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https://www.readbyqxmd.com/read/27919278/microrna-19b-3p-regulates-nasopharyngeal-carcinoma-radiosensitivity-by-targeting-tnfaip3-nf-%C3%AE%C2%BAb-axis
#1
Teng Huang, Li Yin, Jing Wu, Jia-Jia Gu, Jian-Zhong Wu, Dan Chen, Hong-Liang Yu, Kai Ding, Nan Zhang, Ming-Yu Du, Lu-Xi Qian, Zhi-Wei Lu, Xia He
BACKGROUND: Nasopharyngeal carcinoma (NPC) is among the most common squamous cell carcinoma in South China and Southeast Asia. Radiotherapy is the primary treatment for NPC. However, radioresistance acts as a significant factor that limits the efficacy of radiotherapy for NPC patients. Growing evidence supports that microRNAs (miRNAs) play an important role in radiation response. METHODS: Real-time quantitative PCR was used to analyze the expression of miR-19b-3p in NPC cell lines and NP69...
December 5, 2016: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/27863501/mutations-in-lrrk2-impair-nf-%C3%AE%C2%BAb-pathway-in-ipsc-derived-neurons
#2
Rakel López de Maturana, Valérie Lang, Amaia Zubiarrain, Amaya Sousa, Nerea Vázquez, Ana Gorostidi, Julio Águila, Adolfo López de Munain, Manuel Rodríguez, Rosario Sánchez-Pernaute
BACKGROUND: Mutations in leucine-rich repeat kinase 2 (LRRK2) contribute to both familial and idiopathic forms of Parkinson's disease (PD). Neuroinflammation is a key event in neurodegeneration and aging, and there is mounting evidence of LRRK2 involvement in inflammatory pathways. In a previous study, we described an alteration of the inflammatory response in dermal fibroblasts from PD patients expressing the G2019S and R1441G mutations in LRRK2. METHODS: Taking advantage of cellular reprogramming, we generated induced pluripotent stem cell (iPSC) lines and neurons thereafter, harboring LRRK2(G2019S) and LRRK2(R1441G) mutations...
November 18, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27861577/identifying-causal-genes-at-the-multiple-sclerosis-associated-region-6q23-using-capture-hi-c
#3
Paul Martin, Amanda McGovern, Jonathan Massey, Stefan Schoenfelder, Kate Duffus, Annie Yarwood, Anne Barton, Jane Worthington, Peter Fraser, Stephen Eyre, Gisela Orozco
BACKGROUND: The chromosomal region 6q23 has been found to be associated with multiple sclerosis (MS) predisposition through genome wide association studies (GWAS). There are four independent single nucleotide polymorphisms (SNPs) associated with MS in this region, which spans around 2.5 Mb. Most GWAS variants associated with complex traits, including these four MS associated SNPs, are non-coding and their function is currently unknown. However, GWAS variants have been found to be enriched in enhancers and there is evidence that they may be involved in transcriptional regulation of their distant target genes through long range chromatin looping...
2016: PloS One
https://www.readbyqxmd.com/read/27849177/the-interplay-of-tlr9-myeloid-cells-and-a20-in-periodontal-inflammation
#4
Katie E Crump, Jennifer C Oakley, Xia Xia-Juan, Theandra C Madu, Swathi Devaki, Erin C Mooney, Sinem E Sahingur
TLR9 deficient (TLR9(-/-)) mice are resistant to periodontitis, a disease characterized by a dysbiotic microbiota and deregulated immune response resulting in tooth loss and various systemic conditions. However, the mechanisms and biological pathways by which TLR9 instigates periodontal inflammation are yet to be identified. In a ligature-induced model of periodontitis, we demonstrate TLR9(-/-) mice exhibited significantly less alveolar bone loss compared to their wild-type (WT) counterparts. Consistent with the disease phenotype, gingival tissues showed significantly more inflammatory cell infiltrate in the WT ligated but not in the TLR9(-/-) ligated mice compared to their unligated controls...
