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https://www.readbyqxmd.com/read/29665074/parkin-deficiency-modulates-nlrp3-inflammasome-activation-by-attenuating-an-a20-dependent-negative-feedback-loop
#1
François Mouton-Liger, Thibault Rosazza, Julia Sepulveda-Diaz, Amélie Ieang, Sidi-Mohamed Hassoun, Emilie Claire, Graziella Mangone, Alexis Brice, Patrick P Michel, Jean-Christophe Corvol, Olga Corti
Neuroinflammation and mitochondrial dysfunction, key mechanisms in the pathogenesis of Parkinson's disease (PD), are usually explored independently. Loss-of-function mutations of PARK2 and PARK6, encoding the E3 ubiquitin protein ligase Parkin and the mitochondrial serine/threonine kinase PINK1, account for a large proportion of cases of autosomal recessive early-onset PD. PINK1 and Parkin regulate mitochondrial quality control and have been linked to the modulation of innate immunity pathways. We report here an exacerbation of NLRP3 inflammasome activation by specific inducers in microglia and bone marrow-derived macrophages from Park2-/- and Pink1-/- mice...
April 17, 2018: Glia
https://www.readbyqxmd.com/read/29622561/o-linked-%C3%AE-n-acetylglucosamine-modification-of-a20-enhances-the-inhibition-of-nf-%C3%AE%C2%BAb-nuclear-factor-%C3%AE%C2%BAb-activation-and-elicits-vascular-protection-after-acute-endoluminal-arterial-injury
#2
Dan Yao, Lijuan Xu, Oufan Xu, Rujun Li, Mingxing Chen, Hui Shen, Huajiang Zhu, Fengyi Zhang, Deshang Yao, Yiu-Fai Chen, Suzanne Oparil, Zhengang Zhang, Kaizheng Gong
OBJECTIVE: Recently, we have demonstrated that acute glucosamine-induced augmentation of protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels inhibits inflammation in isolated vascular smooth muscle cells and neointimal formation in a rat model of carotid injury by interfering with NF-κB (nuclear factor-κB) signaling. However, the specific molecular target for O-GlcNAcylation that is responsible for glucosamine-induced vascular protection remains unclear. In this study, we test the hypothesis that increased A20 O-GlcNAcylation is required for glucosamine-mediated inhibition of inflammation and vascular protection...
April 5, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29608924/a20-ameliorates-inflammatory-bowel-disease-in-mice-via-inhibiting-nf-%C3%AE%C2%BAb-and-stat3-activation
#3
Seung Hoon Lee, Hye-Rim Lee, Ji Ye Kwon, KyungAh Jung, Se-Young Kim, Keun-Hyung Cho, JeongWon Choi, Han Hee Lee, Bo-In Lee, Dae-Myung Jue, Mi-La Cho
A20 is a zinc finger protein that effectively inhibits the activation of nuclear factor (NF)-κB to downregulate the expression of tumor necrosis factor-α, interleukin (IL)-1β, and IL-17. A20 also plays a crucial role as a feedback inhibitor of the inflammatory response. Due to its inhibitory role, A20 may be useful in regulating diseases resulting from chronic inflammation and excessive pro-inflammatory cytokine production, such as colitis. Patients with colitis produce high levels of pro-inflammatory cytokines in the intestine...
March 30, 2018: Immunology Letters
https://www.readbyqxmd.com/read/29602308/gold-nanoparticles-stabilize-peptide-drug-conjugates-for-sustained-targeted-drug-delivery-to-cancer-cells
#4
Kalishwaralal Kalimuthu, Bat-Chen Lubin, Andrii Bazylevich, Gary Gellerman, Ofer Shpilberg, Galia Luboshits, Michael A Firer
BACKGROUND: Peptide-drug-conjugates (PDCs) are being developed as an effective strategy to specifically deliver cytotoxic drugs to cancer cells. However one of the challenges to their successful application is the relatively low stability of peptides in the blood, liver and kidneys. Since AuNPs seem to have a longer plasma half-life than PDCs, one approach to overcoming this problem would be to conjugate the PDCs to gold nanoparticles (AuNPs), as these have demonstrated favorable physico-chemical and safety properties for drug delivery systems...
