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1.
Membranes (Basel) ; 11(10)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34677524

RESUMO

By a sol-gel method, a BiFeO3 (BFO) capacitor is fabricated and connected with the control thin film transistor (TFT). Compared with a control thin-film transistor, the proposed BFO TFT achieves 56% drive current enhancement and 7-28% subthreshold swing (SS) reduction. Moreover, the effect of the proposed BiFeO3 capacitor on IDS-VGS hysteresis in the BFO TFT is 0.1-0.2 V. Because dVint/dVGS > 1 is obtained at a wide range of VGS, it reveals that the incomplete dipole flipping is a major mechanism to obtain improved SS and a small hysteresis effect in the BFO TFT. Experimental results indicate that sol-gel BFO TFT is a potential candidate for digital application.

2.
BMC Pulm Med ; 21(1): 22, 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33435937

RESUMO

BACKGROUND: The interaction between the pulmonary function and cardiovascular mechanics is a crucial issue, particularly when treating patients with chronic obstructive pulmonary disease (COPD). Synchrogram index is a new parameter that can quantify this interaction and has the potential to apply in COPD patients. Our objective in this study was to characterize cardiorespiratory interactions in terms of cardiorespiratory coupling (CRC) using the synchrogram index of the heart rate and respiratory flow signals in patients with chronic obstructive pulmonary disease. METHODS: This is a cross-sectional and preliminary data from a prospective study, which examines 55 COPD patients. K-means clustering analysis was applied to cluster COPD patients based on the synchrogram index. Linear regression and multivariable regression analysis were used to determine the correlation between the synchrogram index and the exercise capacity assessed by a six-minute walking test (6MWT). RESULTS: The 55 COPD patients were separated into a synchronized group (median 0.89 (0.64-0.97), n = 43) and a desynchronized group (median 0.23 (0.02-0.51), n = 12) based on K-means clustering analysis. Synchrogram index was correlated significantly with six minutes walking distance (r = 0.42, p = 0.001) and distance saturation product (r = 0.41, p = 0.001) assessed by 6MWT, and still was an independent variable by multivariable regression analysis. CONCLUSION: This is the first result studying the heart-lung interaction in terms of cardiorespiratory coupling in COPD patients by the synchrogram index, and COPD patients are clustered into synchronized and desynchronized groups. Cardiorespiratory coupling is associated with exercise capacity in patients with COPD.


Assuntos
Tolerância ao Exercício/fisiologia , Frequência Cardíaca/fisiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Ventilação Pulmonar/fisiologia , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Teste de Caminhada
3.
Immun Inflamm Dis ; 9(1): 183-195, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33236850

RESUMO

BACKGROUND: Toll-like receptor (TLR)-7-associated rhinovirus (RV) activation is involved in the pathogenesis of asthma. Plasmacytoid dendritic cells (pDCs) are the main interferon-α-producing cells against viruses. OBJECTIVE: To determine whether asthmatic patients and control subjects differ in terms of interferon-α expression in pDCs under TLR-7 or RV stimulation. METHODS: pDCs were identified in BDCA-2+ and HLA-DR+ peripheral blood mononuclear cells. Interferon-α expression of pDCs was analyzed after TLR-7 stimulation with or without interleukin 4 (IL-4)/IL-13 pretreatment. Interferon-α expression was also analyzed after RV stimulation over periods of 24, 48, or 96 h with or without IL-4 pretreatment. RV detection and molecular typing were assayed from throat swabs. RESULTS: Following TLR-7 stimulation, the expression of intracellular interferon-α was higher in the pDCs of normal subjects than those of asthmatic patients; however, pretreatment with IL-4 was shown to reduce this effect. After 48- and 96-h RV stimulation, we observed a notable increase in the production of interferon-α of pDCs in normal subjects but not in asthmatic patients. Baseline interferon-α expression in pDCs and the incidence of asthma exacerbation to emergency was higher among the 13% of patients identified as rhinovirus+ than among their RV counterparts. CONCLUSION: Our study discovered the response to TLR-7 stimulation in pDCs was compromised and the sustainability of interferon-α expression to RV stimulation was reduced in pDCs of asthmatic patients, which provide further evidence of defective innate response and subspeciality to RV infection in asthma. The high exacerbation history founded in RV+ patients agrees with these findings. Further research is required for the modulatory effect of IL-4 on TLR-7 stimulated pDCs.


