Pathogenesis Of Allergic Rhinitis Research Articles

The barrier-protective effect of β-eudesmol against type 2-inflammatory cytokine-induced tight junction disassembly in airway epithelial cells.

Allergic inflammation, which is the pathogenesis of allergic rhinitis and asthma, is associated with disruption of the airway epithelial barrier due to the effects of type 2 inflammatory cytokines, i.e. interleukin-4 and interleukin-13 (IL-4/13). The anti-allergic inflammatory effect of β-eudesmol (BE) on the tight junction (TJ) of the airway epithelium has not previously been reported. Herein, the barrier protective effect of BE was determined by measurement of transepithelial electrical resistance and by paracellular permeability assay in an IL-4/13-treated 16HBE14o- monolayer. Pre-treatment of BE concentration- and time- dependently inhibited IL-4/13-induced TJ barrier disruption, with the most significant effect observed at 20 μM. Cytotoxicity analyses showed that BE, either alone or in combination with IL-4/13, had no effect on cell viability. Western blot and immunofluorescence analyses showed that BE inhibited IL-4/13-induced mislocalization of TJ components, including occludin and zonula occludens-1 (ZO-1), without affecting the expression of these two proteins. In addition, the mechanism of the TJ-protective effect of BE was mediated by inhibition of IL-4/13-induced STAT6 phosphorylation, in which BE might serve as an antagonist of cytokine receptors. In silico molecular docking analysis demonstrated that BE potentially interacted with the site I pocket of the type 2 IL-4 receptor, likely at Asn-126 and Tyr-127 amino acid residues. It can therefore be concluded that BE is able to prevent IL-4/13-induced TJ disassembly by interfering with cytokine-receptor interaction, leading to suppression of STAT6-induced mislocalization of occludin and ZO-1. BE is a promising candidate for a therapeutic intervention for inflammatory airway epithelial disorders driven by IL-4/13.

Identifying allergic-rhinitis-associated genes with random-walk-based method in PPI network

Allergic rhinitis is a common allergic disease with a complex pathogenesis and many unresolved issues. Studies have shown that the incidence of allergic rhinitis is closely related to genetic factors, and research on the related genes could help further understand its pathogenesis and develop new treatment methods. In this study, 446 allergic rhinitis-related genes were obtained on the basis of the DisGeNET database. The protein–protein interaction network was searched using the random-walk-with-restart algorithm with these 446 genes as seed nodes to assess the linkages between other genes and allergic rhinitis. Then, this result was further examined by three screening tests, including permutation, interaction, and enrichment tests, which aimed to pick up genes that have strong and special associations with allergic rhinitis. 52 novel genes were finally obtained. The functional enrichment test confirmed their relationships to the biological processes and pathways related to allergic rhinitis. Furthermore, some genes were extensively analyzed to uncover their special or latent associations to allergic rhinitis, including IRAK2 and MAPK, which are involved in the pathogenesis of allergic rhinitis and the inhibition of allergic inflammation via the p38-MAPK pathway, respectively. The new found genes may help the following investigations for understanding the underlying molecular mechanisms of allergic rhinitis and developing effective treatments.

Deciphering the Systemic Impact of Herbal Medicines on Allergic Rhinitis: A Network Pharmacological Approach.

Allergic rhinitis (AR) is a systemic allergic disease that has a considerable impact on patients' quality of life. Current treatments include antihistamines and nasal steroids; however, their long-term use often causes undesirable side effects. In this context, traditional Asian medicine (TAM), with its multi-compound, multi-target herbal medicines (medicinal plants), offers a promising alternative. However, the complexity of these multi-compound traits poses challenges in understanding the overall mechanisms and efficacy of herbal medicines. Here, we demonstrate the efficacy and underlying mechanisms of these multi-compound herbal medicines specifically used for AR at a systemic level. We utilized a modified term frequency-inverse document frequency method to select AR-specific herbs and constructed an herb-compound-target network using reliable databases and computational methods, such as the Quantitative Estimate of Drug-likeness for compound filtering, STITCH database for compound-target interaction prediction (with a high confidence score threshold of 0.7), and DisGeNET and CTD databases for disease-gene association analysis. Through this network, we conducted AR-related targets and pathway analyses, as well as clustering analysis based on target-level information of the herbs. Gene ontology enrichment analysis was conducted using a protein-protein interaction network. Our research identified 14 AR-specific herbs and analyzed whether AR-specific herbs are highly related to previously known AR-related genes and pathways. AR-specific herbs were found to target several genes related to inflammation and AR pathogenesis, such as PTGS2, HRH1, and TBXA2R. Pathway analysis revealed that AR-specific herbs were associated with multiple AR-related pathways, including cytokine signaling, immune response, and allergic inflammation. Additionally, clustering analysis based on target similarity identified three distinct subgroups of AR-specific herbs, corroborated by a protein-protein interaction network. Group 1 herbs were associated with the regulation of inflammatory responses to antigenic stimuli, while Group 2 herbs were related to the detection of chemical stimuli involved in the sensory perception of bitter taste. Group 3 herbs were distinctly associated with antigen processing and presentation and NIK/NF-kappa B signaling. This study decodes the principles of TAM herbal configurations for AR using a network pharmacological approach, providing a holistic understanding of drug effects beyond specific pathways.

