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https://www.readbyqxmd.com/read/28812539/investigating-ebola-virus-pathogenicity-using-molecular-dynamics
#1
Morena Pappalardo, Francesca Collu, James Macpherson, Martin Michaelis, Franca Fraternali, Mark N Wass
BACKGROUND: Ebolaviruses have been known to cause deadly disease in humans for 40 years and have recently been demonstrated in West Africa to be able to cause large outbreaks. Four Ebolavirus species cause severe disease associated with high mortality in humans. Reston viruses are the only Ebolaviruses that do not cause disease in humans. Conserved amino acid changes in the Reston virus protein VP24 compared to VP24 of other Ebolaviruses have been suggested to alter VP24 binding to host cell karyopherins resulting in impaired inhibition of interferon signalling, which may explain the difference in human pathogenicity...
August 11, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28811972/uncovering-the-immunotherapeutic-cycle-initiated-by-p19arf-and-interferon-%C3%AE-gene-transfer-to-cancer-cells-an-inducer-of-immunogenic-cell-death
#2
REVIEW
Ruan F V Medrano, Aline Hunger, João P P Catani, Bryan E Strauss
Simultaneous reestablishment of p53/p19(Arf) and interferon-β pathways in melanoma cells culminates in a cell death process that displays features of necroptosis along with the release of immunogenic cell death molecules and unleashes an antitumor immune response mediated by natural killer cells, neutrophils as well as CD4(+) and CD8(+) T lymphocytes.
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811964/pd-l2-expression-in-colorectal-cancer-independent-prognostic-effect-and-targetability-by-deglycosylation
#3
Huanbin Wang, Han Yao, Chushu Li, Lunxi Liang, Yao Zhang, Hubing Shi, Chongzhi Zhou, Yingxuan Chen, Jing-Yuan Fang, Jie Xu
Colorectal cancer (CRC) is the second leading cause of cancer death worldwide, and immune checkpoint blockade therapy provides an opportunity for improving the outcome of CRC patients. Recent studies suggest that programmed death ligand-1 (PD-L1) is only expressed in 12% of CRCs. Here, we demonstrate that PD-L2 is expressed in approximately 40% CRCs, and its expression independently associates with poor survival of CRC patients. By detection of PD-L2 expression by immunofluorescence in 124 CRC cases with 10-y survival data, we found significant association between PD-L2 overexpression in cancer cells and worse overall survival (46...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811960/rehmannia-glutinosa-polysaccharide-induces-toll-like-receptor-4-dependent-spleen-dendritic-cell-maturation-and-anti-cancer-immunity
#4
Li Xu, Minseok Kwak, Wei Zhang, Ling Zeng, Peter Chang-Whan Lee, Jun-O Jin
Rehmannia glutinosa polysaccharide (RGP) has shown an activation of immune cells in vitro. However, the immune stimulatory effect of RGP in a mouse in vivo is not well studied. In this study, we examined the effect of RGP on dendritic cell (DC) activation and anticancer immunity in vivo. Treatments of RGP in C56BL/6 mice induced increased levels of co-stimulatory molecule expression and pro-inflammatory cytokine production in spleen DCs dependent on toll-like receptor 4 (TLR4), and those DCs promoted interferon-gamma (IFNγ) production in CD4(+) and CD8(+) T cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811654/characterization-of-the-mollusc-rig-i-mavs-pathway-reveals-an-archaic-antiviral-signalling-framework-in-invertebrates
#5
Baoyu Huang, Linlin Zhang, Yishuai Du, Fei Xu, Li Li, Guofan Zhang
Despite the mitochondrial antiviral signalling protein (MAVS)-dependent RIG-I-like receptor (RLR) signalling pathway in the cytosol plays an indispensable role in the antiviral immunity of the host, surprising little is known in invertebrates. Here we characterized the major members of RLR pathway and investigated their signal transduction a Molluscs. We show that genes involved in RLR pathway were significantly induced during virus challenge, including CgRIG-I-1, CgMAVS, CgTRAF6 (TNF receptor-associated factor 6), and CgIRFs (interferon regulatory factors...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811492/interferon-alpha-treatment-rapidly-clears-hepatitis-e-virus-infection-in-humanized-mice
