-poor-prognosis-in-digestive-cancers
#8
Y Liu, Y Cheng, Y Xu, Z Wang, X Du, C Li, J Peng, L Gao, X Liang, C Ma
Abnormal expression of activating/inhibitory receptors leads to natural killer (NK) cells dysfunction in tumor. Here we show that programmed cell death protein 1 (PD-1), a well-known immune checkpoint of T cells, is highly expressed on peripheral and tumor-infiltrating NK cells from patients with digestive cancers including esophageal, liver, colorectal, gastric and biliary cancer. The increased PD-1 expression on NK cells indicates poorer survival in esophageal and liver cancers. Blocking PD-1/PD-L1 signaling markedly enhances cytokines production and degranulation and suppresses apoptosis of NK cells in vitro...
July 10, 2017: Oncogene
https://www.readbyqxmd.com/read/28690098/m%C3%A3-llerian-adenosarcoma-of-the-urinary-bladder-clinicopathologic-and-immunohistochemical-features-with-novel-genetic-aberrations
#9
Joseph Sanfrancesco, Sean R Williamson, Jennifer B Kum, Shaobo Zhang, Mingsheng Wang, Antonio Lopez-Beltran, Rodolfo Montironi, Thomas A Gardner, Liang Cheng
BACKGROUND: Müllerian adenosarcoma is a biphasic neoplasm most commonly occurring in the uterus and less frequently of the ovary. It has been rarely described to occur in other sites such as peritoneum and liver. PATIENTS AND METHODS: In this study, we report the clinicopathologic, immunohistochemical and molecular features of a primary Müllerian adenosarcoma of the urinary bladder in a 62-year-old woman. To our knowledge, this is the first report of detailed pathologic characterization of Müllerian adenosarcoma primary to the urinary bladder in the literature...
May 25, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28686707/molecular-characterization-of-occult-hepatitis-b-virus-infection-in-patients-with-end-stage-liver-disease-in-colombia
#10
Julio Cesar Rendon, Fabian Cortes-Mancera, Juan Carlos Restrepo-Gutierrez, Sergio Hoyos, Maria-Cristina Navas
BACKGROUND: Hepatitis B virus (HBV) occult infection (OBI) is a risk factor to be taken into account in transfusion, hemodialysis and organ transplantation. The aim of this study was to identify and characterize at the molecular level OBI cases in patients with end-stage liver disease. METHODS: Sixty-six liver samples were obtained from patients with diagnosis of end-stage liver disease submitted to liver transplantation in Medellin (North West, Colombia). Samples obtained from patients who were negative for the surface antigen of HBV (n = 50) were tested for viral DNA detection by nested PCR for ORFs S, C, and X and confirmed by Southern-Blot...
2017: PloS One
https://www.readbyqxmd.com/read/28676625/liver-x-receptor-gene-expression-is-enhanced-in-children-with-obstructive-sleep-apnea-hyperpnoea-syndrome-and-cyclooxygenase-2-cox-2-is-correlated-with-severity-of-obstructive-sleep-apnea-hypopnea-syndrome-osahs
#11
Xin-Hua Ye, Hong Chen, Qin Yu, Qing-Ling Zhu
BACKGROUND Liver X receptor (LXR) is a nuclear receptor presenting in macrophages; it works indispensably in lipid metabolism control and also negatively regulates the expression of inflammatory genes in macrophages. There are many LXR-related studies in adults with metabolic syndrome but rare reports in obese children with obstructive sleep apnea-hypopnea syndrome (OSAHS). The aim of this study was to investigate the expression of LXR, cholesterol ester transfer protein (CETP), and cyclooxygenase-2 (COX-2) genes in obese children with OSAHS compared with obese children without OSAHS and non-obese children...
