Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.506
Filtrar
1.
J Laryngol Otol ; 134(7): 632-635, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32686637

RESUMO

BACKGROUND: Invasive fungal rhinosinusitis is associated with high morbidity and mortality. Rapid pathogen identification is mandatory, but fresh tissue is not always available. A polymerase chain reaction method was designed in order to detect fungi in formalin-fixed paraffin-embedded samples. This was applied to a retrospective series of tissue biopsies from Thai patients with invasive fungal rhinosinusitis. METHODS: Tissue blocks from 64 cases yielded adequate DNA. Three sequential polymerase chain reaction were performed: ZP3 (housekeeping gene) and panfungal polymerase chain reactions, and a differentiating polymerase chain reaction based on the 5.8s ribosomal RNA and internal transcribed spacer 2 regions. The polymerase chain reaction products were then sequenced. RESULTS: Polymerase chain reaction identified a fungal pathogen in 20 of 64 cases (31 per cent). Aspergillus species was the most common cause of invasive fungal rhinosinusitis (nine cases). Other causes included candida (n = 4), cladosporium (n = 4), mucor (n = 1), alternaria (n = 1) and dendryphiella (n = 1) species. CONCLUSION: Polymerase chain reaction can provide rapid identification of fungal pathogens in paraffin-embedded tissue, enabling prompt treatment of invasive fungal rhinosinusitis.


Assuntos
Micoses/microbiologia , Reação em Cadeia da Polimerase/métodos , Rinite/microbiologia , Sinusite/microbiologia , Aspergillus/genética , Biópsia , Candida/genética , Criança , Pré-Escolar , Cladosporium/genética , DNA Fúngico/genética , Humanos , Lactente , Inclusão em Parafina , RNA Ribossômico 5,8S/genética , Estudos Retrospectivos , Rinite/patologia , Sinusite/patologia
2.
Artigo em Chinês | MEDLINE | ID: mdl-32610404

RESUMO

Objective: To investigate the expression and cellular provenance of interleukin 17A (IL-17A) in non-eosinophilic chronic rhinosinusitis with nasal polyps (nECRSwNP), and to analyze the possible reasons for its different expression. Methods: Samples were collected from 14 patients with eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) and 28 patients with nECRSwNP, who underwent functional endoscopic sinus surgery in the Third Affiliated Hospital of Sun Yat-sen University from January 2017 to May 2018, including 33 males and 9 females, with the age ranging from 18 to 65 years old. Enzyme linked immune sorbent assay (ELISA) and flow cytometry were used to investigate the expression and cellular origins of IL-17A in the nasal tissue of ECRSwNP and nECRSwNP groups. Then the difference of quantity and differentiation ability of the major cells producing IL-17A between ECRSwNP and nECRSwNP groups were analyzed by flow cytometry. Finally, the expressions of IL-6, transforming growth factor-ß(TGF-ß), and IL-23, which were considered as the important factors in promoting Th17/Tc17 differentiation in CRSwNP and their correlation with IL-17A, were analyzed by ELISA. Statistical analysis was performed using IBM SPSS 20. Results: The IL-17A protein levels and IL-17A(+)lymphocyte percentages were higher in nECRSwNP group compared with that of the ECRSwNP group (158.56 (167.76) pg/ml (M(QR)) vs. 9.42 (11.33) pg/ml, 10.21%±1.54% (x±s) vs. 3.93%±0.80%, Z=2.95, t=3.62, all P<0.01). Tc17 cells (CD8(+)T cells producing IL-17A) and Th17 cells (CD4(+)T cells producing IL-17A) were major IL-17A producers in both ECRSwNP and nECRSwNP group. Further analysis revealed that there was no significant difference in quantity of CD8(+)and CD4(+)T cells between ECRSwNP and nECRSwNP group, but the differentiation ability about CD8(+)and CD4(+)T cells differentiating into Tc17 and Th17 in nECRSwNP group was stronger than that in ECRSwNP. The high expressions of IL-6 and TGF-ß, which were considered as the important factors in promoting Th17/Tc17 differentiation were also found in nECRSwNP group compared with ECRSwNP (56.07 (234.25) pg/ml vs. 8.27 (12.51) pg/ml, (5.44±0.34) pg/ml vs. (4.17±0.22) pg/ml, Z=2.426, t=2.29, all P<0.05). But the difference in expression of IL-23 was not significant difference between the two groups. Moreover, the expression of IL-17A showed significantly positive correlation with IL-6 (r=0.615, P=0.009). No positive correlation between IL-17A and TGF-ß or IL-23 was observed. Conclusions: The expression of IL-17A in nasal mucosa of nECRSwNP patients is significantly higher than that of ECRSwNP, which is due to the increase of expression and differentiation of Tc17/Th17 cells. IL-17A shows positive correlation with IL-6 in CRSwNP, which is the important factor in promoting Th17/Tc17 differentiation.


