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1.
Int Forum Allergy Rhinol ; 9(11): 1297-1303, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31513736

RESUMO

BACKGROUND: Grass pollen is the most prevalent sensitizing aeroallergen to cause respiratory allergies in northern China. Air pollutants have a substantial effect on respiratory health and some pollens. This study aimed to investigate relationships among airborne grass pollen, air pollutants and allergic diseases, in order to determine their effects on patients with grass pollen allergies in Beijing, China, during the period from 2013 to 2016. METHODS: Data regarding autumnal grass pollens and air pollutants measured in Beijing from 2012 to 2016 were obtained from local governmental agencies. Patient data regarding specific immunoglobulin E (IgE) analyses from 2013 to 2016 were obtained from the Department of Allergy in Beijing Tongren Hospital. Spearman's rank correlation analysis was used to assess associations between the daily number of grass pollen allergen-positive patients and the following parameters: 3 clinically-relevant grass pollen genera (Artemisia, Humulus, and Chenopodium) and inhalable pollutants. RESULTS: Correlation analysis indicated that the daily number of grass pollen-positive patients was significantly associated with the peak period of grass pollens, as well as pollutants SO2 and NOx. Moreover, concentrations of air pollutants (eg, ozone, oxides of nitrogen [NOx ], and SO2 ) were consistently and significantly associated with concentrations of grass pollens; particulate matter 2.5 µm in diameter was negatively associated with Artemisia and Chenopodium pollens. CONCLUSION: Grass pollens exhibited substantial impact on allergic disease morbidity. Air pollutants impacted allergic disease and grass pollen. Thus, public health and clinical approaches to anticipate and reduce allergic disease morbidity from pollen and pollutants are needed.


Assuntos
Poluentes Atmosféricos/análise , Material Particulado/análise , Pólen/imunologia , Hipersensibilidade Respiratória/epidemiologia , Rinite Alérgica Sazonal/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Poluentes Atmosféricos/efeitos adversos , Alérgenos/imunologia , Artemisia , Chenopodium , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Humulus , Imunoglobulina E/sangue , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Hipersensibilidade Respiratória/diagnóstico , Rinite Alérgica Sazonal/diagnóstico , Adulto Jovem
2.
Int Forum Allergy Rhinol ; 8(11): 1342-1348, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30238647

RESUMO

BACKGROUND: The traditional method of evaluating bone remodeling in chronic rhinosinusitis is to measure bone thickness. The objective of this study was to determine the feasibility of measuring the computed tomography (CT) value in Hounsfield units (HU) as an method and explore whether it is superior to measuring bone thickness. METHODS: The study was a prospective animal trial. Twenty normal rabbits were included in the control group, and 60 rabbit models were inoculated with Staphylococcus aureus to induce rhinosinusitis. The rabbit models were divided into 3 groups according to the time of infection. All animals were euthanized after the CT exam. The samples were scored based on mucus and bone changes. The rabbits were divided into negative and positive groups according to whether bone remodeling was observed. We obtained diagnostic threshold values by measuring the bone thickness and HU of each rabbit's maxillary sinus and compared the values obtained using the 2 methods by calculating the area under the receiver operating characteristic curve (AUC). RESULTS: The AUC for the measured bone thickness was 0.838, the diagnostic threshold was 1.165 mm. The AUC for the measured HU value was 0.937, the diagnostic threshold was 904.5. The correlation coefficients were r1 = 0.645 for the measured bone thickness and r2 = 0.797 for the HU measurement (r2 > r1 ; p < 0.01). CONCLUSION: Evaluating bone remodeling is feasible by measuring either the bone wall thickness or the CT value. However, using CT to evaluate the sinus bones in rabbits with rhinosinusitis appears to be a more valuable option.


Assuntos
Remodelação Óssea , Rinite/patologia , Sinusite/patologia , Animais , Doença Crônica , Modelos Animais de Doenças , Feminino , Masculino , Cavidade Nasal/diagnóstico por imagem , Cavidade Nasal/patologia , Mucosa Nasal/patologia , Seios Paranasais/diagnóstico por imagem , Seios Paranasais/patologia , Coelhos , Rinite/diagnóstico por imagem , Rinite/etiologia , Sinusite/diagnóstico por imagem , Sinusite/etiologia , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/diagnóstico por imagem , Infecções Estafilocócicas/patologia , Tomografia Computadorizada por Raios X
3.
Sci Rep ; 8(1): 6326, 2018 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-29679058

