Background: Chronic Obstructive Pulmonary Disease (COPD) is a chronic inflammatory lung condition associated with significant morbidity and mortality. Observational studies indicate a positive correlation between COPD...Background: Chronic Obstructive Pulmonary Disease (COPD) is a chronic inflammatory lung condition associated with significant morbidity and mortality. Observational studies indicate a positive correlation between COPD and the risk of abdominal aortic aneurysm (AAA), suggesting individuals with COPD are more likely to develop AAA. However, the causal relationship between COPD and AAA remains unclear. Method: This study employed a bidirectional Mendelian Randomization (MR) approach to assess the causal relationship between COPD and AAA. A two-step MR analysis was conducted to evaluate the mediating effect of 1400 circulating metabolites between COPD and AAA. Expression quantitative trait loci (eQTL) were sourced from the MRC Integrative Epidemiology Unit (MRC-IEU) database, and MR analysis was performed using the TwoSampleMR R package. The results were filtered using the Inverse Variance Weighted (IVW) method to identify genes strongly associated with both COPD and AAA. Furthermore, the Super Exact Test R package was utilized to determine the overlapping genes between COPD and AAA. Enrichment analysis for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was conducted using the clusterProfiler R package. Protein-protein interaction (PPI) analysis was carried out using STRING v12.0. Results: The IVW method indicated a causal relationship between the risk increase of COPD and AAA (OR: 1.47, 95% CI: 1.16 - 1.86, p = 0.001). Among 1400 circulating metabolites, plasma-free proline was identified as mediating the relationship between COPD and AAA, with a mediation effect proportion of −4.6% (95% CI: −9.032%, −0.164%, p = 0.042). Additionally, PPI analysis revealed 20 functionally interrelated genes mediating the linkage between COPD and AAA. KEGG enrichment analysis showed functional enrichment of these genes in the pathway of aldosterone synthesis and secretion. Conclusion: Our study supports a causal relationship between COPD and an increased risk of AAA. Specifically, plasma-free proline and pathways related to aldosterone synthesis and secretion may play key roles in the connection between COPD and AAA.展开更多
Purpose: The role of GPER in sepsis-induced myocardial cell injury and its potential impact on the risk of death within 28 days in sepsis. Methods: An in vitro experiment was conducted to establish a sepsis-induced my...Purpose: The role of GPER in sepsis-induced myocardial cell injury and its potential impact on the risk of death within 28 days in sepsis. Methods: An in vitro experiment was conducted to establish a sepsis-induced myocardial cell model. H9C2 myocardial cells were treated with 10 μg/ml lipopolysaccharide (LPS) for 24 hours. The effects of different concentrations of the GPER agonist G1 (1, 3, and 10 μmol/L) on cell viability, expression of inflammatory markers, cell apoptosis, and the NF-κB pathway were evaluated. A Mendelian randomization analysis was conducted using Single Nucleotide Polymorphism (SNPs) related to the GPER gene as instrumental variables to investigate the causal relationship between the GPER gene variations and sepsis (28-day death). Results: The results indicate that the group treated with LPS showed a significant decrease in myocardial cell viability, an increase in concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), higher apoptosis rates, and increased phosphorylation levels of NF-κB p65 (p-P65/P65) and IκB-α (p-IκB-α/IκB-α) compared to the control group (P κB pathway. However, genetic evidence did not show a causal relationship between GPER gene variations and sepsis (28-day death) (P κB pathway. However, genetic evidence did not show a causal relationship between GPER gene variations and sepsis (28-day death).展开更多
文摘Background: Chronic Obstructive Pulmonary Disease (COPD) is a chronic inflammatory lung condition associated with significant morbidity and mortality. Observational studies indicate a positive correlation between COPD and the risk of abdominal aortic aneurysm (AAA), suggesting individuals with COPD are more likely to develop AAA. However, the causal relationship between COPD and AAA remains unclear. Method: This study employed a bidirectional Mendelian Randomization (MR) approach to assess the causal relationship between COPD and AAA. A two-step MR analysis was conducted to evaluate the mediating effect of 1400 circulating metabolites between COPD and AAA. Expression quantitative trait loci (eQTL) were sourced from the MRC Integrative Epidemiology Unit (MRC-IEU) database, and MR analysis was performed using the TwoSampleMR R package. The results were filtered using the Inverse Variance Weighted (IVW) method to identify genes strongly associated with both COPD and AAA. Furthermore, the Super Exact Test R package was utilized to determine the overlapping genes between COPD and AAA. Enrichment analysis for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was conducted using the clusterProfiler R package. Protein-protein interaction (PPI) analysis was carried out using STRING v12.0. Results: The IVW method indicated a causal relationship between the risk increase of COPD and AAA (OR: 1.47, 95% CI: 1.16 - 1.86, p = 0.001). Among 1400 circulating metabolites, plasma-free proline was identified as mediating the relationship between COPD and AAA, with a mediation effect proportion of −4.6% (95% CI: −9.032%, −0.164%, p = 0.042). Additionally, PPI analysis revealed 20 functionally interrelated genes mediating the linkage between COPD and AAA. KEGG enrichment analysis showed functional enrichment of these genes in the pathway of aldosterone synthesis and secretion. Conclusion: Our study supports a causal relationship between COPD and an increased risk of AAA. Specifically, plasma-free proline and pathways related to aldosterone synthesis and secretion may play key roles in the connection between COPD and AAA.
文摘Purpose: The role of GPER in sepsis-induced myocardial cell injury and its potential impact on the risk of death within 28 days in sepsis. Methods: An in vitro experiment was conducted to establish a sepsis-induced myocardial cell model. H9C2 myocardial cells were treated with 10 μg/ml lipopolysaccharide (LPS) for 24 hours. The effects of different concentrations of the GPER agonist G1 (1, 3, and 10 μmol/L) on cell viability, expression of inflammatory markers, cell apoptosis, and the NF-κB pathway were evaluated. A Mendelian randomization analysis was conducted using Single Nucleotide Polymorphism (SNPs) related to the GPER gene as instrumental variables to investigate the causal relationship between the GPER gene variations and sepsis (28-day death). Results: The results indicate that the group treated with LPS showed a significant decrease in myocardial cell viability, an increase in concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), higher apoptosis rates, and increased phosphorylation levels of NF-κB p65 (p-P65/P65) and IκB-α (p-IκB-α/IκB-α) compared to the control group (P κB pathway. However, genetic evidence did not show a causal relationship between GPER gene variations and sepsis (28-day death) (P κB pathway. However, genetic evidence did not show a causal relationship between GPER gene variations and sepsis (28-day death).
