RESUMO
IL-39 (Interleukin-39) is a heterodimeric cytokine composed of IL-23p19 and EBI3 (Epstein-Barr virus-induced gene 3) subunits. Despite the evidence that correlates the role of IL-39 in regulating inflammation, its expression in the intestinal microenvironment of IBD (inflammatory bowel disease) patients is still unknown. Thus, this work was focused on characterizing relative mRNA (messenger RNA) IL-39 expression and intestinal synthesis in IBD patients. This study includes 37 patients diagnosed with ulcerative colitis (UC), 15 with Chron's disease (CD), and 22 controls. Gene expression of IL-39 subunits (IL-23p19/EBI3) was measured by RT-PCR (real time polymerase chain reaction). Intestinal synthesis was evaluated by immunohistochemistry and serum levels by ELISA. Statistical analysis was done using Prism GraphPad V6. Relative mRNA IL-39 expression was increased in patients with active UC and active CD compared to the remission UC, remission CD, and control group. High levels of relative mRNA expression of IL-39 (IL-23p19 subunit) were associated with histological activity. IHQ analysis showed increased IL-39 production in mucosa, submucosa, muscular, and serosa layer of patients with active disease. IL-39 serum production was increased in patients with UC. IL-39 gene's upregulation was found in patients with active IBD and was associated with severe histological activity in UC. This is the first report regarding the role of IL-39 in patients with IBD. The findings suggest that IL-39 might play a role as an inflammatory mediator in active IBD and could be considered a new alternative in treating this condition.
RESUMO
Oxysterols are the products of cholesterol oxidation. They have a wide range of effects on several cells, organs, and systems in the body. Oxysterols also have an influence on the physiology of the immune system, from immune cell maturation and migration to innate and humoral immune responses. In this regard, oxysterols have been involved in several diseases that have an immune component, from autoimmune and neurodegenerative diseases to inflammatory diseases, atherosclerosis, and cancer. Here, we review data on the participation of oxysterols, mainly 25-hydroxycholesterol and 7α,25-dihydroxycholesterol, in the immune system and related diseases. The effects of these oxysterols and main oxysterol receptors, LXR and EBI2, in cells of the immune system (B cells, T cells, macrophages, dendritic cells, oligodendrocytes, and astrocytes), and in immune-related diseases, such as neurodegenerative diseases, intestinal diseases, cancer, respiratory diseases, and atherosclerosis, are discussed.
Assuntos
Aterosclerose , Oxisteróis , Linfócitos B , Humanos , Macrófagos , Receptores Acoplados a Proteínas GRESUMO
Tuberculosis is becoming a global issue with raising occurrences; particularly in developing countries, the situation is alarming. Besides environmental factors, host genetic factors are vital in disease development. A demographical and genotypic analysis in relation to tuberculosis commencement is conducted in a Pakistani population, and genotypic frequency of EBI3 (rs4740) was analyzed. Allelic frequencies of EBI3 (rs4740) were significantly associated with disease susceptibility in the reviewed population. Analysis for EBI3 (rs4740) genotyping showed a significant association of "GG" with reduced risk for disease. Moreover, females and older age found to be more perilous to develop TB while smoking and a family history of TB are additional risk factors for disease development. Further work with a larger population is necessary to identify the true causative variants of tuberculosis.
Assuntos
Predisposição Genética para Doença/genética , Interleucinas/genética , Antígenos de Histocompatibilidade Menor/genética , Tuberculose Pulmonar/genética , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Criança , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/imunologia , Paquistão , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Fumar/efeitos adversos , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/microbiologia , Adulto JovemRESUMO
Resumen Contar con herramientas para el diseño y la implementación de intervenciones en alfabetización con niños hispanohablantes reúne cada vez mayor interés entre docentes e investigadores. Para contribuir a esta demanda, realizamos una revisión sistemática con el objetivo de sintetizar la información disponible sobre intervenciones basadas en la evidencia (IBE) con niños de primero a tercer grado escolar. Nuestros resultados recogen información sobre 20 IBE, que buscaron mejorar al menos uno de los siguientes componentes críticos nombrados por el NRP (2000): conciencia fonológica, principio alfabético, fluidez, vocabulario y comprensión. Dado que el 90% de ellos fue realizado con niños angloparlantes nos dedicamos a discutir críticamente la aplicabilidad de esta evidencia al contexto particular de países hispanohablantes. Si bien muchas de las características generales de las IBE implementadas en inglés podrían servir de guía para intervenir en español, resulta imprescindible tener en cuenta las diferencias estructurales en la ortografía de ambas lenguas. A su vez, identificamos estrategias transversales y técnicas de implementación en las IBE, que por su carácter universal podrían ser de utilidad práctica también para intervenir en el desarrollo lector en español.
