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1.
Exp Cell Res ; 389(2): 111897, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32035951

RESUMO

Mucins are major macromolecular components of lung mucus that are mainly responsible for the viscoelastic property of mucus. MUC5AC is a major mucin glycoprotein that is hypersecreted in asthmatic individuals. Vascular endothelial growth factor (VEGF) has been implicated in inflammatory and airway blood vessel remodeling in asthmatics. Our previous studies indicate that VEGF upregulates MUC5AC expression by interacting with VEGF receptor 2 (VEGFR2). It has been shown that dexamethasone (Dex) downregulates MUC5AC expression; however, the underlying mechanisms have not been completely elucidated. Therefore, we sought to investigate the effect of Dex on MUC5AC expression induced by VEGF and study the underlying mechanisms. We tested the effects of Dex on VEGFR2 and RhoA activation, caveolin-1 expression, and the association of caveolin-1 and VEGFR2 in primary bronchial epithelial cells. Dex downregulated MUC5AC mRNA and protein levels in a dose- and time-dependent manner, and suppressed the activation of VEGFR2 and RhoA induced by VEGF. Additionally, Dex upregulated caveolin-1 protein levels in a dose- and time-dependent manner. Furthermore, phospho-VEGFR2 expression was decreased through overexpression of caveolin-1 and increased after caveolin-1 knockdown. Dex treatment attenuated the VEGF-decreased association of caveolin-1 and VEGFR2. Collectively, our findings suggest that Dex downregulates VEGF-induced MUC5AC expression by inactivating VEGFR2 and RhoA. Furthermore, decreased MUC5AC expression by Dex was related to the increased association of caveolin-1 with VEGFR2. Further studies characterizing these mechanisms are required to facilitate the development of improved treatment strategies for asthma.

2.
Respir Res ; 20(1): 282, 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31831011

RESUMO

BACKGROUND: Airway mucus hypersecretion is an important pathophysiological feature in asthma. Mucins are glycoproteins that are mainly responsible for the viscoelastic property of mucus, and MUC5AC is a major mucin glycoprotein that is overproduced in asthma. Vascular endothelial growth factor (VEGF) has been implicated in inflammatory and airway blood vessel remodeling in asthmatics. Therefore, we sought to investigate the effect of VEGF on MUC5AC expression and study the underlying mechanisms. METHODS: In order to elucidate the precise mechanism underlying the effect of VEGF on MUC5AC expression, we tested the effects of VEGF on RhoA activation and the association of caveolin-1 and VEGFR2 in Primary Bronchial Epithelial Cells. RESULTS: VEGF up-regulated MUC5AC mRNA and protein levels in a dose- and time-dependent manner, and activated RhoA. Additionally, VEGF-induced MUC5AC expression and RhoA activation were enhanced by disrupting caveolae with cholesterol depletion and reversed by cholesterol repletion, and inhibited by a selective VEGF receptor 2 (VEGFR2) inhibitor SU1498. Furthermore, phospho-VEGFR2 expression was decreased via overexpression of caveolin-1. VEGF treatment reduced the association of caveolin-1 and VEGFR2. CONCLUSION: Collectively, our findings suggest that VEGF up-regulates MUC5AC expression and RhoA activation by interaction with VEGFR2, and this phenomenon was related with the association of caveolin-1 and VEGFR2. Further studies on these mechanisms are needed to facilitate the development of treatments for asthma.

