BACKGROUND:Focused ultrasound (FUS) has achieved favorable results in the treatment of allergic rhinitis (AR). However, some patients still have poor outcomes, and there are no preoperative, especially machine learning (ML)-based tools to predict them. OBJECTIVE:This paper intends to explore the predictors of the efficacy of FUS in AR and, for the first time, to construct a ML-based predictive model for poor outcomes. METHODS:Clinical data of patients with moderate-to-severe AR receiving FUS were collected from the otolaryngology of the Central Hospital of Wuhan from 2019 to 2023. Patients were assigned to training and internal validation sets in a 3:1 ratio. In the training set, LASSO regression was employed for variable screening, and four machine learning models were constructed. The area under the receiver operating characteristic curve (AUROC) was leveraged to assess the prediction accuracy. The calibration curve was plotted to measure the calibration of models. The decision curve and clinical impact curve were plotted to assess clinical applicability. RESULTS:A total of 330 AR patients were included (247 in the training set and 83 in the validation set). Disease duration, peripheral blood eosinophil (PBE) count, comorbid chronic rhinosinusitis (CRS), nasal endoscopy scores, preoperative TNSS and endoscopy total scores were identified as predictors of efficacy. Logistic regression and XGBoost were the most accurate. The AUROC of logistic regression and XGBoost was 0.732 (95% CI: 0.647-0.816) and 0.811 (95% CI: 0.741-0.881) in the training set, and 0.788 (95% CI: 0.682-0.896) and 0.809 (95% CI: 0.707-0.912) in the validation set. CONCLUSION:The ML-based models can help clinicians identify patients with refractory AR early, providing a theoretical basis for clinical decision-making. This preliminary model was constructed based on single-center data, and only internal validation was performed. Therefore, its clinical applicability should be interpreted with caution, and external validation is needed. Future research should update and refine the model.

BACKGROUND:Nasal polyps (NP) are common upper respiratory conditions with diverse inflammatory subtypes influencing clinical features and prognosis. Manual counting of inflammatory cells in microscopic images (MI) is laborious and subjective, limiting diagnostic precision and treatment decisions. METHODS:A total of 2457 slides from 20 hospitals were used to develop an AI-based NP subtype diagnosis system (NPSS). NPSS-MI was built using 1047 slides (15,705 MIs) annotated by pathologists. NPSS-WSI was trained on 1410 slides (21,150 images) combining PA-P2PNet for cell detection and U-KAN for region segmentation. Three-dimensional reconstruction (3DNP) using registration and point cloud analysis enabled spatial quantification of inflammatory cells. Twelve pathologists evaluated NPSS accuracy and efficiency on 200 slides, and recurrence prediction models were developed using logistic regression in a 131-patient cohort. RESULTS:NPSS achieved performance with a weighted average F1-score of 0.809 for cell detection and an intersection over union (IoU) of 0.827 for region segmentation with an internal dataset. External dataset performance showed an F1-score of 0.792 and an IoU of 0.815. Forty randomly accumulated MIs were approximated WSI results. NPSS-MI and NPSS-WSI reached accuracies of 90% and 91%, reducing diagnostic time from 193 to 8 s and from 10,450 to 250 s, respectively. Junior pathologists using NPSS improved accuracy from 50% to 89%. Inflammatory cells showed distinct spatial patterns in 3DNP. NPSS-WSI prognostic model outperformed the MI-based model (AUC 86.64% vs. 79.81%, p = 0.039). CONCLUSIONS:NPSS integrates MI, WSI, and 3DNP to enable accurate and efficient NP subtype diagnosis and prognosis prediction, greatly enhancing diagnostic precision and clinical utility.

Objective To analyze the characteristics of cytokine profile changes in nasal secretions of allergic rhinitis (AR)patients receiving different treatments, with the aim of informing an objective, biomarker-based system for clinical efficacy assessment and guiding future research and policy development. MethodsTo explore objective evaluation indicators, this study conducted a comprehensive search of the studies related to cytokine detection and analysis of in nasal secretions in databases such as PubMed, Web of Science, CNKI and Wanfang Data, covering the period from July 1, 2015 to July 1, 2025. Results 118 studies met the inclusion criteria. Across multiple investigations, the levels of Th2-related cytokines consistently decreased after treatment, whereas those of Th1-related cytokines generally increased. Conclusions Th1- and Th2-related cytokines in nasal secretions can serve as an objective criterion for evaluating therapeutic efficacy, which can be used in subsequent related studies.

