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https://www.readbyqxmd.com/read/28231510/lipopolyplex-potentiates-anti-tumor-immunity-of-mrna-based-vaccination
#1
Stefano Persano, Maria L Guevara, Zhaoqi Li, Junhua Mai, Mauro Ferrari, Pier Paolo Pompa, Haifa Shen
mRNA-based vaccines have the benefit of triggering robust anti-cancer immunity without the potential danger of genome integration from DNA vaccines or the limitation of antigen selection from peptide vaccines. Yet, a conventional mRNA vaccine comprising of condensed mRNA molecules in a positively charged protein core structure is not effectively internalized by the antigen-presenting cells. It cannot offer sufficient protection for mRNA molecules from degradation by plasma and tissue enzymes either. Here, we have developed a lipopolyplex mRNA vaccine that consists of a poly-(β-amino ester) polymer mRNA core encapsulated into a 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine/1,2-dioleoyl-sn-glycero-3-phosphatidyl-ethanolamine/1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000 (EDOPC/DOPE/DSPE-PEG) lipid shell...
February 20, 2017: Biomaterials
https://www.readbyqxmd.com/read/28231401/reappraisal-of-ebv-in-diffuse-large-b-cell-lymphoma-dlbcl-comparative-analysis-between-ebv-positive-and-negative-dlbcl-with-ebv-positive-bystander-cells
#2
Akiko Ohashi, Seiichi Kato, Akinao Okamoto, Yoko Inaguma, Akira Satou, Toyonori Tsuzuki, Nobuhiko Emi, Masataka Okamoto, Shigeo Nakamura
AIMS: Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) is defined as monoclonal EBV(+) B-cell proliferation affecting patients without any known immunosuppression. Non-neoplastic EBV(+) cells proliferating in or adjacent to EBV(-) DLBCL were reported recently, but their clinical significance is unclear. Thus, we investigated the prognostic impact of EBV(+) cells in DLBCL. METHODS AND RESULTS: We compared the clinico-pathological characteristics of 30 EBV(+) DLBCL patients and 29 and 604 EBV(-) DLBCL patients with and without EBV(+) bystander cells (median age of onset 71, 67, and 62 years, respectively)...
February 23, 2017: Histopathology
https://www.readbyqxmd.com/read/28231386/evaluating-the-effectiveness-of-rna-in-situ-hybridization-for-detecting-lung-adenocarcinoma-with-anaplastic-lymphoma-kinase-rearrangement
#3
Naoki Nakajima, Akihiko Yoshizawa, Kyoko Kondo, Mariyo Rokutan-Kurata, Masahiro Hirata, Ayako Furuhata, Shinji Sumiyoshi, Makoto Sonobe, Toshi Menju, Masanobu Momose, Masakazu Fujimoto, Hiroshi Date, Hironori Haga
AIMS: An easy and rapid assay for detecting mRNA in formalin-fixed paraffin-embedded samples (RNA-in situ hybridization; RNA-ISH) has been reported recently. We investigated the diagnostic accuracy of RNA-ISH for detecting lung adenocarcinoma (LA) with anaplastic lymphoma kinase (ALK) gene rearrangement. METHODS AND RESULTS: We tested ALK RNA-ISH on 11 resected LAs for which ALK fusion was confirmed by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH)...
February 23, 2017: Histopathology
https://www.readbyqxmd.com/read/28231050/original-research-paper-pulmonary-prophylactic-impact-of-melatonin-and-or-quercetin-a-novel-therapy-for-inflammatory-hypoxic-stress-in-rats
#4
Nouf M Al-Rasheed, Laila Fadda, Hala A Attia, Iman A Sharaf, Azza M Mohamed, Nawal M Al-Rasheed
The study aims to compare, through histological and biochemical studies, the effects of quercetin, melatonin and their combination in regulation of immuno-inflammatory mediators and heat shock protein expressions in sodium nitrite induced hypoxia in rat lungs. The results revealed that NaNO2 injection caused a significant decrease in Hb in rats, while serum levels of TNF-α, IL-6 and CRP, VEGF and HSP70 were elevated compared to the control group. Administration of melatonin, quercetin or their combination before NaNO2 injection markedly reduced these parameters...