LINC00998 Modulating M2 Macrophage Activation in Allergic Rhinitis by Stabilizing BOB.1 mRNA.

Allergic rhinitis (AR) is globally recognized as a considerable threat to human health with a rising prevalence and a substantial medical and socioeconomic burden. Numerous studies have emphasized the significance of long noncoding RNAs (lncRNAs) in allergic responses. Hence, this research dealt with exploring the involvement of the lncRNA LINC00998 in the mechanism of AR. LINC00998 expression was assessed by qRT-PCR in peripheral blood mononuclear cells acquired from individuals with AR. Additionally, the potential relationship between LINC00998 and macrophage polarization was observed in vitro. Then we constructed AR mice model and macrophage polarization models using THP-1 cells as well as primary human macrophages to verify the M2 shift in AR and the low expression level of LINC00998 in M2 macrophages. We used gain- and loss-of-function experiments to explore the modification of LINC00998 in macrophage polarization. Furthermore, we explored the underlying mechanism of LINC00998 mediates through qRT-PCR, flow cytometry, and Western blot. The analysis revealed a significant decrease in LINC00998 expression in the samples obtained from patients with AR. LINC00998 is markedly increased in M1 macrophages whereas decreased in M2 macrophages in vitro. Furthermore, suppression of LINC00998 caused a remarkable enhancement in M2 polarization, whereas its overexpression led to its attenuation. Knockdown of LINC00998 led to a remarkable downregulation of BOB.1 mRNA and protein, while overexpression of LINC00998 upregulated their expression. Moreover, it was found that BOB.1 modulated macrophage polarization through the PU.1/IL-1β axis. Meanwhile, the modulation of LINC00098 overexpression on macrophage polarization and PU.1/ IL-1β can be reversed by BOB.1 siRNA. This research revealed the lncRNA LINC00998 altered M2 macrophage polarization by regulating the BOB.1/PU.1/IL-1β axis, which open up new avenues for studying the pathogenesis of AR.

Fecal Microbiota Transplantation Alleviates Allergic Rhinitis via CD4+ T Cell Modulation Through Gut Microbiota Restoration.

Allergic rhinitis (AR) is an allergic condition of the upper respiratory tract with a complex pathogenesis, including epithelial barrier disruption, immune regulation, and gut microbiota, which is not yet fully understood. Gut microbiota is closely linked to allergic diseases, including AR. Fecal microbiota transplantation (FMT) has recently been recognized as a potentially effective therapy for allergic diseases. However, the efficacy and mechanism of action of FMT in AR remain unknown. Herein, we aimed to observe the implications of gut microbiota on epithelial barrier function and T cell homeostasis, as well as the effect of FMT in AR, using the ovalbumin (OVA)-induced AR mice. The intestinal microbiota of recipient mice was cleared using an antibiotic cocktail; thereafter, FMT was performed. Subsequently, the nasal symptom scores and histopathological features of colon and nasal mucosa tissues of mice were monitored, and serum OVA-sIgE and cytokines of IL-4, IFNγ, IL-17A, and IL-10 cytokine concentrations were examined. Thereafter, tight junction protein and CD4+ T cell-related transcription factor and cytokine expressions were observed in the colon and nasal mucosa, and changes in the expression of PI3K/AKT/mTOR and NFκB signaling pathway were detected by WB assay in each group. Fecal DNA was extracted from the four mice groups for high-throughput 16S rRNA sequencing. FMT ameliorated nasal symptoms and reduced nasal mucosal inflammation in AR mice. Moreover, according to 16S rRNA sequencing, FMT restored the disordered gut microbiota in AR mice. Following FMT, ZO-1 and claudin-1 and Th1/Th2/Th17-related transcription factor and cytokine expressions were upregulated, whereas Treg cell-related Foxp3 and IL-10 expressions were downregulated. Mechanistic studies have revealed that FMT also inhibited PI3K/AKT/mTOR and NF-κB pathway protein phosphorylation in AR mouse tissues. FMT alleviates allergic inflammation in AR by repairing the epithelial barrier and modulating CD4+ T cell balance and exerts anti-inflammatory effects through the PI3K/AKT/mTOR and NF-κB signaling pathways. Moreover, gut microbiota disorders are involved in AR pathogenesis. Disturbed gut microbiota causes an altered immune-inflammatory state in mice and increases susceptibility to AR. This study suggested the regulatory role of the gut-nose axis in the pathogenesis of AR is an emerging field, which provides novel directions and ideas for the treatment of AR.

