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https://www.readbyqxmd.com/read/29200018/the-diagnostic-and-prognostic-role-of-interleukin-12b-and-interleukin-6r-gene-polymorphism-in-patients-with-ankylosing-spondylitis
#1
Wen-Feng Ruan, Jiang-Tao Xie, Qi Jin, Wen-Da Wang, An-Song Ping
OBJECTIVES: Interleukin 23 (IL-23) pathway and IL-1 cluster genes play prominent role in the etiopathology of ankylosing spondylitis (AS). The aim of this study was to investigate the diagnostic and prognostic role of 5 single-nucleotide polymorphisms related to IL-23 pathway and IL-1 cluster genes in AS patients. METHODS: Four hundred thirty-one patients with AS and 206 age- and sex-matched healthy controls were recruited in this prospective cohort study. Five potential single-nucleotide polymorphisms (IL-23R [rs11209026], IL-12B [rs6871626], TYK2 [rs6511701], IL-6R [rs4129267], and IL-1R2 [rs2192752]) related to IL-23 pathway and IL-1 cluster genes by analyzing previous studies were genotyped...
December 1, 2017: Journal of Clinical Rheumatology: Practical Reports on Rheumatic & Musculoskeletal Diseases
https://www.readbyqxmd.com/read/29162862/tyk2-induced-phosphorylation-of-y640-suppresses-stat3-transcriptional-activity
#2
Raffaele Mori, Joris Wauman, Laura Icardi, José Van der Heyden, Lode De Cauwer, Frank Peelman, Karolien De Bosscher, Jan Tavernier
STAT3 is a pleiotropic transcription factor involved in homeostatic and host defense processes in the human body. It is activated by numerous cytokines and growth factors and generates a series of cellular effects. Of the STAT-mediated signal transduction pathways, STAT3 transcriptional control is best understood. Jak kinase dependent activation of STAT3 relies on Y705 phosphorylation triggering a conformational switch that is stabilized by intermolecular interactions between SH2 domains and the pY705 motif...
November 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29157973/when-the-good-go-bad-mutant-npm1-in-acute-myeloid-leukemia
#3
REVIEW
Preethi Kunchala, Sudhakiranmayi Kuravi, Roy Jensen, Joseph McGuirk, Ramesh Balusu
Nucleophosmin 1 (NPM1) is a nucleolar phosphoprotein that performs diverse biological functions including molecular chaperoning, ribosome biogenesis, DNA repair, and genome stability. Acute myeloid leukemia (AML) is a heterogeneous disease, more than half of the AML cases exhibit normal karyotype (NK). Approximately 50-60 percent of patients with NK-AML carry NPM1 mutations which are characterized by cytoplasmic dislocation of the NPM1 protein. In AML, mutant NPM1 (NPM1c+) acts in a dominant negative fashion and also blocks the differentiation of myeloid cells through gain-of-function for the AML phenotype...
November 4, 2017: Blood Reviews
https://www.readbyqxmd.com/read/29157944/down-regulation-of-tyk2-cblb-and-lmp7-genes-expression-in-relapsing-remitting-multiple-sclerosis-patients-treated-with-interferon-beta
#4
Mehrdokht Mazdeh, Najmeh Moradi, Elnaz Khoshroo, Zahra Shayesteh, Mohammad Taheri, Arezou Sayad, Mir Davood Omrani, Mehrdad Hajilooi, Ghodratollah Roshanaei, Ghasem Solgi
This study aimed to examine the expression of TYK2, CBLB and LMP7 genes at both mRNA and protein levels in relapsing-remitting MS (RRMS) patients in compare with healthy controls. Seventy-eight RRMS patients treated with IFNβ-1a and 79 age- and ethnic-matched healthy subjects were studied. The mRNA expression levels of TYK2, CBLB and LMP7 in PBMCs were quantified by real-time PCR and plasma concentrations of three molecules were measured by ELISA. Results were compared between patients and controls, IFNβ-responders and non-responders...