RESUMO

Particulate matter (PM) air pollution has been associated with an increase in the incidence of chronic allergic diseases; however, the mechanisms underlying the effect of exposure to natural ambient air pollution in chronic allergic diseases have not been fully elucidated. In the present study, we aimed to investigate the cellular responses induced by exposure to natural ambient air pollution, employing a mouse model of chronic allergy. The results indicated that exposure to ambient air pollution significantly increased the number of eosinophils in the nasal mucosa. The modulation of gene expression profile identified a set of regulated genes, and the Triggering Receptor Expressed on Myeloid cells1(TREM1) signaling canonical pathway was increased after exposure to ambient air pollution. In vitro, PM2.5 increased Nucleotide-binding oligomerization domain-containing protein 1 (Nod1) and nuclear factor (NF)-κB signaling pathway activation in A549 and HEK293 cell cultures. These results suggest a novel mechanism by which, PM2.5 in ambient air pollution may stimulate the innate immune system through the PM2.5-Nod1-NF-κB axis in chronic allergic disease.


Assuntos
Hipersensibilidade/genética , Material Particulado/efeitos adversos , Células A549 , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Animais , Exposição Ambiental/análise , Monitoramento Ambiental/métodos , Eosinófilos/metabolismo , Feminino , Células HEK293 , Humanos , Hipersensibilidade/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Mucosa Nasal/metabolismo , Proteína Adaptadora de Sinalização NOD1/genética , Proteína Adaptadora de Sinalização NOD1/metabolismo , Material Particulado/análise , Transcriptoma/genética , Receptor Gatilho 1 Expresso em Células Mieloides/genética , Receptor Gatilho 1 Expresso em Células Mieloides/metabolismo
5.
Sci Rep ; 7(1): 10006, 2017 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-28855645

RESUMO

Meteorological factors have been shown to affect the physiology, distribution, and amounts of inhaled allergens. The aim of this study was to develop a model to predict the trends for onset of allergic rhinitis (AR) patients. A total of 10,914 consecutive AR outpatients were assessed for the number of daily patient visits over a period of 4 years. Meteorological data were used to assess the relationship between meteorological factors and AR incidence by time-series data and regression analysis. Predictive models for incidence of AR were established in pollen-, dust mite- and mould-sensitive groups of patients, and the predictive performances of meteorological factors on the incidence of AR were estimated using root mean squared errors (RMSEs). The incidence of pollen-, dust mites- and mould-sensitive AR patients was significantly correlated with minimum temperature, vapour pressure, and sea-level pressure, respectively. The correlation between comprehensive meteorological parametric (CMP) and incidence of AR was higher than the correlation between the individual meteorological parameters and AR incidence. CMP had higher performance than individual meteorological parameters for predicting the incidence of AR patients. These findings suggest that the incidence of pollen-, dust mites- and mould-sensitive AR can be predicted employing models based on prevailing meteorological conditions.


Assuntos
Exposição Ambiental , Conceitos Meteorológicos , Modelos Estatísticos , Rinite Alérgica/epidemiologia , Adulto , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Adulto Jovem
6.
Acta Otolaryngol ; 137(5): 534-540, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27834111

RESUMO

CONCLUSIONS: There is clear correspondence between HU and histopathological evaluation of osteitis. It is feasible to evaluate bone remodeling in rabbit models with rhinosinusitis by measuring the HU. OBJECTIVE: The objective of this study was to determine whether the HUs of rabbit CRS models can be used to objectively evaluate the degree of osteitis. METHODS: Sixty rabbit models were inoculated with staphylococcus aureus. The rabbits were divided into three groups. Each group was divided into a medication administration team and a control team. The HU of the bone in each image was measured. All of the animals were executed after the CT exam. The samples for the mucous and bone changes using light microscope observation were scored. These scores and the HU measurements were compared to the actual bone remodeling over time to examine whether we could evaluate bone remodeling by measuring the HU. RESULTS: The average HU scores in Groups A, B, and C were significantly higher than those of normal rabbits (p < .05). The mucous and bone scores increased as the experimental period lengthened (p = .042, 0.002). HU correlated with the mucous and bone scores in rabbit models with rhinosinusitis (coefficient r = .830, 0.641, 0.586, p = .000).


Assuntos
Osteíte/diagnóstico por imagem , Sinusite/complicações , Tomografia Computadorizada por Raios X/métodos , Animais , Osso e Ossos/patologia , Feminino , Masculino , Mucosa Nasal/patologia , Osteíte/etiologia , Osteíte/patologia , Coelhos , Rinite/complicações , Rinite/diagnóstico por imagem , Sinusite/diagnóstico por imagem
7.
Int Forum Allergy Rhinol ; 6(12): 1221-1228, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27557563

