Changes In Nasal Mucosa Research Articles

Expression of prostacyclin receptor in chronic rhinosinusitis and its relationship with type 2 inflammation

Objective:The purpose of this study is to explore the expression of prostacyclin receptor（IP） in patients with chronic rhinosinusitis（CRS） and its possible association with type 2 inflammation. Methods:HE staining was used to observe the morphological changes of nasal mucosa, qRT-PCR was used to detect the expression of IP in polyps and nasal mucosa, and IHC was used to detect the expression of IP, IL-4, IL-5 and IL-13 in polyps and nasal mucosa. Results:Compared with the control group, the nasal mucosa of patients with various types of CRS was obviously thickened, accompanied by inflammatory cell infiltration and gland hyperplasia. The statistical results of IHC showed that the expression levels of IL-4, IL-5 and IL-13 in CRS group were significantly higher than those in control group（P<0.05）, and the IP expression in control group was significantly higher than that in ECRS group and non-ECRS group（P<0.05）. The IP expression in ECRS group was negatively correlated with IL-4, IL-5 and IL-13. The results of qRT-PCR showed that the expression of IP mRNA in control group was significantly higher than that in ECRS group and non-ECRS group（P<0.05）. Conclusion:IL-4, IL-5 and IL-13 are highly expressed in the nasal mucosa of CRS patients, while IP is poorly expressed in the nasal mucosa of CRS patients, and IP is negatively correlated with IL-4, IL-5 and IL-13, suggesting that IP is related to the occurrence and development of type 2 inflammation and may be a potential therapeutic target for CRS patients.

Acupuncture at "Die E acupoint" alleviates inflammatory reaction via inhibiting TLR4/MyD88/NF-κB signaling in rats with allergic rhinitis.

To observe effects of acupuncture at "Die E acupoint" on the protein expression levels of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear transcription factor κB (NF-κB), transcription factor T-bet (T-bet), and GATA-binding protein-3 (GATA-3) in the nasal mucosa and the serum contents of related inflammatory cytokines in rats with allergic rhinitis, so as to explore the mechanism of acupuncture in treating allergic rhinitis. Twenty-four healthy SD rats were randomly divided into blank, model, acupuncture, and sham acupuncture groups, with 6 rats in each group. The rat model of allergic rhinitis was established by using ovalbumin induction. The rats in the acupuncture group received bilateral acupuncture at the "Die E acupoint" with a depth of 15-20 mm, while the rats in the sham acupuncture group received only sham acupuncture (light and shallow acupunture of the skin at the "Die E acupoint" ). Both interventions were performed once daily for a total of 6 days. Behavioral scores of rats in each group were recorded. Pathological changes of nasal mucosa were observed by H.E. staining. Serum contents of IgE, ovalbumin-specific IgE (OVA-sIgE), interferon(IFN)-γ, interleukin(IL)-4, IL-10 and IL-17 were measured by ELISA and the protein expression levels of T-bet, GATA-3, TLR4, MyD88 and NF-κB p65 in the nasal mucosa were detected by Western blot. After modeling, compared with the blank group, rats in the model group showed increased behavioral scores, serum IgE, OVA-sIgE, IL-4, and IL-17 contents, and nasal mucosal GATA-3, TLR4, MyD88, and NF-κB p65 protein expression levels (P<0.05), whereas the contents of serum IFN-γ, IL-10 and the protein expression level of T-bet in the nasal mucosa were decreased (P<0.05). Comparison between the EA and model groups showed that acupuncture intervention can decrease the behavioral scores of rats with allergic rhinitis, the contents of serum IgE, OVA-sIgE, IL-4, IL-17, and the protein expression levels of GATA-3, TLR4, MyD88, and NF-κB p65 in the nasal mucosa (P<0.05), and up-regulate the contents of serum IFN-γ, IL-10, and the nasal mucosal T-bet protein expression level. Sham acupuncture did not have a significant modulating effect on the above indicators. Inflammatory infiltration of nasal mucosa was seen in the model group and sham acupuncture, and the inflammatory reaction was milder in the acupuncture group. Acupuncture at "Die E acupoint" can alleviate the symptoms of allergic rhinitis and suppress the inflammation of nasal mucosa in rats, which may be related to inhibiting the TLR4/MyD88/NF-κB signaling and balancing the levels of cytokines of Th1/Th2 and Treg/Th17, and T-bet/GATA-3.

A Supramolecular Assembly of EGCG for Long-Term Treatment of Allergic Rhinitis.