March 1, 2017: Acta Pharmaceutica
https://www.readbyqxmd.com/read/28231019/pro-inflammatory-cytokines-impair-vitamin-d-induced-host-defense-in-cultured-airway-epithelial-cells
#5
Jasmijn A Schrumpf, Gimano D Amatngalim, Joris B Veldkamp, Renate M Verhoosel, Dennis K Ninaber, Soledad R Ordonez, Anne M van der Does, Henk P Haagsman, Pieter S Hiemstra
Vitamin D is a regulator of host defense against infections and induces expression of the antimicrobial peptide hCAP18/LL-37. Vitamin D deficiency is associated with chronic inflammatory lung diseases and respiratory infections. However, it is incompletely understood if and how (chronic) airway inflammation affects vitamin D metabolism and action. We hypothesized that long-term exposure of primary bronchial epithelial cells (PBEC) to pro-inflammatory cytokines alters their vitamin D metabolism, antibacterial activity and expression of hCAP18/LL-37...
February 23, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28230277/immune-checkpoint-blockade-biology-in-mouse-models-of-glioblastoma
#6
Alan T Yeo, Al Charest
Glioblastoma Multiforme (GBM) is a highly malignant primary brain cancer that is associated with abysmal prognosis. The median survival of GBM patients is ∼15 months and there have not been any significant advance in therapies in over a decade, leaving treatment options limited. There is clearly an unmet need for GBM treatment. Immunotherapies are treatments based on usurping the power of the host's immune system to recognize and eliminate cancer cells. They have recently proven to be a successful strategy for combating a variety of cancers...
February 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28229819/dabigatran-aggravates-topoisomerase-i-peptide-loaded-dendritic-cells-induced-lung-and-skin-fibrosis
#7
Heena Mehta, Philippe-Olivier Goulet, Jade Desjardins, Gemma Pérez, Martial Koenig, Jean-Luc Senécal, Marika Sarfati
OBJECTIVES: Dysregulated coagulation cascade has been implicated in development of fibrosis in systemic sclerosis (SSc). Thrombin, a key mediator of the coagulation pathway, has both proinflammatory and procoagulant properties. Here, we evaluated the efficacy of oral dabigatran, a direct thrombin inhibitor, on topoisomerase I dendritic cells (TOPOIA DCs)-induced lung and skin fibrosis, an experimental model of SSc. METHODS: Mice were repeatedly immunized with TOPOIA DCs...
February 8, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28229276/effects-of-chlorella-vulgaris-on-tumor-growth-in-mammary-tumor-bearing-balb-c-mice-discussing-association-of-an-immune-suppressed-protumor-microenvironment-with-serum-ifn%C3%AE-and-igg-decrease-and-spleen-igg-potentiation
#8
Ahad Khalilnezhad, Elham Mahmoudian, Nariman Mosaffa, Ali Anissian, Mohsen Rashidi, Davar Amani
PURPOSE: Chlorella vulgaris (CV) has exhibited immune-enhancing and protective activities against cancer and infections. However, there is an increasing concern about the use of Chlorella species in human, regarding its various molecules with antigenic features found in infectious microorganisms. Our goal was to investigate the impact of higher concentrations of CV on tumor growth in spontaneous mouse mammary tumor (SMMT) models. METHODS: Balb/c mice were daily given CV powder at doses of 0, 200, or 300 mg/kg for 42 days (CONTROL, CV200, and CV300 groups, respectively; n = 6/group)...
February 22, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28228486/fruit-and-vegetable-consumption-and-risk-of-copd-a-prospective-cohort-study-of-men
#9
Joanna Kaluza, Susanna C Larsson, Nicola Orsini, Anders Linden, Alicja Wolk
BACKGROUND: Antioxidants present in fruits and vegetables may protect the lung from oxidative damage and prevent COPD. AIMS: To determine the association between fruit and vegetable consumption and risk of COPD by smoking status in men. METHODS: The population-based prospective Cohort of Swedish Men included 44 335 men, aged 45-79 years, with no history of COPD at baseline. Fruit and vegetable consumption was assessed with a self-administered questionnaire...
February 22, 2017: Thorax
https://www.readbyqxmd.com/read/28228336/evaluation-of-hydrophobic-chitosan-based-particulate-formulations-of-porcine-reproductive-and-respiratory-syndrome-virus-vaccine-candidate-t-cell-antigens
#10
Helen Mokhtar, Lucia Biffar, Satyanarayana Somavarapu, Jean-Pierre Frossard, Sarah McGowan, Miriam Pedrera, Rebecca Strong, Jane C Edwards, Margarita Garcia-Durán, Maria Jose Rodriguez, Graham R Stewart, Falko Steinbach, Simon P Graham
PRRS control is hampered by the inadequacies of existing vaccines to combat the extreme diversity of circulating viruses. Since immune clearance of PRRSV infection may not be dependent on the development of neutralising antibodies and the identification of broadly-neutralising antibody epitopes have proven elusive, we hypothesised that conserved T cell antigens represent potential candidates for development of a novel PRRS vaccine. Previously we had identified the M and NSP5 proteins as well-conserved targets of polyfunctional CD8 and CD4 T cells...