November 8, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29137183/lactobacillus-plantarum-enhanced-il-22-production-in-natural-killer-nk-cells-that-protect-the-integrity-of-intestinal-epithelial-cell-barrier-damaged-by-enterotoxigenic-escherichia-coli
#5
Yueqin Qiu, Zongyong Jiang, Shenglan Hu, Li Wang, Xianyong Ma, Xuefen Yang
Interleukin (IL)-22-producing Natural Killer (NK) cells protect the gut epithelial cell barrier from pathogens. A strain of probiotics, Lactobacillus plantarum (L. plantarum, LP), was previously found by our laboratory to significantly improve the mucosal barrier integrity and function of the small intestine in pigs. However, it was unclear whether LP benefited the intestinal mucosal barrier via interactions with the intestinal NK cells. The present study, therefore, was focused on the therapeutic effect of NK cells that were stimulated by LP on attenuating enterotoxigenic Escherichia coli (ETEC)-induced the damage to the integrity of the epithelial cell barrier...
November 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29121062/loss-of-function-jak1-mutations-occur-at-high-frequency-in-cancers-with-microsatellite-instability-and-are-suggestive-of-immune-evasion
#6
Lee A Albacker, Jeremy Wu, Peter Smith, Markus Warmuth, Philip J Stephens, Ping Zhu, Lihua Yu, Juliann Chmielecki
Immune evasion is a well-recognized hallmark of cancer and recent studies with immunotherapy agents have suggested that tumors with increased numbers of neoantigens elicit greater immune responses. We hypothesized that the immune system presents a common selective pressure on high mutation burden tumors and therefore immune evasion mutations would be enriched in high mutation burden tumors. The JAK family of kinases is required for the signaling of a host of immune modulators in tumor, stromal, and immune cells...
2017: PloS One
https://www.readbyqxmd.com/read/29108825/targeting-interferons-and-their-pathways-in-systemic-lupus-erythematosus
#7
REVIEW
François Chasset, Laurent Arnaud
Significant advances in the understanding of the molecular basis of innate immunity have led to the identification of interferons (IFNs), particularly IFN-α, as central mediators in the pathogenesis of Systemic Lupus Erythematosus. Therefore, targeting of IFNs and of their downstream pathways has emerged as important developments for novel drug research in SLE. Based on this, several specific interferon blocking strategies using anti-IFN-α antibodies, anti-type I interferon receptor antibodies, Interferon-α-kinoid, or anti-IFN-γ antibodies have all been assessed in recent clinical trials...
November 4, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/29095108/pharmacogenetics-of-glatiramer-acetate-therapy-for-multiple-sclerosis-the-impact-of-genome-wide-association-studies-identified-disease-risk-loci
#8
Olga Kulakova, Vitalina Bashinskaya, Ivan Kiselev, Natalia Baulina, Ekaterina Tsareva, Ruslan Nikolaev, Maxim Kozin, Sergey Shchur, Alexander Favorov, Alexey Boyko, Olga Favorova
AIM: Association analysis of genome-wide association studies (GWAS) identified multiple sclerosis (MS) risk genetic variants with glatiramer acetate (GA) treatment efficacy. PATIENTS & METHODS: SNPs in 17 GWAS-identified immune response loci were analyzed in 296 Russian MS patients as possible markers of optimal GA treatment response for at least 2 years. RESULTS: Alleles/genotypes of EOMES, CLEC16A, IL22RA2, PVT1 and HLA-DRB1 were associated by themselves with event-free phenotype during GA treatment for at least 2 years (p f  = 0...
