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https://www.readbyqxmd.com/read/29343543/an-autoimmune-disease-associated-risk-variant-in-the-tnfaip3-gene-plays-a-protective-role-in-brucellosis-that-is-mediated-by-the-nf-kappa-b-signaling-pathway
#1
Lixin Lou, Wanguo Bao, Xianjun Liu, Hongxiao Song, Yang Wang, Kaiyu Zhang, Wenjing Gao, Haijun Li, Zhengkun Tu, Shaofeng Wang
Naturally occurring functional variants (rs148314165 and rs200820567, collectively referred to as TT>A) reduce the expression of the tumor necrosis factor α-induced protein 3 (TNFAIP3) gene, a negative regulator of NF-κB signaling, and predispose individuals to autoimmune disease. In this analysis, we conducted a genetic association study of the TT>A variants in 1209 controls and in 150 patients with brucellosis, an infectious disease, and further assessed the role of the variants in brucellosis. Our data demonstrated that the TT>A variants were correlated with cases of brucellosis (P = 0...
January 17, 2018: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/29327472/mesenchymal-stem-cell-deficiency-influences-megakaryocytopoiesis-through-the-tnfaip3-nf-%C3%AE%C2%BAb-smad-pathway-in-patients-with-immune-thrombocytopenia
#2
Yun He, Lin-Lin Xu, Fei-Er Feng, Qian-Ming Wang, Xiao-Lu Zhu, Chen-Cong Wang, Jia-Min Zhang, Hai-Xia Fu, Lan-Ping Xu, Kai-Yan Liu, Xiao-Jun Huang, Xiao-Hui Zhang
Immune thrombocytopenia (ITP) is an autoimmune disease. Mesenchymal stem cells (MSCs) play important roles in the physiology and homeostasis of the haematopoietic system, including supporting megakaryocytic differentiation from CD34+ haematopoietic progenitor cells. Tumour necrosis factor alpha-induced protein 3 (TNFAIP3, also termed A20) plays a key role in terminating NF-κB signalling. Human genetic studies showed that the polymorphisms of the TNFAIP3 gene may contribute to ITP susceptibility. In this study, we showed a significant decrease in TNFAIP3 and increase in NF-κB/SMAD7 in ITP-MSCs...
January 12, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29317407/a20-haploinsufficiency-ha20-clinical-phenotypes-and-disease-course-of-patients-with-a-newly-recognised-nf-kb-mediated-autoinflammatory-disease
#3
Florence A Aeschlimann, Ezgi D Batu, Scott W Canna, Ellen Go, Ahmet Gül, Patrycja Hoffmann, Helen L Leavis, Seza Ozen, Daniella M Schwartz, Deborah L Stone, Annet van Royen-Kerkof, Daniel L Kastner, Ivona Aksentijevich, Ronald M Laxer
OBJECTIVES: The association between mutations in TNFAIP3, encoding the NF-kB regulatory protein A20, and a new autoinflammatory disease has recently been recognised. This study aims at describing the clinical phenotypes and disease course of patients with A20 haploinsufficiency (HA20). METHODS: Data for all cases from the initial publication, and additional cases identified through collaborations since, were collected using standardised data collection forms. RESULTS: A total of 16 patients (13 female) from seven families with a genetic diagnosis of HA20 were included...