November 14, 2016: Infection and Immunity
https://www.readbyqxmd.com/read/27845235/haploinsufficiency-of-tnfaip3-a20-by-germline-mutation-is-involved-in-autoimmune-lymphoproliferative-syndrome
#5
Masatoshi Takagi, Shohei Ogata, Hiroo Ueno, Kenichi Yoshida, Tzuwen Yeh, Akihiro Hoshino, Jinhua Piao, Motoy Yamashita, Mai Nanya, Tsubasa Okano, Michiko Kajiwara, Hirokazu Kanegane, Hideki Muramatsu, Yusuke Okuno, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Yuki Bando, Motohiro Kato, Yasuhide Hayashi, Satoru Miyano, Kohsuke Imai, Seishi Ogawa, Seiji Kojima, Tomohiro Morio
BACKGROUND: Autoimmune diseases in children are rare and can be difficult to diagnose. Autoimmune lymphoproliferative syndrome (ALPS) is a well-characterized pediatric autoimmune disease caused by mutations in genes associated with the FAS-dependent apoptosis pathway. In addition, various genetic alterations are associated with the ALPS-like phenotype. OBJECTIVE: The aim of the present study was to elucidate the genetic etiology of the ALPS-like phenotype. METHODS: Candidate genes associated with the ALPS-like phenotype were screened by whole exome sequencing...
November 11, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27814644/the-nf-kb-regulates-the-shp-1-expression-in-monocytes-in-congestive-heart-failure
#6
Mirko Pesce, Sara Franceschelli, Alessio Ferrone, Antonia Patruno, Alfredo Grilli, Maria Anna De Lutiis, Francesca R Pluchinotta, Sonia Bergante, Guido Tettamanti, Graziano Riccioni, Mario Felaco, Lorenza Speranza
It has been shown that functional recovery of patients with acute congestive heart failure (ACHF) after treatment with conventional drugs (CD) is mediated by suppression of inflammation in peripheral blood mononuclear cells. Here, we analyzed gene expression profiles of monocytes from symptomatic ACHF patients (NYHA Class III-IV) before and after pharmacological treatment with CD. The treatment was associated with selective down-regulation of "TNFR signaling" and pro-inflammatory mediators CCL5, MIP-1α receptor, CD14, ITGAM, and significant up-regulation of "TNFR signaling" as evidenced by increase in anti-inflammatory factors including NF-kBIA, TNFAIP3 and SHP-1...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27799070/capture-hi-c-identifies-a-novel-causal-gene-il20ra-in-the-pan-autoimmune-genetic-susceptibility-region-6q23
#7
Amanda McGovern, Stefan Schoenfelder, Paul Martin, Jonathan Massey, Kate Duffus, Darren Plant, Annie Yarwood, Arthur G Pratt, Amy E Anderson, John D Isaacs, Julie Diboll, Nishanthi Thalayasingam, Caroline Ospelt, Anne Barton, Jane Worthington, Peter Fraser, Stephen Eyre, Gisela Orozco
BACKGROUND: The identification of causal genes from genome-wide association studies (GWAS) is the next important step for the translation of genetic findings into biologically meaningful mechanisms of disease and potential therapeutic targets. Using novel chromatin interaction detection techniques and allele specific assays in T and B cell lines, we provide compelling evidence that redefines causal genes at the 6q23 locus, one of the most important loci that confers autoimmunity risk...
November 1, 2016: Genome Biology
https://www.readbyqxmd.com/read/27779104/tnfaip3-gene-rs10499194-rs13207033-polymorphisms-decrease-the-risk-of-rheumatoid-arthritis
#8
Ming-Jie Wang, Hao-Yu Yang, Hui Zhang, Xindie Zhou, Rui-Ping Liu, Yuan-Yuan Mi
Accumulating evidences suggested that tumor necrosis factor alpha inducible protein 3 (TNFAIP3) gene rs10499194, rs13207033 polymorphisms may be associated with the risk of rheumatoid arthritis (RA). However, these studies yielded contradictory findings. To clarify convincing associations, we conducted a comprehensive meta-analysis by searching in PubMed, Embase, and the China Knowledge Resource Integrated Database. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by using fixed-effect or random-effect models...
