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https://www.readbyqxmd.com/read/28905149/interactions-between-the-canonical-wnt-beta-catenin-pathway-and-ppar-gamma-on-neuroinflammation-demyelination-and-remyelination-in-multiple-sclerosis
#1
REVIEW
Alexandre Vallée, Jean-Noël Vallée, Rémy Guillevin, Yves Lecarpentier
Multiple sclerosis (MS) is marked by neuroinflammation and demyelination with loss of oligodendrocytes in the central nervous system. The immune response is regulated by WNT/beta-catenin pathway in MS. Activated NF-kappaB, a major effector of neuroinflammation, and upregulated canonical WNT/beta-catenin pathway positively regulate each other. Demyelinating events present an upregulation of WNT/beta-catenin pathway, whereas proper myelinating phases show a downregulation of WNT/beta-catenin pathway essential for the promotion of oligodendrocytes precursors cells proliferation and differentiation...
September 13, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28875890/new-onset-diabetes-after-transplant-incidence-risk-factors-and-outcome
#2
S C Alagbe, A Voster, R Ramesar, C R Swanepoel
BACKGROUND: The outcome of renal transplantation depends on achieving effective immunosuppression while minimising the consequences of such treatment. The occurrence of new-onset diabetes in the post-transplant period has been associated with several risk factors including some immunosuppressive medication. Better understanding of the clinical and genetic risk factors associated with new-onset diabetes after transplant (NODAT) could enable risk stratification of patients in the pre-transplant period, with the goal of applying measures that will reduce the incidence...
August 25, 2017: South African Medical Journal, Suid-Afrikaanse Tydskrif Vir Geneeskunde
https://www.readbyqxmd.com/read/28851992/tcf7l2-plays-pleiotropic-roles-in-the-control-of-glucose-homeostasis-pancreas-morphology-vascularization-and-regeneration
#3
Nicola Facchinello, Estefania Tarifeño-Saldivia, Enrico Grisan, Marco Schiavone, Margherita Peron, Alessandro Mongera, Olivier Ek, Nicole Schmitner, Dirk Meyer, Bernard Peers, Natascia Tiso, Francesco Argenton
Type 2 diabetes (T2D) is a disease characterized by impaired insulin secretion. The Wnt signaling transcription factor Tcf7l2 is to date the T2D-associated gene with the largest effect on disease susceptibility. However, the mechanisms by which TCF7L2 variants affect insulin release from β-cells are not yet fully understood. By taking advantage of a tcf7l2 zebrafish mutant line, we first show that these animals are characterized by hyperglycemia and impaired islet development. Moreover, we demonstrate that the zebrafish tcf7l2 gene is highly expressed in the exocrine pancreas, suggesting potential bystander effects on β-cell growth, differentiation and regeneration...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28830217/decreased-glucagon-like-peptide-1-receptor-expression-in-endothelial-and-smooth-muscle-cells-in-diabetic-db-db-mice-tcf7l2-is-a-possible-regulator-of-the-vascular-glucagon-like-peptide-1-receptor
#4
Tomohiko Kimura, Atsushi Obata, Masashi Shimoda, Seizo Okauchi, Hidenori Hirukawa, Kenji Kohara, Tomoe Kinoshita, Yuka Nogami, Shuhei Nakanishi, Tomoatsu Mune, Kohei Kaku, Hideaki Kaneto
AIMS: Incretin signalling is known to prevent the development of arteriosclerosis by relaxation response in endothelial cells via the glucagon-like peptide 1 receptor. It remains unclear, however, whether vascular glucagon-like peptide 1 receptor expression is altered under some conditions. The aim of this study is to examine whether vascular glucagon-like peptide 1 receptor expression is altered by diabetic state as reported in pancreatic β-cells. METHODS: We used 18-week-old male diabetic db/db mice and control db/m mice...
