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1.
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi ; 54(11): 850-856, 2019 Nov 07.
Artigo em Chinês | MEDLINE | ID: mdl-31795547

RESUMO

Objective: To explore the expression of amphiregulin (AREG) in nasal polyps patients with different degrees of eosinophil infiltration, and to analyze the correlation between AREG and tissue remodeling. Methods: Forty-eight patients underwent endoscopic sinus surgery in the Department of Otorhinolaryngology Head and Neck Surgery, Remin Hospital, Wuhan University from July 2017 to August 2018 were recruited, including 40 males and 8 females, aged from 16 to 60 years old. The subjects were divided into three groups: control group (n=14), eosinophilic chronic sinusitis with nasal polyps (ECRSwNP) group (n=19) and noneosinophilic chronic rhinosinusitis with nasal polyps (non-ECRSwNP) group (n=15). The relative expression of AREG in nasal mucosa was detected by Western blot assay and immunohistochemical staining. Tissue remodeling was detected by HE staining, AB-PAS staining and Masson staining. Kruskal-Wallis test was used for comparison among multiple groups, and Spearman correlation analysis was conducted between the expression level of AREG and the related indexes of tissue remodeling. Results: The expression of AREG in ECRSwNP group was significantly higher than that in non-ECRSwNP group and control group (median protein expression of Western blot was 1.592 vs 0.617 vs0.582, all P<0.05). The degree of epithelial injury and goblet cell metaplasia in ECRSwNP group was significantly higher than that in control group (all P<0.05), the percentage of collagen fibrosis area in ECRSwNP group was significantly lower than that in control group (P=0.01). In chronic rhinosinusitis with nasal polyps (CRSwNP) patients, the area of mucous glands was negatively correlated with the expression of AREG (r=-0.616, P<0.05), and the percentage of collagen fibrosis area was negatively correlated with the expression of AREG (r=-0.738, P<0.05). Conclusion: The expression of AREG is higher in ECRSwNP patients, which is related to the process of tissue remodeling.


Assuntos
Anfirregulina/biossíntese , Eosinófilos/metabolismo , Mucosa Nasal/metabolismo , Pólipos Nasais/metabolismo , Rinite/metabolismo , Sinusite/metabolismo , Adolescente , Adulto , Doença Crônica , Feminino , Fibrose/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/patologia , Mucosa Nasal/cirurgia , Pólipos Nasais/patologia , Pólipos Nasais/cirurgia , Rinite/patologia , Rinite/cirurgia , Sinusite/patologia , Sinusite/cirurgia , Adulto Jovem
2.
EBioMedicine ; 46: 330-341, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31331833

RESUMO

BACKGROUND: There is increasing evidence supporting the impact of neoosteogenesis in the pathophysiology of chronic rhinosinusitis (CRS), especially in the recalcitrant group of patients. Runt-related transcription factor 2 (RUNX2), a member of the RUNX family, controls osteoblast differentiation and bone formation. However, the role and regulation of RUNX2 in CRS patients with neoosteogenesis remain unclear. The aim of the study is to determine the role of RUNX2 in neoosteogenesis of CRS patients. METHODS: Sinonasal bone and overlying mucosa samples were obtained from CRS patients with or without neoosteogenesis (n = 67) and healthy controls (n = 11). Double immunofluorescence, immunohistochemistry, and immunoblotting were used to evaluate RUNX2 expression in CRS patients with and without neoosteogenesis. In addition, the osteogenic activity of pro-inflammatory cytokines was examined by measuring alkaline phosphatase (ALP) activity and bone mineralisation in vitro. FINDINGS: RUNX2 was highly expressed in osteoblasts of CRS patients with neoosteogenesis compared with tissues from control subjects and those with CRS without neoosteogenesis. Mucosal extracts from CRS patients with neoosteogenesis showed increased RUNX2 expression and ALP activity in C2C12 cells, whereas those from patients without neoosteogenesis did not. Expression of interleukin (IL)-13 and IL-17A was upregulated in CRS patients with neoosteogenesis. ALP activity and Alizarin Red staining showed IL-13 and IL-17A dose-dependent osteoblast differentiation and mineralisation in vitro. INTERPRETATION: These findings suggested that IL-13- or IL-17A-induced RUNX2 contributed to new bone formation in CRS patients through its effect on the activity of osteoblasts. RUNX2 may be a novel target for preventing neoosteogenesis in CRS patients.


