Intranasally Administered Extracellular Vesicles from Adipose Stem Cells Have Immunomodulatory Effects in a Mouse Model of Asthma.

Asthma is a chronic eosinophilic airway disease characterized by type 2 helper T cell-driven inflammation. Adipose stem cells (ASCs) and the ASC culture supernatant are known to improve allergic airway inflammation; however, the immunomodulatory effects of ASC-derived extracellular vesicles (EVs) on allergic airway diseases remain unclear. Thus, we assessed the effects of ASC-derived EVs on allergic airway inflammation in a mouse model of asthma. EVs were isolated from the culture supernatant of murine ASCs and characterized. Six-week-old female C57BL/6 mice were sensitized to ovalbumin (OVA) by intraperitoneal injection and challenged intranasally with OVA. Before the OVA challenge, 10 µg/50 µl of ASC-derived EVs was administered intranasally to the experimental group. ASC-derived EVs significantly attenuated airway hyperresponsiveness (AHR) in asthmatic mice (p = 0.023). ASC-derived EVs resulted in a remarkable reduction of the total number of inflammatory cells (p = 0.005) and eosinophils (p = 0.023) in the bronchoalveolar lavage fluid (BALF), the degree of eosinophilic lung inflammation (p < 0.001), and the serum total and OVA-specific immunoglobulin (Ig)E (p = 0.048 and p = 0.001) and total IgG1 (p < 0.001). Interleukin- (IL-) 4 was significantly inhibited with ASC-derived EV pretreatment in the BALF and lung draining lymph nodes (LLNs) (p = 0.040 and p = 0.011). Furthermore, ASC-derived EV administration resulted in a significant increase of the regulatory T cell (Treg) populations in LLNs. ASC-derived EVs alleviated AHR and allergic airway inflammation caused by the induction of Treg expansion in a mouse model of asthma. There seems to be a role for ASC-derived EVs as a modifier in allergic airway disease.

Screening and Functional Pathway Analysis of Pulmonary Genes Associated with Suppression of Allergic Airway Inflammation by Adipose Stem Cell-Derived Extracellular Vesicles.

BACKGROUND: Although mesenchymal stem cell- (MSC-) derived extracellular vesicles (EVs) are as effective as MSCs in the suppression of allergic airway inflammation, few studies have explored the molecular mechanisms of MSC-derived EVs in allergic airway diseases. The objective of this study was to evaluate differentially expressed genes (DEGs) in the lung associated with the suppression of allergic airway inflammation using adipose stem cell- (ASC-) derived EVs. METHODS: C57BL/6 mice were sensitized to ovalbumin (OVA) by intraperitoneal injection and challenged intranasally with OVA. To evaluate the effect of ASC-derived EVs on allergic airway inflammation, 10 µg/50 µL of EVs were administered intranasally prior to OVA challenge. Lung tissues were removed and DEGs were compared pairwise among the three groups. DEG profiles and hierarchical clustering of the identified genes were analyzed to evaluate changes in gene expression. Real-time PCR was performed to determine the expression levels of genes upregulated after treatment with ASC-derived EVs. Enrichment analysis based on the Gene Ontology (GO) database and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were also performed to further identify the function of DEGs. RESULTS: Expression of paraoxonase 1 (PON1), brain-expressed X-linked 2 (Bex2), insulin-like growth factor binding protein 6 (Igfbp6), formyl peptide receptor 1 (Fpr1), and secretoglobin family 1C member 1 (Scgb1c1) was significantly increased in asthmatic mice following treatment with ASC-derived EVs. GO enrichment and KEGG pathway analysis showed that these genes were strongly associated with immune system processes and their regulation, cellular processes, single-organism processes, and biological regulation. CONCLUSION: These results suggest that the DEGs identified in this study (PON1, Bex2, Igfbp6, Fpr1, and Scgb1c1) may be involved in the amelioration of allergic airway inflammation by ASC-derived EVs.