Decoding the genetic landscape of allergic rhinitis: a comprehensive network analysis revealing key genes and potential therapeutic targets

Background Allergic Rhinitis (AR), an inflammatory affliction impacting the upper respiratory tract, has been registering a substantial surge in incidence across the globe. Methods We embarked on examination of differentially expressed genes (DEGs) and the Weighted Gene Co-Expression Network Analysis (WGCNA). With this armory of genes identified, we engaged the tools of Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Our study continued with the establishment of a protein-protein interaction (PPI) network and the application of LASSO regression. Finally, we leveraged a docking model to elucidate potential drug-gene interactions involving these key genes. Results Through WGCNA and different express genes screening, PPI network was performed, identifying top 20 key genes, including CD44, CD69, CD274. LASSO regression identified three independent factors, STARD5, CST1, and CHAC1, that were significantly associated with AR. A predictive model was developed with an AUC value over 0.75. Also, 105 potential therapeutic agents were discovered, including Fluorouracil, Cyclophosphamide, Doxorubicin, and Hydrocortisone, offering promising therapeutic strategies for AR. Conclusion By fuzing DEGs with key genes derived from WGCNA, this study has illuminated a comprehensive network of gene interactions involved in the pathogenesis of AR, paving the way for future biomarker and therapeutic target discovery in AR.

Neuroimmune communication in allergic rhinitis.

The prevalence rate of allergic rhinitis (AR) is high worldwide. The inhalation of allergens induces AR, which is an immunoglobulin E-mediated and type 2 inflammation-driven disease. Recently, the role of neuroimmune communication in AR pathogenesis has piqued the interest of the scientific community. Various neuropeptides, such as substance P (SP), vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP), nerve growth factor (NGF), and neuromedin U (NMU), released via "axon reflexes" or "central sensitization" exert regulatory effects on immune cells to elicit "neurogenic inflammation," which contributes to nasal hyperresponsiveness (NHR) in AR. Additionally, neuropeptides can be produced in immune cells. The frequent colocalization of immune and neuronal cells at certain anatomical regions promotes the establishment of neuroimmune cell units, such as nerve-mast cells, nerve-type 2 innate lymphoid cells (ILC2s), nerve-eosinophils and nerve-basophils units. Receptors expressed both on immune cells and neurons, such as TRPV1, TRPA1, and Mas-related G protein-coupled receptor X2 (MRGPRX2) mediate AR pathogenesis. This review focused on elucidating the mechanisms underlying neuroimmune communication in AR.

LncRNA FGD5-AS1 Alleviates Inflammation in Allergic Rhinitis through the miR-223-3p/COX11 Axis

Introduction: Long noncoding RNAs (lncRNAs) have been implicated in the pathogenesis of allergic rhinitis (AR). The current investigation is focused on elucidating the functional impact of a specific lncRNA, FGD5 antisense RNA 1 (FGD5-AS1), on the development and progression of AR through its interaction with miR-223-3p. Methods: An experimental framework for AR was constructed in both cellular and animal models. Quantitative assessment of FGD5-AS1, miR-223-3p, and COX11 mRNA expression was conducted using real-time quantitative reverse transcription PCR. The expression of inflammatory factors, immunoglobulin E, LTC4, and ECP, was examined using ELISA. Apoptosis in human nasal epithelial cells was assessed by the flow cytometry method. The protein expression of COX11 was examined using Western blotting. Nasal mucosal function was further evaluated by hematoxylin and eosin staining. Furthermore, bioinformatics evaluations, dual-luciferase reporter assays, and a series of experimental procedures unveiled a putative competitive endogenous RNA regulatory mechanism. Results: We found the expression of lncRNA FGD5-AS1 was decreased in AR. In vitro lncRNA FGD5-AS1 attenuated the production of inflammatory cytokines in nasal epithelial cells. Furthermore, elevated FGD5-AS1 expression significantly alleviated AR symptoms by reducing nasal epithelial apoptosis and inflammation. MiR-223-3p was identified as a direct target of FGD5-AS1. Moreover, miRNA-223-3p directly downregulated the expression of COX11 mRNA. Subsequent experiments confirmed that FGD5-AS1 regulated AR through the miR-223-3p/COX11 axis, thereby inhibiting inflammation. Conclusion: The FGD5-AS1/miR-223-3p/COX11 axis plays a pivotal role in the pathogenesis of AR, suggesting that FGD5-AS1 could serve as a potential diagnostic biomarker and therapeutic target for AR.

