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https://www.readbyqxmd.com/read/29767372/bayesian-network-to-infer-drug-induced-apoptosis-circuits-from-connectivity-map-data
#1
Jiyang Yu, Jose M Silva
The Connectivity Map (CMAP) project profiled human cancer cell lines exposed to a library of anticancer compounds with the goal of connecting cancer with underlying genes and potential treatments. As most targeted anticancer therapeutics aim to induce tumor-selective apoptosis, it is critical to understand the specific cell death pathways triggered by drugs. This can help to better understand the mechanism of how cancer cells respond to chemical stimulations and improve the treatment of human tumors. In this study, using Connectivity MAP microarray-based gene expression data, we applied a Bayesian network modeling approach and identified apoptosis as a major drug-induced cellular pathway...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29765142/targeted-deep-sequencing-of-gastric-marginal-zone-lymphoma-identified-alterations-of-traf3-and-tnfaip3-that-were-mutually-exclusive-for-malt1-rearrangement
#2
Jiyeon Hyeon, Boram Lee, So-Hyun Shin, Hae Yong Yoo, Seok Jin Kim, Won Seog Kim, Woong-Yang Park, Young-Hyeh Ko
Gastric extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue is a distinct entity in that Helicobacter pylori infection plays the most important causative role in the development of the disease. To investigate the genomic alteration in gastric marginal zone lymphoma that was resistant to the H. pylori eradication therapy, we analyzed 19 cases of the gastric marginal zone lymphoma using fluorescence in situ hybridization for MALT1, BCL10 rearrangement, and targeted sequencing using an Illumina platform...
May 15, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29716623/mir-221-stimulates-breast-cancer-cells-and-cancer-associated-fibroblasts-cafs-through-selective-interference-with-the-a20-c-rel-ctgf-signaling
#3
Maria Francesca Santolla, Rosamaria Lappano, Francesca Cirillo, Damiano Cosimo Rigiracciolo, Anna Sebastiani, Sergio Abonante, Pierfrancesco Tassone, Pierosandro Tagliaferri, Maria Teresa Di Martino, Marcello Maggiolini, Adele Vivacqua
BACKGROUND: MicroRNA (miRNAs) are non-coding small RNA molecules that regulate gene expression by inhibiting the translation of target mRNAs. Among several dysregulated miRNAs in human cancer, the up-regulation of miR-221 has been associated with development of a variety of hematologic and solid malignancies. In this study, we investigated the involvement of miR-221 in breast cancer. METHODS: TaqMan microRNA assay was used to detect the miR-221 levels in normal cells and in MDA-MB 231 and SkBr3 breast cancer cells as well as in main players of the tumor microenvironment, namely cancer-associated fibroblasts (CAFs)...
May 2, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29696068/gene-polymorphisms-of-tnf-238g-a-tnf-308g-a-il10-1082g-a-tnfaip3-and-mc4r-and-comorbidity-occurrence-in-a-romanian-population-with-psoriasis
#4
Vlad Mihai Voiculescu, Iulia Solomon, Alexandra Popa, Carmen Cristina Draghici, Maria Dobre, Calin Giurcaneanu, Laura Maria Lucia Papagheorghe, Mihai Lupu
Rationale. Psoriasis is a prevalent chronic inflammatory disease with worldwide distribution affecting approximately 2% of the Caucasian population. There have been many population- and family-based studies that agree on the strong genetic component of this disease. Several studies have investigated the relationship between cytokine gene polymorphisms, psoriasis, and the occurrence of comorbidities but their data are conflicting. Objective. This study examines cytokine gene single-nucleotide polymorphisms (SNPs) in the context of psoriasis and metabolic syndrome, with a focus on the occurrence of comorbidities in psoriasis patients...
January 2018: Journal of Medicine and Life
https://www.readbyqxmd.com/read/29682366/whole-exome-sequencing-and-molecular-modeling-of-a-missense-variant-in-tnfaip3-that-segregates-with-disease-in-a-family-with-chronic-urticaria-and-angioedema
#5
Antoneicka L Harris, Patrick R Blackburn, John E Richter, Jennifer M Gass, Thomas R Caulfield, Ahmed N Mohammad, Paldeep S Atwal
Chronic urticaria is a common condition characterized by recurrent hives lasting several weeks or months and is usually idiopathic. Approximately half of the individuals with chronic urticaria will present with episodes of angioedema that can be severe and debilitating. In this report, we describe a 47-year-old Hispanic male who presented initially for an evaluation of chronic hives following hospitalization due to hive-induced anaphylaxis. The individual had a history significant for urticaria and angioedema beginning in his early 30s...