RESUMO

BACKGROUND: Precise localization and excision of the originating site of a sinonasal inverted papilloma (SNIP) is essential for decreasing tumor recurrence. In this study we evaluated the use of preoperative computed tomography (CT) and magnetic resonance imaging (MRI) to pinpoint the attachment/originating sites of SNIPs in 143 patients. METHODS: Osteitis signs in CTs and convoluted cerebriform pattern (CCP)-based reverse tracings from MRIs of 143 SNIP patients were analyzed preoperatively to predict the originating site of SNIPs. The predicted sites were compared with actual SNIP attachment sites determined by surgery, and patients were followed-up for evaluation of SNIP recurrence rates over a mean period of about 4 years. RESULTS: Osteitis signs in CT accurately predicted the actual tumor attachment site in 49.7% of all patients. In comparison, convoluted cerebriform pattern (CCP)-based reverse tracings in MRI and combination CT plus MRI accurately predicted the SNIP originating sites in 84.1% and 86% of the patients, respectively. Sensitivity and specificity in predicting the SNIP originating site were: CT, 54.6% and 69.2%; MRI, 93.1% and 76.9%; and CT+MRI, 94.6% and 92.3%, respectively. A single postoperative recurrence occurred in 4.2% of the patients. CONCLUSIONS: Preoperative combination of MRI and CT provides a better option to accurately predict the SNIP originating site, and thus may facilitate accurate and complete excision of the SNIP.


Assuntos
Papiloma Invertido/diagnóstico por imagem , Neoplasias dos Seios Paranasais/diagnóstico por imagem , Adolescente , Adulto , Idoso , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Papiloma Invertido/cirurgia , Neoplasias dos Seios Paranasais/cirurgia , Tomografia Computadorizada por Raios X , Adulto Jovem
8.
Allergy Asthma Immunol Res ; 8(3): 216-22, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26922931

RESUMO

PURPOSE: Group 2 innate lymphoid cells (ILC2s) are a novel population of lineage-negative cells that induce innate type 2 responses by producing the critical Th2-type cytokines IL-5 and IL-13 in response to IL-25 and IL-33 stimulation. ILC2s accumulation in the peripheral blood of patients with allergic rhinitis (AR) is controversial; the precise role of ILC2s in the immunopathogenesis of AR is still not clear. We investigated the role of ILC2s in phenotypic AR sensitized to distinct allergens. METHODS: Flow cytometric analysis of the peripheral blood of 7 healthy controls (HCs), 9 patients monosensitized to house dust mite (HDM), and 8 patients monosensitized to mugwort was performed to quantify ILC2s frequency. Peripheral blood mononuclear cells (PBMCs) were isolated from HDM-AR and mugwort-AR patients, and Lineage⁻ and Lineage⁺ cells were separated using a fluorescence-activated cell sorter (FACS). IL-5 and IL-13 levels in the supernatants of PBMCs, and Lineage⁻ and Lineage⁺ cells stimulated with IL-25 and/or IL-33 combined with IL-2 in vitro were assessed using the Milliplex magnetic bead kit. RESULTS: The percentage of ILC2s was significantly elevated in HDM-AR patients compared to mugwort-AR patients and HCs, while no significant difference was found between mugwort-AR patients and HCs. IL-33±IL-25 plus IL-2 induced a significantly greater release of IL-5 and IL-13 in the PBMCs of HDM-AR patients compared to PBMCs of mugwort-AR patients. IL-25 plus IL-2 also induced a significantly greater release of IL-13 in the PBMCs of HDM-AR patients compared to PBMCs of mugwort-AR patients. Stimulation with IL-33 and/or IL-25 combined with IL-2 also induced a significantly greater IL-5 and IL-13 release from Lineage⁻ cells compared to Lineage⁺ cells. CONCLUSIONS: AR patients sensitized to HDM or mugwort allergen have distinct phenotypic and functional profiles in ILC2s frequencies. ILC2s mediate major type 2 immunity in the development of HDM-AR and may be a potential therapeutic target.

9.
Int Forum Allergy Rhinol ; 6(1): 95-100, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26332319

RESUMO

BACKGROUND: Nitrogen dioxide (NO2) and sulfur dioxide (SO2) generated by excessive coal combustion and motor vehicle emissions are major air pollutants in the large cities of China. The objective of our study was to determine the effects of the exposure of oak pollens (Quercusmongolica) to several concentrations of NO2 or SO2. METHODS: Pollen grains were exposed to 0.5 ppm to 5.0 ppm NO2 or SO2 for 4 hours and assessed for morphological damage by field emission scanning electron microscopy and for viability using the trypan blue stain. Morphological changes in pollen grains were also examined after contact with acid solutions at pH 4.0 to pH 7.0. RESULTS: Exposure to NO2 or SO2 significantly damaged pollen grains at all concentrations investigated, compared to exposure to air; with exposure to concentrations of 0.5 ppm to 2 ppm resulting in fissures or complete breaks in the exine and a concentration of 5 ppm resulting in complete breakdown and release of pollen cytoplasmic granules. Significantly greater amounts of pollen grain were damaged after exposure to SO2 (15.5-20.4%) than after exposure to NO2 (7.1-14.7%). Similarly, exposure to NO2 or SO2 significantly decreased the viability of pollen grains, compared with exposure to air; with SO2 being slightly more detrimental than NO2. Exposure to acid solutions also induced pollen damage, which appeared to be pH-dependent (from 24.6% at pH 6.0 to 55.8% at pH 4.0; compared to 3.8% at pH 7.0). CONCLUSION: Short-term exposure of oak pollen to high concentrations of SO2 or NO2 significantly increases their fragility and disruption, leading to subsequent release of pollen cytoplasmic granules into the atmosphere. These results suggest that heightened air pollution during the oak pollen season may possibly increase the incidence of allergic airway disease in sensitized individuals by facilitating the bioavailability of airborne pollen allergens.


