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https://www.readbyqxmd.com/read/29782908/deficits-in-temporal-order-memory-induced-by-interferon-alpha-ifn-%C3%AE-treatment-are-rescued-by-aerobic-exercise
#1
Sally Barlow, Briana Fahey, Kimberley J Smith, Johannes Passecker, Andrea Della-Chiesa, Vincent Hok, Jennifer S Day, Charlotte K Callaghan, Shane M O'Mara
Patients receiving cytokine immunotherapy with IFN-α frequently present with neuropsychiatric consequences and cognitive impairments, including a profound depressive-like symptomatology. While the neurobiological substrates of the dysfunction that leads to adverse events in IFN-α-treated patients remains ill-defined, dysfunctions of the hippocampus and prefrontal cortex (PFC) are strong possibilities. To date, hippocampal deficits have been well-characterised; there does however remain a lack of insight into the nature of prefrontal participation...
May 18, 2018: Brain Research Bulletin
https://www.readbyqxmd.com/read/29782795/rna-modulates-the-interaction-between-influenza-a-virus-ns1-and-human-pabp1
#2
Bryan H Arias-Mireles, Cyrus M de Rozieres, Kevin Ly, Simpson Joseph
Non-Structural Protein 1 (NS1) is a multifunctional protein involved in preventing host-interferon response in Influenza A Virus (IAV). Previous studies have indicated that NS1 also stimulates the translation of viral mRNA by binding to conserved sequences in the viral 5'-UTR. Additionally, NS1 binds to Poly (A) Binding Protein (PABP1) and eukaryotic Initiation Factor 4G (eIF4G). The interaction of NS1 with the viral 5'-UTR, PABP1, and eIF4G has been suggested to specifically enhance the translation of viral mRNAs...
May 21, 2018: Biochemistry
https://www.readbyqxmd.com/read/29782541/an-unappreciated-role-for-neutrophil-dc-hybrids-in-immunity-to-invasive-fungal-infections
#3
J Scott Fites, Michael Gui, John F Kernien, Paige Negoro, Zeina Dagher, David B Sykes, Jeniel E Nett, Michael K Mansour, Bruce S Klein
Neutrophils are classically defined as terminally differentiated, short-lived cells; however, neutrophils can be long-lived with phenotypic plasticity. During inflammation, a subset of neutrophils transdifferentiate into a population called neutrophil-DC hybrids (PMN-DCs) having properties of both neutrophils and dendritic cells. While these cells ubiquitously appear during inflammation, the role of PMN-DCs in disease remains poorly understood. We observed the differentiation of PMN-DCs in pre-clinical murine models of fungal infection: blastomycosis, aspergillosis and candidiasis...
May 21, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29782532/hepatitis-c-virus-ns4b-induces-the-degradation-of-trif-to-inhibit-tlr3-mediated-interferon-signaling-pathway
#4
Yisha Liang, Xuezhi Cao, Qiang Ding, Yanan Zhao, Zhenliang He, Jin Zhong
Toll-like receptor 3 (TLR3) senses dsRNA intermediates produced during RNA virus replication to activate innate immune signaling pathways through adaptor protein TRIF. Many viruses have evolved strategies to block TLR3-mediated interferon signaling via targeting TRIF. Here we studied how hepatitis C virus (HCV) antagonizes the TLR3-mediated interferon signaling. We found that HCV-encoded NS4B protein inhibited TLR3-mediated interferon signaling by down-regulating TRIF protein level. Mechanism studies indicated that the downregulation of TRIF by NS4B was dependent on caspase8...
May 21, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29782483/magnolol-and-honokiol-attenuate-apoptosis-of-enterotoxigenic-escherichia-coli-induced-intestinal-epithelium-by-maintaining-secretion-and-absorption-homeostasis-and-protecting-mucosal-integrity
#5
Yanli Deng, Xuefeng Han, Shaoxun Tang, Chengjian Li, Wenjun Xiao, Zhiliang Tan
BACKGROUND The cortex of Magnolia officinalis has long been used as an element of traditional Chinese medicine for the treatment of anxiety, chronic bronchitis, and gastrointestinal dysfunction. This study aimed to elucidate the underlying mechanism of its functional ingredients (magnolol and honokiol) in modifying the secretion and absorption homeostasis and protecting mucosal integrity in an Enterotoxigenic Escherichia coli (ETEC)-induced diarrhea mouse model. MATERIAL AND METHODS This study established a diarrhea mouse model infected by ETEC at a dosage of 0...