Dendritic cells and M2 macrophage play an important role in suppression of Th2-mediated inflammation by adipose stem cells-derived extracellular vesicles.

Although stem cell-derived extracellular vesicles (EVs) have been shown to facilitate regeneration of injured tissue, there is no report that evaluates the immune-modulating effect of stem cell-derived EVs on Th2-mediated inflammation. In this study, we evaluated the immunomodulatory effects of adipose stem cells (ASCs)-derived EVs on Th2-mediated inflammation induced by Aspergillus protease antigen in lung epithelial cells. The EVs were isolated from supernatant of ASCs and the diameters of EVs were measured by using dynamic light scattering. The mice primary lung epithelial cells and mouse lung epithelial cell line (MLE12) were pre-treated with 200 ng/ml of Aspergillus protease and then treated with 1 µg/ml of ASC-derived EVs. Real time PCR was performed to determine the expression levels of eotaxin, IL-25, TGF-ß, and IL-10 mRNAs after EV treatment. To evaluate the role of EVs in macrophage polarization and dendritic cells (DCs) differentiation, in vitro bone marrow-derived macrophage and DCs stimulation assay was performed. EV treatment significantly decreased the expression of eotaxin and IL-25 and increased TGF-ß and IL-10 in both lung epithelial cells. EV treatment significantly increased the expression of co-stimulatory molecules such as CD40, CD80, and CD 86 in immature DCs. Furthermore, EV treatment significantly enhanced the gene expression of M2 macrophage marker such as Arg1, CCL22, IL-10, and TGF-ß. In conclusion, EVs of ASCs ameliorated Th2-mediated inflammation induced by Aspergillus protease antigen through the activation of dendritic cells and M2 macrophage, accompanied by down-regulation of eotaxin and IL-25, and up-regulation of TGF-ß and IL-10 in mouse lung epithelial cells.

Long-term Breastfeeding in the Prevention of Allergic Rhinitis: Allergic Rhinitis Cohort Study for Kids (ARCO-Kids Study).

OBJECTIVES: There is a great deal of interest in the possibility that environmental factors may influence the risk of developing allergic rhinitis (AR) in early life. We investigated the simultaneous effects of mode of delivery and duration of breastfeeding on the development of AR in children. METHODS: Data from 1,374 children participating in the Allergic Rhinitis Cohort Study for kids (ARCO-kids study) was analyzed. All subjects were divided into AR or non-allergic rhinitis (NAR) groups. Data on environmental factors, mode of delivery and duration of breastfeeding were collected using a questionnaire. RESULTS: Compared with short-term breastfeeding (<6 months), long-term breastfeeding (≥12 months) was significantly associated with a lower prevalence of AR (adjusted odds ratio [aOR], 0.54; 95% confidence interval [CI], 0.34 to 0.88). Children in the AR group also had a higher cesarean delivery rate than those in the NAR group (39.1% vs. 32.8%, P=0.05). Regarding the combined effects of mode of delivery and duration of breastfeeding, long-term breastfeeding with a vaginal delivery strongly suppressed the development of AR, compared to short-term breastfeeding with a cesarean delivery (aOR, 0.47; 95% CI, 0.30 to 0.73). CONCLUSION: Long-term breastfeeding (≥12 months) and a vaginal delivery are associated with a lower risk of developing childhood AR.

Therapeutic efficacy of regional and systemic chemotherapy in advanced maxillary sinus cancer.

BACKGROUND: To compare the efficacy of regional chemotherapy through the superficial temporal artery and systemic chemotherapy in patients with advanced maxillary sinus cancer. METHODS: Nine of 22 patients with over TNM stage III maxillary sinus cancer received regional chemotherapy and 13 received systemically. The change of tumor volume, the degree of response according to the tumor location, and side effects after chemotherapy were analyzed. RESULTS: Tumor volume reduction was significantly higher in the regional than systemic chemotherapy. Tumor response to chemotherapy was greater in regional than systemic chemotherapy in most maxillary sinus wall. The tumor response in anterior, posterior, and lateral wall of maxillary sinus was greater more than two times in the regional than systemic chemotherapy. There were no severe side effects related to regional chemotherapy. CONCLUSION: Regional chemotherapy was superior to systemic chemotherapy regarding tumor volume reduction, especially located in the anterior, posterior, and lateral wall of maxillary sinus.

