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https://www.readbyqxmd.com/read/28088707/dna-sensing-and-immune-responses-in-cancer-therapy
#1
REVIEW
Jian Qiao, Haidong Tang, Yang-Xin Fu
The identification of critical DNA sensors and their pathways has led to revealing the central role of DNA sensing in immune system. It has been initially demonstrated that DNA sensing and immune responses have high impacts on the development and prevention of infection and inflammatory. In addition to toll-like receptor pathways, there is now also emerging evidence that cytosolic enzyme cyclic GMP-AMP synthase (cGAS) is essential for the recognition of not only pathogen-derived DNA but also tumor DNA for innate sensing...
January 12, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28087918/-research-progress-on-the-role-of-tank-binding-kinase-1-in-anti-virus-innate-immune-response
#2
Xue Wang, Yuchuan Zhang, Wei Chen
The innate immune response against viral infection is mainly relies on type I interferon, the production of which is mediated by TANK-binding kinase 1 (TBK1). It is revealed that the downstream TBK1 is activated by viral nucleic acid sensors RIG-I, cGAS and TLR3. The activity of TBK1 is complexly and precisely regulated by different type of protein modifications, including phosphorylation, ubiquitination and Sumolylation. This article focuses on the role of TBK1 in anti-viral innate immunity and the regulatory mechanism for the TBK1 activation...
May 25, 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/28077645/herpes-simplex-virus-1-abrogates-cgas-sting-mediated-cytosolic-dna-sensing-pathway-via-its-virion-host-shutoff-protein-ul41
#3
Chenhe Su, Chunfu Zheng
: Cyclic GMP-AMP synthase (cGAS) is a key DNA sensor capable of detecting microbial DNA and activating the adaptor protein stimulator of interferon genes (STING), leading to interferon (IFN) production and host antiviral responses. Cells exhibited reduced type I IFN production in response to cytosolic DNA in the absence of cGAS. Although cGAS/STING-mediated DNA-sensing signal is crucial for host defense against many viruses, especial for DNA viruses, few viral components have been identified to specifically target this signaling pathway...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28073693/crosstalk-between-cytoplasmic-rig-i-and-sting-sensing-pathways
#4
REVIEW
Alessandra Zevini, David Olagnier, John Hiscott
Detection of evolutionarily conserved molecules on microbial pathogens by host immune sensors represents the initial trigger of the immune response against infection. Cytosolic receptors sense viral and intracellular bacterial genomes, as well as nucleic acids produced during replication. Once activated, these sensors trigger multiple signaling cascades, converging on the production of type I interferons and proinflammatory cytokines. Although distinct classes of receptors are responsible for the RNA and DNA sensing, the downstream signaling components are physically and functionally interconnected...
January 7, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28069950/chronic-innate-immune-activation-of-tbk1-suppresses-mtorc1-activity-and-dysregulates-cellular-metabolism
#5
Maroof Hasan, Vijay K Gonugunta, Nicole Dobbs, Aktar Ali, Guillermo Palchik, Maria A Calvaruso, Ralph J DeBerardinis, Nan Yan
Three-prime repair exonuclease 1 knockout (Trex1(-/-)) mice suffer from systemic inflammation caused largely by chronic activation of the cyclic GMP-AMP synthase-stimulator of interferon genes-TANK-binding kinase-interferon regulatory factor 3 (cGAS-STING-TBK1-IRF3) signaling pathway. We showed previously that Trex1-deficient cells have reduced mammalian target of rapamycin complex 1 (mTORC1) activity, although the underlying mechanism is unclear. Here, we performed detailed metabolic analysis in Trex1(-/-) mice and cells that revealed both cellular and systemic metabolic defects, including reduced mitochondrial respiration and increased glycolysis, energy expenditure, and fat metabolism...
January 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28041929/the-chlamydia-trachomatis-inclusion-membrane-protein-cpos-counteracts-sting-mediated-cellular-surveillance-and-suicide-programs
#6
Barbara S Sixt, Robert J Bastidas, Ryan Finethy, Ryan M Baxter, Victoria K Carpenter, Guido Kroemer, Jörn Coers, Raphael H Valdivia
Evading cell death is critical for Chlamydia to maintain a replicative niche, but the underlying mechanisms are unknown. We screened a library of Chlamydia mutants for modulators of cell death. Inactivation of the inclusion membrane protein CpoS (Chlamydia promoter of survival) induced rapid apoptotic and necrotic death in infected cells. The protection afforded by CpoS is limited to the inclusion in which it resides, indicating that it counteracts a spatially restricted pro-death signal. CpoS-deficient Chlamydia induced an exacerbated type I interferon response that required the host cGAS/STING/TBK1/IRF3 signaling pathway...
