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https://www.readbyqxmd.com/read/28089349/development-of-new-ptk7-targeting-aptamer-fluorescent-and-radiolabelled-probes-for-evaluation-as-molecular-imaging-agents-lymphoma-and-melanoma-in-vivo-proof-of-concept
#1
Victoria Calzada, María Moreno, Jessica Newton, Joel González, Marcelo Fernández, Juan Pablo Gambini, Manuel Ibarra, Alejandro Chabalgoity, Susan Deutscher, Thomas Quinn, Pablo Cabral, Hugo Cerecetto
Aptamers are single-stranded oligonucleotides that recognize molecular targets with high affinity and specificity. Aptamer that selectively bind to the protein tyrosine kinase-7 (PTK7) receptor, overexpressed on many cancers, has been labelled as probes for molecular imaging of cancer. Two new PTK7-targeting aptamer probes were developed by coupling frameworks from the fluorescent dye AlexaFluor647 or the 6-hydrazinonicotinamide (HYNIC) chelator-labelled to (99m)Tc. The derivatizations via a 5'-aminohexyl terminal linker were done at room temperature and under mild buffer conditions...
December 24, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28088970/-tnfaip3-deletion-status-in-classical-hodgkin-lymphoma-and-its-relation-to-epstein-barr-virus
#2
Y F Shi, Z F Gao, C L Liu, M Li, D M Lin, L X Zhou, Y M Lai, X L Liu, X Huang
Objective: To investigate the TNFAIP3/A20 abnormalities and its association with Epstein-Barr virus (EBV) in classical Hodgkin lymphoma (CHL). Methods: Formalin-fixed, paraffinembedded tissue blocks of 54 CHL patients were collected and subjected to the construction of tissue microarray (TMA) for further analyses. EBV status was evaluated by in situ hybridization (ISH) for EBER1/2 and immunohistochemistry (IHC) with anti-LMP-1 antibody. Fluorescence in situ hybridization (FISH) and IHC were performed to determine the copy number alterations of TNFAIP3 and A20 protein expression respectively...
December 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28088611/lactobacillus-paracasei-modulates-lps-induced-inflammatory-cytokine-release-by-monocyte-macrophages-via-the-up-regulation-of-negative-regulators-of-nf-kappab-signaling-in-a-tlr2-dependent-manner
#3
Ke-Yi Sun, Dong-Hua Xu, Chao Xie, Susan Plummer, James Tang, Xiao Fan Yang, Xiao Hui Ji
The application of the probiotic lactobacillus is suggested in the treatment of some inflammatory diseases of intestines due to its potential ability to attenuate inflammation. However, the mechanism is not completely understood. In PBMCs, Lactobacillus paracasei (L. Paracasei) down-regulated the LPS-induced production of TNF-α and IL-6. Using a macrophage-like differentiated THP-1 cell line induced by PMA, we investigated the effect of L. paracasei on the production of pro-inflammatory cytokines by monocyte-macrophages...
January 12, 2017: Cytokine
https://www.readbyqxmd.com/read/28077334/the-neuroprotective-compound-p7c3-a20-promotes-neurogenesis-and-improves-cognitive-function-after-ischemic-stroke
#4
Zachary B Loris, Andrew A Pieper, W Dalton Dietrich
Ischemic stroke is a devastating condition with few therapeutic interventions available. The neuroprotective compound P7C3-A20 inhibits mature neuronal cell death while also increasing the net magnitude of postnatal neurogenesis in models of neurodegeneration and acute injury. P7C3 compounds enhance flux of nicotinamide adenine dinucleotide (NAD) in mammalian cells, a proposed therapeutic approach to treating cerebral ischemia. The effectiveness of P7C3-A20 treatment on chronic histopathological and behavioral outcomes and neurogenesis after ischemic stroke has not previously been established...
January 8, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28039858/arabidopsis-stress-associated-protein-9-mediates-biotic-and-abiotic-stress-responsive-aba-signaling-via-the-proteasome-pathway
#5
Miyoung Kang, Seonghee Lee, Haggag Abdelmageed, Angelika Reichert, Hee-Kyung Lee, Mohamed Fokar, Kirankumar S Mysore, Randy D Allen
Arabidopsis thaliana Stress Associated Protein 9 (AtSAP9) is a member of the A20/AN1 zinc finger protein family known to play important roles in plant stress responses and in the mammalian immune response. Though SAPs of several plant species were shown to be involved in abiotic stress responses, the underlying molecular mechanisms are largely unknown and little is known about the involvement of SAPs in plant disease responses. Expression of SAP9 in Arabidopsis is up-regulated in response to dehydration, cold, salinity, and ABA, as well as pathogen infection...
