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2.
PLoS One ; 15(9): e0239866, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32986786

RESUMO

INTRODUCTION: First study of social inequalities in tobacco-attributable mortality (TAM) in Spain considering the joint influence of sex, age, and education (intersectional perspective). METHODS: Data on all deaths due to cancer, cardiometabolic and respiratory diseases among people aged ≥35 years in 2016 were obtained from the Spanish Statistical Office. TAM was calculated based on sex-, age- and education-specific smoking prevalence, and on sex-, age- and disease-specific relative risks of death for former and current smokers vs lifetime non-smokers. As inequality measures, the relative index of inequality (RII) and the slope index of inequality (SII) were calculated using Poisson regression. The RII is interpreted as the relative risk of mortality between the lowest and the highest educational level, and the SII as the absolute difference in mortality. RESULTS: The crude TAM rate was 55 and 334 per 100,000 in women and men, respectively. Half of these deaths occurred among people with the lowest educational level (27% of the population). The RII for total mortality was 0.39 (95%CI: 0.35-0.42) in women and 1.61 (95%CI: 1.55-1.67) in men. The SII was -41 and 111 deaths per 100,000, respectively. Less-educated women aged <55 years and men (all ages) showed an increased mortality risk; nonetheless, less educated women aged ≥55 had a reduced risk. CONCLUSIONS: TAM is inversely associated with educational level in men and younger women, and directly associated with education in older women. This could be explained by different smoking patterns. Appropriate tobacco control policies should aim to reduce social inequalities in TAM.


Assuntos
Escolaridade , Fumar/mortalidade , Classe Social , Tabaco/efeitos adversos , Adulto , Fatores Etários , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Prevalência , Fatores de Risco , Fatores Sexuais , Fumar/epidemiologia , Espanha/epidemiologia
3.
N Z Med J ; 133(1520): 99-103, 2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32994598

RESUMO

In this viewpoint we briefly review the evidence for smoke-free car legislation. We find that this legislation has been consistently associated with reduced secondhand exposure in cars with children/youth in all nine jurisdictions studied. Despite this, there are various aspects of this intervention that warrant further study-especially determining its impact on reducing tobacco-related ethnic inequalities. So we argue that the New Zealand Ministry of Health should invest in a thorough evaluation of this important upcoming public health intervention. This could both help the country in further refining the design of the law (if necessary) and would also be a valuable contribution to advancing the knowledge base for international tobacco control.


Assuntos
Automóveis/legislação & jurisprudência , Exposição Ambiental/prevenção & controle , Política Antifumo/legislação & jurisprudência , Poluição por Fumaça de Tabaco/legislação & jurisprudência , Adolescente , Automóveis/normas , Criança , Exposição Ambiental/efeitos adversos , Grupos Étnicos/estatística & dados numéricos , Humanos , Nova Zelândia/epidemiologia , Saúde Pública/economia , Saúde Pública/legislação & jurisprudência , Fatores Socioeconômicos , Tabaco/efeitos adversos , Poluição por Fumaça de Tabaco/efeitos adversos , Poluição por Fumaça de Tabaco/prevenção & controle
4.
Am J Physiol Lung Cell Mol Physiol ; 319(4): L742-L751, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32783621

RESUMO

Prenatal smoke exposure is a risk factor for impaired lung development in children. Recent studies have indicated that amphiregulin (AREG), which is a ligand of the epidermal growth factor receptor (EGFR), has a regulatory role in airway epithelial cell differentiation. In this study, we investigated the effect of prenatal smoke exposure on lung epithelial cell differentiation and linked this with AREG-EGFR signaling in 1-day-old mouse offspring. Bronchial and alveolar epithelial cell differentiations were assessed by immunohistochemistry. Areg, epidermal growth factor (Egf), and mRNA expressions of specific markers for bronchial and alveolar epithelial cells were assessed by RT-qPCR. The results in neonatal lungs were validated in an AREG-treated three-dimensional mouse lung organoid model. We found that prenatal smoke exposure reduced the number of ciliated cells and the expression of the cilia-related transcription factor Foxj1, whereas it resulted in higher expression of mucus-related transcription factors Spdef and Foxm1 in the lung. Moreover, prenatally smoke-exposed offspring had higher numbers of alveolar epithelial type II cells (AECII) and lower expression of the AECI-related Pdpn and Gramd2 markers. This was accompanied by higher expression of Areg and lower expression of Egf in prenatally smoke-exposed offspring. In bronchial organoids, AREG treatment resulted in fewer ciliated cells and more basal cells when compared with non-treated bronchiolar organoids. In alveolar organoids, AREG treatment led to more AECII cells than non-treated AECII cells. Taken together, the observed impaired bronchial and alveolar cell development in prenatally smoke-exposed neonatal offspring may be induced by increased AREG-EGFR signaling.