January 11, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28031360/herpes-simplex-virus-type-1-ubiquitin-specific-protease-ul36-abrogates-nf-%C3%AE%C2%BAb-activation-in-dna-sensing-signal-pathway
#7
Ruijie Ye, Chenhe Su, Haiyan Xu, Chunfu Zheng
: The DNA sensing pathway triggers innate immune responses against DNA virus infection and the NF-κB signaling plays a critical role in establishing the innate immunity. Here we report that the herpes simplex virus type 1 (HSV-1) ubiquitin-specific protease (UL36USP), which is a deubiquitinase (DUB), antagonizes the NF-κB activation, depending on its DUB activity. In this study, ectopically expressed UL36USP blocked promoter activation of interferon (IFN)-β and NF-κB induced by cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING)...
December 28, 2016: Journal of Virology
https://www.readbyqxmd.com/read/28012692/mediation-of-coffee-induced-improvements-in-human-vascular-function-by-chlorogenic-acids-and-its-metabolites-two-randomized-controlled-crossover-intervention-trials
#8
Charlotte E Mills, Andreas Flury, Cynthia Marmet, Laura Poquet, Stefano F Rimoldi, Claudio Sartori, Emrush Rexhaj, Roman Brenner, Yves Allemann, Diane Zimmermann, Glenn R Gibson, Don S Mottram, Maria-Jose Oruna-Concha, Lucas Actis-Goretta, Jeremy P E Spencer
BACKGROUND & AIMS: Polyphenol intake has been linked to improvements in human vascular function, although data on hydroxycinnamates, such as chlorogenic acid (CGA) have not yet been studied. We aimed to investigate the impact of coffee intake rich in chlorogenic acid on human vascular function and whether CGAs are involved in potential effects. METHODS: Two acute randomized, controlled, cross-over human intervention trials were conducted. The impact of coffee intake, matched for caffeine but differing in CGA content (89, and 310 mg) on flow-mediated dilatation (FMD) was assessed in 15 healthy male subjects...
November 30, 2016: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28008674/understanding-the-effects-of-roasting-on-antioxidant-components-of-coffee-brews-by-coupling-on-line-abts-assay-to-high-performance-size-exclusion-chromatography
#9
Sebastian E W Opitz, Bernard A Goodman, Marco Keller, Samo Smrke, Marco Wellinger, Stefan Schenker, Chahan Yeretzian
INTRODUCTION: Coffee is a widely consumed beverage containing antioxidant active compounds. During roasting the phytochemical composition of the coffee bean changes dramatically and highly polymeric substances are produced. Besides chlorogenic acids that are already present in green coffee beans, melanoidins show antioxidant capacity as well. OBJECTIVE: To employ post-column derivatisation by coupling high performance size exclusion chromatography (HPSEC) to an antioxidant assay to investigate the effect of roasting on the properties of antioxidant active compounds in coffee brews...
December 23, 2016: Phytochemical Analysis: PCA
https://www.readbyqxmd.com/read/28007901/a-rat-model-of-ataxia-telangiectasia-evidence-for-a-neurodegenerative-phenotype
#10
Hazel Quek, John Luff, KaGeen Cheung, Sergei Kozlov, Magtouf Gatei, C Soon Lee, Mark C Bellingham, Peter G Noakes, Yi Chieh Lim, Nigel L Barnett, Steven Dingwall, Ernst Wolvetang, Tomoji Mashimo, Tara L Roberts, Martin F Lavin
Ataxia-telangiectasia (A-T), an autosomal recessive disease caused by mutations in the ATM gene is characterised by cerebellar atrophy and progressive neurodegeneration which has been poorly recapitulated in Atm mutant mice. Consequently, pathways leading to neurodegeneration in A-T are poorly understood. We describe here the generation of an Atm knockout rat model that does not display cerebellar atrophy but instead paralysis and spinal cord atrophy, reminiscent of that seen in older patients and milder forms of the disorder...