#6
Martijn D B van de Garde, Suzan D Pas, Gertine W van Oord, Lucio Gama, Youkyung Choi, Robert A de Man, Andre Boonstra, Thomas Vanwolleghem
Antiviral treatment options for chronic Hepatitis E Virus (HEV) infections are limited and immunological determinants of viral persistence remain largely unexplored. We studied the antiviral potency of pegylated interferon-α (pegIFNα) against HEV infections in humanized mice and modelled intrahepatic interferon stimulated gene (ISG) responses. Human gene expression levels in humanized mouse livers were analyzed by qPCR and Nanostring. Human CXCL10 was measured in mouse serum. HEV genotype 3 (gt3) infections were cleared from liver and feces within 8 pegIFNα doses in all mice and relapsed after a single pegIFNα injection in only half of treated animals...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811340/type-iii-interferon-mediated-signaling-is-critical-for-controlling-live-attenuated-yellow-fever-virus-infection-in-vivo
#7
Florian Douam, Yentli E Soto Albrecht, Gabriela Hrebikova, Evita Sadimin, Christian Davidson, Sergei V Kotenko, Alexander Ploss
Yellow fever virus (YFV) is an arthropod-borne flavivirus, infecting ~200,000 people worldwide annually and causing about 30,000 deaths. The live attenuated vaccine strain, YFV-17D, has significantly contributed in controlling the global burden of yellow fever worldwide. However, the viral and host contributions to YFV-17D attenuation remain elusive. Type I interferon (IFN-α/β) signaling and type II interferon (IFN-γ) signaling have been shown to be mutually supportive in controlling YFV-17D infection despite distinct mechanisms of action in viral infection...
August 15, 2017: MBio
https://www.readbyqxmd.com/read/28811159/implementing-and-scaling-up-hcv-treatment-services-for-people-who-inject-drugs-and-other-high-risk-groups-in-ukraine-an-evaluation-of-programmatic-and-treatment-outcomes
#8
Alyona Mazhnaya, Anna Meteliuk, Tetiana Barnard, Alexei Zelenev, Sergii Filippovych, Frederick L Alticec
BACKGROUND: HCV prevalence estimates among people who inject drugs (PWID) in Ukraine is high (60-90%), yet barriers to HCV treatment and care remain substantial including limited access to direct acting antiviral (DAA) medications. A feasibility scale-up project implemented HCV treatment in community-based settings to improve access to DAA treatment for key populations in this context. METHODS: Using program-level data and verified medical records, we describe the development, implementation processes and outcomes for HCV treatment for PWID and other risks groups...
August 12, 2017: International Journal on Drug Policy
https://www.readbyqxmd.com/read/28810822/gamma-irradiated-%C3%AE-glucan-modulates-signaling-molecular-targets-of-hepatocellular-carcinoma-in-rats
#9
Sawsan M Elsonbaty, Walid E Zahran, Fatma Sm Moawed
β-glucans are one of the most abundant forms of polysaccharides known as biological response modifiers which influence host's biological response and stimulate immune system. Accordingly, this study was initiated to evaluate irradiated β-glucan as a modulator for cellular signaling growth factors involved in the pathogenesis of hepatocellular carcinoma in rats. Hepatocellular carcinoma was induced with 20 mg diethylnitrosamine/kg BW. Rats received daily by gastric gavage 65 mg irradiated β-glucan/kg BW. It was found that treatment of rats with diethylnitrosamine induced hepatic injury and caused significant increase in liver injury markers with a concomitant significant increase in both hepatic oxidative and inflammatory indices: alpha-fetoprotein, interferon gamma, and interleukin 6 in comparison with normal and irradiated β-glucan-treated groups...
