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https://www.readbyqxmd.com/read/28223834/bile-salt-receptor-tgr5-is-highly-expressed-in-esophageal-adenocarcinoma-and-precancerous-lesions-with-significantly-worse-overall-survival-and-gender-differences
#1
Chunhong Pang, Amy LaLonde, Tony E Godfrey, Jianwen Que, Jun Sun, Tong Tong Wu, Zhongren Zhou
Bile acid reflux in the esophagus plays an important role in the carcinogenesis of esophageal adenocarcinoma (EAC). The G-protein coupled bile acid receptor (TGR5) has been associated with the development of gastrointestinal cancer. However, little is known regarding the role of TGR5 in esophageal carcinoma and precancerous lesions. We analyzed genomic DNA from 116 EACs for copy number aberrations via Affymetrix SNP6.0 microarrays. The TGR5 gene locus was amplified in 12.7% (14/116) of the EACs. The TGR5 protein expression was also assessed using immunohistochemistry from tissue microarrays, including Barrett's esophagus (BE), low-(LGD) and high-grade dysplasia (HGD), columnar cell metaplasia (CM), squamous epithelium (SE), EAC and squamous cell carcinoma...
2017: Clinical and Experimental Gastroenterology
https://www.readbyqxmd.com/read/28223719/hepatitis-c-virus-associated-pruritus-etiopathogenesis-and-therapeutic-strategies
#2
EDITORIAL
Youssef Alhmada, Denis Selimovic, Fadi Murad, Sarah-Lilly Hassan, Youssef Haikel, Mossaad Megahed, Matthias Hannig, Mohamed Hassan
In addition to its contributing role in the development of chronic liver diseases, chronic hepatitis C virus (HCV) infection is associated with extrahepatic manifestations, particularly, cutaneous-based disorders including those with pruritus as a symptom. Pruritus is frequently associated with the development of chronic liver diseases such as cholestasis and chronic viral infection, and the accumulation of bile acids in patients' sera and tissues as a consequence of liver damage is considered the main cause of pruritus...
February 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28222247/bile-acids-and-cardiovascular-function-in-cirrhosis
#3
Andrei Voiosu, Signe Wiese, Theodor Voiosu, Flemming Bendtsen, Søren Møller
Cirrhotic cardiomyopathy and the hyperdynamic syndrome are clinically important complications of cirrhosis but their exact pathogenesis is still partly unknown. Experimental models have proven the cardiotoxic effects of bile acidsand recent studies of their varied receptor-mediated functions offer new insight into their involvement in cardiovascular dysfunction in cirrhosis. Bile acid receptors such as farnesoid X-activated receptor and TGR5 are currently under investigation as potential therapeutic targets in a variety of pathological conditions...
February 21, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28219198/-effects-and-mechanisms-of-ursodeoxycholic-acid-on-isoprenaline-induced-myocardial-fibrosis-in-mice
#4
X Li, K Q Han, Y N Shi, S Z Men, S Li, M H Sun, H Dong, J J Lu, L J Ma, M Zhao, D Li, W Liu
Objective: To investigate the effects and possible mechanisms of ursodeoxycholic acid (UDCA) on myocardial fibrosis in mice. Method: To observe the expression of transforming growth factor(TGF) -β1, CTGF, MMPs and the degree of myocardial fibrosis, 61 male Kunming mice were randomly divided into normal group, low dose UDCA group, high dose of UDCA group, spironolactone group, and the control group.Isoproterenol (ISO) injection was given subcutaneously (30 d) to make the model of myocardial fibrosis.Corresponding anti-fibrosis drugs (UDCA or spironolactone) were given by gavage...
