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https://www.readbyqxmd.com/read/28445152/multiplexed-gene-expression-profiling-identifies-the-fgfr4-pathway-as-a-novel-biomarker-in-intrahepatic-cholangiocarcinoma
#1
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...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28424617/targeting-bile-acid-receptors-discovery-of-a-potent-and-selective-farnesoid-x-receptor-agonist-as-a-new-lead-in-the-pharmacological-approach-to-liver-diseases
#2
Carmen Festa, Simona De Marino, Adriana Carino, Valentina Sepe, Silvia Marchianò, Sabrina Cipriani, Francesco S Di Leva, Vittorio Limongelli, Maria C Monti, Angela Capolupo, Eleonora Distrutti, Stefano Fiorucci, Angela Zampella
Bile acid (BA) receptors represent well-defined targets for the development of novel therapeutic approaches to metabolic and inflammatory diseases. In the present study, we report the generation of novel C-3 modified 6-ethylcholane derivatives. The pharmacological characterization and molecular docking studies for the structure-activity rationalization, allowed the identification of 3β-azido-6α-ethyl-7α-hydroxy-5β-cholan-24-oic acid (compound 2), a potent and selective FXR agonist with a nanomolar potency in transactivation assay and high efficacy in the recruitment of SRC-1 co-activator peptide in Alfa Screen assay...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28364638/nrf2-is-crucial-for-the-down-regulation-of-cyp7a1-induced-by-arachidonic-acid-in-hepg2-cells
#3
Jin-Ming Zhang, Xing-He Wang, Li-Hong Hao, He Wang, Xiu-Ying Zhang, Ishfaq Muhammad, Yue Qi, Guang-Liang Li, Xiao-Qi Sun
In former research, cyp7a1 expression was decreased but Nrf2 transcription and hepatic arachidonic acid (AA) concentration were increased in high-fat diet fed mice. This study aims to investigate the influence of AA in CYP7A1 expression and the role of Nrf2 in regulating CYP7A1 in the process. HepG2 cells were administered with different concentrations of AA. Nrf2 and CYP7A1 expressions were analyzed by real-time PCR and western blot. Nrf2 silenced and over-expressed cell models were constructed by Nrf2 siRNA and eukaryotic expression vector transient transfections and were used to investigate the role of Nrf2 in regulating CYP7A1 following AA administration...
March 7, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28357032/meta-analysis-reveals-up-regulation-of-cholesterol-processes-in-non-alcoholic-and-down-regulation-in-alcoholic-fatty-liver-disease
#4
Wasco Wruck, James Adjaye
AIM: To compare transcriptomes of non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) in a meta-analysis of liver biopsies. METHODS: Employing transcriptome data from patient liver biopsies retrieved from several public repositories we performed a meta-analysis comparing ALD and NAFLD. RESULTS: We observed predominating commonalities at the transcriptome level between ALD and NAFLD, most prominently numerous down-regulated metabolic pathways and cytochrome-related pathways and a few up-regulated pathways which include ECM-receptor interaction, phagosome and lysosome...
March 18, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28356314/high-throughput-and-reliable-isotope-label-free-approach-for-profiling-24-metabolic-enzymes-in-fvb-mice-and-gender-differences
#5
Jiamei Chen, Lijun Zhu, Xiaoyan Li, Haihui Zheng, Tongmeng Yan, Cong Xie, Sijing Zeng, Jia Yu, Huangyu Jiang, Linlin Lu, Xiaoxiao Qi, Ying Wang, Ming Hu, Zhongqiu Liu
FVB mice are extensively used in transgenic and pharmacokinetic research. In this study, a validated isotope label-free method of using ultrahigh-performance liquid chromatography (UHPLC)-MS/MS was established for quantifying 24 drug-metabolizing enzymes (DMEs) in FVB mice. The DMEs include cytochrome P450 (CYPs/Cyps), UDP-glucuronsyltransferases (UGTs/Ugts), and sulfotransferases (SULTs/Sults), which are the major phase I and II metabolic enzymes responsible for clearing and detoxifying xenobiotic and endogenous substances...
March 29, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28302129/cholesterol-lowing-effect-of-taurine-in-hepg2-cell
#6
Junxia Guo, Ya Gao, Xuelian Cao, Jing Zhang, Wen Chen
BACKGROUND: A number of studies indicate that taurine promotes cholesterol conversion to bile acids by upregulating CYP7A1 gene expression. Few in vitro studies are concerned the concentration change of cholesterol and its product of bile acids, and the molecular mechanism of CYP7A1 induction by taurine. METHODS: The levels of intracellular total cholesterol (TC), free cholesterol (FC), cholesterol ester (EC), total bile acids (TBA) and medium TBA were determined after HepG2 cells were cultured for 24/48 h in DMEM supplemented with taurine at the final concentrations of 1/10/20 mM respectively...