3.
Medicine (Baltimore) ; 98(30): e16332, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348232

RESUMO

RATIONALE: Multiple primary carcinoma (MPM) refers to simultaneous or successive occurrence of ≥2 types of primary malignant tumors in a single organ or in different organs of the same individual. It is rarely seen in clinical practice. Among the various types of MPM, hilar cholangiocarcinoma combined with gastric cancer is extremely rare. PATIENT CONCERNS: The patient was a 61-year-old man who was admitted to our hospital due to upper abdominal discomfort and yellow-stained skin mucosa for 9 days. DIAGNOSES: Preoperative diagnosis: Considering the typical preoperative painless jaundice as well as his clinical imaging report, the patient received the following preoperative diagnosis: obstructive jaundice, type IV hilar cholangiocarcinoma based on Bismuth-Corlette classification, and no intrahepatic distant metastasis. Intraoperative diagnosis: The results of intraoperative snap freezing and laboratory examination indicated gastric adenocarcinoma. Therefore, the patient received an intraoperative diagnosis of obstructive jaundice, hilar cholangiocarcinoma, and gastric cancer. Postoperative pathological diagnosis: Postoperative pathological examination of the gastric lesion revealed the following results: ulcerative, moderately differentiated gastric adenocarcinoma and intestinal type in the Lauren classification of stomach cancer; moderately differentiated adenocarcinoma of the bile duct. INTERVENTIONS: Surgical resection operation was carried out and the patient received chemotherapy after operation. But we could not strictly follow the relevant clinical guidelines to perform standardized operations and provide comprehensive treatment because of his economic situation, psychological factors, and the current medical environment in China. OUTCOMES: The patient did not receive standardized postoperative therapy. Although he lived and worked normally for 8 months after the operation, he died 10 months after surgery. LESSONS: This report reminds us to pay close attention to the likelihood of MPM and other low-incidence diseases. The physicians and imaging clinicians should explore all clinical possibilities to avoid misdiagnosis of this rare disease and formulate effective treatment plans to maximize the therapeutic benefits for the patient.


Assuntos
Neoplasias dos Ductos Biliares/patologia , Tumor de Klatskin/patologia , Neoplasias Primárias Múltiplas/patologia , Neoplasias Gástricas/patologia , Neoplasias dos Ductos Biliares/complicações , Neoplasias dos Ductos Biliares/cirurgia , Humanos , Icterícia Obstrutiva/etiologia , Tumor de Klatskin/complicações , Tumor de Klatskin/cirurgia , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/cirurgia , Neoplasias Gástricas/cirurgia
4.
World J Gastroenterol ; 25(17): 2086-2098, 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31114135

RESUMO

BACKGROUND: Pancreatic cancer is a highly invasive malignant tumor. Expression levels of the autophagy-related protein microtubule-associated protein 1A/1B-light chain 3 (LC3) and perineural invasion (PNI) are closely related to its occurrence and development. Our previous results showed that the high expression of LC3 was positively correlated with PNI in the patients with pancreatic cancer. In this study, we further searched for differential genes involved in autophagy of pancreatic cancer by gene expression profiling and analyzed their biological functions in pancreatic cancer, which provides a theoretical basis for elucidating the pathophysiological mechanism of autophagy in pancreatic cancer and PNI. AIM: To identify differentially expressed genes involved in pancreatic cancer autophagy and explore the pathogenesis at the molecular level. METHODS: Two sets of gene expression profiles of pancreatic cancer/normal tissue (GSE16515 and GSE15471) were collected from the Gene Expression Omnibus. Significance analysis of microarrays algorithm was used to screen differentially expressed genes related to pancreatic cancer. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to analyze the functional enrichment of the differentially expressed genes. Protein interaction data containing only differentially expressed genes was downloaded from String database and screened. Module mining was carried out by Cytoscape software and ClusterOne plug-in. The interaction relationship between the modules was analyzed and the pivot nodes between the functional modules were determined according to the information of the functional modules and the data of reliable protein interaction network. RESULTS: Based on the above two data sets of pancreatic tissue total gene expression, 6098 and 12928 differentially expressed genes were obtained by analysis of genes with higher phenotypic correlation. After extracting the intersection of the two differential gene sets, 4870 genes were determined. GO analysis showed that 14 significant functional items including negative regulation of protein ubiquitination were closely related to autophagy. A total of 986 differentially expressed genes were enriched in these functional items. After eliminating the autophagy related genes of human cancer cells which had been defined, 347 differentially expressed genes were obtained. KEGG pathway analysis showed that the pathways hsa04144 and hsa04020 were related to autophagy. In addition, 65 clustering modules were screened after the protein interaction network was constructed based on String database, and module 32 contains the LC3 gene, which interacts with multiple autophagy-related genes. Moreover, ubiquitin C acts as a pivot node in functional modules to connect multiple modules related to pancreatic cancer and autophagy. CONCLUSION: Three hundred and forty-seven genes associated with autophagy in human pancreatic cancer were concentrated, and a key gene ubiquitin C which is closely related to the occurrence of PNI was determined, suggesting that LC3 may influence the PNI and prognosis of pancreatic cancer through ubiquitin C.


