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https://www.readbyqxmd.com/read/28334792/gwas-identifies-population-specific-new-regulatory-variants-in-fut6-associated-with-plasma-b12-concentrations-in-indians
#1
Suraj S Nongmaithem, Charudatta V Joglekar, Ghattu V Krishnaveni, Sirazul A Sahariah, Meraj Ahmad, Swetha Ramachandran, Meera Gandhi, Harsha Chopra, Anand Pandit, Ramesh D Potdar, Caroline Hd Fall, Chittaranjan S Yajnik, Giriraj R Chandak
Vitamin B12 is an important cofactor in one-carbon metabolism whose dysregulation is associated with various clinical conditions. Indians have a high prevalence of B12 deficiency but little is known about the genetic determinants of circulating B12 concentrations in Indians. We performed a genome-wide association study in 1001 healthy participants in the Pune Maternal Nutrition Study (PMNS), replication studies in 3418 individuals from other Indian cohorts and by meta-analysis identified new variants, rs3760775 (p = 1...
February 27, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28331449/cyclin-d1-in-the-liver-role-of-noncanonical-signaling-in-liver-steatosis-and-hormone-regulation
#2
Kelley G Núñez, Janet Gonzalez-Rosario, Paul T Thevenot, Ari J Cohen
BACKGROUND: Cyclin D1 is an important protein for cell cycle progression; however, functions independent of the cell cycle have been described in the liver. Cyclin D1 is also involved in DNA repair, is overexpressed in many cancers, and functions as a proto-oncogene. The lesser-known roles of Cyclin D1, specifically in hepatocytes, impact liver steatosis and hormone regulation in the liver. METHODS: A comprehensive search of PubMed was conducted using the keywords Cyclin D1, steatosis, lipogenesis, and liver transplantation...
2017: Ochsner Journal
https://www.readbyqxmd.com/read/28322895/baicalin-benefits-the-anti-hbv-therapy-via-inhibiting-hbv-viral-rnas
#3
Hai Huang, Wei Zhou, Haiyan Zhu, Pei Zhou, Xunlong Shi
BACKGROUND: Although current antiviral treatments (nucleoside analogs, NAs) for chronic hepatitis B virus (HBV) infection are effective in suppressing HBV-DNA replication, their clinical outcomes can be compromised by the increasing drug resistance and the inefficiency in promoting HBsAg/HBeAg seroconversion. OBJECTIVES: In this study, we will explore possible effects and mechanism of a natural product baicalin (BA) with the anti-HBV efficacy of entecavir (ETV), a first-line anti-HBV drug, in HBV-DNA, HBsAg/HBeAg seroconversion and drug-resistance...
March 18, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28302129/cholesterol-lowing-effect-of-taurine-in-hepg2-cell
#4
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/28230250/metformin-attenuates-angiotensin-ii-induced-tgf%C3%AE-1-expression-by-targeting-hepatocyte-nuclear-factor-4%C3%AE
#5
Ruifei Chen, Yenan Feng, Jimin Wu, Yao Song, Hao Li, Qiang Shen, Dan Li, Jianshu Zhang, Zhizhen Lu, Han Xiao, Youyi Zhang
BACKGROUND AND PURPOSE: Metformin, a small molecule antihyperglycaemic agent, is well-known as an AMP-activated protein kinase (AMPK) activator and protects against cardiac fibrosis. However, the underlying mechanisms remain elusive. Transforming growth factor-β1 (TGFβ1) is a key cytokine mediating cardiac fibrosis. Here, we investigated the effects of metformin on TGFβ1 production induced by angiotensin II (AngII) and the underlying mechanisms. EXPERIMENTAL APPROACH: Wild-type and AMPKα2(-/-) C57BL/6 mice were subcutaneously injected with metformin or saline and infused with AngII (3 mg kg(-1) day(-1) ) for 7 days...
February 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28217257/regulation-of-hepatic-microrna-expression-by-hepatocyte-nuclear-factor-4-alpha
#6
Hong Lu, Xiaohong Lei, Jerry Liu, Curtis Klaassen
AIM: To uncover the role of hepatocyte nuclear factor 4 alpha (HNF4α) in regulating hepatic expression of microRNAs. METHODS: Microarray and real-time PCR were used to determine hepatic expression of microRNAs in young-adult mice lacking Hnf4α expression in liver (Hnf4α-LivKO). Integrative genomics viewer software was used to analyze the public chromatin immunoprecipitation-sequencing datasets for DNA-binding of HNF4α, RNA polymerase-II, and histone modifications to loci of microRNAs in mouse liver and human hepatoma cells...
