scholarly journals Identification of Molecular Mechanisms Underlying Sex-Associated Differences in the Chronic Obstructive Pulmonary Disease through Bioinformatics Analysis

2021 ◽  
Author(s):  
Fengshou Chen ◽  
Haijia Hou ◽  
Jie Han ◽  
Bing Tang
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Cholesterol Metabolism ◽  
Chronic Obstructive ◽  
Hub Genes ◽  
Obstructive Pulmonary Disease ◽  
P53 Signaling ◽  
Copd Patients ◽  
P53 Signaling Pathway

Abstract Background Accumulating evidence suggests the existence sex associated differences in the Chronic Obstructive Pulmonary Disease (COPD). However, limited knowledge exists on the molecular mechanisms underlying sex associated differences in COPD patients. Methods The GSE8581 dataset obtained from the GEO database was used to analyze differentially expressed genes (DEGs). Then enrichment analysis for DEGs were conducted through Metascape. PPI and the hub genes-pathway networks were constructed using the STRING database and Cytoscape software. Finally, the CTD was used to examine the relationships between the hub DEGs and COPD. Results The results revealed that different subsets of DEGs had different characteristics in GO functions and KEGG pathways. Different subsets of hub genes were obtained based on PPI network. The study then constructed the hub genes-pathway network for different subsets to explore the key signaling pathways and hub genes involved. The findings showed that NRAS and RAC1 functioned through “Rap1 signaling pathway” and “PI3K-Akt signaling pathway”, in male COPD patients. On the other hand, “Cholesterol metabolism” was among the important pathways in female COPD patients while the hub genes, APOE and APOC3 functioned through “Cholesterol metabolism”. Moreover, “Ubiquitin mediated proteolysis” and the “p53 signaling pathway” were shown to play more important roles in male COPD patients compared to their female counterparts. Furthermore, CDK2 and UBE2N were the hub genes involved in “p53 signaling pathway” and “Ubiquitin mediated proteolysis”, respectively. Finally the study identified the relationship between the hub genes and COPD in CTD. Conclusions The present study uncovered different molecular mechanisms in COPD patients based on sex. Additionally, distinct pathways and hub genes including NRAS, RAC1, APOE, APOC3, CDK2 and UBE2N were identified in the two genders of COPD patients. Further studies are needed to explore individualized treatment for COPD based on the findings.

scholarly journals Identification of Common Mechanisms and Key Genes in the Chronic Obstructive Pulmonary Disease and Acute Myocardial Infarction

2021 ◽  
Author(s):  
Fengshou Chen ◽  
Haijia Hou ◽  
Bing Tang
Keyword(s):  
Myocardial Infarction ◽  
Chronic Obstructive Pulmonary Disease ◽  
Acute Myocardial Infarction ◽  
Pulmonary Disease ◽  
Signaling Pathway ◽  
Chronic Obstructive ◽  
Biological Processes ◽  
Hub Genes ◽  
Obstructive Pulmonary Disease ◽  
The Relationship

Abstract Background: Chronic obstructive pulmonary disease (COPD) and acute myocardial infarction (AMI) have a strong association. We aimed to study the relationships between COPD and AMI, and reveal potential therapeutic targets and biomarkers. Materials and methods: The dataset GSE38974 and GSE60993 were downloaded from the Gene Expression Omnibus (GEO) database to analyze the intersections among differentially expressed genes (DEGs). Common DEGs were identified and performed functional enrichment analyses. The hub genes were obtained based on the protein-protein interaction (PPI) network by cytoHubba in Cytoscape software. The receiver operator characteristic (ROC) curve analysis was applied to identify the diagnosis efficacy of hub genes. The relationship between hub genes and these two diseases in the CTD database were validated. Finally, the transcription factors (TFs) corresponding to hub genes were also analyzed. Results: In our study, sixty-five common DEGs were obtained in COPD and AMI. GO enrichment analysis indicated that inflammation or apoptotic biological processes are significant enriched biological processes. Common DEGs were mostly enriched in pathways including apoptosis, HIF-1 signaling pathway, TNF signaling pathway, and cytokine-cytokine receptor interaction. MMP9, SOCS3, MCL1, ERBB2 and S100A12 were identified as the hub genes. Furthermore, we found that the expression of hub genes was significantly associated with a diagnosis efficacy of COPD and AMI. We also validated the relationship between the hub genes and these two diseases in the CTD database. We also found that ELK1, ETV4, STAT3 and TFAP2A were significant TFs, which interacted with the hub genes. Conclusion: In conclusion, our study revealed the communal DEGs and related mechanisms between the pathophysiology of COPD and AMI. MMP9, SOCS3, MCL1, ERBB2 and S100A12 were identified as the hub genes that are associated with COPD and AMI. Our study provides new ideas and evidence for further exploration of the mechanisms and treatment of COPD and AMI.