Background and Objective:The treatment available for chronic rhinosinusitis with nasal polyps (CRSwNP) has remained unsatisfactory. Patient-reported outcome measures (PROMs), capturing patient-perceived health status and well-being, are vehicles for measuring and improving the efficacy of care. This study aimed to establish machine learning (ML) models to predict PROMs in CRSwNP patients using minimally invasive and easily acquired clinical data. Methods:We collected commonly available clinical predictive data from 437 patients and established four separate ML models in the training set: a least absolute shrinkage and selection operator (LASSO)-based Logistic regression, a random forest (RF) regression, a gradient-boosted decision tree (GBDT), and a deep neural network (DNN). In the test and independent external validation sets, the predictive performance of these models was measured by calculating C statistics, expected prediction results, and decision curves. A feature-ranking analysis was performed using the ML algorithm. We then developed a predictive nomogram using LASSO-based Logistic regression. Results:The models performed well on an independent external validation set, with no statistically significant differences in generalization ability metrics between groups. LASSO regression identified key features of the predictive PROMs. A nomogram was created based on multivariate Logistic regression with LASSO regularization. Conclusions:All four ML models demonstrated similar performance in predicting PROMs in CRSwNP patients from which a clinical nomogram was developed. Early prediction of the subjective treatment response is crucial, as it influences clinician decisions and facilitates effective doctor-patient communication preoperatively; this could lead to more precise and personalized treatment for CRSwNP patients.

BackgroundChronic Rhinosinusitis with Nasal Polyps (CRSwNP) is characterized by persistent mucosal inflammation and tissue remodeling, driven by the crosstalk between epithelial and immune cells. Emerging evidence indicates that, in addition to IL-13, TSLP, and IL-33, other mediators also significantly contribute to the crosstalk. In this study, we investigate the mechanism by which epithelial cell mitochondrial dysfunction drives immune dysregulation in CRSwNP, aiming to uncover novel therapeutic targets.MethodsWe analyzed transcriptomic data from three GEO datasets (GSE194282, GSE72713, GSE36830) to identify Differentially Expressed Genes (DEGs). By integrating mitochondrial-associated genes (MitoCarta3.0), we performed functional enrichment (GO/KEGG) and PPI network analyses to identify hub genes. In vitro experiments, including western blotting, flow cytometry, and immunofluorescence, were applied to elucidated the role of COX5A in mediating M2 macrophage polarization via ROS production. A murine nasal polyp (NP) model further confirmed key findings.ResultsWe identified 110 mitochondrial-related DEGs (80 upregulated, 30 downregulated), prominently enriched in immune regulation and mitochondrial respiratory chain. Immune infiltration analysis revealed significant upregulation of M2 macrophages and resting memory CD4+T cells in CRSwNP tissues. Strikingly, IL-13-stimulated epithelial cells (ECs) drove M2 polarization via COX5A-mediated ROS production-an effect abolished by COX5A knockdown or ROS scavengers. Furthermore, a murine nasal polyps model confirmed elevated COX5A and M2 marker expression, reinforcing the clinical relevance of our findings.ConclusionOur research highlights the crucial role of mitochondrial dysfunction, particularly through COX5A-mediated reactive oxygen species (ROS) generation, in promoting the polarization of M2 macrophages and the progression of CRSwNP. These findings emphasize the potential for targeting mitochondrial-immune crosstalk as an effective therapeutic strategy, thereby opening new avenues for addressing CRSwNP.

