O USO DE ÍNDICES DE AVALIAÇÃO COMO ARGUMENTO DE QUALIDADE DAS INSTITUIÇÕES DE EDUCAÇÃO SUPERIOR

CpGs differentially methylated in lung DNA in relation to COPD vs. non-smokers (P < 0.01). (CSV 273 kb

Additional file 1 of Tobacco-derived and tobacco-free nicotine cause differential inflammatory cell influx and MMP-9 in mouse lung

Additional file 1: Figure S1. Differential effects of synthetic and tobacco-derived nicotine salts on infiltrating inflammatory cells in lung homogenates. Figure S2: Full images of MMP-9 for PG/VG with TFN salts and PG/VG with TDN salts exposure. Figure S3: Full images of MMP-2 for PG/VG with TFN salts and PG/VG with TDN salts exposure. Figure S4: Full images of MMP-12 for PG/VG with TFN salts and PG/VG with TDN salts exposure. Figure S5: Full images of GAPDH for MMP-9, MMP-2, and MMP-12 for PG/VG with TFN salts and PG/VG with TDN salts exposure. Figure S6: Full images of TIMP-1 for PG/VG with TFN salts and PG/VG with TDN salts exposure. Figure S7: Full images of GAPDH for TIMP-1 for PG/VG with TFN salts and PG/VG with TDN salts exposure. Figure S8: Full images of gelatin gels for PG/VG with TDN salts and PG/VG with TFN salts exposure

p21 deletion increased the levels of PAR, which was reduced by 3-AB treatment.

<p>The levels of PAR and PARP-1 were determined by Western blot in lungs of C57BL/6J (<b>A</b>), and p21^-/- mice as well as WT littermates (<b>B</b>) in response to CS. PAR levels were increased in lungs of p21^-/- mice as compared to WT mice. 3-AB treatment reduced PAR level in lungs of both p21^-/- and WT mice. Intact PARP-1 level was not altered by either p21 deficiency or 3-AB treatment. Gel pictures shown are representative of at least 3 separate mice. Fold change is indicative of the alteration of PAR and PARP-1 compared with air-exposed and vehicle (Veh)-treated WT mice after normalizing to corresponding GAPDH or β-actin. Data are shown as mean ± SEM (n = 3-13 per group).^*<i>P</i><0.05 <i>vs</i> air group; ⁺<i>P</i><0.05, ⁺⁺<i>P</i><0.01, ⁺⁺⁺<i>P</i><0.001 <i>vs</i> Veh group; ^†††<i>P</i><0.001 <i>vs</i> WT mice.</p

3-AB increases CS-induced cellular senescence, but does not affect neutrophil influx in mouse lungs.

<p>3-AB augmented CS-induced increase in SA-β-gal activity in WT, but not p21^-/- mice (<b>A</b>). p21 deletion increased the expression of PCNA in lungs as compared to WT mice exposed to CS, which was reduced by 3-AB treatment (<b>B</b>). p21 deletion attenuated CS-induced neutrophil influx in BAL fluid, which was not affected by 3-AB (<b>C</b>). Original magnification, ×200. Gel pictures shown are representative of at least 3 separate mice. Relative density ratio is indicative of results after normalizing to corresponding GAPDH. Data are shown as mean ± SEM (n = 3-4 per group). ^*<i>P</i><0.05, ^**<i>P</i><0.01 <i>vs</i> air group; ⁺<i>P</i><0.05, ⁺⁺⁺<i>P</i><0.001 <i>vs</i> Veh group; ^††<i>P</i><0.01, ^†††<i>P</i><0.001 <i>vs</i> WT mice.</p

A schematic model showing the role of p21-PARP-1 in acute cigarette smoke (CS)-induced DNA damage and cellular senescence.

<p>CS exposure causes DNA damage including double-strand break (DSB). CS exposure also increases the level of p21, and p21 gene deletion augments PARP-1 activity and the levels of non-homologous end joining (NHEJ) proteins to repair damaged DNA. Consequently, CS-induced cellular senescence is attenuated by p21 deletion.</p

Additional file 1 of Tobacco and menthol flavored nicotine-free electronic cigarettes induced inflammation and dysregulated repair in lung fibroblast and epithelium

Supplementary Material 1: Full western blot images reflecting all blots/bands are given in Suppl Fig

Cigarette Smoke Induces Distinct Histone Modifications in Lung Cells: Implications for the Pathogenesis of COPD and Lung Cancer