Assuntos
Anfirregulina/metabolismo , Anfirregulina/farmacologia , Células Epiteliais/efeitos dos fármacos , Receptores ErbB/metabolismo , Fumaça/efeitos adversos , Animais , Animais Recém-Nascidos , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Fator de Crescimento Epidérmico/metabolismo , Células Epiteliais/metabolismo , Camundongos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Tabaco/efeitos adversos
6.
Am J Physiol Lung Cell Mol Physiol ; 319(2): L391-L402, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32640840

RESUMO

Genetic predispositions and environmental exposures are regarded as the main predictors of respiratory disease development. Although the impact of dietary essential nutrient deficiencies on cardiovascular disease, obesity, and type II diabetes has been widely studied, it remains poorly explored in chronic respiratory diseases. Dietary choline and methionine deficiencies are common in the population, and their impact on pulmonary homeostasis is currently unknown. Mice were fed choline- and/or methionine-deficient diets while being exposed to room-air or cigarette smoke for up to 4 wk. Lung functions were assessed using the FlexiVent. Pulmonary transcriptional activity was assessed using gene expression microarrays and quantitative PCR. Immune cells, cytokines, and phosphatidylcholine were quantified in the bronchoalveolar lavage. In this study, we found that short-term dietary choline and/or methionine deficiencies significantly affect lung function in mice in a reversible manner. It also reduced transcriptional levels of collagens and elastin as well as pulmonary surfactant phosphatidylcholine levels. We also found that dietary choline and/or methionine deficiencies markedly interfered with the pulmonary response to cigarette smoke exposure, modulating lung function and dampening inflammation. These findings clearly show that dietary choline and/or methionine deficiencies can have dramatic pathophysiological effects on the lungs and can also affect the pathobiology of cigarette smoke-induced pulmonary alterations. Expanding our knowledge in the field of "nutri-respiratory research" may reveal a crucial role for essential nutrients in pulmonary health and disease, which may prove to be as relevant as genetic predispositions and environmental exposures.


Assuntos
Colina/farmacologia , Homeostase/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Metionina/farmacologia , Fumaça/efeitos adversos , Tabaco/efeitos adversos , Animais , Líquido da Lavagem Broncoalveolar , Citocinas/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Dieta , Feminino , Inflamação/metabolismo , Pulmão/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Surfactantes Pulmonares/metabolismo , Fumar/efeitos adversos
7.
Tumour Biol ; 42(7): 1010428320938494, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32628088

RESUMO

Radiotherapy and cisplatin lead to cell killing in head and neck squamous cell carcinoma patients, but adverse events and response to treatment are not the same in patients with similar clinicopathological aspects. The aim of this prospective study was to evaluate the roles of TP53 c.215G > C, FAS c.-671A > G, FAS c.-1378G > A, FASL c.-844 C > T, CASP3 c.-1191A > G, and CASP3 c.-182-247G > T single nucleotide variants in toxicity, response rate, and survival of cisplatin chemoradiation-treated head and neck squamous cell carcinoma patients. Genomic DNA was analyzed by polymerase chain reaction for genotyping. Differences between groups of patients were analyzed by chi-square test or Fisher's exact test, multiple logistic regression analysis, and Cox hazards model. One hundred nine patients with head and neck squamous cell carcinoma were enrolled in study. All patients were smokers and/or alcoholics. Patients with FAS c.-671GG genotype, FAS c.-671AG or GG genotype, and FASL c.-844CC genotype had 5.52 (95% confidence interval (CI): 1.42-21.43), 4.03 (95% CI: 1.51-10.79), and 5.77 (95% CI: 1.23-27.04) more chances of presenting chemoradiation-related anemia of grades 2-4, lymphopenia of grade 3 or 4, and ototoxicity of all grades, respectively, than those with the remaining genotypes. FAS c.-671GG genotype was also seen as an independent predictor of shorter event-free survival (hazard ratio (HR): 2.05; P = 0.007) and overall survival (HR: 1.83; P = 0.02) in our head and neck squamous cell carcinoma patients. These findings present, for the first time, preliminary evidence that inherited abnormalities in apoptosis pathway, related to FAS c.-671A > G and FASL c.-844 C > T single nucleotide variants, can alter toxicity and survival of tobacco- and alcohol-related head and neck squamous cell carcinoma patients homogeneously treated with cisplatin chemoradiation.