Xiaoqinglong decoction improves allergic rhinitis by inhibiting NLRP3-mediated pyroptosis in BALB/C mice

Ethnopharmacological relevanceXiaoqinglong decoction (XQLD), first recorded in Shang Han Lun, is a traditional Chinese medicine prescribed for the treatment of allergic rhinitis (AR). XQLD alleviates the clinical symptoms of AR by inhibiting the occurrence of an inflammatory response, but the specific regulatory mechanism remains unclear. Aim of the studyNLRP3-mediated pyroptosis is closely related to AR pathogenesis. Hence, this study aimed to explore the potential role of NLRP3-mediated pyroptosis pathway in the AR-associated pharmacological mechanism of XQLD. Materials and methodsBALB/C mice models of AR was established by using ovalbumin (OVA) and aluminum hydroxide sensitization. After intragastric administration of different dosages of XQLD, nasal allergic symptoms were observed. The expression of OVA-sIgE and Th2 inflammatory factors (IL-4, IL-5, and IL-13) in serum was detected by ELISA. The histopathological morphology and expression of inflammatory factors in nasal mucosa along with pyroptosis were investigated. Molecular docking was performed to analyze the binding of representative compounds of XQLD with NLRP3. Activation of the NLRP3 inflammasome was detected by immunofluorescence and western blotting. ResultsXQLD significantly improved the nasal allergic symptoms of mice, reduced the degree of goblet cell proliferation, mast cell infiltration, and collagen fiber hyperplasia in nasal mucosa. Meanwhile, it could downregulate the expression of Th2 inflammatory factors (IL-4, IL-5, and IL-13) in serum and nasal mucosa. XQLD significantly reduced the number of GSDMD and TUNEL double-positive cells and IL-1β and IL-18 expression. Molecular docking confirmed that seven representative compounds of XQLD had good binding properties with NLRP3 and were able to inhibit the activation of the NLRP3 inflammasome. ConclusionsThe representative compounds of XQLD might inhibit pyroptosis in nasal mucosa mediated by the NLRP3 inflammasome to helping the recovery of AR, which provides a new modern pharmacological proof for XQLD to treat AR.

CircMIRLET7BHG, upregulated in an m6A-dependent manner, induces the nasal epithelial barrier dysfunction in allergic rhinitis pathogenesis

ObjectiveAllergic rhinitis (AR) remains a frequent aspiratory allergic inflammatory disorder with a high incidence. Circular RNAs (circRNAs) have been revealed to participate in the pathogenesis of AR. This study investigated the biological function of circMIRLET7BHG (hsa_circ_0008668) in AR progression. MethodsOvalbumin (OVA)-exposed human nasal epithelial cell line (HNEpC) and mice were adopted as the in vitro and in vivo models of AR. Immunofluorescence staining was used to determine epithelial tight junction protein expression. Target molecule levels were assessed by RT-qPCR and Western blotting. Localization of circMIRLET7BHG and IGF2BP1 was observed by RNA-FISH and immunofluorescence. Epithelial barrier damage was determined by transepithelial electrical resistance and fluorescein isothiocyanate-dextran (FD4) permeability. Serum concentrations of IgE, sIgE, IFN-γ, IL-4, and IL-5 were detected by ELISA. Apoptosis, pathological changes, and eosinophil infiltration in nasal mucosa tissues were evaluated by TUNEL, H&E, and Sirius red staining, respectively. Molecular mechanism was analyzed by RNA pull-down, RIP, and MeRIP assays. ResultsAn increased expression of circMIRLET7BHG was found in AR patients and experimental models. Down-regulation of circMIRLET7BHG attenuated OVA-induced allergic symptoms via relieving epithelial thicknesses, eosinophil infiltration, apoptosis, and inflammatory response in mice. Subsequently, circMIRLET7BHG deficiency prevented OVA-induced epithelial barrier dysfunction by reducing epithelial permeability, and inhibiting tight junction proteins. Mechanistically, methyltransferase-like 3 (METTL3) enhanced circMIRLET7BHG expression via m6A methylation, which enhanced ADAM10 mRNA stability via interaction with IGF2BP1. ConclusionMETTL3-mediated m6A modification increased circMIRLET7BHG expression that consequently raised ADAM10 mRNA stability via interplay with IGF2BP1, thereby promoting AR by inducing epithelial barrier dysfunction.