Assuntos
Subunidade alfa 1 de Fator de Ligação ao Core/genética , Interleucina-13/metabolismo , Interleucina-17/metabolismo , Osteogênese/genética , Rinite/etiologia , Rinite/metabolismo , Sinusite/etiologia , Sinusite/metabolismo , Adulto , Animais , Biomarcadores , Cálcio/metabolismo , Linhagem Celular , Citocinas/metabolismo , Suscetibilidade a Doenças , Feminino , Regulação da Expressão Gênica , Humanos , Imuno-Histoquímica , Interleucina-13/antagonistas & inibidores , Interleucina-17/antagonistas & inibidores , Masculino , Camundongos , Pessoa de Meia-Idade , Osteoblastos/metabolismo
3.
Immun Inflamm Dis ; 7(3): 191-200, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31210032

RESUMO

BACKGROUND: In the clinical setting, chronic rhinosinusitis with nasal polyps (CRSwNP) is usually divided into eosinophilic-CRS (ECRS) and non-ECRS (NECRS) in Japan. Patients with the former are believed to be at risk for postoperative recurrence of CRS. However, some patients have been missed according to these phenotypic classifications due to the low number of infiltrating eosinophils in polyp tissues. OBJECTIVE: In the present study, we attempted to identify cellular or molecular candidate markers to predict nasal polyp recurrence. METHODS: Nasal polyps were collected from 32 patients with CRSwNP who had undergone an endoscopic sinus surgery. These patients were divided into ECRS and NECRS groups in accordance with the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) scoring system and the number of eosinophils in polyp tissues. Unclassifiable patients were referred to as the unknown group. RESULTS: Eosinophil infiltration in resected nasal polyps was most evident in the ECRS group. However, the number of mast cells and tryptase-positive cells in nasal polyps were significantly lower in ECRS and unknown groups compared with the NECRS group. A significant positive correlation was detected between the JESREC score and number of eosinophils. The numbers of mast cells and tryptase-positive cells were negatively correlated with the JESREC score in all included samples. Significant positive correlations were detected between the number of transforming growth factor ß1-positive cells and the number of mast cells, tryptase-positive cells, and chymase-positive cells mast cells. CONCLUSIONS AND CLINICAL RELEVANCE: These findings indicated that the enumeration of mast cells in resected polyps may be another approach to predict postoperative polyp recurrence in CRSwNP patients.


Assuntos
Mastócitos/patologia , Pólipos Nasais/patologia , Rinite/diagnóstico , Sinusite/diagnóstico , Doença Crônica , Quimases/metabolismo , Feminino , Humanos , Japão , Contagem de Leucócitos , Masculino , Mastócitos/enzimologia , Pessoa de Meia-Idade , Pólipos Nasais/cirurgia , Período Pós-Operatório , Prognóstico , Recidiva , Rinite/metabolismo , Sinusite/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Triptases/metabolismo
4.
Med Hypotheses ; 127: 5-10, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31088648

RESUMO

Chronis rhinosinusitis is considered as a widespread public health issue with a prevalence of 10%. The disease significantly reduces quality of life and increases the risk of cardiovascular diseases as well as certain forms of cancer. Alteration of mucociliary clearance frequently observed in the patients and plays a significant role in disease pathogenesis. Certain studies have demonstrated that patients with chronic rhinosinusitis are characterized by significant reduction of essential trace elements and toxic metal overload. However, the particular mechanisms of the role of trace element dysbalance in chronic rhinosinusitis are unclear. We hypothesize that exposure to toxic trace elements (arsenic, nickel, cadmium) damages ciliary mucosal epithelium thus affecting mucociliary transport. In turn, altered mucociliary transport results in reduced removal of the inhaled metal-containing particles from nasal mucosa leading to their absorption and further aggravation of toxicity. Essential trace elements (zinc, selenium) play a significant role in regulation of mucociliary transport and immunity, thus their deficiency (either dietary or due to antagonism with toxic metals) may be associated with impaired functions and increased toxic metal toxicity. Therefore, a vicious circle involving metal accumulation and toxicity, essential element deficiency, impairment of mucociliary transport and metal particle removal, resulting in further accumulation of metals and aggravation of toxic effects is formed. The present hypothesis is supported by the findings on the impact of trace elements especially zinc and arsenic on mucociliary clearance, the role of mucociliary transport in heavy metal particles elimination from the airways, trace element dysbalance in chronic rhinosinusitis, as well as toxic and essential metal antagonism. The data from hypothesis testing and its verification may be used for development of therapeutic approach for management of chronic rhinosinusitis. Particularly, the use of essential elements (zinc, selenium) may reduce toxic metal toxicity thus destroying the vicious circle of heavy metal exposure, toxicity, alteration of mucociliary clearance, and aggravation of chronic rhinosinusitis. Essential element supplementation may be considered as a tool for management of chronic refractory rhinosinusitis. In addition, analysis of essential and toxic trace element status may provide an additional diagnostic approach to risk assessment of chronic rhinosinusitis in highly polluted environments.


