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https://www.readbyqxmd.com/read/28691284/performance-characteristics-of-serum-c4-and-fgf19-measurements-to-exclude-the-diagnosis-of-bile-acid-diarrhoea-in-ibs-diarrhoea-and-functional-diarrhoea
#1
P Vijayvargiya, M Camilleri, P Carlson, A Lueke, J O'Neill, D Burton, I Busciglio, L Donato
BACKGROUND: The serum biomarkers, elevated 7αC4 (C4) and decreased FGF19, have been proposed as screening tests for bile acid diarrhoea. AIM: To analyse prevalence, specificity and reproducibility of fasting C4 and FGF19 in identifying bile acid diarrhoea in patients with irritable bowel syndrome with predominant diarrhoea or functional diarrhoea (summarised as IBS-D). METHODS: We prospectively studied fasting serum C4 and FGF19 in 101 IBS-D patients; we reviewed data from 37 of the 101 patients with prior fasting serum C4 and FGF19 and from 30 of the 101 patients with prior faecal bile acids per 48 hours...
July 10, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28667746/integrated-gut-liver-microphysiological-systems-elucidates-inflammatory-inter-tissue-crosstalk
#2
Wen Li Kelly Chen, Collin Edington, Emily Suter, Jiajie Yu, Jeremy J Velazquez, Jason G Velazquez, Michael Shockley, Emma M Large, Raman Venkataramanan, David J Hughes, Cynthia L Stokes, David L Trumper, Rebecca L Carrier, Murat Cirit, Linda G Griffith, Douglas A Lauffenburger
A capability for analyzing complex cellular communication among tissues is important in drug discovery and development, and in vitro technologies for doing so are required for human applications. A prominent instance is communication between the gut and the liver, whereby perturbations of one tissue can influence behavior of the other. Here, we present a study on human gut-liver tissue interactions under normal and inflammatory contexts, via an integrative multi-organ platform comprising human liver (hepatocytes and Kupffer cells) and intestinal (enterocyte, goblet cells, and dendritic cells) models...
July 1, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28666948/bile-acid-deficiency-in-subgroup-of-patients-with-irritable-bowel-syndrome-with-constipation-based-on-biomarkers-in-serum-and-fecal-samples
#3
Priya Vijayvargiya, Irene Busciglio, Duane Burton, Leslie Donato, Alan Lueke, Michael Camilleri
BACKGROUND & AIMS: Short-term administration of delayed-release chenodeoxycholic acid to patients with irritable bowel syndrome with constipation (IBS-C) accelerates colonic transit and reduces symptoms. A preliminary study has shown that patients with IBS-C have reduced levels of bile acids (BAs) in feces and reduced synthesis of BA. We compared levels of primary and secondary BAs in fecal samples collected over a 48-hr period from patients with IBS-C on a diet that contained 100 g fat per day, and compared them will levels in samples from healthy volunteers (controls)...
June 27, 2017: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28664920/fgf1-a-new-weapon-to-control-type-2-diabetes-mellitus
#4
REVIEW
Emanuel Gasser, Christopher P Moutos, Michael Downes, Ronald M Evans
A hypercaloric diet combined with a sedentary lifestyle is a major risk factor for the development of insulin resistance, type 2 diabetes mellitus (T2DM) and associated comorbidities. Standard treatment for T2DM begins with lifestyle modification, and includes oral medications and insulin therapy to compensate for progressive β-cell failure. However, current pharmaceutical options for T2DM are limited in that they do not maintain stable, durable glucose control without the need for treatment intensification...
June 30, 2017: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/28650457/fibroblast-growth-factor-19-regulates-skeletal-muscle-mass-and-ameliorates-muscle-wasting-in-mice
#5
Bérengère Benoit, Emmanuelle Meugnier, Martina Castelli, Stéphanie Chanon, Aurélie Vieille-Marchiset, Christine Durand, Nadia Bendridi, Sandra Pesenti, Pierre-Axel Monternier, Anne-Cécile Durieux, Damien Freyssenet, Jennifer Rieusset, Etienne Lefai, Hubert Vidal, Jérôme Ruzzin
The endocrine-derived hormone fibroblast growth factor (FGF) 19 has recently emerged as a potential target for treating metabolic disease. Given that skeletal muscle is a key metabolic organ, we explored the role of FGF19 in that tissue. Here we report a novel function of FGF19 in regulating skeletal muscle mass through enlargement of muscle fiber size, and in protecting muscle from atrophy. Treatment with FGF19 causes skeletal muscle hypertrophy in mice, while physiological and pharmacological doses of FGF19 substantially increase the size of human myotubes in vitro...
