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https://www.readbyqxmd.com/read/29463935/a20-tnfaip3-alterations-in-primary-intestinal-diffuse-large-b-cell-lymphoma
#1
Masayoshi Fujii, Katsuyoshi Takata, Shih-Sung Chuang, Tomoko Miyata-Takata, Midori Ando, Yasuharu Sato, Tadashi Yoshino
The gastrointestinal (GI) tract is the most frequently involved site of extranodal non-Hodgkin lymphomas, and diffuse large B-cell lymphoma (DLBCL) is the most common subtype occurring in the GI tract. TNFAIP3 (A20) genetic alterations were reported to be involved in DLBCL's pathogenesis and a portion of GI-DLBCL cases harbor this alteration. However, the frequency and clinicopathological relations focusing on small and large intestinal DLBCL are unclear. Here, we examined A20 deletion and protein expression and analyzed the clinicopathological features of 52 cases of primary intestinal DLBCL...
February 2018: Acta Medica Okayama
https://www.readbyqxmd.com/read/29457987/the-rap2c-gtpase-facilitates-b-cell-receptor-induced-reorientation-of-the-microtubule-organizing-center
#2
Jia C Wang, Jeff Y-J Lee, May Dang-Lawson, Caitlin Pritchard, Michael R Gold
When B lymphocytes encounter antigen-bearing surfaces, B-cell receptor (BCR) signaling initiates remodeling of the F-actin network and reorientation of the microtubule-organizing center (MTOC) towards the antigen contact site. We have previously shown that the Rap1 GTPase, an evolutionarily conserved regulator of cell polarity, is essential for these processes and that Rap1-regulated actin remodeling is required for MTOC polarization. The role of Rap2 proteins in establishing cell polarity is not well understood...
February 19, 2018: Small GTPases
https://www.readbyqxmd.com/read/29440643/dissection-and-function-of-autoimmunity-associated-tnfaip3-a20-gene-enhancers-in-humanized-mouse-models
#3
Upneet K Sokhi, Mark P Liber, Laura Frye, Sungho Park, Kyuho Kang, Tania Pannellini, Baohong Zhao, Rada Norinsky, Lionel B Ivashkiv, Shiaoching Gong
Enhancers regulate gene expression and have been linked with disease pathogenesis. Little is known about enhancers that regulate human disease-associated genes in primary cells relevant for pathogenesis. Here we use BAC transgenics and genome editing to dissect, in vivo and in primary immune cells, enhancers that regulate human TNFAIP3, which encodes A20 and is linked with autoimmune diseases. A20 expression is dependent on a topologically associating subdomain (sub-TAD) that harbors four enhancers, while another >20 enhancers in the A20 locus are redundant...
February 13, 2018: Nature Communications
https://www.readbyqxmd.com/read/29433938/b-cell-lymphoma-immunotherapy-using-tlr9-targeted-oligonucleotide-stat3-inhibitors
#4
Xingli Zhao, Zhuoran Zhang, Dayson Moreira, Yu-Lin Su, Haejung Won, Tomasz Adamus, Zhenyuan Dong, Yong Liang, Hongwei H Yin, Piotr Swiderski, Raju K Pillai, Larry Kwak, Stephen Forman, Marcin Kortylewski
Growing evidence links the aggressiveness of non-Hodgkin's lymphoma, especially the activated B cell-like type diffuse large B cell lymphomas (ABC-DLBCLs) to Toll-like receptor 9 (TLR9)/MyD88 and STAT3 transcription factor signaling. Here, we describe a dual-function molecule consisting of a clinically relevant TLR9 agonist (CpG7909) and a STAT3 inhibitor in the form of a high-affinity decoy oligodeoxynucleotide (dODN). The CpG-STAT3dODN blocked STAT3 DNA binding and activity, thus reducing expression of downstream target genes, such as MYC and BCL2L1, in human and mouse lymphoma cells...
January 17, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29431121/methotrexate-limits-inflammation-through-an-a20-dependent-cross-tolerance-mechanism
#5
Cristina Municio, Ángeles Dominguez-Soto, Sara Fuentelsaz-Romero, Amalia Lamana, Nuria Montes, Víctor D Cuevas, Raquel García Campos, José L Pablos, Isidoro González-Álvaro, Amaya Puig-Kröger
OBJECTIVES: Methotrexate (MTX) is the anchor drug for treatment of rheumatoid arthritis (RA), but the mechanism of its anti-inflammatory action is not fully understood. In RA, macrophages display a proinflammatory polarisation profile that resembles granulocyte-macrophage colony-stimulating factor (GM-CSF)-differentiated macrophages and the response to MTX is only observed in thymidylate synthase+ GM-CSF-dependent macrophages. To determine the molecular basis for the MTX anti-inflammatory action, we explored toll-like receptor (TLR), RA synovial fluid (RASF) and tumour necrosis factor receptor (TNFR)-initiated signalling in MTX-exposed GM-CSF-primed macrophages...
