scholarly journals p300/Sp1-Mediated High Expression of p16 Promotes Endothelial Progenitor Cell Senescence Leading to the Occurrence of Chronic Obstructive Pulmonary Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Zhihui He ◽  
Huaihuai Peng ◽  
Min Gao ◽  
Guibin Liang ◽  
Menghao Zeng ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Peripheral Blood ◽  
Promoter Region ◽  
High Expression ◽  
Chronic Obstructive ◽  
Histone H4 ◽  
Obstructive Pulmonary Disease ◽  
Acetylation Level ◽  
Copd Patients ◽  
Histone H4 Acetylation

Objective. Chronic obstructive pulmonary disease (COPD) is a common chronic disease and develops rapidly into a grave public health problem worldwide. However, what exactly causes the occurrence of COPD remains largely unclear. Here, we are trying to explore whether the high expression of p16 mediated by p300/Sp1 can cause chronic obstructive pulmonary disease through promoting the senescence of endothelial progenitor cells (EPCs). Methods. Peripheral blood EPCs were isolated from nonsmoking non-COPD, smoking non-COPD, and smoking COPD patients. The expressions of p16, p300, and senescence-related genes were detected by RT-PCR and Western Blot. Then, we knocked down or overexpressed Sp1 and p300 and used the ChIP assay to detect the histone H4 acetylation level in the promoter region of p16, CCK8 to detect cell proliferation, flow cytometry to detect the cell cycle, and β-galactosidase staining to count the proportion of senescent cells. Results. The high expression of p16 was found in peripheral blood EPCs of COPD patients; the cigarette smoke extract (CSE) led to the increase of p16. The high expression of p16 in EPCs promoted cell cycle arrest and apoptosis. The CSE-mediated high expression of p16 promoted cell senescence. The expression of p300 was increased in peripheral blood EPCs of COPD patients. Moreover, p300/Sp1 enhanced the histone H4 acetylation level in the promoter region of p16, thereby mediating the senescence of EPCs. And knockdown of p300/Sp1 could rescue CSE-mediated cell senescence. Conclusion. p300/Sp1 enhanced the histone H4 acetylation level in the p16 promoter region to mediate the senescence of EPCs.

Study on the Expression Spectrum of miRNAs in Peripheral Blood from Patients and the Value of miR-548h-5p in the Diagnosis of Chronic Obstructive Pulmonary Disease

2020 ◽  
Vol 12 (11) ◽  
pp. 1323-1328
Author(s):  
Chun-Tao Li ◽  
Jian-Qing Zhang ◽  
Lu-Ming Dai ◽  
Jia-Qiang Zhang ◽  
Li-Zhou Fang ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Differential Expression ◽  
Pulmonary Disease ◽  
Microarray Analysis ◽  
Peripheral Blood ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Blood Samples ◽  
Qrt Pcr ◽  
Copd Patients

To seek novel miRNAs for the diagnosis of Chronic Obstructive Pulmonary Disease (COPD), this study analyzed the differential expression of miRNA from blood samples of COPD patients and healthy smokers (n = 3) by human microarray analysis. Then, some miRNAs were chosen for qRTPCR validation. A total of 158 miRNAs revealed by microarray analysis have been differentially expressed between the two groups, 33 miRNAs identified to be up-regulated, whereas 125 miRNAs have been down-regulated in COPD. qRT-PCR showed the miR-548h-5p was decreased in the COPD patients compared with healthy smokers (p = 0.04). The sensitivity and specificity of miR-548h-5p to the diagnosis of COPD were 84.6% and 81.8%, respectively. In conclusion, it is recommend that miR-548h-5p as an approach to the diagnosis of COPD.

scholarly journals Local and Systemic Oxidative Stress and Glucocorticoid Receptor Levels in Chronic Obstructive Pulmonary Disease Patients

2013 ◽  
Vol 20 (1) ◽  
pp. 35-41 ◽  
Author(s):  
Mian Zeng ◽  
Yue Li ◽  
Yujie Jiang ◽  
Guifang Lu ◽  
Xiaomei Huang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Obstructive Pulmonary Disease ◽  
Peripheral Blood ◽  
Induced Sputum ◽  
Chronic Obstructive ◽  
Peripheral Blood Leukocytes ◽  
Blood Leukocytes ◽  
Obstructive Pulmonary Disease ◽  
Systemic Oxidative Stress ◽  
Copd Patients

