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

RESUMO

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.


Assuntos
Colágeno/metabolismo , Pulmão/metabolismo , Miofibroblastos/metabolismo , Fibrose Pulmonar/metabolismo , Receptor Notch3/deficiência , Actinas/metabolismo , Animais , Bleomicina , Diferenciação Celular , Sobrevivência Celular , Células Cultivadas , Modelos Animais de Doenças , Progressão da Doença , Humanos , Pulmão/patologia , Pulmão/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miofibroblastos/patologia , Fenótipo , Fibrose Pulmonar/genética , Fibrose Pulmonar/patologia , Fibrose Pulmonar/fisiopatologia , Receptor Notch3/genética
2.
Int J Environ Res Public Health ; 12(8): 8678-90, 2015 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-26213954

RESUMO

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.


Assuntos
Desinfecção/métodos , Escherichia coli O157 , Contaminação de Alimentos/prevenção & controle , Verduras/microbiologia , Cloro/farmacologia , Compostos Clorados/farmacologia , Contagem de Colônia Microbiana , Daucus carota/microbiologia , Desinfetantes/farmacologia , Escherichia coli O157/efeitos dos fármacos , Escherichia coli O157/isolamento & purificação , Manipulação de Alimentos/métodos , Microbiologia de Alimentos/métodos , Lactuca/microbiologia , Óxidos/farmacologia , Ácido Peracético/farmacologia , Pressão , Microbiologia da Água , Qualidade da Água
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