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https://www.readbyqxmd.com/read/29327729/h5n1-influenza-virus-specific-mirna-like-small-rna-increases-cytokine-production-and-mouse-mortality-via-targeting-poly-rc-binding-protein-2
#1
Xihan Li, Zheng Fu, Hongwei Liang, Yanbo Wang, Xian Qi, Meng Ding, Xinlei Sun, Zhen Zhou, Ying Huang, Hongwei Gu, Limin Li, Xi Chen, Donghai Li, Quan Zhao, Fenyong Liu, Hua Wang, Jin Wang, Ke Zen, Chen-Yu Zhang
Infection of H5N1 influenza virus causes the highest mortality among all influenza viruses. The mechanisms underlying such high viral pathogenicity are incompletely understood. Here, we report that the H5N1 influenza virus encodes a microRNA-like small RNA, miR-HA-3p, which is processed from a stem loop-containing viral RNA precursor by Argonaute 2, and plays a role in enhancing cytokine production during H5N1 infection. Mechanistic study shows that miR-HA-3p targets poly(rC)-binding protein 2 (PCBP2) and suppresses its expression...
January 12, 2018: Cell Research
https://www.readbyqxmd.com/read/29317732/the-regulation-of-seventeen-inflammatory-mediators-are-associated-with-patient-outcomes-in-severe-fever-with-thrombocytopenia-syndrome
#2
Li-Fen Hu, Ting Wu, Bo Wang, Yuan-Yuan Wei, Qin-Xiang Kong, Ying Ye, Hua-Fa Yin, Jia-Bin Li
Severe fever with thrombocytopenia syndrome (SFTS) as an emerging infection disease results in high morbidity and mortality in China. In this study, the circulating levels of 36 inflammatory mediators in 33 SFTS patients on days 3-7, 8-12 and 13-20 post-illness were measured by a multiplex Luminex® system dynamically. Among the patients, 15 severe patients recovered, 11 severe patients died within three weeks. We found IL-1RA, IL-6, IL-15, IL-10, TNF-α, IFN-γ, G-CSF, eotaxin, IL-8, IP-10, MCP-1, MIP-1α, MIP-1β and fractalkine were significantly upregulated in SFTS patients...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29312553/development-of-novel-target-modules-for-retargeting-of-unicar-t-cells-to-gd2-positive-tumor-cells
#3
Nicola Mitwasi, Anja Feldmann, Ralf Bergmann, Nicole Berndt, Claudia Arndt, Stefanie Koristka, Alexandra Kegler, Justyna Jureczek, Anja Hoffmann, Armin Ehninger, Marc Cartellieri, Susann Albert, Claudia Rossig, Gerhard Ehninger, Jens Pietzsch, Jörg Steinbach, Michael Bachmann
As the expression of a tumor associated antigen (TAA) is commonly not restricted to tumor cells, adoptively transferred T cells modified to express a conventional chimeric antigen receptor (CAR) might not only destroy the tumor cells but also attack target-positive healthy tissues. Furthermore, CAR T cells in patients with large tumor bulks will unpredictably proliferate and put the patients at high risk of adverse side effects including cytokine storms and tumor lysis syndrome. To overcome these problems, we previously established a modular CAR technology termed UniCAR: UniCAR T cells can repeatedly be turned on and off via dosing of a target module (TM)...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29300777/internal-genes-of-a-highly-pathogenic-h5n1-influenza-virus-determine-high-viral-replication-in-myeloid-cells-and-severe-outcome-of-infection-in-mice
#4
Hui Li, Konrad C Bradley, Jason S Long, Rebecca Frise, Jonathan W Ashcroft, Lorian C Hartgroves, Holly Shelton, Spyridon Makris, Cecilia Johansson, Bin Cao, Wendy S Barclay
The highly pathogenic avian influenza (HPAI) H5N1 influenza virus has been a public health concern for more than a decade because of its frequent zoonoses and the high case fatality rate associated with human infections. Severe disease following H5N1 influenza infection is often associated with dysregulated host innate immune response also known as cytokine storm but the virological and cellular basis of these responses has not been clearly described. We rescued a series of 6:2 reassortant viruses that combined a PR8 HA/NA pairing with the internal gene segments from human adapted H1N1, H3N2, or avian H5N1 viruses and found that mice infected with the virus with H5N1 internal genes suffered severe weight loss associated with increased lung cytokines but not high viral load...
