Downregulation of exosomal let-7d and miR-16 in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is a degenerative interstitial lung disease with both a poor prognosis and quality of life once the diagnosis is made. In the last decade many features of the disease have been investigated to better understand the pathological steps that lead to the onset of the disease and, moreover, different types of biomarkers have been tested to find valid diagnostic, prognostic and therapy response predictive ones. In the complexity of IPF, microRNA (miRNAs) biomarker investigation seems to be promising. METHODS: We analysed the expression of five exosomal miRNAs supposed to have a role in the pathogenesis of the disease from serum of a group of IPF patients (n = 61) and we compared it with the expression of the same miRNAs in a group of healthy controls (n = 15). RESULTS: In the current study what emerged is let-7d down-regulation and, unexpectedly, miR-16 significant down-regulation. Moreover, through a cross-sectional analysis, a clustering of the expression of miR-16, miR-21 and miR-26a was found. CONCLUSIONS: These findings could help the individuation of previously unknown key players in the pathophysiology of IPF and, most interestingly, more specific targets for the development of effective medications.

Searching for Inflammatory and Oxidative Stress Markers Capable of Clustering Severe Asthma / Búsqueda de marcadores de estrés inflamatorio y oxidativo capaces de agrupar asma grave

Objective: Asthma inflammation may feature an imbalance between oxidative stress and antioxidant defenses. Oxidative stress induces propagation of airways inflammation and corticosteroid insensitivity contributing to poor asthma control, and frequent severe acute exacerbations. This study assessed inflammation and oxidative stress in severe asthmatic subjects and evaluated the possible correlations between inflammatory and oxidative stress markers investigated and asthma severity.Material and method: Fifty-three patients with severe asthma, 11 patients with mild-moderate asthma and 12 healthy subjects were enrolled and underwent fractional exhaled nitric oxide (FENO) analysis and blood and sputum count cell collection. The content of mitochondrial DNA (MtDNA) and nuclear DNA (nDNA) was measured in exhaled breath condensate (EBC) by Real Time PCR and the ratio between MtDNA/nDNA was calculated. We detected MtDNA/nDNA in the EBC of severe asthmatics.Results: We found higher exhaled MtDNA/nDNA in severe asthmatics respectively compared to mild-moderate ones and to healthy controls (10.4±2.2 vs 7.9±2.5, p<0.05 and 10.4±2.2 vs 6.51±0.21, p<0.05). The level of exhaled MtDNA/nDNA was significantly higher in Non-T2 endotype severe asthmatics than T2 (14.07±10. 8 vs 6.5±5.5, p<0.05).Conclusion: Oxidative stress marker (MtDNA/nDNA) is increased significantly with asthma severity and may be useful for endotyping severe asthma. (AU)

Objetivo: La inflamación en el asma puede presentar un desequilibrio entre el estrés oxidativo y las defensas antioxidantes. El estrés oxidativo induce la propagación de la inflamación de las vías aéreas y la insensibilidad a los corticosteroides, lo que contribuye a un control deficiente del asma y a frecuentes exacerbaciones agudas graves. Este estudio evaluó la inflamación y el estrés oxidativo en sujetos asmáticos graves y estudió las posibles correlaciones entre los marcadores de estrés inflamatorio y oxidativo investigados y la gravedad del asma.Material y método: Se incluyó a 53 pacientes con asma grave, 11 pacientes con asma leve a moderada y 12 sujetos sanos, a los que se les realizó un análisis de fracción exhalada de óxido nítrico (FeNO) y un recuento celular del esputo y de sangre. Se midió el contenido de ADN mitocondrial (ADNmt) y ADN nuclear (ADNn) en el condensado de aire exhalado (CAE) mediante PCR en tiempo real y se calculó la ratio ADNmt/ADNn. Detectamos ADNmt/ADNn en el CAE de los asmáticos graves.Resultados: Encontramos unos niveles más altos de ADNmt/ADNn exhalados en los asmáticos graves en comparación con los leves moderados y los controles sanos (respectivamente, 10,4±2,2 frente a 7,9±2,5, p<0,05 y 10,4±2,2 frente a 6,51±0,21, p<0,05). El nivel de ADNmt/ADNn exhalado fue significativamente mayor en los asmáticos graves de endotipo no-T2 que en los T2 (14,07±10,8 frente a 6,5±5,5, p<0,05).Conclusión: El marcador de estrés oxidativo (ADNmt/ADNn) aumenta significativamente con la gravedad del asma y puede ser útil para endotipar el asma grave. (AU)

Searching for Inflammatory and Oxidative Stress Markers Capable of Clustering Severe Asthma.

OBJECTIVE: Asthma inflammation may feature an imbalance between oxidative stress and antioxidant defenses. Oxidative stress induces propagation of airways inflammation and corticosteroid insensitivity contributing to poor asthma control, and frequent severe acute exacerbations. This study assessed inflammation and oxidative stress in severe asthmatic subjects and evaluated the possible correlations between inflammatory and oxidative stress markers investigated and asthma severity. MATERIAL AND METHOD: Fifty-three patients with severe asthma, 11 patients with mild-moderate asthma and 12 healthy subjects were enrolled and underwent fractional exhaled nitric oxide (FENO) analysis and blood and sputum count cell collection. The content of mitochondrial DNA (MtDNA) and nuclear DNA (nDNA) was measured in exhaled breath condensate (EBC) by Real Time PCR and the ratio between MtDNA/nDNA was calculated. We detected MtDNA/nDNA in the EBC of severe asthmatics. RESULTS: We found higher exhaled MtDNA/nDNA in severe asthmatics respectively compared to mild-moderate ones and to healthy controls (10.4±2.2 vs 7.9±2.5, p<0.05 and 10.4±2.2 vs 6.51±0.21, p<0.05). The level of exhaled MtDNA/nDNA was significantly higher in Non-T2 endotype severe asthmatics than T2 (14.07±10. 8 vs 6.5±5.5, p<0.05). CONCLUSION: Oxidative stress marker (MtDNA/nDNA) is increased significantly with asthma severity and may be useful for endotyping severe asthma.