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https://www.readbyqxmd.com/read/28498607/human-hepatocellular-carcinomas-with-a-periportal-phenotype-have-the-lowest-potential-for-early-recurrence-after-curative-resection
#1
Romain Désert, Florian Rohart, Frédéric Canal, Marie Sicard, Mireille Desille, Stéphanie Renaud, Bruno Turlin, Pascale Bellaud, Christine Perret, Bruno Clément, Kim-Anh Lê Cao, Orlando Musso
Hepatocellular carcinomas (HCCs) exhibit a diversity of molecular phenotypes, raising major challenges in clinical management. HCCs detected by surveillance programs at an early stage are candidates for potentially curative therapies (local ablation, resection or transplantation). In the long term, transplantation provides the lowest recurrence rates. Treatment allocation is based on tumor number, size, vascular invasion, performance status, functional liver reserve and on the prediction of early (< 2 years) recurrence, which reflects the intrinsic aggressiveness of the tumor...
May 12, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28470094/dna-methylation-controls-unmethylated-transcription-start-sites-in-the-genome-in-trans
#2
David Cheishvili, Steffan Christiansen, Rebecca Stochinsky, Anne-Sophie Pepin, Daniel M Sapozhnikov, Rudy Zhou, Lauren Schmeltzer, Sergey Dymov, Moshe Szyf
AIM: DNA methylation downregulates transcription. However, a large number of genes, which are unmethylated in the promoter region, are inactive. We tested the hypothesis that these genes are regulated by DNA methylation of upstream regulators. METHODS: We inhibited DNMT1 with 5-aza-2'-deoxycytidine or depleted it with shRNA to map the transcription initiation positions controlled by DNMT1 using ChIPseq with RNApolIIser5 antibody. Ingenuity pathway analysis identified potential methylated upstream regulators...
May 4, 2017: Epigenomics
https://www.readbyqxmd.com/read/28465351/an-hnf4%C3%AE-microrna-194-192-signaling-axis-maintains-hepatic-cell-function
#3
Aoi Morimoto, Mana Kannari, Yuichi Tsuchida, Shota Sasaki, Chinatsu Saito, Tsuyoshi Matsuta, Tsukasa Maeda, Megumi Akiyama, Takahiro Nakamura, Masakiyo Sakaguchi, Nobukazu Nameki, Frank J Gonzalez, Yusuke Inoue
HNF4α controls the expression of liver-specific protein-coding genes. However, some microRNAs (miRNAs) are also modulated by HNF4α, and it is not known whether they are direct targets of HNF4α, and whether they influence the hepatic function. In this study, we found that HNF4α regulates miRNAs, indicated by marked down-regulation of miR-194 and miR-192 (miR-194/192) in liver-specific Hnf4a-null (Hnf4a(ΔH)) mice. Transactivation of the shared miR-194/192 promoter was dependent on HNF4α expression, indicating that miR194/192 is a target gene of HNF4α...
May 2, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28458902/hyperinsulinaemic-hypoglycaemia-renal-fanconi-syndrome-and-liver-disease-due-to-a-mutation-in-the-hnf4a-gene
#4
María Clemente, Alejandro Vargas, Gema Ariceta, Rosa Martínez, Ariadna Campos, Diego Yeste
SUMMARY: HNF4A gene mutations have been reported in cases of transient and persistent hyperinsulinaemic hypoglycaemia of infancy (HHI), particularly in families with adulthood diabetes. The case of a patient with HHI, liver impairment and renal tubulopathy due to a mutation in HNF4A is reported. LEARNING POINTS: Urine specimen study in cases of HHI with diazoxide response is necessary to rule out specific metabolic conditions (l-3-hydroxyacyl-coenzyme A dehydrogenase deficiency) or tubular renal involvement...
2017: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/28458900/congenital-hyperinsulinism-and-poland-syndrome-in-association-with-10p13-14-duplication
#5
Dinesh Giri, Prashant Patil, Rachel Hart, Mohammed Didi, Senthil Senniappan
SUMMARY: Poland syndrome (PS) is a rare congenital condition, affecting 1 in 30 000 live births worldwide, characterised by a unilateral absence of the sternal head of the pectoralis major and ipsilateral symbrachydactyly occasionally associated with abnormalities of musculoskeletal structures. A baby girl, born at 40 weeks' gestation with birth weight of 3.33 kg (-0.55 SDS) had typical phenotypical features of PS. She had recurrent hypoglycaemic episodes early in life requiring high concentration of glucose and glucagon infusion...