Assuntos
Autofagia , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Neoplasias Pancreáticas/metabolismo , Ubiquitina C/genética , Análise por Conglomerados , Biologia Computacional , Redes Reguladoras de Genes , Humanos , Análise em Microsséries , Proteínas Associadas aos Microtúbulos/genética , Invasividade Neoplásica , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , Software , Transcriptoma
5.
World J Gastroenterol ; 23(40): 7232-7241, 2017 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-29142470

RESUMO

AIM: To investigate the relationship between autophagy and perineural invasion (PNI), clinical features, and prognosis in patients with pancreatic cancer. METHODS: Clinical and pathological data were retrospectively collected from 109 patients with pancreatic ductal adenocarcinoma who underwent radical resection at the First Affiliated Hospital of Zhengzhou University from January 2011 to August 2016. Expression levels of the autophagy-related protein microtubule-associated protein 1A/1B-light chain 3 (LC3) and PNI marker ubiquitin carboxy-terminal hydrolase (UCH) in pancreatic cancer tissues were detected by immunohistochemistry. The correlations among LC3 expression, PNI, and clinical pathological features in pancreatic cancer were analyzed. The patients were followed for further survival analysis. RESULTS: In 109 cases of pancreatic cancer, 68.8% (75/109) had evidence of PNI and 61.5% (67/109) had high LC3 expression. PNI was associated with lymph node metastasis, pancreatitis, and CA19-9 levels (P < 0.05). LC3 expression was related to lymph node metastasis (P < 0.05) and was positively correlated with neural invasion (P < 0.05, r = 0.227). Multivariate logistic regression analysis indicated that LC3 expression, lymph node metastasis, pancreatitis, and CA19-9 level were factors that influenced neural invasion, whereas only neural invasion itself was an independent factor for high LC3 expression. Univariate analysis showed that LC3 expression, neural invasion, and CA19-9 level were related to the overall survival of pancreatic cancer patients (P < 0.05). Multivariate COX regression analysis indicated that PNI and LC3 expression were independent risk factors for poor prognosis in pancreatic cancer (P < 0.05). CONCLUSION: PNI in patients with pancreatic cancer is positively related to autophagy. Neural invasion and LC3 expression are independent risk factors for pancreatic cancer with a poor prognosis.


Assuntos
Autofagia , Carcinoma Ductal Pancreático/patologia , Proteínas Associadas aos Microtúbulos/metabolismo , Neoplasias Pancreáticas/patologia , Ubiquitina Tiolesterase/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno CA-19-9/sangue , Carcinoma Ductal Pancreático/sangue , Carcinoma Ductal Pancreático/mortalidade , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/mortalidade , Prognóstico , Estudos Retrospectivos , Fatores de Risco
6.
World J Surg Oncol ; 15(1): 139, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28764784

RESUMO

BACKGROUND: This retrospective study and meta-analysis was designed to explore the relationship between E-cadherin (E-cad) expression and the molecular subtypes of invasive non-lobular breast cancer, especially in early-stage invasive ductal carcinoma (IDC). METHODS: A total of 156 post-operative cases of early-stage IDCs were retrospectively collected for the immunohistochemistry (IHC) detection of E-cad expression. The association of E-cad expression with molecular subtypes of early-stage IDCs was analyzed. A literature search was conducted in March 2016 to retrieve publications on E-cad expression in association with molecular subtypes of invasive non-lobular breast cancer, and a meta-analysis was performed to estimate the relational statistics. RESULTS: E-cad was expressed in 82.7% (129/156) of early-stage IDCs. E-cad expression was closely associated with the molecular types of early-stage IDCs (P < 0.050); moreover, the molecular subtypes were an independent factor influencing E-cad expression in early-stage IDCs. A total of 12 observational studies (including our study) were included in the meta-analysis. The meta-analytical results show a significantly greater risk of E-cad expression loss in triple-negative breast cancer (TNBC) than in other molecular subtypes (TNBC vs. luminal A: RR = 3.45, 95% CI = 2.79-4.26; TNBC vs. luminal B: RR = 2.41, 95% CI = 1.49-3.90; TNBC vs. HER2-enriched: RR = 1.95, 95% CI = 1.24-3.07). CONCLUSIONS: Early-stage IDCs or invasive non-lobular breast cancers with the TNBC molecular phenotype have a higher risk for the loss of E-cad expression than do tumors with non-TNBC molecular phenotypes, suggesting that E-cad expression phenotypes were closely related to molecular subtypes and further studies are needed to clarify the underlying mechanism.