scholarly journals Alterations of multiple alveolar macrophage states in chronic obstructive pulmonary disease

2020 ◽  
Author(s):  
Kevin Baßler ◽  
Wataru Fujii ◽  
Theodore S. Kapellos ◽  
Arik Horne ◽  
Benedikt Reiz ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Single Cell ◽  
Pulmonary Disease ◽  
Molecular Mechanisms ◽  
Chronic Obstructive ◽  
Alveolar Space ◽  
Proliferating Cells ◽  
Tissue Samples ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients

AbstractDespite the epidemics of chronic obstructive pulmonary disease (COPD), the cellular and molecular mechanisms of this disease are far from being understood. Here, we characterize and classify the cellular composition within the alveolar space and peripheral blood of COPD patients and control donors using a clinically applicable single-cell RNA-seq technology corroborated by advanced computational approaches for: machine learning-based cell-type classification, identification of differentially expressed genes, prediction of metabolic changes, and modeling of cellular trajectories within a patient cohort. These high-resolution approaches revealed: massive transcriptional plasticity of macrophages in the alveolar space with increased levels of invading and proliferating cells, loss of MHC expression, reduced cellular motility, altered lipid metabolism, and a metabolic shift reminiscent of mitochondrial dysfunction in COPD patients. Collectively, single-cell omics of multi-tissue samples was used to build the first cellular and molecular framework for COPD pathophysiology as a prerequisite to develop molecular biomarkers and causal therapies against this deadly disease.

scholarly journals Molecular and clinical diseasome of comorbidities in exacerbated COPD patients

2015 ◽  
Vol 46 (4) ◽  
pp. 1001-1010 ◽  
Author(s):  
Rosa Faner ◽  
Alba Gutiérrez-Sacristán ◽  
Ady Castro-Acosta ◽  
Solène Grosdidier ◽  
Wenqi Gan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Vascular Tone ◽  
Molecular Mechanisms ◽  
Airflow Limitation ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Smoking Exposure

The frequent occurrence of comorbidities in patients with chronic obstructive pulmonary disease (COPD) suggests that they may share pathobiological processes and/or risk factors.To explore these possibilities we compared the clinical diseasome and the molecular diseasome of 5447 COPD patients hospitalised because of an exacerbation of the disease. The clinical diseasome is a network representation of the relationships between diseases, in which diseases are connected if they co-occur more than expected at random; in the molecular diseasome, diseases are linked if they share associated genes or interaction between proteins.The results showed that about half of the disease pairs identified in the clinical diseasome had a biological counterpart in the molecular diseasome, particularly those related to inflammation and vascular tone regulation. Interestingly, the clinical diseasome of these patients appears independent of age, cumulative smoking exposure or severity of airflow limitation.These results support the existence of shared molecular mechanisms among comorbidities in COPD.

scholarly journals Novel computational analysis of large transcriptome datasets identifies sets of genes distinguishing chronic obstructive pulmonary disease from healthy lung samples

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fabienne K. Roessler ◽  
Birke J. Benedikter ◽  
Bernd Schmeck ◽  
Nadav Bar
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Molecular Mechanisms ◽  
Human Subjects ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Cysteine Rich Protein ◽  
Copd Patients ◽  
Small Set ◽  
Healthy Lung

AbstractChronic obstructive pulmonary disease (COPD) kills over three million people worldwide every year. Despite its high global impact, the knowledge about the underlying molecular mechanisms is still limited. In this study, we aimed to extend the available knowledge by identifying a small set of COPD-associated genes. We analysed different publicly available gene expression datasets containing whole lung tissue (WLT) and airway epithelium (AE) samples from over 400 human subjects for differentially expressed genes (DEGs). We reduced the resulting sets of 436 and 663 DEGs using a novel computational approach that utilises a random depth-first search to identify genes which improve the distinction between COPD patients and controls along the first principle component of the data. Our method identified small sets of 10 and 15 genes in the WLT and AE, respectively. These sets of genes significantly (p < 10–20) distinguish COPD patients from controls with high fidelity. The final sets revealed novel genes like cysteine rich protein 1 (CRIP1) or secretoglobin family 3A member 2 (SCGB3A2) that may underlie fundamental molecular mechanisms of COPD in these tissues.