2017: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/28453780/variation-in-maturity-onset-diabetes-of-the-young-genes-influence-response-to-interventions-for-diabetes-prevention
#6
Liana K Billings, Kathleen A Jablonski, A Sofia Warner, Yu-Chien Cheng, Jarred B McAteer, Laura Tipton, Alan R Shuldiner, David A Ehrmann, Alisa K Manning, Dana Dabelea, Paul W Franks, Steven E Kahn, Toni I Pollin, William C Knowler, David Altshuler, Jose C Florez
CONTEXT: Variation in genes that cause Maturity-Onset Diabetes of the Young (MODY) has been associated with diabetes incidence and glycemic traits. OBJECTIVES: This study aimed to determine whether genetic variation in MODY genes leads to differential responses to insulin-sensitizing interventions. DESIGN AND SETTING: This was a secondary analysis of a multicenter randomized clinical trial, the Diabetes Prevention Program (DPP), involving 27 U...
April 27, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28451462/pulmonary-adenocarcinoma-with-mucin-production-modulates-phenotype-according-to-common-genetic-traits-a-reappraisal-of-mucinous-adenocarcinoma-and-colloid-adenocarcinoma
#7
Angelica Sonzogni, Fabrizio Bianchi, Alessandra Fabbri, Mara Cossa, Giulio Rossi, Alberto Cavazza, Elena Tamborini, Federica Perrone, Adele Busico, Iolanda Capone, Benedetta Picciani, Barbara Valeri, Ugo Pastorino, Giuseppe Pelosi
Whether invasive mucinous adenocarcinoma (IMA) and colloid adenocarcinoma (ICA) of the lung represent separate tumour entities, or simply lie within a spectrum of phenotypic variability, is worth investigating. Fifteen ICA, 12 IMA, 9 ALK-rearranged adenocarcinomas (ALKA), 8 non-mucinous KRAS-mutated adenocarcinomas (KRASA) and 9 mucinous breast adenocarcinomas (MBA) were assessed by immunohistochemistry for alveolar (TTF1, cytoplasmic MUC1), intestinal (CDX-2, MUC2), gastric (membrane MUC1, MUC6), bronchial (MUC5AC), mesenchymal (vimentin), neuroendocrine (chromogranin A, synaptophysin), sex steroid hormone-related (oestrogen and progesterone receptors), pan-mucinous (HNF4A) and pan-epithelial (keratin 7) lineage biomarkers and by targeted next generation sequencing (TNGS) for 50 recurrently altered cancer genes...
April 2017: Journal of Pathology. Clinical Research
https://www.readbyqxmd.com/read/28445515/correlation-of-histopathologic-characteristics-to-protein-expression-and-function-in-malignant-melanoma
#8
Charlotte Welinder, Krzysztof Pawłowski, A Marcell Szasz, Maria Yakovleva, Yutaka Sugihara, Johan Malm, Göran Jönsson, Christian Ingvar, Lotta Lundgren, Bo Baldetorp, Håkan Olsson, Melinda Rezeli, Thomas Laurell, Elisabet Wieslander, György Marko-Varga
BACKGROUND: Metastatic melanoma is still one of the most prevalent skin cancers, which upon progression has neither a prognostic marker nor a specific and lasting treatment. Proteomic analysis is a versatile approach with high throughput data and results that can be used for characterizing tissue samples. However, such analysis is hampered by the complexity of the disease, heterogeneity of patients, tumors, and samples themselves. With the long term aim of quest for better diagnostics biomarkers, as well as predictive and prognostic markers, we focused on relating high resolution proteomics data to careful histopathological evaluation of the tumor samples and patient survival information...
2017: PloS One
https://www.readbyqxmd.com/read/28412976/hepatic-population-derived-from-human-pluripotent-stem-cells-is-effectively-increased-by-selective-removal-of-undifferentiated-stem-cells-using-ym155
#9
Seok-Jin Kang, Young-Il Park, So-Ryeon Hwang, Hee Yi, Nga Tham, Hyun-Ok Ku, Jae-Young Song, Hwan-Goo Kang
BACKGROUND: Pluripotent stem cells (PSCs) such as embryonic stem cells and induced pluripotent stem cells are promising target cells for cell regenerative medicine together with recently advanced technology of in-vitro differentiation. However, residual undifferentiated stem cells (USCs) during in-vitro differentiation are considered a potential risk for development of cancer cells and nonspecific lineage cell types. In this study we observed that USCs still exist during hepatic differentiation, consequently resulting in poor quality of the hepatic population and forming teratoma in vivo...