Role of LINC00240 on T-helper 9 differentiation in allergic rhinitis through influencing DNMT1-dependent methylation of PU.1.

Allergic rhinitis (AR) is a common allergic disease with increasing prevalence globally. However, the molecular mechanism underlying AR pathogenesis remains largely undefined. Peripheral blood and nasal mucosa samples obtained from patients with AR (n = 22), and ovalbumin-induced AR mouse model (n = 8 per group) were prepared for subsequent detection. qRT-PCR and western blot were used to detect the expression of LINC00240, miR-155-5p, PU.1 and other key molecules. ELISA assay and flow cytometry were employed to evaluate the secretion of IL-9 and T-helper 9 (Th9) cell ratio, respectively. Bioinformatics analysis, RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP) and luciferase reporter assays were employed to further elucidate the regulatory network of LINC00240/miR-155-5p/DNMT1. The methylation of PU.1 promoter was assessed by methylation-specific PCR (MSP). This signaling axis was further validated in the mouse model of AR. LINC00240 was downregulated, while miR-155-5p and PU.1 were upregulated in the peripheral blood and nasal mucosa of AR patients, as well as in AR mice. This was accompanied with the increased ratio of Th9 cells and elevated IL-9 secretion. Mechanistically, LINC00240 served as a miR-155-5p sponge, and DNMT1 was a target of miR-155-5p. In addition, DNMT1 mediated the methylation of PU.1 promoter. In vivo studies verified that LINC00240 mitigated AR progression, possibly via miR-155-5p/DNMT1/PU.1-dependent Th9 differentiation. The involvement of LINC00240 in AR pathogenesis is closely associated with Th9 differentiation through modulating DNMT1-dependent methylation of PU.1 by sponging miR-155-5p.

Shexiang Tongxin Dropping Pretreated Mesenchymal Stem Cells-derived Exosomes Attenuate Cardiac Ischemia/Reperfusion Injury by Modulating miR-182-5p and miR-199a-3p-mediated Inflammatory Responses

Background Previous research has highlighted the regulatory role of miR-182-5p in targeting TLR4 during the pathogenesis of allergic rhinitis. In a different context, TLR4 has been identified as a crucial factor in the development of lung ischemia-reperfusion injury, where its upregulation is believed to initiate the injury process. Additionally, miR-199a-3p has been shown to possess cardioprotective properties in simulated ischemia/reperfusion (I/R) injury models. Materials and Methods HE and TUNEL were performed to evaluate the cardiac injury and cellular apoptosis of I/R mice under distinct conditions. Real-time PCR was used to analyze the expression of microRNAs (miRNAs) and mRNAs under differential conditions. Results Pretreatment by Shexiang Tongxin Dropping (SXTXD) has been shown to significantly augment the therapeutic efficacy of MSC-derived exosomes (MSC-EXOs) in attenuating cardiac injury in I/R mice. MSC-EXOs effectively restored the repressed miR-182/miR-199a-3p expressions and activated TLR4/CD44 expressions in I/R mice, while SXTXD pretreatment remarkably strengthened the efficiency of MSC-EXOs. Moreover, SXTXD pretreatment notably reinforced the capability of MSC-EXOs to maintain cardiac parameters, including iNOS and interleukin-1β (IL-1β). Furthermore, the luciferase assay indicated that miR-182-5p and miR-199a-3p effectively suppressed the luciferase activities of TLR4 and CD44, respectively, through binding to the 3´ UTR. The overexpression of miR-182-5p and miR-199a-3p significantly suppressed the expression of TLR4 and CD44 in H2C6 and RAW264.7 cells. Conclusion In conclusion, our investigation indicates that MSC-derived exosomes, pretreated with SXTXD, hold promise in mitigating cardiac I/R injury by modulating inflammatory responses through the miR-182-5p/TLR4 axis and miR-199a-3p/CD44 axis. These findings suggest potential therapeutic strategies for addressing I/R-related cardiac complications.