October 13, 2016: Oncotarget
https://www.readbyqxmd.com/read/27766462/sugar-modified-poly-propylene-imine-dendrimers-stimulate-the-nf-%C3%AE%C2%BAb-pathway-in-a-myeloid-cell-line
#9
Izabela Jatczak-Pawlik, Michal Gorzkiewicz, Maciej Studzian, Dietmar Appelhans, Brigitte Voit, Lukasz Pulaski, Barbara Klajnert-Maculewicz
PURPOSE: Fourth-generation poly(propylene imine) dendrimers fully surface-modified by maltose (dense shell, PPI-m DS) were shown to be biocompatible in cellular models, which is important for their application in drug delivery. We decided to verify also their inherent bioactivity, including immunomodulatory activity, for potential clinical applications. We tested their effects on the THP-1 monocytic cell line model of innate immunity effectors. METHODS: To estimate the cytotoxicity of dendrimers the reasazurin assay was performed...
October 20, 2016: Pharmaceutical Research
https://www.readbyqxmd.com/read/27726311/associations-between-tnfaip3-gene-polymorphisms-and-systemic-lupus-erythematosus-risk-an-updated-meta-analysis
#10
M-Y Zhang, X-K Yang, H-F Pan, D-Q Ye
In order to determine whether tumor necrosis factor alpha inducible protein 3 (TNFAIP3) gene polymorphisms confers susceptibility to systemic lupus erythematosus (SLE) in ethnically different populations. A meta-analysis was conducted to examine the association between TNFAIP3 polymorphisms and susceptibility to SLE. A systematic literature search was conducted to identify all relevant studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the strength of the association...
November 2016: HLA
https://www.readbyqxmd.com/read/27698734/c-ebp-%C3%AE-mrna-expression-is-upregulated-and-positively-correlated-with-the-expression-of-tnip1-tnfaip3-in-peripheral-blood-mononuclear-cells-from-patients-with-systemic-lupus-erythematosus
#11
Tian Qian, Yan Chen, Xiaowei Shi, Jian Li, Fei Hao, Dongmei Zhang
CCAAT/enhancer-binding protein β (C/EBP β) has important roles in numerous signaling pathways. The expression of the majority of regulators and target gene products of C/EBP β, including tumor necrosis factor α-induced protein 3 (TNFAIP3) and TNFAIP3-interacting protein 1 (TNIP1), are upregulated in patients with systemic lupus erythematosus (SLE). The aim of the present study was to investigate whether C/EBP β expression is associated with SLE pathogenesis and correlates with TNIP1 and TNFAIP3 expression...
October 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27659348/upregulation-of-the-c-ebp-%C3%AE-lap-isoform-could-be-due-to-decreased-tnfaip3-tnip1-expression-in-the-peripheral-blood-mononuclear-cells-of-patients-with-systemic-lupus-erythematosus
#12
Tian Qian, Fangru Chen, Xiaowei Shi, Jian Li, Min Li, Yan Chen, Fei Hao, Dongmei Zhang
OBJECTIVES: We aimed to examine CCAAT/enhancer-binding protein β (C/EBP β), TNF-alpha-induced protein 3 (TNFAIP3), and TNFAIP3-interacting protein 1 (TNIP1) expression in peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematosus (SLE) patients to assess their relationship in SLE pathogenesis. METHODS: C/EBP β, TNIP1, and TNFAIP3 expression was assessed in PBMCs from 20 SLE patients and 20 controls by western blotting. The correlation between C/EBP β/TNFAIP3/TNIP1 expression and SLE disease activity was determined by Spearman's rank...