Assuntos
Proteína Ligante Fas/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Receptor fas/genética , Adulto , Idoso , Álcoois/efeitos adversos , Quimiorradioterapia/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/genética , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/induzido quimicamente , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Tabaco/efeitos adversos , Proteína Supressora de Tumor p53/genética
8.
BMC Public Health ; 20(1): 888, 2020 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-32513150

RESUMO

BACKGROUND: Tobacco exposure (TE) is the major contributor for CVD mortality, but few published studies on CVD mortality attributable to TE have analyzed the potential reasons underlying long-term trends in China. Our studysought to find the potential reasons and compared CVD mortality attributable to TE in China, Japan, the United States of America (USA), and the world between 1990 and 2017. METHODS: The mortality data in China, Japan, the USA, and the world were obtained from Global Burden of Disease Study 2017(GBD 2017). Joinpoint regression was used to assess the trend magnitude and directions over time for CVD mortality, while the age-period-cohort method was used to analyzethe temporal trends of CVD mortality according to age, period, and cohort. RESULTS: A significant downward trend was found in the age-standardised mortality rate (ASMR) of CVD attributable to smoking in four regions. China had the smallest decline and the Chinese ASMR became the highest in 2017. All the annual net drifts in the four regions were negative and the local drifts were below zero. The longitudinal age curves of CVD mortality attributable to smoking increased in four regions,with China having the largest increase. The period or cohort RRs indicated a decline, and China had the smallest decline. The researchers further analyzed the IHD and stroke trends, finding that the morality and period or cohort RR of IHD in China was always at a high level. CONCLUSIONS: CVD mortality attributable to TE declined in four regions, and was highest in China. The proportion of IHD mortality attributable to TE was similar to stroke, which significantly changed the traditional cognition of CVD composition, but the control measure was not sufficient for IHD in China.


Assuntos
Doenças Cardiovasculares/mortalidade , Fumar/efeitos adversos , Tabaco/efeitos adversos , Adulto , Distribuição por Idade , Idoso , Causas de Morte/tendências , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Internacionalidade , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Fatores Socioeconômicos , Estados Unidos/epidemiologia
9.
PLoS One ; 15(6): e0234606, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32569331

RESUMO

Skeletal muscle dysfunction is a common complication and an important prognostic factor in patients with chronic obstructive pulmonary disease (COPD). It is associated with intrinsic muscular abnormalities of the lower extremities, but it is not known whether there is an easy way to predict its presence. Using a mouse model of chronic cigarette smoke exposure, we tested the hypothesis that magnetic resonance spectroscopy allows us to detect muscle bioenergetic deficit in early stages of lung disease. We employed this technique to evaluate the synthesis rate of adenosine triphosphate (ATP) and characterize concomitant mitochondrial dynamics patterns in the gastrocnemius muscle of emphysematous mice. The fibers type composition and citrate synthase (CtS) and cytochrome c oxidase subunit IV (COX4) enzymatic activities were evaluated. We found that the rate of ATP synthesis was reduced in the distal skeletal muscle of mice exposed to cigarette smoke. Emphysematous mice showed a significant reduction in body weight gain, in the cross-sectional area of the total fiber and in the COX4 to CtS activity ratio, due to a significant increase in CtS activity of the gastrocnemius muscle. Taken together, these data support the hypothesis that in the early stage of lung disease, we can detect a decrease in ATP synthesis in skeletal muscle, partly caused by high oxidative mitochondrial enzyme activity. These findings may be relevant to predict the presence of skeletal bioenergetic deficit in the early stage of lung disease besides placing the mitochondria as a potential therapeutic target for the treatment of COPD comorbidities.


