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1.
Am J Respir Cell Mol Biol ; 64(4): 465-476, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33493092

RESUMEN

Fibroblast activation includes differentiation to myofibroblasts and is a key feature of organ fibrosis. The Notch pathway has been involved in myofibroblast differentiation in several tissues, including the lung. Here, we identify a subset of collagen-expressing cells in the lung that exhibit Notch3 activity at homeostasis. After injury, this activation increases, being found in αSMA-expressing myofibroblasts in the mouse and human fibrotic lung. Although previous studies suggest a contribution of Notch3 in stromal activation, in vivo evidence of the role of Notch3 in lung fibrosis remains unknown. In this study, we examine the effects of Notch3 deletion in pulmonary fibrosis and demonstrate that Notch3-deficient lungs are protected from lung injury with significantly reduced collagen deposition after bleomycin administration. The induction of profibrotic genes is reduced in bleomycin-treated Notch3-knockout lungs that consistently present fewer αSMA-positive myofibroblasts. As a result, the volume of healthy lung tissue is higher and lung function is improved in the absence of Notch3. Using in vitro cultures of lung primary fibroblasts, we confirmed that Notch3 participates in their survival and differentiation. Thus, Notch3 deficiency mitigates the development of lung fibrosis because of its role in mediating fibroblast activation. Our findings reveal a previously unidentified mechanism underlying lung fibrogenesis and provide a potential novel therapeutic approach to target pulmonary fibrosis.


Asunto(s)
Colágeno/metabolismo , Pulmón/metabolismo , Miofibroblastos/metabolismo , Fibrosis Pulmonar/metabolismo , Receptor Notch3/deficiencia , Actinas/metabolismo , Animales , Bleomicina , Diferenciación Celular , Supervivencia Celular , Células Cultivadas , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Humanos , Pulmón/patología , Pulmón/fisiopatología , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Miofibroblastos/patología , Fenotipo , Fibrosis Pulmonar/genética , Fibrosis Pulmonar/patología , Fibrosis Pulmonar/fisiopatología , Receptor Notch3/genética
2.
Int J Environ Res Public Health ; 12(8): 8678-90, 2015 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-26213954

RESUMEN

Most current disinfection strategies for fresh-cut industry are focused on the use of different chemical agents; however, very little has been reported on the effectiveness of the hurdle technology. The effect of combined decontamination methods based on the use of different sanitizers (peroxyacetic acid and chlorine dioxide) and the application of pressure (vacuum/positive pressure) on the inactivation of the foodborne pathogen E. coli O157:H7 on fresh-cut lettuce (Lactuca sativa) and carrots (Daucus carota) was studied. Fresh produce, inoculated with E. coli O157:H7, was immersed (4 °C, 2 min) in tap water (W), chlorine water (CW), chlorine dioxide (ClO2: 2 mg/L) and peroxyacetic acid (PAA: 100 mg/L) in combination with: (a) vacuum (V: 10 mbar) or (b) positive pressure application (P: 3 bar). The product quality and antimicrobial effects of the treatment on bacterial counts were determined both in process washing water and on fresh-cut produce. Evidence obtained in this study, suggests that the use of combined methods (P/V + sanitizers) results in a reduction on the microorganism population on produce similar to that found at atmospheric pressure. Moreover, the application of physical methods led to a significant detrimental effect on the visual quality of lettuce regardless of the solution used. Concerning the process water, PAA proved to be an effective alternative to chlorine for the avoidance of cross-contamination.


Asunto(s)
Desinfección/métodos , Escherichia coli O157 , Contaminación de Alimentos/prevención & control , Verduras/microbiología , Cloro/farmacología , Compuestos de Cloro/farmacología , Recuento de Colonia Microbiana , Daucus carota/microbiología , Desinfectantes/farmacología , Escherichia coli O157/efectos de los fármacos , Escherichia coli O157/aislamiento & purificación , Manipulación de Alimentos/métodos , Microbiología de Alimentos/métodos , Lactuca/microbiología , Óxidos/farmacología , Ácido Peracético/farmacología , Presión , Microbiología del Agua , Calidad del Agua
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