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https://www.readbyqxmd.com/read/28922406/loss-of-liver-specific-and-sexually-dimorphic-gene-expression-by-aryl-hydrocarbon-receptor-activation-in-c57bl-6-mice
#1
Rance Nault, Kelly A Fader, Jack R Harkema, Tim Zacharewski
The aryl hydrocarbon receptor (AhR) is a highly conserved transcription factor that mediates a broad spectrum of species-, strain-, sex-, age-, tissue-, and cell-specific responses elicited by structurally diverse ligands including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Dose-dependent effects on liver-specific and sexually dimorphic gene expression were examined in male and female mice gavaged with TCDD every 4 days for 28 or 92 days. RNA-seq data revealed the coordinated repression of 181 genes predominately expressed in the liver including albumin (3...
2017: PloS One
https://www.readbyqxmd.com/read/28885228/genetic-and-transcriptomic-bases-of-intestinal-epithelial-barrier-dysfunction-in-inflammatory-bowel-disease
#2
Maaike Vancamelbeke, Tim Vanuytsel, Ricard Farré, Sare Verstockt, Marc Ferrante, Gert Van Assche, Paul Rutgeerts, Frans Schuit, Séverine Vermeire, Ingrid Arijs, Isabelle Cleynen
BACKGROUND: Intestinal barrier defects are common in patients with inflammatory bowel disease (IBD). To identify which components could underlie these changes, we performed an in-depth analysis of epithelial barrier genes in IBD. METHODS: A set of 128 intestinal barrier genes was selected. Polygenic risk scores were generated based on selected barrier gene variants that were associated with Crohn's disease (CD) or ulcerative colitis (UC) in our study. Gene expression was analyzed using microarray and quantitative reverse transcription polymerase chain reaction...
September 6, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28870599/hepatocyte-nuclear-factor-4a-improves-hepatic-differentiation-of-immortalized-adult-human-hepatocytes-and-improves-liver-function-and-survival
#3
Hua-Lian Hang, Xin-Yu Liu, Hai-Tian Wang, Ning Xu, Jian-Min Bian, Jian-Jun Zhang, Lei Xia, Qiang Xia
Immortalized human hepatocytes (IHH) could provide an unlimited supply of hepatocytes, but insufficient differentiation and phenotypic instability restrict their clinical application. This study aimed to determine the role of hepatocyte nuclear factor 4A (HNF4A) in hepatic differentiation of IHH, and whether encapsulation of IHH overexpressing HNF4A could improve liver function and survival in rats with acute liver failure (ALF). Primary human hepatocytes were transduced with lentivirus-mediated catalytic subunit of human telomerase reverse transcriptase (hTERT) to establish IHH...
September 6, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28862987/mody-in-ukraine-genes-clinical-phenotypes-and-treatment
#4
Evgenia Globa, Nataliya Zelinska, Lenka Elblova, Petra Dusatkova, Ondrej Cinek, Jan Lebl, Kevin Colclough, Sian Ellard, Stepanka Pruhova
BACKGROUND: Maturity-onset diabetes of the young (MODY) has not been previously studied in Ukraine. We investigated the genetic etiology in a selected cohort of patients with diabetes diagnosed before 18 years of age, and in their family members. METHODS: Genetic testing of the most prevalent MODY genes (GCK, HNF1A, HNF4A, HNF1B and INS) was undertaken for 36 families (39 affected individuals) by Sanger or targeted next generation sequencing. RESULTS: A genetic diagnosis of MODY was made in 15/39 affected individuals from 12/36 families (33%)...
September 1, 2017: Journal of Pediatric Endocrinology & Metabolism: JPEM
https://www.readbyqxmd.com/read/28855921/diagnosis-and-treatment-of-hyperinsulinaemic-hypoglycaemia-and-its-implications-for-paediatric-endocrinology
#5
REVIEW
Huseyin Demirbilek, Sofia A Rahman, Gonul Gulal Buyukyilmaz, Khalid Hussain
Glucose homeostasis requires appropriate and synchronous coordination of metabolic events and hormonal activities to keep plasma glucose concentrations in a narrow range of 3.5-5.5 mmol/L. Insulin, the only glucose lowering hormone secreted from pancreatic β-cells, plays the key role in glucose homeostasis. Insulin release from pancreatic β-cells is mainly regulated by intracellular ATP-generating metabolic pathways. Hyperinsulinaemic hypoglycaemia (HH), the most common cause of severe and persistent hypoglycaemia in neonates and children, is the inappropriate secretion of insulin which occurs despite low plasma glucose levels leading to severe and persistent hypoketotic hypoglycaemia...