December 31, 2016: Plant, Cell & Environment
https://www.readbyqxmd.com/read/28039105/long-acting-%C3%AE-2-agonists-promote-glucocorticoid-mediated-repression-of-nf-%C3%AE%C2%BAb-by-enhancing-expression-of-the-feedback-regulator-tnfaip3
#6
Mohammed Omar Altonsy, Mahmoud M Mostafa, Anthony N Gerber, Robert Newton
Glucocorticoids, or corticosteroids, are effective treatments for many chronic inflammatory diseases and, in mild/moderate asthma, long-acting β2-adrenoceptor agonists (LABAs) enhance the efficacy of inhaled corticosteroids (ICSs) more than increasing the ICS dose. In human bronchial epithelial, BEAS-2B, cells, expression of TNFα-induced protein 3 (TNFAIP3), or A20, a dual-ubiquitin ligase that provides feedback inhibition of NF-κB, was induced by budesonide, an ICS, formoterol, a LABA, and was further enhanced by budesonide/formoterol combination...
December 29, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28032230/protective-effect-of-p7c3-on-retinal-ganglion-cells-from-optic-nerve-injury
#7
Hidehiro Oku, Seita Morishita, Taeko Horie, Yuko Nishikawa, Teruyo Kida, Masashi Mimura, Shota Kojima, Tsunehiko Ikeda
PURPOSE: To determine whether P7C3-A20, a proneurogenic neuroprotective agent, can protect the retinal ganglion cells (RGCs) of rats from optic nerve crushing. METHODS: The left optic nerve of 67 rats was crushed, and 5.0 mg/kg/day of P7C3-A20 (crush-P7C3) or its vehicle (crush-placebo) was injected intraperitoneally for 3 days from one day prior to the crushing. The protective effects were determined by the number of Tuj-1-stained RGCs and by the ratio of the mRNA levels of BAX/Bcl-2 on day 7...
December 28, 2016: Japanese Journal of Ophthalmology
https://www.readbyqxmd.com/read/28004928/iterative-design-and-in-vivo-evaluation-of-an-oncolytic-antilymphoma-peptide
#8
J Johannes Eksteen, Dominik Ausbacher, Jaione Simon-Santamaria, Trine Stiberg, Cristiane Cavalcanti-Jacobsen, Imin Wushur, John S Svendsen, Øystein Rekdal
Oncolytic peptides represent a promising new strategy within the field of cancer immunotherapy. Here we describe the systematic design and evaluation of short antilymphoma peptides within this paradigm. The peptides were tested in vitro and in vivo to identify a lead compound for further evaluation as novel oncolytic immunotherapeutic. In vitro tests revealed peptides with high activity against several lymphoma types and low cytotoxicity toward normal cells. Treated lymphoma cells exhibited a reduced mitochondrial membrane potential that resulted in an irreversible disintegration of their plasma membranes...
December 22, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28004776/a20-curtails-primary-but-augments-secondary-cd8-t-cell-responses-in-intracellular-bacterial-infection
#9
Sissy Just, Gopala Nishanth, Jörn H Buchbinder, Xu Wang, Michael Naumann, Inna Lavrik, Dirk Schlüter
The ubiquitin-modifying enzyme A20, an important negative feedback regulator of NF-κB, impairs the expansion of tumor-specific CD8(+) T cells but augments the proliferation of autoimmune CD4(+) T cells. To study the T cell-specific function of A20 in bacterial infection, we infected T cell-specific A20 knockout (CD4-Cre A20(fl/fl)) and control mice with Listeria monocytogenes. A20-deficient pathogen-specific CD8(+) T cells expanded stronger resulting in improved pathogen control at day 7 p.i. Imaging flow cytometry revealed that A20-deficient Listeria-specific CD8(+) T cells underwent increased apoptosis and necroptosis resulting in reduced numbers of memory CD8(+) T cells...
December 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27991595/pgrp-negatively-regulates-nod-mediated-cytokine-production-in-rainbow-trout-liver-cells
#10
Ju Hye Jang, Hyun Kim, Mi Jung Jang, Ju Hyun Cho
Pattern-recognition receptors (PRRs) initiate innate immunity via pathogen recognition. Recent studies suggest that signalling pathways downstream of different PRRs and their crosstalk effectively control immune responses. However, the cross-regulation among PRRs and its effects have yet to be fully described in fish. Here, we examined the crosstalk between OmPGRP-L1, a long form of PGRP in rainbow trout, and other PRRs during pathogenic infections. OmPGRP-L1 expression was increased in RTH-149 cells by iE-DAP and MDP, which are agonists of NOD1 and NOD2, respectively...
