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https://www.readbyqxmd.com/read/29040604/associations-of-plasma-cytokine-and-microbial-translocation-biomarkers-with-immune-reconstitution-inflammatory-syndrome
#1
Varghese George, Linda Harrison, Margaret Roach, Xiao-Dong Li, Camlin Tierney, Margaret A Fischl, Judith Aberg, Pablo Tebas, David M Asmuth, Richard B Pollard, Catherine Godfrey, Savita Pahwa
A nested case-cohort study was performed in participants of a clinical trial of first-line human immunodeficiency virus treatments to investigate plasma biomarkers of inflammation and microbial translocation for their association with immune reconstitution inflammatory syndrome (IRIS). Fifty-one of 1452 participants with baseline CD4 count <350 cells/μL developed IRIS. Plasma from 51 IRIS cases, including 6 stratified by preenrollment CD4 count ≤200 cells/μL, were analyzed and compared to 94 non-IRIS controls...
October 13, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29040318/rapid-reversal-of-innate-immune-dysregulation-in-blood-of-patients-and-livers-of-humanized-mice-with-hcv-following-daa-therapy
#2
Matthew A Burchill, Justin A Roby, Nanette Crochet, Megan Wind-Rotolo, Amy E Stone, Michael G Edwards, Rachael J Dran, Michael S Kriss, Michael Gale, Hugo R Rosen
RESULTS: First, in patients receiving two different combinations of DAAs, we found that DAAs induced not only rapid viral clearance, but also a re-setting of antiviral immune responses in the peripheral blood. Specifically, we see a rapid decline in the expression of genes associated with chronic IFN stimulation (IFIT3, USP18, IFIT1) as well as a rapid decline in genes associated with inflammation (IL1β, CXCL10, CXCL11) in the peripheral blood that precedes the complete removal of virus from the blood...
2017: PloS One
https://www.readbyqxmd.com/read/29038005/prednisone-alleviates-demyelination-through-regulation-of-the-nlrp3-inflammasome-in-a-c57bl-6-mouse-model-of-cuprizone-induced-demyelination
#3
Hao Yu, Mingfeng Wu, Geng Lu, Tingting Cao, Nan Chen, Yijia Zhang, Higuo Jiang, Hongbin Fan, Ruiqin Yao
Myelin abnormalities, oligodendrocyte damage, and concomitant glia activation are common in demyelinating diseases of the central nervous system (CNS). Increasing evidence has demonstrated that the inflammatory response triggers demyelination and gliosis in demyelinating disorders. Numerous clinical interventions, including those used to treat multiple sclerosis (MS), have confirmed prednisone (PDN) as a powerful anti-inflammatory drug that reduces the inflammatory response and promotes tissue repair in multiple inflammation sites...
October 13, 2017: Brain Research
https://www.readbyqxmd.com/read/29034104/fibroblasts-the-unknown-sentinels-eliciting-immune-responses-against-microorganisms
#4
REVIEW
Luis Antonio Bautista-Hernández, José Luis Gómez-Olivares, Beatriz Buentello-Volante, Victor Manuel Bautista-de Lucio
Fibroblasts are present in all tissues but predominantly in connective tissues. Some of their functions include contractility, locomotion, collagen and elastin fiber production, and the regulation and degradation of the extracellular matrix. Also, fibroblasts act as sentinels to produce inflammatory mediators in response to several microorganisms. There is evidence that fibroblasts can synthesize toll-like receptors (TLRs), antimicrobial peptides, proinflammatory cytokines, chemokines, and growth factors, which are important molecules involved in innate immune response against microorganisms...