June 26, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28591793/dynamics-of-bile-acid-profiles-glp-1-and-fgf19-after-laparoscopic-gastric-banding
#6
Veronika Thöni, Alexandra Pfister, Andreas Melmer, Barbara Enrich, Karin Salzmann, Susanne Kaser, Claudia Lamina, Christoph F Ebenbichler, Hubert Hackl, Herbert Tilg, Alexander R Moschen
Context: Increase of bile acids (BAs), fibroblast growth factor 19 (FGF19) and glucagon-like peptide 1 (GLP-1) has been implicated in metabolic improvements after Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG), whereas data are still conflicting regarding their role after laparoscopic adjustable gastric banding (LAGB). Objective: To assess fasting BA, FGF19 and GLP-1 concentrations in plasma before and after LAGB and to test for correlations with immuno-metabolic parameters...
June 7, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28589584/editorial-developing-a-stimulation-test-to-identify-fgf19-deficiency-in-bile-acid-diarrhoea
#7
EDITORIAL
J R F Walters
No abstract text is available yet for this article.
July 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28570655/circulating-fgf19-closely-correlates-with-bile-acid-synthesis-and-cholestasis-in-patients-with-primary-biliary-cirrhosis
#8
Zhanyi Li, Bingliang Lin, Guoli Lin, Yuankai Wu, Yusheng Jie, Xiangyong Li, Brian Ko, Yutian Chong, Jian Luo
BACKGROUND AND AIM: Bile acid (BA) synthesis in the liver is regulated by Fibroblast Growth Factor 19 (FGF19) secreted from the ileum as an enterohepatic feedback mechanism. Although FGF19 mRNA is absent in normal liver, FGF19 gene expression was reported to increase in response to both extrahepatic and intrahepatic cholestasis. The impact of upregulated FGF19 expression on BA synthesis is unclear and the overall role of circulating FGF19 and BA synthesis under cholestatic conditions needs to be further investigated...
2017: PloS One
https://www.readbyqxmd.com/read/28532995/histological-subtypes-of-hepatocellular-carcinoma-are-related-to-gene-mutations-and-molecular-tumour-classification
#9
Julien Calderaro, Gabrielle Couchy, Sandrine Imbeaud, Giuliana Amaddeo, Eric Letouzé, Jean-Frédéric Blanc, Christophe Laurent, Yacine Hajji, Daniel Azoulay, Paulette Bioulac-Sage, Jean-Charles Nault, Jessica Zucman-Rossi
BACKGROUND AND AIMS: Our increasing understanding of hepatocellular carcinoma (HCC) biology holds promise for personalized care, however its translation into clinical practice requires a precise knowledge of its relationship to tumour phenotype. METHODS: We aimed at investigating molecular-phenotypic correlations in a large series of HCC. To this purpose, 343 surgically resected HCC were investigated by pathological review, immunohistochemistry, gene expression profiling and sequencing...
May 19, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28511023/efficacy-of-docosahexaenoic-acid-choline-vitamin-e-dha-cho-ve-in-paediatric-nash-a-randomized-controlled-clinical-trial
#10
Evelyn Zöhrer, Alisi Anna, Jörg Jahnel, Antonella Moscla, Claudia Della Corte, Annalisa Crudele, Günter Fauler, Valerio Nobili
Non-alcoholic steatohepatitis (NASH), a progressive form of non-alcoholic fatty liver disease (NAFLD), is one of the most common hepatic diseases in children. We conducted a randomized controlled clinical trial on children with biopsy-proven NASH based on a combinatorial nutritional approach compared to placebo. Participants were assigned to lifestyle modification plus placebo, or lifestyle modification plus a mix containing docosahexaenoic acid, choline and vitamin E (DHA-CHO-VE). Forty children and adolescents concluded the trial...
May 16, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28508871/non-cell-autonomous-activation-of-il-6-stat3-signaling-mediates-fgf19-driven-hepatocarcinogenesis
#11
Mei Zhou, Hong Yang, R Marc Learned, Hui Tian, Lei Ling
Hepatocellular carcinoma (HCC), a primary malignancy of the liver, is the second leading cause of cancer mortality worldwide. Fibroblast Growth Factor 19 (FGF19) is one of the most frequently amplified genes in HCC patients. Moreover, mice expressing an FGF19 transgene have been shown to develop HCC. However, the downstream signalling pathways that mediate FGF19-dependent tumorigenesis remain to be deciphered. Here we show that FGF19 triggers a previously unsuspected, non-cell-autonomous program to activate STAT3 signalling in hepatocytes through IL-6 produced in the liver microenvironment...
