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fibroblast growth factor liver disease

Hwi Young Kim, Dong Hyeon Lee, Jeong-Hoon Lee, Young Youn Cho, Eun Ju Cho, Su Jong Yu, Yoon Jun Kim, Jung-Hwan Yoon
BACKGROUND: Prediction of the outcome of sorafenib therapy using biomarkers is an unmet clinical need in patients with advanced hepatocellular carcinoma (HCC). The aim was to develop and validate a biomarker-based model for predicting sorafenib response and overall survival (OS). METHODS: This prospective cohort study included 124 consecutive HCC patients (44 with disease control, 80 with progression) with Child-Pugh class A liver function, who received sorafenib...
March 20, 2018: BMC Cancer
Jian Zhang, Junhong Li, Junwei Ma, Hongxin Wang, Yin Yi
Hepatitis B cirrhosis is caused by liver cell necrosis, residual liver cell nodular regeneration, connective tissue hyperplasia and fiber formation, which frequently leads to adrenal insufficiency. Previous reports have demonstrated that human fibroblast growth factor (hFGF)-21 is a multifunctional protein that exhibits potential therapeutic value for metabolic diseases. The present study investigated the diagnostic value of hFGF-21 and analyzed the potential molecular mechanism in the progression of hepatitis B cirrhosis combined with adrenal insufficiency...
April 2018: Experimental and Therapeutic Medicine
Preeti Pathak, Xie Cen, Robert G Nichols, Jessica M Ferrell, Shannon Boehme, Kristopher W Krausz, Andrew D Patterson, Frank J Gonzalez, John Y L Chiang
Bile acids activate farnesoid X receptor (FXR) and G protein-coupled bile acid receptor-1 (Gpbar-1, aka TGR5) to regulate bile acid metabolism and glucose and insulin sensitivity. FXR and TGR5 are co-expressed in the enteroendocrine L cells but their roles in integrated regulation of metabolism are not completely understood. We reported recently that activation of FXR induces TGR5 to stimulate glucagon-like peptide-1 (GLP-1) secretion to improve insulin sensitivity and hepatic metabolism. In this study, we used the intestine-restricted FXR agonist fexaramine (FEX) to study the effect of activation of intestinal FXR on the gut microbiome, bile acid metabolism, and FXR and TGR5 signaling...
February 27, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Hideyuki Takeuchi, Derek Wong, Michael Schneider, Hudson H Freeze, Megumi Takeuchi, Steven J Berardinelli, Atsuko Ito, Hane Lee, Stanley F Nelson, Robert S Haltiwanger
Protein O-fucosyltransferase-1 (POFUT1) adds O-fucose monosaccharides to epidermal growth factor-like (EGF) repeats found on approximately 100 mammalian proteins, including Notch receptors. Haploinsufficiency of POFUT1 has been linked to adult-onset Dowling Degos Disease (DDD) with hyperpigmentation defects. Homozygous deletion of mouse Pofut1 results in embryonic lethality with severe Notch-like phenotypes including defects in somitogenesis, cardiogenesis, vasculogenesis, and neurogenesis, but the extent to which POFUT1 is required for normal human development is not yet understood...
February 14, 2018: Glycobiology
Hyun S Kim, Walid L Shaib, Chao Zhang, Ganji Purnachandra Nagaraju, Christina Wu, Olatunji B Alese, Zhengjia Chen, Edith Brutcher, Meredith Renfroe, Bassel F El-Rayes
BACKGROUND: Neuroendocrine tumors (NETs) metastasize to the liver. Everolimus and selective internal radioembolization (SIRT) are approved treatments. Pasireotide is a somatostatin analogue with an affinity for somatostatin receptors 1, 2, 3, and 5. Everolimus and pasireotide may potentiate SIRT radiosensitization and inhibit rebound angiogenesis. This study evaluated the safety of pasireotide, everolimus, and SIRT. METHODS: This 3 + 3 phase 1 trial evaluated 3 dose levels of everolimus (2...