February 3, 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28228256/first-breath-induced-type-2-pathways-shape-the-lung-immune-environment
#11
Simona Saluzzo, Anna-Dorothea Gorki, Batika M J Rana, Rui Martins, Seth Scanlon, Philipp Starkl, Karin Lakovits, Anastasiya Hladik, Ana Korosec, Omar Sharif, Joanna M Warszawska, Helen Jolin, Ildiko Mesteri, Andrew N J McKenzie, Sylvia Knapp
From birth onward, the lungs are exposed to the external environment and therefore harbor a complex immunological milieu to protect this organ from damage and infection. We investigated the homeostatic role of the epithelium-derived alarmin interleukin-33 (IL-33) in newborn mice and discovered the immediate upregulation of IL-33 from the first day of life, closely followed by a wave of IL-13-producing type 2 innate lymphoid cells (ILC2s), which coincided with the appearance of alveolar macrophages (AMs) and their early polarization to an IL-13-dependent anti-inflammatory M2 phenotype...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28226405/comparative-effectiveness-of-long-acting-beta2-agonist-combined-with-a-long-acting-muscarinic-antagonist-or-inhaled-corticosteroid-in-chronic-obstructive-pulmonary-disease
#12
Jennifer C Samp, Min J Joo, Glen T Schumock, Gregory S Calip, A Simon Pickard, Todd A Lee
INTRODUCTION: Several dual bronchodilator fixed dose inhaler medications were recently approved for the treatment of chronic obstructive pulmonary disease (COPD). These products combine a long-acting beta2 -agonist (LABA) and long-acting muscarinic antagonist (LAMA). In clinical trials, the separate mechanisms of the bronchodilators resulted in improved lung function. COPD treatment guidelines currently recommend combination LABA/LAMA as alternative therapy to combination LABA/ inhaled corticosteroid (ICS)...
February 22, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28226180/a33-shows-similar-sensitivity-to-but-is-more-specific-than-cdx2-as-an-immunomarker-of-colorectal-carcinoma
#13
Newton A C S Wong, Lukasz A Adamczyk, Shanna Evans, Jayne Cullen, Anca Oniscu, Karin A Oien
AIMS: CDX2 is widely used as a sensitive and specific immunomarker for colorectal carcinoma (CRC) but neither this sensitivity nor specificity is absolute. This study is the first known comparison of CDX1 and A33 against CDX2 as immunomarkers for CRC. METHODS AND RESULTS: As a pilot study, whole sections of 51 cases of liver metastatic carcinoma of different origins - colorectum (n=32), breast (n=3), oesophagogastric tract (n=4), lung (n=3), pancreas (n=8), and prostate (n=1) - were immunostained with CDX1, CDX2 and A33...
February 22, 2017: Histopathology
https://www.readbyqxmd.com/read/28225890/the-anesthetic-agent-sevoflurane-attenuates-pulmonary-acute-lung-injury-by-modulating-apoptotic-pathways
#14
L Wang, Y Ye, H B Su, J P Yang
The objective of this study was to evaluate lung protection by the volatile anesthetic sevoflurane (SEVO), which inhibits apoptosis. Male Sprague-Dawley rats (250-280 g; n=18) were randomly divided into three groups. The LPS group received 5 mg/kg endotoxin (lipopolysaccharide), which induced acute lung injury (ALI). The control (CTRL) group received normal saline and the SEVO group received sevoflurane (2.5%) for 30 min after ALI was induced by 5 mg/kg LPS. Samples were collected for analysis 12 h after LPS...
February 20, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28225865/continuous-blood-purification-treatment-for-endotoxin-induced-acute-respiratory-distress-syndrome
#15
Y Jiang, R Lin, Y Xu, S Zhang, K Cui, M Zhu, A Li, C Chen, J Yang, W Yang
This study aimed to explore the effects of continuous blood purification (CBP) treatment in pigs affected with acute respiratory distress syndrome (ARDS). A total of 12 healthy male pigs, weighing 12±1.8 kg, were randomly and equally assigned to the control and experimental groups. The ARDS pig model was prepared by intravenous injections of endotoxin (20 µg/kg). The control group was given conventional supportive therapy, while the experimental group was given continuous veno-venous hemofiltration therapy...
