Role of PGE2 in Asthma and Nonasthmatic Eosinophilic Bronchitis

Eosinophilic bronchitis is a common cause of chronic cough, which like asthma is characterized by sputum eosinophilia, but unlike asthma there is no variable airflow obstruction or airway hyperresponsiveness. Several studies suggest that prostaglandins may play an important role in orchestrating interactions between different cells in several inflammatory diseases such as asthma. PGE2 is important because of the multiplicity of its effects on immune response in respiratory diseases; however, respiratory system appears to be unique in that PGE2 has beneficial effects. We described that the difference in airway function observed in patients with eosinophilic bronchitis and asthma could be due to differences in PGE2 production. PGE2 present in induced sputum supernatant from NAEB patients decreases BSMC proliferation, probably due to simultaneous stimulation of EP2 and EP4 receptors with inhibitory activity. This protective effect of PGE2 may not only be the result of a direct action exerted on airway smooth-muscle proliferation but may also be attributable to the other anti-inflammatory actions

Single-cell RNA sequencing of human blood eosinophils reveals plasticity and absence of canonical cell subsets

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAMPI21/0089

Myxomatous Degeneration of the Canine Mitral Valve: From Gross Changes to Molecular Events

Myxomatous mitral valve disease (MMVD) is the single most common acquired heart disease of the dog, but is also of emerging importance in human medicine, with some features of the disease shared between both species. There has been increased understanding of this disease in recent years, with most research aiming to elucidate the cellular and molecular events of disease pathogenesis. For gross and histological changes, much of our understanding is based on historical studies and there has been no comprehensive reappraisal of the pathology of MMVD. This paper reviews the gross, histological, ultrastructural, cellular and molecular changes in canine MMVD. (C) 2017 Elsevier Ltd. All rights reserved

El tratamiento informativo de las noticias de violencia de género en los diarios Ojo y Trome desde la teoría del framing

El trabajo aborda la problemática de violencia de género en nuestro país y cómo se retrata en los diarios populares de mayor nivel de lectoría, Trome y Ojo, desde la Teoría del Framing. Por medio de un relevamiento de noticias referentes a casos conocidos de violencia de género en el Perú, se analizaron elementos que constituyen el encuadre de una noticia, como los titulares, el tipo de imágenes, las fuentes consultadas, la terminología usada en la redacción y el enfoque propuesto. Tras dicha revisión, se identificaron aspectos que dan cabida a la espectacularización de la noticia, tales como titulares tendenciosos o imágenes sin censura de mujeres agredidas. A pesar de muchas veces vincularse a movimientos como “Ni una menos”, predomina más el carácter sensacionalista del medio, que un tratamiento apropiado de las noticias. Por otro lado, un factor que limita una minuciosa observación de la información emitida es la inmediatez que requieren las plataformas digitales de estos diarios, además de una adecuada regulación por parte de los directivos.The present document addresses the problem of gender violence in our country and how it is portrayed in the popular newspapers with the highest level of readership, Trome and Ojo, from the Framing Theory. Through a survey of news referring to known cases of gender violence in Peru, elements that constitute the framing of a news story were analyzed, such as the headlines, the type of images, the consulted sources, the terminology in the writing and the proposed frame. After this review, aspects were identified that give rise to the spectacularization of the news, such as tendentious headlines or uncensored images of assaulted women. Despite often being linked to movements such as “Ni una menos”, the sensational nature of the medium predominates more than an appropriate treatment of the news. On the other hand, a factor that limits a detailed observation of the information issued is the immediacy required by the digital platforms of these newspapers, in addition to the adequate regulation by managers

Gene Expression Profiling in Lungs of Chronic Asthmatic Mice Treated with Galectin-3: Downregulation of Inflammatory and Regulatory Genes

Background. Asthma is a disorder characterized by a predominance of Th2 cells and eosinophilic inflammation. Suppressors of cytokine signaling (SOCS) proteins act as negative regulators of cytokine signaling. In particular, SOCS1 and SOCS3 play an important role in immune response by controlling the balance between Th1 and Th2 cells. In a previous study, we demonstrated that treatment of chronic asthmatic mice with gene therapy using plasmid encoding galectin-3 (Gal-3) led to an improvement in Th2 allergic inflammation. Methods. Using a microarray approach, this study endeavored to evaluate the changes produced by therapeutic Gal-3 delivered by gene therapy in a well-characterized mouse model of chronic airway inflammation. Results were confirmed by real-time RT-PCR, Western blot and immunohistochemical analysis. Results. We identify a set of genes involved in different pathways whose expression is coordinately decreased/increased in mice treated with Gal-3 gene therapy. We report a correlation between Gal-3 treatment and inhibition of SOCS1 and SOCS3 expression in lungs. Conclusion. These results suggest that negative regulation of SOCS1 and 3 following Gal-3 treatment could be a valuable therapeutic approach in allergic disease

Exosomes: A key piece in asthmatic inflammation

Asthma is a chronic disease of the airways that has an important inflammatory compo-nent. Multiple cells are implicated in asthma pathogenesis (lymphocytes, eosinophils, mast cells, basophils, neutrophils), releasing a wide variety of cytokines. These cells can exert their inflammatory functions throughout extracellular vesicles (EVs), which are small vesicles released by do-nor cells into the extracellular microenvironment that can be taken up by recipient cells. Depending on their size, EVs can be classified as microvesicles, exosomes, or apoptotic bodies. EVs are heterogeneous spherical structures secreted by almost all cell types. One of their main functions is to act as transporters of a wide range of molecules, such as proteins, lipids, and microRNAs (miRNAs), which are single-stranded RNAs of approximately 22 nucleotides in length. Therefore, exosomes could influence several physiological and pathological processes, including those involved in asthma. They can be detected in multiple cell types and biofluids, providing a wealth of infor-mation about the processes that take account in a pathological scenario. This review thus summarizes the most recent insights concerning the role of exosomes from different sources (several cell populations and biofluids) in one of the most prevalent respiratory diseases, asthma.This manuscript was supported by Fondo de Investigación Sanitaria–FIS and FEDER (Fondo Europeo de Desarrollo Regional) [PI15/00803, PI18/00044, and FI16/00036], CIBERES, Merck Health Foundation funds, and RTC-2017-6501-1 (Ministerio de Ciencia, Innovación y Universidades)