August 1, 2017: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/28822061/co-ultramicronized-palmitoylethanolamide-luteolin-facilitates-the-development-of-differentiating-and-undifferentiated-rat-oligodendrocyte-progenitor-cells
#5
Stephen D Skaper, Massimo Barbierato, Laura Facci, Mila Borri, Gabriella Contarini, Morena Zusso, Pietro Giusti
Oligodendrocytes, the myelin-producing cells of the central nervous system (CNS), have limited capability to bring about repair in chronic CNS neuroinflammatory demyelinating disorders such as multiple sclerosis (MS). MS lesions are characterized by a compromised pool of undifferentiated oligodendrocyte progenitor cells (OPCs) unable to mature into myelin-producing oligodendrocytes. An attractive strategy may be to replace lost OLs and/or promote their maturation. N-palmitoylethanolamine (PEA) is an endogenous fatty acid amide signaling molecule with anti-inflammatory and neuroprotective actions...
August 18, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28811361/chemoradiotherapy-resistance-in-colorectal-cancer-cells-is-mediated-by-wnt-%C3%AE-catenin-signaling
#6
Georg Emons, Melanie Spitzner, Sebastian Reineke, Janneke Möller, Noam Auslander, Frank Kramer, Yue Hu, Tim Beissbarth, Hendrik A Wolff, Margret Rave-Fränk, Elisabeth Heßmann, Jochen Gaedcke, B Michael Ghadimi, Steven A Johnsen, Thomas Ried, Marian Grade
Activation of Wnt/β-catenin signaling plays a central role in the development and progression of colorectal cancer. The Wnt-transcription factor, TCF7L2, is overexpressed in primary rectal cancers that are resistant to chemoradiotherapy and TCF7L2 mediates resistance to chemoradiotherapy. However, it is unclear whether the resistance is mediated by a TCF7L2 inherent mechanism or Wnt/β-catenin signaling in general. Here, inhibition of β-catenin by siRNAs or a small-molecule inhibitor (XAV-939) resulted in sensitization of colorectal cancer cells to chemoradiotherapy...
August 15, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28795454/the-tcf7l2-pgc1%C3%AE-axis-connects-mitochondrial-biogenesis-and-metabolic-shift-with-stem-cell-commitment-to-hepatic-differentiation
#7
Anaïs Wanet, Marino Caruso, Jean-Baka Domelevo Entfellner, Mehdi Najar, Antoine Fattaccioli, Catherine Demazy, Jonathan Evraerts, Hoda El-Kehdy, Guillaume Pourcher, Etienne Sokal, Thierry Arnould, Nicki Tiffin, Mustapha Najimi, Patricia Renard
Increasing evidence supports that modifications in the mitochondrial content, oxidative phosphorylation (OXPHOS) activity, and cell metabolism influence the fate of stem cells. However, the regulators involved in the crosstalk between mitochondria and stem cell fate remain poorly characterized. Here, we identified a transcriptional regulatory axis, composed of TCF7L2 (transcription factor 7 like 2, a downstream effector of the Wnt/β-catenin pathway, repressed during differentiation) and PGC-1α (peroxisome proliferator-activated receptor gamma coactivator 1 alpha, the master regulator of mitochondrial biogenesis, induced during differentiation), coupling the loss of pluripotency and early commitment to differentiation, to the initiation of mitochondrial biogenesis and metabolic shift toward OXPHOS...
August 10, 2017: Stem Cells
https://www.readbyqxmd.com/read/28791367/molecular-mechanisms-of-breast-cancer-metastasis-by-gene-expression-profile-analysis
#8
Tianying Zheng, Aijun Wang, Dongyan Hu, Yonggang Wang
Metastasis is the main cause of breast cancer‑related mortalities. The present study aimed to uncover the relevant molecular mechanisms of breast cancer metastasis and to explore potential biomarkers that may be used for prognosis. Expression profile microarray data GSE8977, which contained 22 stroma samples (15 were from normal breast and 7 were from invasive ductal carcinoma tumor samples), were obtained from the Gene Expression Omnibus database. Following data preprocessing, differentially expressed genes (DEGs) were selected based on analyses conducted using the linear models for microarray analysis package from R and Bioconductor software...
