RESUMO
BACKGROUND: Asthma is a heterogeneous chronic disease with different phenotypes and treatment responses. Thus, there is a high clinical need for molecular disease biomarkers to aid in differentiating these distinct phenotypes. As MicroRNAs (miRNAs), that regulate gene expression at the post-transcriptional level, are altered in experimental and human asthma, circulating miRNAs are attractive candidates for the identification of novel biomarkers. This study aimed to identify plasmatic miRNA-based biomarkers of asthma, through a translational approach. METHODS: We prescreened miRNAs in plasma samples from two different murine models of experimental asthma (ovalbumin and house dust mite); miRNAs deregulated in both models were further tested in a human training cohort of 20 asthma patients and 9 healthy controls. Candidate miRNAs were then validated in a second, independent group of 26 asthma patients and 12 healthy controls. RESULTS: Ten miRNA ratios consisting of 13 miRNAs were differentially regulated in both murine models. Measuring these miRNAs in the training cohort identified a biomarker signature consisting of five miRNA ratios (7 miRNAs). This signature showed a good sensitivity and specificity in the test cohort with an area under the receiver operating characteristic curve (AUC) of 0.92. Correlation of miRNA ratios with clinical characteristics further revealed associations with FVC % predicted, and oral corticosteroid or antileukotriene use. CONCLUSION: Distinct plasma miRNAs are differentially regulated both in murine and in human allergic asthma and were associated with clinical characteristics of patients. Thus, we suggest that miRNA levels in plasma might have future potential to subphenotype patients with asthma.
Assuntos
Asma/diagnóstico , Asma/genética , Biomarcadores , MicroRNA Circulante , Transcriptoma , Adulto , Idoso , Animais , Asma/sangue , Modelos Animais de Doenças , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Pesquisa Translacional Biomédica , Adulto JovemAssuntos
Ácido Graxo Sintases , Glucose/farmacologia , Fígado/enzimologia , Fosfatase Ácida/análise , Animais , Dióxido de Carbono , Isótopos de Carbono , Núcleo Celular/enzimologia , Embrião de Galinha , Coenzima A , Citoplasma/efeitos dos fármacos , Citoplasma/enzimologia , Complexo IV da Cadeia de Transporte de Elétrons/análise , Ácido Graxo Sintases/análise , Glucose-6-Fosfatase/análise , Ligases/análise , Fígado/citologia , Malonatos , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/enzimologia , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/enzimologia , Fosfogluconato Desidrogenase/análise , Estimulação QuímicaRESUMO
Skin allografts were exchanged between 25 males and 25 female mallards (Anas platyrhynchos) within 2 days after hatching. Of the 42 ducks that survived and whose grafts healed, 14% rejected rapidly before the grafts became feathered, 20% rejected between 3-6 weeks, and one duck rejected when he was 10 weeks old. Twenty-seven of the 42 ducks (64%) retained their grafts for at least 5 months. The results demonstrate that, in mallards, neither inbreeding nor any treatment of the host is necessary for prolonged survival of skin allografts made shortly after hatching.
Assuntos
Patos/imunologia , Sobrevivência de Enxerto , Transplante de Pele , Animais , Animais Recém-Nascidos , Feminino , Masculino , Fatores de Tempo , Transplante HomólogoRESUMO
Embryos of the Rouen duck were treated on day 11 to 18 with a single injection of estradiol benzoate in the air chamber. After hatching, skin grafts were exchanged between male ducklings that had been treated with estrogen in ovo and control males. The results showed that the skin of male embryos can be permanently feminized to the same extent as untreated female embryos simply by exposing embryonic male skin to female sex hormones during embryogenesis.