August 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28810657/anti-exudation-effects-of-sodium-ferulate-and-oxymatrine-combination-via-modulation-of-aquaporin-1
#10
Songmei Sun, Xing Du, Mengxin Xu, Meijuan Liu, Zhifeng Liu
The present study aimed to investigate the anti-exudative effects of sodium ferulate combined with oxymatrine in a mouse model of acetic acid-induced peritonitis. Furthermore, the underlying mechanisms were explored by determining the effects of these drugs on the volume and aquaporin 1 (AQP1) expression in vascular endothelial cells on omentum majus and human umbilical vein endothelial cells (HUVEC). Treatment with sodium ferulate combined with oxymatrine was shown to significantly inhibit acetic acid-induced vascular permeability in the peritonitis model mice and furthermore to significantly decrease the optical density of Evans blue, the leukocyte number and the levels of interleukin-6, C-reactive protein and interferon-γ in peritoneal lavage fluid...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28810602/hepatitis-c-virus-associated-cryoglobulinemia-with-membrano-proliferative-glomerulonephritis-treated-with-prednisolone-and-interferon-a-case-report
#11
Qiao-Yan Guo, Man Wu, Yang-Wei Wang, Guang-Dong Sun
Hepatitis C virus (HCV) is a major cause of liver-associated morbidity and has an increasing prevalence worldwide. Hepatitis C virus infection may lead to chronic hepatitis, cirrhosis and liver failure. However, it is also associated with a wide range of extra-hepatic complications, such as cryoglobulinemia, an immune complex disease associated with cryoglobulin leading to multiple organ damage and, while the major symptom is vasculitis. The present study reported on a-58-year-old woman who was diagnosed with HCV-associated cryoglobulinemia with skin, kidney and blood system damage and biopsy-proven cryoglobulinemia membrano-proliferative glomerulonephritis...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28810265/viral-retinopathy-in-experimental-models-of-zika-infection
#12
Zhenyang Zhao, Matthew Yang, Sasha R Azar, Lynn Soong, Scott C Weaver, Jiaren Sun, Yan Chen, Shannan L Rossi, Jiyang Cai
Purpose: Emerging evidence has shown that both congenital and adult Zika virus (ZIKV) infection can cause eye diseases. The goals of the current study were to explore mechanisms and pathophysiology of ZIKV-induced eye defects. Methods: Wild-type or A129 interferon type I receptor-deficient mice were infected by either FSS13025 or Mex1-7 strain of ZIKV. Retinal histopathology was measured at different time points after infection. The presence of viral RNA and protein in the retina was determined by in situ hybridization and immunofluorescence staining, respectively...
August 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28809742/treatment-of-chronic-hcv-infection-with-the-new-direct-acting-antivirals-daa-first-report-of-a-real-world-experience-in-southern-brazil
#13
Hugo Cheinquer, Hoel Sette-Jr, Fernando H Wolff, Alexandre de Araujo, Silvia Coelho-Borges, Silvia R P Soares, Mauricio F A Barros
INTRODUCTION AND AIM: There is almost no data regarding the efficacy of direct acting antivirals (DAAs) therapy in Brazil. The aim of this historical cohort study is to describe the sustained virologic response (SVR) rate among real-world compensated chronic hepatitis C patients in three hepatology centers from Southern Brazil. MATERIALS AND METHODS: Patients were included if they had at least 12 weeks follow-up after the end of therapy. Patients that were lost to follow-up or had treatment prematurely interrupted for any reason were considered treatment failure in this intention to treat analysis...
August 8, 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28808971/high-throughput-screening-for-identification-of-novel-innate-immune-activators
#14
Bryan J Gall, Victor R DeFilippis
Modern drug discovery has embraced in vitro platforms that enable investigation of large numbers of compounds within tractable timeframes and for feasible costs. These endeavors have been greatly aided in recent years by advances in molecular and cell-based methods such as gene delivery and editing technology, advanced imaging, robotics, and quantitative analysis. As such, the examination of phenotypic impacts of novel molecules may only be limited by the size of the compound collection. Innate immune signaling processes in mammalian cells are especially amenable to high-throughput screening platforms since the cellular responses elicited by their activation often result in high level transcription that can be harnessed in the form of bioluminescent or fluorescent signal...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28808968/cgamp-quantification-in-virus-infected-human-monocyte-derived-cells-by-hplc-coupled-tandem-mass-spectrometry
#15
