RORα overexpression reduced interleukin-33 expression and prevented mast cell degranulation and inflammation by inducing autophagy in allergic rhinitis.

BACKGROUND: Retinoid acid receptor related orphan receptor α (RORα) is a nuclear receptor that along with other bioactive factors regulates cell proliferation, differentiation, and immunomodulation in vivo. AIMS: The objective of this study was to explore the function and mechanism of RORα in allergic rhinitis (AR). MATERIALS AND METHODS: Derp1 was used to construct an AR cell model in HNEpC cells, and RORα was overexpressed or silenced in the AR HNEpC cells. Next, LAD2 cells were co-cultured with the Derp1-treated HNEpC cells. Additionally, an AR mouse model was established using by OVA, and a RORα Adenovirus was delivered by nebulizing. Pathological tissue structures were evaluated by hematoxylin-eosin staining, and the levels of RORα, interleukin-33 (IL-33), and other proteins were analyzed immunohistochemistry, western blotting, and immunofluorescence staining. IL-33, IL-4, IL-5, and IL-13 levels were detected using enzyme-linked immunosorbent assay kits and cell migration was assessed by Transwell assays. RESULTS: Our data showed that RORα was downregulated in the nasal mucosa tissues of AR patients. Derp1 treatment could cause a downregulation of RORα, upregulation of IL-33, the induction of NLRP3 inflammasomes, and cell migration in HNEpC cells. Furthermore, RORα overexpression dramatically attenuated IL-33 levels, NLRP3 inflammasome activity, and the migration of AR HNEpC cells induced with Derp1. Moreover, RORα in AR HNEpC cells could prevent mast cell (MC) degranulation and inflammation by accelerating autophagy, RORα overexpression inhibited MC degranulation and NLRP3-induced inflammation in the AR model mice. RORα overexpression reduced IL-33 expression in nasal epithelial cells, and also suppressed MC degranulation and inflammation by promoting autophagy. CONCLUSION: RORα inhibits NLRP3 inflammasome in HNEpC, and attenuated mast cells degranulation and inflammation through autophagy in AR.

The Long Noncoding RNA Cytoskeleton Regulator RNA (CYTOR)/miRNA-24-3p Axis Facilitates Nasopharyngeal Carcinoma Progression by Modulating GAD1 Expression.

Nasopharyngeal carcinoma (NPC) is a head and neck epithelial carcinoma that is unusually prevalent in Southeast Asia. Noncoding RNAs, including lncRNA and miRNA, and their target genes are considered vital regulators of tumorigenesis and the progression of NPC. However, the detailed underlying mechanisms of GAD1 involved in the regulation of NPC need to be further elucidated. In the present study, we identified that GAD1 was significantly upregulated in NPC tissues. GAD1 overexpression is promoted, while genetic knockdown of GAD1 suppresses proliferation, colony formation, migration, and invasion of NPC cells. Bioinformatics analysis and a luciferase reporter assay demonstrated that GAD1 is a direct target gene of miR-24-3p. In NPC tissues, miR-24-3p was downregulated and the lncRNA CYTOR was upregulated. CYTOR was sponged to suppress the function of miR-24-3p. CYTOR regulates GAD1 expression via modulating miR-24-3p. The CYTOR/miR-24-3p/GAD1 axis is converged to modulate the growth, migration, and invasion of NPC cells. In conclusion, the study identified a novel axis for the regulation of NPC cell growth, providing new insights into the understanding of NPC.

Efficacy of Sublingual Administration of Dermatophagoides Farinae Drops for Treatment of Pediatric Allergic Rhinitis Accompanied by Adenoid Hypertrophy and Improvement of Immune Function.

BACKGROUND The aim of this study was to determine the efficacy of sublingual administration of Dermatophagoides farinae drops for the treatment of allergic rhinitis (AR) accompanied by adenoid hypertrophy and the effect on immune function in children. MATERIAL AND METHODS Eosinophil counts in peripheral blood before and after treatment were determined; serum levels of immunoglobulin E (IgE), total IgE (T-IgE), immunoglobulin G4 (IgG4), interleukin-2 (IL-2), and interleukin-6 (IL-6) before and after treatment were detected by enzyme-linked immunosorbent assay. RESULTS The total effective rate in the study group was significantly higher than that in the control group (P<0.05). In both the study and control groups, symptom scores, medication scores, eosinophil counts in the peripheral blood, and serum levels of IgE, T-IgE, and IL-6 were significantly lower than those before treatment (P<0.05), while the serum levels of IgG4 and IL-2 were significantly higher than those before treatment (P<0.05). After treatment, symptom scores, medication scores, eosinophil counts in the peripheral blood, and serum levels of IgE, T-IgE, and IL-6 in the study group were significantly lower than those in the control group (P<0.05), while the serum levels of IgG4 and IL-2 were significantly higher in the study group than those in the control group (P<0.05). CONCLUSIONS Sublingual administration of D. farinae drops improved the clinical symptoms of pediatric AR caused by Dermatophagoides mites and improved the immune functions in children.