2017: International Journal of Pediatric Endocrinology
https://www.readbyqxmd.com/read/28838957/vascular-endothelium-plays-a-key-role-in-directing-pulmonary-epithelial-cell-differentiation
#6
Jiayi Yao, Pierre J Guihard, Xiuju Wu, Ana M Blazquez-Medela, Melissa J Spencer, Medet Jumabay, Peter Tontonoz, Alan M Fogelman, Kristina I Boström, Yucheng Yao
The vascular endothelium is critical for induction of appropriate lineage differentiation in organogenesis. In this study, we report that dysfunctional pulmonary endothelium, resulting from the loss of matrix Gla protein (MGP), causes ectopic hepatic differentiation in the pulmonary epithelium. We demonstrate uncontrolled induction of the hepatic growth factor (HGF) caused by dysregulated cross talk between pulmonary endothelium and epithelium in Mgp-null lungs. Elevated HGF induced hepatocyte nuclear factor 4 α (Hnf4a), which competed with NK2 homeobox 1 (Nkx2...
August 24, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28792091/the-combination-of-mir-122-overexpression-and-let-7f-silencing-induces-hepatic-differentiation-of-adipose-tissue-derived-stem-cells
#7
Nahid Davoodian, Abbas S Lotfi, Masoud Soleimani, Hori Ghaneialvar
Human adipose tissue-derived stem cells (hADSCs) have been considered as a promising source for cell therapy of liver diseases due to their accessibility, abundance, and expression of hepatocyte markers. Currently, the important role of certain microRNAs (miRNAs) has been reported during hepatic differentiation of stem cells. However, the combination effect of miRNAs on hepatic differentiation of these cells needs to be more investigated. The present study seeks to determine whether the combination of miRNAs can enhance hepatic differentiation of hADSCs in the absence of any other stimulation...
August 9, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28782802/dhqz-17-a-potent-inhibitor-of-the-transcription-factor-hnf4a-suppresses-tumorigenicity-of-head-and-neck-squamous-cell-carcinoma-in-vivo
#8
Shilpa Tentu, Kumarswamyreddy Nandarapu, Prakash Muthuraj, Kesavan Venkitasamy, Ganesh Venkatraman, Suresh K Rayala
A series of 2, 3-dihydroquinazolinone derivatives were synthesized, characterized and their anticancer activity was determined. Among the compounds synthesized and screened, one compound (17) showed potent anticancer activity against human head and neck squamous cell carcinoma cell line, SCC131 and was non-toxic to normal cells. The compound inhibited the growth of SCC131 cells, with an IC50 of 1.75 μM, triggered apoptotic mode of cell death and caused tumor regression of SCC131 tumor xenografts in athymic mice...
August 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28726547/three-dimensional-bio-printing-of-hepatic-structures-with-direct-converted-hepatocyte-like-cells
#9
Kyojin Kang, Yohan Kim, Seung Bum Lee, Ji Sook Kim, Sua Park, Wan-Doo Kim, Heung-Mo Yang, Sung-Joo Kim, Jaemin Jeong, Dongho Choi
Three-dimensional (3D) bio-printing technology is a promising new technology in the field of bio-artificial organ generation with regard to overcoming the limitations of organ supply. The cell source for bio-printing is very important. Here, we generated 3D hepatic scaffold with mouse induced hepatocyte-like cells (miHeps), and investigated whether their function was improved after transplantation in vivo. To generate miHeps, mouse embryonic fibroblasts were transformed with pMX retroviruses individually expressing hepatic transcription factors Hnf4a and Foxa3...
July 20, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28717196/trib1-is-a-positive-regulator-of-hepatocyte-nuclear-factor-4-alpha
#10
Sébastien Soubeyrand, Amy Martinuk, Ruth McPherson
The TRIB1 locus has been linked to both cardiovascular disease and hepatic steatosis. Recent efforts have revealed TRIB1 to be a major regulator of liver function, largely, but not exclusively, via CEBPA degradation. We recently uncovered a functional interaction between TRIB1 and HNF4A, another key regulator of hepatic function, whose molecular underpinnings remained to be clarified. Here we have extended these findings. In hepatoma models, HNF4A levels were found to depend on TRIB1, independently of its impact on CEBPA...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28693455/fainting-fanconi-syndrome-clarified-by-proxy-a-case-report
#11
Stephen Benedict Walsh, Robert Unwin, Robert Kleta, William Van't Hoff, Paul Bass, Khalid Hussain, Sian Ellard, Detlef Bockenhauer
BACKGROUND: Rare diseases may elude diagnosis due to unfamiliarity of the treating physicians with the specific disorder. Yet, advances in genetics have tremendously enhanced our ability to establish specific and sometimes surprising diagnoses. CASE PRESENTATION: We report a case of renal Fanconi syndrome associated with intermittent hypoglycemic episodes, the specific cause for which remained elusive for over 30 years, despite numerous investigations, including three kidney and one liver biopsy...