Jennifer Paijo, Volkhard Kaever, Ulrich Kalinke
Upon virus infection, cells of the innate immune system such as dendritic cells and macrophages can mount type I interferon (IFN-I) responses that restrict viral dissemination. To inform host cells of virus infection, detection of cytosolic DNA is one important mechanism. Inappropriate sensing of endogenous DNA and subsequent induction of IFN-I responses can also cause autoimmunity, highlighting the need to tightly regulate DNA sensing. The cyclic GMP-AMP synthase (cGAS) was recently identified to be the major sensor of cytosolic DNA that triggers IFN-I expression...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28808967/purification-of-cyclic-gmp-amp-from-viruses-and-measurement-of-its-activity-in-cell-culture
#16
Alice Mayer, Jonathan Maelfait, Anne Bridgeman, Jan Rehwinkel
Sensing of cytoplasmic DNA by cGAS is essential for the initiation of immune responses against several viruses. cGAS also plays important roles in some autoinflammatory and autoimmune diseases and may be involved in immune responses targeting cancer cells. Once activated, cGAS catalyzes the formation of the di-nucleotide 2'-3'-cyclic GMP-AMP (cGAMP), which propagates a signaling cascade leading to the production of type I interferons (IFNs). Interestingly, cGAMP is incorporated into enveloped viruses and is transferred to newly infected cells by virions...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28808377/anti-inflammatory-potential-of-petiveria-alliacea-on-activated-raw264-7-murine-macrophages
#17
Rosa Martha Perez Gutierrez, Carlos Hoyo-Vadillo
BACKGROUND: Defense and protection to multiple harmful stimuli are the inflammation, when is self-amplified and uncontrolled is the basis of the pathogenesis of a wide variety of inflammatory illness. The aim of this study was to evaluate if Petiveria alliacea could attenuate inflammation in a murine model of RAW264 macrophages the involved model and its involved mechanism. MATERIALS AND METHODS: The ethanol extract from P. alliacea was precipitated with water and supernatant was used for this study (PW)...
July 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28808318/stress-induced-polarization-of-immune-neuroendocrine-phenotypes-in-gallus-gallus
#18
F Nicolas Nazar, Inma Estevez, Silvia G Correa, Raul H Marin
Immune-neuroendocrine phenotypes (INPs) stand for population subgroups differing in immune-neuroendocrine interactions. While mammalian INPs have been characterized thoroughly in rats and humans, avian INPs were only recently described in Coturnix coturnix (quail). To assess the scope of this biological phenomenon, herein we characterized INPs in Gallus gallus (a domestic hen strain submitted to a very long history of strong selective breeding pressure) and evaluated whether a social chronic stress challenge modulates the individuals' interplay affecting the INP subsets and distribution...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28808111/interferon-tau-promotes-cell-survival-and-inhibits-specific-luteolytic-genes-in-bovine-corpus-luteum
#19
Raghavendra Basavaraja, Emilia Przygrodzka, Bartosz Pawlinski, Zdzislaw Gajewski, Monika Marzena Kaczmarek, Rina Meidan
Interferon-tau (IFNT), a maternal recognition of pregnancy signals in domestic ruminants, suppress the release of luteolytic pulses of uterine prostaglandin F2a (PGF2a), thus extending the corpus luteum (CL) life span. We hypothesized that IFNT also exerts anti-luteolytic actions in bovine CL. To examine the direct effects of IFNT on bovine CL, luteal slices and enriched luteal endothelial cells (LECs) were utilized. We found that recombinant ovine IFNT (roIFNT) markedly elevates interferon-associated genes (STAT1, STAT2, and IRF9) and interferon-stimulated genes (ISGs: MX2, ISG15, & OAS1Y) in both models...
August 14, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28807907/an-original-chemical-series-of-pyrimidine-biosynthesis-inhibitors-that-boost-the-antiviral-interferon-response
#20
Marianne Lucas-Hourani, Daniel Dauzonne, Hélène Munier-Lehmann, Samira Khiar, Sébastien Nisole, Julien Dairou, Olivier Helynck, Philippe V Afonso, Frédéric Tangy, Pierre-Olivier Vidalain
De novo pyrimidine biosynthesis is a key metabolic pathway involved in multiple biosynthetic processes. Here, we identified an original series of 3-(1H-indol-3-yl)-2,3-dihydro-4H-furo[3,2-c]chromen-4-one derivatives as a new class of pyrimidine biosynthesis inhibitors formed by two edge-fused polycyclic moieties. We show that identified compounds exhibit a broad-spectrum antiviral activity as well as immunostimulatory properties, in line with recent reports linking de novo pyrimidine biosynthesis with innate defense mechanisms against viruses...
August 14, 2017: Antimicrobial Agents and Chemotherapy
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