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https://www.readbyqxmd.com/read/28646772/prevalence-of-immune-related-systemic-adverse-events-in%C3%A2-patients-treated-with-anti-programmed-cell-death-1-anti-programmed-cell-death-ligand-1-agents-a-single-centre-pharmacovigilance-database-analysis
#1
Sébastien Le Burel, Stéphane Champiat, Christine Mateus, Aurélien Marabelle, Jean-Marie Michot, Caroline Robert, Rakiba Belkhir, Jean-Charles Soria, Salim Laghouati, Anne-Laure Voisin, Olivier Fain, Arsène Mékinian, Laetitia Coutte, Tali-Anne Szwebel, Laetitia Dunogeant, Bertrand Lioger, Cécile Luxembourger, Xavier Mariette, Olivier Lambotte
AIM: The growing use of immune checkpoint inhibitors (ICIs) is associated with the occurrence of immune-related adverse events (irAEs). Few data are published on systemic, immunohaematological and rheumatic irAEs. In a pharmacovigilance database analysis, we screened for these irAEs and calculated their prevalence. PATIENTS AND METHODS: Participants were recruited via Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie (REISAMIC)(1) a French registry of grade ≥2 irAEs occurring in ICI-treated patients...
June 21, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28646630/characteristics-of-systemic-inflammation-in-hepatitis-b-precipitated-aclf-differentiate-it-from-no-aclf
#2
Wei Wu, Huadong Yan, Hong Zhao, Wenjie Sun, Qiao Yang, Jifang Sheng, Yu Shi
BACKGROUND AND AIMS: Patients with severe exacerbation of chronic hepatitis B (SE-CHB) are at risk of developing acute-on-chronic liver failure (ACLF). Systemic inflammation (SI) is a major driver of ACLF. The aim of this study was to identify characteristics of SI in hepatitis B-precipitated-ACLF (HB-ACLF), which may be distinct from No-ACLF patients with SE-CHB. METHODS: Two cohorts of patients with SE-CHB were enrolled in two tertiary hospitals. The associations between circulating leukocyte counts/subsets and ACLF progression and prognoses were analysed in Cohort A...
June 24, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28646616/curcumin-alleviates-macrophage-activation-and-lung-inflammation-induced-by-influenza-virus-infection-through-inhibiting-the-nf-%C3%AE%C2%BAb-signaling-pathway
#3
Yiming Xu, Ling Liu
BACKGROUND: Influenza A viruses (IAV) result in severe public health problems with worldwide each year. Over-response of immune system to IAV infection leads to complications, and ultimately causing morbidity and mortality. OBJECTIVE: Curcumin has been reported to have anti-inflammatory ability. However, its molecular mechanism in immune responses remains unclear. METHODS: We detected the pro-inflammatory cytokine secretion and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) related protein expression in human macrophages or mice infected by IAV with or without curcumin treatment...
June 24, 2017: Influenza and Other Respiratory Viruses
https://www.readbyqxmd.com/read/28646573/interferon-%C3%AE-regulates-dendritic-cell-activation-and-migration-in-experimental-autoimmune-encephalomyelitis
#4
Leesa M Pennell, Eleanor N Fish
CD11c+ dendritic cells (DCs) exert a critical role as antigen-presenting cells in regulating pathogenic T cells in multiple sclerosis (MS). To determine whether the therapeutic benefit of interferon (IFN)-β treatment for MS is in part influenced by IFN regulation of DC function, we examined the immunophenotype of DCs derived from IFN-β(+/+) and IFN-β(-/-) mice using a myelin oligodendrocyte glycoprotein (MOG) peptide-induced mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Our earlier work identified that IFN-β(-/-) mice exhibit earlier onset and more rapid progression of neurologic impairment compared with IFN-β(+/+) mice...
June 24, 2017: Immunology
https://www.readbyqxmd.com/read/28646511/control-of-autoimmune-inflammation-using-liposomes-to-deliver-positive-allosteric-modulators-of-metabotropic-glutamate-receptors
#5
Joshua M Gammon, Arjun R Adapa, Christopher M Jewell
Multiple sclerosis (MS) is an autoimmune disease where myelin is incorrectly recognized as foreign and attacked by the adaptive immune system. Dendritic cells (DCs) direct adaptive immunity by presenting antigens to T cells, therefore serving as a target for autoimmune therapies. N-Phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide (PHCCC), a positive allosteric modulator of metabotropic glutamate receptor 4 (mGluR4), can promote regulatory T cells by altering cytokine secretion to bias T cell differentiation...