December 22, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/28002511/the-prognostic-and-clinical-significance-of-neuroimagistic-and-neurobiological-vulnerability-markers-in-correlation-with-the-molecular-pharmacogenetic-testing-in-psychoses-and-ultra-high-risk-categories
#11
Laura Alexandra Nussbaum, Lavinia Maria Hogea, Nicoleta Ioana Andreescu, Raluca Claudia Grădinaru, Maria Puiu, Andrei Todica
We approach an integrated, multidisciplinary, innovative research-action model in children and adolescents with psychosis and ultra high-risk categories. Our main focus was: to investigate the prognostic and clinical significance of neuroimagistic and neurobiological vulnerability markers in correlation with the molecular pharmacogenetic testing in psychoses and ultra high-risk categories; the dynamic evaluation of the clinical evolution for the studied groups in correlation with specific neurobiological and neuroimagistic variables and markers...
2016: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/27999287/simultaneous-qualitation-and-quantitation-of-chlorogenic-acids-in-kuding-tea-using-ultra-high-performance-liquid-chromatography-diode-array-detection-coupled-with-linear-ion-trap-orbitrap-mass-spectrometer
#12
Yanyun Che, Zhibin Wang, Zhiyun Zhu, Yangyang Ma, Yaqiong Zhang, Wen Gu, Jiayu Zhang, Gaoxiong Rao
Kuding tea, the leaves of Ilex Kudingcha C.J. Tseng, has been applied for treating obesity, hypertension, cardiovascular disease, hyperlipidemia, and so on. The chlorogenic acids (CGAs) in Kuding tea have shown excellent antioxidative, antiobesity, anti-atherosclerotic and anticancer activities. Nevertheless, the chemical profiles of CGAs in Kuding tea have not been comprehensively studied yet, which hinders further quality control. In the present study, a sensitive ultra-high-performance liquid chromatography-diode array detection coupled with a linear ion trap-Orbitrap (UHPLC-DAD-LTQ-Orbitrap) method was established to screen and identify CGAs in Kuding tea...
December 16, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27988520/dna-sensing-and-nuclease-gene-expressions-as-markers-for-colorectal-cancer-progression
#13
Chin-An Yang, Hsi-Yuan Huang, Ya-Sian Chang, Chia-Li Lin, I-Lu Lai, Jan-Gowth Chang
OBJECTIVE: Oncogene-driven stress-related DNA damage has been observed in lesions of colon cancer. Furthermore, DNA sensors and nucleases are stimulated during active DNA damage and replication. However, their changes and influences with respect to cancer remain largely unknown. METHODS: The gene expression levels of cGAS, IFI16, STING, TBK1, IFNB1, TREX1, SAMHD1, RNASEH2A, RNASEH2B, and RNASEH2C were examined in the paired colorectal cancer and adjacent normal part tissues of 53 patients...
December 17, 2016: Oncology
https://www.readbyqxmd.com/read/27935834/viral-dna-sensors-ifi16-and-cyclic-gmp-amp-synthase-possess-distinct-functions-in-regulating-viral-gene-expression-immune-defenses-and-apoptotic-responses-during-herpesvirus-infection
#14
Benjamin A Diner, Krystal K Lum, Jared E Toettcher, Ileana M Cristea
: The human interferon-inducible protein IFI16 is an important antiviral factor that binds nuclear viral DNA and promotes antiviral responses. Here, we define IFI16 dynamics in space and time and its distinct functions from the DNA sensor cyclic dinucleotide GMP-AMP synthase (cGAS). Live-cell imaging reveals a multiphasic IFI16 redistribution, first to viral entry sites at the nuclear periphery and then to nucleoplasmic puncta upon herpes simplex virus 1 (HSV-1) and human cytomegalovirus (HCMV) infections...
November 15, 2016: MBio
https://www.readbyqxmd.com/read/27933565/kshv-strategies-for-host-dsdna-sensing-machinery
#15
REVIEW
Hang Gao, Yanyan Song, Chengrong Liu, Qiming Liang
The innate immune system utilizes pattern recognition receptors cyclic GMP-AMP synthase (cGAS) to sense cytosolic double-stranded (ds) DNA and initiate type 1 interferon signaling and autophagy pathway, which collaborate to limit pathogen infections as well as alarm the adaptive immune response. The genomes of herpesviruses are large dsDNA, which represent a major class of pathogen signatures recognized by cellular DNA sensor cGAS. However, to successfully establish the persistent infection, herpesviruses have evolved their viral genes to modulate different aspects of host immune signaling...