January 9, 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29285249/retinol-dehydrogenase-10-promotes-development-and-progression-of-human-glioma-via-the-tweak-nf-%C3%AE%C2%BAb-axis
#4
Feng Guan, Liang Wang, Shuyu Hao, Zhen Wu, Jian Bai, Zhuang Kang, Quan Zhou, Hong Chang, Hui Yin, Da Li, Kaibin Tian, Junpeng Ma, Guijun Zhang, Junting Zhang
Retinol dehydrogenase-10 (RDH10) is a member of the short-chain dehydrogenase/reductase family, which plays an important role in retinoic acid (RA) synthesis. Here, we show that RDH10 is highly expressed in human gliomas, and its expression correlates with tumor grade and patient survival times. In vitro, lentivirus-mediated shRNA knockdown of RDH10 suppressed glioma cell proliferation, survival, and invasiveness and cell cycle progression. In vivo, RDH10 knockdown reduced glioma growth in nude mice. Microarray analysis revealed that RDH10 silencing reduces expression of TNFRSF12A (Fn14), TNFSF12 (TWEAK), TRAF3, IKBKB (IKK-β), and BMPR2, while it increases expression of TRAF1, NFKBIA (IκBα), NFKBIE (IκBε), and TNFAIP3...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29274253/mir-200a-enhances-trail-induced-apoptosis-in-gastric-cancer-cells-by-targeting-a20
#5
Tianshu Guo, Ye Zhang, Xiujuan Qu, Xiaofang Che, Ce Li, Yibo Fan, Xing Wan, Rui Ma, Kezuo Hou, Huiming Zhou, Xiaowei He, Xuejun Hu, Yunpeng Liu, Ling Xu
Tumor necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL) triggers apoptosis by inducing the death-inducing signaling complex (DISC) formation. Recently, TNFα-induced protein 3 (TNFAIP3, A20) was reported to prevent TRAIL-induced caspase 8 cleavage in the DISC by mediating ubiquitination of RIP1 in glioblastoma. However, whether A20 regulates caspase 8 cleavage in the DISC when TRAIL induces apoptosis in gastric cancer cells is unknown. In the present study, A20 interacted with RIP1 and DR4 in MGC803 and SGC7901 gastric cancer cells...
December 23, 2017: Cell Biology International
https://www.readbyqxmd.com/read/29248493/tnfaip3-a20-acts-as-master-switch-in-tnf%C3%AE-blockade-driven-il-17a-expression
#6
Paulo Cm Urbano, Raúl Aguirre-Gamboa, Angel Ashikov, Bennie van Heeswijk, Anja Krippner-Heidenreich, Henk Tijssen, Yang Li, Valderilio F Azevedo, Lisa Jt Smits, Frank Hoentjen, Irma Joosten, Hans Jpm Koenen
BACKGROUND: Anti-TNF inhibitors successfully improve life quality of patients suffering from inflammatory disease. Unfortunately, not all patients respond to anti-TNF therapy and some patients show paradoxical immune side-effects, which is poorly understood. Surprisingly, anti-TNF agents were shown to promote IL-17A production, with as yet unknown clinical implications. OBJECTIVE: To investigate the molecular mechanism underlying anti-TNF driven IL-17A expression and the clinical implications of this phenomenon...
December 14, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29227477/the-deubiquitinating-enzyme-tnfaip3-mediates-inactivation-of-hepatic-ask1-and-ameliorates-nonalcoholic-steatohepatitis
#7
Peng Zhang, Pi-Xiao Wang, Ling-Ping Zhao, Xin Zhang, Yan-Xiao Ji, Xiao-Jing Zhang, Chun Fang, Yue-Xin Lu, Xia Yang, Mao-Mao Gao, Yan Zhang, Song Tian, Xue-Yong Zhu, Jun Gong, Xin-Liang Ma, Feng Li, Zhihua Wang, Zan Huang, Zhi-Gang She, Hongliang Li
Activation of apoptosis signal-regulating kinase 1 (ASK1) in hepatocytes is a key process in the progression of nonalcoholic steatohepatitis (NASH) and a promising target for treatment of the condition. However, the mechanism underlying ASK1 activation is still unclear, and thus the endogenous regulators of this kinase remain open to be exploited as potential therapeutic targets. In screening for proteins that interact with ASK1 in the context of NASH, we identified the deubiquitinase tumor necrosis factor alpha-induced protein 3 (TNFAIP3) as a key endogenous suppressor of ASK1 activation, and we found that TNFAIP3 directly interacts with and deubiquitinates ASK1 in hepatocytes...