July 11, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28688048/susceptibility-background-for-type-2-diabetes-in-eleven-mexican-indigenous-populations-hnf4a-gene-analysis
#12
M A Granados-Silvestre, M G Ortiz-López, J Granados, S Canizales-Quinteros, Rosenda I Peñaloza-Espinosa, C Lechuga, V Acuña-Alonzo, K Sánchez-Pozos, M Menjivar
The genetic risk of developing type 2 diabetes (T2D) increases in parallel with the proportion of Native American ancestry. Mestizo Mexicans have a 70% Native Amerindian genetic background. The T130I polymorphism in the HNF4A gene has been associated with early-onset T2D in mestizo Mexicans. Thus, the aim of the present study was to evaluate the frequency and relationship of the T130I variant in the HNF4A gene with risk factors for developing T2D in eleven indigenous groups from Mexico. In two groups, all exons of the HNF4A gene were directly sequenced; in the remaining the T130I polymorphism was analyzed by restriction fragment length polymorphism...
July 7, 2017: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/28684784/probing-the-missing-mature-%C3%AE-cell-proteomic-landscape-in-differentiating-patient-ipsc-derived-cells
#13
Heidrun Vethe, Yngvild Bjørlykke, Luiza M Ghila, Joao A Paulo, Hanne Scholz, Steven P Gygi, Simona Chera, Helge Ræder
MODY1 is a maturity-onset monogenic diabetes, caused by heterozygous mutations of the HNF4A gene. To date the cellular and molecular mechanisms leading to disease onset remain largely unknown. In this study, we demonstrate that insulin-positive cells can be generated in vitro from human induced pluripotent stem cells (hiPSCs) derived from patients carrying a non-sense HNF4A mutation, proving for the first time, that a human HNF4A mutation is neither blocking the expression of the insulin genes nor the development of insulin-producing cells in vitro...
July 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28673327/special-role-of-jun-in-papillary-thyroid-carcinoma-based-on-bioinformatics-analysis
#14
Wenzheng Chen, Qingfeng Liu, Yunxia Lv, Debin Xu, Wanzhi Chen, Jichun Yu
BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common malignancy in thyroid tissue, and the number of patients with PTC has been increasing in recent years. Discovering the mechanism of PTC genesis and progression and finding new potential diagnostic biomarkers/therapeutic target genes of PTC are of great significance. METHODS: In this work, the datasets GSE3467 and GSE3678 were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified with the limma package in R...
July 3, 2017: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28648900/tet-catalyzed-5-hydroxymethylation-precedes-hnf4a-promoter-choice-during-differentiation-of-bipotent-liver-progenitors
#15
Pierre-Benoit Ancey, Szilvia Ecsedi, Marie-Pierre Lambert, Fazlur Rahman Talukdar, Marie-Pierre Cros, Denise Glaise, Diana Maria Narvaez, Veronique Chauvet, Zdenko Herceg, Anne Corlu, Hector Hernandez-Vargas
Understanding the processes that govern liver progenitor cell differentiation has important implications for the design of strategies targeting chronic liver diseases, whereby regeneration of liver tissue is critical. Although DNA methylation (5mC) and hydroxymethylation (5hmC) are highly dynamic during early embryonic development, less is known about their roles at later stages of differentiation. Using an in vitro model of hepatocyte differentiation, we show here that 5hmC precedes the expression of promoter 1 (P1)-dependent isoforms of HNF4A, a master transcription factor of hepatocyte identity...