PURPOSE:The purpose of this study is to examine the influence of allergic rhinitis (AR) and asthma on the incidence of otitis media (OM), which in turn serves as a mediator for the need for tympanostomy tube placement (TTP). METHODS:A comprehensive logistic regression analysis was performed, incorporating multiple variables to assess the relationship between AR, asthma, and the likelihood of TTP. OM was considered the mediating variable in this relationship. The analysis adjusted for a range of demographic and health-related covariates to ascertain the independent effects of the allergic conditions. Mediation analysis was utilized to evaluate the extent to which otitis media influences the association between AR and asthma and the need for TTP. Additionally, sensitivity analyses were conducted to assess the robustness of the findings against potential missing data. RESULTS:The study revealed significant associations between AR and asthma with the prevalence of OM, which in turn significantly increased the odds of TTP. Specifically, the odds ratios (ORs) for AR were 2.46, 2.44, and 2.19 across models 1, 2, and 3, respectively, indicating a robust correlation with TTP. Asthma also showed a consistent positive relationship with TTP, with ORs of 1.95, 1.94, and 1.56 for the respective models. Mediation analysis provided evidence that OM significantly mediated the relationship between AR and TTP, with an Average Causal Mediation Effect (ACME) of 0.02219, translating to 2.22% of the total effect being mediated through OM. For asthma, the ACME was 0.01395, indicating a 1.4% mediation effect. The Average Direct Effects (ADE) for AR and asthma were 0.03151 and 0.02084, respectively, suggesting substantial direct and indirect effects on TTP. Sensitivity analyses, accounting for missing data, further substantiated the robustness of these associations, with adjusted ORs for AR and asthma remaining highly significant. CONCLUSION:The study concludes that AR and asthma are key drivers of OM, which acts as a mediator for TTP. The significant mediation effects highlight the importance of managing these allergic conditions to potentially reduce the incidence of ear infections and the necessity for TT surgery. Further research is encouraged to explore the intricate links between allergic conditions and otological health, facilitating the development of more effective clinical interventions.

Environmental pollutants like PM2.5 contribute to chronic rhinosinusitis (CRS). The aryl hydrocarbon receptor (AhR), a contaminant sensor linked to tryptophan metabolites, is regulated by IL4I. However, how PM2.5 stimulation via IL4I1 influences AhR activation and CRS pathogenesis remains unclear. This study explored the IL4I1-AhR pathway in CRS using patient tissues, HNEpCs, and murine models. Methods included IHC, qRT-PCR, and WB under PM2.5 exposure, with further investigation into downstream effects on CYP1B1 and epithelial-mesenchymal transition (EMT). Significant upregulation of IL4I1, AhR, and CYP1B1 was observed in CRS tissues, with higher expression levels in CRS patients. Exposure to PM2.5 activated the IL4I1-AhR pathway, leading to decreased E-cadherin, increased N-cadherin and vimentin, and impaired nasal mucosal barrier function. In vitro experiments demonstrated that PM2.5-induced EMT in HNEpCs was mediated by IL4I1-dependent AhR activation. CH223191 reduced cell migration and EMT, while IL4I1 knockdown attenuated AhR activation and EMT marker expression. Murine models further confirmed that PM2.5 exacerbated nasal polyp formation and tissue remodeling via the IL4I1-AhR pathway. This study underscores the critical role of the IL4I1-AhR signaling pathway in PM2.5-induced nasal mucosal barrier dysfunction and EMT in CRS. IL4I1, as an upstream regulator of AhR, promotes EMT and nasal mucosal barrier disruption.

Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal mucosa characterized by allergen sensitization and the involvement of multiple inflammatory mediators. Currently, the treatment of AR mainly includes symptomatic relief, anti-inflammatory therapy, and nerve desensitization. However, these treatments have limitations in fully integrating the underlying mechanisms with the clinical manifestations of AR. This review aims to summarize recent research findings on AR phenotypes and endotypes, enhance understanding of endotype-phenotype associations, and outline various treatment options based on phenotypes and endotypes to provide insights for early recognition and personalized clinical management of patients with AR.

BACKGROUND:Basal cells (BCs) play a crucial role in epithelial remodeling, a hallmark of eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP). Single-cell sequencing has revealed an increased number of solitary chemosensory cells (SCCs) alongside BC hyperplasia in eCRSwNP, yet the underlying mechanism of BC hyperplasia in eCRSwNP remains unclear. This study aimed to investigate the role of SCC-derived acetylcholine (Ach) in determining BC fate. METHODS:Tissue samples from healthy individuals, patients with eCRSwNP, and those with non-eCRSwNP (neCRSwNP) were analyzed to investigate BC proliferation, differentiation abnormalities, and the prevalence of SCCs. The relationship between SCC-derived Ach, BC dysfunction, and disease severity was examined. Ach sources and receptor expression patterns were characterized. In vitro studies using submerged cell cultures and air-liquid interface cultures, along with in vivo murine models, were employed to elucidate the mechanisms by which Ach influences BC fate. The inhibitory effects of tiotropium bromide (TB) on Ach-driven processes were also evaluated. RESULTS:Our results indicated that SCC-derived Ach, rather than by parasympathetic nerves, contributed to abnormal BC proliferation and differentiation through muscarinic acetylcholine receptors (mAChRs) and had potential impact on the development of eCRSwNP. These effects were associated with the activation of YAP and could be partially reversed both in vitro and in vivo by blocking mAChRs with TB. CONCLUSION:These results demonstrate that SCC-derived Ach plays a critical role in eCRSwNP by regulating BC fate. This provides a potential translational framework for developing prevention and treatment strategies targeting the cholinergic pathway.