January 4, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29299660/reduction-of-myeloid-derived-suppressor-cells-reinforces-the-anti-solid-tumor-effect-of-recipient-leukocyte-infusion-in-murine-neuroblastoma-bearing-allogeneic-bone-marrow-chimeras
#5
Isabelle Dierckx de Casterlé, Sabine Fevery, Omer Rutgeerts, Fariba Poosti, Sofie Struyf, Caroline Lenaerts, Mark Waer, An D Billiau, Ben Sprangers
Allogeneic hematopoietic stem cell transplantation is an emerging treatment option for solid tumors because of its capacity to elicit immune graft-versus-tumor effects. However, these are often limited and associated with GvHD. Adoptive recipient leukocyte infusion (RLI) was shown to enhance anti-tumor responses of allogeneic bone marrow transplantation in murine neuroblastoma (Neuro2A)-bearing chimeras. In contrast to the clinically used donor leukocyte infusion, the RLI anti-tumor effect-elicited by host-versus-graft lymphohematopoietic reactivity-does not cause GvHD; however, the tumor growth-inhibitory effect is incomplete, because overall survival is not prolonged...
January 3, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29258535/lytic-viral-replication-and-immunopathology-in-a-cytomegalovirus-induced-mouse-model-of-secondary-hemophagocytic-lymphohistiocytosis
#6
Ellen Brisse, Maya Imbrechts, Tania Mitera, Jessica Vandenhaute, Carine H Wouters, Robert Snoeck, Graciela Andrei, Patrick Matthys
BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare immunological disorder caused by unbridled activation of T cells and macrophages, culminating in a life-threatening cytokine storm. A genetic and acquired subtype are distinguished, termed primary and secondary HLH, respectively. Clinical manifestations of both forms are frequently preceded by a viral infection, predominantly with herpesviruses. The exact role of the viral infection in the development of the hemophagocytic syndrome remains to be further elucidated...
December 19, 2017: Virology Journal
https://www.readbyqxmd.com/read/29229740/bone-marrow-derived-cpla2%C3%AE-contributes-to-renal-fibrosis-progression
#7
John R Montford, Allison M B Lehman, Colin D Bauer, Jelena Klawitter, Jost Klawitter, Joanna M Poczobutt, Micah Scobey, Mary Weiser-Evans, Raphael A Nemenoff, Seth B Furgeson
The group IVA calcium dependent cytosolic phospholipase A2 enzyme (cPLA2α) directs a complex eicosanoid storm which accompanies the tissue response to injury. cPLA2α, and its downstream eicosanoid mediators, are also implicated in the pathogenesis of fibrosis in many organs including the kidney. We aimed to determine the role of cPLA2α in bone marrow-derived cells in a murine model of renal fibrosis, unilateral ureteral obstruction (UUO). Wild type (WT) C57BL/6J mice were irradiated and engrafted with donor bone marrow from either WT mice (WT-BMT) or mice deficient in cPLA2α (KO-BMT)...
December 11, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/29227984/microrna-146b-5p-identified-in-porcine-liver-donation-model-is-associated-with-early-allograft-dysfunction-in-human-liver-transplantation
#8
Cheukfai Li, Qiang Zhao, Wei Zhang, Maogen Chen, Weiqiang Ju, Linwei Wu, Ming Han, Yi Ma, Xiaofeng Zhu, Dongping Wang, Zhiyong Guo, Xiaoshun He
BACKGROUND Poor transplant outcome was observed in donation after brain death followed by circulatory death (DBCD), since the donor organs suffered both cytokine storm of brain death and warm ischemia injury. MicroRNAs (miRNAs) have emerged as promising disease biomarkers, so we sought to establish a miRNA signature of porcine DBCD and verify the findings in human liver transplantation. MATERIAL AND METHODS MiRNA expression was determined with miRNA sequencing in 3 types of the porcine model of organ donation, including donation after brain death (DBD) group, donation after circulatory death (DCD) group, and DBCD group...
December 11, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29163498/cytokine-profiles-of-severe-influenza-virus-related-complications-in-children
#9
Andrew Fiore-Gartland, Angela Panoskaltsis-Mortari, Anna A Agan, Anushay J Mistry, Paul G Thomas, Michael A Matthay, Tomer Hertz, Adrienne G Randolph
Rationale: Effective immunomodulatory therapies for children with life-threatening "cytokine storm" triggered by acute influenza infection are lacking. Understanding the immune profiles of children progressing to severe lung injury and/or septic shock could provide insight into pathogenesis. Objectives: To compare the endotracheal and serum cytokine profiles of children with influenza-related critical illness and to identify their associations with severe influenza-associated complications...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29138271/addressing-the-perfect-storm-biomarkers-in-obesity-and-pathophysiology-of-cardiometabolic-risk
#10
REVIEW
Krasimira Aleksandrova, Dariush Mozaffarian, Tobias Pischon
BACKGROUND: The worldwide rise of obesity has provoked intensified research to better understand its pathophysiology as a means for disease prevention. Several biomarkers that may reflect various pathophysiological pathways that link obesity and cardiometabolic diseases have been identified over the past decades. CONTENT: We summarize research evidence regarding the role of established and novel obesity-related biomarkers, focusing on recent epidemiological evidence for detrimental associations with cardiometabolic diseases including obesity-related cancer...