September 2017: European Journal of Microbiology & Immunology
https://www.readbyqxmd.com/read/29033931/plasmodium-berghei-nk65-in-combination-with-ifn-%C3%AE-induces-endothelial-glucocorticoid-resistance-via-sustained-activation-of-p38-and-jnk
#5
Karolina A Zielińska, Lode de Cauwer, Sofie Knoops, Kristof Van der Molen, Alexander Sneyers, Jonathan Thommis, J Brian De Souza, Ghislain Opdenakker, Karolien De Bosscher, Philippe E Van den Steen
Malaria-associated acute respiratory distress syndrome (MA-ARDS) is an often lethal complication of malaria. Currently, no adequate therapy for this syndrome exists. Although glucocorticoids (GCs) have been used to improve clinical outcome of ARDS, their therapeutic benefits remain unclear. We previously developed a mouse model of MA-ARDS, in which dexamethasone treatment revealed GC resistance. In the present study, we investigated GC sensitivity of mouse microvascular lung endothelial cells stimulated with interferon-γ (IFN-γ) and Plasmodium berghei NK65 (PbNK65)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29031499/micrornas-15a-and-16-1-activate-signaling-pathways-that-mediate-chemotaxis-of-immune-regulatory-b-cells-to-colorectal-tumors
#6
Ronghua Liu, Zhou Lu, Jie Gu, Jiajing Liu, Enyu Huang, Xiaoming Liu, Luman Wang, Jiao Yang, Yuting Deng, Jiawen Qian, Feifei Luo, Zhiming Wang, Hushan Zhang, Xuechao Jiang, Dan Zhang, Jing Qian, Guangwei Liu, Hongguang Zhu, Youcun Qian, Zhanju Liu, Yiwei Chu
BACKGROUND & AIMS: B cells infiltrate tumors but little is known about how they affect tumor growth and progression. microRNA15A (MIR15A or miRNA15A) and microRNA16-1 (MIR16-1 or miRNA16-1) regulate cell proliferation, apoptosis and drug resistance. We investigated their involvement in B cell-mediated immune suppression by colorectal tumors. METHODS: Mice with disruptions of the gene cluster that encodes MIR15A and MIR16-1 (KO mice), and control (C57BL/B6) mice were given azoxymethane with dextran sodium sulfate (AD) to induce formation of colorectal tumors...
October 11, 2017: Gastroenterology
https://www.readbyqxmd.com/read/29018944/-nonautonomous-effects-of-oncogenic-yap-in-hepatocarcinogenesis
#7
REVIEW
S Marquard, S Thomann, S M E Weiler, C Sticht, N Gretz, P Schirmacher, K Breuhahn
BACKGROUND: The transcriptional coactivator yes-associated protein (YAP) is a strong oncogene in liver cancer development. OBJECTIVES: To investigate if and how YAP-induced paracrine-acting factors are regulated in hepatocytes and liver cancer cells. MATERIAL AND METHODS: Transcriptome analysis and proteomics of murine wildtype and YAP-transgenic hepatocytes were performed to identify paracrine-acting proteins. Molecular and biochemical techniques were used to examine the mechanisms of YAP-dependent gene regulation...
October 10, 2017: Der Pathologe
https://www.readbyqxmd.com/read/29018427/human-cytomegalovirus-ie2-86-kda-protein-induces-sting-degradation-and-inhibits-cgamp-mediated-ifn-%C3%AE-induction
#8
Jung-Eun Kim, Young-Eui Kim, Mark F Stinski, Jin-Hyun Ahn, Yoon-Jae Song
Stimulator of interferon genes (STING) is a critical signaling molecule in the innate immune response against DNA viruses by either directly sensing intracellular DNA or functioning as an adaptor molecule to activate the type I interferon (IFN) signaling pathway. We determined the functional interaction between STING and human cytomegalovirus (HCMV). A cDNA library containing 133 HCMV ORFs was screened to identify viral genes that inhibit STING-induced IFN-β promoter activation. Among the screened ORFs, UL122, which encodes the immediate-early 2 86 kDa (IE86) protein, strongly abolished STING-induced IFN-β promoter activation...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28994756/screening-assays-to-characterize-novel-endothelial-regulators-involved-in-the-inflammatory-response
#9
María Ángeles Higueras, Lidia Jiménez-García, Sandra Herranz, Sonsoles Hortelano, Alfonso Luque
The endothelial layer is essential for maintaining homeostasis in the body by controlling many different functions. Regulation of the inflammatory response by the endothelial layer is crucial to efficiently fight against harmful inputs and aid in the recovery of damaged areas. When the endothelial cells are exposed to an inflammatory environment, such as the outer component of gram-negative bacteria membrane, lipopolysaccharide (LPS), they express soluble pro-inflammatory cytokines, such as Ccl5, Cxcl1 and Cxcl10, and trigger the activation of circulating leukocytes...
September 15, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28979704/mir-15a-5p-negatively-regulates-cell-survival-and-metastasis-by-targeting-cxcl10-in-chronic-myeloid-leukemia
#10
Dan Chen, Dijiong Wu, Keding Shao, Baodong Ye, Jian Huang, Yanting Gao
Chronic myeloid leukemia (CML) is a common malignant disease from hematopoietic system. Aberrant expression of microRNAs (miRNAs) has been found in CML, however, the roles of many miRNAs including miR-15a-5p in CML are still unknown. In this study, the expression and roles of miR-15a-5p in CML were investigated. We found that restoration miR-15a-5p expression in CML cells decreased cell growth, metastasis and enhanced cell apoptosis. Chemokine ligand 10 (CXCL10) was predicted as a target gene of miR-15a-5p, which was verified by luciferase assay...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28978285/elucidating-pro-inflammatory-cytokine-responses-following-traumatic-brain-injury-in-a-human-stem-cell-model
#11
Eric Peter Thelin, Claire E Hall, Kunal Gupta, Keri Carpenter, Siddharthan Chandran, Peter John Hutchinson, Rickie Patani, Adel Helmy
Cytokine mediated inflammation likely plays an important role in secondary pathology following traumatic brain injury (TBI). The aim of this study was to elucidate secondary cytokine responses in an in vitro enriched (>80%) human stem cell-derived neuronal model. We exposed neuronal cultures to pre-determined and clinically relevant pathophysiological levels of Tumor Necrosis Factor- (TNF), Interleukin-6 (IL-6) and Interleukin-1β (IL-1β), shown to be present in the inflammatory aftermath of TBI. Data from this reductionist human model were then compared to our in vivo data...
