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Xin Yao, Lian-Lian Bian, Wei-Wei Lu, Jing-Xin Li, Qun-Ying Mao, Yi-Ping Wang, Fan Gao, Xing Wu, Qiang Ye, Xiu-Ling Li, Feng-Cai Zhu, Zhenglun Liang
Herpangina (HA) and hand, foot, and mouth disease (HFMD) are common infectious diseases caused by human enteroviruses and frequently occurr in young children. Previous published studies have mainly focused on HFMD, while the HA epidemiological and etiological characteristics in mainland China have not been described. From June, 2013 to March, 2014, HA and HFMD patients were monitored in participants from clinical trial of EV-A71 vaccine conducted during 2012-2013. A total of 95 HA patients and 161 HFMD patients were defined...
October 21, 2016: Human Vaccines & Immunotherapeutics
Swati Bhattacharyya, Wenxia Wang, Lauren Van Duyn Graham, John Varga
BACKGROUND: The ubiquitin-editing cytosolic enzyme A20, the major negative regulator of toll-like receptor (TLR)-mediated cellular inflammatory responses, has tight genetic linkage with systemic sclerosis (SSc). Because recent studies implicate endogenous ligand-driven TLR signaling in SSc pathogenesis, we sought to investigate the regulation, role and mechanism of action of A20 in skin fibroblasts. METHOD: A20 expression and the effects of forced A20 expression or siRNA-mediated A20 knockdown on fibrotic responses induced by transforming growth factor-ß (TGF-ß) were evaluated was evaluated in explanted human skin fibroblasts...
October 3, 2016: Arthritis Research & Therapy
Jian Zhan, Wenyi Qin, Ying Zhang, Jing Jiang, Hongmei Ma, Qiongli Li, Yong Luo
BACKGROUND: Zinc finger protein A20 (tumor necrosis factor alpha-induced protein 3) functions as a potent negative feedback inhibitor of the nuclear factor-kB (NF-kB) signaling. It exerts these effects by interrupting the activation of IkB kinase beta (IKKβ), the most critical kinase in upstream of NF-kB, and thereby controlling inflammatory homeostasis. We reported previously that electroacupuncture (EA) could effectively suppress IKKβ activation. However, the mechanism underlying these effects was unclear...
October 3, 2016: Journal of Neuroinflammation
Jialing Pan, Tingting Xu, Fengli Xu, Yali Zhang, Zhiguo Liu, Wenbo Chen, Weitao Fu, Yuanrong Dai, Yunjie Zhao, Jianpeng Feng, Guang Liang
Acute lung injury (ALI) is a major cause of acute respiratory failure in critically-ill patients. Resveratrol and curcumin are proven to have potent anti-inflammatory efficacy, but their clinical application is limited by their metabolic instability. Here, a series of resveratrol and the Mono-carbonyl analogs of curcumin (MCAs) hybrids were designed and synthesized by efficient aldol construction strategy, and then screened for anti-inflammatory activities in vitro and in vivo. The results showed that the majority of analogs effectively inhibited the LPS-induced production of IL-6 and TNF-α...
September 10, 2016: European Journal of Medicinal Chemistry
Norbert Schormann, Natalia Zhukovskaya, Gregory Bedwell, Manunya Nuth, Richard Gillilan, Peter E Prevelige, Robert P Ricciardi, Surajit Banerjee, Debasish Chattopadhyay
Uracil-DNA glycosylases are ubiquitous enzymes, which play a key role repairing damages in DNA and in maintaining genomic integrity by catalyzing the first step in the base excision repair pathway. Within the superfamily of uracil-DNA glycosylases family I enzymes or UNGs are specific for recognizing and removing uracil from DNA. These enzymes feature conserved structural folds, active site residues and use common motifs for DNA binding, uracil recognition and catalysis. Within this family the enzymes of poxviruses are unique and most remarkable in terms of amino acid sequences, characteristic motifs and more importantly for their novel non-enzymatic function in DNA replication...
September 29, 2016: Protein Science: a Publication of the Protein Society
Wei Gao, Lu Long, Xinquan Tian, Jingjing Jin, Huili Liu, Hui Zhang, Fuchun Xu, Chunpeng Song
Stress-associated proteins (SAPs) containing the A20/AN1 zinc-finger domain play important roles in response to both biotic and abiotic stresses in plants. Nevertheless, few studies have focused on the SAP gene family in cotton. To explore the distributions and expression patterns of these genes, we performed genome-wide identification and characterization of SAPs in tetraploid Gossypium hirsutum L. TM-1 (AD1). A total of 37 genes encoding SAPs were identified, 36 of which were duplicated in the A and D sub-genomes...
September 28, 2016: Molecular Genetics and Genomics: MGG
Deborah Schofield, Rupendra N Shrestha, Michelle M Cunich, Robert Tanton, Lennert Veerman, Simon J Kelly, Megan E Passey
OBJECTIVES: To project the number of older workers with lost productive life years (PLYs) due to chronic disease and resultant lost income; and lost taxes and increased welfare payments from 2015 to 2030. DESIGN, SETTING AND PARTICIPANTS: Using a microsimulation model, Health&WealthMOD2030, the costs of chronic disease in Australians aged 45-64 were projected to 2030. The model integrates household survey data from the Australian Bureau of Statistics Surveys of Disability, Ageing and Carers (SDACs) 2003 and 2009, output from long-standing microsimulation models (STINMOD (Static Incomes Model) and APPSIM (Australian Population and Policy Simulation Model)) used by various government departments, population and labour force growth data from Treasury, and disease trends data from the Australian Burden of Disease and Injury Study (2003)...