October 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28783164/effect-of-sequence-variants-on-variance-in-glucose-levels-predicts-type-2-diabetes-risk-and-accounts-for-heritability
#9
Erna V Ivarsdottir, Valgerdur Steinthorsdottir, Maryam S Daneshpour, Gudmar Thorleifsson, Patrick Sulem, Hilma Holm, Snaevar Sigurdsson, Astradur B Hreidarsson, Gunnar Sigurdsson, Ragnar Bjarnason, Arni V Thorsson, Rafn Benediktsson, Gudmundur Eyjolfsson, Olof Sigurdardottir, Isleifur Olafsson, Sirous Zeinali, Fereidoun Azizi, Unnur Thorsteinsdottir, Daniel F Gudbjartsson, Kari Stefansson
Sequence variants that affect mean fasting glucose levels do not necessarily affect risk for type 2 diabetes (T2D). We assessed the effects of 36 reported glucose-associated sequence variants on between- and within-subject variance in fasting glucose levels in 69,142 Icelanders. The variant in TCF7L2 that increases fasting glucose levels increases between-subject variance (5.7% per allele, P = 4.2 × 10(-10)), whereas variants in GCK and G6PC2 that increase fasting glucose levels decrease between-subject variance (7...
September 2017: Nature Genetics
https://www.readbyqxmd.com/read/28755500/bidirectional-reporter-assay-using-hal-promoter-and-topflash-improves-specificity-in-high-throughput-screening-of-wnt-inhibitors
#10
Kiyoshi Yamaguchi, Chi Zhu, Tomoyuki Ohsugi, Yuko Yamaguchi, Tsuneo Ikenoue, Yoichi Furukawa
Constitutive activation of Wnt signaling plays an important role in colorectal and liver tumorigenesis. Cell-based assays using synthetic TCF/LEF (T-cell factor/lymphoid enhancer factor) reporters, as readouts of β-catenin/TCF-dependent transcriptional activity, have contributed greatly to the discovery of small molecules that modulate Wnt signaling. In the present study, we report a novel screening method, called a bidirectional dual reporter assay. Integrated transcriptome analysis identified a histidine ammonia-lyase gene (HAL) that was negatively regulated by β-catenin/TCF-dependent transcriptional activity...
July 29, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28744146/rna-sequencing-identifies-gene-expression-profile-changes-associated-with-%C3%AE-estradiol-treatment-in-u2os-osteosarcoma-cells
#11
Bin Chen, Zude Liu, Jidong Zhang, Hantao Wang, Bo Yu
This study was conducted to identify gene expression profile changes associated with β-estradiol (E2) treatment in U2OS osteosarcoma cells by high-throughput RNA sequencing (RNA-seq). Two U2OS cell samples treated with E2 (15 μmol/L) and two untreated control U2OS cell samples were subjected to RNA-seq. Differentially expressed genes (DEGs) between the groups were identified, and main biological process enrichment was performed using gene ontology (GO) analysis. A protein-protein interaction (PPI) network was constructed using Cytoscape based on the Human Protein Reference Database...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28699988/type-2-diabetes-associated-genetic-variants-of-fto-lepr-pparg-and-tcf7l2-in-gestational-diabetes-in-a-brazilian-population
#12
Mauren Isfer Anghebem-Oliveira, Bruna Rodrigues Martins, Dayane Alberton, Edneia Amancio de Souza Ramos, Geraldo Picheth, Fabiane Gomes de Moraes Rego
Objective: Gestational diabetes mellitus (GDM) is a metabolic disorder that shares pathophysiologic features with type 2 diabetes mellitus. The aim of this study was to investigate the association of the polymorphisms fat mass and obesity-associated (FTO) rs1421085, leptin receptor (LEPR) rs1137100, rs1137101, peroxisome proliferator-activated receptor gamma (PPARg) rs1801282, and transcription factor 7-like 2 (TCF7L2) rs7901695 with GDM. Subjects and methods: 252 unrelated Euro-Brazilian pregnant women were classified into two groups according to the 2015 criteria of the American and Brazilian Diabetes Association: healthy pregnant women (n = 125) and pregnant women with GDM (n = 127), matched by age...