Purpose:The study aimed to identify key genes related to lipid metabolism in chronic sinusitis and understand their biological implications, considering the growing interest in the association between chronic sinusitis - a complex inflammatory condition - and lipid metabolism due to lipids' role in inflammation and immunity. Methods:Gene expression data from bulk - RNA sequence was analyzed and intersected with lipid metabolism genes and WGCNA module genes from the MSigDB database. Immune infiltration analysis was conducted. Machine learning techniques were used to develop a diagnostic model. qRT - PCR and immunofluorescence techniques were employed to confirm gene involvement. Potential targeted drugs were identified through relevant analyses. Results:41 hub genes were identified, which were involved in pathways like G protein - coupled receptor signaling, TGF - beta receptor signaling, and responses to oxidative stress and nitrogen compounds. Enrichment analyses suggested links to ubiquitin - mediated proteolysis, mTOR signaling, and MAPK signaling. A significant presence of immune cells was detected in the chronic sinusitis group. A combined RF+Stepglm model was developed, comprising six genes (KPNA3, RAB35, GLE1, RNF139, OSMR, and PDPK1), which demonstrated good diagnostic performance (AUC = 0.848). Potential targeted drugs such as Raloxifene and Hesperidin were identified. qRT - PCR and immunofluorescence confirmed that the expression levels of RAB35, GLE1, and OSMR were significantly higher in CRS samples compared to normal ones. Conclusion:This research highlights the role of lipid metabolism in chronic sinusitis and provides a basis for the development of targeted therapies.

Background and purpose:Chronic rhinosinusitis with nasal polyps (CRSwNP) is a persistent inflammatory condition marked by high recurrence and limited therapeutic efficacy. This study investigates the role of long non-coding RNA NEAT1 in promoting epithelial-mesenchymal transition (EMT) in CRSwNP, focusing on its regulatory interaction with the miR-199-3p/PAK4 axis. Methods:NEAT1 expression was assessed in nasal epithelial cells from CRSwNP patients using qPCR and FISH. Primary human nasal epithelial cells and BEAS-2B cells were subjected to NEAT1 knockdown via siRNA. Cell migration, barrier function, and cytoskeletal dynamics were evaluated through scratch assays, Transwell migration, FITC-Dextran permeability testing, and phalloidin staining. EMT marker expression was analyzed via Western blotting and immunofluorescence. Transcriptome sequencing identified PAK4 as a downstream effector. In vivo validation was performed using a mouse nasal polyp model, and molecular interactions among NEAT1, miR-199-3p, and PAK4 were confirmed via dual-luciferase reporter assays. Rescue experiments further elucidated mechanistic pathways. Results:In comparison to controls, NEAT1 expression was significantly elevated in the epithelial tissues of CRSwNP. NEAT1 knockdown inhibited cell migration, enhanced epithelial barrier integrity, and reversed EMT-associated cytoskeletal remodeling. E-cadherin levels increased, while N-cadherin and vimentin decreased. Transcriptomic and functional analyses identified PAK4 as a NEAT1-regulated target. NEAT1 was shown to sponge miR-199-3p, thereby relieving its inhibitory effect on PAK4. Overexpression of miR-199-3p suppressed PAK4 and mitigated EMT-related changes induced by NEAT1. Conclusion:NEAT1 promotes EMT in nasal polyp epithelial cells by modulating the miR-199-3p/PAK4 axis, highlighting its potential as a diagnostic biomarker and therapeutic target in CRSwNP.

