Background: Allergic rhinitis (AR) is a common disease characterized by chronic inflammation of the nasal mucosa, but we have not fully understood the mechanism responsible for the development of AR. MicroRNAs (miRNAs) are short endogenous noncoding RNAs regulating protein translation through a mechanism known as RNA interference. To understand the molecular mechanisms of miRNA involved in the pathogenesis of AR, expressed miRNAs in AR were investigated through genomewide microarray analysis. Methods: Mammalian miRNA microarrays containing whole human mature and precursor miRNA sequences were used for analyzing eight samples of nasal mucosa of AR and eight samples of nonallergic patients. Quantitative reverse transcriptase–polymerase chain reaction (RT-PCR) of some different expressed miRNAs was used to confirm the array results. Results: The miRNA microarray chip analysis identified 421 miRNAs differentially expressed in the nasal mucosa of AR, and a total of 9 miRNAs were identified in the AR group with twofold change compared with control samples (p < 0.05). These included up-regulated miRNAs, hsa-hsa-miR-7, and hsa-miRPlus-E1194, and down-regulated miRNAs, hsa-miR-498, hsa-miR-187, hsa-miR-874, hsa-miR-143, hsa-miR-886–3p, hsa-miR-224, and hsa-miR-767–5p. RT-PCR results also confirmed that part of differentially expressed miRNAs as hsa-miR-224, hsa-miR-187, and hsa-miR-143 were down-regulated in AR. Conclusion: The report indicated that many miRNA expressions were altered in AR and differentially expressed miRNAs appear to be involved in the development of AR. The study of miRNAs may lead to a better understanding about the roles of identified miRNAs in the pathogenesis of AR; this would be considered in future therapeutic strategies.

Severe eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) remains the most relapsed subtype of uncontrolled CRSwNP. CM310, a humanised anti-interleukin (IL)-4 receptor alpha monoclonal antibody, inhibits IL-4 and IL-13 signaling which underlying eosinophilic inflammation. This study aims to evaluate the efficacy and safety of CM310 in patients with severe ECRSwNP. A multicentre, randomised, double-blind, and placebo-controlled phase 2 clinical trial was conducted. 56 eligible adult patients with severe ECRSwNP were randomised 1:1 to receive subcutaneously either CM310 (300 mg) or placebo every 2 weeks under the background therapy of mometasone furoate nasal spray (MFNS) for 16 weeks, with 8 weeks of follow-up. Coprimary endpoints included the changes from baseline in nasal polyp score (NPS) and nasal congestion score (NCS) at week 16. Key secondary endpoints included sinus Lund-Mackay CT score, change in sinus volume occupied by disease, University of Pennsylvania Smell Identification Test score, 22-item Sino-nasal Outcome Test score, and total symptom score. Safety, pharmacodynamics, and changes in type 2 inflammation biomarkers were assessed. This study is registered with ClinicalTrials.gov, NCT04805398. Between April 6, 2021, and March 18, 2022, 27 patients respectively in both the CM310 and placebo groups completed the study. Findings suggested that CM310 improved the coprimary efficacy endpoints of decreasing nasal polyp size and alleviating nasal congestion compared with the placebo. Least squares (LS) mean differences (CM310 vs placebo) of change from baseline in NPS and NCS at week 16 were −2.1 (95% CI −2.9, −1.4; p < 0.0001) and −0.9 (95% CI −1.4, −0.5; p < 0.0001), respectively. Sinus CT scan revealed that Lund-Mackay CT score (LS mean difference [95% CI] −7.6, [−9.4, −5.8]; p < 0.0001) and sinus volume occupied by disease (LS mean difference [95% CI] −37%, [−47%, −28%]; p < 0.0001) were significantly improved with CM310 compared with placebo. In addition, CM310 significantly relieved the daily symptoms of patients with CRSwNP and improved their quality of life reflected by the improvements in the TSS (−2.6 [95% CI −3.5, −1.6]), UPSIT (10.4 [95% CI 6.8, 14.0]) and SNOT-22 score (−19.1 [95% CI −29.8, −8.5]). Compared with placebo, CM310 administration significantly reduced type 2-related biomarkers including the serum TARC and total IgE, and tissue eosinophils. The most common adverse events were upper respiratory tract infection, blood cholesterol increased, and tinnitus, but none were considered drug-related. These findings support CM310 as an effective additional treatment option to the standard of care in patients with severe ECRSwNP. KeyMed Biosciences (Chengdu) Limited.

It is well considered that reactive oxygen species (ROS) plays a prominent causative role in the development of allergic rhinitis (AR), and eosinophils cells as important allergic inflammatory cells contribute to elevating oxidative stress. Hydrogen, emerging as a novel antioxidant, has been proven effective in selectively reducing ROS in animals models of oxidative damage. We herein aim to verify protective effects of hydrogen on eosinophils cells in guinea pigs models of AR. Thirty two guinea pigs were random divided into four groups, and AR model was established through ovalbumin sensitization. The guinea pigs were injected with hydrogen-rich saline (Normal-HRS and AR-HRS group) or normal saline (control and AR group). The frequencies of sneezing and scratching were recorded. The IgE level, blood eosinophil count and eosinophil cationic protein (ECP) level in serum were measured. The serum malondialdehyde (MDA) and superoxide dismutase (SOD) assays were also measured to evaluate oxidative stress. The expression levels of eotaxin mRNA and protein in the nasal mucosa were also determined by real-time RT-PCR, Western blot and immunofluorescence. HRS reduced the ROS and MDA levels and increased SOD level in guinea pigs of AR-HRS group accompanied with decreased frequency of sneezing and scratches. Meanwhile, there was a decline of the number of eosinophils cells in blood and of thelevel of ECP in serum in the AR-HRS group. HRS also significantly decreased the expression of eotaxin in nasal mucosa. HRS may play a protective role in attenuating allergic inflammation, and suppressing the increase and activation of eosinophils in AR possibly through antioxidation effect of hydrogen.

MicroRNA-143 (miR-143) was found to be downregulated in allergic rhinitis, and bioinformatics analysis predicted that IL-13Rα1 was a target gene of miR-143. To understand the molecular mechanisms of miR-143 involved in the pathogenesis of allergic inflammation, recombinant miR-143 plasmid vectors were constructed, and human mast cell-1(HMC-1) cells which play a central role in the allergic response were used for study. The plasmids were transfected into HMC-1 cells using a lentiviral vector. Expression of IL-13Rα1 mRNA was then detected by reverse transcriptase polymerase chain reaction (RT-PCR) and Western Blotting. The miR-143 lentiviral vector was successfully stably transfected in HMC-1 cells for target gene expression. Compared to the control, the target gene IL-13Rα1 was less expressed in HMC-1 transfected with miR-143 as determined by RT-PCR and Western Blotting (p < 0.05); this difference in expression was statistically significant and the inhibition efficiency was 71%. It indicates that miR-143 directly targets IL-13Rα1 and suppresses IL-13Rα1 expression in HMC-1 cells. Therefore, miR-143 may be associated with allergic reaction in human mast cells.