February 3, 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29416753/co-targeting-of-tiam1-rac1-and-notch-ameliorates-chemoresistance-against-doxorubicin-in-a-biomimetic-3d-lymphoma-model
#6
Muhammad Ikram, Yeseon Lim, Sun-Yong Baek, Songwan Jin, Young Hun Jeong, Jong-Young Kwak, Sik Yoon
Lymphoma is a heterogeneous disease with a highly variable clinical course and prognosis. Improving the prognosis for patients with relapsed and treatment-resistant lymphoma remains challenging. Current in vitro drug testing models based on 2D cell culture lack natural tissue-like structural organization and result in disappointing clinical outcomes. The development of efficient drug testing models using 3D cell culture that more accurately reflects in vivo behaviors is vital. Our aim was to establish an in vitro 3D lymphoma model that can imitate the in vivo 3D lymphoma microenvironment...
January 5, 2018: Oncotarget
https://www.readbyqxmd.com/read/29397835/-establishment-of-a20-murine-b-lymphoma-transplantation-model-labeled-with-luciferase
#7
Sha-Sha Zhao, Li-Xun Guan, Zhe Gao, Fei-Yan Wang, Li-Li Wang, Chun-Ji Gao
OBJECTIVE: To establish the animal model of luciferase-transfected A20 murine B cell lymphoma, so as to provide experimental tools to explore the effect of graft versus tumor. METHODS: Luciferase- labeled A20 cells were cloned with puromycin selection. Transfected A20 cells and C57BL/6 bone marrow were inoculated into the irradiated BALB/c mice by injection in tailvein to establish the transplantation model. The bioluminescent imaging technique was used to monitor the tumor growth, and then the survival, body weight, tumor formation and pathological characteristics of target organs were observed...
February 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29387134/molecular-changes-associated-with-increased-tnf-%C3%AE-induced-apoptotis-in-na%C3%A3-ve-tn-and-central-memory-tcm-cd8-t-cells-in-aged-humans
#8
Sudhir Gupta, Houfen Su, Sudhanshu Agrawal, Sastry Gollapudi
Background: Progressive T cell decline in aged humans is associated with a deficiency of naïve (TN) and central memory (TCM) T cells. We have previously reported increased Tumor necrosis factor-α (TNF-α)-induced apoptosis in TN and TCM T cells in aged humans; however, the molecular basis of increased apoptosis remains to be defined. Since expression of TNF receptors (TNFRs) was reported to be comparable in young and aged, we investigated signaling events downstream of TNFRs to understand the molecular basis of increased TNF-α-induced apoptosis in aged TN and TCM CD8+ cells...
2018: Immunity & Ageing: I & A
https://www.readbyqxmd.com/read/29380463/clinicopathologic-implications-of-tnfaip3-a20-deletions-in-extranodal-nk-t-cell-lymphoma
#9
Hyein Ahn, Jeong Mi Yang, Yoon Kyung Jeon, Jin Ho Paik
The A20/Tumor necrosis factor-alpha-induced protein 3 (A20/TNFAIP3) is a negative regulator of NF-κB signaling. We analyzed the clinicopathologic implications of A20 deletions in extranodal NK/T-cell lymphoma (NKTL). Fluorescence in situ hybridization analysis of the A20 gene was performed using archived formalin-fixed tissues in 49 cases of NKTL. Among the 49 NKTL patients (median age, 48 years [10-79]), stage I-II (75% [36/48]) and upper aerodigestive tract (UAT)-origin (84% [41/49]) were predominant. All A20 deletions were monoallelic and found in cases with UAT-origin, accounting for 18% (9/49) of all NKTLs and 22% (9/41) of UAT-origin...
January 30, 2018: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/29377149/misfolded-proinsulin-in-the-endoplasmic-reticulum-during-development-of-beta-cell-failure-in-diabetes
#10
REVIEW
Anoop Arunagiri, Leena Haataja, Corey N Cunningham, Neha Shrestha, Billy Tsai, Ling Qi, Ming Liu, Peter Arvan
The endoplasmic reticulum (ER) is broadly distributed throughout the cytoplasm of pancreatic beta cells, and this is where all proinsulin is initially made. Healthy beta cells can synthesize 6000 proinsulin molecules per second. Ordinarily, nascent proinsulin entering the ER rapidly folds via the formation of three evolutionarily conserved disulfide bonds (B7-A7, B19-A20, and A6-A11). A modest amount of proinsulin misfolding, including both intramolecular disulfide mispairing and intermolecular disulfide-linked protein complexes, is a natural by-product of proinsulin biosynthesis, as is the case for many proteins...