Abstract An area of increasing interest amongst teachers and researchers is the availability of tools for the design and implementation of literacy interventions with Spanish speaking children. The present systematic literature review contributes to this need by summarizing available findings on evidence-based literacy interventions (EBI) for children from first to third year of primary school. Our results are based on 20 EBI that aimed at improving at least one of the critical components mentioned by the NRP (2000): phonological awareness, phonics, fluency, vocabulary and comprehension. As 90% of the studies were completed with English-speaking children, we critically discussed the applicability of this evidence to the specific context of Spanish-speaking countries. Although many of the general characteristics of the EBI completed with English speaking children could also guide interventions in Spanish, it remains crucial to take into account structural differences between the orthographies of both languages. Moreover, we identified transversal strategies and implementation techniques that due to their universal character could also be useful for early literacy interventions in Spanish.
Assuntos
Educação , Prática Clínica Baseada em Evidências , Alfabetização , Revisão Sistemática , IdiomaRESUMO
The identification of anti-inflammatory mediators can reveal important targetable molecules capable of counterbalancing Trypanosoma cruzi-induced myocarditis. Composed of Ebi3 and IL-27p28 subunits, IL-27 is produced by myeloid cells and is able to suppress inflammation by inducing IL-10-producing Tr1 cells, thus emerging as a potential candidate to ameliorate cardiac inflammation induced by T. cruzi. Although IL-27 has been extensively characterized as a suppressive cytokine that prevents liver immunopathogenesis after T. cruzi infection, the mechanisms underlying its effects on T. cruzi-induced myocarditis remain largely unknown. Here, wild-type (WT) and Ebi3-deficient animals were intraperitoneally infected with trypomastigotes of T. cruzi Y strain and used to evaluate the potential anti-inflammatory properties of Ebi3 during T. cruzi infection. The survival rates of mice were daily recorded, the frequency of inflammatory cells was analyzed by flow cytometry and inflammatory mediators were measured by ELISA, real-time PCR and PCR array. We reported that T. cruzi-induced myocarditis was prevented by Ebi3. Stressors mainly recognized by TLR2 and TLR4 receptors on myeloid cells were essential to trigger IL-27p28 production. In addition, Ebi3 regulated IFN-γ-mediated myocarditis by promoting an anti-inflammatory environment through IL-10, which was most likely produced by Tr1 cells rather than classical regulatory T cells (Tregs), in the heart tissue of T. cruzi-infected animals. Furthermore, in vivo IFN-γ blockade ameliorated the host survival without compromising the parasite control in the bloodstream. In humans, IL-27p28 was correlated with cardiac protection during Chagas disease. Patients with mild clinical forms of the disease produced high levels of IL-27p28, whereas lower levels were found in those with severe forms. In addition, polymorphic sites at Ebi3 gene were associated with severe cardiomyopathy in patients with Chagas disease. Collectively, we describe a novel regulatory mechanism where Ebi3 dampens cardiac inflammation by modulating the overproduction of IFN-γ, the bona fide culprit of Chagas disease cardiomyopathy.
RESUMO
Data processing, management and visualization are central and critical components of a state of the art high-throughput mass spectrometry (MS)-based proteomics experiment, and are often some of the most time-consuming steps, especially for labs without much bioinformatics support. The growing interest in the field of proteomics has triggered an increase in the development of new software libraries, including freely available and open-source software. From database search analysis to post-processing of the identification results, even though the objectives of these libraries and packages can vary significantly, they usually share a number of features. Common use cases include the handling of protein and peptide sequences, the parsing of results from various proteomics search engines output files, and the visualization of MS-related information (including mass spectra and chromatograms). In this review, we provide an overview of the existing software libraries, open-source frameworks and also, we give information on some of the freely available applications which make use of them. This article is part of a Special Issue entitled: Computational Proteomics in the Post-Identification Era. Guest Editors: Martin Eisenacher and Christian Stephan.