Subglottic stenosis in children: Our experience at a pediatric tertiary center for 8 years in South Korea.

OBJECTIVE: The incidence of SGS has been reported to be less than 8% after endotracheal intubation. Therefore there is an increasing trend in the number of patients with acute acquired SGS due to mechanical ventilation in the intensive care unit. However, there have been no reports describing the treatment of SGS in children in South Korea. The objective of this study was to evaluate the management and outcomes of children with SGS at a pediatric tertiary center in South Korea over an 8-year period. METHODS: All patients underwent microlaryngobronchoscopy (MLB) with bougination, incision using cold knife or laser and balloon dilatation. Data on age, sex, grade of SGS, number of management interventions, tracheostomy, comorbidities, mean follow-up period, complications, and outcome were reviewed from patient medical charts. RESULTS: Twenty patients (13 [65%] males, 7 [35%] females; mean [±SD] age at the diagnostic procedure 15.26 ±â€¯22.54 months) underwent MLB between March 2009 and December 2017. According to the Myer-Cotton scale, twelve of the 20 (60%) patients had grade III SGS, 7 (35%) had grade II and 1 (5%) had grade 1; there were no patients with grade IV SGS. Nine (45%) patients were diagnosed with acute SGS, and 11 (55%) with chronic SGS. Patients with SGS underwent MLB with interventions (mean 2.41 ±â€¯2.23 per patient). Tracheostomy was performed in 13 of 20 (65%) patients, 2 of 9 (22.2%) with acute SGS, and 11 of 11 (100%) with chronic SGS. Two of 13 (15.3%) patients underwent successful decannulation. One of 2 (50%) patients with acute SGS underwent successful decannulation. Seven of 9 (77.7%) patients with acute SGS underwent MLB only without tracheostomy. CONCLUSIONS: In patients with acute acquired SGS, the outcome was good due to the lower rate of tracheostomy and higher decannulation rate. Therefore, it is recommended that MLB with balloon laryngoplasty be performed at the earliest in patients with acute acquired SGS.

Copy number variation in progression of inverted papilloma to squamous cell carcinoma of the nasal cavity.

Inverted papilloma (IP) is a benign tumor occurring in nasal cavity. It can recur or progress to squamous cell carcinoma (SCC). The molecular mechanism of their biologic behavior is not fully revealed. Copy number variation (CNV) may contribute to progression of IP. We performed microarray comparative genome hybridization (aCGH). Five cases of IP, 2 cases of IP with dysplasia, 7 cases of SCC arising in a background of IP were submitted. The average numbers of somatic CNVs and copy number variable regions (CNVRs) were 991.9 and 866.9, respectively. Gain of 19p13.3, including 30 protein-coding genes, was observed in 2 IP and 7 SCC cases. Among those genes, BSG encoding the extracellular matrix metalloproteinase (MMP) inducer (EMMPRIN)/CD147 may play more important role in the progression of IP to SCC. Further study for validation of the aCGH result is necessary.

Culture supernatant of adipose stem cells can ameliorate allergic airway inflammation via recruitment of CD4+CD25+Foxp3 T cells.

