Upregulated microRNA-125b-5p in patients with asthma-COPD overlap mediates oxidative stress and late apoptosis via targeting IL6R/TRIAP1 signaling.

BACKGROUND: Among patients with chronic obstructive pulmonary disease (COPD), some have features of both asthma and COPD-a condition categorized as asthma-COPD overlap (ACO). Our aim was to determine whether asthma- or COPD-related microRNAs (miRNAs) play a role in the pathogenesis of ACO. METHODS: A total of 22 healthy subjects and 27 patients with ACO were enrolled. We selected 6 miRNAs that were found to correlate with COPD and asthma. The expression of miRNAs and target genes was analyzed using quantitative reverse-transcriptase polymerase chain reaction. Cell apoptosis and intracellular reactive oxygen species production were evaluated using flow cytometry. In vitro human monocytic THP-1 cells and primary normal human bronchial epithelial (NHBE) cells under stimuli with cigarette smoke extract (CSE) or ovalbumin (OVA) allergen or both were used to verify the clinical findings. RESULTS: We identified the upregulation of miR-125b-5p in patients with ACO and in THP-1 cells stimulated with CSE plus OVA allergen. We selected 16 genes related to the miR-125b-5p pathway and found that IL6R and TRIAP1 were both downregulated in patients with ACO and in THP-1 cells stimulated with CSE plus OVA. The percentage of late apoptotic cells increased in the THP-1 cell culture model when stimulated with CSE plus OVA, and the effect was reversed by transfection with miR-125b-5p small interfering RNA (siRNA). The percentage of reactive oxygen species-producing cells increased in the NHBE cell culture model when stimulated with CSE plus OVA, and the effect was reversed by transfection with miR-125b-5p siRNA. In NHBE cells, siRNA transfection reversed the upregulation of STAT3 under CSE+OVA stimulation. CONCLUSIONS: Our study revealed that upregulation of miR-125b-5p in patients with ACO mediated late apoptosis in THP-1 cells and oxidative stress in NHBE cells via targeting IL6R and TRIAP1. STAT3 expression was also regulated by miR-125b-5p.

Sex Differences in the Expression of Cardiac Remodeling and Inflammatory Cytokines in Patients with Obstructive Sleep Apnea and Atrial Fibrillation.

Although there is a link between obstructive sleep apnea (OSA) and atrial fibrillation (AF) and numerous investigations have examined the mechanism of AF development in OSA patients, which includes cardiac remodeling, inflammation, and gap junction-related conduction disorder, there is limited information regarding the differences between the sexes. This study analyzes the impact of sex differences on the expression of cardiac remodeling, inflammatory cytokines, and gap junctions in patients with OSA and AF. A total of 154 individuals diagnosed with sleep-related breathing disorders (SRBDs) were enrolled in the study and underwent polysomnography and echocardiography. Significant OSA was defined as an apnea-hypopnea index (AHI) of ≥15 per hour. Exosomes were purified from the plasma of all SRBD patients and incubated in HL-1 cells to investigate their effects on inflammatory cytokines and GJA1 expression. The differences in cardiac remodeling and expression of these biomarkers in both sexes were analyzed. Of the 154 enrolled patients, 110 patients were male and 44 patients were female. The LA sizes and E/e' ratios of male OSA patients with concomitant AF were greater than those of control participants and those without AF (all p < 0.05). Meanwhile, female OSA patients with AF had a lower left ventricular ejection fraction than those OSA patients without AF and control subjects (p < 0.05). Regarding the expression of inflammatory cytokines and GJA1, the mRNA expression levels of GJA1 were lower and those of IL-1ß were higher in those male OSA patients with AF than in those male OSA patients without AF and control subjects (p < 0.05). By contrast, mRNA expression levels of HIF-1α were higher in those female OSA patients with and without AF than in control subjects (p < 0.05). In conclusion, our study revealed sex-specific differences in the risk factors and biomarkers associated with AF development in patients with OSA.