Assuntos
Neoplasias da Mama/patologia , Caderinas/metabolismo , Carcinoma Ductal de Mama/patologia , Neoplasias de Mama Triplo Negativas/patologia , Adulto , Antígenos CD , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fenótipo , Prognóstico , Estudos Retrospectivos
7.
Growth Factors ; 35(1): 39-47, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28635361

RESUMO

Asthma is a chronic respiratory disease characterized by reversible airway obstruction with persistent airway inflammation and airway remodeling, which is associated with increased airway smooth muscle (ASM) mass. Licochalcone A is the predominant characteristic chalcone in licorice root. We found that licochalcone A inhibited vascular endothelial growth factor (VEGF)-induced ASM cell proliferation and induced cell cycle arrest. Additionally, VEGF-induced ASM cell proliferation was suppressed via inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) activity, but not that of Akt. Furthermore, licochalcone A treatment inhibited VEGF-induced activation of VEGF receptor 2 (VEGFR2) and ERK and blocked the downregulation of caveolin-1 in a concentration-dependent manner. Collectively, our findings suggested that licochalcone A inhibited VEGF-induced ASM cell proliferation by suppressing VEGFR2 and ERK1/2 activation and downregulating caveolin-1. Further studies of these mechanisms are needed to facilitate the development of treatments for smooth muscle hyperplasia-associated diseases of the airway, such as asthma.


Assuntos
Asma/metabolismo , Proliferação de Células , Chalconas/farmacologia , Miócitos de Músculo Liso/efeitos dos fármacos , Sistema Respiratório/citologia , Caveolina 1/metabolismo , Células Cultivadas , Humanos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/fisiologia , Fator A de Crescimento do Endotélio Vascular/farmacologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
8.
Respir Res ; 18(1): 7, 2017 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-28056993

RESUMO

BACKGROUND: Asthma is a chronic respiratory disease characterized by reversible airway obstruction with persistent airway inflammation and airway remodeling, which is associated with increased airway smooth muscle (ASM) mass. Vascular endothelial growth factor (VEGF) has been implicated in inflammatory and airway blood vessel remodeling in asthma. Recent evidence indicates that a deficiency of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) may influence asthma pathogenesis. A disintegrin and metalloproteinase (ADAM)33 has been identified as playing a role in the pathophysiology of asthma. ADAM33, which is expressed in ASM cells, is suggested to play a role in the function of these cells. Recent studies show that 1,25-(OH)2D3 exerts direct inhibitory effects on passively sensitized human ASM cells in vitro, including inhibition of ADAM33 expression and cell proliferation; however, the mechanism has not been fully understood. METHODS: In order to elucidate the precise mechanism underlying the effect of 1,25(OH)2D3 on VEGF-induced ADAM33 expression and ASM cell proliferation, we tested the effects of 1,25(OH)2D3 on cell cycle progression and evaluated the levels of phospho-VEGF receptor 2 (VEGFR2), phospho-extracellular signal-regulated kinase 1/2 (ERK1/2), and phospho-Akt in VEGF-stimulated ASM cells. RESULTS: We found that 1,25(OH)2D3 inhibited VEGF-induced ADAM33 expression and ASM cell proliferation, as well as cell cycle arrest. Additionally, VEGF-induced ADAM33 expression and ASM cell proliferation was suppressed via inhibition of ERK1/2 activity, but not that of Akt. Furthermore, 1,25(OH)2D3 treatment inhibited VEGF-induced activation of VEGFR2 as well as that of ERK and Akt in a concentration-dependent manner. 1,25(OH)2D3 also inhibited transforming growth factor (TGF)-ß-induced VEGF secretion by ASM cells. CONCLUSIONS: Collectively, our findings suggest that 1,25(OH)2D3 inhibits VEGF-induced ASM cell proliferation by suppressing VEGFR2 and ERK1/2 activation and downregulating ADAM33. Further studies of these mechanisms are needed to facilitate the development of treatments for smooth muscle hyperplasia-associated diseases of the airway such as asthma.