Assuntos
Interleucina-17 , Pólipos Nasais , Rinite , Sinusite , Adolescente , Adulto , Idoso , Doença Crônica , Feminino , Humanos , Interleucina-17/metabolismo , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/patologia , Pólipos Nasais/metabolismo , Pólipos Nasais/patologia , Rinite/metabolismo , Rinite/patologia , Sinusite/metabolismo , Sinusite/patologia , Adulto Jovem
3.
PLoS One ; 15(6): e0234731, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32544181

RESUMO

Airborne fungi are associated with upper and lower airway inflammatory diseases. Alternaria is commonly found in nasal secretions and induces the production of chemical mediators from sinonasal mucosa. This study aimed to establish an Alternaria-induced chronic rhinosinusitis (CRS) mouse model and determine the influence of host allergic background on the immunopathological characteristics of CRS. BALB/c mice were used for establishing the CRS model. Alternaria was intranasally instilled for 8 or 16 weeks with or without ovalbumin (OVA) presensitization. Total serum IgE and Alternaria-specific IgE levels were measured by enzyme-linked immunosorbent assay (ELISA). Interleukin (IL)-4, IL-10, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α levels in nasal lavage fluid (NLF) and splenocytes were measured by ELISA and their mRNAs and levels of associated transcription factors in sinonasal mucosa were determined with quantitative reverse-transcriptase polymerase chain reaction (RT-PCR). Hematoxylin-eosin staining and periodic acid-Schiff staining were performed to evaluate histological changes. Total serum IgE was increased in both allergic and non-allergic CRS. IL-4 was strongly expressed in NLF in both allergic and non-allergic CRS at 16 weeks and not only eosinophils but also neutrophils were increased in NLF of non-allergic CRS mice. The levels of Th1, Th2, and Treg cytokines and transcription factor mRNAs were significantly increased in sinonasal mucosa of non-allergic CRS mice. Both inflammatory cell infiltration and goblet cell hyperplasia were increased in CRS mice. Repeated intranasal instillation of Alternaria results in sinonasal inflammation with inflammatory cell infiltration. The sinonasal mucosal immune responses against Alternaria were shown to differ depending on the host allergic background.


Assuntos
Alternaria/patogenicidade , Rinite/patologia , Sinusite/patologia , Alternaria/imunologia , Animais , Doença Crônica , Modelos Animais de Doenças , Feminino , Imunoglobulina E/sangue , Interleucina-10/análise , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-4/análise , Interleucina-4/genética , Interleucina-4/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Líquido da Lavagem Nasal/química , Mucosa Nasal/metabolismo , Mucosa Nasal/patologia , RNA Mensageiro/metabolismo , Rinite/imunologia , Sinusite/imunologia , Baço/metabolismo , Baço/microbiologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
4.
Hum Genet ; 139(10): 1273-1283, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32367404