September 23, 2016: Modern Rheumatology
https://www.readbyqxmd.com/read/27647909/whole-exome-sequencing-identifies-multiple-loss-of-function-mutations-of-nf-%C3%AE%C2%BAb-pathway-regulators-in-nasopharyngeal-carcinoma
#13
Hong Zheng, Wei Dai, Arthur Kwok Leung Cheung, Josephine Mun Yee Ko, Rebecca Kan, Bonnie Wing Yan Wong, Merrin Man Long Leong, Mingdan Deng, Tommy Chin Tung Kwok, Jimmy Yu-Wai Chan, Dora Lai-Wan Kwong, Anne Wing-Mui Lee, Wai Tong Ng, Roger Kai Cheong Ngan, Chun Chung Yau, Stewart Tung, Victor Ho-Fun Lee, Ka-On Lam, Chung Kong Kwan, Wing Sum Li, Stephen Yau, Kwok-Wah Chan, Maria Li Lung
Nasopharyngeal carcinoma (NPC) is an epithelial malignancy with a unique geographical distribution. The genomic abnormalities leading to NPC pathogenesis remain unclear. In total, 135 NPC tumors were examined to characterize the mutational landscape using whole-exome sequencing and targeted resequencing. An APOBEC cytidine deaminase mutagenesis signature was revealed in the somatic mutations. Noticeably, multiple loss-of-function mutations were identified in several NF-κB signaling negative regulators NFKBIA, CYLD, and TNFAIP3 Functional studies confirmed that inhibition of NFKBIA had a significant impact on NF-κB activity and NPC cell growth...
October 4, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27640899/tnfaip3-a-negative-regulator-of-the-tlr-signaling-pathway-is-a-potential-predictive-biomarker-of-response-to-antidepressant-treatment-in-major-depressive-disorder
#14
Yi-Yung Hung, Chin-Chuen Lin, Hong-Yo Kang, Tiao-Lai Huang
Inflammation and abnormalities in Toll-like receptor (TLR) expression and activation have been linked to major depressive disorder (MDD). However, negative regulators of TLR pathways have not been previously investigated in this context. Here, we sought to investigate the association of depression severity, measured by the 17-item Hamilton Depression Rating Scale (HAMD-17), with mRNA expression levels of negative regulators of the TLR pathway, including SOCS1, TOLLIP, SIGIRR, MyD88s, NOD2 and TNFAIP3, in peripheral blood mononuclear cells (PBMCs) from 100 patients with MDD and 53 healthy controls, before and after treatment with antidepressants...
September 15, 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/27637078/mir-125b-regulates-differentiation-and-metabolic-reprogramming-of-t-cell-acute-lymphoblastic-leukemia-by-directly-targeting-a20
#15
Zixing Liu, Kelly R Smith, Hung T Khong, Jingshan Huang, Eun-Young Erin Ahn, Ming Zhou, Ming Tan
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematopoietic malignancy. Although it has been reported that overexpression of miR-125b leads to T-ALL development, the underlying mechanisms of miR-125b action are still unclear. The goal of this study is to delineate the role of miR-125b in T-ALL development. We found that miR-125b is highly expressed in undifferentiated leukemic T cells (CD4-negative) while its expression is low in differentiated T cells (CD4-positive). Overexpression of miR-125b increased the CD4-negative population in T cells, whereas depletion of miR-125b by miR-125b-sponge decreased the CD4-negative cell population...
September 14, 2016: Oncotarget
https://www.readbyqxmd.com/read/27588072/tumor-necrosis-factor-%C3%AE-induced-protein-3-protects-zinc-transporter-8-against-proinflammatory-cytokine-induced-downregulation
#16
Liqing Cheng, Dongmei Zhang, Bing Chen
Zinc transporter 8 (ZnT8) is exclusively expressed in the pancreatic islet and is essential for insulin crystallization, hexamerization and secretion. Tumor necrosis factor α-induced protein-3 (TNFAIP3) is a zinc finger protein that serves a major role in the negative feedback regulation of NF-κB signaling in response to multiple stimuli, and is a central regulator of immunopathology. Although the role of TNFAIP3 in diabetes has been extensively studied, its effect on ZnT8 has not been fully elucidated. The present study aimed to verify whether proinflammatory cytokines, tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β), are able to affect ZnT8 expression in islet cells...