BACKGROUND: In a previous study, we demonstrated that intravenous administration of adipose tissue stem cells (ASCs) could significantly reduce allergic symptoms and suppress eosinophilic inflammation. METHODS: To evaluate the secretome of ASCs, we administrated culture supernatant of ASCs (ASC sup, which contains the ASC secretome) and uncultured fresh medium (con sup) into a mouse model of allergic airway inflammation. Subsequently we observed the mice for signs of inflammation and investigated Th1-, Th2-, and Treg-related cytokine levels as well as recruitment of Treg cells into the airway. RESULTS: We found that ASC sup could ameliorate allergic airway inflammation in this model; the value of airway hyperresponsiveness, and the occurrence of inflammatory cell infiltration in the lung, as well as the number of eosinophils, and goblet cells in the lung epithelium were all significantly decreased by ASC sup treatment. In addition, ASC sup treatment significantly decreased the levels of IL-4, IL-5, and IL-13 in the bronchial alveolar lavage fluid and in culture medium of lung-draining lymph node cells of the animal model of acute asthma. We detected numerous CTLA-4 and Foxp3-expressing cells in the lung after ASC sup treatment. ASC sup was found to have a higher concentration of IL-10 and TGF-ß compared to con sup. CONCLUSIONS: Stem cells have powerful potential for therapeutic functions in various diseases, but they also have many drawbacks. In this study, we found strong immunosuppressive ability of ASC sup in an allergic airway mouse model. It may be possible to use ASC sup for treatment of many immunological diseases in the near future.

Prognostic value of tumoral heterogeneity and volumetric parameters as measured by F18-FDG PET/CT in sinonasal cancer.

The objective of this study was to investigate the value of parameters assessed with F18-FDG PET/CT in predicting recurrence-free survival (RFS) and disease-specific survival (DSS) in patients with cancer of nasal cavity and paranasal sinus. Thirty-eight patients with cancer of nasal cavity (n = 14) and paranasal sinus (n = 24) who underwent PET/CT prior to curative treatment were enrolled. A volume of interest was placed on PET/CT images covering the entire tumor volume, and the maximum SUV (SUVmax), the mean SUV (SUVmean), and volumetric parameters of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured using thresholds of 40 % of SUVmax. The heterogeneity factor (HF) defined as the derivative of volume-threshold function from 40 to 80 % of SUV thresholds. RFS and DSS were defined as the time from the diagnosis to recurrence and death. Median values of SUVmax, SUVmean, MTV, TLG, and HF were 14.81, 9.16, 25.84, 150.74, and -0.496. SUVmax was higher in patients with advanced stage and nodal metastasis. High MTV and low HF group showed shorter RFS. Cox proportional hazards regression analysis revealed low HF was the only significant predictive factor on RFS. Furthermore, high TLG was associated with shorter DSS. High TLG was potent predictor of DSS by Cox proportional hazards regression analysis. In conclusion, the tumoral heterogeneity and volumetric parameters as measured by F18-FDG PET/CT could be significant prognostic surrogate markers in patients with sinonasal cancer.

Indoleamine 2,3-Dioxygenase Is Not a Pivotal Regulator Responsible for Suppressing Allergic Airway Inflammation through Adipose-Derived Stem Cells.

BACKGROUND: Although indoleamine 2,3-dioxygenase (IDO)-mediated immune suppression of mesenchymal stem cells (MSCs) has been revealed in septic and tumor microenvironments, the role of IDO in suppressing allergic airway inflammation by MSCs is not well documented. We evaluated the effects of adipose-derived stem cells (ASCs) on allergic inflammation in IDO-knockout (KO) asthmatic mice or asthmatic mice treated with ASCs derived from IDO-KO mice. METHODS AND FINDINGS: ASCs were injected intravenously in wild-type (WT) and IDO-KO asthmatic mice. Furthermore, asthmatic mice were injected with ASCs derived from IDO-KO mice. We investigated the immunomodulatory effects of ASCs between WT and IDO-KO mice or IDO-KO ASCs in asthmatic mice. In asthmatic mice, ASCs significantly reduced airway hyperresponsiveness, the number of total inflammatory cells and eosinophils in bronchoalveolar lavage fluid (BALF), eosinophilic inflammation, goblet hyperplasia, and serum concentrations of total and allergen-specific IgE and IgG1. ASCs significantly inhibited Th2 cytokines, such as interleukin (IL)-4, IL-5, and IL-13, and enhanced Th1 cytokine (interferon-γ) and regulatory cytokines (IL-10, TGF-ß) in BALF and lung draining lymph nodes (LLNs). ASCs led to significant increases in regulatory T-cells (Tregs) and IL-10+ T cell populations in LLNs. However, the immunosuppressive effects of ASCs did not significantly differ between WT and IDO-KO mice. Moreover, ASCs derived from IDO-KO mice showed immunosuppressive effects in allergic airway inflammation. CONCLUSIONS: IDO did not play a pivotal role in the suppression of allergic airway inflammation through ASCs, suggesting that it is not the major regulator responsible for suppressing allergic airway inflammation.