RESUMO

Unlike disorders of primary cilium, primary ciliary dyskinesia (PCD) has a much narrower clinical spectrum consistent with the limited tissue distribution of motile cilia. Nonetheless, PCD diagnosis can be challenging due to the overlapping features with other disorders and the requirement for sophisticated tests that are only available in specialized centers. We performed exome sequencing on all patients with a clinical suspicion of PCD but for whom no nasal nitric oxide test or ciliary functional assessment could be ordered. Among 81 patients (56 families), in whom PCD was suspected, 68% had pathogenic or likely pathogenic variants in established PCD-related genes that fully explain the phenotype (20 variants in 11 genes). The major clinical presentations were sinopulmonary infections (SPI) (n = 58), neonatal respiratory distress (NRD) (n = 2), laterality defect (LD) (n = 6), and combined LD/SPI (n = 15). Biallelic likely deleterious variants were also encountered in AKNA and GOLGA3, which we propose as novel candidates in a lung phenotype that overlaps clinically with PCD. We also encountered a PCD phenocopy caused by a pathogenic variant in ITCH, and a pathogenic variant in CEP164 causing Bardet-Biedl syndrome and PCD presentation as a very rare example of the dual presentation of these two disorders of the primary and motile cilia. Exome sequencing is a powerful tool that can help "democratize" the diagnosis of PCD, which is currently limited to highly specialized centers.


Assuntos
Cílios/metabolismo , Transtornos da Motilidade Ciliar/genética , Predisposição Genética para Doença , Pneumonia/genética , Síndrome do Desconforto Respiratório do Recém-Nascido/genética , Sinusite/genética , Autoantígenos/genética , Cílios/patologia , Transtornos da Motilidade Ciliar/complicações , Transtornos da Motilidade Ciliar/diagnóstico , Transtornos da Motilidade Ciliar/patologia , Consanguinidade , Proteínas de Ligação a DNA/genética , Feminino , Expressão Gênica , Proteínas da Matriz do Complexo de Golgi/genética , Humanos , Masculino , Proteínas dos Microtúbulos/genética , Mutação , Proteínas Nucleares/genética , Linhagem , Fenótipo , Pneumonia/complicações , Pneumonia/diagnóstico , Pneumonia/patologia , Proteínas Repressoras/genética , Síndrome do Desconforto Respiratório do Recém-Nascido/complicações , Síndrome do Desconforto Respiratório do Recém-Nascido/diagnóstico , Síndrome do Desconforto Respiratório do Recém-Nascido/patologia , Mucosa Respiratória/metabolismo , Mucosa Respiratória/patologia , Arábia Saudita , Sinusite/complicações , Sinusite/diagnóstico , Sinusite/patologia , Fatores de Transcrição/genética , Ubiquitina-Proteína Ligases/genética , Sequenciamento Completo do Exoma
5.
Ann Allergy Asthma Immunol ; 125(3): 304-310.e1, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32387168

RESUMO

BACKGROUND: Predicting postoperative olfactory decline in patients with chronic rhinosinusitis (CRS) remains a considerable challenge. OBJECTIVE: To evaluate patterns of postoperative olfactory function in patients with CRS and explore potential predictors of postoperative olfactory decline. METHODS: A total of 76 patients with CRS electing endoscopic sinus surgery (ESS) were enrolled in this prospective study. Olfaction was assessed with Sniffin' Sticks preoperatively and 3 months postoperatively. Preoperative peripheral venous blood and superior turbinate at surgery were collected for eosinophil quantification. Olfactory cleft was evaluated by computed tomography and endoscopy. Postoperative olfactory decline was defined by a decrease in threshold-discrimination-identification (TDI) score more than 0 point. Multivariable logistic regression analysis was conducted to identify potential predictors associated with postoperative olfactory decline in TDI score. RESULTS: A total of 30.26% of patients with CRS (23/76) presented with olfactory decline 3 months post-ESS. Patients with CRS with olfactory decline showed significantly higher preoperative tissue eosinophils (P < .001), blood eosinophil count (P = .002), blood eosinophil percentage (P = .009), and preoperative TDI scores (P = .017) than patients with CRS without olfactory decline. After adjusting for patient demographics and comorbidities, the preoperative tissue eosinophilia was significantly associated with patients with CRS with postoperative olfactory decline (odds ratio = 1.103; P = .038). An absolute count of 23.5 eosinophils per high-power field in superior turbinate was the best predictor of olfactory decline with the highest area under the receiver operating characteristic curve of 0.901. CONCLUSION: Superior turbinate eosinophilia is highly associated with olfactory decline in patients with CRS 3 months after ESS.