December 19, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27986908/a20-ameliorates-intracerebral-hemorrhage-induced-inflammatory-injury-by-regulating-traf6-polyubiquitination
#11
Zhaoyou Meng, Ting Zhao, Kai Zhou, Qi Zhong, Yanchun Wang, Xiaoyi Xiong, Faxiang Wang, Yuanrui Yang, Wenyao Zhu, Juan Liu, Maofan Liao, Lirong Wu, Chunmei Duan, Jie Li, Qiuwen Gong, Liang Liu, Ao Xiong, Meihua Yang, Jian Wang, Qingwu Yang
Reducing excessive inflammation is beneficial for the recovery from intracerebral hemorrhage (ICH). Here, the roles and mechanisms of A20 (TNFAIP3), an important endogenous anti-inflammatory factor, are examined in ICH. A20 expression in the PBMCs of ICH patients and an ICH mouse model was detected, and the correlation between A20 expression and neurologic deficits was analyzed. A20 expression was increased in PBMCs and was negatively related to the modified Rankin Scale score. A20 expression was also increased in mouse perihematomal tissues...
January 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27965655/repression-of-rgg-but-not-upregulation-of-lacd-1-in-emm1-type-covs-mutant-mediates-the-speb-repression-in-group-a-streptococcus
#12
Chuan Chiang-Ni, Teng-Ping Chu, Jiunn-Jong Wu, Cheng-Hsun Chiu
CovR/CovS is an important two-component regulatory system in human pathogen group A Streptococcus (GAS). Epidemiological studies have shown that inactivation of the sensor kinase CovS is correlated with invasive clinical manifestations. The phosphorylation level of response regulator CovR decreases dramatically in the absence of CovS, resulting in the derepression of virulence factor expression and an increase in bacterial invasiveness. Streptococcal pyrogenic exotoxin B (SpeB) is a cysteine protease and is negatively regulated by CovR; however, the expression of SpeB is almost completely repressed in the covS mutant...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27965637/genome-sequencing-of-sulfolobus-sp-a20-from-costa-rica-and-comparative-analyses-of-the-putative-pathways-of-carbon-nitrogen-and-sulfur-metabolism-in-various-sulfolobus-strains
#13
Xin Dai, Haina Wang, Zhenfeng Zhang, Kuan Li, Xiaoling Zhang, Marielos Mora-López, Chengying Jiang, Chang Liu, Li Wang, Yaxin Zhu, Walter Hernández-Ascencio, Zhiyang Dong, Li Huang
The genome of Sulfolobus sp. A20 isolated from a hot spring in Costa Rica was sequenced. This circular genome of the strain is 2,688,317 bp in size and 34.8% in G+C content, and contains 2591 open reading frames (ORFs). Strain A20 shares ~95.6% identity at the 16S rRNA gene sequence level and <30% DNA-DNA hybridization (DDH) values with the most closely related known Sulfolobus species (i.e., Sulfolobus islandicus and Sulfolobus solfataricus), suggesting that it represents a novel Sulfolobus species. Comparison of the genome of strain A20 with those of the type strains of S...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27916521/structural-insights-into-linear-tri-ubiquitin-recognition-by-a20-binding-inhibitor-of-nf-%C3%AE%C2%BAb-abin-2
#14
Shan-Meng Lin, Su-Chang Lin, Jhen-Yi Hong, Tsung-Wei Su, Bai-Jiun Kuo, Wei-Hsin Chang, Yi-Fan Tu, Yu-Chih Lo
Recognition of linear polyubiquitin by specific ubiquitin-binding proteins plays an important role in mediating nuclear factor-κB (NF-κB) signaling. A20 binding proteins, ABINs, recognize linear polyubiquitin and A20 through UBAN and AHD1, respectively, for the inhibition of NF-κB activation. Here we report the crystal structure of the AHD1-UBAN fragment of ABIN2 in complex with linear tri-ubiquitin, which reveals a 2:1 stoichiometry of the complex. Structural analyses together with mutagenesis, pull-down, and isothermal titration calorimetry assays show that the hABIN2:tri-ubiquitin interaction is mainly through the primary ubiquitin-binding site, and also through the secondary ubiquitin-binding site under a high local protein concentration...
