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Background: Although oxidative stress is involved in the pathophysiological process of chronic rhinosinusitis with nasal polyps (CRSwNP), the specific underlying mechanism is still unclear. Whether antioxidant therapy can treat CRSwNP needs further investigation., Methods: Immunohistochemistry, immunofluorescence, western blotting and quantitative polymerase chain reaction (qPCR) analyses were performed to detect the distribution and expression of oxidants and antioxidants in nasal polyp tissues. qPCR revealed correlations between oxidase, antioxidant enzymes and inflammatory cytokine levels in CRSwNP patients. Human nasal epithelial cells (HNEpCs) and primary macrophages were cultured to track the cellular origin of oxidative stress in nasal polyps(NPs) and to determine whether crocin can reduce cellular inflammation by increasing the cellular antioxidant capacity., Results: The expression of NOS2, NOX1, HO-1 and SOD2 was increased in nasal epithelial cells and macrophages derived from nasal polyp tissue. Oxidase levels were positively correlated with those of inflammatory cytokines (IL-5 and IL-6). Conversely, the levels of antioxidant enzymes were negatively correlated with those of IL-13 and IFN-γ. Crocin inhibited M1 and M2 macrophage polarization as well as the expression of NOS2 and NOX1 and improved the antioxidant capacity of M2 macrophages. Moreover, crocin enhanced the ability of antioxidants to reduce inflammation via the KEAP1/NRF2/HO-1 pathway in HNEpCs treated with SEB or LPS. Additionally, we observed the antioxidant and anti-inflammatory effects of crocin in nasal explants., Conclusion: Oxidative stress plays an important role in the development of CRSwNP by promoting various types of inflammation. The oxidative stress of nasal polyps comes from epithelial cells and macrophages. Antioxidant therapy may be a promising strategy for treating CRSwNP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhou, Zhou, Liu, Liu, Meng, Wen, Luo, Liu, Li, Ba and Du.)

Chronic rhinosinusitis (CRS) is a chronic inflammatory disease of the nasal cavity characterized by excessive nasal mucus secretion and nasal congestion. The development of CRS is related to pathological mechanisms induced by hypoxia. Under hypoxic conditions, the stable expression of both Hypoxia inducible factor-1 (HIF-1) α and HIF-2α are involved in the immune response and inflammatory pathways of CRS. The imbalance in the composition of nasal microbiota may affect the hypoxic state of CRS and perpetuate existing inflammation. Hypoxia affects the differentiation of nasal epithelial cells such as ciliated cells and goblet cells, induces fibroblast proliferation, and leads to epithelial-mesenchymal transition (EMT) and tissue remodeling. Hypoxia also affects the proliferation and differentiation of macrophages, eosinophils, basophils, and mast cells in sinonasal mucosa, and thus influences the inflammatory state of CRS by regulating T cells and B cells. Given the multifactorial nature in which HIF is linked to CRS, this study aims to elucidate the effect of hypoxia on the pathogenic mechanisms of CRS., (© 2022 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: CRSwNP is an inflammatory disease but the mechanism is not yet fully understood. MiR-21, a member of miRNAs, has been reported to play roles in mediating inflammation. However, the expression of miR-21 and its role in patients with CRSwNP remain elusive., Methods: Turbinates from control subjects, uncinate processes from CRSsNP, polyp tissues from CRSwNP, and nasal epithelial cells brushed from nasal mucosa were collected. The expression of miR-21 and cytokines in nasal tissues and epithelial cells were detected by qPCR. The localization of miR-21 was detected by ISH, and its target was identified by bioinformation analysis, qPCR, IHC, WB, and luciferase reporter system. The protein and mRNA of PDCD4 and NF-κB P65 were determined by WB and qPCR after miR-21 transfection in HNEpC. The role of miR-21 on cytokines was analyzed in HNEpC and nasal polyp explants., Results: MiR-21 was upregulated in CRSwNP relative to control subjects by qPCR, which was determined mainly in nasal epithelial cells of CRSwNP by ISH. Both pro-inflammation cytokines (IL-1β, IL-6, IL-8, IL-25, and TSLP) and a suppressive cytokine (IL-10) were overexpressed in the epithelial cells of CRSwNP. The expression of miR-21 was positively correlated with IL-10 and negatively correlated with IL-6, IL-8, IL-33, and TSLP in the epithelial cells of CRSwNP. As a potential target of miR-21, the expression of PDCD4 was negatively correlated with miR-21 in CRSwNP. In HNEpC, miR-21 could reduce the expression of PDCD4 at both mRNA and protein levels, and bioinformation analysis and luciferase reporter system confirmed PDCD4 as one target of miR-21. Furthermore, miR-21 could decrease the activation of NF-κB and increase IL-10 mRNA. Both SEB and LPS could elevate miR-21, with IL-25, IL-33, TSLP induced by SEB and IL-1β, IL-6, IL-8 induced by LPS, while the miR-21 could regulate the expression of IL-33, TSLP, IL-1β, IL- 6 and IL-8 in vitro and ex vivo . Clinically, miR-21 expression was inversely correlated with the Lund-Mackay CT scores and the Lund-Kennedy scores in CRSwNP., Conclusion: MiR-21 could be a prominent negative feedback factor in the inflammation process to attenuate the expression of pro-inflammatory cytokines, thereby playing an anti-inflammation role in CRSwNP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Du, Zhou, Zhong, Ba, Zhang, Liu and Liu.)