Assuntos
Poluentes Atmosféricos/toxicidade , Alérgenos/efeitos dos fármacos , Dióxido de Nitrogênio/toxicidade , Pólen/efeitos dos fármacos , Quercus/efeitos dos fármacos , Dióxido de Enxofre/toxicidade , Alérgenos/fisiologia , Sobrevivência Celular , China , Grânulos Citoplasmáticos/efeitos dos fármacos , Grânulos Citoplasmáticos/fisiologia , Pólen/anatomia & histologia , Pólen/fisiologia , Quercus/anatomia & histologia , Quercus/fisiologia
10.
Chin Med J (Engl) ; 128(21): 2913-8, 2015 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-26521790

RESUMO

BACKGROUND: Adenoid hypertrophy (AH) is associated with pediatric chronic rhinosinusitis (pCRS), but its role in the inflammatory process of pCRS is unclear. It is thought that innate immunity gene expression is disrupted in the epithelium of patients with chronic rhinosinusitis (CRS), including antimicrobial peptides and pattern recognition receptors (PRRs). The aim of this preliminary study was to detect the expression of innate immunity genes in epithelial cells of hypertrophic adenoids with and without pCRS to better understand their role in pCRS. METHODS: Nine pCRS patients and nine simple AH patients undergoing adenoidectomy were recruited for the study. Adenoidal epithelium was isolated, and real-time quantitative polymerase chain reaction (RT-qPCR) was employed to measure relative expression levels of the following messenger RNAs in hypertrophic adenoid epithelial cells of pediatric patients with and without CRS: Human ß-defensin (HBD) 2 and 3, surfactant protein (SP)-A and D, toll-like receptors 1-10, nucleotide-binding oligomerization domain (NOD)-like receptors NOD 1, NOD 2, and NACHT, LRR and PYD domains-containing protein 3, retinoic acid-induced gene 1, melanoma differentiation-associated gene 5, and nuclear factor-κB (NF-κB). RT-qPCR data from two groups were analyzed by independent sample t-tests and Mann-Whitney U-tests. RESULTS: The relative expression of SP-D in adenoidal epithelium of pCRS group was significantly lower than that in AH group (pCRS 0.73 ± 0.10 vs. AH 1.21 ± 0.15; P = 0.0173, t = 2.654). The relative expression levels of all tested PRRs and NF-κB, as well as HBD-2, HBD-3, and SP-A, showed no statistically significant differences in isolated adenoidal epithelium between pCRS group and AH group. CONCLUSIONS: Down-regulated SP-D levels in adenoidal epithelium may contribute to the development of pCRS. PRRs, however, are unlikely to play a significant role in the inflammatory process of pCRS.


Assuntos
Células Epiteliais/metabolismo , Imunidade Inata/fisiologia , Sinusite/metabolismo , Tonsila Faríngea/citologia , Peptídeos Catiônicos Antimicrobianos/metabolismo , Criança , Feminino , Humanos , Imunidade Inata/genética , Masculino , Receptores de Reconhecimento de Padrão/metabolismo , Receptores Toll-Like/metabolismo
12.
PLoS One ; 10(5): e0126463, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26020249