Assuntos
Asma , Leucócitos Mononucleares , Asma/tratamento farmacológico , Células Dendríticas , Humanos , Interferon-alfa , Receptor Toll-Like 9
4.
Front Med (Lausanne) ; 8: 783720, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34977086

RESUMO

Background: Traffic-related pollution is associated with the onset of asthma and the development of different phenotypes of asthma. Few studies have investigated the association between traffic proximity and late-onset of asthma (LOA) and early-onset asthma (EOA). This study was conducted to investigate the associations of LOA phenotypes with a function of the distance between residence and heavy traffic roads (HTRs). Methods: The study group consisted of 280 patients who were (LOA: 78.4%) recruited consecutively from a pay-for-performance asthma program to clarify the patient characteristics and proximity to HTRs within 1,000 m from their residences between EOA and LOA in three urban centers in Taiwan. The subsequent analysis focused on patients with LOA (n = 210) linking phenotypes and distance to HTRs. Results: Subjects with LOA tended to be older than those with EOA and had shorter asthma duration, poorer lung function, lower atopy, and less exposure to fumes or dust at home. Patients with LOA were more likely than those with EOA to live within 900 m of two or more HTRs (14.3 vs. 3.4%, p = 0.02). Among patients with LOA, minimum distance to an HTR was negatively associated with numbers of specific IgE as well as positively associated with the age of onset and body weight significantly. A higher proportion of patients with atopy (26.3 vs. 20.6%, p = 0.001. odds ratio [OR]: 2.82) and anxiety/depression (21.0 vs. 18.1%, p = 0.047. OR: 1.81) and a trend of lower proportion of patients with obese (5.7 vs. 12.4%, p = 0.075) were found to be living within 900 m from HTRs. Conclusions: Late-onset of asthma (LOA) tended to live in areas of higher HTR density compared to EOAs. Among patients with LOA living close to HTRs, the interaction between traffic-related pollution, allergy sensitization, and mood status were the factors associated with asthma onset early. Obesity may be the factor for later onset who live far from HTRs.

5.
Respir Res ; 18(1): 194, 2017 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-29162108

RESUMO

BACKGROUND: Patients with severe asthma have increased airway remodelling and elevated numbers of circulating fibrocytes with enhanced myofibroblastic differentiation capacity, despite being treated with high doses of corticosteroids, and long acting ß2-adrenergic receptor (AR) agonists (LABAs). We determined the effect of ß2-AR agonists, alone or in combination with corticosteroids, on fibrocyte function. METHODS: Non-adherent non-T cells from peripheral blood mononuclear cells isolated from healthy subjects and patients with non-severe or severe asthma were treated with the ß2-AR agonist, salmeterol, in the presence or absence of the corticosteroid dexamethasone. The number of fibrocytes (collagen I+/CD45+ cells) and differentiating fibrocytes (α-smooth muscle actin+ cells), and the expression of CC chemokine receptor 7 and of ß2-AR were determined using flow cytometry. The role of cyclic adenosine monophosphate (cAMP) was elucidated using the cAMP analogue 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP) and the phosphodiesterase type IV (PDE4) inhibitor, rolipram. RESULTS: Salmeterol reduced the proliferation, myofibroblastic differentiation and CCR7 expression of fibrocytes from healthy subjects and non-severe asthma patients. Fibrocytes from severe asthma patients had a lower baseline surface ß2-AR expression and were relatively insensitive to salmeterol but not to 8-Br-cAMP or rolipram. Dexamethasone increased ß2-AR expression and enhanced the inhibitory effect of salmeterol on severe asthma fibrocyte differentiation. CONCLUSIONS: Fibrocytes from patients with severe asthma are relatively insensitive to the inhibitory effects of salmeterol, an effect which is reversed by combination with corticosteroids.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Asma/fisiopatologia , Fibroblastos/efeitos dos fármacos , Leucócitos Mononucleares/efeitos dos fármacos , Xinafoato de Salmeterol/farmacologia , Índice de Gravidade de Doença , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Adulto , Asma/tratamento farmacológico , Asma/imunologia , Células Cultivadas , Relação Dose-Resposta a Droga , Feminino , Fibroblastos/fisiologia , Humanos , Leucócitos Mononucleares/fisiologia , Masculino , Pessoa de Meia-Idade , Xinafoato de Salmeterol/uso terapêutico , Resultado do Tratamento
6.
Medicine (Baltimore) ; 94(20): e878, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25997069

