Possible role of Krüppel-like factor 5 in the remodeling of small airways and pulmonary vessels in chronic obstructive pulmonary disease

BACKGROUND: Small airway remodeling is an important cause of the airflow limitation in chronic obstructive pulmonary disease (COPD). A large population of patients with COPD also have pulmonary hypertension. Krüppel-like factor 5 (KLF5) is a zinc-finger transcription factor that contributes to tissue remodeling in cardiovascular diseases. Here, we evaluate the possible involvement of KLF5 in the remodeling of small airways and pulmonary vessels in COPD. METHODS: Lung tissues were obtained from 23 control never-smokers, 17 control ex-smokers and 24 ex-smokers with COPD. The expression of KLF5 in the lung tissues was investigated by immunohistochemistry. We investigated whether oxidative/nitrosative stress, which is a major cause of the pathogenesis in COPD, could augment the production of KLF5. We examined the role of KLF5 in the stress-mediated tissue remodeling responses. We also investigated the susceptibility of KLF5 expression to nitrosative stress using bronchial fibroblasts isolated from the lung tissues. RESULTS: The expression of KLF5 was up-regulated in the small airways and pulmonary vessels of the COPD patients and it was mainly expressed in bronchial fibroblasts and cells of the pulmonary vessels. The extent of the KLF5 expression in the small airway of the COPD group had a significant correlation with the severity of the airflow limitation. Oxidative/nitrosative stress augmented the production of KLF5 in lung fibroblasts as well as the translocation of KLF5 into the nuclei. Silencing of KLF5 suppressed the stress-augmented differentiation into myofibroblasts, the release of collagens and metalloproteinases. Bronchial fibroblasts from the patients with COPD highly expressed KLF5 compared to those from the control subjects under basal condition and were more susceptible to the induction of KLF5 expression by nitrosative stress compared to those from the control subjects. CONCLUSION: We provide the first evidence that the expression of KLF5 is up-regulated in small airways and pulmonary vessels of patients with COPD and may be involved in the tissue remodeling of COPD

Effects of annealing time on structural and magnetic properties of L10-FePt nanoparticles synthesized by the SiO2-nanoreactor method

We investigated effects of annealing time on structural and magnetic properties of the L10-FePt nanoparticles synthesized by the SiO2-nanoreacter method. The magnetization and powder X-ray diffraction studies revealed that the annealing at 900 oC for 9 hr could convert all of the fcc-nanoparticles to the well-crystallized L10 structure with a large coercivity while keeping their particle size. Such monodisperse and highly crystalline L10-FePt nanoparticles are a promising material for the realization of ultra-high density recording.Comment: 9 pages, 2 figure

Aula laboratorial sobre microrganismos: a importância da experiência para a construção do conhecimento científico

Anais do II Seminário Seminário Estadual PIBID do Paraná: tecendo saberes / organizado por Dulcyene Maria Ribeiro e Catarina Costa Fernandes — Foz do Iguaçu: Unioeste; Unila, 2014Novos métodos para aperfeiçoar o aprendizado nas escolas de ensino fundamental e médio são continuamente buscados e sugeridos por diferentes autores. Porém, não é tarefa fácil modificar o cotidiano atual das escolas e inserir vertentes inovadoras de ensino. É nesse contexto que a utilização de aulas práticas pode abrir um viés para exploração da construção do conhecimento científico, passando pela observação dos fatos e a formulação de hipóteses. O laboratório, sendo um ambiente de múltiplas possibilidades, favorece um desenvolvimento mais pleno dos educandos, uma vez que a utilização de aulas experimentais contribui diretamente para que progridam de maneira a compreender e apropriar-se de conceitos científicos. Nessa perspectiva, buscou-se explorar o ensino de Ciências através de experimentos em laboratório, conduzidos pelos próprios educandos e mediados pelos professores, para a construção de uma aprendizagem significativa por experimentaçã

Prevalence of Hepatitis C Virus and its genotypes among a cohort of drug users in Kenya

Background: Prevalence of hepatitis C virus and that of its main genotypes varies between the worlds geographic regions. The risk factors for infection with HCV include blood transfusion, tattoing and injecting drug use. Objectives: To examine the prevalence of HCV and determine its main genotypes among a cohort of drug users in Kenya. Design: A laboratory based study. Setting: Hepatitis research laboratory in the Centre for Virus Research at the Kenya Medical Research Institute, Nairobi. Subjects: Three hundred and fourteen male and 19 female intravenous and non-intravenous drug users aged between 15-55 years. Results: Seventy four (22.2%) out of 333 samples tested positive for anti-HCV. Sixty nine out of the 74 serum samples were assayed for HCV RNA and 38 (55.5%) were positive. The RNA positive samples were further subjected to sequencing and 19 (73%) of the samples were classified as genotype la, while seven (27%) samples were classified as genotype 4. Genotypes 2, 3, 5 and 6 were not identified in this study. Conclusions: These results demonstrate a high HCV infection prevalence among this cohort of drug users (22.2 %) as compared to that of the general population, which is estimated to be 0.2- 0.9%. The study also confirms the presence of at least two major genotypes among Kenyan drug users (genotypes 1 and 4). East African Medical Journal Vol. 85 (7) 2008: pp. 318-32

Role of anion exchangers in Cl- and HCO3- secretion by the human airway epithelial cell line Calu-3

Despite the importance of airway surface liquid pH in the lung's defenses against infection, the mechanism of airway HCO3- secretion remains unclear. Our aim was to assess the contribution of apical and basolateral Cl-/HCO3- exchangers to Cl- and HCO3- transport in the Calu-3 cell line, derived from human airway submucosal glands. Changes in intracellular pH (pH(i)) were measured following substitution of Cl- with gluconate. Apical Cl- substitution led to an alkalinization in forskolin-stimulated cells, indicative of Cl-/HCO3- exchange. This was unaffected by the anion exchange inhibitor DIDS but inhibited by the CFTR blocker CFTRinh-172, suggesting that the HCO3- influx might occur via CFTR, rather than a solute carrier family 26 (SLC26) exchanger, as recently proposed. The anion selectivity of the recovery process more closely resembled that of CFTR than an SLC26 exchanger, and quantitative RT-PCR showed only low levels of SLC26 exchanger transcripts relative to CFTR and anion exchanger 2 (AE2). For pHi to rise to observed values (similar to 7.8) through HCO3- entry via CFTR, the apical membrane potential must reverse to at least + 20 mV following Cl- substitution; this was confirmed by perforated-patch recordings. Substitution of basolateral Cl- evoked a DIDS-sensitive alkalinization, attributed to Cl-/HCO3- exchange via AE2. This appeared to be abolished in forskolin-stimulated cells but was unmasked by blocking apical efflux of HCO3- via CFTR. We conclude that Calu-3 cells secrete HCO3- predominantly via CFTR, and, contrary to previous reports, the basolateral anion exchanger AE2 remains active during stimulation, providing an important pathway for basolateral Cl- uptake