RESUMO

BACKGROUND: Sinonasal squamous cell carcinoma (SSCC) and nasal inverted papilloma (NIP) represent the predominant type of malignant and benign tumors in sinonasal tract, respectively. CD4+ CD25+ Foxp3+ natural regulatory T (Treg) cells might play critical role(s) in the suppression of anti-tumor immune response and thus shed light on tumor progression from benign to malignant. OBJECTIVE: This study aimed to evaluate the frequency and suppressive capacity of Treg cells in SSCC compared to NIP and further to explore the underlying mechanisms. PATIENTS AND METHODS: Frequencies of Treg, Th1 and Th2 cells were evaluated by flow cytometry in tissue homogenate and peripheral blood from 31 SSCC patients, 32 NIP patients and 35 normal controls. Treg cells were tested for regulatory function by co-culture with effector T cells. CCR4 and its ligands, CCL22 and CCL17, were analyzed by flow cytometry and Luminex, respectively. The chemoattractant properties of CCR4/CCL22 and CCR4/CCL17 for Treg cells were assessed using the Boyden chamber technique, to elucidate the potential mechanisms of Treg recruitment in tumor microenvironment. Treg cells induction via TGF-ß was assessed with transwells after local CD4+ Foxp3+ T cells were assessed by immunohistochemistry and TGF-ß concentration was measured by Luminex. RESULTS: Tumor-infiltrating Treg cells increased significantly from normal to NIP to SSCC (P ≤ 0.001 for normal vs. NIP and P = 0.004 for NIP vs. SSCC). Significantly elevated frequency and enhanced suppression capacity of circulating Treg cells in SSCC were detected compared to NIP and healthy controls, concomitant with Th1 decrease and Th2 increase. Apparently increased CCL22 attracted CCR4-expressing Treg cells to tumor microenvironment in SSCC, compared to NIP. SSCC produced significantly more TGF-ß than NIP and thus possessed greater potential for Treg cell induction. CONCLUSION: Frequency and suppressive capacity of Treg cells enhanced with progression of malignancy from NIP to SSCC. Circulating Treg cells were recruited to tumor tissue via CCR4/CCL22 signalling, whereas tumor-synthesised TGF-ß contributed to induction of peripheral Treg cells.


Assuntos
Carcinoma de Células Escamosas/imunologia , Neoplasias do Seio Maxilar/imunologia , Pólipos Nasais/imunologia , Linfócitos T Reguladores/imunologia , Microambiente Tumoral/imunologia , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Quimiocina CCL17/imunologia , Quimiocina CCL22/imunologia , Feminino , Humanos , Masculino , Neoplasias do Seio Maxilar/patologia , Pessoa de Meia-Idade , Pólipos Nasais/patologia , Linfócitos T Reguladores/patologia , Fator de Crescimento Transformador beta/imunologia
13.
Allergy Asthma Immunol Res ; 7(4): 367-75, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25749771

RESUMO

PURPOSE: Chronic rhinosinusitis with nasal polyps (CRSwNP), a mainly Th2 cytokine-mediated disease, often involves mucus secretion. Recent evidence suggests that transmembrane protein 16A (TMEM16A), a calcium-activated Cl- channel (CaCC), can regulate mucus secretion from airway epithelium by transepithelial electrolyte transport and hydration. However, the role of TMEM16A in mucin production/secretion in the airway epithelium is not clear. This study was conducted to determine the role of TMEM16A in mediating mucin secretion in human nasal polyp epithelial cells (HNPECs) induced by IL-13. METHODS: Human sinonasal mucosa tissue and dissociated sinonasal epithelium from control subjects and patients with CRSwNP were assessed for the expression of TMEM16A and the secretion of human mucin 5AC (MUC5AC) by immunohistochemistry, Western blot analysis, and enzyme-linked immuno-sorbent assay (ELISA). A model of the Th2 inflammatory environment was created by exposure of primary air-liquid interface (ALI)-cultured HNPECs to interleukin-13 (IL-13) for 14 days, with subsequent assessment of TMEM16A expression in cell lysates by Western blotting and MUC5AC secretion in apical washings of cells by ELISA. RESULTS: The expressions of TMEM16A and MUC5AC were increased in human nasal polyp tissue and dissociated nasal polyp epithelium. TMEM16A was detected in IL-13-treated HNPECs, specifically in MUC5AC-positive cells but not in ciliated cells. IL-13 treatment increased percentages of TMEM16A-positive cells, MUC5AC-positive cells, and cells coexpressing TMEM16A/MUC5AC, the expression of TMEM16A protein, and the secretion of MUC5AC. T16Ainh-A01, a TMEM16A inhibitor, attenuated these IL-13-induced effects. CONCLUSIONS: The expression of TMEM16A and MUC5AC are increased in CRSwNP, which might be a direct effect of Th2 cytokines present in the sinonasal mucosa in CRSwNP. Down-regulation of TMEM16A expression and MUC5AC secretion in HNPECs by T16Ainh-A01 indicates that TMEM16A might play an important role in mucin secretion in upper airway inflammatory diseases.

