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https://www.readbyqxmd.com/read/29443656/highlights-for-dengue-immunopathogenesis-antibody-dependent-enhancement-cytokine-storm-and-beyond
#1
Diogo Kuczera, João Paulo Assolini, Fernanda Tomiotto-Pellissier, Wander Rogério Pavanelli, Guilherme Ferreira Silveira
Infection with dengue virus (DENV) can lead to a wide spectrum of clinical presentations, ranging from asymptomatic infection to death. It is estimated that the disease manifests only in 90 million cases out of the total 390 million yearly infections. Even though research has not yet elucidated which are the precise pathophysiological mechanisms that trigger severe forms of dengue, the infection elicits a critical immune response significant for dengue pathogenesis development. Understanding how the immune response to DENV is established and how it can resolve the infection or turn into an immunopathology is of great importance in DENV research...
February 2018: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/29428565/steroid-pulse-therapy-in-patients-with-encephalopathy-associated-with-severe-fever-with-thrombocytopenia-syndrome
#2
Shingen Nakamura, Momoyo Azuma, Tomoko Maruhashi, Kimiko Sogabe, Ryohei Sumitani, Munenori Uemura, Masami Iwasa, Shiro Fujii, Hirokazu Miki, Kumiko Kagawa, Takashi Hiraga, Noriyasu Kondo, Hiromi Fujita, Fumihiko Mahara, Masahiro Abe
Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infectious disease caused by the SFTS virus (SFTSV). Clinical symptoms of SFTS often involve encephalopathy and other central neurological symptoms, particularly in seriously ill patients; however, pathogenesis of encephalopathy by SFTSV is largely unknown. Herein, we present case reports of three patients with SFTS, complicated by encephalopathy, admitted to Tokushima University hospital: one patient was a 63-year-old man, while the other two were 83- and 86-year-old women...
February 7, 2018: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/29427908/kinetics-of-viral-load-and-cytokines-in-severe-fever-with-thrombocytopenia-syndrome
#3
Ji-Soo Kwon, Min-Chul Kim, Ji Yeun Kim, Na-Young Jeon, Byung-Han Ryu, Jeongmin Hong, Min-Jae Kim, Yong Pil Chong, Sang-Oh Lee, Sang-Ho Choi, Yang Soo Kim, Jun Hee Woo, Sung-Han Kim
BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease in China, Japan, and Korea, which is characterized by high fever, thrombocytopenia, and high mortality. It is hypothesized that a cytokine storm plays an important role in the pathophysiology of SFTS. However, limited data have been published on the detailed kinetics of the viral load and cytokine profiles throughout the course of this disease. OBJECTIVES: We investigated the patterns of changes in cytokines and viral load in SFTS patients...
January 31, 2018: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/29410422/a-ligand-specific-blockade-of-the-integrin-mac-1-selectively-targets-pathologic-inflammation-while-maintaining-protective-host-defense
#4
Dennis Wolf, Nathaly Anto-Michel, Hermann Blankenbach, Ansgar Wiedemann, Konrad Buscher, Jan David Hohmann, Bock Lim, Marina Bäuml, Alex Marki, Maximilian Mauler, Daniel Duerschmied, Zhichao Fan, Holger Winkels, Daniel Sidler, Philipp Diehl, Dirk M Zajonc, Ingo Hilgendorf, Peter Stachon, Timoteo Marchini, Florian Willecke, Maximilian Schell, Björn Sommer, Constantin von Zur Muhlen, Jochen Reinöhl, Teresa Gerhardt, Edward F Plow, Valentin Yakubenko, Peter Libby, Christoph Bode, Klaus Ley, Karlheinz Peter, Andreas Zirlik
Integrin-based therapeutics have garnered considerable interest in the medical treatment of inflammation. Integrins mediate the fast recruitment of monocytes and neutrophils to the site of inflammation, but are also required for host defense, limiting their therapeutic use. Here, we report a novel monoclonal antibody, anti-M7, that specifically blocks the interaction of the integrin Mac-1 with its pro-inflammatory ligand CD40L, while not interfering with alternative ligands. Anti-M7 selectively reduces leukocyte recruitment in vitro and in vivo...
February 6, 2018: Nature Communications
https://www.readbyqxmd.com/read/29404438/a-global-perspective-on-hepatitis-b-related-single-nucleotide-polymorphisms-and-evolution-during-human-migration
#5
Dar-In Tai, Wen-Juei Jeng, Chun-Yen Lin
Genome-wide association studies have indicated that human leukocyte antigen (HLA)-DP and HLA-DQ play roles in persistent hepatitis B virus (HBV) infection in Asia. To understand the evolution of HBV-related single nucleotide polymorphisms (SNPs) and to correlate these SNPs with chronic HBV infection among different populations, we conducted a global perspective study on hepatitis-related SNPs. We selected 12 HBV-related SNPs on the HLA locus and two HBV and three hepatitis C virus immune-related SNPs for analysis...
December 2017: Hepatology Communications
https://www.readbyqxmd.com/read/29379043/early-immune-anergy-towards-recall-antigens-and-mitogens-in-patients-at-onset-of-septic-shock
#6
M Feuerecker, L Sudhoff, B Crucian, J-I Pagel, C Sams, C Strewe, A Guo, G Schelling, J Briegel, I Kaufmann, A Choukèr
The pathology of sepsis is typically characterized by an infection and excessive initial inflammation including a cytokine storm, followed by a state of immune suppression or paralysis. This classical view of a two peak kinetic immune response is currently controversially discussed. This study was a sub-study of the randomized clinical Trial SISPCT registered with www.clinicaltrials.gov (NCT00832039, Registration date: 29/01/2009). Blood samples from 76 patients with severe sepsis and septic shock were incubated for 48 h at 37 °C in vitro with bacterial or fungal recall-antigens or specific mitogen antigens within 24 hours of sepsis onset...
January 29, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29377242/an-update-on-cell-intrinsic-negative-regulators-of-the-nlrp3-inflammasome
#7
REVIEW
Barun Poudel, Prajwal Gurung
Inflammasomes are multimeric protein complexes that promote inflammation (through specific cleavage and production of bioactive IL-1β and IL-18) and pyroptotic cell death. The central role of inflammasomes in combating infection and maintaining homeostasis has been studied extensively. Although inflammasome-mediated inflammation and cell death are vital to limit pathogenic insults and to promote wound healing/tissue regeneration, unchecked/uncontrolled inflammation, and cell death can cause cytokine storm, tissue damage, autoinflammatory and autoimmune diseases, and even death in the afflicted individuals...
January 26, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29361119/imaging-fibroblast-activation-protein-to-monitor-therapeutic-effects-of-neutralizing-interleukin-22-in-collagen-induced-arthritis
#8
Tessa van der Geest, Debbie M Roeleveld, Birgitte Walgreen, Monique M Helsen, Tapan K Nayak, Christian Klein, Martin Hegen, Gert Storm, Josbert M Metselaar, Wim B van den Berg, Peter M van der Kraan, Peter Laverman, Otto C Boerman, Marije I Koenders
Objectives: RA is a chronic autoimmune disease leading to progressive destruction of cartilage and bone. RA patients show elevated IL-22 levels and the amount of IL-22-producing Th cells positively correlates with the extent of erosive disease, suggesting a role for this cytokine in RA pathogenesis. The purpose of this study was to determine the feasibility of SPECT/CT imaging with 111In-labelled anti-fibroblast activation protein antibody (28H1) to monitor the therapeutic effect of neutralizing IL-22 in experimental arthritis...
January 18, 2018: Rheumatology
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
#9
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
#10
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
#11
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
#12
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 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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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