BACKGROUND: Previous studies have indicated that oxidative stress plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD).OBJECTIVES: To study local and systemic oxidative stress status in COPD patients, and to clarify the relationship between local and systemic oxidative stress.METHODS: Lipid peroxide malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) and GSH peroxidase (GSH-PX) levels in induced sputum and plasma, as well as glucocorticoid receptor (GR) levels in peripheral blood leukocytes were examined in 43 acute exacerbation of COPD patients (group A), 35 patients with stable COPD (group B) and 28 healthy controls (14 smokers [group C]; 14 nonsmokers [group D]).RESULTS: MDA levels in induced sputum and plasma decreased progressively in groups A to D, with significant differences between any two groups (P<0.001). GSH, SOD and GSH-PX levels in both induced sputum and plasma increased progressively in groups A to D, with significant differences between any two groups (P<0.001). GR levels in peripheral blood leukocytes decreased progressively in groups D to A (all comparisons P<0.001). Pearson analysis revealed strong correlations between MDA, GSH, SOD and GSH-PX levels in plasma and induced sputum. The activity of SOD in plasma and sputum were both positively correlated with GR levels (partial correlation coefficients 0.522 and 0.574, respectively [P<0.001]).CONCLUSIONS: Oxidative stress levels were elevated in COPD patients. There was a correlation between local and systemic oxidative status in COPD, and between decreased SOD activity and decreased GR levels in COPD patients.

scholarly journals Effect of Physical Exercise on the Level of DNA Damage in Chronic Obstructive Pulmonary Disease Patients

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Andréa Lúcia G. da Silva ◽  
Helen T. da Rosa ◽  
Eduarda Bender ◽  
Paulo Ricardo da Rosa ◽  
Mirian Salvador ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Lipid Peroxidation ◽  
Dna Damage ◽  
Dna Repair ◽  
Physical Exercise ◽  
Pulmonary Disease ◽  
Peripheral Blood ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients

This study assessed the chronic effects of physical exercise on the level of DNA damage and the susceptibility to exogenous mutagens in peripheral blood cells of chronic obstructive pulmonary disease (COPD) patients. The case-control study enrolled COPD patients separated into two groups (group of physical exercise (PE-COPD; n=15); group of nonphysical exercise (COPD; n=36)) and 51 controls. Peripheral blood was used to evaluate DNA damage by comet assay and lipid peroxidation by measurement of thiobarbituric acid reactive species (TBARS). The cytogenetic damage was evaluated by the buccal micronucleus cytome assay. The results showed that the TBARS values were significantly lower in PE-COPD than in COPD group. The residual DNA damage (induced by methyl methanesulphonate alkylating agent) in PE-COPD was similar to the controls group, in contrast to COPD group where it was significantly elevated. COPD group showed elevated frequency of nuclear buds (BUD) and condensed chromatin (CC) in relation to PE-COPD and control groups, which could indicate a deficiency in DNA repair and early apoptosis of the damaged cells. We concluded that the physical exercise for COPD patients leads to significant decrease of lipid peroxidation in blood plasma, decrease of susceptibility to exogenous mutagenic, and better efficiency in DNA repair.

scholarly journals DNA Damage and Oxidative Stress in Patients with Chronic Obstructive Pulmonary Disease

2013 ◽  
Vol 6 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Andréa Lúcia G da Silva ◽  
Helen T da Rosa ◽  
Clara F Charlier ◽  
Miriam Salvador ◽  
Dinara J Moura ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Obstructive Pulmonary Disease ◽  
Dna Damage ◽  
Comet Assay ◽  
Blood Plasma ◽  
Peripheral Blood ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Exogenous Dna ◽  
Copd Patients

Background: We aimed to assess the level of DNA damage and susceptibility to exogenous mutagens in peripheral blood cells of Chronic Obstructive Pulmonary Disease (COPD) patients and healthy individuals by comet assay. Oxidative stress was also evaluated by means of thiobarbituric acid reactive species (TBARS) in blood plasma. Methods: Case-control study enrolling 51 COPD patients and 51 controls. Peripheral blood was used to perform the alkaline (pH>13) and neutral (pH=8.5) comet assay. For the assessment of susceptibility to exogenous DNA damage, the cells were treated with methylmethane sulfonate (MMS) for 1-hour or 3-hour at 37° C. The percentage of residual DNA damage after 3-h MMS treatment was calculated using the value of 1-h MMS treatment for each subject as 100%. Lipid peroxidation was evaluated by measuring TBARS in blood plasma. Results: DNA damage in patients was significantly higher than in controls as measured by the neutral and alkaline comet assay. Residual DNA damage detected after MMS treatment increased in patients, in contrast to controls, indicating higher susceptibility to alkylation damage and/or repair inhibition. High susceptibility to exogenous DNA damage in COPD patients correlates with high amount of TBARS and low forced vital capacity and expiratory volume. Conclusion: The positive correlation between increased susceptibility to exogenous DNA damage and TBARS levels in COPD patients suggests the possible involvement of oxidative stress in damage induction and/or repair inhibition.