May 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28507750/effects-of-conventional-and-a-novel-colonic-release-bile-acid-sequestrant-a3384-on-fibroblast-growth-factor-19-and-bile-acid-metabolism-in-healthy-volunteers-and-patients-with-bile-acid-diarrhoea
#12
R N Appleby, A Bajor, P-G Gillberg, H Graffner, M Simrén, K A Ung, Jrf Walters
BACKGROUND: Primary bile acid diarrhoea (BAD) is associated with increased bile acid synthesis and low fibroblast growth factor 19 (FGF19). Bile acid sequestrants are used as therapy, but are poorly tolerated and may exacerbate FGF19 deficiency. AIM: The purpose of this study was to evaluate the pharmacological effects of conventional sequestrants and a colonic-release formulation preparation of colestyramine (A3384) on bile acid metabolism and bowel function in patients with BAD...
April 2017: United European Gastroenterology Journal
https://www.readbyqxmd.com/read/28498614/hepatic-uptake-of-conjugated-bile-acids-is-mediated-by-both-ntcp-and-oatps-and-modulated-by-intestinal-sensing-of-plasma-bile-acid-levels-in-mice
#13
Davor Slijepcevic, Reinout L P Roscam Abbing, Takeshi Katafuchi, Antje Blank, Joanne M Donkers, Stéphanie van Hoppe, Dirk R de Waart, Dagmar Tolenaars, Jonathan H M van der Meer, Manon Wildenberg, Ulrich Beuers, Ronald P J Oude Elferink, Alfred H Schinkel, Stan F J van de Graaf
BACKGROUND & AIMS: The Na(+) -taurocholate cotransporting polypeptide (NTCP/SLC10A1) is believed to be pivotal for hepatic uptake of conjugated bile acids. However, plasma bile acid levels are normal in a subset of NTCP knockout mice and in mice treated with myrcludex B, a specific NTCP inhibitor. Here, we elucidated which transport proteins mediate the hepatic uptake of conjugated bile acids and demonstrated intestinal sensing of elevated bile acid levels in plasma in mice. METHODS: Mice or healthy volunteers were treated with myrcludex B...
May 12, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28487440/cholestyramine-treatment-of-healthy-humans-rapidly-induces-transient-hypertriglyceridemia-when-treatment-is-initiated
#14
Beatrice Sjöberg, Sara Straniero, Bo Angelin, Mats Rudling
Bile acid (BA) production in mice is regulated by hepatic farnesoid X receptors and by intestinal fibroblast growth factor (FGF) 15, (in humans FGF19) a suppressor of BA synthesis that also reduces serum triglycerides and glucose. Cholestyramine treatment reduces FGF19 and induces BA synthesis while plasma triglycerides may increase of unclear reasons. We explored if FGF19 may suppress BA synthesis and plasma triglycerides in humans by modulation of FGF19 levels through long-term cholestyramine at increasing doses...
May 9, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28460066/co-clinical-trials-demonstrate-predictive-biomarkers-for-dovitinib-an-fgfr-inhibitor-in-lung-squamous-cell-carcinoma
#15
H R Kim, H N Kang, H S Shim, E Y Kim, J Kim, D J Kim, J G Lee, C Y Lee, M H Hong, S-M Kim, H Kim, K-H Pyo, M R Yun, H J Park, J Y Han, H A Youn, M-J Ahn, S Paik, T-M Kim, B C Cho
Background: We conducted co-clinical trials in patient-derived xenograft (PDX) models to identify predictive biomarkers for the multikinase inhibitor dovitinib in lung squamous cell carcinoma (LSCC). Methods: The PDX01-02 were established from LSCC patients enrolled in the phase II trial of dovitinib (NCT01861197) and PDX03-05 were established from LSCC patients receiving surgery. These five PDX tumors were subjected to in vivo test of dovitinib efficacy, whole exome sequencing and gene expression profiling...