May 21, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29782060/autosomal-dominant-early-onset-spastic-paraparesis-with-brain-calcification-due-to-ifih1-gain-of-function
#6
Lyse Ruaud, Gillian I Rice, Christelle Cabrol, Juliette Piard, Mathieu Rodero, Lien van Eyk, Elise Boucher-Brischoux, Alain Maertens de Noordhout, Ricardo Maré, Emmanuel Scalais, Fernand Pauly, François-Guillaume Debray, William Dobyns, Carolina Uggenti, Ji Woo Park, Sun Hur, John H Livingston, Yanick J Crow, Lionel Van Maldergem
We describe progressive spastic paraparesis in two male siblings and the daughter of one of these individuals. Onset of disease occurred within the first decade, with stiffness and gait difficulties. Brisk deep tendon reflexes and extensor plantar responses were present, in the absence of intellectual disability or dermatological manifestations. Cerebral imaging identified intracranial calcification in all symptomatic family members. A marked upregulation of interferon stimulated gene (ISG) transcripts was recorded in all three affected individuals and in two clinically unaffected relatives...
May 21, 2018: Human Mutation
https://www.readbyqxmd.com/read/29781535/mir-1178-regulates-mycobacterial-survival-and-inflammatory-responses-in-mycobacterium-tuberculosis-infected-macrophages-partly-via-tlr4
#7
Ge Shi, Guofeng Mao, Kejie Xie, Dongdong Wu, Wei Wang
Tuberculosis is chronic respiratory infectious disease and is caused by the infection of Mycobacterium tuberculosis (M.tb). Macrophages play an important role in host immune response against M.tb infection, which is regulated by various factors, including microRNAs (miRNAs). The present study aimed to examine the in vitro functional role of miR-1178 in mycobacterial survival and inflammatory responses induced by M.tb infection in human macrophages. Our results showed that M.tb infection increased the expression of miR-1178 in human macrophages (HTP-1 and U937 cells) in a concentration- and time-dependent manner...
May 21, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29781188/a-novel-anti-malarial-drug-derivative-inhibits-cyclic-gmp-amp-synthase-in-trex1-deficient-mice
#8
Jie An, Joshua J Woodward, Weinan Lai, Mark Minie, Xizhang Sun, Lena Tanaka, Jessica M Snyder, Tomikazu Sasaki, Keith B Elkon
OBJECTIVE: Type I interferon (IFN-I) is strongly implicated in the pathogenesis of Systemic Lupus Erythematosus (SLE) as well as rare monogenic 'interferonopathies' such as Aicardi-Goutieres Syndrome (AGS) caused by mutations in the DNA exonuclease, TREX1. The DNA-activated IFN-I pathway, cyclic GMP-AMP (cGAMP) synthase (cGAS), is linked to subsets of AGS and lupus. We identified inhibitors of DNA-cGAS interaction and tested lead candidate, X6, in a mouse model of AGS. METHODS: Trex1-/- mice were treated orally from birth with either X6 or HCQ for 8 weeks...
May 21, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29780383/human-metapneumovirus-infection-inhibits-cathelicidin-antimicrobial-peptide-expression-in-human-macrophages
#9
Youxian Li, Stine Østerhus, Ingvild B Johnsen
Human cathelicidin antimicriobial peptide (CAMP) is a critical component of host innate immunity with both antimicrobial and immunomodulatory functions. Several pathogens have been shown to downregulate CAMP expression, yet it is unclear if such modulation occurs during a viral infection. In this study, we showed that infection with human metapneumovirus (hMPV), one of the leading causes of respiratory tract infections in young children, strongly suppressed basal and vitamin-D induced CAMP expression in human macrophages...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29780381/interferon-gamma-at-the-crossroads-of-tumor-immune-surveillance-or-evasion
#10
REVIEW
Flávia Castro, Ana Patrícia Cardoso, Raquel Madeira Gonçalves, Karine Serre, Maria José Oliveira
Interferon-gamma (IFN-γ) is a pleiotropic molecule with associated antiproliferative, pro-apoptotic and antitumor mechanisms. This effector cytokine, often considered as a major effector of immunity, has been used in the treatment of several diseases, despite its adverse effects. Although broad evidence implicating IFN-γ in tumor immune surveillance, IFN-γ-based therapies undergoing clinical trials have been of limited success. In fact, recent reports suggested that it may also play a protumorigenic role, namely, through IFN-γ signaling insensitivity, downregulation of major histocompatibility complexes, and upregulation of indoleamine 2,3-dioxygenase and of checkpoint inhibitors, as programmed cell-death ligand 1...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29780305/comparing-effects-of-transforming-growth-factor-%C3%AE-1-on-microglia-from-rat-and-mouse-transcriptional-profiles-and-potassium-channels