December 11, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29212169/ccctc-binding-factor-inhibits-breast-cancer-cell-proliferation-and-metastasis-via-inactivation-of-the-nuclear-factor-kappab-pathway
#8
Jie Wu, Peng-Chang Li, Jun-Yi Pang, Guo-You Liu, Xue-Min Xie, Jia-Yao Li, Yi-Cong Yin, Jian-Hua Han, Xiu-Zhi Guo, Ling Qiu
CCCTC-binding factor (CTCF) is an important epigenetic regulator implicated in multiple cellular processes, including growth, proliferation, differentiation, and apoptosis. Although CTCF deletion or mutation has been associated with human breast cancer, the role of CTCF in breast cancer is questionable. We investigated the biological functions of CTCF in breast cancer and the underlying mechanism. The results showed that CTCF expression in human breast cancer cells and tissues was significantly lower than that in normal breast cells and tissues...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29202196/effects-of-dlc1-deficiency-on-endothelial-cell-contact-growth-inhibition-and-angiosarcoma-progression
#9
David Sánchez-Martín, Atsushi Otsuka, Kenji Kabashima, Taekyu Ha, Dunrui Wang, Xiaolan Qian, Douglas R Lowy, Giovanna Tosato
Background: Deleted in Liver Cancer 1 (DLC1) is a tumor suppressor gene frequently deleted in cancer. However, DLC1 is not known to be deleted in angiosarcoma, an aggressive malignancy of endothelial cell derivation. Additionally, the physiologic functions of DLC1 protein in endothelial cells are poorly defined. Methods: We investigated the effects of shRNA-induced DLC1 depletion in endothelial cells. Cell growth was measured by 3H thymidine incorporation, IncuCyte imaging, and population doublings; cell death by cell cycle analysis; gene expression by Affimetrix arrays and quantitative polymerase chain reaction; NF-κB activity by reporter assays; and protein levels by immunoblotting and immunofluorescence staining...
November 30, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29190981/a20-enhances-the-radiosensitivity-of-hepatocellular-carcinoma-cells-to-60co-%C3%AE-ionizing-radiation
#10
Rui Liu, Dongli Zhao, Xiaozhi Zhang, Suxia Han, Yunyi Yang, Jinlu Ma, Du Meng
The radioresistance of hepatocellular carcinoma (HCC) cells is a critical obstacle for effectively applying radiotherapy (RT) in HCC treatment. NF-κB, an important transcription factor, can influence critical cell fate decisions by promoting cell survival or anti-apoptosis in response to cell-stress, e.g. chemotherapies or ionizing radiation (IR). A20, also named as tumor necrosis factor α induced protein 3 (TNFAIP3), is a dominant negative regulator of NF-κB pathway and its functions in HCC are largely unknown...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29140941/phenotype-and-management-of-infantile-onset-inflammatory-bowel-disease-experience-from-a-tertiary-care-center-in-china
#11
Ziqing Ye, Ying Zhou, Ying Huang, Yuhuan Wang, Junping Lu, Zifei Tang, Shijian Miao, Kuiran Dong, Zhinong Jiang
BACKGROUND: Infantile-onset inflammatory bowel disease (IBD) comprises rare and clinically severe disorders. We examined the phenotypes and genetic causes of patients with infantile-onset IBD from a tertiary medical center. METHODS: We enrolled 38 patients with infantile-onset IBD and applied standardized treatment with medical, surgical, and supportive care. Targeted sequencing and whole-exome sequencing were performed. Clinical data were retrieved from medical records...
December 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/29101382/deconvolution-of-transcriptional-networks-in-post-traumatic-stress-disorder-uncovers-master-regulators-driving-innate-immune-system-function
#12
Abolfazl Doostparast Torshizi, Kai Wang
Post-Traumatic Stress Disorder (PTSD) is a psychiatric disorder that develops in individuals experiencing a shocking incident, but the underlying disease susceptibility gene networks remain poorly understood. Breen et al. conducted a Weighted Gene Co-expression Network Analysis on PTSD, and identified a dysregulated innate immune module associated with PTSD development. To further identify the Master Regulators (MRs) driving the network function, here we deconvoluted the transcriptional networks on the same datasets using ARACNe (Algorithm for Reconstruction of Accurate Cellular Networks) followed by protein activity analysis...