March 30, 2018: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/29589214/association-of-tumor-necrosis-factor-alpha-induced-protein-3-interacting-protein-1-tnip1-gene-polymorphism-rs7708392-with-lupus-nephritis-in-egyptian-patients
#5
Mohamed Moustafa Rizk, Eman Tayae Elsayed, Ahmed Fathi ElKeraie, Ireny Ramzy
Lupus nephritis (LN) is a major cause of morbidity and mortality in systemic lupus erythematosus (SLE). Previous studies suggest that mutant A20 binding inhibitor of NF-κB 1 (ABIN1) protein encoded by tumor necrosis factor alpha-induced protein 3 interacting protein 1 (TNIP1) gene is associated with LN via NF-κB dysregulation. The aim of the current study was to evaluate the association of TNIP1 gene SNP rs7708392 with SLE and LN in Egyptian patients. 5' nuclease Allelic discrimination was used to evaluate the frequency of TNIP1 SNP rs7708392 in 53 patients with LN, 57 SLE patients without nephritis and 85 healthy controls...
March 27, 2018: Biochemical Genetics
https://www.readbyqxmd.com/read/29574415/response-to-a20-haploinsufficiency-ha20-clinical-phenotypes-and-disease-course-of-patients-with-a-newly-recognised-nf-kb-mediated-autoinflammatory-disease-by-aeschlimann-et-al
#6
Florence A Aeschlimann, Ronald M Laxer
No abstract text is available yet for this article.
March 24, 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29572183/tnfaip3-haploinsufficiency-is-the-cause-of-autoinflammatory-manifestations-in-a-patient-with-a-deletion-of-13mb-on-chromosome-6
#7
Clara Franco-Jarava, Hongying Wang, Andrea Martin-Nalda, de la Sierra Daniel Alvarez, Marina García-Prat, Domingo Bodet, Vicenç García-Patos, Alberto Plaja, Francesc Rudilla, Victor Rodriguez-Sureda, Laura García-Latorre, Ivona Aksentijevich, Roger Colobran, Pere Soler-Palacín
There is scarce literature about autoinflammation in syndromic patients. We describe a patient who, in addition to psychomotor and growth delay, presented with fevers, neutrophilic dermatosis, and recurrent orogenital ulcers. Comparative Genomic Hybridization (CGH) array permitted to identify a 13.13Mb deletion on chromosome 6, encompassing 53 genes, and including TNFAIP3 gene (A20). A20 is a potent inhibitor of the NF-kB signalling pathway and restricts inflammation via its deubiquitinase activity. Western blotting and immunoprecipitation assays showed decreased A20 expression and increased phosphorylation of p65 and IkBa...
March 20, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29558004/effect-of-exogenous-inoculants-on-enhancing-oil-recovery-and-indigenous-bacterial-community-dynamics-in-long-term-field-pilot-of-low-permeability-reservoir
#8
Jing Li, Shuwen Xue, Chunqiu He, Huixia Qi, Fulin Chen, Yanling Ma
Pseudomonas aeruginosa DN1 strain and Bacillus subtilis QHQ110 strain were chosen as rhamnolipid and lipopeptide producer respectively, to evaluate the efficiency of exogenous inoculants on enhancing oil recovery (EOR) and to explore the relationship between injected bacteria and indigenous bacterial community dynamics in long-term filed pilot of Hujianshan low permeability water-flooded reservoir for 26 months. Core-flooding tests showed that the oil displacement efficiency increased by 18.46% with addition of exogenous consortia...
March 20, 2018: World Journal of Microbiology & Biotechnology
https://www.readbyqxmd.com/read/29554594/atorvastatin-dose-dependently-promotes-mouse-lung-repair-after-emphysema-induced-by-elastase
#9
Adriana Correa Melo, Isabella Cattani-Cavalieri, Marina Valente Barroso, Nicolas Quesnot, Lycia Brito Gitirana, Manuella Lanzetti, Samuel Santos Valença
Emphysema results in a proteinase - antiproteinase imbalance, inflammation and oxidative stress. Our objective was to investigate whether atorvastatin could repair mouse lungs after elastase-induced emphysema. Vehicle (50 μL) or porcine pancreatic elastase (PPE) was administered on day 1, 3, 5 and 7 at 0.6 U intranasally. Male mice were divided into a control group (sham), PPE 32d (sacrificed 24 h after 32 days), PPE 64d (sacrificed 24 h after 64 days), and atorvastatin 1, 5 and 20 mg treated from day 33 until day 64 and sacrificed 24 h later (A1 mg, A5 mg and A20 mg, respectively)...