2016: BMJ Open
Veasna Duong, Channa Mey, Marc Eloit, Huachen Zhu, Lucie Danet, Zhong Huang, Gang Zou, Arnaud Tarantola, Justine Cheval, Philippe Perot, Denis Laurent, Beat Richner, Santy Ky, Sothy Heng, Sok Touch, Ly Sovann, Rogier van Doorn, Thanh Tan Tran, Jeremy J Farrar, David E Wentworth, Suman R Das, Timothy B Stockwell, Jean-Claude Manuguerra, Francis Delpeyroux, Yi Guan, Ralf Altmeyer, Philippe Buchy
Human enterovirus 71 (EV-A71) causes hand, foot and mouth disease (HFMD). EV-A71 circulates in many countries and has caused large epidemics, especially in the Asia-Pacific region, since 1997. In April 2012, an undiagnosed fatal disease with neurological involvement and respiratory distress occurred in young children admitted to the Kantha Bopha Children's Hospital in Phnom Penh, Cambodia. Most died within a day of hospital admission, causing public panic and international concern. In this study, we describe the enterovirus (EV) genotypes that were isolated during the outbreak in 2012 and the following year...
2016: Emerging Microbes & Infections
Yong Zhang, Qiang Sun, Hui Cui, Dongmei Yan, Qin Fan, Yang Song, Shuangli Zhu, Xiaolei Li, Guohong Huang, Tianjiao Ji, Lan Hu, Dongyan Wang, Qian Yang, Wenbo Xu
Poliomyelitis associated with circulating vaccine-derived polioviruses (cVDPVs) is a serious public health issue in the post-eradication era, and the occurrence of recombinant cVDPVs emphasizes the need to elucidate enterovirus C (EV-C) epidemiology. Stool samples were collected from 826 healthy children in Southern Xinjiang in 2011 to investigate EV-C circulation and epidemiology. Thirty-six EV-Cs were isolated and assigned to eight EV-C serotypes by molecular serotyping, suggesting the circulation of diverse EV-Cs in Xinjiang...
2016: Scientific Reports
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
Yu-Chen Fan, Yuan-Yuan Zhang, Yan-Yan Sun, Na Wang, Xiao-Yan Xiao, Kai Wang
A20 is an important negative immune regulator but its role in chronic hepatitis B virus (HBV) infection is still unknown. This present study was to investigate the potential role of A20 gene in the progression of chronic HBV infection. A total of 236 chronic HBV patients were included and consisted of 63 hepatocellular carcinoma (HCC), 87 liver cirrhosis (LC) and 86 chronic hepatitis B (CHB). The mRNA level of A20 gene in peripheral blood mononuclear cells was determined using quantitative real-time polymerase chain reaction...
September 13, 2016: Oncotarget
Sai-Nan Zhang, Nai-Bin Yang, Shun-Lan Ni, Jin-Zhong Dong, Chun-Wei Shi, Shan-Shan Li, Sheng-Guo Zhang, Xin-Yue Tang, Ming-Qin Lu
Endotoxin tolerance (ET) is suggested to attenuate the severity of acute liver failure (ALF) in mice, possibly through both innate and adaptive immunity. However, the involvement of regulatory dendritic cells (DCregs) in ET has not been fully elucidated. In this study, their effect on ALF in mice was investigated. Splenic DCregs from ET-exposed mice (ET-DCregs) showed lower expression levels of CD40, CD80, and MHC-II markers and stronger inhibition of allogenic T cells and regulation of IL-10 and IL-12 secretion than splenic DCregs from normal mice (nDCregs)...
September 14, 2016: Scientific Reports
Céline Contesto-Richefeu, Nicolas Tarbouriech, Xavier Brazzolotto, Wim P Burmeister, Christophe N Peyrefitte, Frédéric Iseni
The Vaccinia virus polymerase holoenzyme is composed of three subunits: E9, the catalytic DNA polymerase subunit; D4, a uracil-DNA glycosylase; and A20, a protein with no known enzymatic activity. The D4/A20 heterodimer is the DNA polymerase cofactor, the function of which is essential for processive DNA synthesis. The recent crystal structure of D4 bound to the first 50 amino acids of A20 (D4/A201-50) revealed the importance of three residues, forming a cation-π interaction at the dimerization interface, for complex formation...