Allergic rhinitis (AR) is a type-I hypersensitivity disease mediated by immunoglobulin E (IgE). Although antihistamines, glucocorticoids, leukotriene receptor antagonists, and other drugs are widely used to treat AR, the various adverse side effects of long-term use of these drugs should not be ignored. Therefore, more effective and safe natural alternative strategies are urgently needed. To this end, this study designed a nanosupramolecular delivery system composed of β-cyclodextrin supramolecular polymer (PCD), thiolated chitosan (TCS), and natural polyphenol epigallocatechin gallate (EGCG) for intranasal topical continuous treatment of AR. The TCS/PCD@EGCG nanocarriers exhibited an excellent performance in terms of retention and permeability in the nasal mucosa and released the vast majority of EGCG responsively in the nasal microenvironment, thus resulting in the significantly high antibacterial and antioxidant capacities. According to the in vitro model, compared with free EGCG, TCS/PCD@EGCG inhibited mast cell activity and abnormal histamine secretion in a more long-term and sustained manner. According to the in vivo model, whether in the presence of continuous or intermittent administration, TCS/PCD@EGCG substantially inhibited the secretion of allergenic factors and inflammatory factors, mitigated the pathological changes of nasal mucosa, alleviated the symptoms of rhinitis in mice, and produced a satisfactory therapeutic effect on AR. In particular, the therapeutic effect of TCS/PCD@EGCG systems were even superior to that of budesonide during intermittent treatment. Therefore, the TCS/PCD@EGCG nanocarrier is a potential long-lasting antiallergic medicine for the treatment of AR.

MiR-223-3p regulates the eosinophil degranulation and enhances the inflammation in allergic rhinitis by targeting FBXW7.

MiR-223-3p is a multifunctional microRNA regulated by multiple transcription factors and plays a critical role in inflammation. This paper was designed to investigate the regulatory role and mechanism of miR-223-3p in eosinophils degranulation and allergic rhinitis (AR) inflammation. OVA sensitized AR mouse model and EOL-1 cells model were established. RT-qPCR and FISH were performed to detect the miR-223-3p expression. ELISA and WB were utilized to evaluate mRNA and protein expression. HE staining and transmission electron microscopy were applied to observe the morphological changes in nasal mucosa. Flow cytometry and immunofluorescence staining were performed to measure the proportion of eosinophils and eosinophilic major basic protein expression. The targeting relationship between miR-223-3p and FBXW7 was verified by bioinformatic analysis and dual-luciferase reporter gene assay. The expression of FBXW7 was detected by immunohistochemistry. The level of miR-223-3p in nasal mucosa was significantly up-regulated in AR group. The expression of miR-223-3p, ECP, MBP, and EPO were increased in EOL-1 cells, further increasing the miR-223-3p level could promote the ECP and EPO mRNA expression. Upregulation of miR-223-3p increased eosinophils granule protein expression, aggravated mucosal destruction and enhanced AR inflammation. Luciferase assay verified miR-223-3p directly target the 3'-UTR of FBXW7. In vitro, overexpression of FBXW7 could reverse the increase in MBP expression caused by the up-regulation of miR-223-3p. In vivo, knockdown of FBXW7 could reverse the down-regulation in granule protein level caused by the down-regulation of miR-223-3p, thereby aggravating AR inflammation. Collected evidence elucidated that miR-223-3p could regulate the eosinophil degranulation and enhances the inflammation in AR by targeting FBXW7. The miR-223-3p/FBXW7 axis may provide a novel approach for AR treatment.

Relationship Between the Expression of LC3 (Microtubule-Associated Protein 1A/1B-Light Chain 3) in Nasal Mucosa and Serum IL-5 and IL-4 Concentrations in Allergic Rhinitis Mice.