July 5, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28674261/preliminary-evaluation-of-three-dimensional-primary-human-hepatocyte-culture-system-for-assay-of-drug-metabolizing-enzyme-inducing-potential
#12
Hiroshi Arakawa, Hiroki Kamioka, Tomoko Jomura, Satoshi Koyama, Yoko Idota, Kentaro Yano, Hajime Kojima, Takuo Ogihara
Drug-induced liver injury (DILI) is a common reason for withdrawal of candidate drugs from clinical trials, or of approved drugs from the market. DILI may be induced not only by intact parental drugs, but also by metabolites or intermediates, and therefore should be evaluated in the enzyme-induced state. Here, we present a protocol for assay of drug-metabolizing enzyme-inducing potential using three-dimensional (3D) primary cultures of human hepatocytes (hepatocyte spheroids). Hepatocyte spheroids could be used up to 21 d after seeding (pre-culture for 7 d and exposure to inducer for up to 14 d), based on preliminary evaluation of basal activities of CYP subtypes and mRNA expression of the corresponding transcription factor and xenobiotic receptors (aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR) and pregnane X receptor (PXR))...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28673011/tribbles-homolog-1-enhances-cholesterol-efflux-from-oxidized-low-density-lipoprotein-loaded-thp-1-macrophages
#13
Yanhua Fu, Yang Zhao, Bin Huang
Macrophage foam cell formation plays a pivotal role in the pathogenesis of atherosclerosis. The protein Tribbles homolog 1 (Trib1), a member of the Tribbles protein family, functions as an adaptor or scaffold protein. Recent studies have indicated its implication in lipoprotein metabolism. In the present study, the role of Trib1 in macrophage foam cell formation was investigated. Oil red O staining was used to analyze intracellular lipid deposition, while the effects of Trib1 overexpression on cholesterol efflux were also examined...
July 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28669591/primary-biliary-cholangitis-old-and-novel-therapy
#14
Annarosa Floreani, Chiara Mangini
Primary biliary cholangitis (PBC), formerly called primary biliary cirrhosis, is a chronic cholestatic liver disease that progresses slowly to end-stage liver disease. The first Food and Drug Administration (FDA)-approved treatment for PBC was ursodeoxycholic acid (UDCA). This treatment slows the progress of the disease, but approximatively 30-40% of patients fail to respond to UDCA. A number of options are under investigation as second line treatment. Obeticholic acid (OCA), a Farnesoid X Receptor agonist, has been approved in May 2017 by FDA for patients non responders or intolerant to UDCA...
June 29, 2017: European Journal of Internal Medicine
https://www.readbyqxmd.com/read/28661453/lxr%C3%AE-regulates-hepatic-chrebp%C3%AE-activity-and-lipogenesis-upon-glucose-but-not-fructose-feeding-in-mice
#15
Qiong Fan, Rikke C Nørgaard, Christian Bindesbøll, Christin Lucas, Knut Tomas Dalen, Eshrat Babaie, Harri M Itkonen, Jason Matthews, Hilde I Nebb, Line M Grønning-Wang
Liver X receptors (LXRα/β) and carbohydrate response element-binding proteins (ChREBPα/β) are key players in the transcriptional control of hepatic de novo lipogenesis. LXRα/β double knockout (LXRα(-/-)/β(-/-)) mice have reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling, ChREBPα activity, and lipogenic gene expression in livers, suggesting important roles for LXRs in linking hepatic glucose utilization to lipid synthesis. However, the role of LXRs in fructose-induced ChREBP activation and lipogenesis is currently unknown...
June 29, 2017: Nutrients
https://www.readbyqxmd.com/read/28660384/increased-hepatic-abca1-transporter-is-associated-with-hypercholesterolemia-in-a-cholestatic-rat-model-and-primary-biliary-cholangitis-patients
#16
Yasuaki Takeyama, Yuko Uehara, Akira Anan, Daisuke Morihara, Keiji Yokoyama, Kazuhide Takata, Takashi Tanaka, Makoto Irie, Kaoru Iwata, Satoshi Shakado, Tetsuro Sohda, Shotaro Sakisaka
Hepatic ATP-binding cassette A1 (ABCA1) transporter is the modulator of intrahepatic cholesterol levels via the efflux of cholesterol into plasma. This study aimed to determine the expression of hepatic ABCA1 levels in a cholestatic rat model and patients with primary biliary cholangitis (PBC). A cholesterol efflux study was conducted with Abca1 knock down using siRNA in WIF9 cells. Cholesterol levels in the ABCA1 siRNA cells in the medium were significantly decreased compared with those in controls (P < 0...