Assuntos
Metabolismo Energético , Músculo Esquelético/fisiopatologia , Fumaça/efeitos adversos , Trifosfato de Adenosina/biossíntese , Trifosfato de Adenosina/deficiência , Animais , Pneumopatias/diagnóstico , Espectroscopia de Ressonância Magnética/métodos , Camundongos , Mitocôndrias/metabolismo , Músculo Esquelético/metabolismo , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Tabaco/efeitos adversos
10.
J Environ Pathol Toxicol Oncol ; 39(1): 23-37, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32479010

RESUMO

Diabetes and tobacco use are two of the largest public health challenges of our time. We aim to investigate the association between the two by comparing biochemical profiles of diabetic tobacco users (TUs) and tobacco nonus-ers (TNUs) to provide insight into the joint effect of tobacco and diabetes on body systems. This case-controlled study included 265 subjects, aged 18-60 yr, from the suburban population of Delhi, India. With the help of a questionnaire, participants are interviewed regarding their history of tobacco use. Results show association of tobacco use with elevated body-mass index, blood glucose levels, and insulin resistance in otherwise healthy and diabetic TUs. Even without previous history of coronary heart disease, total cholesterol and triglycerides are significantly further increased in TUs rather than in TNUs, indicative of initiation of lipid metabolism disorders. Tobacco use is also seen as a cause of oxidant/antioxidant imbalance in the body. Low serum albumin coupled with increased markers of inflammation and globulin levels is an indicator of generalized inflammation caused by tobacco's toxic effects. Creatinine levels are significantly higher in diabetic TUs, posing a threat to nephropathy progression. Evidence sufficiently infers that tobacco activates multiple biological pathways, through which the risk of metabolic disease increases. These factors may work in conjunction to increase risk of certain microvascular and macrovascular complications.


Assuntos
Glicemia/análise , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/fisiopatologia , Resistência à Insulina , Tabaco/efeitos adversos , Adulto , Glicemia/efeitos dos fármacos , Estudos de Casos e Controles , Cidades , Diabetes Mellitus Tipo 2/sangue , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
11.
PLoS One ; 15(5): e0232102, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32437367

RESUMO

Cigarette smoke exposure is a risk factor for many pulmonary diseases, including Chronic Obstructive Pulmonary Disease (COPD). Cigarette smokers are more prone to respiratory infections with more severe symptoms. In those with COPD, viral infections can lead to acute exacerbations resulting in lung function decline and death. Epithelial cells in the lung are the first line of defense against inhaled insults such as tobacco smoke and are the target for many respiratory pathogens. Endocytosis is an essential cell function involved in nutrient uptake, cell signaling, and sensing of the extracellular environment, yet, the effect of cigarette smoke on epithelial cell endocytosis is not known. Here, we report for the first time that cigarette smoke alters the function of several important endocytic pathways in primary human small airway epithelial cells. Cigarette smoke exposure impairs clathrin-mediated endocytosis and fluid phase macropinocytosis while increasing caveolin mediated endocytosis. We also show that influenza virus uptake is enhanced by cigarette smoke exposure. These results support the concept that cigarette smoke-induced dysregulation of endocytosis contributes to lung infection in smokers. Targeting endocytosis pathways to restore normal epithelial cell function may be a new therapeutic approach to reduce respiratory infections in current and former smokers.


Assuntos
Caveolinas/metabolismo , Células Epiteliais/efeitos dos fármacos , Infecções/patologia , Pulmão/citologia , Fumaça/efeitos adversos , Tabaco/química , Regulação para Cima/efeitos dos fármacos , Suscetibilidade a Doenças , Células Epiteliais/metabolismo , Células Epiteliais/virologia , Humanos , Infecções/induzido quimicamente , Infecções/virologia , Tabaco/efeitos adversos
12.
Toxicol Appl Pharmacol ; 398: 115026, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32353386