To investigate the expression and correlation of autophagy-related microtubule-associated protein 1 light chain 3 beta LC3 and interleukin-5 IL-5 in allergic rhinitis AR. Fifty-six 7-week-old BALC/C mice were randomly divided into experimental group (n = 56) and control group (n = 8). The experimental group used Dermatophagoides farinae (Der f) for AR modeling, and control group used PBS solution. As the experimental group sampled at 6 time points, and 8 mice were sacrificed each time, while the control group was sacrificed 24 hours after the last dose. The contents of serum IL-4, IL-5, and dust mite specific IgE HDM-sIgE in mice were detected by enzyme-linked immunosorbent assay ELISA, and the morphological changes of nasal mucosa were detected by a hematoxylin-eosin H&E staining. The expression of LC3 in mouse nasal mucosa was detected by immunohistochemical staining. Spearman correlation coefficient was used to assess the relationship between LC3 and IL-5 levels. In AR mice modelled with dust mites, the serum levels of IL-4 and HDM-sIgE increased gradually, and the serum IL-5 concentration had a peak at the early intraperitoneal administration stage similar to that at the end of modelling. The LC3 level in nasal mucosa of AR mice modelled with dust mites increased gradually in the early stages, but stabilized in the later stages. The expression of LC3 level in nasal mucosa was a positively correlated ration between serum IL-5 level in AR mice. In the early stage of AR mice, the level of nasal mucosal autophagy and serum IL-5 levels were significantly increased and correlated, suggesting that nasal mucosal autophagy played a promoting role in the early stage of AR.

Acupoint injection ameliorates Th1/Th2 imbalance through Toll-like receptor 4/activator protein-1 signal pathway and improves inflammatory response in rats with allergic rhinitis

To observe the effect of acupoint injection on serum T helper (Th)1/Th2 related cytokines, and the expression levels of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and activator protein-1 (AP-1) of nasal mucosa in allergic rhinitis (AR) rats, so as to explore its mechanism underlying improvement of AR. Thirty-two SD rats were randomly divided into normal, model, non-acupoint injection and acupoint injection groups (n=8 in each group). The AR model was established by ovalbumin sensitization. In the acupoint injection group, "Yintang" (GV24+) and bilateral "Yingxiang" (LI20) were selected for injection of mixture solution of dexamethasone and lidocaine (0.05 mL/acupoint), once every 4 days for a total of 4 times. The non-acupoints, located at the midpoint between the "Houhai" and "Huantiao" (GB30) on the bilateral hips and the sites 5 cm inferior to the axillary were injected with the same dose of mixture solution as that in the acupoint injection group. The AR severity was assessed by cumulative quantification scoring methods (including the numbers of nose-catching and sneezes, and the amount of nasal secretions in 30 min). The pathological changes of nasal mucosa were observed by HE staining. The contents of immunoglobulin E (IgE), interleukin (IL)-4 and interferon (IFN)-γ in serum were detected by ELISA. The expressions of TLR4 and MyD88 in nasal mucosa was detected by immunofluorescence. The expression of AP-1 in nasal mucosa was detected by Western blot. Following modeling, the AR symptom score, serum IgE and IL-4 contents and expression of TLR4, MyD88 and AP-1 of nasal mucosa were significantly increased in the model group than those in the normal group (P<0.01), while the serum IFN-γ content was significantly decreased (P<0.01). Compared with the model group and non-acupoint injection group, the AR symptom score, the serum contents of IgE and IL-4 and the expressions of TLR4, MyD88 and AP-1 in nasal mucosa were significantly decreased in the acupoint injection group (P<0.01, P<0.05), while the serum IFN-γ content was significantly increased (P<0.01). H.E. staining of the nasal mucosa showed that most of the epithelium fell off, the lamina propria vessels expanded, the glands proliferated, and eosinophils and lymphocytes infiltrated in the model and non-acupoint injection groups, and those were significantly improved in the acupoint injection group. Acupoint injection can effectively improve allergic inflammation of the nose in AR rats, which may be related with its function in inhibiting the abnormal activation of TLR4/AP-1 signaling pathway and regulating the imbalance of Th1/Th2.

Konjac-mulberry leaf compound powder alleviates OVA-induced allergic rhinitis in BALB/c mice

According to the proportion of 1:1, konjac flour and mulberry leaf powder are compounded into a kind of dietary fiber source (KMCP). It is found to be good for anti-inflammation. However, its precise anti-allergic rhinitis effect and mechanism remain unknown. In our work, the effect of KMCP on allergic rhinitis (AR) induced by ovalbumin (OVA) was investigated. We found that the number of nasal rubbing and sneezing, the eosinophil (EOS) count in the nasal mucosa, and the serum levels of histamine (HIS), OVA-specific immunoglobulin E (OVA-sIgE) and interleukin-4 (IL-4) were decreased, and the histopathological changes of nasal mucosa were inhibited. Additionally, the experiments further proved that the KMCP treatment could exert substantial effects on short-chain fatty acids (SCFAs) metabolism in the cecum as well. Overall findings suggest that KMCP could suppress the inflammatory response in AR mice, and serve as a novel curative therapeutic for AR without side effects.