Smoking, not human papilloma virus infection, is a risk factor for recurrence of sinonasal inverted papilloma.

BACKGROUND: The recurrence rate of sinonasal inverted papillomas (SNIP) is 15-20%. However, few studies have investigated patient-dependent factors related to recurrence of SNIPs. OBJECTIVE: To analyze risk factors, including human papilloma virus (HPV) infection and smoking, as well as other factors, for recurrence of SNIPs. METHODS: Fifty-four patients who were diagnosed with SNIP and underwent surgery were enrolled: 39 men and 15 women, with the mean age of 54.0 years. Their mean follow-up was 40.6 months. Demographics and information about the history of smoking, previous surgery, tumor extent, follow-up, and recurrence were reviewed retrospectively. Those patients whose tumors were associated with malignant transformation were excluded in this study. HPV detection and genotyping in the tumor specimens were performed with the HPV DNA chip, a polymerase chain reaction-based DNA microarray system. RESULTS: Seven patients (13.0%) had recurrence, with a mean time to recurrence of 39.8 months. Recurrence rates in T1, T2, T3, and T4 of the Krouse staging system were 0% (0/4), 8.3% (2/24), 17.4% (4/23), and 33.3% (1/3), respectively (p > 0.5). Eight patients (14.8%) were positive for HPV DNA. All of these patients belonged to the group without recurrence (p > 0.5). However, recurrence rates according to HPV DNA positivity were not statistically different (0% versus 15.2%). Three (42.9%) in the group with recurrence and four (8.5%) in the group without recurrence were smokers (p < 0.5). CONCLUSION: Smoking was associated with recurrence of SNIP. However, HPV infection is not a recurrence of SNIP risk factor.

A comparison of dexmedetomidine versus propofol during drug-induced sleep endoscopy in sleep apnea patients.

OBJECTIVES/HYPOTHESIS: In this study, we compared the effects of propofol and dexmedetomidine on the upper airway collapse pattern and cardiopulmonary parameters of patients with obstructive sleep apnea (OSA) undergoing drug-induced sleep endoscopy (DISE). STUDY DESIGN: Prospective, single center, observational study MATERIALS AND METHODS: The 50 patients with OSA underwent 30 minutes of DISE on 2 different days, the first time with propofol target-controlled infusion (TCI) and the second time with dexmedetomidine TCI. Both the characteristics of upper airway obstruction and cardiopulmonary parameters in response to the depth of sedation achieved with each drug were evaluated. RESULTS: The results obtained with propofol and dexmedetomidine DISE were in excellent agreement for all sites of obstruction irrespective of the depth of sedation. Although partial or total obstruction at all areas was consistently observed using both drugs, the degree of upper airway narrowing was slightly lower with dexmedetomidine than with propofol. However, the percentage of patients with a greater than 20% change in blood pressure and heart rate compared to baseline was significantly higher in response to propofol than to dexmedetomidine (P = 0.003 and P < 0.001, respectively). Minimal oxygen saturation was significantly lower in DISE with propofol than with dexmedetomidine (P = 0.004). The percentage of patients with oxygen saturation less than 90% or 80% during DISE was significantly higher in response to propofol than to dexmedetomidine (P = 0.032 and P < 0.001, respectively). CONCLUSION: The DISE findings achieved with propofol and dexmedetomidine were in excellent agreement. However, during DISE, dexmedetomidine provided greater hemodynamic stability and less respiratory depression than propofol. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:763-767, 2016.