June 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28451950/the-role-and-potential-therapeutic-implications-of-the-fibroblast-growth-factors-in-energy-balance-and-type-2-diabetes
#16
REVIEW
Maitane Izaguirre, María J Gil, Ignacio Monreal, Fabrizio Montecucco, Gema Frühbeck, Victoria Catalán
PURPOSE OF REVIEW: Obesity and its associated metabolic diseases have reached epidemic proportions worldwide, reducing life expectancy and quality of life. Several drugs have been tested to treat these diseases but many of them have damaging side effects. Consequently, there is an urgent need to develop more effective therapies. Recently, endocrine fibroblast growth factors (FGFs) have become attractive targets in the treatment of metabolic diseases. This review summarizes their most important functions as well as FGF-based therapies for the treatment of obesity and type 2 diabetes (T2D)...
June 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28446510/a-postprandial-fgf19-shp-lsd1-regulatory-axis%C3%A2-mediates-epigenetic-repression-of-hepatic%C3%A2-autophagy
#17
Sangwon Byun, Young-Chae Kim, Yang Zhang, Bo Kong, Grace Guo, Junichi Sadoshima, Jian Ma, Byron Kemper, Jongsook Kim Kemper
Lysosome-mediated autophagy is essential for cellular survival and homeostasis upon nutrient deprivation, but is repressed after feeding. Despite the emerging importance of transcriptional regulation of autophagy by nutrient-sensing factors, the role for epigenetic control is largely unexplored. Here, we show that Small Heterodimer Partner (SHP) mediates postprandial epigenetic repression of hepatic autophagy by recruiting histone demethylase LSD1 in response to a late fed-state hormone, FGF19 (hFGF19, mFGF15)...
June 14, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28445152/multiplexed-gene-expression-profiling-identifies-the-fgfr4-pathway-as-a-novel-biomarker-in-intrahepatic-cholangiocarcinoma
#18
Changhoon Yoo, Jihoon Kang, Deokhoon Kim, Kyu-Pyo Kim, Baek-Yeol Ryoo, Seung-Mo Hong, Jung Jin Hwang, Seong-Yun Jeong, Shin Hwang, Ki-Hun Kim, Young-Joo Lee, Klaus P Hoeflich, Oleg Schmidt-Kittler, Stephen Miller, Eun Kyung Choi
BACKGROUND: The fibroblast growth factor receptor 4 (FGFR4) pathway is an essential regulatory component of bile acid synthesis, and its relationship with hepatocellular carcinoma (HCC) has been reported. We investigated the gene expression and clinical significance of FGFR4 and related pathways in intrahepatic cholangiocarcinoma (iCCA). RESULTS: The median age was 56 years (range 30-78) and 34 patients (74%) were male. Six patients (13%) had hepatitis B virus infection, with or without liver cirrhosis...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413172/the-effects-of-metformin-on-fibroblast-growth-factor-19-21-and-fibroblast-growth-factor-receptor-1-in-high-fat-diet-and-streptozotocin-induced-diabetic-rats
#19
Yan Wang, Ningning Dang, Pei Sun, Jin Xia, Chunxue Zhang, Shuguang Pang
To understand metformin’s effects on fibroblast growth factors (FGFs) and fibroblast growth factor receptor 1 (FGFR1), we investigated circulating fibroblast growth factor-19 (FGF19), FGF21 levels, and FGFR1 in type 2 diabetes mellitus (T2DM). In addition, protein kinase B (Akt) signaling pathway was detected to explain the possible mechanisms. T2DM was induced by feeding rats with high-fat diet for 11 weeks, followed by a low dose of streptozotocin (STZ, 30-35 mg/kg, intraperitoneally). Control rats (Con) were fed on a normal chow; diabetic rats (DM) were fed on high-fat diet supplemented with or without metformin (METF) for 12 weeks (500 mg・kg(-1)・d(-1))...
April 11, 2017: Endocrine Journal
https://www.readbyqxmd.com/read/28378364/chenodeoxycholic-acid-stimulated-fibroblast-growth-factor-19-response-a-potential-biochemical-test-for-bile-acid-diarrhoea
#20
C Borup, S Wildt, J J Rumessen, P N Bouchelouche, J Graff, M Damgaard, C McQuitty, D Rainteau, L K Munck
BACKGROUND: Bile acid diarrhoea is underdiagnosed and better diagnostic tests are needed. Fasting serum fibroblast growth factor-19 (FGF19) has insufficient diagnostic value, but this may be improved by stimulation. AIM: To explore if an impaired FGF19 response identifies primary bile acid diarrhoea. METHODS: Eight patients with primary bile acid diarrhoea and eight healthy volunteers ingested (i) a meal plus 1250 mg chenodeoxycholic acid (CDCA), (ii) 1250 mg CDCA or (iii) the meal...
June 2017: Alimentary Pharmacology & Therapeutics
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