Assuntos
Eosinofilia/etiologia , Transtornos do Olfato/etiologia , Complicações Cognitivas Pós-Operatórias/etiologia , Rinite/etiologia , Sinusite/complicações , Conchas Nasais/patologia , Doença Crônica , Endoscopia/métodos , Eosinofilia/patologia , Eosinófilos/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/patologia , Transtornos do Olfato/patologia , Complicações Cognitivas Pós-Operatórias/patologia , Período Pré-Operatório , Rinite/patologia , Sinusite/patologia , Sinusite/cirurgia , Olfato/fisiologia
6.
Ann Allergy Asthma Immunol ; 124(4): 333-341, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32007569

RESUMO

OBJECTIVE: To review the latest discoveries on airway epithelial cell diversity and remodeling in type 2 inflammation, including nasal polyposis. DATA SOURCES: Reviews and primary research manuscripts were identified from PubMed, Google, and Bioarchives, using the search words airway epithelium, nasal polyposis, or chronic rhinosinusitis with nasal polyposis AND basal cell, ciliated cell, secretory cell, goblet cell, neuroendocrine cell, pulmonary neuroendocrine cell, ionocyte, brush cell, solitary chemosensory cell, microvillus cell, or tuft cell. STUDY SELECTIONS: Studies were selected based on novelty and likely relevance to airway epithelial innate immune functions or the pathobiology of type 2 inflammation. RESULTS: Airway epithelial cells are more diverse than previously appreciated, with specialized subsets, including ionocytes, solitary chemosensory cells, and neuroendocrine cells that contribute to important innate immune functions. In chronic rhinosinusitis with nasal polyposis, the composition of the epithelium is significantly altered. Loss of ciliated cells and submucosal glands and an increase in basal airway epithelial progenitors leads to loss of innate immune functions and an expansion of proinflammatory potential. Type 2 cytokines play a major role in driving this process. CONCLUSION: Airway epithelial remodeling in chronic rhinosinusitis is extensive, leading to loss of innate immune function and enhanced proinflammatory potential. The mechanisms driving airway remodeling and its sequelae deserve further attention before restitution of epithelial differentiation can be considered a reasonable therapeutic target.


Assuntos
Remodelação das Vias Aéreas , Mucosa Nasal/patologia , Pólipos Nasais/patologia , Rinite/patologia , Sinusite/patologia , Doença Crônica , Humanos , Inflamação/imunologia , Inflamação/patologia , Mucosa Nasal/imunologia , Pólipos Nasais/imunologia , Rinite/imunologia , Sinusite/imunologia
7.
J Allergy Clin Immunol ; 145(2): 550-562, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32035607

RESUMO

BACKGROUND: Airway eosinophilia is a prominent feature of asthma and chronic rhinosinusitis (CRS), and the endothelium plays a key role in eosinophil trafficking. To date, microRNA-1 (miR-1) is the only microRNA known to be regulated in the lung endothelium in asthma models. OBJECTIVE: We sought to determine the role of endothelial miR-1 in allergic airway inflammation. METHODS: We measured microRNA and mRNA expression using quantitative RT-PCR. We used ovalbumin and house dust mite models of asthma. Endothelium-specific overexpression of miR-1 was achieved through lentiviral vector delivery or induction of a transgene. Tissue eosinophilia was quantified by using Congo red and anti-eosinophil peroxidase staining. We measured eosinophil binding with a Sykes-Moore adhesion chamber. Target recruitment to RNA-induced silencing complex was assessed by using anti-Argonaute2 RNA immunoprecipitation. Surface P-selectin levels were measured by using flow cytometry. RESULTS: Serum miR-1 levels had inverse correlations with sputum eosinophilia, airway obstruction, and number of hospitalizations in asthmatic patients and sinonasal tissue eosinophilia in patients with CRS. IL-13 stimulation decreased miR-1 levels in human lung endothelium. Endothelium-specific overexpression of miR-1 reduced airway eosinophilia and asthma phenotypes in murine models and inhibited IL-13-induced eosinophil binding to endothelial cells. miR-1 recruited P-selectin, thymic stromal lymphopoietin, eotaxin-3, and thrombopoietin receptor to the RNA-induced silencing complex; downregulated these genes in the lung endothelium; and reduced surface P-selectin levels in IL-13-stimulated endothelial cells. In our asthma and CRS cohorts, miR-1 levels correlated inversely with its target genes. CONCLUSION: Endothelial miR-1 regulates eosinophil trafficking in the setting of allergic airway inflammation. miR-1 has therapeutic potential in asthmatic patients and patients with CRS.