Alto valor de la combinación de la concentración sérica de proteína C reactiva y la puntuación BODE para la predicción de la mortalidad en pacientes con EPOC estable / High Value of Combined Serum C-Reactive Protein and BODE Score for Mortality Prediction in Patients with Stable COPD

Introducción: Tanto la puntuación BODE (índice de masa corporal, grado de obstrucción del flujo aéreo,disnea funcional y capacidad de ejercicio) como la concentración sérica de proteína C reactiva (PCR)son variables pronósticas validadas de mortalidad en pacientes con enfermedad pulmonar obstructivacrónica (EPOC). El objetivo del presente estudio fue investigar el valor predictivo de la combinación de laconcentración sérica de PCR y la puntuación BODE para la mortalidad en pacientes con EPOC.Pacientes y métodos: Se evaluó una cohorte de 114 pacientes con EPOC, clínicamente estables, en buscade las variables pronósticas de mortalidad longitudinal. Las variables incluyeron edad, sexo, tabaquismoactual, paquetes-año, presión inspiratoria/espiratoria máxima, puntuación BODE (body mass index, degreeof airflow obstruction, functional dyspnea, and exercise capacity), concentración sérica de PCR y fibrinógeno.Las variables pronósticas se evaluaron mediante un modelo de regresión de riesgos proporcionales deCox. La supervivencia se estimó mediante el método de Kaplan-Meier y la prueba del log-rank.Resultados: La concentración sérica de PCR (p = 0,005; CR = 1,042; IC del 95% = 1,019-1,066) y la puntuaciónBODE (p = 0,032; CR = 1,333; IC del 95% = 1,025-1,734) fueron variables pronósticas independientes de lasupervivencia en el análisis multivariante. Las tasas de supervivencia acumulativas de los pacientes conEPOC se clasificaron desde las peores hasta las mejores del modo siguiente: concentración sérica de PCR>3 mg/l y cuartil 3-4; concentración sérica de PCR >3 mg/l y cuartil 1-2; concentración sérica de PCR≤3 mg/l y cuartil 3-4; concentración sérica de PCR ≤3 mg/l y cuartil 1-2 (p < 0,001). Conclusiones: La concentración sérica de PCR y la puntuación BODE son variables pronósticas independientesde la supervivencia en pacientes con EPOC estable. La combinación de la concentración sérica dePCR y la puntuación BODE posee el mayor valor predictivo en la práctica clínica (AU)

Introduction: Both BODE score (body mass index, degree of airflow obstruction, functional dyspnea, andexercise capacity) and serum C-reactive protein (CRP) are validated predictors of mortality in patientswith chronic obstructive pulmonary disease (COPD). The aim of this study is to investigate the predictivevalue of combined serum CRP and BODE score for mortality in COPD patients.Patients and methods: A cohort of 114 clinically stable COPD patients was assessed for predictors oflongitudinal mortality. Variables included age, gender, current smoking status, pack-years, maximal inspiratory/expiratory pressure, BODE score (body mass index, degree of airflow obstruction, functionaldyspnea, and exercise capacity), serum CRP, and fibrinogen. Predictors were assessed by Cox proportionalhazards regression model. Survival was estimated by Kaplan-Meier method and log-rank test.Results: Serum CRP (P = 0.005; HR= 1.042; 95% CI = 1.019-1.066) and BODE score (P = 0.032; HR= 1.333;95%CI = 1.025-1.734) were independent predictors of survival in the multivariate analysis. The cumulative survival rates of COPD patients were sorted from the worst to the best as following: serum CRP >3 mg/L& quartile 3-4; serum CRP >3 mg/L & quartile 1-2; serum CRP ≤3 mg/L & quartile 3-4; serum CRP ≤3 mg/L& quartile 1-2 (P < 0.001).Conclusions: Serum CRP and BODE score are independent predictors of survival in stable COPD patients.Combination of serum CRP and BODE score has higher predictive value in clinical practice (AU)