May 2017: Archives of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28656232/transcription-factor-7-like-2-promotes-oligodendrocyte-differentiation-and-remyelination
#13
Chao Weng, Man Ding, Shanghua Fan, Qian Cao, Zuneng Lu
Transcription factor 7 like 2 (TCF7L2, also termed TCF4), is a Wnt effector induced transiently in the oligodendroglial lineage. The current well accepted hypothesis is that TCF7L2 inhibits oligodendrocyte differentiation and remyelination through canonical Wnt/β‑catenin signaling. However, recent studies indicated that TCF7L2 activity is required during oligodendrocyte differentiation and remyelination. In order to clarify this, in situ hybridization, immunofluorescence and western blot analysis using in vivo TCF7L2 conditional knockout mice, were performed and it was found that TCF7L2 promotes oligodendrocyte differentiation during myelin formation and remyelination...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28649285/introduction-of-the-diagene-study-clinical-characteristics-pathophysiology-and-determinants-of-vascular-complications-of-type-2-diabetes
#14
Thijs T W van Herpt, Roosmarijn F H Lemmers, Mandy van Hoek, Janneke G Langendonk, Ronald J Erdtsieck, Bert Bravenboer, Annelies Lucas, Monique T Mulder, Harm R Haak, Aloysius G Lieverse, Eric J G Sijbrands
BACKGROUND: Type 2 diabetes is a major healthcare problem. Glucose-, lipid-, and blood pressure-lowering strategies decrease the risk of micro- and macrovascular complications. However, a substantial residual risk remains. To unravel the etiology of type 2 diabetes and its complications, large-scale, well-phenotyped studies with prospective follow-up are needed. This is the goal of the DiaGene study. In this manuscript, we describe the design and baseline characteristics of the study...
2017: Diabetology & Metabolic Syndrome
https://www.readbyqxmd.com/read/28611053/the-rs7903146-variant-in-the-tcf7l2-gene-increases-the-risk-of-prediabetes-type-2-diabetes-in-obese-adolescents-by-impairing-%C3%AE-cell-function-and-hepatic-insulin-sensitivity
#15
Catrina Cropano, Nicola Santoro, Leif Groop, Chiara Dalla Man, Claudio Cobelli, Alfonso Galderisi, Romy Kursawe, Bridget Pierpont, Martina Goffredo, Sonia Caprio
OBJECTIVE: In this study, we aimed to explore the mechanism by which TCF7L2 rs7903146 risk allele confers susceptibility to impaired glucose tolerance (IGT) or type 2 diabetes (T2D) in obese adolescents. RESEARCH DESIGN AND METHODS: The rs7903146 variant in the TCF7L2 gene was genotyped in a multiethnic cohort of 955 youths. All subjects underwent an oral glucose tolerance test with the use of the Oral Minimal Model to assess insulin secretion, and 33 subjects underwent a hyperinsulinemic-euglycemic clamp...
August 2017: Diabetes Care
https://www.readbyqxmd.com/read/28607931/genetic-epidemiology-of-type-2-diabetes-in-mexican-mestizos
#16
REVIEW
Eiralí Guadalupe García-Chapa, Evelia Leal-Ugarte, Valeria Peralta-Leal, Jorge Durán-González, Juan Pablo Meza-Espinoza
There are currently about 415 million people with diabetes worldwide, a figure likely to increase to 642 million by 2040. In 2015, Mexico was the second Latin American country and sixth in the world in prevalence of this disorder with nearly 11.5 million of patients. Type 2 diabetes (T2D) is the main kind of diabetes and its etiology is complex with environmental and genetic factors involved. Indeed, polymorphisms in several genes have been associated with this disease worldwide. To estimate the genetic epidemiology of T2D in Mexican mestizos a systematic bibliographic search of published articles through PubMed, Scopus, Google Scholar, and Web of Science was conducted...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28595632/a-comparison-of-gene-expression-profiles-in-patients-with-coronary-artery-disease-type-2-diabetes-and-their-coexisting-conditions
#17
Rui Gong, Menghui Chen, Cuizhao Zhang, Manli Chen, Haibin Li
BACKGROUND: To support a hypothesis that there is an intrinsic interplay between coronary artery disease (CAD) and type 2 diabetes (T2D), we used RNA-seq to identify unique gene expression signatures of CAD, T2D, and coexisting conditions. METHODS: After transcriptome sequencing, differential expression analysis was performed between each disordered state and normal control group. By comparing gene expression profiles of CAD, T2D, and coexisting conditions, common and specific patterns of each disordered state were displayed...