Changes of immunological biomarkers in pediatric patients with seasonal allergic rhinitis

Background. Seasonal allergic rhinitis shows a constant upward trend not only among the adults but also in the children’s population. A significant percentage of patients have a moderate and severe course of the disease, which leads to a significant deterioration in their quality of life. Since the pathogenesis of allergic rhinitis is represented by a complex cascade of immunological reactions involving a number of cytokines that play a role in the development of allergic inflammation of the upper respiratory tract, the priority direction of our work was an in-depth study of the pathogenetic mechanisms of this disease. The purpose was to investigate the levels of interleukin-33 (IL-33) and its suppression of tumorigenicity 2 (ST2) receptor in the blood serum of children with hay fever, depending on the age and severity of the disease, followed by the determination of correlations of these indicators with various clinical and immunological parameters of seasonal allergic rhinitis. Materials and methods. Forty-two patients aged 6–17 years with seasonal allergic rhinitis and 26 healthy children (controls) took part in the study. Severity of nasal and extra-nasal symptoms of allergic rhinitis was determined using a visual analog scale. Skin prick testing was performed according to generally accepted standards during remission using a standard pollen panel. Quantitative measurement of serum indicators of interleukin-33 and ST2 was carried out by the method of solid-phase enzyme immunoassay. A mandatory condition for conducting the study was the presence of written informed consent from the parents. Results. The study of serum levels of IL-33 and ST2 showed statistically higher concentrations in the group of children with a severe course of seasonal allergic rhinitis, a direct correlation of medium strength between content of the above cytokines in children with a mild SAR (τ = 0.65; p < 0.05) and a strong dependence in patients with moderate (τ = 0.76; p < 0.01) and severe (τ = 0.80; p < 0.05) course. When comparing the mean values of IL-33 and ST2, no significant changes were found depending on age and the presence of mono- or polysensitisation among patients with allergic rhinitis. In children with seasonal allergic rhinitis and concomitant bronchial asthma, there was a statistically significant tendency towards a more severe course of the disease with correspondingly higher values of IL-33 and ST2 compared to patients with isolated seasonal allergic rhinitis. Conclusions. The obtained results of the immunological study made it possible to emphasize the diagnostic significance of IL-33 and its receptor ST2 as potential biomarkers in the development of allergic inflammation in pediatric patients with seasonal manifestations of rhinitis.

Clinical values of serum neuropeptide changes in patients with chronic urticaria complicated with allergic rhinitis.

Neurogenic inflammation has been recognized as an important contributing factor in the pathogenesis of allergic rhinitis. The aim of this study was to investigate the clinical values of substance P, vasoactive intestinal peptide (VIP), and neuropeptide Y as biomarkers of disease severity and treatment outcomes of chronic urticaria complicated with allergic rhinitis. Our prospective study included 150 patients with chronic urticaria complicated with allergic rhinitis and 80 healthy control patients. Before treatment, the serum samples of all study subjects were collected and analyzed using enzyme-linked immunosorbent analysis. The intervention group received imipramine of 10mg/day orally for 2weeks, and the Symptom Score Reduction Index (SSRI) was used to analyze clinical outcomes, which were categorized as effectual and ineffectual. Our data suggested that substance P, VIP, and neuropeptide Y were significantly correlated to each other. Lower levels of substance P, VIP, and neuropeptide Y were associated with better treatment outcomes. A good detection sensitivity (69.49%) and specificity (80.22%) could be achieved using a combination of these markers (area under curve = 0.85). Our data indicates that substance P, VIP, and neuropeptide Y levels before treatment correlate strongly with the treatment outcomes of the patients, which could potentially serve as a decision support tool in clinical management of chronic urticaria complicated with allergic rhinitis.

Association of LOX gene G473A polymorphism with the occurrence of allergic rhinitis and efficacy of montelukast sodium in children

ABSTRACT Allergic rhinitis (AR) is very common in adolescents, and current treatment options are complex and unsatisfactory. The objective of this study was to analyze the association of lysyl oxidase (LOX) gene G473A polymorphism with susceptibility to AR in children. In addition, we analyzed the therapeutic effect of montelukast sodium on AR. Forty-five children with AR (research group, 8.16±2.88 years old) and 51 healthy children (control group, 8.22±3.87 years old) during the same period were selected. The LOX gene G473A polymorphism was detected with polymerase chain reaction (PCR)-restriction fragment length polymorphism method. The effect of G473A polymorphism in the occurrence of AR was assessed by logistic regression analysis. In addition, the levels of C-reactive protein (CRP), Interleukin (IL-6), and IL-8 were measured to observe the relationship between G473A polymorphism and inflammatory factors. Finally, montelukast sodium was given to children with AR to investigate the effect of G473A polymorphism on clinical outcomes. The number of G473A polymorphisms in the research group was not significantly different from the control group for GA-type (P = 0.521). However, the number of GG-type polymorphisms was less while the number of type AA was more than the control group (P = 0.044 and 0.046). Children carrying the AA gene had an approximately 4-fold increased risk of AR, while those carrying the GG gene had a decreased risk (P < 0.001). Moreover, children carrying the GG gene had lower levels of CRP, IL-6, and IL-8 and better clinical outcomes, while those carrying the AA gene had higher levels of inflammatory factors and worse outcomes (P<0.05). LOX gene G473A polymorphism is closely associated with AR pathogenesis and may have an important research value in antagonizing the therapeutic effect of montelukast sodium.