Background: The concept "one airway, one disease" for childhood rhinitis and asthma has been challenged in recent years. This study aimed to evaluate associations of environmental exposures with alone and co-morbid symptoms of rhinitis and asthma and identify critical risk factor. Methods: 5828 children aged 3-6 years in Shanghai were surveyed in 2019. Rhinitis and wheezing symptoms in the past 12 months were collected using questionnaire. 11 outdoor environment exposure factors were assessed by high-resolution spatial-temporal model based on residences. Logistic regression and random forest were applied to evaluate and rank the association of environmental exposure with rhinitis and wheezing symptoms. Results: The proportions of children with rhinitis alone, wheezing & rhinitis, and wheezing alone were 37.2 %, 4.6 %, and 2.6 %, respectively. Regression modeling of two exposure factors adjusted for each other showed that PM1, PM 2.5 and nighttime light(NTL) remained the robust significant associations with rhinitis alone, whereas NO2 had the robust significant association with wheezing & rhinitis and wheezing alone. Random forest ranking analysis further corroborated the most significant environmental exposure for rhinitis alone was PM1, and for wheezing symptoms (both wheezing & rhinitis and wheezing alone) was NO2. Significant additive and multiplicative interactions were examined between indoor dampness and PM1 exposure on rhinitis alone. Conclusion: Children's current rhinitis alone was more susceptible to ambient PM1 and PM 2.5, while asthmatic wheezing symptom, either with or without rhinitis, was more susceptible to NO2. Co-exposure to indoor dampness and PM1 exposure had synergistic effects on rhinitis alone.

Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) is encoded by a gene strongly associated with lupus and other autoimmune diseases. PTPN22 regulates T cell receptor (TCR) signaling through dephosphorylation of the kinases lymphocyte-specific protein tyrosine kinase (LCK) and zeta-chain-associated protein kinase 70 (ZAP70). The regulation of PTPN22 remains poorly understood. Here, we identify PTPN22 Ser449 as a protein kinase A phosphorylation site, which is triggered by TCR engagement and is hyperphosphorylated in lupus peripheral blood cells. PTPN22 Ser449 phosphorylation selectively lowered the affinity of PTPN22 for ZAP70 versus LCK but also indirectly suppressed inhibitory LCK Tyr192 phosphorylation through a ZAP70-CD45 signaling axis. The resulting dephosphorylation of LCK Tyr192 not only enhanced TCR signaling but also modulated pathway activation downstream the TCR. In vivo loss of PTPN22 Ser449 phosphorylation reduced T cell responses and suppressed experimental lupus nephritis. These results suggest that PTPN22 Ser449 phosphorylation promotes a CD45-mediated retrograde ZAP70-LCK feedback loop that enhances T cell responses and promotes autoimmunity.

INTRODUCTION:Allergic diseases are common clinical diseases. Although allergen-specific immunotherapy (AIT) and biologics have been widely recognized, the clinical efficacy, safety, advantages, and disadvantages of the combined application have not yet been sufficiently recognized. We aimed to investigate the efficacy and safety of AIT combined with biologics in patients with allergic rhinitis and asthma. METHODS:PubMed, Embase, the Cochrane Library, and Web of Science were systematically searched to identify studies investigating AIT combined with biologics for treating allergic rhinitis and asthma. The relevant outcome indicators, including incidences of emergency drug use, severe nasal symptoms, severe adverse effects (AEs), local reactions at the site of administration, headache, and general AEs, were collected and extracted. Routine and network meta-analyses were conducted using RevMan-5.4 and STATA-MP-14 to assess efficacy and safety. RESULTS:Eight RCTs and a retrospective study involving 1,494 patients aged 5-65 years with allergic rhinitis and asthma were included in this review. (1) Routine meta-analysis revealed that AIT combined with biologics was significantly better than control treatment (placebo, AIT, or biologics) in terms of the incidence of emergency drug use, severe nasal symptoms, and severe AEs (p = 0.0002; p = 0.01; p = 0.02). However, the differences in the incidence of local reactions at the site of administration, headache, and general AEs were not significant. (2) In the network meta-analysis, compared with AIT or placebo alone, AIT combined with biologics observably reduced the incidence of emergency drug use and severe nasal symptoms (OR = 0.32, 95% CI 0.14-0.73; OR = 0.41, 95% CI: 0.26-0.63). Furthermore, AIT combined with biologics yielded an evidently lower incidence of serious adverse reactions than AIT alone (OR = 0.42, 95% CI: 0.23-0.74). CONCLUSION:The combined application of AIT and biologics has promising prospects in the clinical treatment of allergic rhinitis and asthma due to the improvement of both clinical efficacy and safety (trial registration: Systemic Review Registration; PROSPERO #CRD42024496277).