The effect of glucocorticoids in combination with azithromycin or theophylline on cytokine production by NK and NKT-like blood cells of patients with chronic obstructive pulmonary disease

2021 ◽  
Vol 67 (4) ◽  
pp. 352-359
Author(s):  
A.G. Kadushkin ◽  
A.D. Tahanovich ◽  
L.V. Movchan ◽  
T.S. Kolesnikova ◽  
A.V. Khadasouskaya ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Nk Cells ◽  
Pulmonary Disease ◽  
Blood Cells ◽  
Molecular Mechanisms ◽  
Low Dose ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Anti Inflammatory

Chronic obstructive pulmonary disease (COPD) is characterized by reduced sensitivity of cells to the anti-inflammatory effects of glucocorticoids (GCs). Azithromycin and a low dose theophylline have a significant impact on molecular mechanisms leading to corticosteroid resistance. The aim of this study was to evaluate the ability of azithromycin and theophylline to enhance the anti-inflammatory effects of GCs on the production of cytokines by NK and NKT-like blood cells of COPD patients. Whole blood cells from COPD patients (n=21) were incubated in the presence of budesonide (10 nM), azithromycin (10 μg/mL), theophylline (1 μM), or their combinations and stimulated with phorbol myristate acetate (50 ng/mL). Intracellular production of proinflammatory cytokines in NK (CD3-CD56+) and NKT-like (CD3+CD56+) blood cells was analyzed by flow cytometry. Budesonide reduced synthesis of interleukin 4 (IL-4), CXCL8, tumor necrosis factor α (TNFα) by NK and NKT-like cells, as well as production of interferon γ (IFNγ) by NK cells. Azithromycin suppressed production of IL-4 and CXCL8 by NK and NKT-like cells, and theophylline inhibited IL-4 synthesis by these lymphocytes. The combination of azithromycin and budesonide had a more pronounced inhibitory effect on the production of IL-4 and CXCL8 by NK and NKT-like cells than the effect of these drugs alone. The combination of theophylline and budesonide suppressed synthesis of IL-4 and CXCL8 by NK and NKT-like cells, as well as the production of TNFα and IFNγ by NK cells stronger than budesonide alone. The obtained results demonstrate the benefits for the combined use of GCs with theophylline at a low dose or azithromycin to suppress the inflammatory process in patients with COPD.

scholarly journals Identification of potential biomarkers and therapeutic targets in the chronic obstructive pulmonary disease and acute myocardial infarction

2021 ◽  
Author(s):  
Fengshou Chen ◽  
Haijia Hou ◽  
Bing Tang
Keyword(s):  
Myocardial Infarction ◽  
Chronic Obstructive Pulmonary Disease ◽  
Acute Myocardial Infarction ◽  
Pulmonary Disease ◽  
Signaling Pathway ◽  
Chronic Obstructive ◽  
Biological Processes ◽  
Hub Genes ◽  
Obstructive Pulmonary Disease ◽  
The Relationship

Abstract Background Chronic obstructive pulmonary disease (COPD) and acute myocardial infarction (AMI) have a strong association. We aimed to study the relationships between COPD and AMI, and reveal potential therapeutic targets and biomarkers. , Methods The dataset GSE38974 and GSE60993 were downloaded from the Gene Expression Omnibus (GEO) database to analyze the intersections among differentially expressed genes (DEGs). Common DEGs were identified and performed functional enrichment analyses. The hub genes were obtained based on the protein-protein interaction (PPI) network by cytoHubba in Cytoscape software. The receiver operator characteristic (ROC) curve analysis was applied to identify the diagnosis efficacy of hub genes. The relationship between hub genes and these two diseases in the CTD database were validated. Finally, the transcription factors (TFs) corresponding to hub genes were also analyzed. Results In our study, sixty-five common DEGs were obtained in COPD and AMI. GO enrichment analysis indicated that inflammation or apoptotic biological processes are significant enriched biological processes. Common DEGs were mostly enriched in pathways including apoptosis, HIF-1 signaling pathway, TNF signaling pathway, and cytokine-cytokine receptor interaction. MMP9, SOCS3, MCL1, ERBB2 and S100A12 were identified as the hub genes. Furthermore, we found that the expression of hub genes was significantly associated with a diagnosis efficacy of COPD and AMI. We also validated the relationship between the hub genes and these two diseases in the CTD database. We also found that ELK1, ETV4, STAT3 and TFAP2A were significant TFs, which interacted with the hub genes. Conclusions In conclusion, our study revealed the communal DEGs and related mechanisms between the pathophysiology of COPD and AMI. MMP9, SOCS3, MCL1, ERBB2 and S100A12 were identified as the hub genes that are associated with COPD and AMI. Our study provides new ideas and evidence for further exploration of the mechanisms and treatment of COPD and AMI.

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.

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