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1.
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
2.
Cell Physiol Biochem ; 54(2): 230-251, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32153152

RESUMO

BACKGROUND/AIMS: Adverse effects of cigarette smoke on health are widely known. Heating rather than combusting tobacco is one of strategies to reduce the formation of toxicants. The sensitive nature of mitochondrial dynamics makes the mitochondria an early indicator of cellular stress. For this reason, we studied the morphology and dynamics of the mitochondrial network in human bronchial epithelial cells (BEAS-2B) exposed to total particulate matter (TPM) generated from 3R4F reference cigarette smoke and from aerosol from a new candidate modified risk tobacco product, the Tobacco Heating System (THS 2.2). METHODS: Cells were subjected to short (1 week) and chronic (12 weeks) exposure to a low (7.5 µg/mL) concentration of 3R4F TPM and low (7.5 µg/mL), medium (37.5 µg/mL), and high (150 µg/mL) concentrations of TPM from THS 2.2. Confocal microscopy was applied to assess cellular and mitochondrial morphology. Cytosolic Ca2+ levels, mitochondrial membrane potential and mitochondrial mass were measured with appropriate fluorescent probes on laser scanning cytometer. The levels of proteins regulating mitochondrial dynamics and biogenesis were determined by Western blot. RESULTS: In BEAS-2B cells exposed for one week to the low concentration of 3R4F TPM and the high concentration of THS 2.2 TPM we observed clear changes in cell morphology, mitochondrial network fragmentation, altered levels of mitochondrial fusion and fission proteins and decreased biogenesis markers. Also cellular proliferation was slowed down. Upon chronic exposure (12 weeks) many parameters were affected in the opposite way comparing to short exposure. We observed strong increase of NRF2 protein level, reorganization of mitochondrial network and activation of the mitochondrial biogenesis process. CONCLUSION: Comparison of the effects of TPMs from 3R4F and from THS 2.2 revealed, that similar extent of alterations in mitochondrial dynamics and biogenesis is observed at 7.5 µg/mL of 3R4F TPM and 150 µg/mL of THS 2.2 TPM. 7 days exposure to the investigated components of cigarette smoke evoke mitochondrial stress, while upon chronic, 12 weeks exposure the hallmarks of cellular adaptation to the stressor were visible. The results also suggest that mitochondrial stress signaling is involved in the process of cellular adaptation under conditions of chronic stress caused by 3R4F and high concentration of THS 2.2.


Assuntos
Aerossóis/química , Mitocôndrias/metabolismo , Dinâmica Mitocondrial/efeitos dos fármacos , Material Particulado/toxicidade , Cálcio/metabolismo , Linhagem Celular , Corantes Fluorescentes/química , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Microscopia Confocal , Mitocôndrias/efeitos dos fármacos , Material Particulado/química , Fumaça/efeitos adversos , Fatores de Tempo , Produtos do Tabaco/análise
3.
Adv Exp Med Biol ; 1225: 53-69, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32030647

RESUMO

Tobacco smoke is a multicomponent mixture of chemical, organic, and inorganic compounds, as well as additive substances and radioactive materials. Many studies have proved the carcinogenicity of various of these compounds through the induction of DNA adducts, mutational potential, epigenetic changes, gene fusions, and chromosomal events. The tumor microenvironment plays an important role in malignant tumor formation and progression through the regulation of expression of key molecules which mediate the recruitment of immune cells to the tumor site and subsequently regulate tumor growth and metastasis. In this chapter, we discuss the effects of inhaled tobacco smoke in the tumor microenvironment of the respiratory tract. The mechanisms underlying these effects as well as their link with tumor progression are analyzed.


Assuntos
Neoplasias Pulmonares/patologia , Fumaça/efeitos adversos , Tabaco , Microambiente Tumoral/efeitos dos fármacos , Progressão da Doença , Humanos , Tabaco/efeitos adversos , Poluição por Fumaça de Tabaco/efeitos adversos
4.
Toxicol Lett ; 322: 20-31, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31923465