July 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28642491/a-cross-species-approach-to-identify-transcriptional-regulators-exemplified-for-dnajc22-and-hnf4a
#16
A C Aschenbrenner, K Bassler, M Brondolin, L Bonaguro, P Carrera, K Klee, T Ulas, J L Schultze, M Hoch
There is an enormous need to make better use of the ever increasing wealth of publicly available genomic information and to utilize the tremendous progress in computational approaches in the life sciences. Transcriptional regulation of protein-coding genes is a major mechanism of controlling cellular functions. However, the myriad of transcription factors potentially controlling transcription of any given gene makes it often difficult to quickly identify the biological relevant transcription factors. Here, we report on the identification of Hnf4a as a major transcription factor of the so far unstudied DnaJ heat shock protein family (Hsp40) member C22 (Dnajc22)...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28628668/dose-dependent-effects-of-gamma-radiation-on-the-early-zebrafish-development-and-gene-expression
#17
Selma Hurem, Leonardo Martín Martín, Dag Anders Brede, Eystein Skjerve, Rasoul Nourizadeh-Lillabadi, Ole Christian Lind, Terje Christensen, Vidar Berg, Hans-Christian Teien, Brit Salbu, Deborah Helen Oughton, Peter Aleström, Jan Ludvig Lyche
Ionizing radiation from natural sources or anthropogenic activity has the potential to cause oxidative stress or genetic damage in living organisms, through the ionization and excitation of molecules and the subsequent production of free radicals and reactive oxygen species (ROS). The present work focuses on radiation-induced biological effects using the zebrafish (Danio rerio) vertebrate model. Changes in developmental traits and gene expression in zebrafish were assessed after continuous external gamma irradiation (0...
2017: PloS One
https://www.readbyqxmd.com/read/28605664/soy-compared-with-milk-protein-in-a-western-diet-changes-fecal-microbiota-and-decreases-hepatic-steatosis-in-obese-oletf-rats
#18
Matthew R Panasevich, Colin M Schuster, Kathryn E Phillips, Grace M Meers, Sree V Chintapalli, Umesh D Wankhade, Kartik Shankar, Dustie N Butteiger, Elaine S Krul, John P Thyfault, R Scott Rector
Soy protein is effective at preventing hepatic steatosis; however, the mechanisms are poorly understood. We tested the hypothesis that soy vs. dairy protein-based diet would alter microbiota and attenuate hepatic steatosis in hyperphagic Otsuka Long-Evans Tokushima fatty (OLETF) rats. Male OLETF rats were randomized to "Western" diets containing milk protein isolate (MPI), soy protein isolate (SPI) or 50:50 MPI/SPI (MS) (n=9-10/group; 21% kcal protein) for 16 weeks. SPI attenuated (P<.05) fat mass and percent fat by ~10% compared with MS, but not compared with MPI...
August 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28597946/comprehensive-screening-for-monogenic-diabetes-in-89-japanese-children-with-insulin-requiring-antibody-negative-type-1-diabetes
#19
Kikumi Ushijima, Maki Fukami, Tadayuki Ayabe, Satoshi Narumi, Misako Okuno, Akie Nakamura, Toshikazu Takahashi, Kenji Ihara, Kazuhiro Ohkubo, Emiko Tachikawa, Shoji Nakayama, Junichi Arai, Nobuyuki Kikuchi, Toru Kikuchi, Tomoyuki Kawamura, Tatsuhiko Urakami, Kenichiro Hata, Kazuhiko Nakabayashi, Yoichi Matsubara, Shin Amemiya, Tsutomu Ogata, Ichiro Yokota, Shigetaka Sugihara
BACKGROUND: Mutations in causative genes for neonatal diabetes or maturity-onset diabetes of the young have been identified in multiple patients with autoantibody-negative type 1 diabetes (T1D). OBJECTIVES: We aimed to clarify the prevalence and phenotypic characteristics of monogenic abnormalities among 89 children with autoantibody-negative insulin-requiring T1D. METHODS: Mutations in 30 genes were screened using next-generation sequencing, and copy-number alterations of 4 major causative genes were examined using multiplex-ligation-dependent probe amplification...
June 9, 2017: Pediatric Diabetes
https://www.readbyqxmd.com/read/28591938/variants-in-mody-genes-associated-with-maternal-lipids-profiles-in-second-trimester-of-pregnancy
#20
Xiaojing Wang, Wei Li, Liangkun Ma, Fan Ping, Juntao Liu, Xueyan Wu, Jiangfeng Mao, Xi Wang, Min Nie
BACKGROUND: Dyslipidemia during pregnancy increases the risk of complications of pregnancy. Lipid profiles have a strong genetic determinant and numerous susceptibility loci have been identified. However, very few studies have focused on the association of lipid-related loci and maternal serum lipids during pregnancy. For the first time, we investigated the association of common variants in three maturity onset diabetes of the young (MODY) genes (HNF1A, HNF4A and HNF1B) with serum lipid concentrations and glucose metabolism related quantitative traits in the second trimester of pregnancy...
June 2017: Journal of Gene Medicine
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