March 16, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28288854/irinotecan-induced-bile-acid-malabsorption-is-associated-with-down-regulation-of-ileal-asbt-slc10a2-in-mice
#7
A-Xi Shi, Yan Zhou, Xiao-Yi Zhang, Yan-Shu Zhao, Hong-Yan Qin, Yan-Ping Wang, Xin-An Wu
Irinotecan, (CPT-11), an antitumor agent primarily used for the treatment of solid tumors, has often compromised clinical application due to the inducement of severe delay-onset diarrhea. Bile acid malabsorption (BAM) is widely accepted as the common cause of diarrhea. However, whether CPT-11-induced diarrhea has correlation with BAM is unknown. The aim of this study was to investigate the effect of CPT-11 on the bile acid homeostasis in mice. The mice were administrated with CPT-11 intravenously for four consecutive days...
March 10, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28283178/activation-of-constitutive-androstane-receptor-prevents-cholesterol-gallstone-formation
#8
Shihai Cheng, Min Zou, Qinhui Liu, Jiangying Kuang, Jing Shen, Shiyun Pu, Lei Chen, Hong Li, Tong Wu, Rui Li, Yanping Li, Wei Jiang, Zhiyong Zhang, Jinhan He
Cholesterol gallstone disease (CGD) is one of the most common gastrointestinal diseases. Lithogenic hepatic bile secretion precedes the formation of cholesterol gallstones. Constitutive androstane receptor (CAR), a member of nuclear family, plays an important role in cholesterol and bile acid metabolism. To examine whether activation of CAR can prevent cholesterol gallstone formation, we treated C57BL6/J mice maintained on a lithogenic diet with CAR agonist 1,4-bis-[2-(3, 5-dichlorpyridyloxy)] benzene and performed bile duct cannulation to study the dynamics of biliary lipids...
April 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28275692/endoplasmic-reticulum-stress-regulates-hepatic-bile-acid-metabolism-in-mice
#9
Anne S Henkel, Brian LeCuyer, Shantel Olivares, Richard M Green
BACKGROUND & AIMS: Cholestasis promotes endoplasmic reticulum (ER) stress in the liver, however, the effect of ER stress on hepatic bile acid metabolism is unknown. We aim to determine the effect of ER stress on hepatic bile acid synthesis and transport in mice. METHODS: ER stress was induced pharmacologically in C57BL/6J mice and human hepatoma (HepG2) cells. The hepatic expression of genes controlling bile acid synthesis and transport was determined. To measure the activity of the primary bile acid synthetic pathway, the concentration of 7α-hydroxy-4-cholesten-3-1 was measured in plasma...
March 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28275691/targeting-the-enterohepatic-bile-acid-signaling-induces-hepatic-autophagy-via-a-cyp7a1-akt-mtor-axis-in-mice
#10
Yifeng Wang, Yifeng Ding, Jibiao Li, Hemantkumar Chavan, David Matye, Hong-Min Ni, John Y L Chiang, Partha Krishnamurthy, Wen-Xing Ding, Tiangang Li
BACKGROUND & AIMS: Hepatic cholesterol accumulation and autophagy defects contribute to hepatocyte injury in fatty liver disease. Bile acid synthesis is a major pathway for cholesterol catabolism in the liver. This study aims to understand the molecular link between cholesterol and bile acid metabolism and hepatic autophagy activity. METHODS: The effects of cholesterol and cholesterol 7α-hydroxylase (CYP7A1) expression on autophagy and lysosome function were studied in cell models...
March 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28251657/hypolipidemic-effect-and-mechanism-of-paprika-seed-oil-on-sprague-dawley-rats
#11
Xuhui Chen, Yongbo Ding, Jiaxin Song, Jianquan Kan
BACKGROUND: The functional properties of paprika seed oil are relatively lack, the hyperlipidemic effects and mechanisms of paprika seed oil on Sprague-Dawley rats are explored, which may improve the usage of paprika seed source and provide a theoretical basis of paprika seed oil for the alleviation of hyperlipidemia. RESULTS: In capsaicin and paprika seed oil (PSO) groups, total cholesterol (TC) and total triglyceride (TG) in serum and liver lipids of rats were significantly decreased (P < 0...