2018: Case Reports in Genetics
https://www.readbyqxmd.com/read/29674500/novel-gpr34-and-ccr6-mutation-and-distinct-genetic-profiles-in-malt-lymphomas-of-different-sites
#6
Sarah Moody, Joe Sneath Thompson, Shih-Sung Chuang, Hongxiang Liu, Markus Raderer, George Vassiliou, Iwona Wlodarska, Fangtian Wu, Sergio Cogliatti, Alistair Robson, Margaret Ashton-Key, Yingwen Bi, John Goodlad, Ming-Qing Du
MALT lymphoma originates from a background of diverse chronic inflammatory disorders at various anatomic sites. The genetics underlying its development, particularly in those associated with autoimmune disorders, is poorly characterised. By whole exome sequencing of 21 cases of MALT lymphomas of the salivary gland and thyroid, we have identified recurrent somatic mutations in 2 G-protein coupled receptors (GPR34 and CCR6) not previously reported in human malignancies, 3 genes (PIK3CD, TET2, TNFRSF14) not previously implicated in MALT lymphoma, and a further 2 genes (TBL1XR1, NOTCH1) recently described in MALT lymphoma...
April 19, 2018: Haematologica
https://www.readbyqxmd.com/read/29618830/evaluation-of-the-tlr-negative-regulatory-network-in-cvid-patients
#7
Roozbeh Sanaei, Nima Rezaei, Asghar Aghamohammadi, Ali-Akbar Delbandi, Shahram Teimourian, Reza Yazdani, Parsova Tavasolian, Fatemeh Kiaee, Nader Tajik
Common variable immunodeficiency (CVID), a clinically symptomatic primary immunodeficiency disease (PID), is characterized by hypogammaglobulinemia leading to recurrent infections and various complications. Recently, some defects in the signaling of TLRs have been identified in CVID patients which led us to investigate the expression of TLR4 and 9 negative regulatory molecules and their upregulation status following their activation. Using TaqMan real-time PCR, SOCS1, TNFAIP3, RFN216, and IRAK-M transcripts among peripheral blood mononuclear cells (PBMCs) were measured with/without TLR4 and 9 activations...
April 5, 2018: Genes and Immunity
https://www.readbyqxmd.com/read/29590618/telomere-dysfunction-disturbs-macrophage-mitochondrial-metabolism-and-the-nlrp3-inflammasome-through-the-pgc-1%C3%AE-tnfaip3-axis
#8
Yanhua Kang, Hang Zhang, Yufang Zhao, Yan Wang, Wei Wang, Yan He, Wei Zhang, Weiwei Zhang, Xudong Zhu, Yong Zhou, Lingling Zhang, Zhenyu Ju, Liyun Shi
Immune and inflammation dysregulation have been associated with the aging process and contribute to age-related disorders, but the underlying mechanism remains elusive. Here, we employed late-generation Terc knockout (Terc-/- ) mice to investigate the impact of telomere dysfunction on the host defense and function of innate immune cells. Terc-/- mice displayed exaggerated lung inflammation and increased mortality upon respiratory staphylococcal infection, although their pathogen-clearing capacity was uncompromised...
March 27, 2018: Cell Reports
https://www.readbyqxmd.com/read/29584776/retraction-rs10499194-polymorphism-in-the-tumor-necrosis-factor-%C3%AE-inducible-protein-3-tnfaip3-gene-is-associated-with-type-1-autoimmune-hepatitis-risk-in-chinese-han-population
#9
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
#10
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/29560554/effects-of-exosomes-from-lps-activated-macrophages-on-adipocyte-gene-expression-differentiation-and-insulin-dependent-glucose-uptake
#11
Nicolás De Silva, Mirian Samblas, J Alfredo Martínez, Fermín I Milagro
Obesity is usually associated with low-grade inflammation, which determines the appearance of comorbidities like atherosclerosis and insulin resistance. Infiltrated macrophages in adipose tissue are partly responsible of this inflammatory condition. Numerous studies point to the existence of close intercommunication between macrophages and adipocytes and pay particular attention to the proinflammatory cytokines released by both cell types. However, it has been recently described that in both, circulation and tissue level, there are extracellular vesicles (including microvesicles and exosomes) containing miRNAs, mRNAs, and proteins that can influence the inflammatory response...