RESUMO

To determine plasma concentrations of angiopoietin (Ang)-1, Ang-2, Tie-2, and vascular endothelial growth factor (VEGF) in patients with sepsis-induced multiple organ dysfunction syndrome (MODS) and determine their association with mortality.The study prospectively recruited 96 consecutive patients with severe sepsis in a l intensive care unit of a tertiary hospital. Plasma Ang-1, Ang-2, Tie-2, and VEGF levels and MODS were determined in patients on days 1, 3, and 7 of sepsis. Univariate and Cox proportional hazards analysis were performed to develop a prognostic model.Days 1, 3, and 7 plasma Ang-1 concentrations were persistently decreased in MODS patients than in non-MODS patients (day1: 4.0 ±â€Š0.5 vs 8.0 ±â€Š0.5 ng/mL, P < 0.0001; day 3, 3.2 ±â€Š0.6 vs 7.3 ±â€Š0.5 ng/mL, P < 0.0001, day 7, 2.8 ±â€Š0.6 vs 10.4 ±â€Š0.7 ng/mL, P < 0.0001). In patients with resolved MODS on day 7 of sepsis, Ang-1 levels were increased from day 1 (4.7 ±â€Š0.6 ng/mL vs 9.1 ±â€Š1.4 ng/mL, n = 43, P = 0.004). Plasma Ang-1 levels were lower in nonsurvivors than in survivors on days 1 (4.0 ±â€Š0.5 vs 7.1 ±â€Š0.5 ng/mL, P < 0.0001), 3 (3.8 ±â€Š0.6 vs 7.1 ±â€Š0.5 ng/mL, P < 0.0001), and 7 (4.7 ±â€Š0.7 vs 11.0 ±â€Š0.8 ng/mL, P < 0.0001) of severe sepsis. In contrast, plasma Ang-2 levels were higher in nonsurvivors than in survivors only on day 1 (15.8 ±â€Š2.0 vs 9.5 ±â€Š1.2 ng/mL, P = 0.035). VEGF and Tie-2 levels were not associated with MODS and mortality. Ang-1 level less than the median value was the only independent predictor of mortality (hazard ratio, 2.57; 95% CI 1.12-5.90, P = 0.025).Persistently decreased Ang-1 levels are associated with MODS and subsequently, mortality in patients with sepsis.


Assuntos
Angiopoietina-1/sangue , Insuficiência de Múltiplos Órgãos/sangue , Sepse/sangue , APACHE , Idoso , Angiopoietina-2/sangue , Feminino , Humanos , Masculino , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/mortalidade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Receptor TIE-2/sangue , Sepse/complicações , Sepse/mortalidade , Índice de Gravidade de Doença , Fator A de Crescimento do Endotélio Vascular/sangue
7.
Am J Respir Crit Care Med ; 191(1): 54-62, 2015 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-25411910