June 24, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28646491/sickle-cells-produce-functional-immune-modulators-and-cytotoxics
#6
Chiao-Wang Sun, Li-Chen Wu, Peter L Knopick, David S Bradley, Tim Townes, David S Terman
Sickle erythrocytes' (SSRBCs) unique physical adaptation to hypoxic conditions renders them able to home to hypoxic tumor niches in vivo, shut down tumor blood flow and induce tumoricidal responses. SSRBCs are also useful vehicles for transport of encapsulated drugs and oncolytic virus into hypoxic tumors with enhanced anti-tumor effects. In search of additional modes for arming sickle cells with cytotoxics, we turned to a lentiviral β-globin vector with optimized Locus Control Region/β-globin coding region/promoter/enhancers...
June 24, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28646487/immunotoxic-effects-of-thymus-in-mice-following-exposure-to-nanoparticulate-tio2
#7
Fashui Hong, Yaoming Zhou, Yingjun Zhou, Ling Wang
Titanium dioxide nanoparticles (TiO2 NPs) have been extensively used in industry, medicine, and daily life, and have shown potential toxic effects for animals or humans. We noted that the effects of TiO2 NPs on the immune system and its mechanism of action in animals or humans have not been elucidated. Thus, mice were exposed to the TiO2 NPs (0, 1.25, 2.5, or 5 mg kg(-1) body weight) for 9 consecutive months. Exposure to TiO2 NPs was accumulated in the thymus, leading to a decrease in body weight and increases in the weight of the thymus or thymus indices...
June 24, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28646409/neuroprotective-effects-of-g-csf-administration-in-microglia-mediated-reactive-t-cell-activation-in-vitro
#8
Wei Peng
G-CSF is a growth factor that has known neuroprotective effects in a variety of experimental brain injury models. As both antigen-presenting microglia and reactive T cells are key components in the development and progression of EAE, the aim of this study is to investigate the neuroprotective effects of recombinant human G-CSF, as administered in microglia-mediated reactive T cell assay in vitro. Our results indicate that G-CSF treatment has no apparent effect for the resting un-activated microglia. G-CSF pre-protection of microglia increased protective cytokine IL-4 production and effectively inhibited the productions of NO and other inflammatory mediators (IFN-γ, TNF-α, IL-1β, IL-17, and chemokine MCP-1) after LPS stimulation...
June 23, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28646367/ifn%C3%AE-producing-cd4-t-lymphocytes-the-double-edged-swords-in-tuberculosis
#9
Pawan Kumar
IFNγ-producing CD4(+) T cells (IFNγ(+)CD4(+) T cells) are the key orchestrators of protective immunity against Mycobacterium tuberculosis (Mtb). Primarily, these cells act by enabling Mtb-infected macrophages to enforce phagosome-lysosome fusion, produce reactive nitrogen intermediates (RNIs), and activate autophagy pathways. However, TB is a heterogeneous disease and a host of clinical and experimental findings has also implicated IFNγ(+)CD4(+) T cells in TB pathogenesis. High frequency of IFNγ(+)CD4(+) T cells is the most invariable feature of the active disease...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28646339/roles-of-non-coding-rnas-in-respiratory-syncytial-virus-rsv-infection
#10
Ralph A Tripp, Abhijeet A Bakre
Analysis of host gene expression profiles following viral infections of target cells/tissues can reveal crucial insights into the host: virus interaction and enables the development of novel therapeutics and prophylactics. Regions of the host genome that do not code for protein, encode structural, and functional non-coding RNAs that are important not only in regulation of host gene expression but also may impact viral replication. This review summarizes the role of host non-coding RNAs during replication of multiple respiratory viruses with a focus on Respiratory Syncytial Virus (RSV), an important pediatric pathogen...