March 20, 2018: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/29527211/the-footprints-of-poly-autoimmunity-evidence-for-common-biological-factors-involved-in-multiple-sclerosis-and-hashimoto-s-thyroiditis
#12
Simona Perga, Serena Martire, Francesca Montarolo, Ilaria Giordani, Michela Spadaro, Gabriele Bono, Stefania Corvisieri, Ilaria Messuti, Giancarlo Panzica, Fabio Orlandi, Antonio Bertolotto
Autoimmune diseases are a diverse group of chronic disorders and affect a multitude of organs and systems. However, the existence of common pathophysiological mechanisms is hypothesized and reports of shared risk are emerging as well. In this regard, patients with multiple sclerosis (MS) have been shown to have an increased susceptibility to develop chronic autoimmune thyroid diseases, in particular Hashimoto's thyroiditis (HT), suggesting an autoimmune predisposition. However, studies comparing such different pathologies of autoimmune origin are still missing till date...
2018: Frontiers in Immunology
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
#13
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/29486471/tnfaip3-mrna-level-is-associated-with-psychological-anxiety-in-major-depressive-disorder
#14
Ruei-An Chen, Tiao-Lai Huang, Kai-Wei Huang, Yi-Yung Hung
BACKGROUND: Major depressive disorder has been shown to be associated with inflammation and the dysregulation of innate immune responses. Previously, we showed an inverse correlation between the severity of depression and level of TNFAIP3 mRNA expression. The present study further evaluated the association between TNFAIP3 mRNA expression level and symptoms of major depressive disorder (MDD) in 91 patients (20 men and 71 women). METHODS: The relationships between subscores on the 17-item Hamilton Depression Rating Scale (HAMD-17) and TNFAIP3 mRNA levels were assessed by multiple linear regression...
2017: Neuroimmunomodulation
https://www.readbyqxmd.com/read/29483615/crispr-cas9-mediated-knockout-of-an-intergenic-variant-rs6927172-identified-il-20ra-as-a-new-risk-gene-for-multiple-autoimmune-diseases
#15
Jianfeng Wu, Sirui Yang, Di Yu, Wenjing Gao, Xianjun Liu, Kun Zhang, Xueqi Fu, Wanguo Bao, Kaiyu Zhang, Jiaao Yu, Liankun Sun, Shaofeng Wang
Genetic variants near the tumor necrosis factor-α-induced protein 3 gene (TNFAIP3) at the chromosomal region 6q23 demonstrated significant associations with multiple autoimmune diseases. The signals of associations have been explained to the TNFAIP3 gene, the most likely causal gene. In this study, we employed CRISPR/cas9 genome-editing tool to generate cell lines with deletions including a candidate causal variant, rs6927172, at 140 kb upstream of the TNFAIP3 gene. Interestingly, we observed alterations of multiple genes including IL-20RA encoding a subunit of the receptor for interleukin 20...
February 23, 2018: Genes and Immunity
https://www.readbyqxmd.com/read/29463935/a20-tnfaip3-alterations-in-primary-intestinal-diffuse-large-b-cell-lymphoma
#16
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/29440643/dissection-and-function-of-autoimmunity-associated-tnfaip3-a20-gene-enhancers-in-humanized-mouse-models
#17
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/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...
May 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29423077/integrating-the-dysregulated-inflammasome-based-molecular-functionome-in-the-malignant-transformation-of-endometriosis-associated-ovarian-carcinoma
#19
Chia-Ming Chang, Mong-Lien Wang, Kai-Hsi Lu, Yi-Ping Yang, Chi-Mou Juang, Peng-Hui Wang, Ren-Jun Hsu, Mu-Hsien Yu, Cheng-Chang Chang
The coexistence of endometriosis (ES) with ovarian clear cell carcinoma (CCC) or endometrioid carcinoma (EC) suggested that malignant transformation of ES leads to endometriosis associated ovarian carcinoma (EAOC). However, there is still lack of an integrating data analysis of the accumulated experimental data to provide the evidence supporting the hypothesis of EAOC transformation. Herein we used a function-based analytic model with the publicly available microarray datasets to investigate the expression profiling between ES, CCC, and EC...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29380463/clinicopathologic-implications-of-tnfaip3-a20-deletions-in-extranodal-nk-t-cell-lymphoma
#20
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 y [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...
May 2018: Genes, Chromosomes & Cancer
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