Assuntos
Metais Pesados/metabolismo , Depuração Mucociliar , Sinusite/fisiopatologia , Oligoelementos/metabolismo , Animais , Arsênico/metabolismo , Cádmio/metabolismo , Quelantes , Doença Crônica , Cílios/patologia , Exposição Ambiental , Humanos , Mercúrio/metabolismo , Camundongos , Modelos Biológicos , Medição de Risco , Selênio/metabolismo , Sinusite/metabolismo , Zinco/metabolismo
6.
Inflammation ; 42(4): 1370-1382, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31028575

RESUMO

Chronic rhinosinusitis (CRS) is a common disease characterized by inflammation of the nose and paranasal sinuses lasting over 12 weeks. This study aims to evaluate the effect of desmoglein 3 (DSG3) on inflammatory response and goblet cell mucin secretion in a mouse model of CRS. The CRS-related differentially expressed genes and disease genes were screened using microarray-based gene expression analysis. Subsequently, CRS mouse models were established. The levels of pro-inflammatory factors TNF-α, IL-6, and IL-8 were measured by ELISA. In addition, loss-of-function experiment was conducted using siRNAs targeting DSG3 and ß-catenin. The secretion of mucins MUC5B and MUC5AC in goblet cells was detected, and the apoptosis of goblet cells was assessed. The regulatory effect of DSG3 on the Wnt/ß-catenin signaling pathway was analyzed by determining the mRNA and protein levels of DSG3, Wnt, ß-catenin, and GSK3ß. DSG3 was identified to be an upregulated gene in CRS, which was further documented in CRS mice models. Elevated inflammation and mucin production were noted in CRS mice models. Also, it was found that DSG3 or ß-catenin silencing could decrease the levels of TNF-α, IL-6, and IL-8, and the positive rates of MUC5B and MUC5AC while enhancing goblet cell apoptosis. The Wnt/ß-catenin signaling pathway was blocked by DSG3, evidenced by downregulated Wnt and ß-catenin as well as upregulated GSK3ß mRNA and protein levels. Overall, this study provides evidence that silencing DSG3 could inhibit the activation of the Wnt/ß-catenin signaling pathway, thus alleviating CRS.


Assuntos
Desmogleína 3/genética , Células Caliciformes/efeitos dos fármacos , Inflamação/tratamento farmacológico , Rinite/metabolismo , Sinusite/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Doença Crônica , Desmogleína 3/farmacologia , Modelos Animais de Doenças , Inativação Gênica , Células Caliciformes/metabolismo , Camundongos , Mucinas/efeitos dos fármacos , Mucinas/metabolismo , Rinite/tratamento farmacológico , Sinusite/tratamento farmacológico , beta Catenina/efeitos dos fármacos , beta Catenina/metabolismo
9.
Pathology ; 51(3): 268-273, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30837082

RESUMO

Eosinophilic chronic rhinosinusitis (ECRS) is characterised by formation of nasal polyps with prominent eosinophilic infiltration; however, how eosinophils are recruited in this pathological setting remains unclear. In the present study, we carried out quantitative immunohistochemical analysis of nasal polyps associated with ECRS (n=30) and non-ECRS (n=30) to evaluate expression of an L-selectin ligand peripheral lymph node addressin (PNAd) on vascular endothelial cells. We found that PNAd was induced primarily on the luminal surface of venular vessels present in nasal mucosa in both ECRS and non-ECRS, while the number of PNAd-expressing vessels in ECRS significantly exceeded that seen in non-ECRS. Moreover, the number of eosinophils attached to the luminal surface of PNAd-expressing vessels in ECRS was significantly greater than that in non-ECRS, while the number of neutrophils and lymphocytes attached did not differ significantly between conditions. Furthermore, eosinophils, which express cell surface L-selectin, adhered to PNAd-expressing Chinese hamster ovary (CHO) cells in a calcium-dependent manner, and that adhesion was significantly inhibited by pretreatment of eosinophils with DREG-56, an anti-human L-selectin monoclonal antibody. These findings combined suggest that interaction between L-selectin and PNAd plays at least a partial role in eosinophil recruitment in human nasal mucosa with ECRS.


Assuntos
Antígenos de Superfície/metabolismo , Eosinófilos/metabolismo , Proteínas de Membrana/metabolismo , Mucosa Nasal/metabolismo , Pólipos Nasais/metabolismo , Rinite/metabolismo , Sinusite/metabolismo , Animais , Células CHO , Cricetinae , Cricetulus , Eosinófilos/patologia , Humanos , Mucosa Nasal/patologia , Pólipos Nasais/patologia , Rinite/patologia , Sinusite/patologia
10.
Int Immunopharmacol ; 71: 169-180, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30909132