February 7, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28214524/bile-acid-control-of-metabolism-and-inflammation-in-obesity-type-2-diabetes-dyslipidemia-and-nafld
#5
Oscar Chávez-Talavera, Anne Tailleux, Philippe Lefebvre, Bart Staels
Bile acids are signaling molecules, which coordinately regulate metabolism and inflammation via the nuclear farnesoid X receptor (FXR) and the Takeda G protein-coupled receptor 5 (TGR5). These receptors activate transcriptional networks and signaling cascades controlling the expression and activity of genes involved in bile acid, lipid and carbohydrate metabolism, energy expenditure, and inflammation by acting predominantly in entero-hepatic tissues, but also in peripheral organs. In this review, we discuss the most recent findings on the inter-organ signaling and interplay with the gut microbiota of bile acids and their receptors in meta-inflammation, with a focus on their pathophysiological roles in obesity, type 2 diabetes, dyslipidemia and non-alcoholic steatohepatitis and their potential therapeutic applications...
February 15, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28212604/high-expression-of-claudin-2-in-esophageal-carcinoma-and-precancerous-lesions-is-significantly-associated-with-the-bile-salt-receptors-vdr-and-tgr5
#6
Sohaib Abu-Farsakh, Tongtong Wu, Amy Lalonde, Jun Sun, Zhongren Zhou
BACKGROUND: Claudins are a family of integral membrane proteins and are components of tight junctions (TJs). Many TJ proteins are known to tighten the cell structure and maintain a barrier. Claudin-2 forms gated paracellular channels and allows sodium ions and other small positively charged ions to cross between adjacent cells. Recently, we found that vitamin D receptor (VDR) enhanced Claudin-2 expression in colon and that bile salt receptors VDR and Takeda G-protein coupled receptor5 (TGR5) were highly expressed in esophageal adenocarcinoma (EAC) and precancerous lesions...
February 17, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28202805/chenodeoxycholic-acid-stimulates-glucagon-like-peptide-1-secretion-in-patients-after-roux-en-y-gastric-bypass
#7
Signe Nielsen, Maria S Svane, Rune E Kuhre, Trine R Clausen, Viggo B Kristiansen, Jens F Rehfeld, Jens J Holst, Sten Madsbad, Kirstine N Bojsen-Moller
Postprandial secretion of glucagon-like peptide-1 (GLP-1) is enhanced after Roux-en-Y gastric bypass (RYGB), but the precise molecular mechanisms explaining this remain poorly understood. Plasma concentrations of bile acids (BAs) increase after RYGB, and BAs may act as molecular enhancers of GLP-1 secretion through activation of TGR5-receptors. We aimed to evaluate GLP-1 secretion after oral administration of the primary bile acid chenodeoxycholic acid (CDCA) and the secondary bile acid ursodeoxycholic acid (UDCA) (which are available for oral use) in RYGB-operated participants...
February 2017: Physiological Reports
https://www.readbyqxmd.com/read/28169840/bile-acid-disease-the-emerging-epidemic
#8
Ibironke Oduyebo, Michael Camilleri
PURPOSE OF REVIEW: Our objective was to review advances in bile acids in health and disease published in the last 2 years. Bile acid diarrhea (BAD) is recognized as a common cause of chronic diarrhea, and its recognition has been facilitated by development of new screening tests. RECENT FINDINGS: Primary BAD can account for 30% of cases of chronic diarrhea. The mechanisms leading to BAD include inadequate feedback regulation by fibroblast growth factor 19 (FGF-19) from ileal enterocytes, abnormalities in synthesis or degradation of proteins involved in FGF-19 regulation in hepatocytes and variations as a function of the bile acid receptor, TGR5 (GPBAR1)...
February 6, 2017: Current Opinion in Gastroenterology
https://www.readbyqxmd.com/read/28153453/bile-acids-and-their-receptors
#9
REVIEW
Emmanuelle Martinot, Lauriane Sèdes, Marine Baptissart, Jean-Marc Lobaccaro, Françoise Caira, Claude Beaudoin, David H Volle
Primary bile acids are synthetized from cholesterol within the liver and then transformed by the bacteria in the intestine to secondary bile acids. In addition to their involvement in digestion and fat solubilization, bile acids also act as signaling molecules. Several receptors are sensors of bile acids. Among these receptors, this review focuses on the nuclear receptor FXRα and the G-protein-coupled receptor TGR5. This review briefly presents the potential links between bile acids and cancers that are discussed in more details in the other articles of this special issue of Molecular Aspects of Medicine focused on "Bile acids, roles in integrative physiology and physiopathology"...