Inverted papilloma of the maxillary sinus: Surgical approach and long-term results.

BACKGROUND: Inverted papillomas (IP) commonly develop in the maxillary sinus (MS). However, the MS is a complex structure, and all areas in the MS are not easily approachable. OBJECTIVE: This study reviewed our surgical outcome of patients with IPs that originated from the MS in long-term follow-up and suggests appropriate approaches according to the tumor origin. METHODS: Thirty-one patients who were diagnosed with IP that originated from the MS, underwent surgery by a single operator between 1999 and 2011, and had postoperative follow-up of >3 years were enrolled. RESULTS: In all the cases, the endoscopic endonasal approach (EEA) was attempted at first and then canine fossa puncture (CP), canine fossa opening via the Caldwell-Luc approach (CO), and Caldwell-Luc operation (CLO) were added in consecutive order as the occasion demands. Six patients (19.4%) were treated only with EEA, and they had IPs from the superior, posterior, or medial wall. Five (16.1%) were treated with EEA plus CP, which was added for removal of IPs that originated from the lateral wall. Sixteen (51.6%) were treated with EEA plus CO, which was for removal of tumors from the medial, anterior, or inferior wall. Four patients (12.5%) whose IP attached to the whole MS mucosa underwent CLO. Three (9.7%) experienced recurrences, and the mean period to recurrence was 20.7 months. CONCLUSION: The overall recurrence rate was 9.7%. IPs that originated from the lateral wall of the MS can be removed by using CP. When IPs originate from the anterior, inferior, or medial wall of the MS, CO may be needed for the thorough removal of them.

Prostaglandin E2 and Transforming Growth Factor-ß Play a Critical Role in Suppression of Allergic Airway Inflammation by Adipose-Derived Stem Cells.

BACKGROUND: The role of soluble factors in the suppression of allergic airway inflammation by adipose-derived stem cells (ASCs) remains to be elucidated. Moreover, the major soluble factors responsible for the immunomodulatory effects of ASCs in allergic airway diseases have not been well documented. We evaluated the effects of ASCs on allergic inflammation in asthmatic mice treated with a prostaglandin E2 (PGE2) inhibitor or transforming growth factor-ß (TGF-ß) neutralizing antibodies. METHODS AND FINDINGS: Asthmatic mice were injected intraperitoneally with a PGE2 inhibitor or TGF-ß neutralizing antibodies at approximately the same time as ASCs injection and were compared with non-treated controls. In asthmatic mice, ASCs significantly reduced airway hyperresponsiveness, the number of total inflammatory cells and eosinophils in the bronchoalveolar lavage fluid (BALF), eosinophilic inflammation, goblet cell hyperplasia, and serum total and allergen-specific IgE and IgG1. ASCs significantly inhibited Th2 cytokines, such as interleukin (IL)-4, IL-5, and IL-13, and enhanced the Th1 cytokine (Interferon-γ) and regulatory cytokines (IL-10 and TGF-ß) in the BALF and lung draining lymph nodes (LLNs). ASCs engraftment caused significant increases in the regulatory T cell (Treg) and IL-10+ T cell populations in LLNs. However, blocking PGE2 or TGF-ß eliminated the immunosuppressive effect of ASCs in allergic airway inflammation. CONCLUSIONS: ASCs are capable of secreting PGE2 and TGF-ß, which may play a role in inducing Treg expansion. Furthermore, treatment with a PGE2 inhibitor or TGF-ß neutralizing antibodies eliminated the beneficial effect of ASCs treatment in asthmatic mice, suggesting that PGE2 and TGF-ß are the major soluble factors responsible for suppressing allergic airway inflammation.