June 24, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28646302/t-regulatory-cells-exhibit-a-biphasic-response-to-prolonged-endurance-exercise-in-humans
#11
Tom Clifford, Matthew J Wood, Philip Stocks, Glyn Howatson, Emma J Stevenson, Catharien M U Hilkens
PURPOSE: T-regulatory cells (Tregs) are a sub-population of lymphocytes that act to suppress aberrant immune responses. We investigated changes in the numbers of naïve and terminally differentiated Tregs in the peripheral blood to establish their role in the immuno-suppressive response to prolonged exercise. METHODS: Blood was drawn from seventeen experienced runners (age 40 ± 12 years; height 1.75 ± 0.08 m; mass 71.4 ± 10.8 kg) before, ~1 h after (POST-1h), and on the day following the marathon (POST-1d)...
June 23, 2017: European Journal of Applied Physiology
https://www.readbyqxmd.com/read/28646284/chd1l-expression-increases-tumor-progression-and-acts-as-a-predictive-biomarker-for-poor-prognosis-in-pancreatic-cancer
#12
Chuan Liu, Xiaowei Fu, Zhiwei Zhong, Jing Zhang, Haiyan Mou, Qiong Wu, Tianle Sheng, Bo Huang, Yeqing Zou
BACKGROUND: The chromodomain helicase/ATPase DNA binding protein 1-like gene (CHD1L) plays a key role in controlling various cellular phenomena, including immune-mediated inflammation, transformation, apoptosis, cell cycle progression, and proliferation. METHODS: This study investigated the function and clinical significance of CHD1L protein expression in pancreatic cancer (PC). We analyzed CHD1L expression in surgical specimens from 112 PC patients. The correlation between the clinical characteristics and prognosis was also determined...
June 23, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28646236/rapamycin-adjuvant-and-exacerbation-of-severe-influenza-in-an-experimental-mouse-model
#13
Ching-Tai Huang, Chen-Yiu Hung, Tse-Ching Chen, Chun-Yen Lin, Yung-Chang Lin, Chia-Shiang Chang, Yueh-Chia He, Yu-Lin Huang, Avijit Dutta
Influenza virus infection often causes severe disease and acute respiratory distress syndrome. It is a common belief that overwhelming immune response contributes to the severe illness. Physicians and researchers have put forth immune modulation as salvage therapy for better recovery. However, empiric corticosteroid failed in both humans and animal models. Reported success with Rapamycin in humans prompted a comprehensive animal study and mechanistic dissection. Here we report the effect of Rapamycin alone or in combination with Oseltamivir for severe influenza in BALB/c mice...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646234/electroporation-as-a-vaccine-delivery-system-and-a-natural-adjuvant-to-intradermal-administration-of-plasmid-dna-in-macaques
#14
Biliana Todorova, Lucille Adam, Slobodan Culina, Raphaël Boisgard, Frédéric Martinon, Antonio Cosma, Mart Ustav, Thierry Kortulewski, Roger Le Grand, Catherine Chapon
In vivo electroporation (EP) is used to enhance the uptake of nucleic acids and its association with DNA vaccination greatly stimulates immune responses to vaccine antigens delivered through the skin. However, the effect of EP on cutaneous cell behavior, the dynamics of immune cell recruitment and local inflammatory factors, have not been fully described. Here, we show that intradermal DNA vaccination combined with EP extends antigen expression to the epidermis and the subcutaneous skin muscle in non-human primates...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646166/atp-release-during-cell-swelling-activates-a-ca-2-dependent-cl-current-by-autocrine-mechanism-in-mouse-hippocampal-microglia
#15
E Murana, F Pagani, B Basilico, M Sundukova, L Batti, S Di Angelantonio, B Cortese, A Grimaldi, A Francioso, P Heppenstall, P Bregestovski, C Limatola, D Ragozzino
Microglia cells, resident immune cells of the brain, survey brain parenchyma by dynamically extending and retracting their processes. Cl(-) channels, activated in the cellular response to stretch/swelling, take part in several functions deeply connected with microglia physiology, including cell shape changes, proliferation, differentiation and migration. However, the molecular identity and functional properties of these Cl(-) channels are largely unknown. We investigated the properties of swelling-activated currents in microglial from acute hippocampal slices of Cx3cr1 (+/GFP) mice by whole-cell patch-clamp and imaging techniques...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646156/mahanine-exerts-in-vitro-and-in-vivo-antileishmanial-activity-by-modulation-of-redox-homeostasis