February 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28196117/the-transcriptional-activity-of-hepatocyte-nuclear-factor-4-alpha-is-inhibited-via-phosphorylation-by-erk1-2
#7
Borbála Vető, Dóra Bojcsuk, Caroline Bacquet, Judit Kiss, Szabolcs Sipeki, Ludovic Martin, László Buday, Bálint L Bálint, Tamás Arányi
Hepatocyte nuclear factor 4 alpha (HNF4α) nuclear receptor is a master regulator of hepatocyte development, nutrient transport and metabolism. HNF4α is regulated both at the transcriptional and post-transcriptional levels by different mechanisms. Several kinases (PKA, PKC, AMPK) were shown to phosphorylate and decrease the activity of HNF4α. Activation of the ERK1/2 signalling pathway, inducing proliferation and survival, inhibits the expression of HNF4α. However, based on our previous results we hypothesized that HNF4α is also regulated at the post-transcriptional level by ERK1/2...
2017: PloS One
https://www.readbyqxmd.com/read/28185444/effect-of-cis-palmitoleic-acid-an-omega-7-fatty-acid-supplementation-on-inflammation-and-expression-of-hnf4%C3%AE-hnf4%C3%AE-and-il-6-in-patients-with-ulcerative-colitis-a-double-blind-randomized-pilot-study
#8
Nalley Bueno-Hernandez, Maria S Sixtos-Alonso, Maria Del Pilar Milke GARCíA, Jesus K Yamamoto-Furusho
BACKGROUND: Cis-palmitoleic acid (Omega-7 fatty acid) is a monounsaturated fatty acid (MUFA) associated with anti-inflammatory process through specific protein interactions such as HNF4γ and HNF4α, these two genes are related to the immune response in ulcerative colitis (UC) they may act as a mediator of anti- inflammatory action. The aim of this study was to evaluate the effect of Cis- palmitoleic acid supplementation on inflammatory activity and the expression of genes HNF4γ, HNF4α and IL-6 in the colonic mucosa of patients with active UC...
February 9, 2017: Minerva Gastroenterologica e Dietologica
https://www.readbyqxmd.com/read/28163723/activin-a-modulates-cripto-1-hnf4%C3%AE-cells-to-guide-cardiac-differentiation-from-human-embryonic-stem-cells
#9
Robin Duelen, Guillaume Gilbert, Abdulsamie Patel, Nathalie de Schaetzen, Liesbeth De Waele, Llewelyn Roderick, Karin R Sipido, Catherine M Verfaillie, Gunnar M Buyse, Lieven Thorrez, Maurilio Sampaolesi
The use of human pluripotent stem cells in basic and translational cardiac research requires efficient differentiation protocols towards cardiomyocytes. In vitro differentiation yields heterogeneous populations of ventricular-, atrial-, and nodal-like cells hindering their potential applications in regenerative therapies. We described the effect of the growth factor Activin A during early human embryonic stem cell fate determination in cardiac differentiation. Addition of high levels of Activin A during embryoid body cardiac differentiation augmented the generation of endoderm derivatives, which in turn promoted cardiomyocyte differentiation...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28108339/transcriptome-analysis-of-the-effect-of-polyunsaturated-fatty-acids-against-vibrio-vulnificus-infection-in-oreochromis-niloticus
#10
Chieh-Yu Pan, Yu-Hao Liu, Hong-Yi Gong, Jyh-Yih Chen
Vibrio vulnificus infection causes severe economic losses in Oreochromis niloticus aquaculture by inducing pro-inflammatory cytokines, that lead to inflammation and mortality. Omega-3 fatty acids, such as Docosahexaenoic acid (DHA) and Eicosapentaenoic acid (EPA), have been reported for their anti-inflammatory and antibacterial abilities in murine and zebrafish models. However, the anti-inflammatory and antibacterial functions of DHA and EPA in commercial aquaculture organisms such as Oreochromis niloticus remain unknown...
January 17, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28089783/characterization-of-rat-or-human-hepatocytes-cultured-in-microphysiological-systems-mps-to-identify-hepatotoxicity
#11
Shih-Yu Chang, Jenna L Voellinger, Kirk P Van Ness, Brian Chapron, Rachel M Shaffer, Thomas Neumann, Collin C White, Terrance J Kavanagh, Edward J Kelly, David L Eaton
The liver is the main site for drug and xenobiotics metabolism, including inactivation or bioactivation. In order to improve the predictability of drug safety and efficacy in clinical development, and to facilitate the evaluation of the potential human health effects from exposure to environmental contaminants, there is a critical need to accurately model human organ systems such as the liver in vitro. We are developing a microphysiological system (MPS) based on a new commercial microfluidic platform (Nortis, Inc...