Assuntos
Proteínas ADAM/metabolismo , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Colecalciferol/administração & dosagem , Pulmão/fisiologia , Miócitos de Músculo Liso/fisiologia , Fator A de Crescimento do Endotélio Vascular/administração & dosagem , Asma/tratamento farmacológico , Asma/metabolismo , Asma/patologia , Células Cultivadas , Relação Dose-Resposta a Droga , Humanos , Pulmão/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos
9.
Medicine (Baltimore) ; 95(48): e5486, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27902606

RESUMO

Preoperative aspartate aminotransferase-to-platelet ratio index (APRI) has been identified as a biochemical marker for histological fibrogenesis and fibrosis in cirrhosis and prognosis of hepatocellular carcinoma (HCC). Whether preoperative APRI can predict postoperative short-term outcomes has not been studied. The purpose of this study was to investigate the ability of preoperative APRI to predict short-term outcomes following liver resection for HCC. APRI was evaluated in 360 patients undergoing liver resection for HCC. The receiver operating characteristic curve analysis was conducted to determine the cutoff value of the APRI in predicting postoperative morbidity. Univariate and multivariate analysis was performed to identify the risk factors for postoperative outcomes. The correlation of the preoperative APRI value with clinicopathological parameters was also examined. We found that the optimal cutoff value of the APRI was set at 9.5 for postoperative complications. APRI was an independent risk factor for overall complications by univariate and multivariate analyses. HCC patients with elevated APRI (>9.5) had a worse liver function and significantly higher postoperative complication rate. In conclusion, preoperative APRI is a useful biochemical marker to predict postoperative outcomes in HCC patients.


Assuntos
Aspartato Aminotransferases/metabolismo , Carcinoma Hepatocelular/sangue , Neoplasias Hepáticas/sangue , Contagem de Plaquetas , Carcinoma Hepatocelular/cirurgia , Feminino , Hepatectomia , Humanos , Testes de Função Hepática , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Valor Preditivo dos Testes , Período Pré-Operatório , Prognóstico , Fatores de Risco , Resultado do Tratamento
10.
Exp Cell Res ; 347(2): 378-84, 2016 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-27587274

RESUMO

Asthma is a chronic respiratory disease characterized by reversible airway obstruction with persistent airway inflammation and airway remodelling, which is associated with increased airway smooth muscle (ASM) mass. Roxithromycin (RXM) has been widely used in asthma treatment; however, its mechanism of action is poorly understood. Vascular endothelial growth factor (VEGF) has been implicated in inflammatory and airway blood vessel remodelling in patients with asthma, and shown to promote ASM cell proliferation. Here, we investigated the effect of RXM on VEGF-induced ASM cell proliferation and attempted to elucidate the underlying mechanisms of action. We tested the effect of RXM on proliferation and cell cycle progression, as well as on the expression of phospho-VEGF receptor 2 (VEGFR2), phospho-extracellular signal-regulated kinase 1/2 (ERK1/2), phospho-Akt, and caveolin-1 in VEGF-stimulated ASM cells. RXM inhibited VEGF-induced ASM cell proliferation and induced cell cycle arrest. Additionally, VEGF-induced ASM cell proliferation was suppressed by inhibiting the activity of ERK1/2, but not that of Akt. Furthermore, RXM treatment inhibits VEGF-induced activation of VEGFR2 and ERK and downregulation of caveolin-1 in a dose-dependent manner. RXM also inhibited TGF-ß-induced VEGF secretion by ASM cells and BEAS-2B cells. Collectively, our findings suggest that RXM inhibits VEGF-induced ASM cell proliferation by suppression of VEGFR2 and ERK1/2 activation and caveolin-1 down-regulation, which may be involved in airway remodelling. Further elucidation of the mechanisms underlying these observations should enable the development of treatments for smooth muscle hyperplasia-associated diseases of the airway such as asthma.