January 28, 2018: Annals of the New York Academy of Sciences
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
#11
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/29323140/loss-of-a20-in-bm-mscs-regulates-the-th17-treg-balance-in-rheumatoid-arthritis
#12
Zhuan Feng, Yue Zhai, Zhaohui Zheng, Lijie Yang, Xing Luo, Xiwen Dong, Qing Han, Jin Jin, Zhi-Nan Chen, Ping Zhu
Mesenchymal stem cells (MSCs) are multi-potent cells that are self-renewable and possess the potential to differentiate into multiple lineages. Several studies demonstrated that MSCs could regulate a Th17/Treg balance and could be a potential therapeutic target for Rheumatoid Arthritis (RA). A20 is highly expressed in many cell types after the stimulation of TNF-α, where it may inhibit pro-inflammatory cytokine secretion. However, the expression of A20 in BM-MSCs in RA is not fully understood. In our study, we found that A20 was decreased in RA patients' bone marrow MSCs (BM-MSCs), and with more IL-6 secretion, the balance of Th17/Treg was broken...
January 11, 2018: Scientific Reports
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
#13
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/29298453/preoperative-fibtem-predicts-postoperative-hemorrhage-in-total-knee-arthroplasty
#14
Seong-Hyop Kim, Chung-Sik Oh, Tae-Hoon Kim, Sewon Park, Ka Young Rhee
FIBTEM parameters might predict the amount of postoperative hemorrhage following total knee arthroplasty (TKA), because fibrin polymerization and fibrinolysis have a central role in postoperative hemorrhage following TKA. This study retrospectively evaluated 54 patients who had undergone unilateral primary TKA. Laboratory coagulation parameters, including FIBTEM, were recorded before anesthesia induction and after admission to the postanesthetic care unit. The decrease in hemoglobin (Hb), amount of hemorrhage via closed suction drainage, fluid administration, and amount transfused were reviewed postoperatively...
January 3, 2018: Journal of Knee Surgery
https://www.readbyqxmd.com/read/29274253/mir-200a-enhances-trail-induced-apoptosis-in-gastric-cancer-cells-by-targeting-a20
#15
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
#16
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/29241730/haploinsufficiency-of-a20-causes-autoinflammatory-and-autoimmune-disorders
#17
Tomonori Kadowaki, Hidenori Ohnishi, Norio Kawamoto, Tomohiro Hori, Kenichi Nishimura, Chie Kobayashi, Tomonari Shigemura, Shohei Ogata, Yuzaburo Inoue, Tomoki Kawai, Eitaro Hiejima, Masatoshi Takagi, Kohsuke Imai, Ryuta Nishikomori, Shuichi Ito, Toshio Heike, Osamu Ohara, Tomohiro Morio, Toshiyuki Fukao, Hirokazu Kanegane
No abstract text is available yet for this article.
December 11, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29237725/abin-1-negatively-regulates-%C3%AE-opioid-receptor-function
#18
Peilan Zhou, Jiebing Jiang, Hui Yan, Yulei Li, Junru Zhao, Xiao Wang, Ruibin Su, Zehui Gong
The μ-opioid receptor (MOR) is a Gi/o protein-coupled receptor that mediates analgesic, euphoric, and reward effects. Using a bacterial two-hybrid screen, we reported that the carboxyl tail of the rat MOR associates with A20-binding inhibitor of nuclear factor (NF)-κB (ABIN-1) (Zhou et al., 2015). This interaction was confirmed by direct protein - protein binding and co-immunoprecipitation of MOR and ABIN-1 proteins in cell lysates. Saturation binding studies showed that ABIN-1 had no effect on MOR binding...
December 13, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/29233925/a20-regulates-the-dna-damage-response-and-mediates-tumor-cell-resistance-to-dna-damaging-therapy
#19
Chuanzhen Yang, Weicheng Zang, Zefang Tang, Yapeng Ji, Ruidan Xu, Yongfeng Yang, Aiping Luo, Bin Hu, Zemin Zhang, Zhihua Liu, Xiaofeng Zheng
A competent DNA damage response (DDR) helps prevent cancer, but once cancer has arisen DDR can blunt the efficacy of chemotherapy and radiotherapy which cause lethal DNA breakage in cancer cells. Thus, blocking DDR may improve the efficacy of these modalities. Here we report a new DDR mechanism that interfaces with inflammatory signaling and might be blocked to improve anticancer outcomes. Specifically, we report that the ubiquitin-editing enzyme A20 binds and inhibits the E3 ubiquitin ligase RNF168, which is responsible for regulating histone H2A turnover critical for proper DNA repair...
December 12, 2017: Cancer Research
https://www.readbyqxmd.com/read/29212706/phosphorylation-of-the-e3-ubiquitin-protein-ligase-itch-diminishes-binding-to-its-cognate-e2-ubiquitin-ligase
#20
Jessica M Perex, Tsan S Xiao, Derek W Abbott
Heightened and extended inflammation underlies the pathogenesis of many disorders, including inflammatory bowel disease, sepsis, and inflammatory arthritis. Ubiquitin networks help dictate the strength and duration of inflammatory signaling. In innate immunity, the itchy E3 ubiquitin protein ligase (ITCH-)-A20 ubiquitin--editing complex inhibits receptor-interacting Ser/Thr kinase (RIPK) activation by removing K63-Lys-63-linked polyubiquitinated chains from key proteins in the nuclear factor kappa B (NF-κB) signaling pathway...
December 6, 2017: Journal of Biological Chemistry
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