Treatment outcomes of sinonasal malignant melanoma: a Korean multicenter study.

BACKGROUND: The aim of this work was to evaluate factors that influence local recurrence and survival after surgical resection of sinonasal malignant melanoma, using a large population-based multicenter study in Korea. METHODS: Retrospective analysis was performed for 155 newly diagnosed sinonasal malignant melanoma patients gathered from 15 university hospitals throughout Korea. Demographic data, tumor characteristics, surgical approach, adjuvant treatment, recurrence, and outcomes were analyzed. RESULTS: Three-year and 5-year overall survival rates were 48.8% and 40.1%, respectively. Local recurrence rate was 46.6%, with a mean recurrence time of 15.5 months. On multivariate analysis, patients who underwent surgery that included an endoscopic approach showed decreased local recurrence rate (p = 0.042) and increased survival rate (hazard ratio [HR], 1.702; 95% confidence interval [CI], 1.007 to 2.875; p = 0.047) compared to those who underwent an external approach. Patients with postoperative radiotherapy showed a decreased local recurrence rate (p = 0.001), but without impact on survival rate. Male gender, tumor beyond the nasal cavity, and presence of distant metastasis were associated with poor survival. CONCLUSION: An endoscopic-including surgical approach was associated with improved local control and survival in sinonasal malignant melanoma patients. Postoperative radiotherapy helped increase the local control rate.

Role of Wnt signaling pathway in progression of sinonasal inverted papilloma to squamous cell carcinoma.

BACKGROUND: Sinonasal inverted papilloma (IP) is one of the most common benign tumors of the sinonasal area and malignant transformation has frequently been reported. However, the exact mechanism of the transition from benign lesion to malignancy is not known. The Wnt signaling pathway involves a network of multiple signaling glycoproteins that are known to play an important role in embryogenesis and carcinogenesis. OBJECTIVE: The purpose of this study was to evaluate the role of the Wnt pathway and signaling proteins in malignant transformation of IP to dysplasia and squamous cell carcinoma. METHODS: Expression of the Wnt signaling pathway proteins, including Wnt-1, beta-catenin, cyclin D1, and Dishevelled-1 (Dvl-1), were detected by immunohistochemistry by using 3-mm tissue core microarrays that consisted of 115 cores of IP tissue. Each of the IP cores was graded as I (prominent squamous metaplasia), II (inverted pattern), III (dysplasia), or IV (squamous cell carcinoma). The expression pattern of each protein and the correlation between the expression of each target protein and IP grade were evaluated. RESULTS: Membranous staining of beta-catenin showed a significant positive correlation with IP grade (ρ = 0.247, p < 0.001), as did staining of cyclin D1 (ρ = 0.365, p < 0.001), which showed a nuclear pattern and staining of Dvl-1 (ρ = 0.380, p < 0.001), which showed a membranous, cytoplasmic, and nuclear pattern. For Dvl-1, a nuclear expression pattern was more frequently observed in grade III and IV IP (p = 0.036). In the case of Wnt-1, cytoplasmic expression was observed; however, it did not show a significant correlation with IP grade (ρ = 0.141, p = 0.130). CONCLUSIONS: Wnt signaling proteins, including beta-catenin, cyclin D1, and Dvl-1, may play crucial roles in the malignant transformation of IP.

Comparative analysis of Cutanplast and Spongostan nasal packing after endoscopic sinus surgery: a prospective, randomized, multicenter study.