November 24, 2016: Structure
https://www.readbyqxmd.com/read/27914808/influenza-a-virus-ns1-protein-induced-a20-contributes-to-viral-replication-by-suppressing-interferon-induced-antiviral-response
#15
Wenjing Feng, Xiaoning Sun, Ning Shi, Maolin Zhang, Zhenhong Guan, Ming Duan
The innate immune response provides the first line of defense against viruses and other pathogens by responding to specific microbial molecules. A20 is a cytoplasmic ubiquitin-editing protein that negatively regulates the retinoic acid-inducible gene I (RIG-I)-mediated activation of interferon regulatory factors (IRF) 3. Here, we found that influenza A virus (IAV) non-structural protein (NS) 1 dramatically induced the protein level of A20 in A549 cells whose expression levels were positively associated with the viral virulence...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27906774/lessons-from-characterization-and-treatment-of-the-autoinflammatory-syndromes
#16
Ivona Aksentijevich, Michael F McDermott
PURPOSE OF REVIEW: The list of genes associated with systemic inflammatory diseases has been steadily growing because of the explosion of new genomic technologies. Significant advances in the past year have deepened our understanding of the molecular mechanisms linked to inflammation and elucidated insights on the efficacy of specific therapies for these and related conditions. We review the molecular pathogenesis of four recently characterized monogenic autoinflammatory diseases: haploinsufficiency of A20, otulipenia, a severe form of pyrin-associated disease, and a monogenic form of systemic juvenile idiopathic arthritis...
November 30, 2016: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/27900342/cacna1c-protecting-young-hippocampal-neurons-in-the-adult-brain
#17
Héctor De Jesús-Cortés, Anjali M Rajadhyaksha, Andrew A Pieper
Neuropsychiatric disease is the leading cause of disability in the United States, and fourth worldwide.(1,2) Not surprisingly, human genetic studies have revealed a common genetic predisposition for many forms of neuropsychiatric disease, potentially explaining why overlapping symptoms are commonly observed across multiple diagnostic categories. For example, the CACNA1C gene was recently identified in the largest human genome-wide association study to date as a risk loci held in common across 5 major forms of neuropsychiatric disease: bipolar disorder, schizophrenia, major depressive disorder (MDD), autism spectrum disorder and attention deficit-hyperactivity disorder...
2016: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/27876058/a-novel-non-hodgkin-lymphoma-murine-model-closer-to-the-standard-clinical-scenario
#18
Thais Bascuas, María Moreno, Amy Mónaco, Laura Reyes, Andrea Paolino, Patricia Oliver, María G Kramer, Henry Engler, José P Pacheco, Sofía Grille, José A Chabalgoity
BACKGROUND: Non-Hodgkin lymphomas (NHL) are the most frequent hemato-oncological malignancies. Despite recent major advances in treatment, a substantial proportion of patients relapses highlighting the need for new therapeutic modalities. Promissory results obtained in pre-clinical studies are usually not translated when moving into clinical trials. Pre-clinical studies are mainly conducted in animals with high tumor burden; instead patients undergo chemotherapy as first line of treatment and most likely are under remission when immunotherapies are applied...
November 22, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27869252/resin-dentin-bond-stability-of-experimental-4-meta-based-etch-and-rinse-adhesives-solvated-by-ethanol-or-acetone
#19
Cristiane Mariote Amaral, Alice Marques Diniz, Eugênio Braz Rodrigues Arantes, Glauco Botelho Dos Santos, Jaime Dutra Noronha-Filho, Eduardo Moreira da Silva
PURPOSE: To investigate the influence of 4-META concentration and type of solvent on the degree of conversion (DC%) and resin-dentin bond stability of experimental etch-and-rinse adhesives. MATERIALS AND METHODS: Four different concentrations of 4-META (12 wt%, 20 wt%, 30 wt%, 40 wt%) were added to a model adhesive system consisting of TEG-DMA (25 wt%), UDMA (20 wt%), HEMA (30 wt%), water (4 wt%), camphorquinone (0.5 wt%), and tertiary amine (0.5 wt%) dissolved in 20% acetone (A12, A20, A30 and A40) or 20% ethanol (E12, E20, E30 and E40)...
November 18, 2016: Journal of Adhesive Dentistry
https://www.readbyqxmd.com/read/27867687/a20-inhibits-lipopolysaccharide-induced-inflammation-in-enterocytes
#20
Cui-Fang Zheng, Jie-Ru Shi, Ying Huang, Sheng-Nan Wang
AIM: To examine the role of A20 in the regulation of intestinal epithelial cells (IECs) inflammation. METHODS: Using gene transfection, both stable overexpression and knockdown A20-expressed HT-29 cell lines were established. Accordingly, the cells were divided into the following groups: The control group, the A20 overexpression group, the A20 knockdown group and the respective controls. A20 was stimulated with lipopolysaccharide (LPS) in a dose- and time-dependent manner and was detected using western blotting and real-time polymerase chain reaction (PCR) analyses...
November 6, 2016: World Journal of Gastrointestinal Pharmacology and Therapeutics
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