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https://www.readbyqxmd.com/read/28228593/er-protein-scap-inhibits-dengue-virus-ns2b3-protease-by-suppressing-its-k27-linked-polyubiquitylation
#1
Heng Liu, Lele Zhang, Jin Sun, Wei Chen, Senlin Li, Qiang Wang, Huansha Yu, Zanxian Xia, Xia Jin, Chen Wang
Dengue viruses (DENVs) are an emerging threat to global public health. The NS2B3 protease complex of DENV has recently been shown to cleave antiviral protein STING and thereby subverting the innate immune signaling to facilitate virus replication. Whether host cells have mechanism to counteract this virus-mediated immunosuppression is unclear. We discovered that the K27-linked poly-ubiquitination of NS3 protein facilitates its recruitment of NS2B and the formation of NS2B3, and consequently the enhanced cleavage of STING...
February 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28224828/with-strings-attached
#2
James Buchan
At the end of last year, it was announced that bursaries will continue to be available to new nursing students in Wales in 2017-18, but with a sting in the tail. Under the proposals, nurses who train in Wales will be required to spend the first two years of their careers in the country. This follows the suggestion that doctors trained in England will have to 'give back' four years of service after qualifying, or buy themselves out of this commitment.
February 22, 2017: Nursing Standard
https://www.readbyqxmd.com/read/28224203/nucleic-acid-sensing-pattern-recognition-receptors-in-the-development-of-colorectal-cancer-and-colitis
#3
REVIEW
Liangmei He, Yayun Chen, Yuanbing Wu, Ying Xu, Zixiang Zhang, Zhiping Liu
Colorectal cancer (CRC) is a leading cause of cancer-related deaths that is often associated with inflammation initiated by activation of pattern recognition receptors (PRRs). Nucleic acid sensing PRRs are one of the major subsets of PRRs that sense nucleic acid (DNA and RNA), mainly including some members of Toll-like receptors (TLR3, 7, 8, 9), AIM2-like receptors (AIM2, IFI16), STING, cGAS, RNA polymerase III, and DExD/H box nucleic acid helicases (such as RIG-I like receptors (RIG-I, MDA5, LPG2), DDX1, 3, 5, 7, 17, 21, 41, 60, and DHX9, 36)...
February 21, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28219022/rationale-for-stimulator-of-interferon-genes-targeted-cancer-immunotherapy
#4
REVIEW
Thaiz Rivera Vargas, Isis Benoit-Lizon, Lionel Apetoh
The efficacy of checkpoint inhibitor therapy illustrates that cancer immunotherapy, which aims to foster the host immune response against cancer to achieve durable anticancer responses, can be successfully implemented in a routine clinical practice. However, a substantial proportion of patients does not benefit from this treatment, underscoring the need to identify alternative strategies to defeat cancer. Despite the demonstration in the 1990's that the detection of danger signals, including the nucleic acids DNA and RNA, by dendritic cells (DCs) in a cancer setting is essential for eliciting host defence, the molecular sensors responsible for recognising these danger signals and eliciting anticancer immune responses remain incompletely characterised, possibly explaining the disappointing results obtained so far upon the clinical implementation of DC-based cancer vaccines...
February 17, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28216981/real-case-of-primitive-embryonal-duodenal-carcinoma-in-a-young-man
#5
Julien Barbieux, Riccardo Memeo, Vito De Blasi, Sebastian Suciu, Vanina Faucher, Gerlinde Averous, Catherine Roy, Jacques Marescaux, Didier Mutter, Patrick Pessaux
We report here the case of a young man suffering from a rare germ cell tumour. The patient was a 25-year-old man who was referred to our centre for asthenia, stinging epigastric pain, and an iron deficiency anaemia. Gastroscopy revealed a circumferential vegetating lesion on the second portion of the duodenum. The lesion was indurated at the third portion of the duodenum, responsible for a tight stenosis. A computerized tomography-scan of the chest, abdomen and pelvis, and a pancreatic MRI showed a circumferential lesion with a bi-ductal dilatation (i...