Assuntos
Asma/tratamento farmacológico , Asma/patologia , Pulmão/patologia , Miócitos de Músculo Liso/patologia , Roxitromicina/farmacologia , Roxitromicina/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/farmacologia , Caveolina 1/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fase G1/efeitos dos fármacos , Humanos , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Fosforilação/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
11.
Cell Cycle ; 15(20): 2819-26, 2016 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-27579513

RESUMO

Asthma is a chronic respiratory disease characterized by reversible airway obstruction with persistent airway inflammation and airway remodeling. Features of airway remodeling include increased airway smooth muscle (ASM) mass. A disintegrin and metalloproteinase (ADAM)-33 has been identified as playing a role in the pathophysiology of asthma. ADAM-33 is expressed in ASM cells and is suggested to play a role in the function of these cells. However, the regulation of ADAM-33 is not fully understood. Vascular endothelial growth factor (VEGF) has been implicated in inflammatory and airway blood vessel remodeling in asthmatics. Although VEGF was initially thought of as an endothelial-specific growth factor, recent reports have found that VEGF can promote proliferation of other cell types, including ASM cells. To investigate the precise mechanism of VEGF's effect on ASM cell proliferation, we tested the expression of ADAM-33, phospho-extracellularsignal-regulated kinase 1/2 (ERK1/2), and phospho-Akt in VEGF-stimulated ASM cells. We found that VEGF up-regulates ADAM-33 mRNA and protein levels in a dose- and time-dependent manner as well as phosphorylation of ERK1/2 and Akt. We also found that VEGF-induced ASM cell proliferation is inhibited by both ADAM-33 knockdown and a selective VEGF receptor 2 (VEGFR2) inhibitor (SU1498). Furthermore, VEGF-induced ADAM-33 expression and ASM cell proliferation were suppressed by inhibiting ERK1/2 activity, but not by inhibiting Akt activity. Collectively, our findings suggest that VEGF enhances ADAM-33 expression and ASM cell proliferation by activating the VEGFR2/ERK1/2 signaling pathway, which might be involved in the pathogenesis of airway remodeling. Further elucidation of the mechanisms underlying these observations might help develop therapeutic strategies for airway diseases associated with smooth muscle hyperplasia such as asthma.


Assuntos
Proteínas ADAM/genética , Asma/genética , Pulmão/patologia , Miócitos de Músculo Liso/metabolismo , Regulação para Cima/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/farmacologia , Proteínas ADAM/metabolismo , Asma/patologia , Butadienos/farmacologia , Proliferação de Células , Cinamatos/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Miócitos de Músculo Liso/efeitos dos fármacos , Nitrilos/farmacologia , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Transfecção , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
12.
Sex Transm Dis ; 41(3): 188-93, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24521725

RESUMO

BACKGROUND: Untreated maternal syphilis can result in the fetuses being infected. Severe adverse pregnancy outcomes include stillbirth, perinatal death, low birth weight, and congenital syphilis (CS). The World Health Organization has already classified global elimination of CS as a priority. However, this preventable disease is still threatening people's health in the world. METHODS: A Programme of Prevention of Mother-to-Child Transmission of Syphilis in Shenzhen was launched in 2002. All pregnant women in Shenzhen were screened for syphilis by serological methods at their first prenatal care visit. The infected individuals were treated with 3 weekly injections of 2.4 million units of benzathine penicillin. The babies were followed up until 18 months old to diagnose CS. RESULTS: Up to 2011, the Programme of Prevention of Mother-to-Child Transmission of Syphilis in Shenzhen screened 2,077,362 pregnant women and intervened in 7668 mothers infected with syphilis. The screened rate among pregnant women increased from 89.8% in 2002 to 97.4% in 2011. The proportion of those having adverse pregnant outcomes (including spontaneous abortion, premature delivery, and stillbirth) decreased from 27.3% in 2003 to 8.2% in 2011. The incidence of CS decreased from 115/100,000 in 2002 to 10/100,000 (live births) in 2011. CONCLUSIONS: In 2002, in the face of rising CS numbers, Shenzhen adapted a syphilis control program that involved cost-free testing for pregnant women, commitment and collaboration at multiple levels of the health system, and strong supervision and government guidance. Local program and surveillance data suggest that the program has been very successful in reducing CS incidence.