RESUMO

The presence of flavors is one of the commonly cited reasons for use of e-cigarettes by youth; however, the potential harms from inhaling these chemicals and byproducts have not been extensively studied. One mechanism of interest is DNA adduct formation, which may lead to carcinogenesis. We identified two chemical classes of flavors found in tobacco products and byproducts, alkenylbenzenes and aldehydes, documented to form DNA adducts. Using in silico toxicology approaches, we identified structural analogs to these chemicals without DNA adduct information. We conducted a structural similarity analysis and also generated in silico model predictions of these chemicals for genotoxicity, mutagenicity, carcinogenicity, and skin sensitization. The empirical and in silico data were compared, and we identified strengths and limitations of these models. Good concordance (80-100%) was observed between DNA adduct formation and models predicting mammalian mutagenicity (mouse lymphoma sassy L5178Y) and skin sensitization for both chemical classes. On the other hand, different prediction profiles were observed for the two chemical classes for the modeled endpoints, unscheduled DNA synthesis and bacterial mutagenicity. These results are likely due to the different mode of action between the two chemical classes, as aldehydes are direct acting agents, while alkenylbenzenes require bioactivation to form electrophilic intermediates, which form DNA adducts. The results of this study suggest that an in silico prediction for the mouse lymphoma assay L5178Y, may serve as a surrogate endpoint to help predict DNA adduct formation for chemicals found in tobacco products such as flavors and byproducts.


Assuntos
Adutos de DNA/efeitos dos fármacos , Aromatizantes/farmacologia , Produtos do Tabaco/efeitos adversos , Tabaco/efeitos adversos , Animais , Simulação por Computador , Sistemas Eletrônicos de Liberação de Nicotina , Camundongos , Mutagênese/efeitos dos fármacos , Mutagênicos/efeitos adversos
13.
PLoS One ; 15(4): e0231095, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32348306

RESUMO

INTRODUCTION: Varenicline tartrate is superior for smoking cessation to other tobacco cessation therapies by 52 weeks, in the outpatient setting. We aimed to evaluate the long-term (104 week) efficacy following a standard course of inpatient-initiated varenicline tartrate plus Quitline-counselling compared to Quitline-counselling alone. METHODS: Adult patients (n = 392, 20-75 years) admitted with a smoking-related illnesses to one of three hospitals, were randomised to receive either 12-weeks of varenicline tartrate (titrated from 0.5mg daily to 1mg twice-daily) plus Quitline-counselling, (n = 196) or Quitline-counselling alone, (n = 196), with continuous abstinence from smoking assessed at 104 weeks. RESULTS: A total of 1959 potential participants were screened for eligibility between August 2008 and December 2011. The proportion of participants who remained continuously abstinent (intention-to-treat) at 104 weeks were significantly greater in the varenicline tartrate plus counselling arm (29.2% n = 56) compared to counselling alone (18.8% n = 36; p = 0.02; odds ratio 1.78; 95%CI 1.10 to 2.86, p = 0.02). Twenty-two deaths occurred during the 104 week study (n = 10 for varenicline tartrate plus counselling and n = 12 for Quitline-counselling alone). All of these participants had known or developed underlying co-morbidities. CONCLUSIONS: This is the first study to examine the efficacy and safety of varenicline tartrate over 104 weeks within any setting. Varenicline tartrate plus Quitline-counselling was found to be an effective opportunistic treatment when initiated for inpatient smokers who had been admitted with tobacco-related disease.


Assuntos
Abandono do Hábito de Fumar/métodos , Fumar/tratamento farmacológico , Fumar Tabaco/tratamento farmacológico , Vareniclina/administração & dosagem , Adulto , Idoso , Feminino , Humanos , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Agonistas Nicotínicos/administração & dosagem , Pacientes Ambulatoriais , Fumar/epidemiologia , Fumar/psicologia , Tabaco/efeitos adversos , Fumar Tabaco/epidemiologia , Fumar Tabaco/psicologia , Resultado do Tratamento
15.
PLoS One ; 15(4): e0230932, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32251484