Torque Teno Virus in Nasopharyngeal Aspirate of Children With Viral Respiratory Infections

Background: Torque teno virus (TTV) is a ubiquitous anellovirus responsible for persistent infections and is considered a marker of immune function. The role of TTV as a facilitator of respiratory infections (RIs) is unknown. Objectives: Our aim was to estimate, in a prospective study, the prevalence of TTV in the nasopharyngeal aspirate (NPA) of hospitalized children <5 years old, with RIs and correlate them with outcomes and immune response. Patients and methods: NPA was taken for testing of 16 respiratory viruses by reverse transcription-polymerase chain reaction (PCR), TTV PCR, and immunologic study. Results: Sixty hospitalized children with an RI were included. A total of 51/60 patients had positive common respiratory viral (CRV) identification. A total of 23/60 (38.3%) children were TTV+ in NPA. TTV+ patients had other CRVs in 100% of cases versus 78.3% in TTV- ( P = 0.029). The TTV+ patients tended to be older, have fever, and to need pediatric intensive care unit admission more often than TTV- patients. Abnormal chest radiograph was more frequent in the TTV+ patients, odds ratios 2.6 (95% CI: 1.3-5.2). The genetic expression of filaggrin (involved in epithelial barrier integrity) was lower in TTV+ patients; however, the levels of filaggrin in the NPA were increased. Conclusions: TTV infection is common in children with RI and could be associated with abnormal imaging in radiograph, greater severity and an alteration in filaggrin gene expression and protein release.Funded by projects PI18CIII/0009, PI18/00177, and PI21/00377, funded by Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union. There are no conflicts of interest.S

Mechanistic investigation into the selective anticancer cytotoxicity and immune system response of surface-functionalised, dichloroacetate-loaded, UiO-66 nanoparticles

The high drug loading and excellent biocompatibilities of metal-organic frameworks (MOFs) have led to their application as drug delivery systems (DDSs). Nanoparticle surface chemistry dominates both biostability and dispersion of DDSs while governing their interactions with biological systems, cellular and/or tissue targeting, and cellular internalisation, leading to a requirement for versatile and reproducible surface functionalisation protocols. Herein, we explore not only the effect of introducing different surface functionality to the biocompatible Zr-MOF UiO-66, but also the efficacy of three surface modification protocols: (i) direct attachment of biomolecules (folic acid, biotin) introduced as modulators of UiO-66 synthetic, (ii) our previously reported ‘’click-modulation” approach to covalently attach polymers (poly(ethylene glycol), poly-L-lactide, poly-N-isopropylacrylamide) to the surface of UiO-66 through click chemistry, and (iii) surface ligand exchange, to postsynthetically coordinate folic acid, biotin and heparin to UiO-66. The innovative use of a small molecule with metabolic anticancer activity, dichloroacetic acid (DCA), as a modulator during synthesis is described, and found to be compatible with all three protocols, yielding surface-coated, DCA-loaded (10-20% w/w) nanoMOFs (70-170 nm). External surface modification generally enhances stability and colloidal dispersion of UiO-66. Cellular internalisation routes and efficiencies of UiO-66 by HeLa cervical cancer cells can be tuned by surface chemistry, and anticancer cytotoxicity of DCA-loaded MOFs correlates with endocytosis efficiency and mechanisms. The MOFs with the most promising coatings (folic acid, poly(ethylene glycol), poly-L-lactide, and poly-N-isopropylacrylamide) were extensively tested for selectivity of anti-cancer cytotoxicity against MCF-7 breast cancer cells and HEK293 healthy kidney cells, as well as for cell proliferation and ROS production against J774 macrophages and peripheral blood lymphocytes (PBLs) isolated from the blood of human donors. DCA-loaded, folic acid modified UiO-66 selectively kills cancer cells without harming healthy ones or provoking immune system response in vitro, suggesting a significant targeting effect and great potential in anticancer drug delivery. The results provide mechanistic insight into the design and functionalisation of MOFs for drug delivery, and underline the availability of various in vitro techniques to potentially minimise early-stage in vivo animal studies, following the three Rs: reduction, refinement and replacement

Suppressors of Cytokine Signaling 3 Expression in Eosinophils: Regulation by PGE2 and Th2 Cytokines

Asthma and nonasthmatic eosinophilic bronchitis (NAEB) are respiratory disorders characterized by a predominance of Th2 cells and eosinophilic inflammation. Suppressors of cytokine signaling (SOCS) proteins play an important role in Th2-mediated allergic responses through control of the balance between Th1 and Th2 cells, particularly, SOCS3 and SOCS5. The aim of this study was to analyze SOCS expression in human peripheral blood eosinophils from patients with asthma, NAEB and healthy controls. SOCS expression in eosinophils from subjects was demonstrated by different techniques. Results showed that expression of SOCS3 in eosinophils and CD4 T cells from patients was higher than in healthy subjects. In addition, we demonstrated that prostaglandin E2 (PGE2) and Th2 cytokines are able to upregulate SOCS3 production in eosinophils and attenuate its degranulation. In conclusion, eosinophils are able to transcribe and translate SOCS3 protein and can contribute to the regulation of the Th1/Th2 balance through SOCS3 production