Assuntos
Asma/imunologia , Quimiotaxia de Leucócito/imunologia , MicroRNAs/imunologia , MicroRNAs/metabolismo , Rinite Alérgica Perene/imunologia , Sinusite/imunologia , Animais , Asma/metabolismo , Asma/patologia , Células Endoteliais/metabolismo , Eosinófilos , Humanos , Camundongos , Eosinofilia Pulmonar/imunologia , Eosinofilia Pulmonar/metabolismo , Eosinofilia Pulmonar/patologia , Rinite Alérgica Perene/metabolismo , Rinite Alérgica Perene/patologia , Sinusite/metabolismo , Sinusite/patologia
8.
J Leukoc Biol ; 107(5): 749-762, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32108379

RESUMO

This review focuses on recent developments related to asthma, chronic rhinosinusitis, atopic dermatitis (AD), eosinophilic esophagitis, and inflammatory bowel diseases (IBD), with a particular focus on tight junctions (TJs) and their role in the pathogenetic mechanisms of these diseases. Lung, skin, and intestinal surfaces are lined by epithelial cells that interact with environmental factors and immune cells. Therefore, together with the cellular immune system, the epithelium performs a pivotal role as the first line physical barrier against external antigens. Paracellular space is almost exclusively sealed by TJs and is maintained by complex protein-protein interactions. Thus, TJ dysfunction increases paracellular permeability, resulting in enhanced flux across TJs. Epithelial TJ dysfunction also causes immune cell activation and contributes to the pathogenesis of chronic lung, skin, and intestinal inflammation. Characterization of TJ protein alteration is one of the key factors for enhancing our understanding of allergic diseases as well as IBDs. Furthermore, TJ-based epithelial disturbance can promote immune cell behaviors, such as those in dendritic cells, Th2 cells, Th17 cells, and innate lymphoid cells (ILCs), thereby offering new insights into TJ-based targets. The purpose of this review is to illustrate how TJ dysfunction can lead to the disruption of the immune homeostasis in barrier tissues and subsequent inflammation. This review also highlights the various TJ barrier dysfunctions across different organ sites, which would help to develop future drugs to target allergic diseases and IBD.


Assuntos
Inflamação/imunologia , Junções Íntimas/imunologia , Junções Íntimas/patologia , Animais , Asma/imunologia , Asma/patologia , Doença Crônica , Dermatite Atópica/imunologia , Dermatite Atópica/patologia , Esofagite Eosinofílica/imunologia , Esofagite Eosinofílica/patologia , Humanos , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/patologia , Permeabilidade , Rinite/imunologia , Rinite/patologia , Sinusite/imunologia , Sinusite/patologia
9.
Eur J Histochem ; 64(1)2020 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-31988531

RESUMO

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a persistent sinonasal mucosa inflammatory disease with still unclear pathophysiologic mechanisms that imply events of tissue repair and structural remodelling. Several cascades seem to have a considerable role in the onset and progression of mucosa hyperproliferation in nasal polyps including transforming growth factor ß/Small mother against decapentaplegic (TGFß/Smads), mitogenactivated protein kinases (MAPKs), advanced glycosylation end-products (AGEs) together with epithelial-tomesenchymal transition (EMT). Since many inflammatory mediators are reported to play important roles in the development of nasal polyps (NP) disease, this study aimed to analyse the correlation between the AGEs/receptor of advanced glycosylation end-products (RAGE)/extracellular signal-regulated kinase (ERK) signalling pathway and the main markers of EMT to better understand the influence that they exert on the remodelling of nasal mucous membranes in patients affected by CRSwNP vs normal controls. A total of 30 patients were enrolled in this study. Immunohistochemical analysis, using AGE, RAGE, p-ERK, MMP-3, TGF-ß1, Smad2/3, Collagen I-III, α-SMA, E-cadherin, IL-6 and Vimentin antibodies, was performed. AGE, RAGE, ERK, p-ERK and MMP3 were also evaluated using western blot analysis. We observed an overexpression of the AGE/RAGE/p-ERK and the main mesenchymal markers of EMT (Vimentin and IL-6) in CRSwNP vs controls whereas the TGF-ß/Smad3 pathway did not show any significant differences between the two groups of patients. These observations suggest a complex network of processes in the pathogenesis of NP, and the AGE/RAGE/ERK pathway and EMT might work together in promoting tissue remodelling in the formation of CRSwNP.