October 5, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28975621/role-of-interferon-regulatory-factor-1-in-governing-treg-depletion-th1-polarization-inflammasome-activation-and-antitumor-efficacy-of-cyclophosphamide
#12
Carla Buccione, Alessandra Fragale, Federica Polverino, Giovanna Ziccheddu, Eleonora Aricò, Filippo Belardelli, Enrico Proietti, Angela Battistini, Federica Moschella
The antitumor effectiveness of cyclophosphamide (CTX) and other chemotherapeutics was shown to rely not only on direct cytotoxicity but also on immunogenic tumor cell death and systemic immunomodulatory mechanisms, including regulatory T cell (Treg) depletion, Th1 cell polarization, type I interferon (IFN) and proinflammatory cytokine production. IFN regulatory factor (IRF)-1 is a transcriptional regulator of IFNs and IFN-inducible genes, involved in the control of Th1 and Treg differentiation and in sterile inflammation...
October 4, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28973330/prehematopoietic-stem-cell-transplantation-tear-cytokines-as-potential-susceptibility-biomarkers-for-ocular-chronic-graft-versus-host-disease
#13
Lidia Cocho, Itziar Fernández, Margarita Calonge, Maite Sainz de la Maza, Montserrat Rovira, Michael E Stern, Carmen Garcia-Vazquez, Amalia Enríquez-de-Salamanca
Purpose: To determine if cytokine tear levels before hematopoietic stem cell transplantation (HSCT) can help anticipate the occurrence of ocular chronic graft-versus-host disease (cGVHD). Methods: In this pilot study, 25 patients undergoing HSCT were followed prospectively for ≤43 months. After ocular examinations, tears were collected before HSCT. Levels of 19 cytokines (epidermal growth factor [EGF], eotaxin 1/CCL11, fractalkine/CX3CL1, IL-1Ra, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8/CXCL8, IL-10, IL-12p70, IL-13, IL-17A, IP-10/CXCL10, IFN-γ, VEGF, TNF-α, and RANTES/CCL5) were measured by multiplex bead assay...
September 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28972011/effective-activated-pi3k%C3%AE-syndrome-targeted-therapy-with-the-pi3k%C3%AE-inhibitor-leniolisib
#14
V Koneti Rao, Sharon Webster, Virgil A S H Dalm, Anna Šedivá, P Martin van Hagen, Steven Holland, Sergio D Rosenzweig, Andreas D Christ, Birgitte Sloth, Maciej Cabanski, Aniket D Joshi, Stefan de Buck, Julie Doucet, Danilo Guerini, Christoph Kalis, Ilona Pylvaenaeinen, Nicolas Soldermann, Anuj Kashyap, Gulbu Uzel, Michael J Lenardo, Dhavalkumar D Patel, Carrie L Lucas, Christoph Burkhart
Pathogenic gain-of-function variants in the genes encoding PI3Kδ (phosphoinositide 3-kinase delta) lead to accumulation of transitional B cells and senescent T cells, lymphadenopathy and immune-deficiency (Activated PI3Kδ Syndrome, APDS). Knowing the genetic etiology of APDS afforded us the opportunity to explore PI3Kδ inhibition as a precision-medicine therapy. Here, we report in vitro and in vivo effects of inhibiting PI3Kδ in APDS. Treatment with leniolisib (CDZ173), a selective PI3Kδ inhibitor, caused a dose-dependent suppression of PI3Kδ pathway hyperactivation (measured as phosphorylation of AKT/S6) in cell lines ectopically expressing APDS-causative p110δ variants and in T cell blasts derived from patients...