Human placental extract regulates polarization of macrophages via IRGM/NLRP3 in allergic rhinitis

Allergic rhinitis (AR) is globally prevalent and its pathogenesis remains unclear. Alternative activation of macrophages is suggested in AR and thought to be involved in natural immunoregulatory processes in AR. Aberrant activation of Nod-like receptor protein 3 (NLRP3) inflammasome is linked with AR. Human placenta extract (HPE) is widely used in clinics due to its multiple therapeutic potential carried by diverse bioactive molecules in it. We aim to investigate the effect of HPE on AR and the possible underlying mechanism. Ovalbumin (OVA)-induced AR rat model was set up and treated by HPE or cetirizine. General manifestation of AR was evaluated along with the histological and biochemical analysis performed on rat nasal mucosa. A proteomic analysis was performed on AR rat mucosa. Mouse alveolar macrophages (MH-S cells) were cultured under OVA stimulation to investigate the regulation of macrophages polarization. The morphological changes and the expression of NLRP3 inflammasome and immunity-related GTPase M (IRGM) in nasal mucosa as well as in MH-S cells were evaluated respectively. The results of our study showed the general manifestation of AR along with the histological changes in nasal mucosa of AR rats were improved by HPE. HPE suppresses NLRP3 inflammasome and the decline of IRGM in AR rats and MH-S cells. HPE regulates macrophage polarization through IRGM/NLRP3. We demonstrated that HPE had protection for AR and the protection is achieved partly through suppressing M1 while promoting M2, the process which is mediated by IRGM via inhibiting NLRP3 inflammasome in AR.

Chronic clinical signs of upper respiratory tract disease associate with gut and respiratory microbiomes in a cohort of domestic felines.

Feline upper respiratory tract disease (FURTD), often caused by infections etiologies, is a multifactorial syndrome affecting feline populations worldwide. Because of its highly transmissible nature, infectious FURTD is most prevalent anywhere cats are housed in groups such as animal shelters, and is associated with negative consequences such as decreasing adoption rates, intensifying care costs, and increasing euthanasia rates. Understanding the etiology and pathophysiology of FURTD is thus essential to best mitigate the negative consequences of this disease. Clinical signs of FURTD include acute respiratory disease, with a small fraction of cats developing chronic sequelae. It is thought that nasal mucosal microbiome changes play an active role in the development of acute clinical signs, but it remains unknown if the microbiome may play a role in the development and progression of chronic clinical disease. To address the knowledge gap surrounding how microbiomes link to chronic FURTD, we asked if microbial community structure of upper respiratory and gut microbiomes differed between cats with chronic FURTD signs and clinically normal cats. We selected 8 households with at least one cat exhibiting chronic clinical FURTD, and simultaneously collected samples from cohabitating clinically normal cats. Microbial community structure was assessed via 16S rDNA sequencing of both gut and nasal microbiome communities. Using a previously described ecophylogenetic method, we identified 136 and 89 microbial features within gut and nasal microbiomes respectively that significantly associated with presence of active FURTD clinical signs in cats with a history of chronic signs. Overall, we find that nasal and gut microbial community members associate with the presence of chronic clinical course, but more research is needed to confirm our observations.

Knockdown of Cadherin 26 Prevents the Inflammatory Responses of Allergic Rhinitis.

Allergic rhinitis (AR) is an inflammatory autoimmune disease with disorder of the nasal mucosa. Cadherin 26 (CDH26), an alpha integrin-binding epithelial receptor, is regulated during allergic inflammation. This study aimed to investigate whether CDH26 contributes to the severity of AR. In vivo and in vitro. We investigated the effects of CDH26 knockdown by lentivirus (LV)-mediated shRNA on ovalbumin (OVA)-induced AR mice and IL-13-stimulated human nasal epithelial cells (NECs). CDH26 mRNA and protein expression was significantly increased in the nasal mucosa of AR patients and mice. Intranasal instillation of LV-shCDH26 alleviated allergic symptoms and decreased the histological changes of nasal mucosa in AR mice. Furthermore, the serum levels of OVA-specific IgE, IgG, pro-inflammatory factors IL-25, IL-33, and TSLP were decreased in AR mice with CDH26 knockdown. With regard to AR-induced Th2 inflammation, LV-shCDH26 intervention effectively decreased the distribution of CD4+ /GATA3+ Th2 cells, and the mRNA expression of IL-4, IL-5, and IL-13 in the nasal mucosa. CDH26 knockdown down-regulated the expression of β-catenin but not for E-cadherin and ZO-1 in nasal mucosa induced by AR. In vitro, CDH26 knockdown inhibited the protein expression of TSLP, GM-CSF and eotaxin in NECs, and CDH26 overexpression remarkably promoted the production of these inflammatory factors in IL-13-induced NECs. CDH26 knockdown attenuates the AR-induced inflammatory response both in vivo and in vitro. NA Laryngoscope, 133:1558-1567, 2023.