RESUMO

RATIONALE: Patients with severe asthma (SA) are less responsive to the beneficial effects of corticosteroid (CS) therapy, and relative CS insensitivity has been shown in airway smooth muscle cells (ASMC) from patients with SA. OBJECTIVES: We investigated whether there was a defect in the actions of the glucocorticoid receptor (GR) underlying the ability of CS to suppress the inflammatory response in ASMC of patients with SA. ASMC from healthy subjects (n = 10) and subjects with severe (n = 8) and nonsevere asthma (N-SA; n = 8) were cultured from endobronchial biopsies. MEASUREMENTS AND MAIN RESULTS: GR expression in ASMC from SA and N-SA was reduced compared with that from healthy subjects by 49% (P < 0.01). Although baseline levels of nuclear GR were similar, GR nuclear translocation induced by dexamethasone (10(-7) M) in SA was 60% of that measured in either healthy subjects or subjects with N-SA. Tumor necrosis factor (TNF)-α induced greater nuclear factor (NF)-κB (p65) mRNA expression in ASMC from subjects with SA (5.6- vs. 2.0-fold; P < 0.01), whereas baseline and TNF-α-induced nuclear translocation and dexamethasone-mediated suppression of p65 expression were similar between groups. Dexamethasone, although not modulating TNF-α-induced p65 nuclear translocation, attenuated p65 recruitment to the CCL11 promoter in the healthy and N-SA groups, but this suppressive effect was impaired in subjects with SA. CONCLUSIONS: Decreased GR expression with impaired nuclear translocation in ASMC, associated with reduced dexamethasone-mediated attenuation of p65 recruitment to NF-κB-dependent gene promoters, may underlie CS insensitivity of severe asthma.


Assuntos
Corticosteroides/uso terapêutico , Asma/fisiopatologia , Miócitos de Músculo Liso/efeitos dos fármacos , Receptores de Glucocorticoides/efeitos dos fármacos , Sistema Respiratório/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Corticosteroides/imunologia , Corticosteroides/farmacologia , Adulto , Asma/tratamento farmacológico , Asma/imunologia , Resistência a Medicamentos , Feminino , Humanos , Masculino , Miócitos de Músculo Liso/imunologia , Miócitos de Músculo Liso/metabolismo , Receptores de Glucocorticoides/imunologia , Receptores de Glucocorticoides/metabolismo , Sistema Respiratório/imunologia , Sistema Respiratório/fisiopatologia , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/farmacologia
8.
PLoS One ; 9(1): e86316, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24466020

RESUMO

BACKGROUND: Isoniazid (INH) resistance is now the most common type of tuberculosis (TB) infection resistance worldwide. The aim of this study was to evaluate the clinical characteristics and treatment outcomes of patients with low- and high-concentration INH-monoresistant TB. METHODS: One hundred and thirty-four patients with culture-confirmed INH-monoresistant TB during 2006 January to 2007 December were retrospectively enrolled. INH resistance was classified as either low-concentration or high-concentration resistance according to the critical concentrations of 0.2 µg/mL or 1 µg/mL of INH, respectively. The patients' clinical outcomes, treatment regimens, and treatment duration were analyzed. RESULTS: The treatment success rates between low- and high-concentration INH-resistant TB were similar (81.8% vs. 86.7%). The treatment regimens and treatment duration were similar between both groups. Only a minor percentage of the patients in both groups received 6-month treatment regimens (low vs. high concentration resistance, 9.1% vs. 13.3%; respectively, p = 0.447) The most common reason for treatment duration longer than 6 months was pyrazinamide given for less than 6 months, followed by a delay in clinical response to treatment. Multivariable analysis showed that prior tuberculosis treatment (Odds ratio, 2.82, 95% C.I., 1.02-7.77, p = 0.045) was the only independent risk factor for unsuccessful treatment outcome. CONCLUSION: Different levels of INH resistance did not affect the treatment outcomes of patients with INH-monoresistant tuberculosis. Prolonged Rifampin-containing regimens may achieve those good outcomes in patients with low- and high-concentration INH-monoresistant TB.