June 8, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/28594147/casein-kinase-1-epsilon-deletion-increases-mu-opioid-receptor-dependent-behaviors-and-binge-eating1
#18
L R Goldberg, S L Kirkpatrick, N Yazdani, K P Luttik, O A Lacki, R Keith Babbs, D F Jenkins, W Evan Johnson, C D Bryant
Genetic and pharmacological studies indicate that casein kinase 1 epsilon (Csnk1e) contributes to psychostimulant, opioid, and ethanol motivated behaviors. We previously used pharmacological inhibition to demonstrate that Csnk1e negatively regulates the locomotor stimulant properties of opioids and psychostimulants. Here, we tested the hypothesis that Csnk1e negatively regulates opioid and psychostimulant reward using genetic inhibition and the conditioned place preference assay in Csnk1e knockout mice. Similar to pharmacological inhibition, Csnk1e knockout mice showed enhanced opioid-induced locomotor activity with the mu opioid receptor agonist fentanyl (0...
June 8, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28592605/interaction-between-genes-and-macronutrient-intake-on-the-risk-of-developing-type-2-diabetes-systematic-review-and-findings-from-european-prospective-investigation-into-cancer-epic-interact
#19
Sherly X Li, Fumiaki Imamura, Zheng Ye, Matthias B Schulze, Jusheng Zheng, Eva Ardanaz, Larraitz Arriola, Heiner Boeing, Courtney Dow, Guy Fagherazzi, Paul W Franks, Antonio Agudo, Sara Grioni, Rudolf Kaaks, Verena A Katzke, Timothy J Key, Kay Tee Khaw, Francesca R Mancini, Carmen Navarro, Peter M Nilsson, N Charlotte Onland-Moret, Kim Overvad, Domenico Palli, Salvatore Panico, J Ramón Quirós, Olov Rolandsson, Carlotta Sacerdote, María-José Sánchez, Nadia Slimani, Ivonne Sluijs, Annemieke Mw Spijkerman, Anne Tjonneland, Rosario Tumino, Stephen J Sharp, Elio Riboli, Claudia Langenberg, Robert A Scott, Nita G Forouhi, Nicholas J Wareham
Background: Gene-diet interactions have been reported to contribute to the development of type 2 diabetes (T2D). However, to our knowledge, few examples have been consistently replicated to date.Objective: We aimed to identify existing evidence for gene-macronutrient interactions and T2D and to examine the reported interactions in a large-scale study.Design: We systematically reviewed studies reporting gene-macronutrient interactions and T2D. We searched the MEDLINE, Human Genome Epidemiology Network, and WHO International Clinical Trials Registry Platform electronic databases to identify studies published up to October 2015...
July 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28587604/kcnj11-abcc8-and-tcf7l2-polymorphisms-and-the-response-to-sulfonylurea-treatment-in-patients-with-type-2-diabetes-a-bioinformatics-assessment
#20
Jingwen Song, Yunzhong Yang, Franck Mauvais-Jarvis, Yu-Ping Wang, Tianhua Niu
BACKGROUND: Type 2 diabetes (T2D) is a worldwide epidemic with considerable health and economic consequences. Sulfonylureas are widely used drugs for the treatment of patients with T2D. KCNJ11 and ABCC8 encode the Kir6.2 (pore-forming subunit) and SUR1 (regulatory subunit that binds to sulfonylurea) of pancreatic β cell KATP channel respectively with a critical role in insulin secretion and glucose homeostasis. TCF7L2 encodes a transcription factor expressed in pancreatic β cells that regulates insulin production and processing...
June 6, 2017: BMC Medical Genetics
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