February 16, 2018: Cancer
Guicheng Wu, Yanlong Liu, Yunhuan Liu, Lihua Zhang, Haiyang Zhao, Liming Liu, Cuiqing Zhao, Wenke Feng
Excess alcohol consumption can lead to alcoholic liver disease. Fibroblast growth factor 21 (FGF21) is a metabolic regulator with multiple physiologic functions. Previous study demonstrated that FGF21 deficiency exacerbated alcohol-induced liver injury and exogenous FGF21 administration protected liver from chronic alcohol-induced injury. In this study, we aimed to explore the role of FGF21 in alcohol metabolism in mice. FGF21 knockout (KO) mice and the wild time (WT) control mice were divided into two groups and fasted for 24 h followed by a bonus of alcohol treatment at a dose of 5 g/kg body weight via gavage...
February 12, 2018: Biochemical and Biophysical Research Communications
Mei Zhou, R Marc Learned, Stephen J Rossi, Alex M DePaoli, Hui Tian, Lei Ling
Nonalcoholic fatty liver disease (NAFLD) is an increasingly prevalent chronic liver disease for which no approved therapies are available. Despite intensive research, the cellular mechanisms that mediate NAFLD pathogenesis and progression are poorly understood. Although obesity, diabetes, insulin resistance, and related metabolic syndrome, all consequences of a Western diet lifestyle, are well-recognized risk factors for NAFLD development, dysregulated bile acid metabolism is emerging as a novel mechanism contributing to NAFLD pathogenesis...
December 2017: Hepatology communications
Zhen Dong, Raghu Sinha, John P Richie
Sulfur amino acids (SAAs) play numerous critical roles in metabolism and overall health maintenance. Preclinical studies have demonstrated that SAA-restricted diets have many beneficial effects, including extending life span and preventing the development of a variety of diseases. Dietary sulfur amino acid restriction (SAAR) is characterized by chronic restrictions of methionine and cysteine but not calories and is associated with reductions in body weight, adiposity and oxidative stress, and metabolic changes in adipose tissue and liver resulting in enhanced insulin sensitivity and energy expenditure...
February 5, 2018: Annals of the New York Academy of Sciences
Magdalene K Montgomery, Ruzaidi Mokhtar, Jacqueline Bayliss, Helena C Parkington, Victor M Suturin, Clinton R Bruce, Matthew J Watt
Lipid droplets are critical for the regulation of lipid metabolism, and dysregulated lipid metabolism contributes to the pathogenesis of several diseases including type 2 diabetes. We generated mice with muscle-specific deletion of the lipid droplet-associated protein, perilipin 5 (PLIN5, Plin5MKO ), and investigated PLIN5's role in regulating skeletal muscle lipid metabolism, intracellular signalling and whole-body metabolic homeostasis. High-fat feeding induced changes in muscle lipid metabolism of Plin5MKO mice, which included increased fatty acid oxidation and oxidative stress, but surprisingly, a reduction in inflammation and endoplasmic reticulum (ER) stress...
January 29, 2018: Diabetes
Rui Lin, Yufeng Wang, Kun Ji, Zhongyan Liu, Shuai Xiao, Dehua Zhou, Quanning Chen, Baomin Shi
Due to the lack of potential organs, hepatocellular transplantation has been considered for treating end-stage liver disease. Induced pluripotent stem cells (iPSCs) are reverted from somatic cells and are able to differentiate into hepatocytes. The present study aimed to investigate the mechanisms underlying iPSC differentiation to hepatocytes. GSE66076 was downloaded from the Gene Expression Omnibus; this database includes data from 3 undifferentiated (T0), 3 definitive endoderm (T5), and 3 early hepatocyte (T24) samples across hepatic‑directed differentiation of iPSCs...