January 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28216728/marine-and-other-aquatic-dermatoses
#6
Surg Capt Jandhyala Sridhar, Surg Cdr Rajeev Deo
Occupational and recreational aquatic activity predisposes our population to a wide variety of dermatoses. Sunburn, urticaria, jellyfish stings, and contact dermatitis to rubber equipment are common allergies that are encountered in the aquatic environment. Among the infections, tinea versicolor, intertrigo, and verruca vulgaris are widespread. Swimmer's itch may occur due to skin penetration by schistosome cercariae, while free-floating nematocysts of marine coelenterates may precipitate seabather's eruption...
January 2017: Indian Journal of Dermatology
https://www.readbyqxmd.com/read/28216575/promising-targets-for-cancer-immunotherapy-tlrs-rlrs-and-sting-mediated-innate-immune-pathways
#7
REVIEW
Kai Li, Shuai Qu, Xi Chen, Qiong Wu, Ming Shi
Malignant cancers employ diverse and intricate immune evasion strategies, which lead to inadequately effective responses of many clinical cancer therapies. However, emerging data suggest that activation of the tolerant innate immune system in cancer patients is able, at least partially, to counteract tumor-induced immunosuppression, which indicates triggering of the innate immune response as a novel immunotherapeutic strategy may result in improved therapeutic outcomes for cancer patients. The promising innate immune targets include Toll-like Receptors (TLRs), RIG-I-like Receptors (RLRs), and Stimulator of Interferon Genes (STING)...
February 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28208885/study-on-distribution-of-scorpions-to-provide-prevention-and-interventions-in-combating-scorpionism-in-poldokhtar-county-lorestan-province-iran
#8
Mansour Nazari, Rastgar Hassan
INTRODUCTION: Scorpions are arthropods of medical importance classified in the class Arachnida, inhabiting hot and dry environments. All scorpions have a venomous sting and several thousand people die each year from scorpion stings, but this mortality is due to the venom of about 25 species located in northern Africa, the Middle East, India, Mexico and parts of South America. Poldokhtar County belongs to one of the southern cities of Lorestan Province, providing suitable habitats for many different species of scorpions due to its specific climatic conditions...
December 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28202760/restriction-of-hcmv-replication-by-isg15-a-host-effector-regulated-by-cgas-sting-dsdna-sensing
#9
Christopher Bianco, Ian Mohr
Accumulation of the interferon-stimulated gene (ISG) 15 protein product, which is reversibly conjugated to numerous polypeptide targets, impacts the proteome and physiology of uninfected and infected cells. While many viruses, including human cytomegalovirus (HCMV) blunt host antiviral defenses by limiting ISG expression, the overall abundance of ISG15 monomer and protein conjugates rises in HCMV-infected cells. However, the molecular signals underlying ISG15 accumulation and whether the ISG15 polypeptide itself influences HCMV infection biology remain unknown...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28196712/ipomoea-pes-caprae-l-r-br-convolvulaceae-as-a-topical-herbal-medicine-to-relieve-pain-and-inflammation-promising-tool-against-effects-due-to-toxin-skin-contact
#10
Cristiane da Silva Barth, Hugo Guilherme Tolentino de Souza, Lilian W Rocha, Gislaine Francieli da Silva, Mariana Ferreira Dos Anjos, Veronica D'Avila Pastor, Tania Mari Belle Bresolin, Angelica Garcia Couto, José Roberto Santin, Nara Lins Meira Quintão
ETHNOPHARMACOLOGICAL RELEVANCE: Ipomoea pes-caprae is known as bayhops, beach morning glory or goat's foot, and in Brazil as salsa-de-praia. Its leaves are used in worldwide folk medicine for the relief of jellyfish-stings symptoms. The literature only reports the anti-inflammatory and neutralizing effects of a nonpolar plant derived, without validating the popular use or exploring the mechanism of action. AIM OF THE STUDY: This study aimed to evaluate and validate the topical effects of a semisolid containing hydroethanolic extract obtained from the aerial parts of I...