Assuntos
Transição Epitelial-Mesenquimal/fisiologia , Sistema de Sinalização das MAP Quinases/fisiologia , Pólipos Nasais/etiologia , Sinusite/etiologia , Adulto , Doença Crônica , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Imuno-Histoquímica , Interleucina-6/metabolismo , Masculino , Mucosa Nasal/patologia , Pólipos Nasais/patologia , Pólipos Nasais/fisiopatologia , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Sinusite/patologia , Sinusite/fisiopatologia , Vimentina/metabolismo
10.
Ann Allergy Asthma Immunol ; 124(4): 326-332, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31830587

RESUMO

OBJECTIVE: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common and heterogeneous inflammatory condition, for which the drivers of the underlying inflammation are not yet fully understood. The use of biologic therapies to target specifically relevant effector cells or cytokines in CRSwNP is a growing field of interest. The objectives of this review are to provide an update on the existing studies of biologics in CRSwNP and to identify potential future areas for further research. DATA SOURCES: An initial literature review of biologic therapies in CRS was performed through publications gathered from a PubMed search for title/abstract containing "biologic" and "chronic rhinosinusitis." Further manuscripts describing scientific premise for each biologic were then reviewed. STUDY SELECTIONS: A detailed review of all studies describing biologic therapies targeting inflammation in CRSwNP was performed. RESULTS: Biologic therapies targeting interleukin (IL)-4Rα, IL-5, IL-5Rα, IL-33, immunoglobulin (Ig)E, and thymic stromal lymphopoietin (TSLP) have all been developed and have been investigated for treatment in CRSwNP, or current research suggests that they may have utility in this area. Only dupilumab, which inhibits IL-4Rα, has gained Food and Drug Administration approval for the treatment of adults with inadequately controlled CRSwNP. CONCLUSION: Recent advances in our understanding of the fundamental drivers of the chronic respiratory inflammation in CRSwNP has led to the identification of several potential therapeutic targets for this disease. Future clinical success will rely on the availability of biomarker-based endotyping and responder analyses so that clinicians can precisely match each patient to the appropriate biologic, thereby optimizing the proper treatment strategy.


Assuntos
Produtos Biológicos/uso terapêutico , Pólipos Nasais/tratamento farmacológico , Rinite/tratamento farmacológico , Sinusite/tratamento farmacológico , Doença Crônica , Humanos , Pólipos Nasais/patologia , Rinite/patologia , Sinusite/patologia
14.
J Ethnopharmacol ; 248: 112262, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31585162