January 5, 2018: Molecular Medicine Reports
Hye Jin An, Bonggi Lee, Seong Min Kim, Dae Hyun Kim, Ki Wung Chung, Su Gyeong Ha, Kyung Chul Park, Yeo Jin Park, Seong Jin Kim, Hwi Young Yun, Pusoon Chun, Byung Pal Yu, Hyung Ryong Moon, Hae Young Chung
Nonalcoholic fatty liver disease (NAFLD) is frequently observed in obese and aged individuals. Peroxisome proliferator-activated receptors (PPARs) play a role in regulating hepatic lipid accumulation, a hallmark of NAFLD development. A PPAR pan agonist, 2-(4-(5,6-methylenedioxybenzo[d]thiazol-2-yl)-2-methylphenoxy)-2-methylpropanoic acid (MHY2013) has been shown to prevent fatty liver formation and insulin resistance in obese mice (db/db) model. However, the beneficial effects of MHY2013 in aged model remain unknown...
2018: Biological & Pharmaceutical Bulletin
Yeonsoo Joe, Sena Kim, Hyo Jeong Kim, Jeongmin Park, Yingqing Chen, Hyeok-Jun Park, Seung-Joo Jekal, Stefan W Ryter, Uh Hyun Kim, Hun Taeg Chung
The prevalence of metabolic diseases, including type 2 diabetes, obesity, and cardiovascular disease, has rapidly increased, yet the molecular mechanisms underlying the metabolic syndrome, a primary risk factor, remain incompletely understood. The small, gaseous molecule carbon monoxide (CO) has well-known anti-inflammatory, antiproliferative, and antiapoptotic effects in a variety of cellular- and tissue-injury models, whereas its potential effects on the complex pathways of metabolic disease remain unknown...
January 2, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Mohammad Zarei, Emma Barroso, Xavier Palomer, Jianli Dai, Patricia Rada, Tania Quesada-López, Joan Carles Escolà-Gil, Lidia Cedó, Mohammad Reza Zali, Mahsa Molaei, Reza Dabiri, Santiago Vázquez, Eugènia Pujol, Ángela M Valverde, Francesc Villarroya, Yong Liu, Walter Wahli, Manuel Vázquez-Carrera
OBJECTIVE: The very low-density lipoprotein receptor (VLDLR) plays an important role in the development of hepatic steatosis. In this study, we investigated the role of Peroxisome Proliferator-Activated Receptor (PPAR)β/δ and fibroblast growth factor 21 (FGF21) in hepatic VLDLR regulation. METHODS: Studies were conducted in wild-type and Pparβ/δ-null mice, primary mouse hepatocytes, human Huh-7 hepatocytes, and liver biopsies from control subjects and patients with moderate and severe hepatic steatosis...
December 19, 2017: Molecular Metabolism
Yoshio Sumida, Masashi Yoneda
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide, and there is no approved pharmacotherapy. The efficacy of vitamin E and pioglitazone has been established in nonalcoholic steatohepatitis (NASH), a progressive form of NAFLD. GLP-1RA and SGLT2 inhibitors, which are currently approved for use in diabetes, have shown early efficacy in NASH, and also have beneficial cardiovascular or renal effects. Innovative NASH therapies include four main pathways. The first approach is targeting hepatic fat accumulation...
December 16, 2017: Journal of Gastroenterology
Xiaojiao Zheng, Fengjie Huang, Aihua Zhao, Sha Lei, Yunjing Zhang, Guoxiang Xie, Tianlu Chen, Chun Qu, Cynthia Rajani, Bing Dong, Defa Li, Wei Jia
BACKGROUND: Intestinal bacteria are known to regulate bile acid (BA) homeostasis via intestinal biotransformation of BAs and stimulation of the expression of fibroblast growth factor 19 through intestinal nuclear farnesoid X receptor (FXR). On the other hand, BAs directly regulate the gut microbiota with their strong antimicrobial activities. It remains unclear, however, how mammalian BAs cross-talk with gut microbiome and shape microbial composition in a dynamic and interactive way. RESULTS: We quantitatively profiled small molecule metabolites derived from host-microbial co-metabolism in mice, demonstrating that BAs were the most significant factor correlated with microbial alterations among all types of endogenous metabolites...