February 11, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28194635/using-the-slug-mucosal-irritation-assay-to-investigate-the-tolerability-of-tablet-excipients-on-human-skin-in-the-context-of-the-use-of-a-nipple-shield-delivery-system
#11
Richard Kendall, Joke Lenoir, Stephen Gerrard, Rebekah L Scheuerle, Nigel K H Slater, Catherine Tuleu
PURPOSE: Neonates are particularly challenging to treat. A novel patented drug delivery device containing a rapidly disintegrating tablet held within a modified nipple shield (NSDS) was designed to deliver medication to infants during breastfeeding. However concerns exist around dermatological nipple tolerability with no pharmaceutical safety assessment guidance to study local tissue tolerance of the nipple and the areola. This is the first Slug Mucosal Irritation (SMI) study to evaluate irritancy potential of GRAS excipients commonly used to manufacture rapidly disintegrating immediate release solid oral dosage form METHODS: Zinc sulphate selected as the antidiarrheal model drug that reduces infant mortality, was blended with functional excipients at traditional levels [microcrystalline cellulose, sodium starch glycolate, croscarmellose sodium, magnesium stearate]...
February 13, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28194029/ifi16-and-cgas-cooperate-in-the-activation-of-sting-during-dna-sensing-in-human-keratinocytes
#12
Jessica F Almine, Craig A J O'Hare, Gillian Dunphy, Ismar R Haga, Rangeetha J Naik, Abdelmadjid Atrih, Dympna J Connolly, Jordan Taylor, Ian R Kelsall, Andrew G Bowie, Philippa M Beard, Leonie Unterholzner
Many human cells can sense the presence of exogenous DNA during infection though the cytosolic DNA receptor cyclic GMP-AMP synthase (cGAS), which produces the second messenger cyclic GMP-AMP (cGAMP). Other putative DNA receptors have been described, but whether their functions are redundant, tissue-specific or integrated in the cGAS-cGAMP pathway is unclear. Here we show that interferon-γ inducible protein 16 (IFI16) cooperates with cGAS during DNA sensing in human keratinocytes, as both cGAS and IFI16 are required for the full activation of an innate immune response to exogenous DNA and DNA viruses...
February 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28193791/epinephrine-for-first-aid-management-of-anaphylaxis
#13
Scott H Sicherer, F Estelle R Simons
Anaphylaxis is a severe, generalized allergic or hypersensitivity reaction that is rapid in onset and may cause death. Epinephrine (adrenaline) can be life-saving when administered as rapidly as possible once anaphylaxis is recognized. This clinical report from the American Academy of Pediatrics is an update of the 2007 clinical report on this topic. It provides information to help clinicians identify patients at risk of anaphylaxis and new information about epinephrine and epinephrine autoinjectors (EAs). The report also highlights the importance of patient and family education about the recognition and management of anaphylaxis in the community...
February 13, 2017: Pediatrics
https://www.readbyqxmd.com/read/28191486/rigulation-of-sting-expression-at-the-crossroads-of-viral-rna-and-dna-sensing-pathways
#14
Yiliu Liu, Rongtuan Lin, David Olagnier
The innate immune sensing of pathogens is important for host to mount defensive responses. STING has emerged in recent years as a critical signaling adaptor in the immune response to cytosolic DNA and RNA derived from pathogens. Liu et al. (2016) demonstrate that the RIG-I-dependent RNA sensing signaling induces STING expression via a TNF-α and IFN-α synergy. The up-regulation of STING is vital for 5'pppRNA restriction of HSV, a DNA virus that infects humans and causes herpes, in vitro and in vivo. This study provides new insights into the cross talk between DNA and RNA pathogen-sensing systems via the control of STING...
January 1, 2017: Inflammation and Cell Signaling
https://www.readbyqxmd.com/read/28188292/cytosolic-dna-promotes-signal-transducer-and-activator-of-transcription-3-stat3-phosphorylation-by-tank-binding-kinase-1-tbk1-to-restrain-stat3-activity
#15
Hung-Ching Hsia, Jessica E Hutti, Albert S Baldwin
Cytosolic DNA can elicit beneficial as well as undesirable immune responses. For example, viral or microbial DNA triggers cell-intrinsic immune responses to defend against infections, whereas aberrant cytosolic accumulation of self-DNA results in pathological conditions, such as autoimmunity. Given the importance of these DNA-provoked responses, a better understanding of their molecular mechanisms is needed. Cytosolic DNA engages stimulator of interferon genes (STING) to activate TANK-binding kinase 1 (TBK1), which subsequently phosphorylates the transcription factor interferon regulatory factor 3 (IRF3) to promote interferon expression...