January 30, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28091894/mechanisms-of-action-of-surgical-interventions-on-weight-related-diseases-the-potential-role-of-bile-acids
#10
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...
March 2017: Obesity Surgery
https://www.readbyqxmd.com/read/28034761/bile-acid-receptor-tgr5-overexpression-is-associated-with-decreased-intestinal-mucosal-injury-and-epithelial-cell-proliferation-in-obstructive-jaundice
#11
Chen-Guang Ji, Xiao-Li Xie, Jie Yin, Wei Qi, Lei Chen, Yun Bai, Na Wang, Dong-Qiang Zhao, Xiao-Yu Jiang, Hui-Qing Jiang
Bile acids stimulate intestinal epithelial proliferation in vitro. We sought to investigate the role of the bile acid receptor TGR5 in the protection of intestinal epithelial proliferation in obstructive jaundice. Intestinal tissues and serum samples were obtained from patients with malignant obstructive jaundice and from bile duct ligation (BDL) rats. Intestinal permeability and morphological changes in the intestinal mucosa were observed. The functions of TGR5 in cell proliferation in intestinal epithelial injury were determined by overexpression or knockdown studies in Caco-2 and FHs 74 Int cells pretreated with lipopolysaccharide (LPS)...
December 18, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28027575/dual-role-of-the-bile-acid-receptor-takeda-g-protein-coupled-receptor-5-for-hepatic-lipid-metabolism-in-feast-and-famine
#12
EDITORIAL
Dieter Häussinger, Verena Keitel
No abstract text is available yet for this article.
December 27, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27997980/new-therapeutic-concepts-in-bile-acid-transport-and-signaling-for-management-of-cholestasis
#13
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/27987324/tudca-an-agonist-of-the-bile-acid-receptor-gpbar1-tgr5-with-anti-inflammatory-effects-in-microglial-cells
#14
Natalia Yanguas-Casás, M Asunción Barreda-Manso, Manuel Nieto-Sampedro, Lorenzo Romero-Ramírez
Bile acids are steroid acids found in the bile of mammals. The bile acid conjugate tauroursodeoxycholic acid (TUDCA) is neuroprotective in different animal models of stroke and neurological diseases. We have previously shown that TUDCA has anti-inflammatory effects on glial cell cultures and in a mouse model of acute neuroinflammation. We show now that microglial cells (central nervous system resident macrophages) express the G protein-coupled bile acid receptor 1/ Takeda G protein-coupled receptor 5 (GPBAR1/TGR5) in vivo and in vitro...
December 17, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27924062/chenodeoxycholic-acid-activates-nlrp3-inflammasome-and-contributes-to-cholestatic-liver-fibrosis
#15
Zizhen Gong, Jiefei Zhou, Shengnan Zhao, Chunyan Tian, Panliang Wang, Congfeng Xu, Yingwei Chen, Wei Cai, Jin Wu
Accumulation of hydrophobic bile acids in the liver contributes to cholestatic liver injury. Inflammation induced by excessive bile acids is believed to play a crucial role, however, the mechanisms of bile acids triggered inflammatory response remain unclear. Recent studies have highlighted the effect of NLRP3 inflammasome in mediating liver inflammation and fibrosis. In this study, we for the first time showed that chenodeoxycholic acid (CDCA), the major hydrophobic primary bile acid involved in cholestatic liver injury, could dose-dependently induce NLRP3 inflammasome activation and secretion of pro-inflammatory cytokine-IL-1β in macrophages by promoting ROS production and K+ efflux...
December 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27908836/gq-and-gs-signaling-acting-in-synergy-to-control-glp-1-secretion
#16
Maria Hauge, Jeppe Pio Ekberg, Maja Storm Engelstoft, Pascal Timshel, Andreas N Madsen, Thue W Schwartz
GPR40 is generally known to signal through Gq. However, in transfected cells, certain synthetic agonists can make the receptor signal also through Gs and cAMP (Hauge et al., 2015). Here we find that, in colonic crypt cultures, the GLP-1 secretion induced by such Gq + Gs GPR40 agonists is indeed inhibited by blockers of both Gq and Gs and is eliminated by combining these. This in contrast to Gq-only GPR40 agonists which only are affected by the Gq inhibitor. Importantly, Gq-only GPR40 agonists in combination with low doses of selective synthetic agonists for Gs coupled receptors, e...