RESUMO

BACKGROUND: Autophagy is a lysosomal degradation pathway that protects the body and is essential for cell survival and differentiation. Mucins (MUCs) are important components of secreted mucus, mucin (MUC)5 AC is the major MUC secreted in the normal airway. OBJECTIVE: Investigated the role of autophagy in pathogenic mucin (MUC)5 AC production during chronic rhinosinusitis (CRS). METHODS: The expression of human neutrophil elastase (HNE) and the autophagic proteins microtubule-associated protein 1 light chain (LC)3B-II, c-Jun N-terminal kinase (JNK), c-Jun, and MUC5AC were analyzed in the sinonasal mucosa and human nasal epithelial cells (HNECs) using immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and quantitative real-time polymerase chain reaction (qRT-PCR). Autophagic vacuoles were studied using transmission electron microscopy (TEM). Primary HNECs were treated with HNE, bafilomycin A1, and SP600125. In some experiments, cultured primary HNECs were transfected with small interfering RNAs (siRNAs) to target Beclin-1 (BECN1; BECN1-siRNA), autophagy-related gene 5 (Atg5; Atg5-siRNA), and c-Jun (c-Jun-siRNA). Cultured cells were analyzed using western blotting, qRT-PCR, and ELISA. RESULTS: In CRS patients, both with and without nasal polyps, the expression levels of HNE, LC3B, JNK, c-Jun, and MUC5AC were upregulated. Bafilomycin A1 upregulated LC3B-II expression and inhibited MUC secretion in HNE-treated normal primary HNECs. Autophagosomes were observed in HNE-treated primary HNECs using TEM. HNE-induced secretion of MUC5AC was suppressed in normal primary HNECs by BECN1-siRNA, Atg5-siRNA, c-Jun-siRNA, and SP600125. CONCLUSIONS: In HNE-induced CRS, autophagy increases the secretion of MUC5AC by promoting the phosphorylation of JNK and c-Jun.


Assuntos
Autofagia , Mucina-5AC/metabolismo , Mucosa Nasal/fisiologia , Pólipos Nasais/metabolismo , Rinite/metabolismo , Sinusite/metabolismo , Adolescente , Adulto , Idoso , Células Cultivadas , Criança , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucina-5AC/genética , Pólipos Nasais/genética , Rinite/genética , Sinusite/genética , Regulação para Cima , Adulto Jovem
11.
Artigo em Chinês | MEDLINE | ID: mdl-30909336

RESUMO

Objective: To evaluate the expression of immunological and inflammatory biomarkers as well as to analyze their predictive value for recurrence of chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: Seventy-seven CRSwNP patients were enrolled in this survey from January 2011 to December 2012 in Beijing Tongren Hospital. There were 13 males and 64 females, with the range of age from 14 to 74 years old. The average follow-up period was more than 2 years. The demographic and clinical features of patients were compared between recurrence and non-recurrence groups, and 43 kinds of cytokines, chemokines and inflammatory mediators, tissue and serum total IgE, and morphological and cytology indexes were compared between the two groups. The receiver operating characteristic (ROC) curves were used to evaluate the predictive value of significant indicators for the postoperative recurrence of CRSwNP and to calculate the best diagnostic cut-off values. Results: The recurrence rate of CRSwNP was 44.2% (34/77). Compared with non-recurrence CRSwNP, there were higher risk of aspirin intolerance and asthma in the recurrence group, as well as higher CT and endoscopic polyp scores and lower olfactory sense (7/34 vs 0/43, 10/34 vs 4/43, 18.5[3.0, 24.0] vs 13.8[2.0, 24.0], 2.1[0.5, 3.0] vs 1.5[0.5, 3.0], 5.0[4.5, 5.0] vs 3.0[1.0, 5.0], χ(2) value was 9.738, 5.161, Z value was -3.267, -2.705, -3.213, respectively, all P<0.05). At the same time, the level of interleukin-5 (IL-5), eosinophilic cationic protein / myeloperoxidase (ECP/MPO), tissue inhibitor of metalloproteinase 1 (TIMP1), chemokine (C-C motif) ligand 2 (CCL2), CCL3, CCL4 and tissue and serum total IgE were higher in the recurrence group than those of the non-recurrence. Moreover, the oedema of the lamina propria were more severe. The total IgE, IL-5, ECP/MPO and CCL4 in the tissue had a acceptable discrimination value for the prediction of CRSwNP recurrence. The best diagnostic cut-off values and corresponding sensitivity and specificity were 124.85 pg/ml (82.4%, 60.5%), 6.22 pg/ml (76.5%, 58.1%), 0.61 (55.9%, 83.7%) and 2 456.96 pg/ml (61.8%, 79.1%), respectively. Conclusions: The profile of the immunological and inflammatory biomarkers was different between the non-recurrence CRSwNP and recurrence CRSwNP groups. And a variety of biomarkers can be considered as indicators of recurrence of CRSwNP with acceptable predictive value.