RESUMO

RATIONALE: Chronic smoke exposure is associated with weight loss in patients with Chronic Obstructive Pulmonary Disease (COPD). However, the biological contribution of chronic smoking and sex on the cecal microbiome has not been previously investigated. METHODS: Adult male, female and ovariectomized mice were exposed to air (control group) or smoke for six months using a standard nose-only smoke exposure system. DNA was extracted from the cecal content using the QIAGEN QIAamp® DNA Mini Kit. Droplet digital PCR was used to generate total 16S bacterial counts, followed by Illumina MiSeq® analysis to determine microbial community composition. The sequencing data were resolved into Amplicon Sequence Variants and analyzed with the use of QIIME2®. Alpha diversity measures (Richness, Shannon Index, Evenness and Faith's Phylogenetic Diversity) and beta diversity (based on Bray-Curtis distances) were assessed and compared according to smoke exposure and sex. RESULTS: The microbial community was different between male and female mice, while ovariectomy made the cecal microbiome similar to that of male mice. Chronic smoke exposure led to significant changes in the cecal microbial community in both male and female mice. The organism, Alistipes, was the most consistent bacteria identified at the genus level in the cecal content that was reduced with chronic cigarette exposure and its expression was positively related to the whole-body weight of these mice. CONCLUSION: Chronic smoke exposure is associated with changes in the cecal content microbiome; these changes may play a role in the weight changes that are observed in cigarette smokers.


Assuntos
Ceco/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Fumaça/efeitos adversos , Fumar/efeitos adversos , Produtos do Tabaco/efeitos adversos , Tabaco/efeitos adversos , Animais , Bactérias/efeitos dos fármacos , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Filogenia , Doença Pulmonar Obstrutiva Crônica/microbiologia
16.
Asian Pac J Cancer Prev ; 21(3): 667-673, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32212792

RESUMO

BACKGROUND: Lung cancer coexisting with idiopathic pulmonary fibrosis (IPF) or chronic obstructive pulmonary disease (COPD) can lead to poor prognosis.  Telomere-related polymorphisms may be implicated in the pathogenesis of these three lung diseases.  As to elucidate the mechanism of lung cancer via IPF or COPD may enable early detection and early treatment of the disease, we firstly examined the association between telomere-related polymorphisms and the risk of IPF and COPD in a case-control study. MATERIALS AND METHODS: A total of 572 patients with IPF (n = 155) or COPD (n = 417), who were derived from our on-going cohort study, and controls (n = 379), who were derived from our previous case-control study, were included in this study.  Telomerase reverse transcriptase (TERT) rs2736100, telomere RNA component (TERC) rs1881984, and oligonucleotide/oligosaccharide-binding fold containing1 (OBFC1) rs11191865 were genotyped with real-time PCR using TaqMan fluorescent probes. Unconditional logistic regression was used to assess the adjusted odds ratios and 95% confidence intervals. RESULTS: TERT rs2736100 was significantly associated with the risk of IPF; increases in the number of this risk allele increased the risk of IPF (Ptrend = 0.008).  Similarly, TERT rs2736100 was associated with the risk of COPD.  In regard to the combined action of the three loci, increasing numbers of "at-risk" genotypes increased the risk of IPF in a dose-dependent manner (P trend=0.003). CONCLUSIONS: TERT rs2736100 was associated with the risks of both IPF and COPD in a Japanese population. A combination of the "at-risk" genotypes might be important to identify the population at risk for IPF more clearly.


Assuntos
Fibrose Pulmonar Idiopática/genética , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único , Doença Pulmonar Obstrutiva Crônica/genética , Telomerase/genética , Feminino , Humanos , Masculino , Sistema de Registros , Fatores de Risco , Tabaco/efeitos adversos
17.
Med Sci Monit ; 26: e920793, 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32201430

RESUMO

BACKGROUND Chronic obstructive pulmonary disease (COPD), a general airway disease, is featured by progressive and chronic immunoreaction in the lung. Increasing evidences have showed that cigarette smoking is the main reason in the COPD progression, and human pulmonary microvascular endothelial cell (HPMEC) apoptosis often be observed in COPD, while its pathogenesis is not yet fully described. Upregulation of long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) was observed in COPD patients, but the specific mechanism of lncRNA MEG3 in COPD remains unknown. The objective of this research was to explore the role of lncRNA MEG3 in cigarette smoke extract (CSE)-induced HPMECs. MATERIAL AND METHODS HPMECs were induced by a series of concentrations of CSE (0%, 0.1%, 1%, and 10%). Then cell apoptosis was analyzed by flow cytometry. Cell apoptosis related proteins were tested using western blot assay. Finally, we applied knockdown and over-expression system to explore the lncRNA MEG3 functions in CSE-induced HPMECs. RESULTS Our results indicated that various concentrations of CSE (0%, 0.1%, 1%, and 10%) significantly promoted cell apoptosis, augmented caspase-3 activity, upregulated Bax expression, decreased Bcl-2 expression, and enhanced lncRNA MEG3 level in HPMECs. LncRNA MEG3-plasmid transfection resulted in the upregulation of lncRNA MEG3, more apoptotic HPMECs, and higher caspase-3 activity. While lncRNA MEG3 knockdown presented the opposite effects. Further investigation suggested that all the effects of CSE treatment on HPMECs were markedly reversed by lncRNA MEG3-shRNA (short hairpin RNA). CONCLUSIONS Our study illustrated a protective effect of lncRNA MEG3-shRNA on CSE-induced HPMECs, indicting lncRNA MEG3 can be a new therapeutic approach for COPD treatment.