Assuntos
Antituberculosos/uso terapêutico , Farmacorresistência Bacteriana , Isoniazida/uso terapêutico , Tuberculose/tratamento farmacológico , Antituberculosos/administração & dosagem , Feminino , Humanos , Isoniazida/administração & dosagem , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Falha de Tratamento , Resultado do Tratamento , Tuberculose/diagnóstico , Tuberculose/mortalidade
9.
Cough ; 9(1): 24, 2013 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-24188336

RESUMO

BACKGROUND: Obstructive sleep apnoea (OSA) has recently been identified as a possible aetiology for chronic cough. The aim of this study was to compare the incidence of chronic cough between patients with and without OSA and the impact of continuous positive airway pressure (CPAP) treatment in resolving chronic cough. METHODS: Patients referred to the sleep laboratory from January 2012 to June 2012 were retrospectively enrolled. Clinical data, treatment course and resolution of chronic cough were analysed. Specifically, gastro-oesophageal reflux (GERD), upper airway cough syndrome, asthma, apnoea-hypopnoea index and the impact of CPAP treatment on chronic cough were assessed. RESULTS: A total of 131 patients were reviewed. The incidence of chronic cough in the OSA group was significantly higher than the non-OSA group (39/99 (39.4%) vs. 4/32 (12.5%), p = 0.005). Both GERD and apnoea-hypopnoea index were significantly associated with chronic cough in univariate analysis. After multivariate logistic regression, GERD was the only independent factor for chronic cough. Moreover, the resolution of chronic cough was more significant in the OSA patients with CPAP treatment compared with those not receiving CPAP treatment (12/18 (66.7%) vs. 2/21 (9.5%), p = 0.010). CONCLUSION: The incidence of chronic cough was significantly higher in the OSA patients. In addition, CPAP treatment significantly improved chronic cough. Therefore, OSA may be a contributory factor to chronic cough.

10.
PLoS One ; 8(6): e66265, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23776649

RESUMO

OBJECTIVES: Bronchiectasis is characterized by an irreversible dilatation of bronchi and is associated with lung fibrosis. MMP-1 polymorphism may alter its transcriptional activity, and differentially modulate bronchial destruction and lung fibrosis. DESIGN: To investigate the association of MMP-1 polymorphisms with disease severity in non-cystic fibrosis (CF) bronchiectasis patients, 51 normal subjects and 113 patients with bronchiectasis were studied. The associations between MMP-1 polymorphisms, lung function, and disease severity evaluated by high resolution computed tomography (HRCT) were analyzed. RESULTS: The frequency of MMP-1(-1607G) allele was significantly higher in patients with bronchiectasis than normal subjects (70.8% vs 45.1%, p<0.01). Forced expiratory volume in 1 second (FEV1) was decreased in bronchiectasis patients with 1G/1G (1.2±0.1 L, n = 14) and 1G/2G (1.3±0.1 L, n = 66) genotypes compared to the 2G/2G genotype (1.7±0.1 L, n = 33, p<0.01). Six minute walking distance was decreased in bronchiectasis patients with 1G/1G and 1G/2G compared to that of 2G/2G genotype. Disease severity evaluated by HRCT score significantly increased in bronchiectasis patients with 1G/1G and 1G/2G genotypes compared to that of 2G/2G genotype. Bronchiectasis patients with at least one MMP-1 (-1607G) allele showed increased tendency for hospitalization. Serum levels of pro-MMP-1, active MMP-1 and TGF-ß1 were significantly increased in patients with bronchiectasis with 1G/1G and 1G/2G genotype compared with 2G/2G genotype or normal subjects. Under IL-1ß stimulation, peripheral blood monocytes from subjects with 1G/2G or 1G/1G genotype secreted higher levels of TGF-ß1compared to subjects with 2G/2G genotype. CONCLUSION: This is the first report to address the influence of MMP-1 polymorphisms on lung function and airway destruction in non-CF bronchiectasis patients. Bronchiectasis patients with MMP-1(-1607G) polymorphism may be more vulnerable to permanent lung fibrosis or airway destruction due to the enhanced MMP-1 and TGF-ß1 activity. Upregulated MMP-1 activity results in proteolytic destruction of matrix, and leads to subsequent fibrosis.