#11
Starlee Lively, Doris Lam, Raymond Wong, Lyanne C Schlichter
The cytokine, transforming growth factor β1 (TGFβ1), is up-regulated after central nervous system (CNS) injuries or diseases involving microglial activation, and it has been proposed as a therapeutic agent for treating neuroinflammation. Microglia can produce and respond to TGFβ1. While rats and mice are commonly used for studying neuroinflammation, very few reports directly compare them. Such studies are important for improving pre-clinical studies and furthering translational progress in developing therapeutic interventions...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29780258/influence-of-different-ex-vivo-cell-culture-methods-on-the-proliferation-and-anti-tumor-activity-of-cytokine-induced-killer-cells-from-gastric-cancer-patients
#12
Bin Shi, Aixia Sun, Xiaorui Zhang
Purpose: In cytokine-induced killer (CIK) cell therapy, the phenotypes and the numbers of CIK cells have a great influence on the therapeutic effects. This study aimed to investigate the effects of different ex vivo cell culture methods on the proliferation and cytotoxicity of CIK cells that were obtained from gastric cancer patients. Patients and methods: CIK precursor (Pre-CIK) cells were collected by either hydroxyethyl starch (HES) sedimentation (HES method, unpurified group) or Ficoll-Hypaque density gradient centrifugation (Ficoll method, purified group)...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29780147/disseminated-mycobacterium-avium-infection-presenting-with-bladder-lesions-in-a-patient-with-interferon-%C3%AE-neutralizing-autoantibodies
#13
Koichi Miyashita, Shun Matsuura, Kenichi Tajima, Shogo Tajima, Ami Aoki, Takuro Sakagami, Naoki Koshimizu, Mikio Toyoshima, Takafumi Suda
A 63-year-old woman presented with a fever, eruption, and sterile pyuria. A cystoscopic examination revealed submucosal nodular lesions in the trigone of the bladder, and a biopsy specimen showed epithelioid cell granulomas in the lamina propria of the bladder. Mycobacterium avium grew in the urine culture. Other organ involvement, such as the lungs, spleen, bones, muscles, and pelvic lymph nodes, was observed on radiological examinations, and M. avium was isolated from some organ lesions. Interferon-γ-neutralizing autoantibodies were detected in the patient' s serum...
May 18, 2018: Internal Medicine
https://www.readbyqxmd.com/read/29779923/a-viral-vectored-rsv-vaccine-induces-long-lived-humoral-immunity-in-cotton-rats
#14
Jessica L Grieves, Zhiwei Yin, Adolfo Garcia-Sastre, Ignacio Mena, Mark E Peeples, Heidi P Risman, Hannah Federman, Marvin J Sandoval, Russell K Durbin, Joan E Durbin
Human respiratory syncytial virus (RSV) is the leading cause of lower airway disease in infants worldwide and repeatedly infects immunocompetent individuals throughout life. Severe lower airway RSV infection during infancy can be life-threatening, but is also associated with important sequelae including development of asthma and recurrent wheezing in later childhood. The basis for the inadequate, short-lived adaptive immune response to RSV infection is poorly understood, but it is widely recognized that RSV actively antagonizes Type I interferon (IFN) production...
May 17, 2018: Vaccine
https://www.readbyqxmd.com/read/29779769/seasonal-variation-in-the-performance-of-quantiferon-tb-gold-in-tube-assays-used-for-the-diagnosis-of-tuberculosis-infection
#15
Marc Tebruegge, Nigel Curtis, Vanessa Clifford, Cristina Fernandez-Turienzo, Nigel Klein, Katy Fidler, Salah Mansour, Paul Elkington, Stephen Morris-Jones
This study aimed to determine whether there are seasonal changes in the performance of QuantiFERON-TB Gold In-Tube (QFT-GIT) assays, an interferon-gamma release assay widely used for the diagnosis of tuberculosis infection. Results of 31,932 QFT-GIT assays performed at a large independent, accredited diagnostic service provider in London, UK over a 4.5-year-period were analysed. The proportion of positive results was significantly lower in autumn (14.8%) than in spring (16.0%; p = 0.0366) and summer (17...