RESUMO

Particulate matter (PM) from combustion processes has been associated with oxidative stress to DNA, whereas effects related to telomere dysfunction are less investigated. We collected air-borne PM from a passenger cabin of a diesel-propelled train and at a training facility for smoke diving exercises. Effects on oxidative stress biomarkers, genotoxicity measured by the comet assay and telomere length in PM-exposed A549 cells were compared with the genotoxicity and telomere length in peripheral blood mononuclear cells (PBMCs) from human volunteers exposed to the same aerosol source. Although elevated levels of DNA strand breaks and oxidatively damaged DNA in terms of Fpg-sensitive sites were observed in PBMCs from exposed humans, the PM collected at same locations did not cause genotoxicity in the comet assay in A549 cells. Nevertheless, A549 cells displayed telomere length shortening after four weeks exposure to PM. This is in line with slightly shorter telomere length in PBMCs from exposed humans, although it was not statistically significant. In conclusion, the results indicate that genotoxic potency measured by the comet assay of PM in A549 cells may not predict genotoxicity in exposed humans, whereas telomere length measurements may be a novel indicator of genotoxic stress in cell cultures and humans.


Assuntos
Dano ao DNA , Exposição por Inalação/efeitos adversos , Material Particulado/toxicidade , Fumaça/efeitos adversos , Homeostase do Telômero/efeitos dos fármacos , Emissões de Veículos/toxicidade , Células A549 , Poluentes Ocupacionais do Ar/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Bombeiros , Humanos , Exposição por Inalação/análise , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/patologia , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Tamanho da Partícula , Homeostase do Telômero/genética
6.
Fitoterapia ; 140: 104434, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31760067

RESUMO

Fritillaria cirrhosa bulbus is a Chinese folk herb famous for its antitussive, expectorant, anti-asthma and anti-inflammatory properties, and is widely used to treat respiratory diseases. However, the impacts of F. cirrhosa bulbus on oxidative stress are still unkown. In the present study, we investigated the potential effect and mechanism of six isosteroid alkaloids with different chemical structures from F. cirrhosa bulbus on protection against cigarette smoke-induced oxidative stress in RAW264.7 macrophages. The results showed that six isosteroid alkaloids reduced reactive oxygen species (ROS) production, elevated glutathione (GSH) level and promoted heme oxygenase (HO-1) expression, which is in association with induction of NF-E2-related factor 2 (Nrf2) nuclear translocation and up-regulation of Nrf2 expression. Among these alkaloids, verticinone, verticine, imperialine-3-ß-D-glucoside, delavine and peimisine exhibited more potent effect against CSE-induced oxidative stress than that of imperialine. These findings for the first time demonstrated that F. cirrhosa bulbus may play a protective role in cellular oxidative stress by activating Nrf2-mediated antioxidant pathway. Furthermore, the differences in antioxidant effects of these alkaloids were compared, as well as the corresponding structure-activity relationships were preliminarily elucidated. This suggested that F. cirrhosa bulbus might be a promising therapeutic treatment for the prevent of oxidative stress-related diseases.


Assuntos
Alcaloides/farmacologia , Fritillaria/química , Estresse Oxidativo/efeitos dos fármacos , Fumaça/efeitos adversos , Alcaloides/isolamento & purificação , Animais , Glutationa/metabolismo , Heme Oxigenase-1/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Estrutura Molecular , Fator 2 Relacionado a NF-E2/metabolismo , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Raízes de Plantas/química , Plantas Medicinais/química , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade , Produtos do Tabaco
7.
Life Sci ; 241: 117132, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31837327

RESUMO

INTRODUCTION: This study aimed to verify the effects of cigarette smoke exposure in bone mineralization and fibrillar matrix composition as well as in bone healing after tibial fracture induction. METHODS: C57Bl/6 Mice were assigned according to exposure and surgery: C room air; F room air and tibia open osteotomy; CS cigarette smoke; FCS cigarette smoke and tibia open osteotomy. In order to study fracture healing we performed, under anesthesia, a bone injury through a tibial shaft osteotomy. Bone samples were obtained to evaluate bone histomorphometry, trabecular morphology and volume, trabecular collagen types composition and presence of inflammatory cytokines and growth factors. RESULTS: CS exposure significantly reduced the thickness of bone trabeculae associated with decrease in mineralizing surface and mineral deposition rate, leading a lower bone formation rate and longer mineralization time. Resorption surface and osteoclastic surface were greater in the CS group, attesting increased resorptive action. There was a decrease in type I collagen deposition and genes expression in the CS and FCS groups compared to C group and in contrast there was an increase in type V collagen deposition and genes expression in the CS, FC and FSC groups compared to C group. Also, CS exposure induced a decrease in bone forming cytokines and an increase in inflammatory associated cytokines, and these changes were intensified under fracture conditions. CONCLUSION: Cigarette smoke exposure alters bone matrix composition and worsens bone mineralization, leading to bone fragility by increasing collagen V synthesis and deposition and impairing collagen I fibril forming and assembling. And these deleterious effects contributed to the worsening in fracture healing after tibia osteotomy.


Assuntos
Calcificação Fisiológica/efeitos dos fármacos , Fumar Cigarros/efeitos adversos , Osteogênese/efeitos dos fármacos , Fumaça/efeitos adversos , Tíbia/patologia , Fraturas da Tíbia/patologia , Animais , Colágeno Tipo I/metabolismo , Citocinas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Tíbia/efeitos dos fármacos , Tíbia/lesões , Tíbia/metabolismo , Fraturas da Tíbia/etiologia , Fraturas da Tíbia/metabolismo
8.
Chem Biol Interact ; 315: 108887, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31705857

RESUMO

AIM: To investigate the molecular, structural, and functional impact of aerosols from candidate modified risk tobacco products (cMRTP), the Carbon Heated Tobacco Product (CHTP) 1.2 and Tobacco Heating System (THS) 2.2, compared with that of mainstream cigarette smoke (CS) on the cardiovascular system of ApoE-/- mice. METHODS: Female ApoE-/- mice were exposed to aerosols from THS 2.2 and CHTP 1.2 or to CS from the 3R4F reference cigarette for up to 6 months at matching nicotine concentrations. A Cessation and a Switching group (3 months exposure to 3R4F CS followed by filtered air or CHTP 1.2 for 3 months) were included. Cardiovascular effects were investigated by echocardiographic, histopathological, immunohistochemical, and transcriptomics analyses. RESULTS: Continuous exposure to cMRTP aerosols did not affect atherosclerosis progression, heart function, left ventricular (LV) structure, or the cardiovascular transcriptome. Exposure to 3R4F CS triggered atherosclerosis progression, reduced systolic ejection fraction and fractional shortening, caused heart LV hypertrophy, and initiated significant dysregulation in the transcriptomes of the heart ventricle and thoracic aorta. Importantly, the structural, functional, and molecular changes caused by 3R4F CS were improved in the smoking cessation and switching groups. CONCLUSION: Exposure to cMRTP aerosols lacked most of the CS exposure-related functional, structural, and molecular effects. Smoking cessation or switching to CHTP 1.2 aerosol caused similar recovery from the 3R4F CS effects in the ApoE-/- model, with no further acceleration of plaque progression beyond the aging-related rate.


Assuntos
Aerossóis/efeitos adversos , Apolipoproteínas E/metabolismo , Carbono/efeitos adversos , Sistema Cardiovascular/efeitos dos fármacos , Fumaça/efeitos adversos , Produtos do Tabaco/efeitos adversos , Tabaco/efeitos adversos , Animais , Aorta Torácica/efeitos dos fármacos , Aterosclerose/metabolismo , Sistema Cardiovascular/metabolismo , Feminino , Calefação/efeitos adversos , Exposição por Inalação/efeitos adversos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Camundongos , Fumar/efeitos adversos , Transcriptoma/efeitos dos fármacos
9.
Environ Toxicol ; 35(1): 66-77, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31507073

RESUMO

The heart is the first organ formed in the developing fetus, and abnormal development of the heart is a major cause of fetal death. The adverse effects of cigarette smoke on the heart have been well established, but it is not well understood how cigarette smoke components regulate signaling molecules and cardiac specific functions during the early differentiation stage of the embryonic heart. In this study, we identified changes in the size of mouse embryoid bodies (mEBs) in response to treatment with cigarette smoke extract (CSE) via regulation of HDAC2, p53, p21, and cyclin D1 protein expression, which are cardiac differentiation and cell-cycle markers, respectively. In addition, exposure of mouse embryonic stem cells (mESCs) to cigarette smoke components inhibited myocardial differentiation and development through the expression of HDAC1, HDAC2, GATA4, NKX2-5, TBX5, HAND1, and Troponin I. Long-term exposure studies showed that CSE and nicotine may delay the development of mouse cardiomyocytes from mESCs and inhibit the contractibility, which is a fundamental function of the heart. Taken together, these findings suggest that cigarette smoke components, including nicotine, may affect abnormal myocardial differentiation and development.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Células-Tronco Embrionárias Murinas/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Fumaça/efeitos adversos , Tabaco/toxicidade , Animais , Ciclo Celular/efeitos dos fármacos , Ciclina D1/metabolismo , Histona Desacetilase 2/metabolismo , Camundongos , Células-Tronco Embrionárias Murinas/citologia , Células-Tronco Embrionárias Murinas/metabolismo , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fumar/efeitos adversos
10.
J Agric Food Chem ; 67(51): 14137-14142, 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31802665

RESUMO

Smoke-taint is a wine defect that may occur when ripening grape crops absorb volatile phenols (VPs), compounds associated with the negative sensory attributes of smoke-taint, due to exposure of grapes to wildfire smoke. This study examined potential methods to reduce the impact that smoke-exposure has on wine grapes. Specifically, agricultural sprays normally used to protect grapes from fungal pathogens and a spray used to prevent cracking in soft-fleshed fruits were assessed for their capacity to inhibit increases in VP concentrations in wine grapes following on-vine smoke-exposure. The results indicated that an artificial grape cuticle applied 1 week before exposure to simulated forest fire smoke (at 1-2 weeks after veraison) can significantly hinder an increase in VP concentrations in smoke-exposed grapes at commercial maturity. This reduction in VP concentrations may mitigate crop losses experienced globally by the wine industry due to exposure of grapes on-vine (at key phenological stages) to wildfire smoke.


Assuntos
Produção Agrícola/métodos , Frutas/efeitos dos fármacos , Fumaça/efeitos adversos , Vitis/crescimento & desenvolvimento , Vinho/análise , Frutas/química , Frutas/crescimento & desenvolvimento , Frutas/metabolismo , Fenóis/metabolismo , Fumaça/análise , Vitis/química , Vitis/efeitos dos fármacos , Vitis/metabolismo , Incêndios Florestais
11.
Zhonghua Jie He He Hu Xi Za Zhi ; 42(12): 907-915, 2019 Dec 12.
Artigo em Chinês | MEDLINE | ID: mdl-31826534

RESUMO

Objective: To investigate the mechanism of fine particulate matter (PM2.5) on the phagocytosis of alveolar macrophages (AM) in mice with chronic obstructive pulmonary disease (COPD) through actin-related protein (Arp) 2/3 complex. Methods: Forty mice were divided into healthy control(A) group, healthy PM2.5 (B) group, COPD(C) group, and COPD PM2.5(D) group according to the random number table method. A mouse model of COPD was established by cigarette smoke exposure method. PM2.5 (662 µg/m(3)) model was established by continuously inhalation for 90 days in healthy PM2.5 group and COPD PM2.5 group. Flow cytometry was used to detect the ability of AM to phagocytose fluorescein isothiocyanate-labeled E.coli (FITC-E.coli), expressed as mean fluorescence intensity (MFI) and percentage of phagocytic positive cells (phagocytosis percentage); Western blotting was used to detect AM Arp2 and F-actin content, and laser confocal microscopy for AM Arp2 and F-actin and phagocytic FITC-E.coli average optical density and colocalization of Arp2 and F-actin, while scanning electron microscopy was used to observes the morphology of AM after phagocytizing FITC-E.coli. Results: AM phagocytosis: MFI and phagocytosis percentage in the COPD group [4 656±251, (31.9±1.7)%] were lower than the healthy control group [8 657±247, (65.7±1.9)%] (both P<0.01); and healthy PM2.5 group and COPD PM2.5 group [7 653±228, (47.9±1.6)% and 3 660±237, (19.2±1.2)%] were lower than the respective control groups (all P<0.01), and the decrease in the COPD group was more pronounced. AM Arp2, F-actin content: the COPD group (0.51±0.02, 0.46±0.03) were lower than the healthy control group (0.81±0.04, 0.71±0.04, both P<0.01); the healthy PM2.5 group and the COPD PM2.5 group [(0.64±0.03, 0.56±0.04) and (0.29±0.02, 0.26±0.02)] were lower than the respective control groups (all P<0.01), and the decrease in COPD group was more significant. Arp2, F-actin, and phagocytic FITC-E.coli mean optical density values: the COPD group (33.0±2.3, 62.0±0.7, 41.0±0.4) were lower than the healthy control group (141.0±4.2, 145.0±2.9, 189.0±2.6, both P<0.01); the healthy PM2.5 group and the COPD PM2.5 group (127.0±2.8, 124.0±0.7, 154.0±0.9, and 24.0±2.4, 37.0±0.4, 29.0±0.8) were lower than the respective control groups (all P<0.01), and the decrease in the COPD group was more significant. Colocalization of AM Arp2 and F-actin: Montessori colocalization coefficient (MOC) (0.38±0.03) in the COPD group was lower than the healthy control group (0.88±0.03, P<0.01); healthy PM2.5 group and COPD PM2.5 group [(0.58±0.03) and (0.14±0.02)] were lower than the respective control groups (both P<0.01), and the decrease in COPD group was more significant. Morphology of AM phagocytosis of FITC-E.coli: AM in the healthy control group was obviously deformed, and the surface of the cell membrane was slightly wrinkled and high, and the free edge of the micro-pleated fold had a long and dense filamentous pseudopodia extension. The changes of morphology of AM in the COPD group was not obvious, the micro-wrinkles on the surface of the cell membrane were rare, and the filopodia poorly extended or even absent. The AM form of the healthy PM2.5 group changed slightly, mostly irregular circular or elliptical. The micro-wrinkles on the surface of the cell membrane were less and flat, and the filopodia protrudes short and less; the AM form of the COPD PM2.5 group was stiff, and the micro-wrinkles on the surface of the cell membrane were few and flat, no obvious filopodia or protrusions. Correlation analysis: After basal state and PM2.5 intervention, AM Arp2, F-actin content and MOC values of Arp2 and F-actin were positively correlated with MFI. Conclusions: The phagocytic function of AM in COPD mice was low, which was related to the abnormal rearrangement of cytoskeleton involved in Arp2/3 complex and F-actin. It was speculated that PM2.5 might inhibit Arp2/3 complex and F-actin. The cytoskeletal rearrangement of proteins was involved in the aggravation of AM phagocytosis in mice with COPD.


Assuntos
Complexo 2-3 de Proteínas Relacionadas à Actina/metabolismo , Macrófagos Alveolares/metabolismo , Material Particulado/efeitos adversos , Fagocitose/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/metabolismo , Animais , Camundongos , Distribuição Aleatória , Fumaça/efeitos adversos
13.
Environ Health Prev Med ; 24(1): 65, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31775610

RESUMO

BACKGROUND: Little is known regarding the effect of exposure to biomass fuel smoke inhalation on respiratory symptoms in the Bangladeshi population which is a major health hazard in most of the developing countries. This study aims to explore the association between respiratory symptoms and biomass fuel smoke exposure among children under 5 years of age. METHODS: Data were extracted from the Bangladesh Urban Health Survey conducted in 2013. A total of 10,575 mothers with at least one surviving children were selected. Respiratory symptoms among children under 5 years of age were considered as the primary outcome. Sequential multiple logistic regression models were used to observe the association between respiratory symptoms and biomass fuel smoke exposure adjusting the effect of residential factors and mother and child characteristics. RESULTS: Around 40% of the mothers exclusively used biomass fuel irrespective of the kitchen location and 54% of them were habituated in indoor cooking. The prevalence of respiratory symptoms of under-five children among in-house and outdoor biomass fuel users was 23.0% and 21.9%, respectively. Results of fitted multiple logistic regression models showed that the odds of having respiratory symptoms among children under 5 years of age were increased due to in-house biomass fuel use [OR = 1.18; 95% CI, 1.04-1.36] compared with the non-biomass user. An increased risk of respiratory symptoms was also significantly associated with mother's birth complication [OR = 1.51; 95% CI, 1.36-1.67], non-government organization (NGO) membership of mothers [OR = 1.32; 95% CI, 1.16-1.51], age of the child (6-23m) [OR = 1.29; 95% CI, 1.10-1.52], and nutritional status (stunting) [OR = 1.18; 95% CI, 1.06-1.31]. CONCLUSION: This study found the use of in-house biomass fuel as a significant risk factor associated with respiratory symptoms of children under 5 years of age. More longitudinal studies should be designed to establish a causal relationship between HAP (household air pollution) and respiratory symptoms among children with more direct measures of HAP and clinical procedure.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Exposição por Inalação/efeitos adversos , Transtornos Respiratórios/epidemiologia , Transtornos Respiratórios/etiologia , Fumaça/efeitos adversos , Poluição do Ar em Ambientes Fechados/efeitos adversos , Bangladesh/epidemiologia , Biomassa , Pré-Escolar , Culinária/métodos , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Lactente , Recém-Nascido , Masculino , Mães , Prevalência , Fatores de Risco , Saúde da População Urbana
14.
Artigo em Inglês | MEDLINE | ID: mdl-31581673

RESUMO

Colorado is regularly impacted by long-range transport of wildfire smoke from upwind regions. This smoke is a major source of ambient PM2.5. Maternal exposure to total PM2.5 during pregnancy has been linked to decreased birth weight and other adverse outcomes, although the impact of wildfire smoke contribution has only recently been investigated. The objective of this study was to estimate associations between adverse pregnancy outcomes and ambient wildfire smoke PM2.5. Wildfire smoke PM2.5 exposures were estimated using a previously published method incorporating ground-based monitors and remote sensing data. Logistic regression models stratified by ZIP code and mixed models with random intercept by ZIP code were used to test for associations. The primary outcomes of interest were preterm birth and birth weight. Secondary outcomes included gestational hypertension, gestational diabetes, neonatal intensive care unit admission, assisted ventilation, small for gestational age, and low birth weight. Exposure to wildfire smoke PM2.5 over the full gestation and during the second trimester were positively associated with pre-term birth (OR = 1.076 (µg/m3)-1 [95% CI = 1.016, 1.139; p = 0.013] and 1.132 (µg/m3)-1 [95% CI = 1.088, 1.178]; p < 0.0001, respectively), while exposure during the first trimester was associated with decreased birth weight (-5.7 g/(µg/m3) [95% CI: -11.1, -0.4; p = 0.036]). Secondary outcomes were mixed.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Exposição Materna/estatística & dados numéricos , Material Particulado/efeitos adversos , Resultado da Gravidez , Fumaça/efeitos adversos , Incêndios Florestais , Adolescente , Adulto , Peso ao Nascer , Colorado , Feminino , Humanos , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Modelos Logísticos , Masculino , Gravidez , Primeiro Trimestre da Gravidez , Adulto Jovem
15.
Int J Occup Med Environ Health ; 32(5): 595-634, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31584041

RESUMO

Heated tobacco products (HTPs) are a form of nicotine delivery intended to provide an alternative to traditional cigarettes. The aim of this systematic review was to present the current state of knowledge on HTPs with an emphasis on the potential impact of HTP use on human health. During the preparation of this systematic review, the literature on HTPs available within Medline/PubMed, EMBASE, CINAHL, ScienceDirect, and Google Scholar was retrieved and examined. In the final review, 97 research papers were included. The authors specifically assessed the construction and operation of HTPs, as well as the chemical composition of HTP tobacco sticks and the generated aerosol, based on evidence from experimental animal and cellular studies, and human-based studies.Heated tobacco products were found to generate lower concentrations of chemical compounds compared to traditional cigarettes, except for water, propylene glycol, glycerol, and acetol. The nicotine levels delivered to the aerosol by HTPs were 70-80% as those of conventional combustion. The results of in vitro and in vivo assessments of HTP aerosols revealed reduced toxicity, but these were mainly based on studies sponsored by the tobacco industry. Independent human-based studies indicated that there was a potentially harmful impact of the active and passive HTP smoking on human health. Currently, a large body of knowledge on HTP exposures and health effects is provided by the tobacco industry (52% of identified studies). Based on the available evidence, HTPs produce lower levels of toxic chemicals, compared to conventional cigarettes, but they are still not risk-free. Int J Occup Med Environ Health. 2019;32(5):595-634.


Assuntos
Aerossóis/química , Nicotina/análise , Produtos do Tabaco/efeitos adversos , Aerossóis/toxicidade , Animais , Temperatura Alta , Humanos , Fumaça/efeitos adversos , Fumaça/análise , Produtos do Tabaco/análise
16.
Toxicol Lett ; 317: 92-101, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31593750

RESUMO

Cigarette smoke (CS) is known to cause mitochondrial dysfunction leading to cellular senescence in lung cells. We determined the mechanism of mitochondrial dysfunction by CS in lung epithelial cells. CS extract (CSE) treatment differentially affected mitochondrial function, such as membrane potential, mitochondrial reactive oxygen species (mtROS) and mitochrondrial mass as analyzed by FACS, and were associated with altered oxidative phosphorylation (OXPHOS) protein levels (Complexes I-IV) in primary lung epithelial cells (SAEC and NHBE), and (complexes I and II) in BEAS2B cells. There were dose- and time-dependent changes in mitochondrial respiration (oxygen consumption rate parameters i.e. maximal respiration, ATP production and spare capacity, measured by the Seahorse analyzer) in control vs. CSE treated BEAS2B and NHBE/DHBE cells. Electron microscopy (EM) analysis revealed perinuclear clustering by localization and increased mitochondrial fragmentation by fragement length analysis. Immunoblot analysis revealed CS-mediated increase in Drp1 and decrease in Mfn2 levels that are involved in mitochondrial fission/fusion process. CSE treatment reduced Miro1 and Pink1 abundance that play a crucial role in the intercellular transfer mechanism and mitophagy process. Overall, these findings highlight the role of Miro1 in context of CS-induced mitochondrial dysfunction in lung epithelial cells that may contribute to the pathogenesis of chronic inflammatory lung diseases.


Assuntos
Fumar Cigarros/efeitos adversos , Células Epiteliais/metabolismo , Pulmão/metabolismo , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Doença Pulmonar Obstrutiva Crônica/etiologia , Fumaça/efeitos adversos , Proteínas rho de Ligação ao GTP/metabolismo , Estudos de Casos e Controles , Células Cultivadas , Regulação para Baixo , Metabolismo Energético , Células Epiteliais/ultraestrutura , Humanos , Pulmão/ultraestrutura , Mitocôndrias/ultraestrutura , Estresse Oxidativo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Transdução de Sinais
17.
Toxicol Lett ; 317: 102-109, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31574306

RESUMO

BACKGROUND: Cigarette smoke is considered a risk factor for lung and colorectal cancer. A convincing link between epithelial-to-mesenchymal transition (EMT) with colorectal cancer progression and therapeutic resistance has emerged. Deregulated expression of E-Cadherin and Claudin-1 and increased miR-21 expression and invasiveness represent hallmarks of EMT. The effects of cigarette smoke exposure on EMT in colorectal adenocarcinoma cells are largely unknown. AIM: The aim of the study is to evaluate the effect of cigarette smoke extract (CSE) on miR-21, Claudin-1 and E-Cadherin, molecules associated to EMT in colorectal cancer cells. METHODS: A human colorectal adenocarcinoma cell line (Caco-2) was treated with CSE at different concentration (5% and 10%) and for different time points (3 h and 24 h). Metabolic activity (by MTS assay), cell necrosis/cell apoptosis (evaluating Propidium Iodide/Annexin V expression by flow cytometry), miR-21, Claudin-1 and E-Cadherin gene expression were evaluated by Real time PCR. Cell permeability, actin polymerization and cancer cell migration was assessed by Trans-Epitelial Electrical Resistance (TEER), Phalloidin expression and matrigel system, respectively. RESULTS: CSE at all the tested concentrations and at all time points reduced cell necrosis. CSE at 10% increased miR-21 and reduced the metabolic activity, cell necrosis, Claudin-1 and E-cadherin mRNA at 3 h. Cell permeability, actin polymerization and cancer cell migration were all increased upon CSE exposure. CONCLUSION: These results showed that CSE increasing miR-21, Claudin-1 and E-Cadherin and enhancing the aggressiveness of cancer cells, may concur to colorectal cancer progression.


Assuntos
Adenocarcinoma/metabolismo , Antígenos CD/metabolismo , Caderinas/metabolismo , Movimento Celular , Fumar Cigarros/efeitos adversos , Claudina-1/metabolismo , Neoplasias Colorretais/metabolismo , MicroRNAs/metabolismo , Fumaça/efeitos adversos , Adenocarcinoma/genética , Adenocarcinoma/patologia , Antígenos CD/genética , Células CACO-2 , Caderinas/genética , Claudina-1/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Progressão da Doença , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Invasividade Neoplásica , Transdução de Sinais
18.
Chem Biol Interact ; 314: 108846, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31606474

RESUMO

Matrix metalloproteinases (MMPs) have been implicated in EMT but their role in the regulation of cigarette smoke-induced EMT in airway epithelium is not clear. We have therefore investigated the potential role of MMP-2 and -9 in cigarette smoke extract (CSE) induced EMT using A549 lung epithelial cells and human small airway epithelial cells (SAEC). The cells were treated with different concentration of CSE, and MTT and trypan blue assays, acridine orange-ethidium bromide assay, gelatin zymography, Western blotting, immunofluorescence studies, Boyden-chamber assay, wound healing assay and air-liquid interface (ALI) culture were used to assess different cellular and molecular changes associated with EMT. The results depict that CSE increased the cytotoxicity along with a concurrent increase in the expression and activity of MMP-2 and -9. CSE further altered EMT markers like E-cadherin, N-cadherin, vimentin, and the molecular modulators of EMT such as ß-catenin and pGSK-3ß. Further, CSE also upregulated EGFR, AKT, and ERK1/2 in airway epithelial cells. SB-3CT, a known inhibitor of MMP-2 and -9, altered and reversed the expression of markers of EMT and kinases, validating the role of MMP-2 and -9 in CSE-induced EMT. Fisetin, a plant-derived bioflavonoid, also reversed the expression of EMT markers and molecular regulators in a similar fashion as SB-3CT. In summary, this study highlights the role of MMP-2 and -9 in CSE-induced EMT and curate its molecular cascade through EGFR/AKT/ERK/ß-catenin axis, which could be restored by MMP-2 and -9 inhibitor and fisetin. Fisetin is hitherto unknown to modulate CSE-induced MMPs activity in airway epithelial cells, and our study suggests its potential role as a therapeutic approach in CSE-induced EMT in lung epithelial cells.