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia ordosica Krasch. (AOK) has been used for rheumatic arthritis, cold headache, sore throat, etc. in traditional Chinese/Mongolian medicine and is used for nasosinusitis by local Mongolian "barefoot" doctors. Up to now, their mechanisms are still unclear. AIM: To evaluate the in vivo anti-inflammatory and allergic rhinitis (AR) alleviating effect as well as in vitro antimicrobial activities of AOK extracts to verify its ethno-medicinal claims. MATERIALS AND METHODS: Crude extracts (methanol/95%-ethanol/ethyl acetate) of AOK root/stem/leaf and fractions (petroleum ether/ethyl acetate/n-butanol/aqueous) of AOK root extract were prepared. Xylene-induced ear swelling model in mouse and ovalbumin (OVA)-induced AR model in guinea pig were established. Ear swelling degrees of mice were measured. The numbers of rubbing movement and sneezes of guinea pigs were counted to evaluate the symptoms of AR. The serum levels of histamine, INF-γ, IL-2/4/10, and VCAM-1 were measured by ELISA assay. The histological changes of nasal mucosa were investigated by light microscope after H&E staining. Antimicrobial activities of AOK extracts were also tested. LC-MS/MS analysis was performed to characterize the constituents of active extract and molecular docking was conducted to predict the biological mechanism. RESULTS: In ear-swelling model, extract (100.00 mg/kg) from the ethyl acetate layer of 95% ethanol (100.00 mg/kg) showed better swelling inhibition in mice than positive control (dexamethasone, 191.91 mg/kg). In AR model, extract from the ethyl acetate layer of 95% ethanol significantly alleviated the AR symptoms in guinea pigs, decreased the serum levels of histamine, INF-γ, IL-2/4/10, and VCAM-1, and reduced the infiltration of eosinophil in nasal mucosa. For Staphylococcus aureus, the ethyl acetate extract of AOK stem showed the highest inhibition (MIC=1.25 mg/mL), for Escherichia coli, n-butanol layer of 95% ethanol extract of AOK root showed the highest inhibition (MIC=15.00 mg/mL), for Candida glabrata, 95%-ethyl acetate extract of AOK leaf showed the best inhibition (MIC=0.064 mg/mL), while ethyl acetate and n-butanol layers showed similar inhibition on MRSA (MIC=7.50 mg/mL). LC-MS/MS characterization showed that dicaffeoylquinic acids account for more than 30% of ethyl acetate layer of AOK extract. Dicaffeoylquinic acids bind with histamine-1 receptor with high affinities and interesting modes. CONCLUSIONS: Extracts from AOK had interesting anti-inflammatory activity in mice, alleviating effect against OVA-induced AR in guinea pigs, and antimicrobial activities in vitro, which support the ethno-medicinal use of it. The main constituents in ethyl acetate layer of AOK root extract are dicaffeoylquinic acids and could bind with histamine-1 receptor well. These findings highlighted the importance of natural product chemistry study of AOK.


Assuntos
Antialérgicos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Artemisia , Extratos Vegetais/uso terapêutico , Rinite Alérgica/tratamento farmacológico , Sinusite/tratamento farmacológico , Alérgenos , Animais , Antialérgicos/farmacologia , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/farmacologia , Candida glabrata/efeitos dos fármacos , Candida glabrata/crescimento & desenvolvimento , Citocinas/imunologia , Edema/induzido quimicamente , Edema/tratamento farmacológico , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Cobaias , Masculino , Medicina Tradicional Chinesa , Medicina Tradicional da Mongólia , Camundongos , Simulação de Acoplamento Molecular , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/patologia , Ovalbumina , Extratos Vegetais/farmacologia , Receptores Histamínicos H1/metabolismo , Rinite Alérgica/imunologia , Rinite Alérgica/patologia , Sinusite/imunologia , Sinusite/patologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Xilenos
15.
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
16.
Int J Med Sci ; 16(12): 1631-1641, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31839751

RESUMO

Epithelial-mesenchymal transition (EMT) has been reported to occur in eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP). Among the cytokines that cause EMT, high mobility group box 1 (HMGB1) has been shown to give rise to EMT in airway epithelial cells. However, the mechanism of HMGB1-induced EMT in ECRSwNP is unknown. We explored the mechanism and possible inhibitor. Immunohistochemistry (IHC), immunofluorescence (IF), and western blot assay were used to detect the expression and location of HMGB1, peroxisome proliferator-activated receptor-γ (PPAR-γ), and EMT markers in eighteen ECRSwNP and twelve normal nasal mucosa tissues. Epithelial cells isolated from ECRSwNP were cultured with various doses of recombinant human HMGB1 (rhHMGB1) to study the expression of PPAR-γ, and EMT markers. Additionally, the ligand of PPAR-γ was incubated with epithelial cells to interfere with the effects of lipopolysaccharide (LPS) or rhHMGB1 to explore the effect on expression of HMGB1 and EMT markers. These results suggest that HMGB1 was highly expressed in ECRSwNP compared with its expression in control tissues, and EMT was also found highly in ECRSwNP compared with control tissues. Moreover, the cytoplasmic accumulation of HMGB1 in ECRSwNP was obvious compared with normal tissues. We also found dose-dependent induction by rhHMGB1 of up-regulation of N-cadherin and vimentin and down-regulation of ZO-1 and E-cadherin in epithelial cells isolated from ECRSwNP. The agonist of PPAR-γ not only reduced release of HMGB1 induced by LPS, but also reversed the EMT. The protective role of PPAR-γ also appeared in cells that had been incubated with rhHMGB1. In the current study, we discovered that the agonist of PPAR-γ has a potential role in inhibited HMGB1-induced EMT in ECRSwNP. The agonist of PPAR-γ may contribute to inhabit epithelial cells to become mesenchymal-like cells which play an important role in the pathogenesis of ECRSwNP.