May 2018: Tuberculosis
https://www.readbyqxmd.com/read/29779403/lipids-glucose-and-iron-metabolic-alterations-in-chronic-hepatitis-c-after-viral-eradication-comparison-of-the-new-direct-acting-antiviral-agents-with-the-old-regimens
#16
Joana Rita Carvalho, José Velosa, Fátima Serejo
BACKGROUND: Hepatitis C virus (HCV) is a unique virus which interacts with cholesterol, iron and insulin metabolism. There is limited data on the effects of direct-acting antiviral agents (DAAs) on metabolic profiles. We aimed at evaluating the behavior of metabolic risk factors of chronically HCV-infected patients after sustained virologic response (SVR), comparing the outcomes with the new DAAs versus the old treatment regimen Peg-interferon ± ribavirin. METHODS: A total of 178 patients who achieved SVR and completed one year of follow-up were prospectively included in this study: group 1 with 105 patients treated with DAAs and group 2 with 73 patients treated with old regimens...
May 20, 2018: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/29779267/%C3%AE-synuclein-activates-innate-immunity-but-suppresses-interferon-%C3%AE-expression-in-murine-astrocytes
#17
Jintang Wang, Zheng Chen, Jeremy Walston, Peisong Gao, Maolong Gao, Sean X Leng
Glial activation and neuroinflammation contribute to pathogenesis of neurodegenerative diseases, linked to neuron loss and dysfunction. α-Synuclein (α-syn), as a metabolite of neuron, can induce microglia activation to trigger innate immune response. However, whether α-syn, as well as its mutants (A53T, A30P and E46K), induces astrocyte activation and inflammatory response is not fully elucidated. In this study, we used A53T mutant and wildtype α-syns to stimulate primary astrocytes in dose- and time-dependent manners (0...
May 19, 2018: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29778205/immunopathological-changes-and-apparent-recovery-from-infection-revealed-in-cattle-in-an-experimental-model-of-johne-s-disease-using-a-lyophilised-culture-of-mycobacterium-avium-subspecies-paratuberculosis
#18
Douglas J Begg, Karren M Plain, Kumudika de Silva, Ratna Gurung, Alison Gunn, Auriol C Purdie, Richard J Whittington
Johne's disease (JD) or paratuberculosis is an economically significant, chronic enteropathy of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP). Experimental models of JD in cattle are logistically challenging due to the need for long term monitoring, because the clinical disease can take years to manifest. Three trials were undertaken, the largest involving 20 cattle exposed orally to a low dose of C strain MAP and 10 controls studied for 4.75 years. Frequent blood and faecal sampling was used to monitor immunological and infection parameters, and intestinal biopsies were performed at two time points during the subclinical disease phase...
June 2018: Veterinary Microbiology
https://www.readbyqxmd.com/read/29777870/profiling-modifications-for-glioblastoma-proteome-using-ultra-tolerant-database-search-are-the-peptide-mass-shifts-biologically-relevant-or-chemically-induced
#19
Irina A Tarasova, Peter M Chumakov, Sergei A Moshkovskii, Mikhail V Gorshkov
Peptide mass shifts were profiled using ultra-tolerant database search strategy for shotgun proteomics data sets of human glioblastoma cell lines demonstrating strong response to the type I interferon (IFNα-2b) treatment. The main objective of this profiling was revealing the cell response to IFN treatment at the level of protein modifications. To achieve this objective, statistically significant changes in peptide mass shift profiles between IFN treated and untreated glioblastoma samples were analyzed. Detailed analysis of MS/MS spectra allowed further interpretation of the observed mass shifts and differentiation between post-translational and artifact modifications...
May 16, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29777224/progression-of-whole-blood-transcriptional-signatures-from-interferon-induced-to-neutrophil-associated-patterns-in-severe-influenza
#20
Jake Dunning, Simon Blankley, Long T Hoang, Mike Cox, Christine M Graham, Philip L James, Chloe I Bloom, Damien Chaussabel, Jacques Banchereau, Stephen J Brett, Miriam F Moffatt, Anne O'Garra, Peter J M Openshaw
Transcriptional profiles and host-response biomarkers are used increasingly to investigate the severity, subtype and pathogenesis of disease. We now describe whole-blood mRNA signatures and concentrations of local and systemic immunological mediators in 131 adults hospitalized with influenza, from whom extensive clinical and investigational data were obtained by MOSAIC investigators. Signatures reflective of interferon-related antiviral pathways were common up to day 4 of symptoms in patients who did not require mechanical ventilator support; in those who needed mechanical ventilation, an inflammatory, activated-neutrophil and cell-stress or death ('bacterial') pattern was seen, even early in disease...
May 18, 2018: Nature Immunology
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