February 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28186168/ifi16-is-required-for-dna-sensing-in-human-macrophages-by-promoting-production-and-function-of-cgamp
#16
K L Jønsson, A Laustsen, C Krapp, K A Skipper, K Thavachelvam, D Hotter, J H Egedal, M Kjolby, P Mohammadi, T Prabakaran, L K Sørensen, C Sun, S B Jensen, C K Holm, R J Lebbink, M Johannsen, M Nyegaard, J G Mikkelsen, F Kirchhoff, S R Paludan, M R Jakobsen
Innate immune activation by macrophages is an essential part of host defence against infection. Cytosolic recognition of microbial DNA in macrophages leads to induction of interferons and cytokines through activation of cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING). Other host factors, including interferon-gamma inducible factor 16 (IFI16), have been proposed to contribute to immune activation by DNA. However, their relation to the cGAS-STING pathway is not clear. Here, we show that IFI16 functions in the cGAS-STING pathway on two distinct levels...
February 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28181006/cyclic-dinucleotides-in-the-scope-of-the-mammalian-immune-system
#17
Arun K Mankan, Martina Müller, Gregor Witte, Veit Hornung
First discovered in prokaryotes and more recently in eukaryotes, cyclic dinucleotides (CDNs) constitute a unique branch of second messenger signaling systems. Within prokaryotes CDNs regulate a wide array of different biological processes, whereas in the vertebrate system CDN signaling is largely dedicated to activation of the innate immune system. In this book chapter we summarize the occurrence and signaling pathways of these small-molecule second messengers, most importantly in the scope of the mammalian immune system...
February 9, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28179534/impaired-sting-pathway-in-the-human-osteosarcoma-u2os-cells-contributes-to-the-growth-of-icp0-null-mutant-herpes-simplex-virus
#18
Thibaut Deschamps, Maria Kalamvoki
Human herpes simplex virus-1 (HSV-1) is a wide spread pathogen with 80% of the population being latently infected. To successfully evade the host the virus has evolved strategies to counteract antiviral responses, including the gene silencing and innate immunity machineries. The immediately early protein of the virus, Infected Cell Protein 0 (ICP0) plays central role in these processes. ICP0 blocks innate immunity and one mechanism is by degrading hostile factors with its intrinsic E3 ligase activity. ICP0 functions also as a promiscuous transactivator and it blocks repressor complexes to enable viral gene transcription...
February 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28178416/single-mutations-reshape-the-structural-correlation-network-of-dmxaa-human-sting-complex
#19
Xing Che, Xiao-Xia Du, Xiaoxia Cai, Jun Zhang, Wen Jun Xie, Zhuoran Long, Zhaoyang Ye, Heng Zhang, Lijiang Yang, Xiaodong Su, Yi Qin Gao
Subtle changes in protein sequence are able to alter ligand-protein interactions. Unraveling the mechanism of such phenomena is important for understanding ligand-protein interaction, including the DMXAA-STING interaction. DMXAA specifically binds to mouse STING instead of human STING. However, the S162A mutation and a newly discovered E260I mutation endow human STINGAQ with DMXAA sensitivity. Through MD simulations, we revealed how these single mutations alter the DMXAA-STING interaction. Compared to mutated systems, structural correlations in the interaction of STINGAQ with DMXAA are stronger and the correlations are cross-protomer in the dimeric protein...
February 8, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28176788/decreased-expression-of-sting-predicts-poor-prognosis-in-patients-with-gastric-cancer
#20
Shushu Song, Peike Peng, Zhaoqing Tang, Junjie Zhao, Weicheng Wu, Haojie Li, Miaomiao Shao, Lili Li, Caiting Yang, Fangfang Duan, Mingming Zhang, Jie Zhang, Hao Wu, Can Li, Xuefei Wang, Hongshan Wang, Yuanyuan Ruan, Jianxin Gu
STING (stimulator of interferon genes) has recently been found to play an important role in host defenses against virus and intracellular bacteria via the regulation of type-I IFN signaling and innate immunity. Chronic infection with Helicobacter pylori is identified as the strongest risk factor for gastric cancer. Thus, we aim to explore the function of STING signaling in the development of gastric cancer. Immunohistochemistry was used to detect STING expression in 217 gastric cancer patients who underwent surgical resection...
February 8, 2017: Scientific Reports
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