September 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27575017/single-cell-analyses-reveal-an-attenuated-nf-%C3%AE%C2%BAb-response-in-the-salmonella-infected-fibroblast
#17
Estel Ramos-Marquès, Samuel Zambrano, Alberto Tiérrez, Marco E Bianchi, Alessandra Agresti, Francisco García-Del Portillo
The eukaryotic transcriptional regulator Nuclear Factor kappa B (NF-κB) plays a central role in the defense to pathogens. Despite this, few studies have analyzed NF-κB activity in single cells during infection. Here, we investigated at the single cell level how NF-κB nuclear localization - a proxy for NF-κB activity - oscillates in infected and uninfected fibroblasts co-existing in cultures exposed to Salmonella enterica serovar Typhimurium. Fibroblasts were used due to the capacity of S. Typhimurium to persist in this cell type...
August 30, 2016: Virulence
https://www.readbyqxmd.com/read/27566587/recurrent-mutations-in-nf-%C3%AE%C2%BAb-pathway-components-kmt2d-and-notch1-2-in-ocular-adnexal-malt-type-marginal-zone-lymphomas
#18
Patricia Johansson, Ludger Klein-Hitpass, Florian Grabellus, Georg Arnold, Wolfram Klapper, Roman Pförtner, Ulrich Dührsen, Anja Eckstein, Jan Dürig, Ralf Küppers
The pathogenesis of ocular adnexal marginal zone lymphomas of mucosa-associated lymphatic tissue-type (OAML) is still poorly understood. We analyzed 63 cases of such lymphomas for non-synonymous mutations in 24 candidate genes by amplicon sequencing. We validated frequent mutations in the NF-κB regulators MYD88, TNFAIP3 and TNIP1 in OAML, but also identified recurrent mutations in several additional components of the NF-κB pathway, including BCL10 and NFKBIA. Overall, 60% of cases had mutations in at least one component of NF-κB signaling, pointing to a central role of its genetic deregulation in OAML pathogenesis...
August 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27564082/polymorphisms-in-cd84-il12b-and-tnfaip3-are-associated-with-response-to-biologics-in-patients-with-psoriasis
#19
J M P A van den Reek, M J H Coenen, M van de L'Isle Arias, J Zweegers, D Rodijk-Olthuis, J Schalkwijk, S H Vermeulen, I Joosten, P C M van de Kerkhof, M M B Seyger, P L J M Zeeuwen, E M G J de Jong
BACKGROUND: The effectiveness of biologics for psoriasis shows heterogeneity among patients. With pharmacogenetic markers, it might be possible to predict treatment response. OBJECTIVES: We aimed to test the association between genetic markers and the response to biologics in psoriasis (etanercept, adalimumab, ustekinumab) in a prospective cohort. METHODS: We investigated the copy number variation in LCE3B and 3C genes, and eight single nucleotide polymorphisms (SNPs) in HLA-C*06, CD84, IL12b, IL23R, TRAF3IP2, ERAP1, IFIH1 and TNFAIP3...
August 26, 2016: British Journal of Dermatology
https://www.readbyqxmd.com/read/27554374/generation-of-%C3%AE-1-3-galactosyltransferase-knocked-out-transgenic-cloned-pigs-with-knocked-in-five-human-genes
#20
Dae-Jin Kwon, Dong-Hwan Kim, In-Sul Hwang, Dong-Ern Kim, Hyung-Joo Kim, Jang-Seong Kim, Kichoon Lee, Gi-Sun Im, Jeong-Woong Lee, Seongsoo Hwang
Recent progress in genetic manipulation of pigs designated for xenotransplantation ha6s shown considerable promise on xenograft survival in primates. However, genetic modification of multiple genes in donor pigs by knock-out and knock-in technologies, aiming to enhance immunological tolerance against transplanted organs in the recipients, has not been evaluated for health issues of donor pigs. We produced transgenic Massachusetts General Hospital piglets by knocking-out the α-1,3-galactosyltransferase (GT) gene and by simultaneously knocking-in an expression cassette containing five different human genes including, DAF, CD39, TFPI, C1 inhibitor (C1-INH), and TNFAIP3 (A20) [GT(-(DAF/CD39/TFPI/C1-INH/TNFAIP3)/+)] that are connected by 2A peptide cleavage sequences to release individual proteins from a single translational product...
August 23, 2016: Transgenic Research
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