Distinct indexes of immunological reactivity in surgical alteration of ORL organs

The data are provided on applications of optical radiation at various spectral ranges in the treatment of disorders of ORL organs. Some issues of pathophysiological and immune changes of nasal mucosa in response to surgical alteration are considered for the early postoperative period. In order to increase efficiency of postoperative rehabilitation in the patients subjected to rhinosurgical interventions, we have used low-frequency ultrasonic cavitation in combination with photochromotherapy in complex treatment schedules. Assessment of clinical and immunological effects of this treatment was performed as based on the study of clinical and functional pattern at the early stages of postoperative period and stabilization of the cytokine profile. In general, an opportunity of using optical radiation at different wavelength was confirmed, as shown by studies of physical characteristics of light irradiation, explaining the mechanisms of action on the damaged mucous membrane, to apply inflammatory response to surgical trauma and restore immunological abnormalities. The work was carried out in order to draw attention to the non-drug methods of early rehabilitation of persons subjected to rhinosurgical interventions.

A Novel Strategy for the Treatment of Allergic Rhinitis: Regulating Treg/Th17 and Th1/Th2 Balance In Vivo by Vitamin D.

Objective This prospective study is aimed at observing the number of nasal itching and sneezing in rats from the macroscopic level and examine the pathological changes of nasal mucosa, Th1 and Th2-related cytokines, and Treg/Th17 by vitamin D3 administration from the microscopic level, in order to explore the role of vitamin D in allergic rhinitis and to provide theoretical guidance for prevention and treatment. Results There were significant differences in nasal itching and sneezing between the administration groups and the positive groups. Meanwhile, the level of Th1 and Treg in the administration groups increased, while the level of Th2 and Th17 decreased, indicating that the balance of Th1/Th2 was corrected. Our study revealed that vitamin D3 has preventive and therapeutic effects on allergic rhinitis, which provides theoretical guidance for practical application.

Effects of ursolic acid on oxidative stress and inflammatory factors in a rat model of AR after PM2.5 exposure

Objective: To investigate the effects of ursolic acid (UA) on oxidative stress and inflammatory factors in a rat model of AR after PM2.5 exposure. Methods: Sixty healthy female SD rats were randomly divided into five groups: normal control group (NC group), PM2.5 unexposed AR group (AR group), PM2.5 exposed AR group (ARE group), UA intervention AR group (AR+UA group), and UA intervention PM2.5 exposed AR group (ARE+UA group), with 12 rats in each group. AR model was performed by a basal sensitization with intraperitoneal injection of ovalbumin (OVA) and followed by nasal instillation. PM2.5 exposure was carried out by inhalation exposure system at a concentration of 200 μg/m3 for 3 h/d for 30 days. UA intervention group was given UA intragastric administration at 20 mg/(kg·d). AR symptoms including sneezing, nasal scratching and nasal secretion of rats in each group were observed. The activities of superoxide dismutase (SOD) and the level of malondialdehyde (MDA) in nasal mucosa were tested. The pathological changes of nasal mucosa were observed by HE staining. The levels of OVA-sIgE, IL-6 and IL-17 in serum were measured by enzyme-linked immunosorbent assay (ELISA). Protein microarray was used to measure the expression of multiple inflammation cell factors in nasal mucosa. Statistical analysis was performed with SPSS 20.0. Results: After UA intervention, the frequency of nasal sneezing, scratching and nasal secretion in ARE+UA group were lower than those of ARE group (P<0.05). Pathological examination of nasal mucosa showed that ARE+UA group had less inflammatory granulocyte infiltration and less pathological damage to the epithelial layer than ARE group. The activities of SOD in nasal mucosa of ARE+UA group were higher than those of ARE group ((50.10±3.09) U/mg vs (20.13±1.30) U/mg, F value was 597.54, P<0.01). The contents of MDA in nasal mucosa of ARE+UA group were lower than those of ARE group ((57.78±12.36) nmol/g vs (124.12±9.40) nmol/g, F value was 115.51, P<0.01). The expression levels of OVA-sIgE, IL-6 and IL-17 proteins were lower in the ARE+UA group than those in ARE group ((11.61±0.27) ng/ml vs (20.30±0.67) ng/ml, (47.59±15.49) pg/ml vs (98.83±10.98) pg/ml, (623.30±8.75) pg/ml vs (913.32±9.06) pg/ml, F value was 283.42, 80.45, 683.73, respectively, all P<0.01). After UA intervention, protein microarray analysis showed that the expression of IL-4, IL-6, IL-13, chemokine CXCL7, IL-1α, IL-1β, MMP-8 and MCP-1 in ARE+UA group was decreased compared with ARE group while IFN-γ and IL-10 increased (all P<0.01). Conclusion: UA can reduce the aggravated AR symptoms and pathological damage of nasal mucosa, inhibit oxidative stress and release of inflammatory factors after PM2.5 exposure, and thus plays a protective role in the pathological damage of AR induced by PM2.5 exposure.