November 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28988144/intracelluar-delivery-of-a20-protein-inhibits-tnf%C3%AE-induced-nf-%C3%AE%C2%BAb-activation
#13
Hye-Rim Lee, Jin Choi, Seung Hoon Lee, Mi-La Cho, Dae-Myung Jue
A20 (also known as TNFAIP3) is a potent anti-inflammatory protein that suppresses many intracellular signaling pathways induced by inflammatory cytokines and bacterial and viral pathogens. The anti-inflammatory function of A20 depends on its modulation of or binding to polyubiquitin chains on key signaling proteins in the nuclear factor-κB (NF-κB) pathway. To test whether A20 can be used as therapeutic agent in these inflammatory diseases, we prepared a recombinant cell-penetrating form of A20 (TAT-A20) for intracellular delivery and examined its effect on tumor necrosis factor-α (TNFα)-induced NF-κB activation...
October 4, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28983055/pattern-of-somatic-mutations-in-patients-with-waldenstr%C3%A3-m-macroglobulinemia-or-igm-monoclonal-gammopathy-of-undetermined-significance
#14
Marzia Varettoni, Silvia Zibellini, Irene Defrancesco, Virginia Valeria Ferretti, Ettore Rizzo, Luca Malcovati, Anna Gallì, Matteo Giovanni Della Porta, Emanuela Boveri, Luca Arcaini, Chiara Candido, Marco Paulli, Mario Cazzola
We analyzed MYD88 and CXCR4 mutation status of 260 patients with Waldenström macroglobulinemia or IgM monoclonal gammopathy of undetermined significance using allele-specific real time quantitative PCR and Sanger sequencing respectively. A subgroup of 119 patients was further studied with next-generation sequencing of 11 target genes (MYD88, CXCR4, ARID1-A, KMT2D, NOTCH2, TP53, PRDM1, CD79B, TRAF3, MYBBP1A, TNFAIP3). MYD88 (L265P) was found at diagnosis in 91% of patients with Waldenström macroglobulinemia and in 60% of patients with IgM monoclonal gammopathy of undetermined significance using allele-specific PCR...
October 5, 2017: Haematologica
https://www.readbyqxmd.com/read/28962035/immune-cell-and-transcriptomic-analysis-of-the-human-decidua-in-term-and-preterm-parturition
#15
S F Rinaldi, S Makieva, P T Saunders, A G Rossi, J E Norman
STUDY QUESTION: Is labour, both at term and preterm, associated with alterations in decidual lymphocyte densities and widespread changes to the decidual transcriptome? SUMMARY ANSWER: The onset of parturition, both at term and preterm, is associated with widespread gene expression changes in the decidua, many of which are related to inflammatory signalling, but is not associated with changes in the number of any of the decidual lymphocyte populations examined. WHAT IS KNOWN ALREADY: Given its location, directly at the maternal-foetal interface, the decidua is likely to play a pivotal role in the onset of parturition, however, the molecular events occurring in the decidua in association with the onset of labour, both at term and preterm, remain relatively poorly defined...
August 18, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28960754/genetic-heterogeneity-of-uncharacterized-childhood-autoimmune-diseases-with-lymphoproliferation
#16
Masatoshi Takagi, Akihiro Hoshino, Kenichi Yoshida, Hiroo Ueno, Kohsuke Imai, Jinhua Piao, Hirokazu Kanegane, Motoi Yamashita, Tsubasa Okano, Hideki Muramatsu, Yusuke Okuno, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Seishi Ogawa, Yasuhide Hayashi, Seiji Kojima, Tomohiro Morio
Autoimmune diseases in children are rare and can be difficult to diagnose.  Single causative genes have been identified for some pediatric autoimmune diseases. Such orphan diseases may not be diagnosed properly due to the variability of patients' phenotypes. Guidelines for the diagnostic process need to be developed. Fifteen patients with uncharacterized childhood autoimmune diseases with lymphoproliferation that had negative testing for autoimmune lymphoproliferative syndrome were subjected to whole-exome sequencing to identify genes associated with these conditions...