Assuntos
Doença Pulmonar Obstrutiva Crônica/metabolismo , RNA Longo não Codificante , Transdução de Sinais/fisiologia , Tabaco/efeitos adversos , Apoptose/fisiologia , Células Cultivadas , Células Endoteliais/metabolismo , Regulação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Fumaça/efeitos adversos
19.
Sci Rep ; 10(1): 2544, 2020 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-32054887

RESUMO

Since electronic-cigarettes (e-cigarettes) are considered less toxic than conventional tobacco smoking, the use of e-cigarettes has increased, and the market for e-cigarette liquids (e-liquids) is continuously increasing. However, many studies showed that e-cigarettes may cause various harmful effects in lung, oral and heart. In this study, we investigated the effects of e-liquids on otitis media (OM) using human middle ear epithelial cells (HMEECs). Menthol-flavored e-liquid induced significant cell death in HMEECs (IC50: 1.45 ± 0.14%) and tobacco-flavored e-liquid led to increase in inflammatory cytokine levels and higher mucin production. Flavored e-liquids decreased the mRNA levels of genes encoding epithelial sodium channels (ENaCs) in HMEECs. Apoptosis and autophagy reactions were induced by exposure of HMEECs to menthol- and tobacco-flavored e-liquids. Tobacco-flavored e-liquids caused a greater increase in the levels of autophagosome marker, LC3-II, compared to menthol-flavored e-liquids, which was followed by cell death. These results demonstrate that flavored e-liquids cause cytotoxicity via apoptosis, autophagy, inflammatory response, and mucin production in HMEECs. The flavors present in e-liquids might be a risk factor for the development of otitis media.


Assuntos
Orelha Média/efeitos dos fármacos , Sistemas Eletrônicos de Liberação de Nicotina , Células Epiteliais/efeitos dos fármacos , Tabaco/toxicidade , Morte Celular/efeitos dos fármacos , Linhagem Celular , Orelha Média/citologia , Aromatizantes/efeitos adversos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Estudos Longitudinais , Pulmão/efeitos dos fármacos , Pulmão/patologia , Mentol/química , Proteínas Associadas aos Microtúbulos/genética , Tabaco/efeitos adversos
20.
Exp Cell Res ; 389(1): 111888, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32027864

RESUMO

Neutrophil extracellular traps (NETs) were initially identified as an important antimicrobial barrier to capture and kill microorganisms. Emerging evidence suggests that NETs play a crucial role in chronic airway inflammation induced by cigarette smoke (CS). However, how NETs form and the mechanisms by which NETs function in CS-related airway diseases are still unclear. To explore NET formation and its potential role in CS-related airway diseases, we first established a CS-induced subacute airway inflammation model in mice and verified NET formation in the airways. Moreover, NETs degradation by aerosolized DNase I treatment significantly inhibited the airway inflammation induced by CS in mice. More importantly, by in vitro experiments, we found that cigarette smoke extract (CSE) induces NET formation in an NADPH oxidase-dependent manner, and that macrophages and human bronchial epithelial cells (HBEs) are important targets for the NETs-induced secretion of inflammatory cytokines. Therefore, NETs may represent a critical link among neutrophils, macrophages and HBEs under chronic inflammation conditions induced by CS.


Assuntos
Armadilhas Extracelulares/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Pneumonia/induzido quimicamente , Fumaça/efeitos adversos , Tabaco/efeitos adversos , Adulto , Animais , Células Cultivadas , Armadilhas Extracelulares/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/imunologia , Pneumonia/imunologia , Pneumonia/patologia , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/imunologia , Mucosa Respiratória/metabolismo , Mucosa Respiratória/patologia , Células THP-1
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