Assuntos
Pólipos Nasais/metabolismo , Rinite/metabolismo , Sinusite/metabolismo , Adolescente , Adulto , Idoso , Biomarcadores/metabolismo , Doença Crônica , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/complicações , Curva ROC , Recidiva , Rinite/complicações , Sinusite/complicações , Inibidor Tecidual de Metaloproteinase-1 , Adulto Jovem
13.
Mol Med Rep ; 19(5): 3855-3863, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30864741

RESUMO

Chronic rhinosinusitis with nasal polyps (CRSwNP) is one of the most prevalent chronic diseases. In patients with CRSwNP, the present study performed comprehensive bioinformatics analyses to characterize the transcriptome profiles of mRNAs and long non­coding RNAs (lncRNAs). A total of 265 differentially expressed lncRNAs and 994 mRNAs were identified. The majority of up­ and downregulated differentially expressed genes were significantly enriched in the biological process of 'signal transduction'. The most significantly enriched molecular function was 'protein binding' and the most significantly enriched cellular component was 'membrane'. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis led to identification of several significantly enriched pathways [false discovery rate (FDR)<0.05], including 'cytokine­cytokine receptor interaction' (FDR=3.94x1016) and 'cell adhesion molecules' (CAMs) (FDR=1.28x10­5). Key differentially expressed lncRNAs were identified, including lncRNA XLOC_010280, which regulates chemokine (C­C motif) ligand 18 (CCL18) and inflammation, and RP11­798M19.6, which regulates polypeptide N­acetylgalactosaminyltransferase 7 (GALNT7) and cell proliferation. Based on the results of reverse transcription­quantitative polymerase chain reaction, except for CCL8, neural precursor cell expressed developmentally downregulated gene 4­like and GALNT7, the expression of 3 other selected genes was consistent with the results of integrated analysis. The results of the present study provide a foundation for future investigations into mRNAs and lncRNAs as diagnostic and therapeutic targets in CRSwNP.


Assuntos
Perfilação da Expressão Gênica , Genoma Humano , Pólipos Nasais/metabolismo , RNA Longo não Codificante/genética , RNA Mensageiro/metabolismo , Rinite/metabolismo , Sinusite/metabolismo , Estudos de Casos e Controles , Doença Crônica , Biologia Computacional , Redes Reguladoras de Genes , Humanos , Pólipos Nasais/patologia , Mapas de Interação de Proteínas , RNA Mensageiro/genética , Rinite/genética , Rinite/patologia , Transdução de Sinais , Sinusite/genética , Sinusite/patologia
14.
Artigo em Chinês | MEDLINE | ID: mdl-30704168

RESUMO

Objective: To investigate the regulation of IL-25 on type Ⅱ innate lymphoid cells (ILC2s) activation in the pathogenesis of allergic fungal rhinosinusitis (AFRS). Methods: Nasal mucosa tissues were collected from 16 AFRS patients and 12 patients, who underwent nasal endoscopic surgery for cerebrospinal rhinorrhea or skull base benign tumor during the period from June 2016 to June 2017 in Department of Rhinology, the First Affiliated Hospital of Zhengzhou University. Firstly, flow cytometry was used to detect ILC2s in nasal mucosa of both groups. Secondly, the expression of IL-25, IL-5 and IL-13 in nasal mucosa was detected by immunofluorescence and/or Western Blot assay. Finally, fungal extracts, IL-25 and glucocorticoids were used to stimulate nasal mucosal epithelial cells and tissues in vitro respectively to detect the regulatory effect of IL-25 on ILC2s. SPSS 16.0 software was used to analyze the data. Results: The prevalence of ILC2s in nasal tissues was higher in patients with AFRS than those of the control group ((3.85±1.52)%(Mean±SD) vs (0.32±0.10)%, U=9.00, P<0.05). There was a positive correlation between the prevalence of ILC2s and the number of eosinophils in nasal mucosa of patients with ARFS (r=0.80, P<0.05). The expression of IL-25, IL-5 and IL-13 in nasal mucosa epithelium of AFRS group was significantly higher than that of the control group (0.49±0.13 vs 0.23±0.09, 0.23±0.05 vs 0.10±0.04, 0.31±0.08 vs 0.14±0.07, t value was 5.90, 7.21, 5.69, respectively, all P<0.05). Fungal stimulation enhanced the expression of IL-25 protein in nasal epithelial cells of both groups (0.67±0.19 vs 0.25±0.12 (AFRS group), 0.62±0.17 vs 0.27±0.16 (control group), q value was 8.65, 9.26, respectively, all P<0.05). In the IL-25 stimulated nasal mucosa at a concentration of 1, 10 and 100 ng/ml, the expression level of retinoid acid-related orphan receptor α (RORα) mRNA was 2.07±1.53, 5.06±0.93, 7.38±2.30, respectively; the expression level of GATA binding protein 3 (GATA3) mRNA was 3.58±1.29, 6.14±1.55, 7.64±2.28, respectively; the expression level of IL-5 protein was 0.21±0.06, 0.32±0.06, 0.38±0.10, respectively; the expression level of IL-13 was 0.52±0.13, 0.69±0.22, 0.82±0.21, respectively, which were significantly higher than that in the unstimulated nasal mucosa (1.00±0.00, 1.00±0.00, 0.11±0.05, 0.35±0.15, F value was 63.45, 59.27, 49.35, 20.20, respectively, all P<0.05). The up-regulation could be inhibited by dexamethasone (F value was 89.20, 92.47, 99.63, 49.82, respectively, all P<0.05). Conclusions: Epithelial-derived IL-25 up-regulates the expression of IRC2s-dependent transcription factors RORα and GATA3 mRNA, which are positively correlated with elevated IL-13 and IL-5 expression levels in tissues, may be involved in AFRS inflammatory response, and are inhibited by glucocorticoids.