Oral and Oropharyngeal Sensory Function in Adults With Chronic Obstructive Pulmonary Disease

2020 ◽  
Vol 29 (2) ◽  
pp. 864-872
Author(s):  
Fernanda Borowsky da Rosa ◽  
Adriane Schmidt Pasqualoto ◽  
Catriona M. Steele ◽  
Renata Mancopes
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Oral Cavity ◽  
Pulmonary Disease ◽  
Thermal Sensation ◽  
Sensory Function ◽  
Control Group ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Age Related ◽  
Copd Patients

Introduction The oral cavity and pharynx have a rich sensory system composed of specialized receptors. The integrity of oropharyngeal sensation is thought to be fundamental for safe and efficient swallowing. Chronic obstructive pulmonary disease (COPD) patients are at risk for oropharyngeal sensory impairment due to frequent use of inhaled medications and comorbidities including gastroesophageal reflux disease. Objective This study aimed to describe and compare oral and oropharyngeal sensory function measured using noninstrumental clinical methods in adults with COPD and healthy controls. Method Participants included 27 adults (18 men, nine women) with a diagnosis of COPD and a mean age of 66.56 years ( SD = 8.68). The control group comprised 11 healthy adults (five men, six women) with a mean age of 60.09 years ( SD = 11.57). Spirometry measures confirmed reduced functional expiratory volumes (% predicted) in the COPD patients compared to the control participants. All participants completed a case history interview and underwent clinical evaluation of oral and oropharyngeal sensation by a speech-language pathologist. The sensory evaluation explored the detection of tactile and temperature stimuli delivered by cotton swab to six locations in the oral cavity and two in the oropharynx as well as identification of the taste of stimuli administered in 5-ml boluses to the mouth. Analyses explored the frequencies of accurate responses regarding stimulus location, temperature and taste between groups, and between age groups (“≤ 65 years” and “> 65 years”) within the COPD cohort. Results We found significantly higher frequencies of reported use of inhaled medications ( p < .001) and xerostomia ( p = .003) in the COPD cohort. Oral cavity thermal sensation ( p = .009) was reduced in the COPD participants, and a significant age-related decline in gustatory sensation was found in the COPD group ( p = .018). Conclusion This study found that most of the measures of oral and oropharyngeal sensation remained intact in the COPD group. Oral thermal sensation was impaired in individuals with COPD, and reduced gustatory sensation was observed in the older COPD participants. Possible links between these results and the use of inhaled medication by individuals with COPD are discussed.

Clinical and functional peculiarities at patients with bronchial asthma, chronic obstructive pulmonary disease and overlap of asthma-chronic obstructive pulmonary disease

2020 ◽  
Vol 24 (4) ◽  
pp. 80-86
Author(s):  
V. I. Trofimov ◽  
D. Z. Baranov
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Bronchial Asthma ◽  
Blood Test ◽  
Chronic Obstructive ◽  
Inflammation Markers ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Functional Features ◽  
Lower Airways

BACKGROUND: a comparative analysis of laboratory and instrumental tests at patients with bronchial obstructive diseases seems very actual due to the wide prevalence of these diseases. THE AIM: to evaluate characteristics of spirometry as well as allergic (total IgE, sputum eosinophils) and infectious (blood and sputum leucocytes, ESR, CRP, fibrinogen) inflammation markers at patients with bronchial obstructive diseases. PATIENTS AND METHODS: 104 case histories of patients with bronchial asthma, chronic obstructive pulmonary disease and overlap were analyzed including age, duration of smoking (pack-years), laboratory (clinical blood test, biochemical blood test, general sputum analysis, sputum culture) and instrumental (spirometry, body plethysmography, echocardiography) tests. Data were processed statistically with non-parametric methods. RESULTS: COPD patients were older than other groups’ patients, had the highest pack-years index. ACO patients were marked with maximal TLC and Raw, minimal FEV1, FEF25-75, FEV1/FVC. Patients with COPD had the highest inflammation markers (leucocyte count, CRP, fibrinogen). CONCLUSION: high active inflammation may cause severe lower airways possibility disorders at patients with COPD. Data related to a possible role of K. pneumoniaе in the pathogenesis of eosinophilic inflammation in lower airways are of significant interest. Patients with ACO occupy an intermediate position between asthma and COPD patients based on clinical and functional features.

scholarly journals LINC01414/LINC00824 genetic polymorphisms in association with the susceptibility of chronic obstructive pulmonary disease