Synergistic effect of acupoint injection and moxibustion or catgut embedding or acupuncture on symptoms and expression of Th1/Th2 related cytokines in nasal mucosa of rats with allergic rhinitis

To observe the effect of moxibustion, catgut embedding and acupuncture on allergic symptoms and expression of interferon-γ (IFN-γ) and interleukin-4 (IL-4) of nasal mucosa in rats with allergic rhinitis (AR) based on acupoint injection, so as to explore their synergistic effect and related mechanism in relieving AR. SD rats (half male half female) were randomly divided into normal control, model, acupoint injection (AI), AI+moxibustion, AI+catgut embedding and AI+acupuncture groups, with 8 rats in each group. The AR model was established by intraperitoneal injection of ovalbumin suspension (once every other day for 7 times), and intranasal drop of 0.5% ovalbumin solution (once daily for 7 days). After successful modeling, rats of the AI group received injection of a mixture solution of equal proportion of 1% lidocaine, dexamethasone and transfer factor into "Yingxiang" (LI20) and "Yintang" (EX-HN3) once every 4 days, 4 times altogether. Mild moxibustion or catgut embedment or manual acupuncture was applied to bilateral "Feishu" (BL13) and "Zusanli" (ST36). Both moxibustion (20 min every time) and acupuncture (with the needles retained for 30 min every time) were conducted once daily for 14 times, and catgut embedding was conducted once a week, twice altogether based on acupoint injection. The rats' nasal allergic reaction score (symptom score, 1-3 points) was given according to the times of nose scratching and sneezing, and the running nose state in 30 min, and histopathological changes of nasal mucosa were observed by H.E. staining. The expression levels of IFN-γ and IL-4 in the nasal mucosa were detected by immunohistochemistry and Western blot, separately. Compared with the normal group, the symptom score and the expression of IL-4 positive cells and protein in nasal mucosa were significantly increased (P<0.05), while the expression of IFN-γ positive cells and protein were considerably decreased in the model group (P<0.05). In comparison with the model group, the symptom score and the expression of IL-4 positive cells and protein were obviously decreased (P<0.05), while the expression of IFN-γ positive cells and protein were remarkably increased in the 4 treatment groups (P<0.05). The effects of AI+moxibustion, AI+catgut embedment, AI+acupuncture were signi-ficantly superior to those of simple AI in up-regulating the expression of IFN-γ positive cells and protein and in down-regulating the expression of IL-4 positive cells and protein (P<0.05). Both the symptom score and the expression of IL-4 were notably lower in the AI+moxibustion group than in the AI+catgut embedment and AI+acupuncture groups (P<0.05), whereas the expression of IFN-γ was apparently higher in the AI+moxibustion group than in the other 3 treatment groups (P<0.05). No significant differences were found between the AI+catgut embedment and AI+acupuncture groups in the levels of symptom score, IFN-γ and IL-4 expressions (P>0.05). Moxibustion or catgut embedment or acupuncture and AI have a synergistic effect in relieving symptoms of AR rats, which may be related to their function in regulating the expression levels of nasal IFN-γ and IL-4 proteins. The therapeutic effect of moxibustion is obviously superior to those of both acupuncture and catgut embedment.

Effects of rosmarinic acid on the inflammatory response in allergic rhinitis rat models after PM2.5 exposure.