March 2, 2017: Journal of the Science of Food and Agriculture
https://www.readbyqxmd.com/read/28249806/application-of-quantitative-targeted-absolute-proteomics-to-profile-protein-expression-changes-of-hepatic-transporters-and-metabolizing-enzymes-during-cholic-acid-promoted-liver-regeneration
#12
Takayuki Miura, Masanori Tachikawa, Hideo Ohtsuka, Koji Fukase, Shun Nakayama, Naoaki Sakata, Fuyuhiko Motoi, Takeshi Naitoh, Yu Katayose, Yasuo Uchida, Sumio Ohtsuki, Tetsuya Terasaki, Michiaki Unno
Preoperative administration of cholic acid (CA) may be an option to increase the liver volume before elective liver resection surgery, so it is important to understand its effects on liver functionality for drug transport and metabolism. The purpose of this study is to clarify the absolute protein expression dynamics of transporters and metabolizing enzymes in the liver of mice fed with CA-containing diet for 5 days (CA1) and mice fed with CA-containing diet for 5 days followed by diet without CA for 7 days (CA2), in comparison with non-CA-fed control mice...
February 27, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28214689/paeoniflorin-ameliorates-cholestasis-via-regulating-hepatic-transporters-and-suppressing-inflammation-in-anit-fed-rats
#13
Yanling Zhao, Xuan He, Xiao Ma, Jianxia Wen, Pengyan Li, Jiabo Wang, Ruisheng Li, Yun Zhu, Shizhang Wei, Haotian Li, Xuelin Zhou, Kun Li, Honghong Liu, Xiaohe Xiao
Paeoniflorin has shown the obvious effect on cholestasis according to our previous research. However, its mechanism has not been absolutely explored yet. This study aims at evaluating the potential effect of paeoniflorin on alpha-naphthylisothiocyanate (ANIT) -induced cholestasis by inhibiting nuclear factor kappa-B (NF-κB) and simultaneously regulating hepatocyte transporters. Cholestasis was induced by administration of ANIT. The effect of paeoniflorin on serum indices such as total bilirubin (TBIL), direct bilirubin (DBIL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyltranspeptidase (γ-GT), total bile acid (TBA) and histopathology of liver were determined...
May 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28202906/bar502-a-dual-fxr-and-gpbar1-agonist-promotes-browning-of-white-adipose-tissue-and-reverses-liver-steatosis-and-fibrosis
#14
Adriana Carino, Sabrina Cipriani, Silvia Marchianò, Michele Biagioli, Chiara Santorelli, Annibale Donini, Angela Zampella, Maria Chiara Monti, Stefano Fiorucci
Non-alcoholic steatohepatitis (NASH) is a highly prevalent chronic liver disease. Here, we have investigated whether BAR502, a non-bile acid, steroidal dual ligand for FXR and GPBAR1, reverses steato-hepatitis in mice fed a high fat diet (HFD) and fructose. After 9 week, mice on HFD gained ≈30% of b.w (P < 0.01 versus naïve) and were insulin resistant. These overweighting and insulin resistant mice were randomized to receive HFD or HFD in combination with BAR502. After 18 weeks, HFD mice developed NASH like features with severe steato-hepatitis and fibrosis, increased hepatic content of triacylglycerol and cholesterol and expression of SREPB1c, FAS, ApoC2, PPARα and γ, α-SMA, α1 collagen and MCP1 mRNAs...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28199789/cholesterol-lowering-activity-of-tartary-buckwheat-protein
#15
Chengnan Zhang, Rui Zhang, Yuk Man Li, Ning Liang, Yimin Zhao, Hanyue Zhu, Zouyan He, Jianhui Liu, Wangjun Hao, Rui Jiao, Ka Ying Ma, Zhen-Yu Chen
Previous research has shown that Tartary buckwheat flour is capable of reducing plasma cholesterol. The present study was to examine the effect of rutin and Tartary buckwheat protein on plasma total cholesterol (TC) in hypercholesterolemia hamsters. In the first animal experiment, 40 male hamsters were divided into four groups fed either the control diet or one of the three experimental diets containing 8.2 mmol rutin, 8.2 mmol quercetin, or 2.5 g kg(-1) cholestyramine, respectively. Results showed that only cholestyramine but not rutin and its aglycone quercetin decreased plasma TC, which suggested that rutin was not the active ingredient responsible for plasma TC-lowering activity of Tartary buckwheat flour...