Assuntos
Interleucina-17/metabolismo , Ativação Linfocitária , Rinite Alérgica/etiologia , Sinusite/etiologia , Eosinófilos/citologia , Fator de Transcrição GATA3/metabolismo , Humanos , Interleucina-13/metabolismo , Interleucina-17/imunologia , Interleucina-5/metabolismo , Linfócitos , Mucosa Nasal/citologia , Mucosa Nasal/metabolismo , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Rinite Alérgica/metabolismo , Sinusite/metabolismo
15.
Eur Arch Otorhinolaryngol ; 276(5): 1367-1372, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30739179

RESUMO

PURPOSE: The aim of this study is to investigate serum and tissue procalcitonin (PCT) levels in patients with nasal polyps. METHODS: The study was designed to be prospectively controlled and included 26 patients chronic rhinosinusitis with nasal polyp (CRSwNP) endoscopically diagnosed and as a control group 25 chronic rhinosinusitis without nasal polyp (CRSsNP). NP specimens, nasal mucosal tissue and venous blood samples of both groups were collected and PCT levels determined by Elisa method. The results were compared statistically. RESULTS: Serum PCT values were 1319.5 pg/mL in the NP group and 818.8 pg/mL in the control group. The difference between the groups was statistically significant (p = 0.0001). In the NP group, the average PCT value of the polyp tissue was 1521.5 pg/gr, while the mean PCT value of the control group in the nasal mucosa was 414.6 pg/gr. There was a statistically significant difference between the groups (p = 0.0001). The tissue cut-off value of PCT 750 was significant [area under curve 0.940 (0.863-1.00)]. Serum PCT 950 cut-off value was significant [area under curve 0.860 (0.748-0.972)] activity (CI: 95%). CONCLUSIONS: This is the first study of its kind to objectively examine PCT in the polyp and serum of CRSwNP patients. PCT may serve as a diagnostic biomarker in nasal polyps.


Assuntos
Pólipos Nasais , Pró-Calcitonina , Adulto , Área Sob a Curva , Biomarcadores/sangue , Biomarcadores/metabolismo , Biópsia/métodos , Doença Crônica , Endoscopia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/metabolismo , Mucosa Nasal/patologia , Pólipos Nasais/metabolismo , Pólipos Nasais/patologia , Pró-Calcitonina/sangue , Pró-Calcitonina/metabolismo , Reprodutibilidade dos Testes , Rinite/metabolismo , Rinite/patologia , Sinusite/metabolismo , Sinusite/patologia
16.
Mol Med Rep ; 19(4): 2792-2800, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30720103

RESUMO

The present study focused on the assessment of the inflammatory infiltrate that characterizes nasal polyps in patients with chronic rhinosinusitis and nasal polyposis. Inflammatory cell type was determined using specific markers. This evaluation was made possible by determining the expression of the following markers: CD20, a marker of B lymphocytes [using activated T cells (ATC) armed with CD20 antibody]; CD3, a marker of T lymphocytes (using ATC armed with anti­CD3 antibody); CD45, the leukocyte common antigen (using ATC armed with anti­CD45 antibody; and CD34, for the microvasculature of the nasal polyp (using anti­CD34 antibody). The diagnosis of chronic rhinosinusitis with nasal polyps (CRSwNP) was made according to current EPOS guidelines based on patient history, clinical examination and nasal endoscopy. We examined surgically resected nasal polyps from 127 patients diagnosed with CRSwNP, who benefited from surgical procedures at the Department of Otorhinolaryngology of our institution. The polyps were analyzed at the Department of Pathology of our institution utilizing histopathological and immunohistochemical methods as follows: Firstly, the tissues were paraffin­impregnated, sectioned and stained with hematoxylin and eosin. We then examined the expression of CD3, CD20, CD34 and CD45RO by immunohistochemistry with soluble labeled streptavidin biotin (LSAB)/horseradish peroxidase (HRP) complexes. We observed the following histopathological changes: The structure of the epithelium was evidenced by collagenous subjacent stroma with mixed areas, sometimes associated with hyaline zones. In all types of polyps, we also observed a diffuse underlayer or periglandular lymphoplasmacytic in filtrate composed predominantly from T lymphocytes and eosinophils. The histopathological changes suggest the chronic inflammation of the sinus mucosa, which was diffusely distributed in allergic polyps and with nodular distribution in fibro­inflammatory polyps. The number of B lymphocytes was greater in the fibro­inflammatory polyps. On the whole, the findings of this study indicate that the inflammatory infiltrate in nasal polyps from patients with CRSwNP is mainly composed of T cells and eosinophils in all types of polyposis. In addition, a diffuse distribution of allergic polyps and the nodular distribution of fibro­inflammatory polyps, and the hyperplasia of the seromucous glands was observed. The determination of CD20, CD3, CD34 and CD45RO could be used to assess the inflammatory infiltrate of the nasal poplyps in these patients.