December 2016: Virologica Sinica
https://www.readbyqxmd.com/read/27902332/inhibition-of-hepatitis-b-virus-replication-by-activation-of-the-cgas-sting-pathway
#16
Jing He, Ruidong Hao, Dan Liu, Xing Liu, Shaoshuai Wu, Shuting Guo, Yuan Wang, Po Tien, Deyin Guo
Cyclic GMP-AMP (cGAMP) synthase (cGAS) senses cytosolic DNA and catalyses synthesis of the second messenger cGAMP, which activates the downstream signalling adaptor protein STING, leading to the expression of type I interferons. Hepatitis B virus (HBV) is a small DNA virus, and the cGAS-STING pathway may inhibit HBV RNA synthesis and viral assembly in cell culture, but the exact roles of the cGAS pathway in the restriction of HBV replication in infection systems remain to be elucidated. In this study, replication of HBV was significantly inhibited both in cell culture and in vivo in a mouse model when the cGAS-STING pathway was activated by dsDNA or cGAMP...
December 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27889408/an-rna-based-fluorescent-biosensor-for-high-throughput-analysis-of-the-cgas-cgamp-sting-pathway
#17
Debojit Bose, Yichi Su, Assaf Marcus, David H Raulet, Ming C Hammond
In mammalian cells, the second messenger (2'-5',3'-5') cyclic guanosine monophosphate-adenosine monophosphate (2',3'-cGAMP), is produced by the cytosolic DNA sensor cGAMP synthase (cGAS), and subsequently bound by the stimulator of interferon genes (STING) to trigger interferon response. Thus, the cGAS-cGAMP-STING pathway plays a critical role in pathogen detection, as well as pathophysiological conditions including cancer and autoimmune disorders. However, studying and targeting this immune signaling pathway has been challenging due to the absence of tools for high-throughput analysis...
December 22, 2016: Cell Chemical Biology
https://www.readbyqxmd.com/read/27863906/post-translational-control-of-intracellular-pathogen-sensing-pathways
#18
REVIEW
Cindy Chiang, Michaela U Gack
Mammalian cells recognize virus-derived nucleic acids using a defined set of intracellular sensors including the DNA sensors cyclic GMP-AMP (cGAMP) synthase (cGAS) and interferon gamma (IFNγ)-inducible protein 16 (IFI16) as well as viral RNA receptors of the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family. Following innate immune recognition, these sensors launch an immune response that is characterized by the transcriptional upregulation of many antiviral molecules, including proinflammatory cytokines, chemokines, and IFN-stimulated genes...
January 2017: Trends in Immunology
https://www.readbyqxmd.com/read/27863149/cgas-expression-in-patients-with-systemic-lupus-erythematosus
#19
Jie An, Laura Durcan, Reynold M Karr, Tracy A Briggs, Gillian I Rice, Thomas H Teal, Joshua J Woodward, Keith B Elkon
OBJECTIVES Type I interferon (IFN-I) is implicated in the pathogenesis of Systemic Lupus Erythematosus (SLE) and 'interferonopathies' such as Aicardi-Goutieres Syndrome. A recently discovered DNA-activated IFN-I pathway, cyclic GMP-AMP (cGAMP) synthase (cGAS) is linked to AGS and mouse models of lupus. The aim of this study was to determine whether the cGAS pathway contributes to IFN-I production in SLE patients. METHODS SLE disease activity was measured by SELENA-SLEDAI. cGAS and interferon stimulated gene (ISG) mRNA expression was quantified by quantitative PCR ...
November 18, 2016: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/27830700/sensing-of-hsv-1-by-the-cgas-sting-pathway-in-microglia-orchestrates-antiviral-defence-in-the-cns
#20
Line S Reinert, Katarína Lopušná, Henriette Winther, Chenglong Sun, Martin K Thomsen, Ramya Nandakumar, Trine H Mogensen, Morten Meyer, Christian Vægter, Jens R Nyengaard, Katherine A Fitzgerald, Søren R Paludan
Herpes simplex encephalitis (HSE) is the most common form of acute viral encephalitis in industrialized countries. Type I interferon (IFN) is important for control of herpes simplex virus (HSV-1) in the central nervous system (CNS). Here we show that microglia are the main source of HSV-induced type I IFN expression in CNS cells and these cytokines are induced in a cGAS-STING-dependent manner. Consistently, mice defective in cGAS or STING are highly susceptible to acute HSE. Although STING is redundant for cell-autonomous antiviral resistance in astrocytes and neurons, viral replication is strongly increased in neurons in STING-deficient mice...
November 10, 2016: Nature Communications
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