Purpose:Chronic rhinosinusitis with nasal polyps (CRSwNP) is a prevalent upper respiratory disease with eosinophilic infiltration. Epithelial-to-mesenchymal transition (EMT) has been considered an important pathological mechanism of CRSwNP. The Wnt signaling pathway is a well-established promoter of EMT, while Protein Phosphatase 2A (PP2A) exerts dual regulatory effects on Wnt pathway. However, the contribution of PP2A to CRSwNP has not been reported. This research aimed to explore the possible mechanisms by which PP2A modulates EMT in CRSwNP. Patients and Methods:About 56 patients with CRSwNP and 20 control subjects were enrolled in this study. We collected nasal polyps (NPs) and inferior turbinate tissues; the expression of PP2A, EMT markers, and Wnt signaling-related mediators in tissues were analyzed by Western blotting, immunohistochemistry, and quantitative RT-PCR. Primary cells isolated from NPs were cultured with PP2A inhibitor LB-100. The rhWNT3A-induced EMT cell model using BEAS-2B cell line was established in vitro and treated with either LB-100 or the PP2A agonist DT-061. Murine NP model was developed in vivo and treated with LB-100. The expression changes of EMT markers and Wnt signaling mediators were detected using Western blotting, immunofluorescence staining, and hematoxylin-eosin staining to estimate the effect of PP2A in the pathogenesis of CRSwNP. Results:Compared to controls, NPs exhibited increased PP2A expression and activity, activation of Wnt signaling, and evidence of EMT. These changes were more pronounced in eosinophilic NPs. PP2A inhibition alleviated, whereas PP2A activation promoted, EMT in epithelial cells by regulating Wnt pathway. PP2A inhibition could also suppress the formation of NPs and alleviate eosinophilic inflammation in the murine NP models. Conclusion:PP2A promotes EMT through the activation of Wnt/β-catenin signaling pathway, leading to epithelial barrier dysfunction in NPs. PP2A exerts a positive regulatory effect on the modulation of Wnt signaling in CRSwNP. Targeting PP2A might represent a viable therapeutic option for treating CRSwNP.

Gut dysbiosis is observed in patients with rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA), however, how it promotes disease in interaction with other environmental and genetic risk factors remains unclear. Here we assessed interactions between gut dysbiosis and RA/JIA-associated loss of function haplotypes of the RA/JIA-associated PTPN2 gene by inducing mannan-induced arthritis in germ-free PTPN2+/+ and PTPN2 haploinsufficient (PTPN2+/-) SKG mice reconstituted with fecal microbiota from six patients with seropositive RA. Mannan-induced arthritis and lymph node T cell immunophenotypes were identical in germ free PTPN2+/+ vs PTPN2+/- SKG mice. While no difference in arthritis severity was seen among PTPN2+/+ mice recipient of RA gut microbiota, two microbiomes (RA#02 and RA#86) enhanced arthritis in PTPN2+/- mice. The microbiome of RA patient microbiota recipient mice exclusively clustered by patient of origin and the RA#86 microbiome was found to carry a significant expansion of Prevotella genera, which is associated with RA dysbiosis. RA#86 microbiota-recipient PTPN2+/- mice selectively displayed increased joint GM-CSF expression and an expansion of CD4+RORγt+FoxP3- T cells in the joints, without evidence of increased intestinal inflammation, gut barrier leakage or expansion of P. copri in post-mannan fecal samples. Monocolonization with P. copri caused enhanced arthritis and CD4+RORγt+FoxP3- T cells expansion in PTPN2+/- vs PTPN2+/+ mice. Our data support current views about P. copri promotion of autoimmune arthritis and suggest that its pathogenicity can be amplified via interaction with a dysbiotic context and risk factors that enhance gut mucosa immune responses.

BACKGROUND:Epithelial-mesenchymal transition (EMT) is involved in local tissue remodeling in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the function of Piezo1 in EMT process remains unclear. This study aimed to characterize potential roles of Piezo1 in EMT process in CRSwNP. METHODS:Overall, 22 nasal polyp (NP) tissues from patients with CRSwNP and 20 middle turbinate from healthy individuals were obtained during surgery. The expression of Piezo1, E-cadherin, vimentin, and α-smooth muscle actin (α-SMA) was measured by using western blot (Wb) in NP tissues and primary human nasal epithelial cells (pHNECs) and the location and level were assessed by immunofluorescence staining. BEAS-2B cells were stimulated with transforming growth factor (TGF)-β1 to induce EMT in vitro model and examined using qRT-PCR. BEAS-2B cells were treated with Yoda1 and RuR to calculate protein level by Wb analysis. Yoda1 and RuR treated NP murine model was evaluated by H&E (hematoxylin-eosin) staining and immunohistochemistry. RESULTS:Compared with the control group, E-cadherin was decreased while the level of Piezo1, vimentin, and α-SMA was increased in NP group. Piezo1, vimentin, and α-SMA were upregulated in TGF-β1-induced BEAS-2B cells. Yoda1 inhibited E-cadherin expression and promoted Piezo1 and the aforementioned mesenchymal markers, whereas RuR showed contrary results. The results from the murine model treated with Yoda1 and RuR were consistent with those results in the EMT model in vitro. CONCLUSION:Piezo1 is linked with EMT process in CRSwNP and the activation of Piezo1 exacerbates EMT process of nasal polyps.