14.
Int J Clin Exp Pathol ; 8(11): 13886-99, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26823701

RESUMO

Zinc finger protein, X-linked (ZFX) gene locus on the human X chromosome is structurally similar to the zinc finger protein, Y-linked gene. Its role in human laryngeal squamous cell carcinoma (LSCC) is still not clearly defined. This study was focused on investigating the role of zinc-finger protein X-linked (ZFX) in human LSCC. Expression levels of ZFX were examined in LSCC tissues, corresponding adjacent non-tumoral tissues and vocal leukoplakia tissues by immunohistochemistry (IHC). The association with the expression level of ZFX and LSCC clincopathological parameters was analyzed. The prognostic value of ZFX expression was also analyzed. Lentivirus-mediated RNA interference was applied to silence ZFX expression and the effects of ZFX knockdown on the growth of human LSCC primary cells was investigated. Overexpression of ZFX was found in LSCC tissues. The expression of ZFX was associated with the clinical stage of LSCC. Patients with higher level of ZFX experienced a poorer prognosis compared to those with lower level of ZFX. Knockdown of ZFX inhibited cell proliferation, colony formation and migration of LSCC primary cells. Moreover, ZFX silencing induced cell apoptosis. These results provide the convincing evidence for the first time that ZFX plays an important role in LSCC development and could be a potential therapeutic target or prognostic predictor for LSCC.


Assuntos
Apoptose , Carcinoma de Células Escamosas/metabolismo , Proliferação de Células , Neoplasias de Cabeça e Pescoço/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Neoplasias Laríngeas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Movimento Celular , Feminino , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Estimativa de Kaplan-Meier , Fatores de Transcrição Kruppel-Like/genética , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/mortalidade , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/cirurgia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Interferência de RNA , Transdução de Sinais , Carcinoma de Células Escamosas de Cabeça e Pescoço , Fatores de Tempo , Transfecção , Resultado do Tratamento , Células Tumorais Cultivadas
15.
J Allergy Clin Immunol ; 135(4): 922-929.e6, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25483598

RESUMO

BACKGROUND: There is little evidence on the efficacy of glucocorticoid transnasal nebulization therapy in patients with eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP). OBJECTIVE: We sought to evaluate the immunologic and remodeling effects of budesonide transnasal nebulization in patients with eosinophilic CRSwNP. METHODS: Sixty patients with eosinophilic CRSwNP were randomized to receive budesonide or placebo treatment for 14 days by means of transnasal nebulization in a double-blind manner. Endoscopic polyp size scores (maximum = 6 points, Kennedy score) and visual analog scale scores for nasal symptoms were assessed before and after treatment. Similarly, polyp samples were evaluated for inflammatory cytokines, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs) by using an immunoassay; collagen by using histochemistry; eosinophils by using hematoxylin and eosin stain; and T-cell subsets by using flow cytometry. RESULTS: Budesonide transnasal nebulization significantly reduced polyp size compared with placebo (mean difference between groups, -0.73 units; 95% CI, -1.15 to -0.32 units; P = .002) and improved symptoms. Polyp IL-5 and eotaxin expression decreased significantly, whereas TGF-ß and IL-10 expression increased. Expression of IFN-γ and IL-17 was not altered. Budesonide transnasal nebulization consistently reduced eosinophil infiltration and TH2 cell frequency and increased natural regulatory T-cell and type 1 regulatory T-cell frequencies. Indices of remodeling, including albumin, MMP-2, MMP-7, MMP-8, and MMP-9, were significantly decreased, whereas collagen deposition and TIMP-1, TIMP-2, and TIMP-4 levels were significantly increased. Budesonide transnasal nebulization did not suppress the hypothalamic-pituitary-adrenal axis or cause any serious side effects. CONCLUSION: Short-term budesonide transnasal nebulization is an effective and safe treatment option in patients with eosinophilic CRSwNP, achieving clinical improvement by regulating remodeling, cytokine expression, and T-cell subset distribution.


Assuntos
Broncodilatadores/administração & dosagem , Budesonida/administração & dosagem , Rinite/tratamento farmacológico , Sinusite/tratamento farmacológico , Adulto , Idoso , Broncodilatadores/efeitos adversos , Budesonida/efeitos adversos , Doença Crônica , Citocinas/metabolismo , Eosinófilos/patologia , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/complicações , Nebulizadores e Vaporizadores , Rinite/complicações , Rinite/diagnóstico , Sinusite/complicações , Sinusite/diagnóstico , Resultado do Tratamento , Adulto Jovem
16.
Artigo em Inglês | MEDLINE | ID: mdl-25412964