March 16, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29523657/15-epi-lipoxin-a-4-resolvin-d2-and-resolvin-d3-induce-nf-%C3%AE%C2%BAb-regulators-in-bacterial-pneumonia
#10
Ho Pan Sham, Katherine H Walker, Raja-Elie E Abdulnour, Nandini Krishnamoorthy, David N Douda, Paul C Norris, Ioanna Barkas, Sarah Benito-Figueroa, Jennifer K Colby, Charles N Serhan, Bruce D Levy
Specialized proresolving mediators (SPMs) decrease NF-κB activity to prevent excessive tissue damage and promote the resolution of acute inflammation. Mechanisms for NF-κB regulation by SPMs remain to be determined. In this study, after LPS challenge, the SPMs 15-epi-lipoxin A4 (15-epi-LXA4 ), resolvin D1, resolvin D2, resolvin D3, and 17-epi-resolvin D1 were produced in vivo in murine lungs. In LPS-activated human bronchial epithelial cells, select SPMs increased expression of the NF-κB regulators A20 and single Ig IL-1R-related molecule (SIGIRR)...
March 9, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29515565/a20-tumor-necrosis-factor-%C3%AE-induced-protein-3-in-immune-cells-controls-development-of-autoinflammation-and-autoimmunity-lessons-from-mouse-models
#11
REVIEW
Tridib Das, Zhongli Chen, Rudi W Hendriks, Mirjam Kool
Immune cell activation is a stringently regulated process, as exaggerated innate and adaptive immune responses can lead to autoinflammatory and autoimmune diseases. Perhaps the best-characterized molecular pathway promoting cell activation is the nuclear factor-κB (NF-κB) signaling pathway. Stimulation of this pathway leads to transcription of numerous pro-inflammatory and cell-survival genes. Several mechanisms tightly control NF-κB activity, including the key regulatory zinc finger (de)ubiquitinating enzyme A20/tumor necrosis factor α-induced protein 3 (TNFAIP3)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29505600/a20-upregulation-during-treated-hiv-disease-is-associated-with-intestinal-epithelial-cell-recovery-and-function
#12
Avantika S Chitre, Michael G Kattah, Yenny Y Rosli, Montha Pao, Monika Deswal, Steven G Deeks, Peter W Hunt, Mohamed Abdel-Mohsen, Luis J Montaner, Charles C Kim, Averil Ma, Ma Somsouk, Joseph M McCune
ClinicalTrials.gov Clinical Trial NCT00594880.
March 5, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29487860/-leishmania-guyanensis-parasites-block-the-activation-of-the-inflammasome-by-inhibiting-maturation-of-il-1%C3%AE
#13
Mary-Anne Hartley, Remzi O Eren, Matteo Rossi, Florence Prevel, Patrik Castiglioni, Nathalie Isorce, Chantal Desponds, Lon-Fye Lye, Stephen M Beverley, Stefan K Drexler, Nicolas Fasel
The various symptomatic outcomes of cutaneous leishmaniasis relates to the type and potency of its underlying inflammatory responses. Presence of the cytoplasmic Leishmania RNA virus-1 (LRV1) within Leishmania guyanensis , worsens lesional inflammation and parasite burden, as the viral dsRNA genome acts as a potent innate immunogen stimulating Toll-Like-Receptor-3 (TLR3). Here we investigated other innate pattern recognition receptors capable of reacting to dsRNA and potentially contributing to LRV1-mediated inflammatory pathology...
January 14, 2018: Microbial Cell
https://www.readbyqxmd.com/read/29463935/a20-tnfaip3-alterations-in-primary-intestinal-diffuse-large-b-cell-lymphoma
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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