Assuntos
Bronquiectasia/genética , Metaloproteinase 1 da Matriz/genética , Polimorfismo Genético/genética , Alelos , Feminino , Predisposição Genética para Doença/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Taiwan
11.
J Allergy Clin Immunol ; 130(4): 877-85.e5, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22947346

RESUMO

BACKGROUND: Patients with severe asthma are less responsive to the beneficial effects of corticosteroid therapy. OBJECTIVE: We investigated whether corticosteroid insensitivity was present in airway smooth muscle cells (ASMCs) of patients with severe asthma. METHODS: ASMCs cultured from bronchial biopsy specimens of nonasthmatic control subjects (n = 12) and patients with nonsevere (n = 10) or severe (n = 10) asthma were compared for the effect of dexamethasone on suppression of TNF-α- and IFN-γ-induced CCL11 (eotaxin), CXCL8 (IL-8), and CX3CL1 (fractalkine) expression. The mechanisms of corticosteroid insensitivity are also determined. RESULTS: CCL11 release was higher in ASMCs of patients with nonsevere but not severe asthma and nonasthmatic control subjects; CXCL8 and CX3CL1 release were similar in all groups. In patients with severe asthma, dexamethasone caused less suppression of CCL11 and CXCL8 release induced by TNF-α. Dexamethasone potentiated TNF-α- and IFN-γ-induced CX3CL1 release equally in all 3 groups. TNF-α-induced phosphorylated p38 mitogen-activated protein kinase levels were increased in ASMCs from patients with severe asthma compared with those from patients with nonsevere asthma and nonasthmatic subjects, whereas TNF-α-induced phosphorylated c-Jun N-terminal kinase and phosphorylated extracellular signal-related kinase levels were increased in all asthmatic groups. A p38 inhibitor increased the inhibitory effect of dexamethasone. CONCLUSIONS: ASMCs of patients with severe asthma are corticosteroid insensitive; this might be secondary to heightened p38 mitogen-activated protein kinase levels.


Assuntos
Asma/tratamento farmacológico , Brônquios/efeitos dos fármacos , Quimiocinas/genética , Dexametasona/farmacologia , Miócitos de Músculo Liso/efeitos dos fármacos , Adulto , Asma/imunologia , Brônquios/imunologia , Células Cultivadas , Quimiocinas/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Miócitos de Músculo Liso/imunologia , Miócitos de Músculo Liso/metabolismo , Regiões Promotoras Genéticas , Fator de Transcrição RelA/fisiologia
12.
Am J Respir Crit Care Med ; 184(8): 894-903, 2011 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-21799075