RESUMO

OBJECTIVE: Regulatory T (Treg) cells play a critical role in the pathophysiology of allergic rhinitis (AR). We investigated the regulatory roles of interleukin (IL)-35, an immunosuppressive cytokine expressed by CD4(+)CD25(+)Foxp3(+) Treg cells, in a murine model of AR. METHODS: The expression of IL-35 subunits (Ebi3, encoded by Ebi3, and IL-12p35, encoded by IL12a) and IL-35 receptor chains (IL12rb and IL6st) in nasal mucosa and in spleen-derived Treg cells from ovalbumin (OVA)-sensitized AR was analyzed by immunohistochemistry and quantitative real-time RT-PCR techniques. RESULTS: IL-35 subunit secretion was associated with local OVA sensitization in this murine model of AR. Ebi3 and IL-12p35, as well as CD3, were expressed differentially in the same regions of nasal mucosa of both AR and control animals. Ebi3 mRNA levels were significantly downregulated in the nasal mucosa of AR mice compared with control mice. Similarly, Ebi3 and IL12a mRNA levels were significantly upregulated in CD4(+)CD25(+) Treg cells and, correspondingly, downregulated in CD4(+)CD25(-) T effector (Teff) cells. IL6st mRNA levels were also significantly downregulated in CD4(+)CD25(-) Teff cells. CONCLUSIONS: Decreased Ebi3 may have a crucial regulatory effect on the nasal mucosa in AR. The increased IL-35 subunit expression in CD4(+)CD25(+) Treg cells may contribute to regulating the pathogenesis of AR.


Assuntos
Interleucinas/imunologia , Rinite Alérgica/imunologia , Linfócitos T Reguladores/imunologia , Animais , Modelos Animais de Doenças , Feminino , Imuno-Histoquímica , Interleucinas/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Mucosa Nasal/imunologia , Mucosa Nasal/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Rinite Alérgica/metabolismo , Linfócitos T Reguladores/metabolismo , Regulação para Cima
17.
Artigo em Chinês | MEDLINE | ID: mdl-24931013

RESUMO

OBJECTIVE: To analyze the clinical feature and treatment methods of Artemisia pollinosis. METHODS: Skin prick test results of 14 426 cases from Beijing Tongren hospital and pollen concentration of Beijing observatory from 2007 to 2011 were analyzed to identify the clinical feature of Artemisia pollinosis patients and its correlation with the pollen concentration. Patients were given leukotriene receptor antagonists (Montelukast) for 2 weeks, followed by 4 weeks of mometasone furoate nasal spray (EIT group: n = 21), or only 4 weeks of mometasone furoate nasal spray (POT group: n = 16). The nasal symptom score was compared between 2 groups.SPSS 16.0 software was used to analyze the data. RESULTS: Artemisia pollinosis accounted for 30.8% (4 442/14 426) of all SPT positive allergic rhinitis patients, and most Artemisia SPT positive results were strong positive(3 793/4 442, 85.4%); onset age peak of Artemisia pollinosis patients was at the age of 19 to 30, onset time concentrated in August to September, was consistent with the peak period of Artemisia pollen concentration; EIT treatment using leukotriene receptor antagonists two weeks before pollen season significantly improved sneeze, sniveling and rhinocnesmus symptoms (t value was 3.28, 3.92, 3.09, respectively, all P < 0.01) compared with post-onset treatment (POT). But nasal obstruction and cough symptoms had no significant difference between two groups (t value was 0.85, 1.52, respectively, all P > 0.05). CONCLUSION: Artemisia pollen is the main pollen allergen in Beijing, EIT treatment was effective to pollinosis.


Assuntos
Alérgenos/imunologia , Artemisia , Pólen/imunologia , Rinite Alérgica Sazonal/diagnóstico , Rinite Alérgica Sazonal/prevenção & controle , Acetatos/uso terapêutico , Adolescente , Adulto , Idade de Início , Criança , China , Ciclopropanos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Furoato de Mometasona , Pregnadienodiois/uso terapêutico , Quinolinas/uso terapêutico , Rinite Alérgica Sazonal/tratamento farmacológico , Estações do Ano , Sulfetos , Resultado do Tratamento , Adulto Jovem
18.
Artigo em Inglês | MEDLINE | ID: mdl-24801627

RESUMO

OBJECTIVE: To evaluate the expression of five epithelial intercellular junctional proteins in the sinonasal tissue of subjects with chronic rhinosinusitis (CRS). METHODS: Forty-one samples of nasal polyp tissue of CRS patients with nasal polyps (wNP), 20 ethmoid sinus mucosa of CRS patients without nasal polyps (sNP) and 19 nasal mucosa of controls were collected and assessed for the expression of zonulae occludens (ZO-1), claudin-1, E-cadherin and desmoglein-1 and -2 (DSG1, DSG2) using immunohistochemical staining. Interleukin (IL)-5, IL-6 and IL-8 concentrations in the tissues were also measured using ELISA. RESULTS: The expression of ZO-1, claudin-1, DSG1 and DSG2 in the CRSwNP patient group and the expression of claudin-1, DSG1 and DSG2 of the CRSsNP patient group was significantly lower compared to that of the control group. Furthermore, the expression of DSG1 in the CRSwNP patient group was also significantly lower than in the CRSsNP patient group. In contrast, the expression of E-cadherin in the CRSwNP and the CRSsNP patient groups was significantly greater compared to the controls. The assessment of associations between the expression of the intercellular junctional proteins and cytokines demonstrated negative correlations between IL-5 and claudin-1, IL-6 and claudin-1, IL-6 and DSG2, IL-8 and DSG1, and IL-8 and DSG2. In contrast, a positive correlation was found between IL-8 and E-cadherin. CONCLUSIONS: Differences in the expression of epithelial intercellular junctional proteins may play an important role in the pathogenesis of CRS.