December 14, 2017: BMC Biology
Fiona Tsui-Fen Cheng, Fu Ou-Yang, Nina Lapke, Kai-Che Tung, Yen-Kung Chen, Yuh-Yu Chou, Shu-Jen Chen
Treatment options for patients with hormone receptor-positive (HR+), HER2-negative (HER2-) breast cancer and resistance to endocrine therapy remain limited. An interesting therapeutic target in these patients is fibroblast growth factor receptor 1 ( FGFR1 ). FGFR1 is amplified in approximately 11% of patients with breast cancer, especially those with HR+ disease. This report presents a patient with metastatic HR+ HER2- breast cancer harboring an FGFR1 amplification who was resistant to endocrine therapy but responded to pazopanib, a multi-tyrosine kinase inhibitor with FGFR -inhibiting activity...
December 2017: Journal of the National Comprehensive Cancer Network: JNCCN
Rowan F van Golen, Pim B Olthof, Lianne R de Haan, Robert J Coelen, Alexandros Pechlivanis, Mark J de Keijzer, Ruud Weijer, Dirk R de Waart, André B P van Kuilenburg, Jeroen Roelofsen, Pim W Gilijamse, Martinus A Maas, Matthew R Lewis, Jeremy K Nicholson, Joanne Verheij, Michal Heger
Obstructive cholestasis causes liver injury via accumulation of toxic bile acids (BAs). Therapeutic options for cholestatic liver disease are limited, partially because the available murine disease models lack translational value. Profiling of time-related changes following bile duct ligation (BDL) in Gold Syrian hamsters revealed a biochemical response similar to cholestatic patients in terms of BA pool composition, alterations in hepatocyte BA transport and signaling, suppression of BA production, and adapted BA metabolism...
March 2018: Biochimica et Biophysica Acta
Liang Wu, Qingchun Pan, Guangyu Wu, Lingling Qian, Jing Zhang, Lei Zhang, Qichen Fang, Guoqing Zang, Yudong Wang, George Lau, Huating Li, Weiping Jia
Fibroblast growth factor 21 (FGF21), a stress-induced hormone in the liver, has been shown the protective functions in pathological conditions. The study investigated the association of circulating FGF21 with hepatitis B virus (HBV) infection and its related diseases. Serum FGF21 levels were measured in 33 acute hepatitis B (AHB), 75 chronic hepatitis B (CHB) and 66 CHB patients with advanced liver diseases including liver cirrhosis, acute-on-chronic liver failure (ALCF) and hepatocellular carcinoma (HCC) together with 200 age- and BMI-matched healthy controls...
November 28, 2017: Scientific Reports
Phillipp Hartmann, Katrin Hochrath, Angela Horvath, Peng Chen, Caroline T Seebauer, Cristina Llorente, Lirui Wang, Yazen Alnouti, Derrick E Fouts, Peter Stärkel, Rohit Loomba, Sally Coulter, Christopher Liddle, Ruth T Yu, Lei Ling, Stephen J Rossi, Alex M DePaoli, Michael Downes, Ronald M Evans, David A Brenner, Bernd Schnabl
Alcoholic liver disease is associated with changes in the intestinal microbiota. Functional consequences of alcohol-associated dysbiosis are largely unknown. The aim of this study was to identify a mechanism of how changes in the intestinal microbiota contribute to alcoholic liver disease. Metagenomic sequencing of intestinal contents demonstrated that chronic ethanol feeding in mice is associated with an overrepresentation of bacterial genomic DNA encoding choloylglycine hydrolase, which deconjugates bile acids in the intestine...
November 21, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Richard N Appleby, Jonathan D Nolan, Ian M Johnston, Sanjeev S Pattni, Jessica Fox, Julian Rf Walters
Background: Bile acid diarrhoea (BAD) is a common cause of chronic diarrhoea with a population prevalence of primary BAD around 1%. Previous studies have identified associations with low levels of the ileal hormone fibroblast growth factor 19 (FGF19), obesity and hypertriglyceridaemia. The aim of this study was to identify further associations of BAD. Methods: A cohort of patients with chronic diarrhoea who underwent 75selenohomocholic acid taurate (SeHCAT) testing for BAD was further analysed retrospectively...
2017: BMJ Open Gastroenterology
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