September 2016: Acta Crystallographica. Section F, Structural Biology Communications
Nongnuch Sirachainan, Ampaiwan Chuansumrit, Praguywan Kadegasem, Werasak Sasanakul, Pakawan Wongwerawattanakoon, Lalita Mahaklan
Thalassemia intermedia (TI), a non-transfusion dependent thalassemia, is divided into α-thalassemia, such as HbH disease, and β-thalassemia diseases, such as HbE/β(+) thromboembolism (TE) in TI has been mostly reported in β-thalassemia diseases with incidence rates of 3.9-29%. The present study enrolled 60 patients with α-thalassemia intermedia. The control groups were thalassemia major (TM) consisting of 17 patients diagnosed with β-thalassemia diseases, 24 patients diagnosed with splenectomized β-thalassemia diseases and 25 normal subjects...
October 2016: Thrombosis Research
Antonio R Lucena-Araujo, Jason P Moran, Paul A VanderLaan, Dora Dias-Santagata, Erik Folch, Adnan Majid, Michael S Kent, Sidharta P Gangadharan, Deepa Rangachari, Mark S Huberman, Susumu S Kobayashi, Daniel B Costa
INTRODUCTION: Anaplastic lymphoma kinase (ALK) rearranged lung adenocarcinomas are responsive to the multitargeted ALK inhibitor crizotinib. One of the common mechanisms of resistance to crizotinib is the acquisition of ALK kinase domain mutations. However, the presence of ALK mutations in crizotinib-naïve tumors has not been widely reported and it is unclear if de novo ALK mutations affect the response to crizotinib. METHODS: We analyzed preclinical models of ALK rearranged lung cancers that were sensitive/resistant to ALK inhibitors, probed our institutional and other lung cancer databases for tumors with ALK kinase domain mutations, and evaluated tumor response to crizotinib...
September 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
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
Anne Müller, Lars Niederstadt, Wenke Jonas, Chun-Xia Yi, Franziska Meyer, Petra Wiedmer, Jana Fischer, Carsten Grötzinger, Annette Schürmann, Matthias Tschöp, Gunnar Kleinau, Annette Grüters, Heiko Krude, Heike Biebermann
Intact melanocortin signaling via the G protein-coupled receptors (GPCRs), melanocortin receptor 4 (MC4R), and melanocortin receptor 3 (MC3R) is crucial for body weight maintenance. So far, no connection between melanocortin signaling and hypothalamic inflammation has been reported. Using a bimolecular fluorescence complementation library screen, we identified a new interaction partner for these receptors, ring finger protein 11 (RNF11). RNF11 participates in the constitution of the A20 complex that is involved in reduction of tumor necrosis factor α (TNFα)-induced NFκB signaling, an important pathway in hypothalamic inflammation...
2016: Frontiers in Endocrinology
Michael B Drennan, Srinath Govindarajan, Eveline Verheugen, Jonathan M Coquet, Jens Staal, Conor McGuire, Tom Taghon, Georges Leclercq, Rudi Beyaert, Geert van Loo, Bart N Lambrecht, Dirk Elewaut
Natural killer T (NKT) cells are innate lymphocytes that differentiate into NKT1, NKT2, and NKT17 sublineages during development. However, the signaling events that control NKT sublineage specification and differentiation remain poorly understood. Here, we demonstrate that the ubiquitin-modifying enzyme TNFAIP3/A20, an upstream regulator of T cell receptor (TCR) signaling in T cells, is an essential cell-intrinsic regulator of NKT differentiation. A20 is differentially expressed during NKT cell development, regulates NKT cell maturation, and specifically controls the differentiation and survival of NKT1 and NKT2, but not NKT17, sublineages...
September 19, 2016: Journal of Experimental Medicine
Katelijne De Wilde, Arne Martens, Stijn Lambrecht, Peggy Jacques, Michael B Drennan, Karlijn Debusschere, Srinath Govindarajan, Julie Coudenys, Eveline Verheugen, Fien Windels, Leen Catrysse, Rik Lories, Dennis McGonagle, Rudi Beyaert, Geert van Loo, Dirk Elewaut
OBJECTIVES: A20 is an important endogenous regulator of inflammation. Single nucleotide polymorphisms in A20 have been associated with various immune-mediated inflammatory diseases, and cell-specific deletion of A20 results in diverse inflammatory phenotypes. Our goal was to delineate the underlying mechanisms of joint inflammation in myeloid-specific A20-deficient mice (A20(myelKO) mice). METHODS: Inflammation in A20(myelKO) mice was assessed in a time-dependent manner...
August 22, 2016: Annals of the Rheumatic Diseases
Niki M Zacharias, Christopher R McCullough, Shawn Wagner, Napapon Sailasuta, Henry R Chan, Youngbok Lee, Jingzhe Hu, William H Perman, Cameron Henneberg, Brian D Ross, Pratip Bhattacharya
PURPOSE: The energy-yielding mitochondrial Krebs cycle has been shown in many cancers and other diseases to be inhibited or mutated. In most cells, the Krebs cycle with oxidative phosphorylation generates approximately 90% of the adenosine triphosphate in the cell. We designed and hyperpolarized carbon-13 labeled succinate (SUC) and its derivative diethyl succinate (DES) to interrogate the Krebs cycle in real-time in cancer animal models. PROCEDURES: Using Parahydrogen Induced Polarization (PHIP), we generated hyperpolarized SUC and DES by hydrogenating their respective fumarate precursors...
June 2016: J Mol Imaging Dyn
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