Assuntos
Caderinas/metabolismo , Claudina-1/metabolismo , Desmogleínas/metabolismo , Rinite/metabolismo , Rinite/patologia , Sinusite/metabolismo , Sinusite/patologia , Proteína da Zônula de Oclusão-1/metabolismo , Adolescente , Adulto , Idoso , Doença Crônica , Citocinas/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Junções Intercelulares/metabolismo , Masculino , Pessoa de Meia-Idade , Adulto Jovem
19.
Artigo em Inglês | MEDLINE | ID: mdl-23571727

RESUMO

OBJECTIVE: To evaluate the differences in clinical features and expression of cytokine thymic stromal lymphopoetin (TSLP) and its receptors in patients with eosinophilic and non-eosinophilic chronic rhinosinusitis (ECRS and NECRS). METHOD: 36 ECRS patients and 50 NECRS patients were evaluated for symptoms, nasal sinus computed tomography scanning, nasal endoscopy, skin prick test (SPT) positivity, and total IgE. Expression of TSLP and receptors in ethmoid sinus mucosa from the ECRS and NECRS groups were investigated by using immunohistochemical staining. RESULTS: ECRS patients demonstrated significantly higher scores of cough and hyposmia. 66.7% of ECRS patients also demonstrated nasal polyps, compared to 50% of NECRS patients, with significantly higher polyp endoscopy scores. 80.6% of ECRS patients demonstrated SPT positivity, compared to 14% of NECRS patients. The overall expression of TSLP, TSLP receptors and IL-7R was significantly greater in eosinophils in the mucosa of ECRS patients than in NECRS patients. The expression of TSLP and receptors in SPT-positive ECRS patients was significantly greater than in SPT-negative patients, with a significant correlation noted between the expression of TSLP and nasal polyp scores. CONCLUSION: The clinical manifestations of ECRS are likely to be influenced by atopic status of an individual and TSLP-mediated eosinophil infiltration of the rhinosinusoidal mucosa.


Assuntos
Citocinas/metabolismo , Rinite/metabolismo , Sinusite/metabolismo , Adolescente , Adulto , Idoso , Doença Crônica , Eosinofilia , Feminino , Humanos , Hipertrofia , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Mucosa/metabolismo , Mucosa/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Rinite/diagnóstico , Sinusite/diagnóstico , Adulto Jovem , Linfopoietina do Estroma do Timo
20.
Chin Med J (Engl) ; 126(2): 248-53, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23324272

RESUMO

BACKGROUND: Gene therapy and epigenetic therapy have gained more attention in cancer treatment. However, the effect of a combined treatment of gene therapy and epigenetic therapy on head and neck squamous cell carcinoma have not been studied yet. To study the mechanism and clinical application, human laryngeal carcinoma cell (Hep-2) tumor-bearing mice were used. METHODS: A xenograft tumor model was established by the subcutaneous inoculation of Hep-2 cells in the right armpit of BALB/c nu/nu mice. The mice with well-formed tumor were randomly divided into six groups. Multisite injections of rAd-p53 and/or 5-aza-dC were used to treat tumor. Tumor growth was monitored by measuring tumor volume and growth rate. p53 and E-cadherin protein levels in tumor tissues were detected by immunohistochemical staining. The mRNA levels were monitored with FQ-PCR. RESULTS: Gene therapy was much more effective than single epigenetic therapy and combined therapy. The gene therapy group has the lowest tumor growth rate and the highest expression levels of p53 and E-cadherin. CONCLUSIONS: The combined treatment of gene and epigenetic therapy is not suggested for treating head and neck carcinoma, because gene therapy shows an antagonistic effect to epigenetic therapy. However, the mechanisms of action are still unclear.


Assuntos
Azacitidina/análogos & derivados , Metilases de Modificação do DNA/antagonistas & inibidores , Epigênese Genética , Genes p53 , Terapia Genética , Neoplasias Laríngeas/terapia , Animais , Azacitidina/uso terapêutico , Caderinas/análise , Decitabina , Humanos , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Proteína Supressora de Tumor p53/análise , Ensaios Antitumorais Modelo de Xenoenxerto
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