Nasal and Serum Immunoglobulin E Levels in Symptomatic Allergic Rhinitis Patients: A Case-Control Study.

Allergic Rhinitis (AR) is an inflammatory condition of the nasal mucosa triggered by Immunoglobulin E (IgE) mediated response to exposure to allergens. The most common symptoms are nasal obstruction, sneezing, runny nose and these in addition to swollen, itchy, red and watery eyes. Recent studies have shown highly elevated immunoglobulin E levels in the airway mucosa independently of serum IgE levels and atopic status. Nasal mucosa has intrinsic capability to produce IgE in allergic rhinitis. The study was conducted to explore the levels of nasal total IgE and serum total IgE and their correlation in symptomatic AR patients. This was a case control-study and two groups participated in the study. The first group included 203 symptomatic patients who were diagnosed in the otorhinolaryngology clinic as cases of AR, known as AR group. The second group was control group and included 203 apparently healthy volunteers without any history suggestive of AR. The associated risk factors for severe allergic symptoms were assessed by logistic regression model. The mean differences between nasal total IgE and serum total IgE levels of both groups were compared by t-test. A correlation was investigated between nasal IgE and serum IgE in both the groups. The mean level of nasal total IgE and serum total IgE was found to be 103.9 and 291.4IU/ml in AR group, respectively, and 17.5 and 67.5IU/ml in the control group, respectively. Levels of nasal total IgE and serum total IgE were significantly higher in the nasal fluids and serum of symptomatic allergic rhinitis patients than in controls (p < 0.001 and < 0.001 respectively). A logistic regression model showed severity of allergic rhinitis was significantly associated with nasal total IgE levels. The correlation of nasal total IgE levels with serum total IgE levels in the control group was found to be statistically insignificant. However a statistically positive correlation was observed between nasal total IgE and serum total IgE levels in the AR group. It is possible that nasal IgE and serum IgE interact in the pathogenesis of AR and this is evident in the current study. Nasal IgE levels should be evaluated in severe symptomatic allergic rhinitis patients. The interaction between nasal IgE to serum IgE levels should be further investigated in AR patients for other possible prevalent endotypes of AR.

Research progress on active ingredients of animal-derived traditional Chinese medicine in treatment of allergic rhinitis

Allergic rhinitis(AR) is a common chronic inflammatory disease of the upper respiratory tract. Due to its high prevalence, high recurrence rate, and lack of a definitive cure, it is considered a global health issue by the World Health Organization. The pathogenesis of AR is complex and mainly involves B cells, helper T cells, eosinophils, basophils, macrophages, as well as the cytokines and inflammatory mediators they secrete. Clinical treatment primarily focuses on inhibiting inflammatory mediators such as histamine and leukotrienes. In recent years, active ingredients of animal-derived traditional Chinese medicine(TCM) have shown unique advantages and potential in AR treatment thanks to their high safety, specificity, selectivity, and biopotency. This study systematically reviewed the therapeutic effects and mechanisms of active ingredients and mixed extracts from animal-derived TCM, such as bovine spleen, honeycomb, bee venom, maggot, and human placenta, which have been shown by modern pharmacological research to regulate the immune function in AR, providing a reference for further exploration and clinical development of active ingredients from animal-derived TCM. Studies have found that the active ingredients from animal-derived TCM can produce definite therapeutic effects in AR by modulating multiple immune balances in the body, with great clinical prospects. However, their mechanisms of action still require further investigation, and the quality control techniques for effective ingredients need to be improved. Currently, the research on active ingredients from animal-derived TCM in China has adopted an interactive system consisting of &quot;traditional medical experience-based research, bioinformatics and artificial intelligence predictions, and validation and development through new experimental techniques&quot;. Based on this system, animal-derived TCM can combine modern scientific and technological means to maximize the therapeutic effects of active ingredients and serve the clinical application of AR in a more efficient and innovative manner.

Exploring the latest understanding on the role of immune mediators, genetic and environmental factors in pathogenesis of allergic rhinitis: a systematic review.