November 2, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29091937/phenome-wide-association-study-using-research-participants-self-reported-data-provides-insight-into-the-th17-and-il-17-pathway
#9
Margaret G Ehm, Jennifer L Aponte, Mathias N Chiano, Laura M Yerges-Armstrong, Toby Johnson, Jonathan N Barker, Suzanne F Cook, Akanksha Gupta, David A Hinds, Li Li, Matthew R Nelson, Michael A Simpson, Chao Tian, Linda C McCarthy, Deepak K Rajpal, Dawn M Waterworth
A phenome-wide association study of variants in genes in the Th17 and IL-17 pathway was performed using self-reported phenotypes and genetic data from 521,000 research participants of 23andMe. Results replicated known associations with similar effect sizes for autoimmune traits illustrating self-reported traits can be a surrogate for clinically assessed conditions. Novel associations controlling for a false discovery rate of 5% included the association of the variant encoding p.Ile684Ser in TYK2 with increased risk of tonsillectomy, strep throat occurrences and teen acne, the variant encoding p...
2017: PloS One
https://www.readbyqxmd.com/read/29071117/variants-of-genes-implicated-in-type-1-interferon-pathway-and-b-cell-activation-modulate-the-eular-response-to-rituximab-at-24-weeks-in-rheumatoid-arthritis
#10
Pierre-Antoine Juge, Steven Gazal, Arnaud Constantin, Xavier Mariette, Bernard Combe, Jacques Tebib, Maxime Dougados, Jean Sibilia, Xavier Le Loet, Philippe Dieudé
BACKGROUND: The type 1 interferon (IFN) pathway has been identified to potentially affect the response to rituximab (RTX) for rheumatoid arthritis (RA), which suggests the contribution of type 1 IFN pathway genes such as IFN regulatory factor 5 and 7 (IRF5 and IRF7), tyrosine kinase 2 (TYK2), signal transducer and activator of transcription 4 (STAT4) and osteopontin (SPP1). Our objective was to study functional variants of these IFN pathway genes as predictors of the European League Against Rheumatism (EULAR) response to RTX for RA at week 24 (W24)...
2017: RMD Open
https://www.readbyqxmd.com/read/29059182/profiling-rna-seq-at-multiple-resolutions-markedly-increases-the-number-of-causal-eqtls-in-autoimmune-disease
#11
Christopher A Odhams, Deborah S Cunninghame Graham, Timothy J Vyse
Genome-wide association studies have identified hundreds of risk loci for autoimmune disease, yet only a minority (~25%) share genetic effects with changes to gene expression (eQTLs) in immune cells. RNA-Seq based quantification at whole-gene resolution, where abundance is estimated by culminating expression of all transcripts or exons of the same gene, is likely to account for this observed lack of colocalisation as subtle isoform switches and expression variation in independent exons can be concealed. We performed integrative cis-eQTL analysis using association statistics from twenty autoimmune diseases (560 independent loci) and RNA-Seq data from 373 individuals of the Geuvadis cohort profiled at gene-, isoform-, exon-, junction-, and intron-level resolution in lymphoblastoid cell lines...
October 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29040919/functional-analyses-of-the-interaction-of-chicken-interleukin-23-subunit-p19-with-il-12-subunit-p40-to-form-the-il-23-complex
#12
Anh Duc Truong, Cong Thanh Hoang, Yeojin Hong, Janggeun Lee, Kyungbaek Lee, Hyun S Lillehoj, Yeong Ho Hong
This study represents the first description of the cloning of chicken IL-23p19 (ChIL-23α) and the function of the IL-23 complex in birds. Multiple alignment of ChIL-23α with other known IL-23α amino acid sequences revealed regions of amino acid conservation. The homologies of ChIL-23α, IL-12p35, and similar mammalian subunits ranged between 26% and 42%. ChIL-23α consisted of four exons and three introns; similar to those in humans and mice, and limited conservation of synteny between the human and chicken genomes was observed...