Assuntos
Mucosa Nasal/metabolismo , Mucosa Nasal/patologia , Pólipos Nasais/etiologia , Pólipos Nasais/metabolismo , Rinite/complicações , Rinite/metabolismo , Sinusite/complicações , Sinusite/metabolismo , Adolescente , Adulto , Biomarcadores , Criança , Pré-Escolar , Doença Crônica , Eosinófilos/imunologia , Eosinófilos/metabolismo , Eosinófilos/patologia , Feminino , Humanos , Imuno-Histoquímica , Lactente , Recém-Nascido , Linfócitos/imunologia , Linfócitos/metabolismo , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
17.
Mucosal Immunol ; 12(3): 601-611, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30804419

RESUMO

Chronic rhinosinusitis (CRS) is a heterogeneous and multifactorial inflammatory disease characterized by involvement of diverse types of inflammatory cells. Asian CRS patients frequently show infiltration of neutrophils and an elevated level of interferon (IFN)-γ; by contrast, western patients exhibit eosinophil infiltration and enhanced levels of Th2-related cytokines. Neutrophilia in tissues decreases sensitivity to corticosteroids, but the mechanisms underlying the progression of neutrophilic CRS are unclear. In this study, we investigated the role of IFN-γ in CRS patients with marked neutrophil infiltration. We report that the IFN-γ level is upregulated in the tissues of these patients, particularly those with non-eosinophilic nasal polyps. The level of IFN-γ was significantly correlated with markers of the epithelial-to-mesenchymal transition (EMT). We further demonstrated that IFN-γ induced the EMT via the p38 and extracellular signal-regulated kinase (ERK) pathways in a manner distinct from the hypoxia-inducible factor (HIF)-1α, SMAD, and NF-κB signaling pathways. In a murine nasal polyp (NP) model, blocking the p38 and ERK signaling pathways prevented NP formation and chemotactic cytokine secretion by neutrophils but not eosinophils. Taken together, our results suggest that IFN-γ can induce the EMT in nasal epithelial cells, and thus blocking the p38 and ERK pathways could be an effective therapeutic strategy against neutrophil-dominant CRS.


Assuntos
Neutrófilos/imunologia , Mucosa Respiratória/fisiologia , Rinite/metabolismo , Sinusite/metabolismo , Adulto , Idoso , Animais , Células Cultivadas , Doença Crônica , Modelos Animais de Doenças , Transição Epitelial-Mesenquimal , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Humanos , Interferon gama/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
18.
Chin Med J (Engl) ; 132(3): 253-258, 2019 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-30681490

RESUMO

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols are a series of perioperative care to optimize preoperative preparation, prevent postoperative complications, minimize stress, and speed up recovery. This study aimed to assess the impact of ERAS protocols for functional endoscopic sinus surgery (FESS) in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: One hundred and two patients with CRSwNP undergoing FESS were randomly divided into the ERAS group and the control group. The outcomes of the Self-Rating Anxiety Scale (SAS), Visual Analogue Scale (VAS), Medical Outcomes Study Sleep Scale (MOS-SS) and Kolcaba Comfort Scale Questionnaire (GCQ) were determined in both groups. The serum levels of C-reactive protein (CRP) were compared preoperatively and 24 hours postoperatively. RESULTS: The ERAS group had a significantly better SAS scores than did the control group (28 [24, 35] vs. 43 [42, 47], Z = 5.968, P < 0.001). The rhinalgia and headache scores at 2, 24 and 48 hours postoperatively were lower in the ERAS group than that in the control group (all P < 0.001). The outcomes of the MOS-SS (43 [42, 39] vs. 28 [22, 35], Z = 7.071, P < 0.001) and GCQ (76 [68, 87] vs. 64 [50, 75], Z = 4.806, P < 0.001) were significantly different between the two groups. No significant difference was found in the preoperative CRP levels between the two groups (1.3 [0.6, 2.8] vs. 0.5 [0.5, 1.2], Z = 3.049, P > 0.05); However, the CRP level in 24 hours postoperatively was significantly lower in the ERAS group than that in the control group (2.5 [1.4, 3.9] vs. 6.6 [3.8, 9.0], Z = 5.027, P < 0.001). The incidence rates of complications, such as nausea/emesis (χ = 0.343, P > 0.05), hemorrhage, aspiration and tumble, were not increased in the ERAS group compared with those in the control group. The ERAS group had a significantly shorter length of hospital stay (5 [4, 5] days vs. 8 [8,9] days, Z = 8.939, P < 0.001) and hospitalization expenses ($ 2670 [2375, 2740] vs. $3129 [3116, 3456], Z = 8.514, P < 0.001). CONCLUSIONS: ERAS protocols might optimize FESS for patients with CRSwNP by reducing psychological and physical stress, shortening the length of hospital stay and lowering hospitalization expenses without increasing postoperative complications. TRIAL REGISTRATION: Chinese Clinical Trial Registry, No. ChiCTR1800015791; http://www.chictr.org.cn/showproj.aspx?proj=26872.