September 29, 2017: Blood
https://www.readbyqxmd.com/read/28968786/influence-of-leishmania-rna-virus-1-on-pro-inflammatory-biomarker-expression-in-a-human-macrophage-model-of-american-tegumentary-leishmaniasis
#15
Ruwandi Kariyawasam, Jugvinder Grewal, Rachel Lau, Andrew Purssell, Braulio M Valencia, Alejandro Llanos-Cuentas, Andrea K Boggild
Backgound: Species of the Leishmania Viannia subgenus harbour the double-stranded Leishmania RNA virus 1 (LRV-1), previously identified in isolates from Brazil and Peru. Higher levels of LRV-1 in metastasizing strains of L. V. guyanensis have been documented in both human and murine models, and correlated to disease severity. Methods: Expression of proinflammatory biomarkers, including IL-1β, TNF-α, CXCL10, CCL5, IL-6, and SOD, in human macrophages infected with 3 ATCC and 5 clinical isolates of L...
August 18, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28968351/urinary-biomarker-cxcl10-identifying-site-specific-allograft-inflammation-in-renal-transplantation
#16
Roshan P George
No abstract text is available yet for this article.
September 29, 2017: Transplantation
https://www.readbyqxmd.com/read/28964902/skin-vaccination-using-microneedles-coated-with-a-plasmid-dna-cocktail-encoding-nucleosomal-histones-of-leishmania-spp
#17
Esther Moreno, Juana Schwartz, Alba Calvo, Laura Blanco, Esther Larrea, Juan M Irache, Carmen Sanmartín, Sion A Coulman, Manuel Soto, James C Birchall, Socorro Espuelas
Vaccine delivery using microneedles (MNs) represents a safe, easily disposable and painless alternative to traditional needle immunizations. The MN delivery of DNA vaccines to the dermis may result in a superior immune response and/or an equivalent immune response at a lower vaccine dose (dose-sparing). This could be of special interest for immunization programs against neglected tropical diseases such as leishmaniasis. In this work, we loaded a MN device with 60μg of a plasmid DNA cocktail encoding the Leishmania infantum nucleosomal histones H2A, H2B, H3 and H4 and compared its immunogenicity and protective capacity against conventional s...
September 28, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28964797/%C3%AF-alkynyl-arachidonic-acid-promotes-anti-inflammatory-macrophage-m2-polarization-against-acute-myocardial-infarction-via-regulating-the-cross-talk-between-pkm2-hif-1%C3%AE-and-inos
#18
Yuanyuan Cheng, Yibin Feng, Zhengyuan Xia, Xuechen Li, Jianhui Rong
Macrophage polarization determines the timing for the switch from the inflammation phase to the inflammation resolution phase after acute myocardial infarction. The aim of the present study was to investigate whether ω-alkynyl arachidonic acid could mitigate the inflammatory lipid mediators in the regulation of macrophage phenotypes and functions with a special regard to myocardial infarction. We initially discovered that ω-alkynyl arachidonic acid selectively suppressed the up-regulation of inducible nitric oxide synthase (iNOS) over cyclooxygenase-2 (COX-2) in LPS-stimulated macrophages...
September 28, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28963880/protective-role-of-indoleamine-2-3-dioxygenase-in-respiratory-syncytial-virus-associated-immune-response-in-airway-epithelial-cells
#19
Devi Rajan, Raghavan Chinnadurai, Evan O Keefe, Seyhan Boyoglu-Barnum, Sean O Todd, Tina V Hartert, Jacques Galipeau, Larry J Anderson
RSV is a major cause of severe lower respiratory infection in infants and young children. With no vaccine yet available, it is important to clarify mechanisms of disease pathogenesis. Since indoleamine-2,3-dioxygenase (IDO) is an immunomodulatory enzyme and is upregulated with RSV infection, we studied it in vivo during infection of BALB/c mice and in vitro in A549 cells. RSV infection upregulated IDO transcripts in vivo and in vitro. IDO siRNA decreased IDO transcripts ~2 fold compared to control siRNA after RSV infection but this decrease did not affect RSV replication...
September 27, 2017: Virology
https://www.readbyqxmd.com/read/28962641/overexpression-of-hypoxia-inducible-factor-1-alpha-improves-immunomodulation-by-dental-mesenchymal-stem-cells
#20
Victor G Martinez, Imelda Ontoria-Oviedo, Carolina P Ricardo, Sian E Harding, Rosa Sacedon, Alberto Varas, Agustin Zapata, Pilar Sepulveda, Angeles Vicente
BACKGROUND: Human dental mesenchymal stem cells (MSCs) are considered as highly accessible and attractive MSCs for use in regenerative medicine, yet some of their features are not as well characterized as other MSCs. Hypoxia-preconditioning and hypoxia-inducible factor 1 (HIF-1) alpha overexpression significantly improves MSC therapeutics, but the mechanisms involved are not fully understood. In the present study, we characterize immunomodulatory properties of dental MSCs and determine changes in their ability to modulate adaptive and innate immune populations after HIF-1 alpha overexpression...
September 29, 2017: Stem Cell Research & Therapy
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