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaoman Zhou ◽  
Yunjun Zhang ◽  
Yutian Zhang ◽  
Quanni Li ◽  
Mei Lin ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Genetic Polymorphisms ◽  
Chronic Obstructive ◽  
Nucleotide Polymorphisms ◽  
Obstructive Pulmonary Disease ◽  
Logistic Analysis ◽  
Copd Patients ◽  
Increased Risk ◽  
And Gender

Abstract Objective Chronic obstructive pulmonary disease (COPD) is a complicated multi-factor, multi-gene disease. Here, we aimed to assess the association of genetic polymorphisms in LINC01414/ LINC00824 and interactions with COPD susceptibility. Methods Three single nucleotide polymorphisms (SNPs) in LINC01414/LINC00824 was genotyped by Agena MassARRAY platform among 315 COPD patients and 314 controls. Logistic analysis adjusted by age and gender were applied to estimate the genetic contribution of selected SNPs to COPD susceptibility. Results LINC01414 rs699467 (OR = 0.73, 95% CI 0.56–0.94, p = 0.015) and LINC00824 rs7815944 (OR = 0.56, 95% CI 0.31–0.99, p = 0.046) might be protective factors for COPD occurrence, while LINC01414 rs298207 (OR = 2.88, 95% CI 1.31–6.31, p = 0.008) risk-allele was related to the increased risk of COPD in the whole population. Rs7815944 was associated with the reduced risk of COPD in the subjects aged > 70 years (OR = 0.29, p = 0.005). Rs6994670 (OR = 0.57, p = 0.007) contribute to a reduced COPD risk, while rs298207 (OR = 7.94, p = 0.009) was related to a higher susceptibility to COPD at age ≤ 70 years. Rs298207 (OR = 2.54, p = 0.043) and rs7815944 (OR = 0.43, p = 0.028) variants was associated COPD risk among males. Rs7815944 (OR = 0.16, p = 0.031) was related to the reduced susceptibility of COPD in former smokers. Moreover, the association between rs298207 genotype and COPD patients with dyspnea was found (OR = 0.50, p = 0.016), and rs7815944 was related to COPD patients with wheezing (OR = 0.22, p = 0.008). Conclusion Our finding provided further insights into LINC01414/LINC00824 polymorphisms at risk of COPD occurrence and accumulated evidence for the genetic susceptibility of COPD.

scholarly journals Blood eosinophil count-guided corticosteroid therapy and as a prognostic biomarker of exacerbations of chronic obstructive pulmonary disease: a systematic review and meta-analysis

2021 ◽  
Vol 12 ◽  
pp. 204062232110287
Author(s):  
Tao Liu ◽  
Zi-Jian Xiang ◽  
Xiao-Meng Hou ◽  
Jing-Jing Chai ◽  
Yan-Li Yang ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Prognostic Biomarker ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Chronic Obstructive ◽  
Blood Eosinophil ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
The Stability

Background: Chronic obstructive pulmonary disease (COPD) is characterized by persistent respiratory symptoms and dyspnea, as well as an increase in the number of leukocytes in the airways, lungs, and pulmonary vessels. A ‘One size fits all’ approach to COPD patients with different clinical features may be considered outdated. The following are the two major objectives of this meta-analysis: the first is to determine if blood eosinophil counts (BEC) can serve as a prognostic biomarker of COPD outcomes, and the second is to determine which level of BEC is effective for inhaled corticosteroid (ICS) treatment. Methods: We searched articles published before 15 May 2021 in the following four electronic databases: Web of Science, Cochrane Library, EMBASE, and PubMed. Results: A total of 42 studies, comprising a sampling of 188,710 subjects, were summarized and compared in this meta-analysis. The rate ratio (RR) of exacerbations of COPD (ECOPD) between ICS and non-ICS treatment was statistically significant for the COPD patients with a baseline BEC ⩾ 2% or ⩾ 200 cells/μl, RR = 0.82 (0.73, 0.93) or 0.79 (0.70, 0.89) respectively, while the RR of ECOPD between ICS and non-ICS treatment was statistically insignificant for the COPD patients with baseline BEC < 2% or <200 cells/μl, RR = 0.97 (0.87, 1.08) or 0.97 (0.86, 1.08), suggested that ICS therapy was beneficial to the improvement of ECOPD in patients with a baseline BEC ⩾ 2% or BEC ⩾ 200 cells/μl. Conclusion: Our research shows that a BEC ⩾ 200 cells/μl or ⩾2% is likely to become the cutoff value of ICS treatment for ECOPD. Moreover, we believe that the baseline BEC can be used as a biomarker for predicting ECOPD. The stability of BEC requires special attention.

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