ABSTRACT
Background: Dendritic cells (DCs) play an important role in allergen signal presentation. Many studies showed that follicular helper T cells (Tfhs) are related to allergic rhinitis (AR). However, the relationship between Tfhs and DCs and the mechanism of their interaction with AR remain unclear. Purpose: To explore the mechanism of Tfhs on DC maturation in AR. Methods: Tfhs were isolated from OVA-sensitized mice and co-cultured with DCs derived from mouse bone marrow. DCs maturity was monitored using flow cytometry and immunofluorescence staining. Exosomes of Tfhs were extracted, and miRNAs inside exosomes were analyzed using RNA-seq to identify differentially expressed genes. Using the TargetScan algorithm, it was predicted that CDK5 is a direct target gene, which is validated in a dual luciferase assay. DCs were treated with miR-142-5p mimics or inhibitors or transfected with CDK5 small interfering RNAs to verify the regulatory effects of miR-142-5p and CDK5 on DC maturation. How CDK5 regulates STAT3 signaling pathway was investigated to elucidate the molecular mechanism of DC maturation. Finally, in an in vivo experiment, the exosomes of AR-derived Tfhs were injected intravenously to detect their promotion of AR. Results: Tfh exosomes derived from AR mice contributed to DC maturation. RNA-seq results showed that miR-142-5p was the differentially decreased gene. Using the TargetScan algorithm, it was predicted that CDK5 was the target gene for the direct action of miR-142-5p. By detecting the effects of changes in the expression levels of miR-142-5p and CDK5 on DC maturation, it was demonstrated that miR-142-5p inhibits DC maturation by inhibiting CDK5 expression. CDK5-regulated STAT3 signaling pathway during DC maturation, and inhibition of the STAT3 signaling pathway can reverse the regulation of miR-142-5p/CDK5 on DC maturation. Finally, in vivo experiment indicated that the injection of AR-derived Tfhs promoted AR in mice. Conclusion: Tfh-derived exosomes induce DC maturation by regulating miR-142-5p/CDK5/STAT3 signaling pathway, thereby promoting the occurrence of AR.
ABSTRACT
This work is aimed at exploring the clinical efficacy of continuous positive airway pressure (CPAP) in treatment of patients with arrhythmias combined with obstructive sleep apnea (OSA). Through evaluating serum native thiol, malonaldehyde (MDA) and nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) in these patients and describing the effects on oxidative parameters of CPAP therapy for 3 months, we confirmed the impact of oxidative stress on arrhythmias. A total of 64 patients with OSA combined with arrhythmias were collected from April 2014 to April 2017 with full clinical information. Patients were divided into two groups (paired experiment design): 32 patients in group A (control group), who received unchanged anti-arrhythmia treatment and 32 patients in group B, who were subjected to unchanged pharmacological anti-arrhythmia therapy combined with CPAP. OSA related parameters were compared between the two groups after 3-month therapy. And the levels of parameters of oxidative stress in patients were measured before and after CPAP therapy. After 3 months of CPAP therapy, compared with the control group, the percentage of sage N3 (NREM 3) and stage R (REM) in total sleep time was significantly increased, while apnea-hypopnea index (AHI) and the Epworth Sleepiness Scale (ESS) score were evidently decreased. Meanwhile, the lowest oxygen saturation (LSpO2) was also elevated after CPAP treatment for 3 months. The CPAP therapy significantly prevented the occurrence of arrhythmias (P<0.05). Both the MDA level and NADPH oxidase levels were significantly lower in the group B than in the group A (P<0.05). But serum native thiol was improved by CPAP treatment (P<0.05). In conclusion, proper use of CPAP therapy provides significant benefits for the treatment of arrhythmia in patients with OSA.