February 24, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28169529/deacetylated-konjac-glucomannan-is-less-effective-in-reducing-dietary-induced-hyperlipidemia-and-hepatic-steatosis-in-c57bl-6-mice
#16
Mei-Ying Li, Guan-Ping Feng, Hong Wang, Rui-Li Yang, Zhenlin Xu, Yuan-Ming Sun
Konjac gel foods that mainly consist of deacetylated konjac glucomannan (Da-KGM) are considered to have the same health benefits as native konjac glucomannan (KGM); however, no definitive data support this notion. The objective of this study was to compare the effects of Da-KGM and KGM on the hyperlipidemia and liver steatosis induced by high-fat diet feeding and to investigate the underlying molecular mechanisms. C57BL/6 mice were fed (1) normal chow diet, (2) high-fat diet, (3) HFD with KGM, or (4) HFD with Da-KGM for 10 weeks...
February 17, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28161535/4-o-sulfation-in-sea-cucumber-fucodians-contribute-to-reversing-dyslipidiaemia-caused-by-hfd
#17
Shan Li, Junhui Li, Zijian Zhi, Yaqin Hu, Jian Ge, Xingqian Ye, Ding Tian, Robert J Linhardt, Shiguo Chen
Fucodians extracted from sea cucumbers (SC-FUCs) possess linear chains with uniform repeating units. Sulfation patterns endow SC-FUCs unique structures and bioactivity. The present study investigated the anti-hyperlipidemic activity of two fucodians isolated from sea cucumbers Pearsonothuria graeffei (fuc-Pg) and Isostichopus badionotus (fuc-Ib). The results indicate fuc-Pg dominated with a 4-O-sulfation pattern shows strong activity in reducing body weight, regulating lipid disorder (TC, TG, HLD-C, and LDL-C level), improving liver function (liver weight, GOP, GPT, and TBA concentrations) and increasing adiponectin level (adiponectin concentration) caused by HFD...
June 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28130274/commensal-bacteria-at-the-crossroad-between-cholesterol-homeostasis-and-chronic-inflammation-in-atherosclerosis
#18
Kazuyuki Kasahara, Takeshi Tanoue, Tomoya Yamashita, Keiko Yodoi, Takuya Matsumoto, Takuo Emoto, Taiji Mizoguchi, Tomohiro Hayashi, Naoki Kitano, Naoto Sasaki, Koji Atarashi, Kenya Honda, Ken-Ichi Hirata
The gut microbiota were shown to play critical roles in the development of atherosclerosis, but the detailed mechanism is limited. The purpose of this study is to clarify the influence of gut microbiota on atherogenesis via lipid metabolism and systemic inflammation. Germ-free or conventionally raised (Conv) ApoE-deficient (ApoE(-/-)) mice were fed chow diet and euthanized at 20 weeks of age. We found that the lack of gut microbiota in ApoE(-/-) mice caused a significant increase in the plasma and hepatic cholesterol levels compared with Conv ApoE(-/-) mice...
March 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28127194/three-dimensional-perfused-human-in-vitro-model-of-non-alcoholic-fatty-liver-disease
#19
Tomasz Kostrzewski, Terri Cornforth, Sophie A Snow, Larissa Ouro-Gnao, Cliff Rowe, Emma M Large, David J Hughes
AIM: To develop a human in vitro model of non-alcoholic fatty liver disease (NAFLD), utilising primary hepatocytes cultured in a three-dimensional (3D) perfused platform. METHODS: Fat and lean culture media were developed to directly investigate the effects of fat loading on primary hepatocytes cultured in a 3D perfused culture system. Oil Red O staining was used to measure fat loading in the hepatocytes and the consumption of free fatty acids (FFA) from culture medium was monitored...
January 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28095641/melatonin-ameliorates-alcohol-induced-bile-acid-synthesis-by-enhancing-mir-497-expression
#20
Yong Deuk Kim, Seung-Lark Hwang, Eun-Joo Lee, Hyeong-Mi Kim, Myung-Jin Chung, Ahmed K Elfadl, Sung-Eun Lee, Balachandar Nedumaran, Robert A Harris, Kyu-Shik Jeong
Alcoholic liver disease is a major cause of chronic liver disease worldwide, and cannabinoid receptor type 1 (CB1R) is involved in a diverse metabolic diseases. B-cell translocation gene 2 (BTG2) and yin yang 1 (YY1) are a potent regulator of biological conditions. Melatonin plays a crucial role in regulating diverse physiological functions and metabolic homeostasis. MicroRNAs are key regulators of various biological processes. Herein, we demonstrate that melatonin improves bile acid synthesis in the liver of alcohol-fed mice by controlling miR-497 expression...
March 2017: Journal of Pineal Research
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