Assuntos
Proteína HMGB1/genética , Pólipos Nasais/genética , PPAR gama/genética , Rinite/genética , Sinusite/genética , Caderinas/genética , Células Epiteliais/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Proteína HMGB1/farmacologia , Humanos , Ligantes , NF-kappa B/genética , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/patologia , Pólipos Nasais/complicações , PPAR gama/antagonistas & inibidores , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacologia , Rinite/complicações , Rinite/patologia , Transdução de Sinais/efeitos dos fármacos , Sinusite/complicações , Sinusite/patologia , Vimentina/genética , Proteína da Zônula de Oclusão-1/genética
18.
Otolaryngol Pol ; 73(5): 1-4, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31701902

RESUMO

CRS is a process involving a number of adverse changes in the mucosa of the paranasal sinuses and nasal polyps, e.g. increased fibroblast proliferation, angiogenesis, increased formation of fibrous tissue (subepithelial fibrosis) and tissue destruction. There are biomarkers whose levels can be increased in chronic inflammation of the paranasal sinuses: peripheral blood eosinophilia, IgE immunoglobulin, cytokines - IL-4, IL-5, IL-13, IL-25, IL-33, periostin, P-glycoprotein, CXCL-12, CXCL-13, INF-Υ, TNFα, TGFß1, albumins, eotaxin. These biomarkers are not pathognomonic for CRS. The concentration of biomarkers is also increased in bronchial asthma and atopic dermatitis. The TGFß, in particular, the ß1 subunit, was identified as the main factor involved in the remodeling of tissue stroma. In conjunction with the continuous improvement of tissue testing methods, it is advisable to search for new factors that will more accurately allow the assessment of tissue remodeling in the chronic processes of paranasal sinuses.


Assuntos
Epitélio/patologia , Mediadores da Inflamação/análise , Mucosa Nasal/imunologia , Rinite/imunologia , Sinusite/imunologia , Biomarcadores/análise , Fibrose/patologia , Humanos , Mucosa Nasal/patologia , Rinite/patologia , Sinusite/patologia
20.
Biomed Res Int ; 2019: 7150942, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534961

RESUMO

To date, topical therapies guarantee a better delivery of high concentrations of pharmacologic agents to the mucosa of the upper airways (UA). Recently, topical administration of ectoine has just been recognized as adjuvant treatment in the Allergic Rhinitis (AR) and Rhinosinusitis (ARS). The aim of this work is to review the published literature regarding all the potential therapeutic effects of ectoine in the acute and chronic inflammatory diseases of UA. Pertinent studies published without temporal limitation were selected searching on MEDLINE the following terms: "ectoine" and "nasal spray," "oral spray," "upper respiratory tract infections," "rhinosinusitis," "rhinitis," "rhinoconjunctivitis," "pharyngitis," and "laryngitis." At the end of our selection process, six relevant publications were included: two studies about the effect of ectoine on AR, one study about ARS, one study about rhinitis sicca anterior, and two studies about acute pharyngitis and/or laryngitis. Due to its moisturizing and anti-inflammatory properties, topical administration of ectoine could play a potential additional role in treatment of acute and chronic inflammatory diseases of UA, in particular in the management of sinonasal conditions improving symptoms and endoscopic findings. However, these results should be viewed cautiously as they are based on a limited number of studies; some of them were probably underpowered because of their small patient samples.


Assuntos
Diamino Aminoácidos/uso terapêutico , Infecções Respiratórias/tratamento farmacológico , Doença Aguda , Administração Tópica , Doença Crônica , Humanos , Inflamação/tratamento farmacológico , Inflamação/patologia , Laringite/tratamento farmacológico , Laringite/patologia , Sprays Orais , Infecções Respiratórias/patologia , Rinite/tratamento farmacológico , Rinite/patologia , Sinusite/tratamento farmacológico , Sinusite/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA