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1.
Front Immunol ; 13: 930476, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35924248

RESUMO

Extracellular vesicles (EVs)-mediated epithelium-macrophage crosstalk has been proved to maintain lung homeostasis in cigarette smoke-induced lung diseases such as chronic obstructive pulmonary disease (COPD). In our previous study, we found that EVs derived from cigarette smoke extract (CSE) treated BEAS-2B promoted M1 macrophage polarization, which probably accelerated the development of inflammatory responses. Naringenin has been proved to suppress M1 macrophage polarization, but whether naringenin regulates macrophage polarization mediated by EVs has not been reported. In this study, we firstly found that EVs derived from naringenin and CSE co-treated BEAS-2B significantly inhibited the expression of CD86 and CD80 and the secretion of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1ß, inducible nitric oxide synthase (iNOS), and IL-12 in macrophage induced by EVs derived from CSE-treated BEAS-2B. Further research revealed that naringenin downregulated BEAS-2B-derived EVs miR-21-3p which targeted phosphatase and tensin homolog deleted on chromosome ten/protein kinase B (PTEN/AKT) cascade in macrophages and then suppressed M1 macrophage polarization. Subsequent proteomics suggested that naringenin decreased BEAS-2B-derived EVs poly ADP-ribose polymerase (PARP)1 expression thereby suppressing M1 macrophage polarization probably. Our study provides novel pharmacological references for the mechanism of naringenin in the treatment of cigarette smoke-induced lung inflammatory diseases.


Assuntos
Fumar Cigarros , Vesículas Extracelulares , Fumar Cigarros/efeitos adversos , Flavanonas , Ativação de Macrófagos , Macrófagos/metabolismo , Tabaco
2.
Biochem Cell Biol ; 100(3): 223-235, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35833632

RESUMO

Cigarette smoke (CS) is a risk factor for chronic obstructive pulmonary disease (COPD), which can exacerbate inflammation and oxidative stress. Pristimerin (Pris) is a natural compound with antioxidant and anti-inflammatory effects. We managed to evaluate the protective effects of Pris on CS-induced COPD. The CS-induced COPD mice model and cell model were constructed. The effects of Pris treatment on lung function, inflammatory cell infiltration, myeloperoxidase (MPO), and pathological changes of lung tissues in mice model were evaluated. The impacts of Pris treatment on inflammatory factors, chemokines, and oxidative stress parameters in mice lung tissues and cells were determined by kits. The viability of human bronchial epithelial cells after Pris treatment was tested by CCK-8. The activation of NF-κB pathway was confirmed by Western blot and immunofluorescence. CS treatment impaired lung function, reduced weight of mice, and enhanced inflammatory cell infiltration, MPO, and lung tissue damage, but these effects of CS were reversed by Pris treatment. Furthermore, Pris treatment downregulated the levels of malondialdehyde, IL-6, IL-1ß, TNF-α, CXCL1, and CXLC2, but upregulated superoxide dismutase and catalase levels. Pris treatment could overturn CS-induced activation of the NF-κB pathway. Pris alleviates CS-induced COPD by inactivating NF-κB pathway.


Assuntos
Fumar Cigarros , Doença Pulmonar Obstrutiva Crônica , Animais , Fumar Cigarros/efeitos adversos , Humanos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Pulmão/metabolismo , Camundongos , NF-kappa B/metabolismo , Triterpenos Pentacíclicos , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Tabaco/metabolismo
3.
Front Immunol ; 13: 803362, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35774797

RESUMO

Research Impact: Cigarette smoke (CS) exposure is strongly associated with chronic obstructive pulmonary disease (COPD). In respiratory airways, CS exposure disrupts airway barrier functions, mucous/phlegm production, and basic immune responses of airway epithelial cells. Based on our recent identification of a specific immunomodulatory long noncoding RNA (lncRNA), we investigated its role in CS-induced responses in bronchial airways of cynomolgus macaque model of CS-induced COPD and in former smokers with and without COPD. The lncRNA was significantly upregulated in CS-induced macaque airways and in COPD airways that exhibited higher mucus expression and goblet cell hyperplasia. Experimental models of cells derived from COPD subjects recapitulated the augmented inflammation and mucus expression following the smoke challenge. Blocking of lncRNA expression in cell culture setting suppressed the smoke-induced and COPD-associated dysregulated mucoinflammatory response suggesting that this airway specific immunomodulatory lncRNA may represent a novel target to mitigate the smoke-mediated inflammation and mucus hyperexpression. Rationale: In conducting airways, CS disrupts airway epithelial functions, mucociliary clearances, and innate immune responses that are primarily orchestrated by human bronchial epithelial cells (HBECs). Mucus hypersecretion and dysregulated immune response are the hallmarks of chronic bronchitis (CB) that is often exacerbated by CS. Notably, we recently identified a long noncoding RNA (lncRNA) antisense to ICAM-1 (LASI) that mediates airway epithelial responses. Objective: To investigate the role of LASI lncRNA in CS-induced airway inflammation and mucin hyperexpression in an animal model of COPD, and in HBECs and lung tissues from former smokers with and without COPD. To interrogate LASI lncRNA role in CS-mediated airway mucoinflammatory responses by targeted gene editing. Methods: Small airway tissue sections from cynomolgus macaques exposed to long-term mainstream CS, and those from former smokers with and without COPD were analyzed. The structured-illumination imaging, RNA fluorescence in-situ hybridization (FISH), and qRT-PCR were used to characterize lncRNA expression and the expression of inflammatory factors and airway mucins in a cell culture model of CS extract (CSE) exposure using HBECs from COPD (CHBEs) in comparison with cells from normal control (NHBEs) subjects. The protein levels of mucin MUC5AC, and inflammatory factors ICAM-1, and IL-6 were determined using specific ELISAs. RNA silencing was used to block LASI lncRNA expression and lentivirus encoding LASI lncRNA was used to achieve LASI overexpression (LASI-OE). Results: Compared to controls, LASI lncRNA was upregulated in CS-exposed macaques and in COPD smoker airways, correlating with mucus hyperexpression and mucus cell hyperplasia in severe COPD airways. At baseline, the unstimulated CHBEs showed increased LASI lncRNA expression with higher expression of secretory mucin MUC5AC, and inflammatory factors, ICAM-1, and IL-6 compared to NHBEs. CSE exposure of CHBEs resulted in augmented inflammation and mucus expression compared to controls. While RNA silencing-mediated LASI knockdown suppressed the mucoinflammatory response, cells overexpressing LASI lncRNA showed elevated mRNA levels of inflammatory factors. Conclusions: Altogether, LASI lncRNA may represent a novel target to control the smoke-mediated dysregulation in airway responses and COPD exacerbations.


Assuntos
Fumar Cigarros , Doença Pulmonar Obstrutiva Crônica , RNA Longo não Codificante , Animais , Fumar Cigarros/efeitos adversos , Células Caliciformes/metabolismo , Humanos , Hiperplasia , Inflamação , Molécula 1 de Adesão Intercelular/genética , Interleucina-6 , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/metabolismo , RNA Longo não Codificante/genética , Tabaco/efeitos adversos
4.
Sci Rep ; 12(1): 12139, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35840660

RESUMO

Tobacco smoking is an important risk factor for peripheral artery disease (PAD), but it remains unknown whether smokeless tobacco, such as Swedish snuff (snus), is also associated with this disease. We used data from the Cohort of Swedish Men including 24,085 men. Individuals were grouped into never, past, and current snus dippers as well as never, past quitting ≥ 10 years, past, quitting < 10 years, and current smokers. Incident PAD cases were defined by linkage of the cohort with the Swedish National Patient Register. Cox proportional hazards regression was used to analyze the data. Over a mean follow-up period of 9.1 years (from July 1, 2009 to December 31, 2019), 655 incident PAD cases were ascertained. Cigarette smoking but not Swedish snus dipping was associated with an increased risk of PAD. Compared with never snus dippers, the hazard ratio of PAD was 0.95 (95% confidence interval [CI] 0.73-1.24) for past snus dippers and 0.88 (95% CI 0.66-1.17) for current snus dippers. Compared to never smokers, the hazard ratio of PAD was 1.38 (95% CI 1.14-1.68) for past smoker who stopped smoking for ≥ 10 years, 2.61 (95% CI 1.89-3.61) for past smoker who stopped smoking for < 10 years, and 4.01 (95% CI 3.17, 5.08) for current smoker. In conclusion, cigarette smoking but not Swedish snus dipping increases the risk of PAD.


Assuntos
Fumar Cigarros , Doença Arterial Periférica , Tabaco sem Fumaça , Fumar Cigarros/efeitos adversos , Fumar Cigarros/epidemiologia , Estudos de Coortes , Humanos , Masculino , Doença Arterial Periférica/epidemiologia , Doença Arterial Periférica/etiologia , Estudos Prospectivos , Suécia/epidemiologia , Tabaco sem Fumaça/efeitos adversos
5.
Nat Commun ; 13(1): 3852, 2022 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-35789151

RESUMO

Although cigarette smoking is known to exacerbate asthma, only a few clinical asthma studies have been conducted involving smokers. Here we show, by comparing paired sputum and blood samples from smoking and non-smoking patients with asthma, that smoking associates with significantly higher frequencies of pro-inflammatory, natural-cytotoxicity-receptor-non-expressing type 3 innate lymphoid cells (ILC3) in the sputum and memory-like, CD45RO-expressing ILC3s in the blood. These ILC3 frequencies positively correlate with circulating neutrophil counts and M1 alveolar macrophage frequencies, which are known to increase in uncontrolled severe asthma, yet do not correlate with circulating eosinophil frequencies that characterize allergic asthma. In vitro exposure of ILCs to cigarette smoke extract induces expression of the memory marker CD45RO in ILC3s. Cigarette smoke extract also impairs the barrier function of airway epithelial cells and increases their production of IL-1ß, which is a known activating factor for ILC3s. Thus, our study suggests that cigarette smoking increases local and circulating frequencies of activated ILC3 cells, plays a role in their activation, thereby aggravating non-allergic inflammation and the severity of asthma.


Assuntos
Asma , Fumar Cigarros , Fumar Cigarros/efeitos adversos , Eosinófilos , Humanos , Imunidade Inata , Linfócitos
6.
Biol Sex Differ ; 13(1): 36, 2022 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-35799275

RESUMO

BACKGROUND: Whether cigarette smoking affects the heart post-myocardial infarction (MI) in a sex-dependent way remains controversial. Using a mouse model, we investigated cardiac remodeling under the influence of acute cigarette smoke (CS) exposure following ischemic injury in both sexes. METHODS: Ten cigarettes were smoked twice daily for 2 weeks followed by MI and then 1 additional week post permanent LAD ligation. Cardiac function, histology, and infarct size were assessed, and inflammatory markers quantified by RT-PCR. Statistical comparisons were performed using an unpaired t test or ANOVA followed by Tukey post hoc test. RESULTS: We observed that cigarette smoking exacerbated both left and right ventricular remodeling only in males at an early stage of post-MI. Females did not display a significant structural and/or functional alteration within 7 days of cardiac remodeling post-MI upon CS exposure. Worsened right ventricular remodeling in males was independent of pulmonary congestion. CS-exposed males exhibited enhanced increases in left ventricular end systolic and diastolic volumes, as well as reductions in ejection fraction and fractional area changes of left ventricular base. At day 7, infarct size was increased by cigarette smoking in males only, which was accompanied by enhanced collagen deposition in both the infarcted and peri-infarcted areas. Both IL-6 and TNF-α mRNA expression significantly increased in CS-exposed MI male group only at day 7 post-MI suggestive of prolonged inflammation. CONCLUSIONS: These findings indicate that CS exposure worsens the progression of cardiac remodeling post-MI in male sex in a significant manner compared to female sex at least at early stages.


Assuntos
Fumar Cigarros , Infarto do Miocárdio , Fumar Cigarros/efeitos adversos , Feminino , Coração , Humanos , Masculino , Infarto do Miocárdio/complicações , Infarto do Miocárdio/patologia , Caracteres Sexuais , Remodelação Ventricular/genética
7.
Birth Defects Res ; 114(13): 746-758, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35757961

RESUMO

BACKGROUND: Congenital diaphragmatic hernia (CDH) occurs when abnormal diaphragm development allows herniation of abdominal organs into the thoracic cavity. Its etiopathogenesis is not well understood, but cigarette smoking and alcohol exposure may impact diaphragm development. Using data from a large, population-based case-control study, we examined associations between maternal cigarette smoking and alcohol consumption and CDH in offspring. METHODS: We analyzed maternal interview reports of cigarette smoking and alcohol consumption during early pregnancy for 831 children with CDH and 11,416 children without birth defects with estimated dates of delivery during 1997-2011. Generalized linear mixed effects models with a random intercept for study site were used to estimate associations between measures of exposure to smoking (any, type, frequency, duration) and alcohol (any, quantity, frequency, variability, type) for all CDH combined and selected subtypes (Bochdalek and Morgagni). RESULTS: Mothers of 280 (34.0%) case and 3,451 (30.3%) control children reported early pregnancy exposure to cigarette smoking. Adjusted odds ratios for all CDH were increased for any (1.3; 95% confidence interval 1.1-1.5), active (1.3, 1.0-1.7), and passive (1.4, 1.1-1.7) smoking. Early pregnancy alcohol consumption was reported by mothers of 286 (34.9%) case and 4,200 (37.0%) control children; odds were near the null for any consumption (0.9, 0.8-1.1) and consumption with (0.9, 0.7, 1.1) or without (0.9, 0.8, 1.1) binging. Estimates for smoking and alcohol tended to be higher for Bochdalek CDH and Morgagni CDH than those for all CDH. CONCLUSIONS: Findings suggest that maternal early pregnancy exposure to cigarette smoking, but less so to alcohol consumption, contributes to CDH. These findings need to be replicated in additional large studies that use systematic case ascertainment and classification, detailed exposure assessment, and examine subtype-specific associations.


Assuntos
Fumar Cigarros , Hérnias Diafragmáticas Congênitas , Consumo de Bebidas Alcoólicas/efeitos adversos , Estudos de Casos e Controles , Criança , Fumar Cigarros/efeitos adversos , Feminino , Hérnias Diafragmáticas Congênitas/etiologia , Humanos , Exposição Materna/efeitos adversos , Gravidez
8.
Eur Respir Rev ; 31(164)2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-35705209

RESUMO

COPD is predicted to become the third leading cause of morbidity and mortality worldwide by 2030. Cigarette smoking (active or passive) is one of its chief causes, with about 20% of cigarette smokers developing COPD from cigarette smoke (CS)-induced irreversible damage and sustained inflammation of the airway epithelium. Inflammasome activation leads to the cleavage of pro-interleukin (IL)-1ß and pro-IL-18, along with the release of pro-inflammatory cytokines via gasdermin D N-terminal fragment membrane pores, which further triggers acute phase pro-inflammatory responses and concurrent pyroptosis. There is currently intense interest in the role of nucleotide-binding oligomerisation domain-like receptor family, pyrin domain containing protein-3 inflammasomes in chronic inflammatory lung diseases such as COPD and their potential for therapeutic targeting. Phytochemicals including polyphenols and flavonoids have phyto-medicinal benefits in CS-COPD. Here, we review published articles from the last decade regarding the known associations between inflammasome-mediated responses and ameliorations in pre-clinical manifestations of CS-COPD via polyphenol and flavonoid treatment, with a focus on the underlying mechanistic insights. This article will potentially assist the development of drugs for the prevention and therapy of COPD, particularly in cigarette smokers.


Assuntos
Fumar Cigarros , Doença Pulmonar Obstrutiva Crônica , Fumar Cigarros/efeitos adversos , Flavonoides/uso terapêutico , Humanos , Inflamassomos , Inflamação , Polifenóis , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/etiologia
9.
Eur Respir Rev ; 31(164)2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-35675921

RESUMO

Cigarette smoke (CS) exposure is a key risk factor for both active and latent tuberculosis (TB). It is associated with delayed diagnosis, more severe disease progression, unfavourable treatment outcomes and relapse after treatment. Critically, CS exposure is common in heavily populated areas with a high burden of TB, such as China, India and the Russian Federation. It is therefore prudent to evaluate interventions for TB while taking into account the immunological impacts of CS exposure. This review is a mechanistic examination of how CS exposure impairs innate barrier defences, as well as alveolar macrophage, neutrophil, dendritic cell and T-cell functions, in the context of TB infection and disease.


Assuntos
Fumar Cigarros , Tuberculose Latente , Tuberculose , Fumar Cigarros/efeitos adversos , Fumar Cigarros/epidemiologia , Humanos , Neutrófilos , Tabaco
10.
Biomed Res Int ; 2022: 9170722, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35769670

RESUMO

Objective: The aims of this study were to screen the gene mutations that are able to predict the risk of cigarette smoking-related lung adenocarcinoma (LUAD) and to evaluate its prognostic significance. Methods: Clinical data and genetic information were retrieved from the TCGA database, and the patients with LUAD were divided into three groups including never smoking, light smoking, and heavy smoking according to cigarette smoking dose. Differentially mutated genes (DMGs) of each group were analyzed. At the same time, the function of DMGs in three smoking groups was evaluated by GO function and KEGG pathway analysis. The driver genes and protein variation effect of DMGs were performed to further screen key genes. The survival characteristics of the gene expression and mutation of those genes were analyzed and plotted to visualize by the Kaplan-Meier model. Result: The DMGs for different smoking doses were identified. The driver and deleterious mutation in the DMGs were screened and gene interaction network was constructed. The DMGs with driver mutations and deleterious mutations that were associated with the overall survival in the heavy smoking patients were considered as the candidate genes for novel markers of smoking-related LUAD. The final novel risk factor gene was identified as MYH7 and the high express of MYH7 in LUAD correlation with patients' gender, lymph node metastasis, T stage, and clinical stage. Conclusions: In summary, it can be concluded that MYH7 is a novel biomarker for heavy smoking-related LUAD and it is significantly correlated with the prognosis of lung cancer and is related to the clinical characteristics of lung cancer.


Assuntos
Adenocarcinoma de Pulmão , Fumar Cigarros , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/patologia , Biomarcadores , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Fumar Cigarros/efeitos adversos , Fumar Cigarros/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , Prognóstico
11.
Respir Res ; 23(1): 148, 2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35676684

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with elevated ATP levels in the extracellular space. Once released, ATP serves as danger signal modulating immune responses by activating purinergic receptors. Accordingly, purinergic signalling has been implicated in respiratory inflammation associated with cigarette smoke exposure. However, the role of P2X4-signalling has not been fully elucidated yet. METHODS: Here, we analysed the P2X4 mRNA expression in COPD patients as well as cigarette smoke-exposed mice. Furthermore, P2X4-signalling was blocked by either using a specific antagonist or genetic depletion of P2rx4 in mice applied to an acute and prolonged model of cigarette smoke exposure. Finally, we inhibited P2X4-signalling in macrophages derived from THP-1 before stimulation with cigarette smoke extract. RESULTS: COPD patients exhibited an increased P2X4 mRNA expression in cells isolated from the bronchoalveolar lavage fluid and peripheral mononuclear cells. Similarly, P2rx4 expression was elevated in lung tissue of mice exposed to cigarette smoke. Blocking P2X4-signalling in mice alleviated cigarette smoke induced airway inflammation as well as lung parenchyma destruction. Additionally, human macrophages derived from THP-1 cells released reduced concentrations of proinflammatory cytokines in response to cigarette smoke extract stimulation when P2X4 was inhibited. CONCLUSION: Taken together, we provide evidence that P2X4-signalling promotes innate immunity in the immunopathologic responses induced by cigarette smoke exposure.


Assuntos
Fumar Cigarros , Pneumonia , Doença Pulmonar Obstrutiva Crônica , Antagonistas do Receptor Purinérgico P2X , Receptores Purinérgicos P2X4 , Trifosfato de Adenosina/metabolismo , Animais , Líquido da Lavagem Broncoalveolar , Fumar Cigarros/efeitos adversos , Humanos , Imunidade Inata , Inflamação/metabolismo , Pulmão/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Pneumonia/induzido quimicamente , Pneumonia/genética , Pneumonia/prevenção & controle , Doença Pulmonar Obstrutiva Crônica/metabolismo , Antagonistas do Receptor Purinérgico P2X/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Purinérgicos P2X4/genética , Células THP-1
12.
Ann Agric Environ Med ; 29(2): 246-251, 2022 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-35767758

RESUMO

INTRODUCTION AND OBJECTIVE: Epidemiological studies have demonstrated a strong association between cigarette smoking (CS) and chronic pancreatitis (CP); however, the exact mechanisms of this phenomenon remains unknown. The authors have previously shown that increased Ras expression activates the NF-κB mediated pathway and promotes development of CP. However, it is unclear whether a similar phenomenon occurs in CS-induced CP. Therefore, the aim of the study was to determine whether CS increases the expression of K-Ras, and promotes the development of CP in mice exposed to repeated episodes of acute pancreatitis (AP). MATERIAL AND METHODS: C57BL6/cmdb mice were exposed to CS or a sham treatment for 12 weeks. After one week of exposure, half of the animals from both groups were additionally subjected to repeated cerulein treatment (once a week, for 10 consecutive weeks) to mimic recurrent episodes of AP. Extension of pancreatic damage was determined histologically by H&E and Trichrome staining. The expression of K-Ras protein and downstream components (NF-κB, Cox-2, TGF-ß) was evaluated by immunohistochemistry. RESULTS: C57BL6/cmdb mice exposed to CS or cerulein alone did not develop any chronic pancreatic damage. However, concomitant treatment with both of these agents caused focal acinar atrophy, with slight intralobular and perivascular areas of fibrosis, and inflammatory cells infiltration resembling mild CP. Moreover, immunohistochemistry examinations revealed increased pancreatic expression of K-Ras and NF-κB only in mice treated both with CS and cerulein. CONCLUSIONS: CS promotes development of CP in mice exposed to repeated episodes of AP. This process may be, at least partially, related to increased expression of K-Ras and NF-κB protein.


Assuntos
Fumar Cigarros , NF-kappa B , Pancreatite Crônica , Proteínas Proto-Oncogênicas p21(ras) , Doença Aguda , Animais , Ceruletídeo/toxicidade , Fumar Cigarros/efeitos adversos , Fumar Cigarros/genética , Fumar Cigarros/metabolismo , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/biossíntese , NF-kappa B/genética , NF-kappa B/metabolismo , Pancreatite Crônica/genética , Pancreatite Crônica/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/biossíntese , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo
13.
Oxid Med Cell Longev ; 2022: 5695005, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35571237

RESUMO

MicroRNAs (miRNAs) have been reported in human diseases, in which chronic obstructive pulmonary disease (COPD) is included. Herein, we assessed the role along with the possible mechanisms of miR-150-5p in cigarette smoke- (CS-) induced COPD. The plasma miR-150-5p expression was lower in patients with COPD and acute exacerbation of COPD (AECOPD) and was related to disease diagnosis, disease severity, and lung function. Consistently, exposure to CS for 3 months or 3 days reduced miR-150-5p in the plasma and lung tissues of mice, and CS extract (CSE) inhibited miR-150-5p in human bronchial epithelial cells (HBECs) in a concentration along with time-dependent approach. In vitro, miR-150-5p overexpression decreased the contents of inflammatory factors interleukin- (IL-) 6, IL-8 along with cyclooxygenase-2 (COX-2), and endoplasmic reticulum (ER) stress markers glucose-regulated protein (GRP) 78 and C/-EBP homologous protein (CHOP) and promoted cell migrate. Mechanistically, miR-150-5p could bind with the 3'-untranslated region (UTR) of inositol requiring enzyme 1α (IRE1α), while IRE1α overexpression obliterated the impacts of miR-150-5p. Besides, N-acetyl-cysteine (NAC) reversed CSE-induced miR-150-5p downregulation and its downstream effects. In vivo, miR-150-5p overexpression counteracted CS-triggered IRE1α upregulation, inflammation, and ER stress in the lung tissues of mice. In conclusion, our findings illustrated that ROS-mediated downregulation of miR-150-5p led to CS-induced COPD by inhibiting IRE1α expression, suggesting to serve as a useful biomarker for diagnosing and treating COPD.


Assuntos
Fumar Cigarros , MicroRNAs , Doença Pulmonar Obstrutiva Crônica , Regiões 3' não Traduzidas , Animais , Biomarcadores/metabolismo , Fumar Cigarros/efeitos adversos , Regulação para Baixo , Endorribonucleases/metabolismo , Humanos , Inositol , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Serina-Treonina Quinases , Doença Pulmonar Obstrutiva Crônica/metabolismo , Espécies Reativas de Oxigênio/metabolismo
14.
BMC Oral Health ; 22(1): 206, 2022 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-35614406

RESUMO

BACKGROUND: The aim was to assess the association between levels of advanced glycation endproducts (AGEs) in the gingival crevicular fluid (GCF) and periodontal parameters among cigarette-smokers and waterpipe-users. METHODS: Self-reported cigarette-smokers; waterpipe-users and never-smokers were included. Demographic data was recorded using a questionnaire. Periodontal parameters (plaque index [PI], gingival index [GI], clinical attachment loss [AL], probing depth [PD], and marginal bone loss [MBL]) were assessed in all groups. The GCF samples were collected using standard techniques and assessed for AGEs levels using enzyme-linked immunosorbent assay. Sample-size estimation was done and group-comparisons were done. Correlation between levels of GCF AGEs levels and periodontal parameters was assessed using a logistic regression model. Level of significance was set at P < 0.01. RESULTS: Eighty-two individuals (28 cigarette-smokers, 28 waterpipe-users and 26 never-smokers) were included. There was no difference in mean ages of all patients. Cigarette-smokers had a smoking history of 5.1 ± 0.2 pack years and waterpipe-users were using waterpipe for 4.4 ± 0.6 years. There was no statistically significant difference in PI, GI, clinical AL, PD and MBL in all groups. Levels of AGEs were significantly higher among cigarette-smokers (P < 0.001) and waterpipe-users (P < 0.001) than never-smokers. There was no significant correlation between levels of GCF AGEs levels and periodontal parameters in all groups. CONCLUSION: Clinical periodontal status of individuals with a short history of cigarette-smoking and waterpipe-usage may appear similar to never-smokers. On a molecular level, cigarette-smoking and waterpipe-users express raised levels of AGEs than never-smokers that sirens about the ongoing yet latent periodontal inflammatory process.


Assuntos
Fumar Cigarros , Produtos Finais de Glicação Avançada , Fumar Cachimbo de Água , Fumar Cigarros/efeitos adversos , Índice de Placa Dentária , Líquido do Sulco Gengival/química , Líquido do Sulco Gengival/efeitos dos fármacos , Produtos Finais de Glicação Avançada/efeitos adversos , Produtos Finais de Glicação Avançada/efeitos dos fármacos , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Doenças Periodontais/etiologia , Fumantes , Produtos do Tabaco/efeitos adversos , Fumar Cachimbo de Água/efeitos adversos
15.
Respir Res ; 23(1): 110, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35509068

RESUMO

BACKGROUND: Retinoid-related orphan receptor-α (RORα) and autophagy dysregulation are involved in the pathophysiology of chronic obstructive pulmonary disease (COPD), but little is known regarding their association. We investigated the role of RORα in COPD-related autophagy. METHODS: The lung tissues and cells from a mouse model were analyzed for autophagy markers by using western blot analysis and transmission electron microscopy. RESULTS: Cigarette smoke increased the LC3-II level and decreased the p62 level in whole lung homogenates of a chronic cigarette smoking mouse model. Although cigarette smoke did not affect the levels of p62 in Staggerer mutant mice (RORαsg/sg), the baseline expression levels of p62 were significantly higher than those in wild type (WT) mice. Autophagy was induced by cigarette smoke extract (CSE) in Beas-2B cells and in primary fibroblasts from WT mice. In contrast, fibroblasts from RORαsg/sg mice failed to show CSE-induced autophagy and exhibited fewer autophagosomes, lower LC3-II levels, and higher p62 levels than fibroblasts from WT mice. Damage-regulated autophagy modulator (DRAM), a p53-induced modulator of autophagy, was expressed at significantly lower levels in the fibroblasts from RORαsg/sg mice than in those from WT mice. DRAM knockdown using siRNA in Beas-2B cells inhibited CSE-induced autophagy and cell death. Furthermore, RORα co-immunoprecipitated with p53 and the interaction increased p53 reporter gene activity. CONCLUSIONS: Our findings suggest that RORα promotes autophagy and contributes to COPD pathogenesis via regulation of the RORα-p53-DRAM pathway.


Assuntos
Fumar Cigarros , Doença Pulmonar Obstrutiva Crônica , Animais , Autofagia , Fumar Cigarros/efeitos adversos , Camundongos , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Tabaco , Proteína Supressora de Tumor p53/efeitos adversos
16.
CNS Neurosci Ther ; 28(8): 1195-1204, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35506354

RESUMO

AIMS: Cigarette smoking is a modifiable risk factor for Alzheimer's disease (AD), and controlling risk factors may curb the progression of AD. However, the underlying neural mechanisms of the effects of smoking on cognition remain largely unclear. Therefore, we aimed to explore the interaction effects of smoking × cognitive status on cortico-striatal circuits, which play a crucial role in addiction and cognition, in individuals without dementia. METHODS: We enrolled 304 cognitively normal (CN) non-smokers, 44 CN smokers, 130 mild cognitive impairment (MCI) non-smokers, and 33 MCI smokers. The mixed-effect analysis was performed to explore the interaction effects between smoking and cognitive status (CN vs. MCI) based on functional connectivity (FC) of the striatal subregions (caudate, putamen, and nucleus accumbens [NAc]). RESULTS: The significant interaction effects of smoking × cognitive status on FC of the striatal subregions were detected in the left inferior parietal lobule (IPL), bilateral cuneus, and bilateral anterior cingulate cortex (ACC). Specifically, increased FC of right caudate to left IPL was found in CN smokers compared with non-smokers. The MCI smokers showed decreased FC of right caudate to left IPL and of right putamen to bilateral cuneus and increased FC of bilateral NAc to bilateral ACC compared with CN smokers and MCI non-smokers. Furthermore, a positive correlation between FC of the NAc to ACC with language and memory was detected in MCI smokers. CONCLUSIONS: Cigarette smoking could affect the function of cortico-striatal circuits in patients with MCI. Our findings suggest that quitting smoking in the prodromal stage of AD may have the potential to prevent disease progression.


Assuntos
Doença de Alzheimer , Fumar Cigarros , Disfunção Cognitiva , Fumar Cigarros/efeitos adversos , Cognição , Disfunção Cognitiva/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Fumar/efeitos adversos
17.
Molecules ; 27(9)2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35566351

RESUMO

Thyroid autoimmunity in Graves' disease (GD) is accompanied by Graves' orbitopathy (GO) in 40% of the cases. Orbital fibroblasts (OF) play a key role in the pathogenesis and cigarette smoking is a known deteriorating factor. Alongside conventional cigarettes (CC) new alternatives became available for smokers, including heated tobacco products (HTP) and E-cigarettes (ECIG). We aimed to study the cellular effects of smoke extracts (SE) in orbital fibroblasts. Primary OF cultures from GO and NON-GO orbits were exposed to different concentrations of SE (1%, 50%) and the changes were followed using Real Time Cell Electronic Sensing (RT-CES). Untreated GO and NON-GO cells had different maximum cell index (CI) values of 3.3 and 2.79 respectively (p < 0.0001). CC, HTP and ECIG treated NON-GO fibroblasts exhibited peak CIs of 2.62, 3.32 and 3.41 while treated GO cells' CIs were higher, 5.38, 6.25 and 6.33, respectively (p < 0.0001). The metabolic activity (MTT) decreased (p < 0.001) and hyaluronan production doubled (p < 0.02) after 50% of CC SE treatment in all cell cultures. GO fibroblasts were more sensitive to low concentration SE then NON-GO fibroblasts (p < 0.0001). The studied SEs exerted different effects. RT-CES is a sensitive technique to detect the effects of very low concentration of SE on fibroblasts.


Assuntos
Fumar Cigarros , Vapor do Cigarro Eletrônico , Sistemas Eletrônicos de Liberação de Nicotina , Oftalmopatia de Graves , Produtos do Tabaco , Células Cultivadas , Fumar Cigarros/efeitos adversos , Eletrônica , Fibroblastos , Oftalmopatia de Graves/complicações , Oftalmopatia de Graves/metabolismo , Oftalmopatia de Graves/patologia , Humanos
18.
J Transl Med ; 20(1): 222, 2022 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-35568871

RESUMO

BACKGROUND: Cigarette smoking (CS) is a strong risk factor for idiopathic pulmonary fibrosis (IPF). It can activate lung fibroblasts (LF) by inducing redox imbalance. We previously showed that clearing mitochondrial reactive oxygen species (mtROS) protects against CS-induced pulmonary fibrosis. However, the precise mechanisms of mtROS in LF need further investigation. Here we focused on mtROS to elucidate how it was regulated by CS in LF and how it contributed to LF activation. METHODS: We treated cells with 1% cigarette smoking extract (CSE) and examined mtROS level by MitoSOX™ indicator. And the effect of CSE on expression of SIRT1, SOD2, mitochondrial NOX4 (mtNOX4), fatty acid oxidation (FAO)-related protein PPARα and CPT1a and LF activation marker Collagen I and α-SMA were detected. Nile Red staining was performed to show cellular lipid content. Then, lipid droplets, autophagosome and lysosome were marked by Bodipy 493/503, LC3 and LAMP1, respectively. And lipophagy was evaluated by the colocalization of lipid droplets with LC3 and LAMP1. The role of autophagy on lipid metabolism and LF activation were explored. Additionally, the effect of mitochondria-targeted ROS scavenger mitoquinone and SIRT1 activator SRT1720 on mitochondrial oxidative stress, autophagy flux, lipid metabolism and LF activation were investigated in vitro and in vivo. RESULTS: We found that CS promoted mtROS production by increasing mtNOX4 and decreasing SOD2. Next, we proved mtROS inhibited the expression of PPARα and CPT1a. It also reduced lipophagy and upregulated cellular lipid content, suggesting lipid metabolism was disturbed by CS. In addition, we showed both insufficient FAO and lipophagy resulted from blocked autophagy flux caused by mtROS. Moreover, we uncovered decreased SIRT1 was responsible for mitochondrial redox imbalance. Furthermore, we proved that both SRT1720 and mitoquinone counteracted the effect of CS on NOX4, SOD2, PPARα and CPT1a in vivo. CONCLUSIONS: We demonstrated that CS decreased SIRT1 to activate LF through dysregulating lipid metabolism, which was due to increased mtROS and impaired autophagy flux. These events may serve as therapeutic targets for IPF patients.


Assuntos
Fumar Cigarros , Fibrose Pulmonar Idiopática , Metabolismo dos Lipídeos , Estresse Oxidativo , Sirtuína 1 , Autofagia , Fumar Cigarros/efeitos adversos , Fibroblastos/metabolismo , Humanos , Fibrose Pulmonar Idiopática/metabolismo , Lipídeos , Pulmão/metabolismo , PPAR alfa/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sirtuína 1/metabolismo
19.
Cells ; 11(10)2022 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-35626724

RESUMO

Toxins present in cigarette and e-cigarette smoke constitute a significant cause of illnesses and are known to have fatal health impacts. Specific mechanisms by which toxins present in smoke impair cell repair are still being researched and are of prime interest for developing more effective treatments. Current literature suggests toxins present in cigarette smoke and aerosolized e-vapor trigger abnormal intercellular responses, damage mitochondrial function, and consequently disrupt the homeostasis of the organelle's biochemical processes by increasing reactive oxidative species. Increased oxidative stress sets off a cascade of molecular events, disrupting optimal mitochondrial morphology and homeostasis. Furthermore, smoking-induced oxidative stress may also amalgamate with other health factors to contribute to various pathophysiological processes. An increasing number of studies show that toxins may affect mitochondria even through exposure to secondhand or thirdhand smoke. This review assesses the impact of toxins present in tobacco smoke and e-vapor on mitochondrial health, networking, and critical structural processes, including mitochondria fission, fusion, hyper-fusion, fragmentation, and mitophagy. The efforts are focused on discussing current evidence linking toxins present in first, second, and thirdhand smoke to mitochondrial dysfunction.


Assuntos
Fumar Cigarros , Sistemas Eletrônicos de Liberação de Nicotina , Poluição por Fumaça de Tabaco , Vaping , Fumar Cigarros/efeitos adversos , Mitocôndrias , Tabaco , Vaping/efeitos adversos
20.
Genes (Basel) ; 13(5)2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35627191

RESUMO

Cigarette smoking (CS) leads to significant bone loss, which is recognized as an independent risk factor for osteoporosis. The number of smokers is continuously increasing due to the addictive nature of smoking. Therefore it is of great value to effectively prevent CS-induced osteoporosis. However, there are currently no effective interventions to specifically counteract CS-induced osteoporosis, owing to the fact that the specific mechanisms by which CS affects bone metabolism are still elusive. This review summarizes the latest research findings of important pathways between CS exposure and bone metabolism, with the aim of providing new targets and ideas for the prevention of CS-induced osteoporosis, as well as providing theoretical directions for further research in the future.


Assuntos
Fumar Cigarros , Osteoporose , Fumar Cigarros/efeitos adversos , Humanos , Osteoporose/induzido quimicamente , Fatores de Risco
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