RESUMO

RATIONALE: Aberrant airway smooth muscle cell (ASMC) function and overexpression of transforming growth factor (TGF)-ß, which modulates ASMC proliferative and inflammatory function and induces oxidant release, are features of asthma. Nuclear factor E2-related factor 2 (Nrf2) activates antioxidant genes conferring protection against oxidative stress. OBJECTIVES: To determine the role of Nrf2 in ASMCs and its modulation by TGF-ß, and compare Nrf2 activity in ASMCs from subjects with severe and nonsevere asthma and healthy subjects. METHODS: ASMCs were cultured from airways of subjects without asthma, and from airway biopsies from patients with severe and nonsevere asthma. We studied Nrf2 activation on antioxidant gene expression and proliferation, the effect of TGF-ß on Nrf2 transcriptional activity, and the impact of Nrf2 activation on TGF-ß­mediated proliferation and IL-6 release. Nrf2­antioxidant response elements binding and Nrf2-dependent antioxidant gene expression was determined in asthmatic ASMCs. MEASUREMENTS AND MAIN RESULTS: Activation of Nrf2 led to up-regulation of the antioxidant genes heme oxygenase (HO)-1, NAD(P)H:quinone oxidoreductase, and manganese superoxide dismutase, and a reduction in proliferation. TGF-ß reduced Nrf2-mediated antioxidant gene transcription through induction of activating transcription factor-3 expression. Nrf2 activation attenuated TGF-ß­mediated reduction in HO-1,ASMC proliferation, and IL-6 release. Nrf2­antioxidant response elements binding was reduced in ASMCs from patients with severe asthma compared with ASMCs from patients with nonsevere asthma and normal subjects. HO-1 expression was reduced in ASMCs from patients with both nonsevere and severe asthma compared with healthy subjects. CONCLUSIONS: Nrf2 regulates antioxidant responses and proliferation in ASMCs and is inactivated by TGF-ß. Nrf2 reduction may underlie compromised antioxidant protection and aberrant ASM function in asthma.


Assuntos
Asma/metabolismo , Proliferação de Células , Músculo Liso/metabolismo , Fator de Transcrição NF-E2/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Adenoviridae/genética , Antioxidantes/metabolismo , Proliferação de Células/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica , Vetores Genéticos , Humanos , Isotiocianatos , Músculo Liso/citologia , Fator de Transcrição NF-E2/antagonistas & inibidores , RNA Interferente Pequeno , Sulfóxidos , Tiocianatos/farmacologia , Transfecção , Fator de Crescimento Transformador beta/farmacologia
13.
J Asthma ; 46(1): 41-6, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19191136

RESUMO

BACKGROUND AND OBJECTIVE: Overexpression of matrix metalloproteinase (MMP)-1 has been demonstrated in asthma, and MMP polymorphisms are known to enhance disease susceptibility. We investigated whether MMP-1 polymorphism is associated with persistent airway obstruction in asthma in the Taiwanese population. METHODS: A total of 131 unrelated Taiwanese subjects were enrolled, age-matched, and divided as follows: (1) those who had asthma with persistent airway obstruction with forced expiratory volume in 1 second (FEV(1)) and FEV(1)/forced vital capacity (FVC) values less than 75% predicted (n = 41); (2) those with asthma without airway obstruction with FEV(1) and FEV(1)/FVC values > or = 75% predicted (n = 47); and (3) normal control subjects (n = 43). All were genotyped for the 1G/2G polymorphism of MMP-1 promoter (-1607 bp). RESULTS: 1G genotypes of MMP-1 containing at least one 1G allele were found in asthmatic patients with persistent airway obstruction (OR = 3.696, 95% CI: 1.489-9.173, p = 0.027), but not in asthmatic patients without airway obstruction (OR = 2.065, 95% CI: 0.890-4.790, p = 0.091) when compared with homozygous 2G (2G/2G). The heterozygous 1G genotype (1G/2G) was more associated with persistent airway obstruction than homozygous 2G (2G/2G) (OR: 4.727, 95% CI: 1.759-12.703, p = 0.012). The adjusted risk estimate of 1G genotypes for asthmatics with persistent airway obstruction was 4.416 (95% CI: 1.651-11.812, p = 0.003). CONCLUSION: 1G genotypes of MMP-1 polymorphism are associated with asthma with persistent airway obstruction, and the heterozygous 1G genotype (1G/2G) poses the most susceptibility to persistent airway obstruction in asthma.


Assuntos
Obstrução das Vias Respiratórias/genética , Asma/genética , Metaloproteinase 1 da Matriz/genética , Polimorfismo Genético , Obstrução das Vias Respiratórias/etnologia , Obstrução das Vias Respiratórias/fisiopatologia , Asma/etnologia , Asma/fisiopatologia , Feminino , Volume Expiratório Forçado/fisiologia , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas/genética , Taiwan , Capacidade Vital/fisiologia
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