October 14, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29031523/6-hydroxy-3-o-methyl-kaempferol-6-o-glucopyranoside-potentiates-the-anti-proliferative-effect-of-interferon-%C3%AE-%C3%AE-by-promoting-activation-of-the-jak-stat-signaling-by-inhibiting-socs3-in-hepatocellular-carcinoma-cells
#13
Orawan Wonganan, Yu-Jiao He, Xiao-Fei Shen, Kanjana Wongkrajang, Apichart Suksamrarn, Guo-Lin Zhang, Fei Wang
Suppressor of cytokine signaling 3 (SOCS3) is a key negative regulator of type I interferon (IFN α/β) signaling. Inhibition of SOCS3 by small molecules may be a new strategy to enhance the efficacy of type I IFN and reduce its side effects. We established a cell-based screening assay using human hepatoma HepG2 cells stably transfected with a plasmid wherein the luciferase reporter activity was propelled by interferon α-stimulated response element (ISRE), which is a motif specifically recognized by type I IFN-induced activation of Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway...
October 12, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29016674/re-evaluation-of-il-10-signaling-reveals-novel-insights-on-the-contribution-of-the-intracellular-domain-of-the-il-10r2-chain
#14
Ruud H P Wilbers, Debbie R van Raaij, Lotte B Westerhof, Jaap Bakker, Geert Smant, Arjen Schots
Interleukin-10 (IL-10) is an anti-inflammatory cytokine that plays a key role in maintaining immune homeostasis. IL-10-mediated responses are triggered upon binding to a heterodimeric receptor complex consisting of IL-10 receptor (IL-10R)1 and IL-10R2. Engagement of the IL-10R complex activates the intracellular kinases Jak1 and Tyk2, but the exact roles of IL-10R2 and IL-10R2-associated signaling via Tyk2 remain unclear. To elucidate the contribution of IL-10R2 and its signaling to IL-10 activity, we re-evaluated IL-10-mediated responses on bone marrow-derived dendritic cells, macrophages and mast cells...
2017: PloS One
https://www.readbyqxmd.com/read/28990043/%C3%AE-he-genetics-of-juvenile-idiopathic-arthritis-searching-for-new-susceptibility-loci
#15
Maria I Zervou, Despoina G Dimopoulou, Elias Eliopoulos, Maria Trachana, Polyxeni Pratsidou-Gkertsi, Athena Andreou, Prodromos Sidiropoulos, Demetrios A Spandidos, Alexandros Garyfallos, George N Goulielmos
Juvenile idiopathic arthritis (JIA) is an autoimmune disease that is characterized by persistent chronic arthritis and affected by genetic and environmental factors. Different genetic variations have been reported as risk factors for JIA. However, given that many results could not be replicated in individuals of different ancestral origin, it was assumed that heterogeneous genetic factors are involved in this disease. In the present study, we analyzed three single nucleotide polymorphisms (SNPs), namely PTPRC (rs10919563), TYK2 (rs34536443) and PRKCQ (rs4750316), which were found to be associated with JIA in previous studies...
December 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28973304/exome-wide-association-study-reveals-novel-psoriasis-susceptibility-locus-at-tnfsf15-and-rare-protective-alleles-in-genes-contributing-to-type-i-ifn-signalling
#16
Nick Dand, Sören Mucha, Lam C Tsoi, Satveer K Mahil, Philip E Stuart, Andreas Arnold, Hansjörg Baurecht, A David Burden, Kristina Callis Duffin, Vinod Chandran, Charles J Curtis, Sayantan Das, David Ellinghaus, Eva Ellinghaus, Charlotta Enerback, Tõnu Esko, Dafna D Gladman, Christopher E M Griffiths, Johann E Gudjonsson, Per Hoffman, Georg Homuth, Ulrike Hüffmeier, Gerald G Krueger, Matthias Laudes, Sang Hyuck Lee, Wolfgang Lieb, Henry W Lim, Sabine Löhr, Ulrich Mrowietz, Martina Müller-Nurayid, Markus Nöthen, Annette Peters, Proton Rahman, André Reis, Nick J Reynolds, Elke Rodriguez, Carsten O Schmidt, Sarah L Spain, Konstantin Strauch, Trilokraj Tejasvi, John J Voorhees, Richard B Warren, Michael Weichenthal, Stephan Weidinger, Matthew Zawistowski, Rajan P Nair, Francesca Capon, Catherine H Smith, Richard C Trembath, Goncalo R Abecasis, James T Elder, Andre Franke, Michael A Simpson, Jonathan N Barker
Psoriasis is a common inflammatory skin disorder for which multiple genetic susceptibility loci have been identified, but few resolved to specific functional variants. In this study, we sought to identify common and rare psoriasis-associated gene-centric variation. Using exome arrays we genotyped four independent cohorts, totalling 11 861 psoriasis cases and 28 610 controls, aggregating the dataset through statistical meta-analysis. Single variant analysis detected a previously unreported risk locus at TNFSF15 (rs6478108; P = 1...