Background and Objective: Rheumatoid arthritis (RA) is a systemic autoimmune disease that causes joint deformities and even complete loss of joint function. Artesunate (ART) is an active ingredient in Chinese herbal medicines, usually used to treat malaria. This study aimed to investigate the effect of Artesunate on collagen-induced arthritis (CIA) in rats, along with its efficacy and underlying mechanism.Methods: The CIA rat model was created using bovine type II collagen and incomplete F-style adjuvants. The rats with CIA were divided into three groups: the Model group, the tripterygium hypoglaucum hutch (THH) group, and the ART group. The model group received 0.9% normal saline, the THH group was given a daily dose of 150 mgkg(-1) THH, and the ART group was given a daily dose of 10 mgkg(-1) artesunate for 30 days. The negative control (NC) group received only an equal volume of 0.9% normal saline. The body weight, arthritis index, and paw thickness of the rats were recorded throughout the treatment. The levels of tumor necrosis factor alpha (TNF-alpha) and interleukin 17A (IL-17A) in the serum of rats with CIA were assessed using enzyme-linked immunosorbent assay (ELISA). Furthermore, the indices of vital immune organs, including the thymus and spleen, were calculated. The hindpaw of each group was collected and subjected to histopathological examinations using hematoxylin-eosin (H&E) staining, safranin O-fast green staining and X-ray methods.Results: The arthritis index, the thickness of the foot, and the contents of IL-17A in the CIA model group were significantly increased compared to the NC group (p < 0.05). Moreover, synovial hyperplasia and cartilage damage were significantly decreased in the ART group (p < 0.05). However, the immune organ index and serum TNF-alpha level did not reach statistical significance (p > 0.05). Additionally, the serum IL-17A level was significantly lower than the model group (p < 0.05).Conclusion: Artesunate exerts a protective effect on joint damage in rats with CIA, which may reduce inflammation and delay the development of the disease by inhibiting the secretion of IL-17A.

Background: The occurrence of nasal polyps is related to mucosal barrier damage. The role of MG53, an important epithelial repair regulator, in nasal polyps remains unclear. This study aimed to investigate the role of MG53 in nasal epithelial repair. Methods: We divided the patients into the following three groups (n=15 each): chronic rhinosinusitis without nasal polyps (CRSsNP), chronic rhinosinusitis with nasal polyps (CRSwNP) and septal deviation (control). We performed qRT-PCR and western blotting to determine the expression of MG53, TGF-β1, Smad2/3, zonula occluden-1 (ZO-1), and collagen-a1 (Col-a1) in nasal tissues and human nasal epithelial cells (HNECs). HNECs were cultured to investigate the regulatory role of MG53 and the TGF-β1/Smad pathway in the repair of nasal epithelial cells. Results: We found that the expression of MG53, TGF-β1, Smad2/3, ZO-1, and Col-a1 was upregulated in the CRSsNP group, whereas it was downregulated in the CRSwNP group. In the HNECs of nasal polyps, the expression of TGF-β1, Smad2/3, ZO-1, and Col-a1 was downregulated after overexpressed MG53, whereas this was reversed by the knockdown of MG53. Additionally, we found that TGF-β1 stimulation resulted in significantly upregulated MG53 expression, which was impeded by TGF-β1 inhibitors. MG53 expression facilitated proliferation, promoted the secretion of Col-a1, and inhibited apoptosis in HNECs. Conclusion: MG53 inhibited the TGF-β1/Smad pathway and fibrosis, enhanced the proliferation of nasal epithelial cells, and supported nasal epithelial repair. The results of this study provide a new therapeutic regimen for the treatment of nasal polyps. Keywords: epithelial repair; mitsugumin53; nasal polyps; tight junction; TGF-β1/Smad.