November 28, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27846919/intestinal-bile-acid-receptors-are-key-regulators-of-glucose-homeostasis
#17
Mohamed-Sami Trabelsi, Sophie Lestavel, Bart Staels, Xavier Collet
In addition to their well-known function as dietary lipid detergents, bile acids have emerged as important signalling molecules that regulate energy homeostasis. Recent studies have highlighted that disrupted bile acid metabolism is associated with metabolism disorders such as dyslipidaemia, intestinal chronic inflammatory diseases and obesity. In particular, type 2 diabetes (T2D) is associated with quantitative and qualitative modifications in bile acid metabolism. Bile acids bind and modulate the activity of transmembrane and nuclear receptors (NR)...
November 16, 2016: Proceedings of the Nutrition Society
https://www.readbyqxmd.com/read/27833095/structural-assemblies-of-the-di-and-oligomeric-g-protein-coupled-receptor-tgr5-in-live-cells-an-mfis-fret-and-integrative-modelling-study
#18
Annemarie Greife, Suren Felekyan, Qijun Ma, Christoph G W Gertzen, Lina Spomer, Mykola Dimura, Thomas O Peulen, Christina Wöhler, Dieter Häussinger, Holger Gohlke, Verena Keitel, Claus A M Seidel
TGR5 is the first identified bile acid-sensing G-protein coupled receptor, which has emerged as a potential therapeutic target for metabolic disorders. So far, structural and multimerization properties are largely unknown for TGR5. We used a combined strategy applying cellular biology, Multiparameter Image Fluorescence Spectroscopy (MFIS) for quantitative FRET analysis, and integrative modelling to obtain structural information about dimerization and higher-order oligomerization assemblies of TGR5 wildtype (wt) and Y111 variants fused to fluorescent proteins...
November 11, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27808040/endobarrier-gastrointestinal-liner-delineation-of-underlying-mechanisms-and-clinical-effects
#19
Ulrich Rohde
Bariatric surgery (e.g. Roux-en-Y gastric bypass (RYGB)) has proven the most effective way of achieving sustainable weight losses and remission of type 2 diabetes (T2D). Studies indicate that the effectiveness of RYGB is mediated by an altered gastrointestinal tract anatomy, which in particular favours release of the gut incretin hormone glucagon-like peptide-1 (GLP-1). The EndoBarrier gastrointestinal liner or duodenal-jejunal bypass sleeve (DJBS) is an endoscopic deployable minimally invasive and fully reversible technique designed to mimic the bypass component of the RYGB...
November 2016: Danish Medical Journal
https://www.readbyqxmd.com/read/27789682/disrupted-murine-gut-to-human-liver-signaling-alters-bile-acid-homeostasis-in-humanized-mouse-liver-models
#20
Edwin C Y Chow, Holly P Quach, Yueping Zhang, Jason Z Y Wang, David C Evans, Albert P Li, Jose Silva, Rommel G Tirona, Yurong Lai, K Sandy Pang
The humanized liver mouse model is being exploited increasingly for human drug metabolism studies. However, its model stability, intercommunication between human hepatocytes and mouse nonparenchymal cells in liver and murine intestine, and changes in extrahepatic transporter and enzyme expressions have not been investigated. We examined these issues in FRGN [fumarylacetoacetate hydrolase (Fah-/-), recombination activating gene 2 (Rag2-/-), and interleukin 2 receptor subunit gamma (IL-2rg -/-) triple knockout] on nonobese diabetic (NOD) background] and chimeric mice: mFRGN and hFRGN (repopulated with mouse or human hepatocytes, respectively)...
January 2017: Journal of Pharmacology and Experimental Therapeutics
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