MARIANGELA MACCHIONE
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Patologia, Faculdade de Medicina
LIM/05 - Laboratório de Poluição Atmosférica Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/05 - Laboratório de Poluição Atmosférica Experimental, Hospital das Clínicas, Faculdade de Medicina
3 resultados
Resultados de Busca
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- Smoking load reduction is insufficient to downregulate miR-301b, a lung cancer promoter(2020) ARCAS, Camila dos Santos; LIN-WANG, Hui Tzu; UMEDA, Iracema Ioco Kikuchi; SOUSA, Marcio Goncalves de; UTIYAMA, Daniela Mitiyo Odagiri; MANSUR, Antonio de Padua; MACCHIONE, Mariangela; HIRATA, Mario Hiroyuki; NAKAGAWA, Naomi KondoSeveral circulating miRNAs identified in the plasma of smokers have been implicated as promoters of nasopharyngeal and lung carcinoma. To investigate the plasma profile of miRNAs in subjects who reduces the number of smoked cigarettes and who quit after six months. We accompanied 28 individuals enrolled in a Smoking Cessation Program over 6 months. At Baseline, clinical characteristics, co-morbidities, and smoking history were similar among subjects. After 6 months, two groups were defined: who successfully quitted smoking (named ""quitters"", n=18, mean age 57 years, 11 male) and who reduced the number of cigarettes smoked (20-90%) but failed to quit smoking (named ""smokers"", n=10, mean age 52 years, 3 male). No significant clinical changes were observed between groups at baseline and after a 6-month period, however, quitters showed significant downregulations in seven miRNAs at baseline: miR-17 (-2.90 -fold, p=0.029), miR-20a (-3.80-fold, p=0.021); miR-20b (-4.71-fold, p=0.027); miR-30a (-3.95-fold, p=0.024); miR-93 (-3.63-fold, p=0.022); miR-125a(-1.70 -fold, p= 0.038); and miR-195 (-5.37-fold, p=0.002), and after a 6-month period in 6 miRNAs: miR-17 (-5.30-fold, p=0.012), miR-20a (-2.04-fold, p=0.017), miR-20b (-5.44-fold, p=0.017), miR-93 (-4.00-fold, p=0.041), miR-101 (-4.82-fold, p=0.047) and miR-125b (-3.65-fold, p=0.025). Using time comparisons, only quitters had significant downregulation in miR-301b (-2.29-fold, p=0.038) after 6-month. Reductions in the number of smoked cigarettes was insufficient to change the plasma profile of miRNA after 6 months. Only quitting smoking (100% reduction) significantly downregulated miR-301b related to hypoxic conditions, promotion of cell proliferation, decreases in apoptosis, cancer development, and progression as increases in radiotherapy and chemotherapy resistance.
- Severe pulmonary disease in an adult primary ciliary dyskinesia population in Brazil(2019) OLM, Mary Anne Kowal; MARSON, Fernando Augusto Lima; ATHANAZIO, Rodrigo Abensur; NAKAGAWA, Naomi Kondo; MACCHIONE, Mariangela; LOGES, Niki Tomas; OMRAN, Heymut; RACHED, Samia Zahi; BERTUZZO, Carmen Silvia; STELMACH, Rafael; SALDIVA, Paulo Hilario Nascimento; RIBEIRO, Jose Dirceu; JONES, Marcus Herbert; MAUAD, ThaisPrimary Ciliary Dyskinesia (PCD) is underdiagnosed in Brazil. We enrolled patients from an adult service of Bronchiectasis over a two-year period in a cross-sectional study. The inclusion criteria were laterality disorders (LD), cough with recurrent infections and the exclusion of other causes of bronchiectasis. Patients underwent at least two of the following tests: nasal nitric oxide, ciliary movement and analysis of ciliary immunofluorescence, and genetic tests (31 PCD genes + CFTR gene). The clinical characterization included the PICADAR and bronchiectasis scores, pulmonary function, chronic Pseudomonas aeruginosa (cPA) colonization, exhaled breath condensate (EBC) and mucus rheology (MR). Forty-nine of the 500 patients were diagnosed with definite (42/49), probable (5/49), and clinical (2/49) PCD. Twenty-four patients (24/47) presented bi-allelic pathogenic variants in a total of 31 screened PCD genes. A PICADAR score > 5 was found in 37/49 patients, consanguinity in 27/49, LD in 28/49, and eight PCD sibling groups. FACED diagnosed 23/49 patients with moderate or severe bronchiectasis; FEV1 <= 50% in 25/49 patients, eight patients had undergone lung transplantation, four had been lobectomized and cPA+ was determined in 20/49. The EBC and MR were altered in all patients. This adult PCD population was characterized by consanguinity, severe lung impairment, genetic variability, altered EBC and MR.
- Nrf2 positively regulates autophagy antioxidant response in human bronchial epithelial cells exposed to diesel exhaust particles(2020) FRIAS, Daniela Perroni; GOMES, Raquel Labiapari Nunes; YOSHIZAKI, Kelly; CARVALHO-OLIVEIRA, Regiani; MATSUDA, Monique; JUNQUEIRA, Mara de Souza; TEODORO, Walcy Rosolia; VASCONCELLOS, Perola de Castro; PEREIRA, Daniela Cristina de Almeida; CONCEICAO, Paulo Roberto da; SALDIVA, Paulo Hilario Nascimento; MAUAD, Thais; MACCHIONE, MariangelaDiesel exhaust particles (DEP) are known to generate reactive oxygen species in the respiratory system, triggering cells to activate antioxidant defence mechanisms, such as Keap1-Nrf2 signalling and autophagy. The aim of this study was to investigate the relationship between the Keap1-Nrf2 signalling and autophagy pathways after DEP exposure. BEAS-2B cells were transfected with silencing RNA (siRNA) specific to Nrf2 and exposed to DEP. The relative levels of mRNA for Nrf2, NQO1, HO-1, LC3B, p62 and Atg5 were determined using RT-PCR, while the levels of LCB3, Nrf2, and p62 protein were determined using Western blotting. The autophagy inhibitor bafilomycin caused a significant decrease in the production of Nrf2, HO-1 and NQO1 compared to DEPs treatment, whereas the Nrf2 activator sulforaphane increased the LC3B (p = 0.020) levels. BEAS-2B cells exposed to DEP at a concentration of 50 mu g/mL for 2 h showed a significant increase in the expression of LC3B (p = 0.001), p62 (p = 0.008), Nrf2 (p = 0.003), HO-1 (p = 0.001) and NQO1 (p = 0.015) genes compared to control. In siRNA-transfected cells, the LC3B (p < 0.001), p62 (p = 0.001) and Atg5 (p = 0.024) mRNA levels and the p62 and LC3II protein levels were decreased, indicating that Nrf2 modulated the expression of autophagy markers (R < 1). These results imply that, in bronchial cells exposed to DEP, the Nrf2 system positively regulates autophagy to maintain cellular homeostasis.