June 28, 2017: Medical Molecular Morphology
https://www.readbyqxmd.com/read/28655204/trak2-a-novel-regulator-of-abca1-expression-cholesterol-efflux-and-hdl-biogenesis
#17
Nicole J Lake, Rachael L Taylor, Hugh Trahair, K N Harikrishnan, Joanne E Curran, Marcio Almeida, Hemant Kulkarni, Nigora Mukhamedova, Anh Hoang, Hann Low, Andrew J Murphy, Matthew P Johnson, Thomas D Dyer, Michael C Mahaney, Harald H H Göring, Eric K Moses, Dmitri Sviridov, John Blangero, Jeremy B M Jowett, Kiymet Bozaoglu
Aims: The recent failures of HDL-raising therapies have underscored our incomplete understanding of HDL biology. Therefore there is an urgent need to comprehensively investigate HDL metabolism to enable the development of effective HDL-centric therapies. To identify novel regulators of HDL metabolism, we performed a joint analysis of human genetic, transcriptomic, and plasma HDL-cholesterol (HDL-C) concentration data and identified a novel association between trafficking protein, kinesin binding 2 (TRAK2) and HDL-C concentration...
June 26, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28655075/-surgical-treatment-of-colorectal-liver-metastases
#18
J M Xu, D X Zhu, L Ren
Surgical resection of the metastases offers the only opportunity for long-term survival in colorectal liver metastases. However, only 10% to 20% of patients present with resectable disease, and so how to increase surgical patients has been a clinical hotspot. In addition to expanding surgical indications, two-stage hepatectomy and convertible therapy are optional. In convertible therapy, initial treatment regimen decides long-term benefit, and it is important to select appropriate patient population in addition to Ras status when anti-epithelial growth factor receptor monoclonal antibody is used...
July 1, 2017: Zhonghua Wai Ke za Zhi [Chinese Journal of Surgery]
https://www.readbyqxmd.com/read/28646516/tofacitinib-restores-the-inhibition-of-reverse-cholesterol-transport-induced-by-inflammation-understanding-the-lipid-paradox-associated-with-rheumatoid-arthritis
#19
S Pérez-Baos, J I Barrasa, P Gratal, A Larrañaga-Vera, I Prieto-Potin, G Herrero-Beaumont, R Largo
BACKGROUND AND PURPOSE: Patients with active rheumatoid arthritis (RA) have increased cardiovascular mortality, paradoxically associated with reduced circulating lipid levels. The Janus kinase (Jak) inhibitor tofacitinib ameliorates systemic and joint inflammation in RA with a concomitant increase in serum lipids. We analyzed the effect of tofacitinib on the lipid profile of hyperlipidemic rabbits with chronic arthritis (CA) and on the regulation of reverse cholesterol transport (RCT) during chronic inflammation...
June 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28637104/-treatment-options-in-non-alcoholic-fatty-liver-disease
#20
REVIEW
Won Kim
The prevalence of non-alcoholic fatty liver disease (NAFLD) has sharply increased over the past several decades in Korea. In most cases of NAFLD, metabolic stress and cellular apoptosis are often driven by metabolic abnormality, eventually leading to inflammation and fibrosis . Along with a dramatic surge in the obesity epidemic, 10-20% of NAFLD patients ultimately progress to non-alcoholic steatohepatitis (NASH), a precursor to cirrhosis and hepatocellular carcinoma, as well as multi-organ systemic diseases...
June 25, 2017: Korean Journal of Gastroenterology, Taehan Sohwagi Hakhoe Chi
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