Assuntos
Transição Epitelial-Mesenquimal/efeitos dos fármacos , Flavonoides/farmacologia , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fumaça/efeitos adversos , Tabaco/química , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Receptores ErbB/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , beta Catenina/metabolismo
19.
Cutis ; 104(2): 120-124, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31603956

RESUMO

Electrosurgery generates smoke that may be harmful. We created a survey to evaluate perceptions of electrosurgical smoke and how information on the harm it potentially causes changes these perceptions. We distributed the survey to the membership of the American College of Mohs Surgery and the American Society for Dermatologic Surgery and received 437 useable responses. Results indicated that many dermatologic surgeons were aware of and bothered by surgical smoke, and these reactions were more prevalent after being educated on the potential hazards of electrosurgical smoke.


Assuntos
Procedimentos Cirúrgicos Ambulatórios/efeitos adversos , Procedimentos Cirúrgicos Dermatológicos/efeitos adversos , Eletrocirurgia/efeitos adversos , Fumaça/efeitos adversos , Procedimentos Cirúrgicos Ambulatórios/métodos , Procedimentos Cirúrgicos Dermatológicos/métodos , Dermatologia/métodos , Eletrocirurgia/métodos , Humanos , Exposição Ocupacional/efeitos adversos , Cirurgiões/estatística & dados numéricos , Inquéritos e Questionários
20.
Toxicol Lett ; 316: 10-19, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31476341

RESUMO

Rapid risk assessment models for different types of cigarette smoke extract (CSE) exposure are critical to understanding the etiology of chronic obstructive pulmonary disease. The present study investigated inflammation of cultured tracheal tissues with CSE exposure. Rat trachea rings were isolated, cultured, then exposed to various concentrations of CSE from 3R4 F reference cigarettes for 4 h. Tissue/cellular morphology, ultrastructure, viability and damage, inflammatory cell infiltration, and inflammatory protein levels were measured and compared to untreated controls. Human bronchial epithelial cells (BEAS-2B) exposed to 0 or 300 µg/mL CSE were cocultured with macrophages to assess extent of mobilization and phagocytosis. Endotracheal epithelium cilia densities were significantly reduced with increasing CSE concentrations, while mucous membranes became increasingly disordered; both eventually disappeared. Macrophages became larger as the CSE concentration increased, with microvilli and extended pseudopodium covering their surface, and many primary and secondary lysosomes present in the cytoplasm. Inflammatory cell infiltration also increased with increasing CSE dose, as did intracellular adhesion molecule-1(ICAM-1), interleukin-6(IL-6). The method described here may be useful to qualitatively characterized the effects of the compound under study. Then, we use BEAS-2B cell line system to strength the observation made in the cultured tissues. Probably, an approach to integrate results from both experiments will facilitate its application. These results demonstrate that cultured rat tracheal rings have a whole-tissue structure that undergoes inflammatory processes similar to in vivo tissues upon CSE exposure.


Assuntos
Células Epiteliais/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/etiologia , Fumaça/efeitos adversos , Fumar/efeitos adversos , Tabaco/efeitos adversos , Traqueia/efeitos dos fármacos , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Cocultura , Células Epiteliais/metabolismo , Células Epiteliais/ultraestrutura , Humanos , Mediadores da Inflamação/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-6/metabolismo , Macrófagos/metabolismo , Macrófagos/ultraestrutura , Masculino , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Ratos Sprague-Dawley , Medição de Risco , Fatores de Tempo , Técnicas de Cultura de Tecidos , Traqueia/metabolismo , Traqueia/ultraestrutura
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