November 14, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/29118755/apoptotic-cells-induced-signaling-for-immune-homeostasis-in-macrophages-and-dendritic-cells
#11
REVIEW
Uriel Trahtemberg, Dror Mevorach
Inefficient and abnormal clearance of apoptotic cells (efferocytosis) contributes to systemic autoimmune disease in humans and mice, and inefficient chromosomal DNA degradation by DNAse II leads to systemic polyarthritis and a cytokine storm. By contrast, efficient clearance allows immune homeostasis, generally leads to a non-inflammatory state for both macrophages and dendritic cells (DCs), and contributes to maintenance of peripheral tolerance. As many as 3 × 10(8) cells undergo apoptosis every hour in our bodies, and one of the primary "eat me" signals expressed by apoptotic cells is phosphatidylserine (PtdSer)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29073262/development-and-validation-of-immune-dysfunction-score-to-predict-28-day-mortality-of-sepsis-patients
#12
Wen-Feng Fang, Ivor S Douglas, Yu-Mu Chen, Chiung-Yu Lin, Hsu-Ching Kao, Ying-Tang Fang, Chi-Han Huang, Ya-Ting Chang, Kuo-Tung Huang, Yi-His Wang, Chin-Chou Wang, Meng-Chih Lin
BACKGROUND: Sepsis-induced immune dysfunction ranging from cytokines storm to immunoparalysis impacts outcomes. Monitoring immune dysfunction enables better risk stratification and mortality prediction and is mandatory before widely application of immunoadjuvant therapies. We aimed to develop and validate a scoring system according to patients' immune dysfunction status for 28-day mortality prediction. METHODS: A prospective observational study from a cohort of adult sepsis patients admitted to ICU between August 2013 and June 2016 at Kaohsiung Chang Gung Memorial Hospital in Taiwan...
2017: PloS One
https://www.readbyqxmd.com/read/29066614/targeting-the-stat6-pathway-in-tumor-associated-macrophages-reduces-tumor-growth-and-metastatic-niche-formation-in-breast-cancer
#13
Karin Binnemars-Postma, Ruchi Bansal, Gert Storm, Jai Prakash
Tumor-associated macrophages (TAMs) are the key effector cells in the tumor microenvironment and induce neoangiogenesis, matrix remodeling, and metastasis while suppressing the tumor immune system. These protumoral macrophages display an M2 phenotype induced by IL-4 and IL-13 cytokines. In this study, we hypothesized that the inhibition of the signal transducer and activator of transcription 6 (Stat6) pathway, a common downstream signaling pathway of IL-4 and IL-13, may be an interesting strategy by which to inhibit TAM differentiation and, thus, their protumorigenic activities...
October 24, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29064197/-reactive-hemophagocytic-syndrome
#14
Fiona Novotny, Federico Simonetta, Kaveh Samii, Yves Chalandon, Jacques Serratrice
The reactive hemophagocytic syndrome comes from an overstimulation of the immune system which causes a cytokine storm. This is a life-threatening condition caracterised by a febrile cytopenia, hepatosplenomegaly and multi-organ failure. The diagnosis is not easy and the HScore can be useful, looking at hyperferritinemia, hypertriglyceridemia, and hypofibrinogenemia. The evidence of hemophagocytosis in the bone marrow is not necessary nor sufficient to make the diagnosis but is part of the workup. The underlying cause has to be actively sought, typically an infectious, malignant or autoimmune disorder...
October 18, 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/29056305/exotoxins-and-endotoxins-inducers-of-inflammatory-cytokines
#15
REVIEW
Jean-Marc Cavaillon
Endotoxins and exotoxins are among the most potent bacterial inducers of cytokines. During infectious processes, the production of inflammatory cytokines including tumor necrosis factor (TNF), interleukin-1β (IL-1β), gamma interferon (IFNγ) and chemokines orchestrates the anti-infectious innate immune response. However, an overzealous production, leading up to a cytokine storm, can be deleterious and contributes to mortality consecutive to sepsis or toxic shock syndrome. Endotoxins of Gram-negative bacteria (lipopolysaccharide, LPS) are particularly inflammatory because they generate auto-amplificatory loops after activation of monocytes/macrophages...