April 17, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28387599/novel-insights-into-systemic-autoimmune-rheumatic-diseases-using-shared-molecular-signatures-and-an-integrative-analysis
#10
Marie Hudson, Sasha Bernatsky, Ines Colmegna, Maximilien Lora, Tomi Pastinen, Kathleen Klein Oros, Celia M T Greenwood
We undertook this study to identify DNA methylation signatures of three systemic autoimmune rheumatic diseases (SARDs), namely rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis, compared to healthy controls. Using a careful design to minimize confounding, we restricted our study to subjects with incident disease and performed our analyses on purified CD4(+) T cells, key effector cells in SARD. We identified differentially methylated (using the Illumina Infinium HumanMethylation450 BeadChip array) and expressed (using the Illumina TruSeq stranded RNA-seq protocol) sites between cases and controls, and investigated the biological significance of this SARD signature using gene annotation databases...
April 7, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28385711/microbiota-regulate-intestinal-epithelial-gene-expression-by-suppressing-the-transcription-factor-hepatocyte-nuclear-factor-4-alpha
#11
James M Davison, Colin R Lickwar, Lingyun Song, Ghislain Breton, Gregory E Crawford, John F Rawls
Microbiota influence diverse aspects of intestinal physiology and disease in part by controlling tissue-specific transcription of host genes. However, host genomic mechanisms mediating microbial control of intestinal gene expression are poorly understood. Hepatocyte nuclear factor 4 (HNF4) is the most ancient family of nuclear receptor transcription factors with important roles in human metabolic and inflammatory bowel diseases, but a role in host response to microbes is unknown. Using an unbiased screening strategy, we found that zebrafish Hnf4a specifically binds and activates a microbiota-suppressed intestinal epithelial transcriptional enhancer...
April 6, 2017: Genome Research
https://www.readbyqxmd.com/read/28364040/hypoxia-reduces-hnf4%C3%AE-mody1-protein-expression-in-pancreatic-%C3%AE-cells-by-activating-amp-activated-protein-kinase
#12
Yoshifumi Sato, Tomonori Tsuyama, Chinami Sato, Md Fazlul Karim, Tatsuya Yoshizawa, Masahiro Inoue, Kazuya Yamagata
Hypoxia plays a role in the deterioration of β-cell function. Hepatocyte nuclear factor 4α (HNF4α) has an important role in pancreatic β-cells, and mutations of the human HNF4A gene cause a type of maturity-onset diabetes of the young (MODY1). However, it remains unclear whether hypoxia affects the expression of HNF4α in β-cells. Here, we report that hypoxia reduces HNF4α protein expression in β-cells. Hypoxia-inducible factor (HIF) was not involved in the down-regulation of HNF4α under hypoxic conditions...
March 31, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28360131/a-small-molecule-screen-reveals-that-hsp90%C3%AE-promotes-the-conversion-of-ipsc-derived-endoderm-to-a-hepatic-fate-and-regulates-hnf4a-turnover
#13
Ran Jing, Cameron B Duncan, Stephen A Duncan
We have previously shown that the transcription factor HNF4A is required for the formation of hepatic progenitor cells from endoderm that has been derived from human induced pluripotent stem cells. We reasoned that we could uncover regulatory pathways with novel roles in hepatocyte differentiation by identifying cellular processes that regulate HNF4A. We, therefore, performed a screen of 1120 small molecules with well-characterized mechanisms of action to detect those that affect the abundance of HNF4A in iPSC-derived hepatic progenitor cells...
March 30, 2017: Development
https://www.readbyqxmd.com/read/28352326/genetic-variants-in-kcnj11-tcf7l2-and-hnf4a-are-associated-with-type-2-diabetes-bmi-and-dyslipidemia-in-families-of-northeastern-mexico-a-pilot-study
#14
Hugo Leonid Gallardo-Blanco, Jesus Zacarías Villarreal-Perez, Ricardo Martin Cerda-Flores, Andres Figueroa, Celia Nohemi Sanchez-Dominguez, Juana Mercedes Gutierrez-Valverde, Iris Carmen Torres-Muñoz, Fernando Javier Lavalle-Gonzalez, Esther Carlota Gallegos-Cabriales, Laura Elia Martinez-Garza
The aim of the present study was to investigate whether genetic markers considered risk factors for metabolic syndromes, including dyslipidemia, obesity and type 2 diabetes mellitus (T2DM), can be applied to a Northeastern Mexican population. A total of 37 families were analyzed for 63 single nucleotide polymorphisms (SNPs), and the age, body mass index (BMI), glucose tolerance values and blood lipid levels, including those of cholesterol, low-density lipoprotein (LDL), very LDL (VLDL), high-density lipoprotein (HDL) and triglycerides were evaluated...