#16
Saptarshi Roy, Devawati Dutta, Eswara M Satyavarapu, Pawan K Yadav, Chhabinath Mandal, Susanta Kar, Chitra Mandal
Earlier we have established a carbazole alkaloid (mahanine) isolated from an Indian edible medicinal plant as an anticancer agent with minimal effect on normal cells. Here we report for the first time that mahanine-treated drug resistant and sensitive virulent Leishmania donovani promastigotes underwent apoptosis through phosphatidylserine externalization, DNA fragmentation and cell cycle arrest. An early induction of reactive oxygen species (ROS) suggests that the mahanine-induced apoptosis was mediated by oxidative stress...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646094/immune-mediated-effects-targeting-hepatitis-c-virus-in-a-syngeneic-replicon-cell-transplantation-mouse-model
#17
Sepideh Levander, Fredrik Holmström, Lars Frelin, Gustaf Ahlén, Daniel Rupp, Gang Long, Ralf Bartenschlager, Matti Sällberg
OBJECTIVE: HCV is characterised by its ability to establish chronic infection in hepatocytes and to replicate in the presence of an inflammation. We mimicked this situation in vivo in immune-competent mice by syngeneic transplantation of HCV replicon-containing mouse hepatoma cells. DESIGN: A total of 5 million H-2(b) positive Hep56.1D cells, carrying a subgenomic genotype (gt) 2a replicon (HCV replicon cells) or stably expressing comparable levels of the HCV NS3/4A protease/helicase complex (NS3/4A hepatoma cells), were injected subcutaneously into syngeneic H-2(b)-restricted mice...
June 23, 2017: Gut
https://www.readbyqxmd.com/read/28646076/transcriptomic-and-proteomic-profiling-provides-insight-into-mesangial-cell-function-in-iga-nephropathy
#18
Peidi Liu, Emelie Lassén, Viji Nair, Celine C Berthier, Miyuki Suguro, Carina Sihlbom, Matthias Kretzler, Christer Betsholtz, Börje Haraldsson, Wenjun Ju, Kerstin Ebefors, Jenny Nyström
IgA nephropathy (IgAN), the most common GN worldwide, is characterized by circulating galactose-deficient IgA (gd-IgA) that forms immune complexes. The immune complexes are deposited in the glomerular mesangium, leading to inflammation and loss of renal function, but the complete pathophysiology of the disease is not understood. Using an integrated global transcriptomic and proteomic profiling approach, we investigated the role of the mesangium in the onset and progression of IgAN. Global gene expression was investigated by microarray analysis of the glomerular compartment of renal biopsy specimens from patients with IgAN (n=19) and controls (n=22)...
June 23, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28646042/on-the-role-il-4-il-13-heteroreceptor-plays-in-regulation-of-type-1-diabetes
#19
Tobechukwu K Ukah, Alexis N Cattin-Roy, Weirong Chen, Mindy M Miller, Subhasis Barik, Habib Zaghouani
Type 1 diabetes (T1D) manifests when the insulin-producing pancreatic β cells are destroyed as a consequence of an inflammatory process initiated by lymphocytes of the immune system. The NOD mouse develops T1D spontaneously and serves as an animal model for human T1D. The IL-4Rα/IL-13Rα1 heteroreceptor (HR) serves both IL-4 and IL-13 cytokines, which are believed to function as anti-inflammatory cytokines in T1D. However, whether the HR provides a responsive element to environmental (i.e., physiologic) IL-4/IL-13 in the regulation of peripheral tolerance and the development of T1D has yet to be defined...
June 23, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28646041/concurrent-ox40-and-cd30-ligand-blockade-abrogates-the-cd4-driven-autoimmunity-associated-with-ctla4-and-pd1-blockade-while-preserving-excellent-anti-cd8-tumor-immunity
#20
Maher G Nawaf, Maria H Ulvmar, David R Withers, Fiona M McConnell, Fabrina M Gaspal, Gwilym J Webb, Nick D Jones, Hideo Yagita, James P Allison, Peter J L Lane
Although strategies that block FOXP3-dependent regulatory T cell function (CTLA4 blockade) and the inhibitory receptor PD1 have shown great promise in promoting antitumor immune responses in humans, their widespread implementation for cancer immunotherapy has been hampered by significant off-target autoimmune side effects that can be lethal. Our work has shown that absence of OX40 and CD30 costimulatory signals prevents CD4 T cell-driven autoimmunity in Foxp3-deficient mice, suggesting a novel way to block these side effects...
June 23, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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