February 16, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28225753/complement-drives-glucosylceramide-accumulation-and-tissue-inflammation-in-gaucher-disease
#16
Manoj K Pandey, Thomas A Burrow, Reena Rani, Lisa J Martin, David Witte, Kenneth D Setchell, Mary A Mckay, Albert F Magnusen, Wujuan Zhang, Benjamin Liou, Jörg Köhl, Gregory A Grabowski
Gaucher disease is caused by mutations in GBA1, which encodes the lysosomal enzyme glucocerebrosidase (GCase). GBA1 mutations drive extensive accumulation of glucosylceramide (GC) in multiple innate and adaptive immune cells in the spleen, liver, lung and bone marrow, often leading to chronic inflammation. The mechanisms that connect excess GC to tissue inflammation remain unknown. Here we show that activation of complement C5a and C5a receptor 1 (C5aR1) controls GC accumulation and the inflammatory response in experimental and clinical Gaucher disease...
February 22, 2017: Nature
https://www.readbyqxmd.com/read/28224698/determinants-of-the-magnitude-of-interaction-between-tacrolimus-and-voriconazole-posaconazole-in-solid-organ-recipients
#17
Thomas Vanhove, Hanneke Bouwsma, Luuk Hilbrands, Jesse J Swen, Isabel Spriet, Pieter Annaert, Bart Vanaudenaerde, Geert Verleden, Robin Vos, Dirk R J Kuypers
Administration of azole antifungals to tacrolimus-treated solid organ recipients results in a major drug-drug interaction characterized by increased exposure to tacrolimus. The magnitude of this interaction is highly variable but cannot currently be predicted. We performed a retrospective analysis of 126 solid organ recipients (95 lung, 31 kidney) co-treated with tacrolimus and voriconazole (n=100) or posaconazole (n=26). Predictors of the change in tacrolimus dose-corrected trough concentrations (C/D) between baseline and tacrolimus - azole co-therapy were assessed using linear mixed modeling...
February 21, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28223486/serum-borne-bioactivity-caused-by-pulmonary-multiwalled-carbon-nanotubes-induces-neuroinflammation-via-blood-brain-barrier-impairment
#18
Mario J Aragon, Lauren Topper, Christina R Tyler, Bethany Sanchez, Katherine Zychowski, Tamara Young, Guy Herbert, Pamela Hall, Aaron Erdely, Tracy Eye, Lindsey Bishop, Samantha A Saunders, Pretal P Muldoon, Andrew K Ottens, Matthew J Campen
Pulmonary exposure to multiwalled carbon nanotubes (MWCNTs) causes indirect systemic inflammation through unknown pathways. MWCNTs translocate only minimally from the lungs into the systemic circulation, suggesting that extrapulmonary toxicity may be caused indirectly by lung-derived factors entering the circulation. To assess a role for MWCNT-induced circulating factors in driving neuroinflammatory outcomes, mice were acutely exposed to MWCNTs (10 or 40 µg/mouse) via oropharyngeal aspiration. At 4 h after MWCNT exposure, broad disruption of the blood-brain barrier (BBB) was observed across the capillary bed with the small molecule fluorescein, concomitant with reactive astrocytosis...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28223377/exopolysaccharide-repressing-small-molecules-with-antibiofilm-and-antivirulence-activity-against-pseudomonas-aeruginosa
#19
Erik van Tilburg Bernardes, Laetitia Charron-Mazenod, David J Reading, Shauna L Reckseidler-Zenteno, Shawn Lewenza
Biofilm formation is a universal virulence strategy in which bacteria grow in dense microbial communities enmeshed within a polymeric extracellular matrix that protects them from antibiotic exposure and the immune system. Pseudomonas aeruginosa is an archetypal biofilm-forming organism that utilizes a biofilm growth strategy to cause chronic lung infections in Cystic Fibrosis (CF) patients. The extracellular matrix of P. aeruginosa biofilms is comprised mainly of exopolysaccharides (EPS) and DNA. Both mucoid and non-mucoid isolates of P...
February 21, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28223235/interleukin-32-inflammation-and-cancer
#20
REVIEW
Jin Tae Hong, Dong Ju Son, Chong Kil Lee, Do-Young Yoon, Dong Hun Lee, Mi Hee Park
Interleukin-32 (IL-32) is a novel cytokine involved in inflammation and cancer development. IL-32 gene consists of eight small exons, and IL-32 mRNA has nine alternative spliced isoforms, and was thought to be secreted because it contains an internal signal sequence and lacks a transmembrane region. IL-32 is initially expressed selectively in activated T cells by mitogen and activated NK cells and their expression is strongly augmented by microbes, mitogens, and other cytokines. The IL-32 is induced mainly by pathogens and pro-inflammatory cytokines, but IL-32 is more prominent in immune cells than in non-immune tissues...
February 13, 2017: Pharmacology & Therapeutics
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