February 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28295042/generation-of-non-viral-transgene-free-hepatocyte-like-cells-with-piggybac-transposon
#15
Hokahiro Katayama, Kentaro Yasuchika, Yuya Miyauchi, Hidenobu Kojima, Ryoya Yamaoka, Takayuki Kawai, Elena Yukie Yoshitoshi, Satoshi Ogiso, Sadahiko Kita, Katsutaro Yasuda, Naoya Sasaki, Ken Fukumitsu, Junji Komori, Takamichi Ishii, Shinji Uemoto
Somatic cells can be reprogrammed to induced hepatocyte-like cells (iHeps) by overexpressing certain defined factors in direct reprogramming techniques. Of the various methods to deliver genes into cells, typically used genome-integrating viral vectors are associated with integration-related adverse events such as mutagenesis, whereas non-integrating viral vectors have low efficiency, making viral vectors unsuitable for clinical application. Therefore, we focused on developing a transposon system to establish a non-viral reprogramming method...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28270372/congenital-hyperinsulinism-in-china-a-review-of-chinese-literature-over-the-past-15-years
#16
Wang Weiyan, Sun Yi, Zhao Wenting, Wu Tai, Wang Liang, Yuan Tianming, Yu Huimin
OBJECTIVE: The present study is investigated the clinical presentation, therapeutic outcomes and genetic mutations of CHI in Chinese individuals over the past 15 years. METHODS: The authors retrospectively reviewed one case in the department and 206 cases reported from January 2002 to October 2016 in China from PubMed, Ovid Medline, Springer and Wanfang Database, CBMD database and CKNI database. RESULTS: In total, 207 cases were recruited: 100 cases (48...
March 8, 2017: Journal of Clinical Research in Pediatric Endocrinology
https://www.readbyqxmd.com/read/28255028/gene-signature-driving-invasive-mucinous-adenocarcinoma-of-the-lung
#17
Minzhe Guo, Koichi Tomoshige, Michael Meister, Thomas Muley, Takuya Fukazawa, Tomoshi Tsuchiya, Rebekah Karns, Arne Warth, Iris M Fink-Baldauf, Takeshi Nagayasu, Yoshio Naomoto, Yan Xu, Marcus A Mall, Yutaka Maeda
Though invasive mucinous adenocarcinoma of the lung (IMA) is pathologically distinctive, the molecular mechanism driving IMA is not well understood, which hampers efforts to identify therapeutic targets. Here, by analyzing gene expression profiles of human and mouse IMA, we identified a Mucinous Lung Tumor Signature of 143 genes, which was unexpectedly enriched in mucin-producing gastrointestinal, pancreatic, and breast cancers. The signature genes included transcription factors FOXA3, SPDEF, HNF4A, mucins MUC5AC, MUC5B, MUC3, and an inhibitory immune checkpoint VTCN1/B7-H4 (but not PD-L1/B7-H1)...
April 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28242437/congenital-hyperinsulinism-and-glycogenosis-like-phenotype-due-to-a-novel-hnf4a-mutation
#18
Juraj Stanik, Martina Skopkova, Katarina Brennerova, Daniel Danis, Monika Rosolankova, Anna Salingova, Vladimir Bzduch, Iwar Klimes, Daniela Gasperikova
AIM: Congenital hyperinsulinism (CHI) and glycogen storage disease (glycogenosis) are both causing hypoglycemia during infancy, but with different additional clinical features and therapeutic approach. We aimed to identify a genetic cause in a child with an ambiguous phenotype. METHODS AND RESULTS: We present a child with hyperinsulinemic hypoglycemia, physiological 3-OH butyrate, increased triglyceride serum levels, increased level of glycogen in erythrocytes, increased liver transaminases, and increased echogenicity on liver ultrasonography...
February 16, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28196117/the-transcriptional-activity-of-hepatocyte-nuclear-factor-4-alpha-is-inhibited-via-phosphorylation-by-erk1-2
#19
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/28193157/whole-genome-association-analysis-of-pork-meat-ph-revealed-three-significant-regions-and-several-potential-genes-in-finnish-yorkshire-pigs
#20
Lucas L Verardo, Marja-Liisa Sevón-Aimonen, Timo Serenius, Ville Hietakangas, Pekka Uimari
BACKGROUND: One of the most commonly used quality measurements of pork is pH measured 24 h after slaughter. The most probable mode of inheritance for this trait is oligogenic with several known major genes, such as PRKAG3. In this study, we used whole-genome SNP genotypes of over 700 AI boars; after a quality check, 42,385 SNPs remained for association analysis. All the boars were purebred Finnish Yorkshire. To account for relatedness of the animals, a pedigree-based relationship matrix was used in a mixed linear model to test the effect of SNPs on pH measured from loin...
February 13, 2017: BMC Genetics
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