BackgroundStudies have shown the promising prospects of rosmarinic acid (RosA) for the prevention and treatment of allergic diseases.ObjectiveThe aim of this study was to investigate the effects of RosA on inflammatory reaction in rat models of allergic rhinitis (AR) after PM2.5 exposure.MethodsAllergic rhinitis rat models were established by ovalbumin sensitization, and PM2.5 was applied at a concentration of 1000 μg/m3, 3 h a day for 30 consecutive days. RosA was administered via intraperitoneal injection (20 mg/kg/d) for seven consecutive days. Allergic nasal symptoms were recorded. The expressions of interleukin (IL)‐4, IL‐13, interferon (INF)‐γ, and OVA‐sIgE were determined by ELISA. Histopathological changes in nasal mucosa were observed by HE staining. mRNA expressions of T‐bet and GATA‐3 in nasal mucosa were detected by RT‐PCR. NF‐κBp65 in cell nuclei and IκBα in cytoplasm were analyzed by Western blot.ResultsPM2.5 exposure worsened allergic nasal symptoms in AR rats, while RosA ameliorated these symptoms. Histopathologically, AR rats exhibited disorganized nasal mucosal epithelium, cell exfoliation, eosinophilic infiltration of lamina propria, gland swelling, and submucosal vascular congestion, which were aggravated by PM2.5 exposure and alleviated by RosA. RosA decreased the expressions of IL‐4, IL‐13, and increased the level of IFN‐γ in PM2.5‐exposed AR rats. After RosA intervention, the expressions of GATA‐3 mRNA and NF‐κBp65 in PM2.5‐exposed AR rats were significantly reduced, while those of T‐bet mRNA and IκBα were markedly increased.ConclusionRosmarinic acid may alleviate symptoms of AR rat models exposed to PM2.5 through the modulation of the NF‐κB pathway and Th1/Th2 balance.

Effect of Echinococcus granulosus hydatid cyst fluid protein on allergic rhinitis induced by ovalbumin in mice

To investigate the protective effect of Echinococcus granulosus hydatid cyst fluid protein (HCFP) on ovalbumin (OVA)-induced allergic rhinitis (AR) in mice. Twenty-four BALB/c mice at ages of 8 to 10 weeks, each weighing approximately 20 g, were randomly divided into four groups, including groups A (blank control group), B (blank intervention group), C (AR model group) and D (AR+HCFP intervention group), with 6 mice in each group. On days 0, 2, 4, 6, 8, 10 and 12, mice in groups A, B, C and D were injected with 200 μL sterile phosphate buffered saline (PBS), 200 μL sterile PBS containing 20 μg HCFP, 200 μL sterile PBS containing 50 μg OVA and 5 mg Al(OH)3 gel, and 200 μL sterile PBS containing 50 μg OVA, 5 mg Al(OH)3 gel and 20 μg HCFP, respectively. On days 14 to 20, mice in groups A, B, C and D were administered with 40 μL sterile PBS, 40 μL sterile PBS containing 20 μg HCFP, 40 μL sterile PBS containing 2 mg OVA and 40 μL sterile PBS containing 2 mg OVA and 20 μL HCFP by nasal drop, respectively. Mouse behavioral changes were observed and behavioral scores were estimated. The serum levels of interferon-γ (IFN-γ), interleukin-4 (IL-4), IL-5, IL-10, transforming growth factor-β (TGF-β) and OVA-specific IgE antibody (OVA-sIgE) were measured using enzyme-linked immunosorbent assay (ELISA), and the pathological changes of mouse nasal mucosa were observed by hematoxylin and eosin (HE) staining. The mean behavioral score was significantly greater in Group C (6.83 ± 0.50) than in groups A (1.17 ± 0.52) and B (1.33 ± 0.52) (P < 0.05), while a lower mean behavioral score was estimated in Group D (3.50 ± 0.50) than in Group C (P < 0.05). There were significant differences among the groups in terms of serum IFN-γ (F = 4.08, P < 0.05), IL-4 (F = 275.90, P < 0.05), IL-5 (F = 96.82, P < 0.05), IL-10 (F = 77.67, P < 0.05), TGF-β (F = 9.98, P < 0.05) and OVA-sIgE levels (F = 44.69, P < 0.05). The serum IFN-γ level was significantly lower in Group C than in groups A, B and C (P < 0.05), and the serum levels of IL-4, IL-5 and OVA-sIgE were significantly higher in Group C than in groups A, B and C (P < 0.05), while the serum IL-10 and TGF-β levels were significantly greater in Group D than in Group C (P < 0.05). Microscopy showed apparent loss of nasal mucosa cilia, increased number and enlargement of goblet cells, interstitial edema and submucous vascular dilation in Group C, while the pathological changes of nasal mucosa were alleviated in Group D relative to Group C. E. granulosus HCFP has a protective activity against OVA-induced allergic rhinitis in mice.