Cigarette smoke (CS)-mediated oxidative stress induces several signaling cascades, including kinases, which results in chromatin modifications (histone acetylation/deacetylation and histone methylation/demethylation). We have previously reported that CS induces chromatin remodeling in pro-inflammatory gene promoters; however, the underlying site-specific histone marks formed in histones H3 and H4 during CS exposure in lungs <i>in vivo</i> and in lung cells <i>in vitro</i>, which can either drive gene expression or repression, are not known. We hypothesize that CS exposure in mouse and human bronchial epithelial cells (H292) can cause site-specific posttranslational histone modifications (PTMs) that may play an important role in the pathogenesis of CS-induced chronic lung diseases. We used a bottom-up mass spectrometry approach to identify some potentially novel histone marks, including acetylation, monomethylation, and dimethylation, in specific lysine and arginine residues of histones H3 and H4 in mouse lungs and H292 cells. We found that CS-induced distinct posttranslational histone modification patterns in histone H3 and histone H4 in lung cells, which may be considered as usable biomarkers for CS-induced chronic lung diseases. These identified histone marks (histone H3 and histone H4) may play an important role in the epigenetic state during the pathogenesis of smoking-induced chronic lung diseases, such as chronic obstructive pulmonary disease and lung cancer

Cigarette Smoke Induces Distinct Histone Modifications in Lung Cells: Implications for the Pathogenesis of COPD and Lung Cancer

Cigarette smoke (CS)-mediated oxidative stress induces several signaling cascades, including kinases, which results in chromatin modifications (histone acetylation/deacetylation and histone methylation/demethylation). We have previously reported that CS induces chromatin remodeling in pro-inflammatory gene promoters; however, the underlying site-specific histone marks formed in histones H3 and H4 during CS exposure in lungs <i>in vivo</i> and in lung cells <i>in vitro</i>, which can either drive gene expression or repression, are not known. We hypothesize that CS exposure in mouse and human bronchial epithelial cells (H292) can cause site-specific posttranslational histone modifications (PTMs) that may play an important role in the pathogenesis of CS-induced chronic lung diseases. We used a bottom-up mass spectrometry approach to identify some potentially novel histone marks, including acetylation, monomethylation, and dimethylation, in specific lysine and arginine residues of histones H3 and H4 in mouse lungs and H292 cells. We found that CS-induced distinct posttranslational histone modification patterns in histone H3 and histone H4 in lung cells, which may be considered as usable biomarkers for CS-induced chronic lung diseases. These identified histone marks (histone H3 and histone H4) may play an important role in the epigenetic state during the pathogenesis of smoking-induced chronic lung diseases, such as chronic obstructive pulmonary disease and lung cancer

Data_Sheet_1_Inhibition of RAGE Attenuates Cigarette Smoke-Induced Lung Epithelial Cell Damage via RAGE-Mediated Nrf2/DAMP Signaling.pdf

<p>The oxidative stress and cellular apoptosis by environmental factor including cigarette smoke induces alveolar airway remodeling leading to chronic obstructive pulmonary disease (COPD). Recently, the receptor for advanced glycan end products (RAGE) which is highly expressed in alveolar epithelium is emerging as a biomarker for COPD susceptibility or progression. However, it still remains unknown how RAGE plays a role in cigarette smoke extract (CSE)-exposed human alveolar type II epithelial cell line. Therefore, we determined the efficacy of RAGE-specific antagonist FPS-ZM1 in response to CSE-induced lung epithelial cells. CSE induced the elevated generation of RONS and release of pro-inflammatory cytokines, and impaired the cellular antioxidant defense system. Further, CSE induced the alteration of RAGE distribution via the activation of redox-sensitive DAMP (Damage-associated molecular patterns) signaling through Nrf2 in cells. Although pre-treatment with SB202190 (p38 inhibitor) or SP600125 (JNK inhibitor) failed to recover the alteration of RAGE distribution, treatment of FPS-ZM1 significantly exhibited anti-inflammatory and anti-oxidative/nitrosative effects, also inhibited the activation of redox-sensitive DAMP signaling through Nrf2 (nuclear factor erythroid 2-related factor 2) migration in the presence of CSE. Taken together, our data demonstrate that RAGE and Nrf2 play a pivotal role in maintenance of alveolar epithelial integrity.</p

Estimated FDR and power of compared RNA-seq differential analysis methods from log-normal distributed RNA-seq count data.

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