September 29, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28934431/genetic-profiling-and-comorbidities-of-zika-infection
#17
Mohammad Ali Moni, Pietro Lio'
Background: The difficulty in distinguishing infection by Zika virus (ZIKV) from other flaviviruses is a global health concern, particularly given the high risk of neurologic complications (including Guillain-Barré syndrome [GBS]) with ZIKV infection. Methods: We developed quantitative frameworks to compare and explore infectome, diseasome, and comorbidity of ZIKV infections. We analyzed gene expression microarray and RNA-Seq data from ZIKV, West Nile fever (WNF), chikungunya, dengue, yellow fever, Japanese encephalitis virus, GBS, and control datasets...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28903990/the-influence-of-type-1-diabetes-genetic-susceptibility-regions-age-sex-and-family-history-to-the-progression-from-multiple-autoantibodies-to-type-1-diabetes-a-teddy-study-report
#18
Jeffrey P Krischer, Xiang Liu, Åke Lernmark, William A Hagopian, Marian J Rewers, Jin-Xiong She, Jorma Toppari, Anette-G Ziegler, Beena Akolkar
This paper seeks to determine whether factors related to autoimmunity risk remain significant after the initiation of two or more diabetes-related autoantibodies and continue to contribute to T1D risk among autoantibody positive children in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Characteristics included are age at multiple autoantibody positivity, sex, selected high-risk HLA-DR-DQ genotypes, relationship to a family member with T1D, autoantibody at seroconversion, INS gene (rs1004446_A), and non-HLA gene polymorphisms identified by the Type 1 Diabetes Genetics Consortium...
September 13, 2017: Diabetes
https://www.readbyqxmd.com/read/28892161/a-gene-is-known-by-the-company-it-keeps-enrichment-of-tnfaip3-gene-aberrations-in-malt-lymphomas-expressing-ighv4-34-antigen-receptors
#19
Andreas Agathangelidis, Aliki Xochelli, Kostas Stamatopoulos
Associations between immunoglobulin (IG) receptors with distinctive immunogenetic features and particular gene mutations are a recurring theme in mature B-cell lymphomas. Relevant observations have been made in chronic lymphocytic leukemia (CLL), where gene mutations are distributed asymmetrically in cases bearing or not somatic hypermutations within the clonotypic immunoglobulin heavy chain variable region (IGHV) genes (e.g. TP53 mutations predominate in IG-unmutated CLL, whereas the opposite is seen for MYD88 mutations, enriched in IG-mutated CLL) and in subsets of cases with stereotyped IG (enrichment for SF3B1 mutations in CLL subset #2)...
September 11, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28888782/tnf-%C3%AE-induced-protein-3-levels-in-lung-dendritic-cells-instruct-th2-or-th17%C3%A2-cell-differentiation-in-eosinophilic-or-neutrophilic-asthma
#20
Heleen Vroman, Ingrid M Bergen, Jennifer A C van Hulst, Menno van Nimwegen, Denise van Uden, Martijn J Schuijs, Saravanan Y Pillai, Geert van Loo, Hamida Hammad, Bart N Lambrecht, Rudi W Hendriks, Mirjam Kool
BACKGROUND: It is currently unknown why allergen exposure or environmental triggers in patients with mild-to-moderate asthma result in TH2-mediated eosinophilic inflammation, whereas patients with severe asthma often present with TH17-mediated neutrophilic inflammation. The activation state of dendritic cells (DCs) is crucial for both TH2 and TH17 cell differentiation and is mediated through nuclear factor κB activation. Ablation of TNF-α-induced protein 3 (TNFAIP3), one of the crucial negative regulators of nuclear factor κB activation in myeloid cells and DCs, was shown to control DC activation...
September 6, 2017: Journal of Allergy and Clinical Immunology
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