Histopathological changes of nasal mucosa after nasal packing with Merocel.

To determine histopathological changes in nasal mucosa associated with duration of nasal packing with Merocel tampons. This study included 24 healthy rabbits, 6 rabbits per group. In group A, no tampon was applied. In group B, Merocel nasal tampons were applied and removed after 24 hours. In group C, the tampons were removed after 48 hours. In group D, the tampons were removed after 5 days. Specimens were obtained from the septum of each rabbit, including cartilage. Histopathological examination was performed. Significant differences were observed in terms of inflammatory infiltration and loss of cilia between groups A and B. Significant differences were also observed in terms of inflammatory infiltration, haematoma, cilia loss, epithelium dysplasia and cartilage degeneration between groups B and C. There were significant differences in terms of cilia loss, epithelium dysplasia and subepithelial fibrosis between groups C and D. Cartilage degeneration was mild in one animal in group B and in two animals in group C, and was moderate in four animals in group C. It is recommended that Merocel nasal tampons are removed within 48 hours to preserve nasal mucosal function. Keeping the pack longer may cause cartilage degeneration and other complications.

Morphological changes in nasal mucosa in patients with sarcoidosis.

•Changes in the microvascular network of the nasal mucosa may be accompanied by changes in olfaction. •Contact endoscopic changes in the microvascular network of the nasal mucosa may be used as a marker of sinonasal sarcoidosis. •A modified version of the Negoro's classification, in use for the tongue mucosa, may be used for the classification of contact endoscopic microvascular patterns of the nasal mucosa in patients with sarcoidosis •The validation of the use of the vascular patterns of nasal mucosa on contact endoscopy as a marker of nasal disease activity is a major future research challenge •Contact endoscopy emerges as a promising technique for on-site diagnosis of early, advanced or late inflammatory mucosal spots or generalized mucosal affection in sarcoidosis.

Roles of Clara cell 10-kD protein and type 2 innate lymphoid cells in allergic rhinitis

ABSTRACT This study examined the potential roles of CC10 (Clara cell 10-kD protein) and ILC2s (type 2 innate lymphoid cells) in allergic rhinitis (AR). After ovalbumin was used to construct the AR model, microarray analysis was performed to reveal the key differentially expressed genes. The phenotypic changes of nasal mucosa were examined by H&E staining. Western blot analysis, qRT-PCR, ELISA and immunohistochemistry were performed to identify the levels of cytokines. The lineage markers (CD127 and CD117) of ILC2s were detected using immunofluorescence. The microarray analysis and qRT-PCR results showed that CC10 overexpression inhibited the expression of A20, BAFF, and IL-4 R in vivo. Also, CC10 overexpression was found to ameliorate the damage of nasal mucosa in AR mice. Investigations revealed that the ILC2s were activated in AR mice and AR patients with high levels of IgE, IgG1, IL-4, IL-5, IL-13, IL-25, and IL-33. Moreover, CD127+ was found to activate ILC2s. However, CC10 overexpression suppressed the activation of ILC2s. In conclusion, this research suggested that CC10 could suppress the activation of ILC2s to attenuate the damage of nasal mucosa and that CD127+ may be a biomarker of the activation of ILC2s in AR mice and AR patients.

Intranasal Ketorolac for Acute Pain in Adult Emergency Department Patients.

Pain is a common complaint in the emergency department. An alternative to opioids is desirable. Oral medications are not feasible with gastrointestinal disorders or NPO. Intravenous medications require skill and time. Intravenous/intramuscular medications are painful with potential needlestick injury. Intranasal medications have rapid onset, easy administration, do not need skilled providers, and no risk of needlestick injury. A total of 28 adults with acute pain (numeric rating scale ≥ 4) received intranasal ketorolac. Numeric rating scale decreased in all: 32% complete pain relief, median (interquartile range) decrease -5 (-6.8 to -4) (p < .001). Pain relief onset was median [interquartile range] 5 (2.3, 15.0) min. Vital signs remained normal. There were no nasal mucosal changes, no complications. Minor side effects, mostly nasal burning, in 43%, resolved within 5 min. Patients and nurses were satisfied with intranasal ketorolac, and would use it again. Intranasal ketorolac had a rapid onset, was effective, safe, well tolerated with minor side effects that resolved quickly.