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common heterogenous disease in the patients with chronic airway diseases. This study investigated the role of blood eosinophil count (BEC) in the classification of CRSwNP and its recurrence in eosinophilic CRSwNP., Methods: Sixty-five patients who underwent nasal endoscopic resection of CRSwNP were recruited and divided into eosinophilic CRSwNP and non-eosinophilic CRSwNP groups based on the levels (10% cutoff) of eosinophil infiltration as indicated by hematoxylin and eosin (H&E) staining., Results: We recruited 30 patients in the eosinophilic CRSwNP group and 35 patients in the non-eosinophilic CRSwNP group. The outcome of preoperative visual analogue scale (VAS) score, preoperative Lund-Mackay score, and preoperative Lund-Kennedy score between the 2 groups were comparable. The level of BEC in the eosinophilic CRSwNP group was significantly higher than that of non-eosinophilic CRSwNP group (0.79 ± 0.27 × 10 9 /L vs 0.30 ± 0.22 × 10 9 /L; p < 0.001). We observed a statistical significance in the number of H&E eosinophils (29.11 ± 2.93 vs 3.17 ± 0.51; p < 0.001) and CRSwNP phenotypes (eosinophilic/non-eosinophilic, 28/3 vs 2/32; p < 0.001) when the cutoff value of BEC was set at 0.39 × 10 9 /L. The disease-free recurrence (DFR) was found to be statistically significant when the cutoff value of BEC was 0.73 × 10 9 /L in eosinophilic CRSwNP (p = 0.009)., Conclusion: Results indicate that BEC may be capable of distinguishing CRSwNP phenotypes as well as predicting polyp recurrence in eosinophilic CRSwNP. Given the relatively small sample size, further studies will be necessary to confirm a role for BEC as a systemic biomarker in CRSwNP., (© 2020 ARS-AAOA, LLC.)

Objective: To observe the expression of interleukin-17 and the infiltration of eosinophilic cells in nasal polyps and allergic rhinitis, and investigate the roles of IL-17 and eosinophils in the etiology of nasal polyps and allergic rhinitis., Method: A study was conducted on 21 patients of nasal polyps, 18 ones of allergic rhinitis and 12 normal individuals. Immunohistochemical stain with the rabbit monoclonal antibodies of IL-17 was carried out. The eosinophilic cells infiltrated in different tissues were stained with HE, then counted under high power filed. The data was analyzed with ANOVA of SPSS12.0 software., Result: Many IL-17 stained cells were found in the samples of nasal polyps and allergic rhinitis, which were significantly higher than those in normal individuals (P < 0.05). Positive cell number in tissues of allergic rhinitis was similar to that in nasal polyps, but higher than in normal individuals. As for HE staining, there was no significant deviation of numbers of eosinophilic cell in tissue between allergic rhinitis and nasal polyps,while which differed from the normal ones (P < 0.05)., Conclusions: 1. IL-17 is a newly cytokine which expressed in mucosa of allergic rhinitis and nasal polyps tissue. It indicates the degree of immunological reaction and inflammatory reaction, and can be used as an index to research the mechanism of nasal polyps as well as allergic rhinitis. 2. The eosinophilic cells count was correlated with the amount of IL-17 positive cells in nasal polyps and with allergic rhinitis correlation coefficients were R = 0. 606 (P < 0 01)and R = 0.446 (P < 0.05) respectively. It seems that eosinophils, which are regulated by IL-17, play an important roles in the development of nasal polyps and allergic rhinitis.