October 19, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/29046356/microrna-302a-suppresses-influenza-a-virus-stimulated-interferon-regulatory-factor-5-expression-and-cytokine-storm-induction
#16
Xueyuan Chen, Li Zhou, Nanfang Peng, Haisheng Yu, Mengqi Li, Zhongying Cao, Yong Lin, Xueyu Wang, Qian Li, Jun Wang, Yinglong She, Chengliang Zhu, Mengji Lu, Ying Zhu, Shi Liu
During influenza A virus (IAV) infection, cytokine storms play a vital and critical role in clinical outcomes. We have previously reported that microRNA (miR)-302c regulates IAV-induced IFN expression by targeting the 3'-UTR of nuclear factor kappa B (NF-κB)-inducing kinase (NIK). In the current study, we found that miR-302a, another member of miR-302 cluster, controls the IAV-induced cytokine storm. According to results from cell-based and knock-out mouse models, IAV induces a cytokine storm via interferon regulatory factor-5 (IRF-5)...
October 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29039102/analysis-of-pro-inflammatory-cytokine-and-type-ii-interferon-induction-by-nanoparticles
#17
Timothy M Potter, Barry W Neun, Jamie C Rodriguez, Anna N Ilinskaya, Marina A Dobrovolskaia
Cytokines, chemokines, and interferons are released by the immune cells in response to cellular stress, damage and/or pathogens, and are widely used as biomarkers of inflammation. Certain levels of cytokines are needed to stimulate an immune response in applications such as vaccines or immunotherapy where immune stimulation is desired. However, undesirable elevation of cytokine levels, as may occur in response to a drug or a device, may lead to severe side effects such as systemic inflammatory response syndrome or cytokine storm...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28987599/anti-sepsis-protection-of-xuebijing-injection-is-mediated-by-differential-regulation-of-pro-and-anti-inflammatory-th17-and-t-regulatory-cells-in-a-murine-model-of-polymicrobial-sepsis
#18
Xi Chen, Yuxin Feng, Xiya Shen, Guixiang Pan, Guanwei Fan, Xiumei Gao, Jihong Han, Yan Zhu
ETHNOPHARMACOLOGICAL RELEVANCE: Xuebijing injection (XBJ), a Chinese herbal medicine containing extracts from 5 herbs, is frequently used as an add-on with standard therapies to treat sepsis or septic shock with fewer side effects in China. Nonetheless, its mechanism of action on septic shock remains to be unveiled. We explored the differential effects of XBJ on subtypes of CD4+ T cell differentiation and septic shock protection in a murine model to understand the contribution of XBJ to regulation of the inflammation-immune axis function...
October 4, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28975999/combining-multiple-biomarkers-differentiates-between-active-sjia-sjia-mas-and-ebv-hlh
#19
L K Weaver
Cytokine storm syndromes are a clinically heterogeneous group of conditions resulting from a maladaptive host response to an inflammatory trigger. These syndromes lead to rapid progression of immune-mediated damage to healthy tissues resulting in life-threatening multi-system organ failure. Prompt recognition of disease and medical intervention to limit damage to healthy tissues is essential to prevent cytokine storm morbidity and mortality. However, the diagnosis of cytokine storm syndromes is challenging, given the clinical heterogeneity in disease presentations...
October 4, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28951472/ebola-virus-binding-to-tim-1-on-t-lymphocytes-induces-a-cytokine-storm
#20
Patrick Younan, Mathieu Iampietro, Andrew Nishida, Palaniappan Ramanathan, Rodrigo I Santos, Mukta Dutta, Ndongala Michel Lubaki, Richard A Koup, Michael G Katze, Alexander Bukreyev
Ebola virus (EBOV) disease (EVD) results from an exacerbated immunological response that is highlighted by a burst in the production of inflammatory mediators known as a "cytokine storm." Previous reports have suggested that nonspecific activation of T lymphocytes may play a central role in this phenomenon. T-cell immunoglobulin and mucin domain-containing protein 1 (Tim-1) has recently been shown to interact with virion-associated phosphatidylserine to promote infection. Here, we demonstrate the central role of Tim-1 in EBOV pathogenesis, as Tim-1(-/-) mice exhibited increased survival rates and reduced disease severity; surprisingly, only a limited decrease in viremia was detected...
September 26, 2017: MBio
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