Commercial gelatin-based packing materials are available under different names and compositions to be used after endoscopic sinus surgery (ESS). The purpose of this study was to investigate the efficacy of Spongostan and Cutanplast nasal packing on patients' subjective symptoms, hemostasis, and wound healing following ESS. One hundred adult patients with chronic sinusitis requiring the same extent of ESS were included. Following surgery, one nasal cavity was packed with Cutanplast and the other one with Spongostan. Patients' subjective symptoms while the packing was in situ, hemostatic properties, degree of remaining amount of packing materials, postoperative wound healing, and the cost of the pack were evaluated. Cutanplast and Spongostan are equally effective in the control of postoperative bleeding following ESS. However, Cutanplast packing was significantly more comfortable than Spongostan for nasal obstruction, postnasal drip, rhinorrhea, and headache. Furthermore, the Cutanplast packing was significantly less painful at all time points. The remaining amount of the pack was significantly lower in the Cutanplast than Spongostan packing. Spongostan packing appears to impair wound healing within the sinus cavities up to 3 months postoperatively. Cutanplast was less expensive than Spongostan as used in this study. Cutanplast may be more useful gelatin-based packing material than Spongostan in terms of efficacy and cost-benefit after ESS.

Changes and recovery of voice quality after sinonasal surgery.

Changes in the configuration of sinonasal cavity after surgery have been assumed to cause changes in the voice quality. The purpose of this study was to know when the hypernasality will be recovered after sinonsal surgery in patients with nasal septal deviation or chronic rhinosinusitis by checking long-term and serially obtained nasalance scores using nasometer. Sixty-five patients underwent sinonasal surgery were included. We classified the subjects into three groups according to the different surgical interventions employed: septoplasty group, endoscopic sinus surgery (ESS) group, and ESS with septoplasty group. The nasalance scores were obtained using a nasometer preoperatively, 1, 2, 3, 4, 5, and 6 months after surgery. The mean nasalance scores for vowels, nasal consonant, plosive consonant-vowel combinations, nasal consonant-vowel combinations, a hypernasality sentence, and hyponasality sentence increased significantly after sinonasal surgery. Hypernasality was most prominent in all groups for all acoustic parameters 1 month after surgery. Thereafter nasality decreased and returned to its preoperative level in all groups at 5 months in the [m], [ma], [mi], and hypernasality sentence, but at 6 months in the [a], [i], [u], [p(h)a], [p(h)i], and hyponasality sentence. Sinonasal surgery can change the acoustic characteristics of the vocal tract and produce a significant increase in nasality. After nasality showed the highest scores at 1-month post-surgery, it returned to its preoperative level at 5 or 6 months after surgery depending on the subtype of speech stimuli.

Adipose-derived stem cells ameliorate allergic airway inflammation by inducing regulatory T cells in a mouse model of asthma.

Although several studies have demonstrated that mesenchymal stem cells derived from adipose tissue (ASCs) can ameliorate allergic airway inflammation, the immunomodulatory mechanism of ASCs remains unclear. In this study, we investigated whether regulatory T cells (Tregs) induction is a potential mechanism in immunomodulatory effects of ASCs on allergic airway disease and how these induced Tregs orchestrate allergic inflammation. Intravenous administration of ASCs significantly reduced allergic symptoms and inhibited eosinophilic inflammation. Airway hyperresponsiveness, total immune cell and eosinophils in the bronchoalveolar lavage fluid, mucus production, and serum allergen-specific IgE and IgG1 were significantly reduced after ASCs administration. ASCs significantly inhibited Th2 cytokines (IL-4, IL-5, and IL-13) and enhanced Th1 cytokine (IFN-γ) and regulatory cytokines (IL-10 and TGF-ß) in the bronchoalveolar lavage fluid and lung draining lymph nodes. Furthermore, levels of IDO, TGF-ß, and PGE2 were significantly increased after ASCs administration. Interestingly, this upregulation was accompanied by increased Treg populations. In conclusion, ASCs ameliorated allergic airway inflammation and improved lung function through the induction of Treg expansion. The induction of Treg by ASCs involves the secretion of soluble factors such as IDO, TGF-ß, and PGE2 and Treg might be involved in the downregulation of Th2 cytokines and upregulation of Th1 cytokines production.