Despite well-defined clinical phenotypes of chronic rhinitis, the underlying in-depth pathophysiological mechanism, particularly with reference to the involvement of immune mediators, genetic, and environmental factors, are still not fully understood. Therefore, our aim was to give updated information on the pathogenesis of allergic rhinitis (AR), with an emphasis on the role of cytokines in adults aged 18 years and above. Additionally, we investigated the impact of genetic and environmental factors in the pathogenesis of AR. A search in various databases identified 1,178 records, and 18 studies were ultimately selected from January 2018 to April 2023. The total sample size in our studies was 4,317, with 2,186 in the experimental and 2,131 in control groups, respectively. The mean age was 33.4 years, with 43% were male, while 57% were female. According to the selected studies, various factors, including immune mediators, particularly cytokines, genetic, and environmental factors, were identified in the development of AR. The selected studies presented findings on different factors and sub-factors in the pathogenesis of AR, making it a challenge for us to compare their results. However, based on our findings, researchers can link our identified factors to potential therapies for AR.

Mahuang Fuzi Xixin decoction ameliorates allergic rhinitis and repairs the airway epithelial barrier by modulating the lung microbiota dysbiosis.

Allergic rhinitis (AR) is a common disorder, that burdens general well-being. Although the lung is connected to the upper respiratory tract, which is rich in microorganisms, no studies have reported the relationship between lung microbiota and AR. Mahuang Fuzi Xixin decoction (MFXD) is a traditional Chinese medicine (TCM) formula that is widely used to treat AR in the clinic but its underlying mechanism remains unclear. We hypothesized that lung microbiota is associated with the pathogenesis of AR, and MFXD can improve AR by regulating microbiota dysbiosis. The ovalbumin-induced mouse AR model was used to evaluate the therapeutic effect of MFXD on AR. Then 16S rDNA amplicon sequencing, untargeted metabolomics, and other molecular biology technology were used to clarify the effects of MFXD on lung microbes dysbiosis and AR progression. Further, the human nasal epithelial cell line (HNEpCs) was used to evaluate the protective effect of MFXD on epithelial barrier damage caused by specific pathogens. MFXD decreased plasma histamine and IgE levels, ameliorated pathological damage, and diminished the expression of tight junction proteins (ZO-1 and occludin) in lung and nasal tissues. MFXD altered AR-induced microbiota dysbiosis in the lungs and also plasma metabolites. Oral administration of MFXD altered microbiota dysbiosis in lung and AR-associated metabolic disorders. The dominant bacteria in the lungs of AR mice damaged the airway barrier, and MFXD reversed this change. This study revealed the correlation between the lung microbiota and AR in the mice model. We confirmed that lung microbiota plays a vital role in AR and that MFXD reduced damage to the epithelial barrier of the lungs and nasal mucosa by regulating lung microbiota and plasma metabolism imbalances. Our research provides a reference for the effect of lung microbiota on AR and provides a new idea for the treatment of AR.

Exosomal lncRNA GAS5 promotes M1 macrophage polarization in allergic rhinitis via restraining mTORC1/ULK1/ATG13-mediated autophagy and subsequently activating NF-кB signaling.

Macrophages are involved in the pathogenesis of allergic rhinitis (AR), but how these macrophages are polarized to M1 or M2 type is undetermined. Long non-coding RNA growth arrest specific transcript 5 (GAS5) is upregulated in exosomes isolated from nasal mucus of AR patients (AR-EXO) and aggravates nasal symptoms in AR mice. In the present study, we are aimed to elucidate the potential role of GAS5 in macrophage polarization during AR pathogenesis. An AR mice model was constructed. The potential function of GAS5 was evaluated by western blot, RNA immunoprecipitation (RIP), biotinylated RNA pull-down assay, co-immunoprecipitation (co-IP) assay, flow cytometry, enzyme-linked immunosorbent assay (ELISA) assay, and immunohistochemistry (IHC) staining. We found that GAS5 is upregulated in ovalbumin-treated human nasal epithelial cells RPMI 2650 (OVA-EXO) and nasal mucus of AR mice. OVA-EXO treatment or forced GAS5 expression promoted M1 macrophage polarization of peripheral blood monocytes (PB monocytes) and THP-1 macrophages in vitro. GAS5 overexpression aggravated the allergic nasal symptoms induced by OVA in AR mice and facilitated M1 macrophage polarization and allergic inflammation, while knockdown of GAS5 exhibited opposite effects in vivo. GAS5 activated NF-кB signaling via suppressing autophagy-dependent degradation of IKKα/β in macrophages. Furthermore, GAS5 acted as a scaffold to strengthen the interaction between mTORC1 and ULK1, thus impaired ULK1/ATG13-mediated autophagy via increasing mTORC1 activity. Finally, restored autophagy by ATG13 overexpression suppressed the effect of GAS5 on M1 macrophage polarization. In conclusion, these results suggested that exosomal transfer of GAS5 promoted M1 macrophage polarization via restraining mTORC1/ULK1/ATG13-mediated autophagy and subsequently activating NF-кB signaling in allergic rhinitis.