January 13, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28065467/lung-adenocarcinoma-with-muc4-expression-is-associated-with-smoking-status-her2-protein-expression-and-poor-prognosis-clinicopathologic-analysis-of-338-cases
#12
Mariyo Rokutan-Kurata, Akihiko Yoshizawa, Shinji Sumiyoshi, Makoto Sonobe, Toshi Menju, Masanobu Momose, Mizuki Koyama, Shohei Shigeto, Masakazu Fujimoto, Meng Zhang, Satoshi Morita, Hiroshi Date, Hironori Haga
BACKGROUND: MUC4 is a transmembrane glycoprotein that plays a role in the cell growth signaling pathway and has been studied in various organ malignancies. This study aimed to analyze MUC4 expression in resected lung adenocarcinomas (ADCs) to define the clinicopathologic characteristics of MUC4-positive cancers. PATIENTS AND METHODS: Immunohistochemical MUC4 analysis was performed using tissue microarray slides containing 338 lung ADCs. Associations between MUC4 expression and the following clinicopathologic parameters were evaluated: sex; age; smoking status; tumor stage; tumor grade; lymphovascular invasion; pleural invasion; TTF-1 and HNF4α expression; EGFR, KRAS, BRAF, and HER2 mutation status; and ALK and ROS1 fusion status...
December 2, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28039934/prostaglandin-e2-promotes-hepatic-bile-acid-synthesis-by-an-e-prostanoid-receptor-3-mediated-hepatocyte-nuclear-receptor-4%C3%AE-cholesterol-7%C3%AE-hydroxylase-pathway-in-mice
#13
Shuai Yan, Juan Tang, Yuyao Zhang, Yuanyang Wang, Shengkai Zuo, Yujun Shen, Qianqian Zhang, Di Chen, Yu Yu, Kai Wang, Sheng-Zhong Duan, Ying Yu
Prostaglandin E2 (PGE2 ) is an important lipid mediator of inflammation. However, whether and how PGE2 regulates hepatic cholesterol metabolism remains unknown. We found that expression of the PGE2 receptor, E prostanoid receptor 3 (EP3) expression is remarkably increased in hepatocytes in response to hyperlipidemic stress. Hepatocyte-specific deletion of EP3 receptor (EP3(hep-/-) ) results in hypercholesterolemia and augments diet-induced atherosclerosis in low-density lipoprotein receptor knockout (Ldlr(-/-) ) mice...
November 5, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28003637/differential-toxicity-between-perfluorooctane-sulfonate-pfos-and-perfluorooctanoic-acid-pfoa
#14
Shuji Tsuda
Perfluoroalkyl substances (PFASs) are persistent environmental contaminants. Perfluorooctane sulfonate (PFOS) and Perfluorooctanoic acid (PFOA) are representatives of PFASs. Recently, the U.S. Environmental Protection Agency (US EPA) set the health advisory level as 70 parts per trillion for lifetime exposure to PFOS and PFOA from drinking water, based on the EPA's 2016 Health Effects Support Documents. Then, a monograph on PFOA was made available online by the International Agency for Research on Cancer, where the agency classified PFOA as "possibly carcinogenic to humans" (Group 2B)...
2016: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28000155/hepatocyte-nuclear-factor-4-alpha-promotes-definitive-endoderm-differentiation-from-human-induced-pluripotent-stem-cells
#15
Morifumi Hanawa, Kazuo Takayama, Fuminori Sakurai, Masashi Tachibana, Hiroyuki Mizuguchi
Hepatocyte nuclear factor 4 alpha (HNF4α) is a key transcription factor for liver development. Although HNF4α is necessary for hepatoblast differentiation, the function of HNF4α before the hepatoblast differentiation, such as in definitive endoderm differentiation, is not well known. In addition, it is known that there are nine HNF4α isoforms, but the expression and function of each HNF4α isoform during the definitive endoderm differentiation is also not clear. In this study, we examined the expression pattern of HNF4α and its functions in the definitive endoderm differentiation from human induced pluripotent stem (iPS) cells...