November 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28972016/philadelphia-chromosome-like-acute-lymphoblastic-leukemia
#17
REVIEW
Sarah K Tasian, Mignon L Loh, Stephen P Hunger
Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia (ALL), also referred to as BCR-ABL1-like ALL, is a high-risk subset with a gene expression profile that shares significant overlap with that of Ph-positive (Ph+) ALL and is suggestive of activated kinase signaling. Although Ph+ ALL is defined by BCR-ABL1 fusion, Ph-like ALL cases contain a variety of genomic alterations that activate kinase and cytokine receptor signaling. These alterations can be grouped into major subclasses that include ABL-class fusions involving ABL1, ABL2, CSF1R, and PDGFRB that phenocopy BCR-ABL1 and alterations of CRLF2, JAK2, and EPOR that activate JAK/STAT signaling...
November 9, 2017: Blood
https://www.readbyqxmd.com/read/28916157/diabetes-the-tyk2-gene-and-the-interferon-response-in-search-for-environmental-causes
#18
Antonio Toniolo, Richard David Leslie
No abstract text is available yet for this article.
October 2017: EBioMedicine
https://www.readbyqxmd.com/read/28883754/the-activation-of-%C3%AE-2-adrenergic-receptor-in-the-spinal-cord-lowers-sepsis-induced-mortality
#19
Sung-Su Kim, Soo-Hyun Park, Jae-Ryung Lee, Jun-Sub Jung, Hong-Won Suh
The effect of clonidine administered intrathecally (i.t.) on the mortality and the blood glucose level induced by sepsis was examined in mice. To produce sepsis, the mixture of D-galactosamine (GaLN; 0.6 g/10 ml)/lipopolysaccharide (LPS; 27 µg/27 µl) was treated intraperitoneally (i.p.). The i.t. pretreatment with clonidine (5 µg/5 µl) increased the blood glucose level and attenuated mortality induced by sepsis in a dose-dependent manner. The i.t. post-treatment with clonidine up to 3 h caused an elevation of the blood glucose level and protected sepsis-induced mortality, whereas clonidine post-treated at 6, 9, or 12 h did not affect...
September 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28846454/glis3-and-tyk2-single-nucleotide-polymorphisms-are-not-associated-with-dermatomyositis-polymyositis-in-chinese-han-population
#20
Liubing Li, Si Chen, Qian Wang, Chanyuan Wu, Xiaoting Wen, Funing Yang, Chenxi Liu, Fengchun Zhang, Yongzhe Li
AIM: Racial differences and genetic overlap have been shown to be responsible for the difference in susceptibility to dermatomyositis (DM)/polymyositis (PM) in a variety of populations. Single nucleotide polymorphisms (SNPs) in the GLI-similar 3 (GLIS3) and tyrosine kinase 2 (TYK2) genes have been associated with various autoimmune diseases. The aim of this study was to investigate whether SNPs in GLIS3 (rs7020673, rs10758593, and rs10814916) and TYK2 (rs280519, rs2304256, rs17000730, and rs280501) were associated with an increase in susceptibility to DM/PM in a Chinese Han population...
September 2017: Genetic Testing and Molecular Biomarkers
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