Assuntos
Pólipos Nasais/cirurgia , Sinusite/cirurgia , Cirurgia Endoscópica Transanal/métodos , Adolescente , Adulto , Proteína C-Reativa/metabolismo , Doença Crônica , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/metabolismo , Assistência Perioperatória , Complicações Pós-Operatórias , Período Pós-Operatório , Sinusite/metabolismo , Inquéritos e Questionários , Adulto Jovem
19.
Med Sci Monit ; 25: 150-156, 2019 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-30612135

RESUMO

BACKGROUND Fractional exhaled nitric oxide (FeNO) participates in the local defense of the upper respiratory tract. Abnormal FeNO level is directly related to the occurrence of nasal diseases. However, the clinical value of FeNO in the upper airway is limited, which greatly impedes the diagnosis and treatment of nasal diseases. Here, we assessed the level of FeNO and evaluated the diagnostic accuracy of FeNO for chronic rhinosinusitis. MATERIAL AND METHODS We enrolled 35 patients with confirmed nasal inflammation and 30 healthy subjects from December 2016 and June 2017. The FeNO level was measured using a fractional exhaled nitric oxide detector. The level of FeNO in patients with different clinicopathological factors was compared. The diagnostic potential of FeNO for chronic rhinosinusitis was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS FeNO level was significantly lower in patients with nasal inflammation than in healthy subjects (P<0.05). For nasal inflammation diagnosis, FeNO had the highest area under the curve (AUC) at 0.760, with a sensitivity of 93.30% and a specificity of 68.60%. FeNO level was significantly downregulated in chronic rhinosinusitis patients relative to chronic rhinitis patients (P<0.05). FeNO had a good ability to discriminate between chronic rhinosinusitis patients and chronic rhinitis patients, with higher AUC, sensitivity, and specificity of 0.760, 93.30%, and 68.60%, respectively. However, FeNO levels were not significantly different between different histological types of chronic rhinosinusitis (P>0.05). CONCLUSIONS Our results show that FeNO is a useful marker for discriminating chronic rhinosinusitis, and has potential to provide valuable information in the early diagnosis of chronic rhinosinusitis.


Assuntos
Testes Respiratórios/métodos , Óxido Nítrico/análise , Sinusite/diagnóstico , Adulto , Idoso , Biomarcadores , China , Doença Crônica , Expiração , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pólipos Nasais , Curva ROC , Rinite , Sinusite/metabolismo
20.
Braz J Otorhinolaryngol ; 85(6): 760-765, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30126769

RESUMO

INTRODUCTION: Chronic rhinosinusitis with nasal polyps is a heterogeneous disease and appropriate diagnostic algorithms in individual cases are necessary for effective medical treatment. OBJECTIVE: The purpose of this study was to clarify the relationship between the pendrin expression of nasal polyps and clinical and pathological characteristic features of eosinophilic chronic rhinosinusitis. METHODS: A total of 68 patients were classified into eosinophilic chronic rhinosinusitis or non-eosinophilic chronic rhinosinusitis groups according to the degree of eosinophilic infiltration into the nasal polyps. Clinical, hematological, and immunohistochemical analyses were performed and statistically compared between both groups. RESULTS: Thirty-eight were classified into eosinophilic chronic rhinosinusitis and 30 into non-eosinophilic chronic rhinosinusitis groups. There were no significant differences in age distribution, sex ratio, prevalence of asthma, or any other complications between the groups. The mean Lund-Mackay score and the number of serum eosinophils was significantly higher in the eosinophilic chronic rhinosinusitis than in the non-eosinophilic chronic rhinosinusitis groups. The pendrin expression was more frequently detected in the epithelial surface layer of nasal polyps in the eosinophilic chronic rhinosinusitis than in the non-eosinophilic chronic rhinosinusitis groups. In addition, mucin 5AC was more widely expressed in the eosinophilic chronic rhinosinusitis than in the non-eosinophilic chronic rhinosinusitis. CONCLUSION: Increased expression of pendrin and mucin 5AC in the nasal polyps would be associated with development of eosinophilic chronic rhinosinusitis. This finding could allow the development of a novel therapeutic agent targeted specifically to patients with eosinophilic chronic rhinosinusitis.


Assuntos
Eosinófilos/metabolismo , Pólipos Nasais/metabolismo , Rinite/metabolismo , Sinusite/metabolismo , Transportadores de Sulfato/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Asma/etiologia , Doença Crônica , Citocinas/metabolismo , Eosinofilia/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro , Adulto Jovem
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