December 21, 2016: Stem Cell Reviews
https://www.readbyqxmd.com/read/27932985/pregnane-x-receptor-pxr-mediated-gene-repression-and-cross-talk-of-pxr-with-other-nuclear-receptors-via-coactivator-interactions
#16
REVIEW
Petr Pavek
Pregnane X receptor is a ligand-activated nuclear receptor (NR) that mainly controls inducible expression of xenobiotics handling genes including biotransformation enzymes and drug transporters. Nowadays it is clear that PXR is also involved in regulation of intermediate metabolism through trans-activation and trans-repression of genes controlling glucose, lipid, cholesterol, bile acid, and bilirubin homeostasis. In these processes PXR cross-talks with other NRs. Accumulating evidence suggests that the cross-talk is often mediated by competing for common coactivators or by disruption of coactivation and activity of other transcription factors by the ligand-activated PXR...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27909409/3-5-3-triiodo-l-thyronine-and-3-5-diiodo-l-thyronine-affected-metabolic-pathways-in-liver-of-ldl-receptor-deficient-mice
#17
Maria Moreno, Elena Silvestri, Maria Coppola, Ira J Goldberg, Li-Shin Huang, Anna M Salzano, Fulvio D'Angelo, Joel R Ehrenkranz, Fernando Goglia
3,5,3'-triiodo-L-thyronine (T3) and 3,5-diiodo-L-thyronine (T2), when administered to a model of familial hypercholesterolemia, i.e., low density lipoprotein receptor (LDLr)-knockout (Ldlr(-/-)) mice fed with a Western type diet (WTD), dramatically reduce circulating total and very low-density lipoprotein/LDL cholesterol with decreased liver apolipoprotein B (ApoB) production. The aim of the study was to highlight putative molecular mechanisms to manage cholesterol levels in the absence of LDLr. A comprehensive comparative profiling of changes in expression of soluble proteins in livers from Ldlr(-/-) mice treated with either T3 or T2 was performed...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27903283/systematic-analysis-of-chromatin-interactions-at-disease-associated-loci-links-novel-candidate-genes-to-inflammatory-bowel-disease
#18
Claartje A Meddens, Magdalena Harakalova, Noortje A M van den Dungen, Hassan Foroughi Asl, Hemme J Hijma, Edwin P J G Cuppen, Johan L M Björkegren, Folkert W Asselbergs, Edward E S Nieuwenhuis, Michal Mokry
BACKGROUND: Genome-wide association studies (GWAS) have revealed many susceptibility loci for complex genetic diseases. For most loci, the causal genes have not been identified. Currently, the identification of candidate genes is predominantly based on genes that localize close to or within identified loci. We have recently shown that 92 of the 163 inflammatory bowel disease (IBD)-loci co-localize with non-coding DNA regulatory elements (DREs). Mutations in DREs can contribute to IBD pathogenesis through dysregulation of gene expression...
November 30, 2016: Genome Biology
https://www.readbyqxmd.com/read/27878730/mesenchymal-epithelial-transition-in-culture-of-stromal-progenitor-cells-isolated-from-the-liver-of-a-patient-with-alcoholic-cirrhosis
#19
I V Kholodenko, R V Kholodenko, G V Manukyan, V V Burunova, K N Yarygin
The cells isolated from biopsy specimen of a patient with alcoholic liver cirrhosis and cultured under standard conditions for obtaining stromal cell culture clearly diverged during early passages into two morphologically and phenotypically different subtypes: epithelial and mesenchymal. Mesenchymal cells expressed CD90 and CD44 and epithelial cells expressed CD166, CD227, and hepatocyte growth factor receptor Met. Starting from passage 6, the culture underwent spontaneous morphological changes and by passages 8-10 contained only epithelium-like cells...
November 2016: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27875772/hnf4%C3%AE-is-a-key-gene-that-can-generate-columnar-metaplasia-in-oesophageal-epithelium
#20
Benjamin J Colleypriest, Zoë D Burke, Leonard P Griffiths, Yu Chen, Wei-Yuan Yu, Ramiro Jover, Michael Bock, Leigh Biddlestone, Jonathan M Quinlan, Stephen G Ward, J Mark Farrant, Jonathan M W Slack, David Tosh
Barrett's metaplasia is the only known morphological precursor to oesophageal adenocarcinoma and is characterized by replacement of stratified squamous epithelium by columnar epithelium. The cell of origin is uncertain and the molecular mechanisms responsible for the change in cellular phenotype are poorly understood. We therefore explored the role of two transcription factors, Cdx2 and HNF4α in the conversion using primary organ cultures. Biopsy samples from cases of human Barrett's metaplasia were analysed for the presence of CDX2 and HNF4α...
January 2017: Differentiation; Research in Biological Diversity
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