Assuntos
Antibacterianos/administração & dosagem , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Penicilina G Benzatina/administração & dosagem , Complicações Infecciosas na Gravidez/prevenção & controle , Cuidado Pré-Natal/métodos , Sífilis/prevenção & controle , Adulto , China/epidemiologia , Comportamento Cooperativo , Feminino , Seguimentos , Programas Governamentais , Humanos , Incidência , Recém-Nascido , Masculino , Mães , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/epidemiologia , Resultado da Gravidez , Serviços Preventivos de Saúde/organização & administração , Sífilis/tratamento farmacológico , Sífilis/transmissão , Sífilis Congênita/prevenção & controle
13.
J Cardiovasc Pharmacol Ther ; 18(2): 133-7, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23008154

RESUMO

OBJECTIVES: To investigate the expression of ß(3)-adrenergic receptor (ß(3)-AR) in the atrium of rats with chronic heart failure (CHF). METHODS: The heart failure rat model was established by aortic constriction. Thirty-six male Wistar rats were divided into Sham group (n = 10) and heart failure model group (n = 26), which were further divided into CHF control (CHF group) and BRL group. The rats in the BRL group were treated with a selective ß(3)-AR agonist, BRL-37344 (4.0 nmol/kg, twice weekly) for 4 weeks. RESULTS: In the BRL group, the left ventricular end-systolic pressure (83.21 ± 13.0 vs 101.50 ± 12.12 mm Hg) and the absolute values of the maximal rate of rise and fall of left ventricular pressure ([±dP/dtmax] 2.81 ± 0.04 vs 0.35 ± 0.04 and -2.72 ± 0.06 vs -3.33 ± 0.06) were lower than in the CHF group (P < .01). The left atrial mass index (LAMI) in the BRL group (0.4132 ± 0.0306) was higher than that in the CHF (0.3212 ± 0.0136) or Sham group (0.2683 ± 0.0145; P < .01). The levels of the left atrial ß(3)-AR messenger RNA (mRNA) expression in the BRL group (0.932 ± 0.055) was higher than that in the CHF (0.706 ± 0.043) or Sham group (0.310 ± 0.020; P < .01). In all animals, there was a positive correlation between the level of ß(3)-AR mRNA expression and the left or right atrial mass index (correlation coefficient ranged from 0.744 to 0.937). CONCLUSION: There is a significant increase in the ß(3)-AR mRNA expression in the atrium of rats with heart failure. The level of ß(3)-AR mRNA expression was associated with the AMI and was enhanced by a selective ß(3)-AR agonist, BRL-37344.


Assuntos
Átrios do Coração/metabolismo , Insuficiência Cardíaca/metabolismo , Receptores Adrenérgicos beta 3/biossíntese , Regulação para Cima , Animais , Doença Crônica , Átrios do Coração/patologia , Insuficiência Cardíaca/patologia , Masculino , RNA Mensageiro/biossíntese , Ratos , Ratos Wistar , Receptores Adrenérgicos beta 3/genética , Regulação para Cima/genética
14.
Arch Dermatol Res ; 304(10): 787-93, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22903496

RESUMO

Filaggrin gene (FLG) mutations and sensitization in patients with atopic dermatitis (AD) have been well documented. However, whether an interaction exists between these mutations and specific sensitization in AD patients is still unknown. The aim of the study was to explore the interaction between FLG mutations and specific sensitization in AD patients. A total of 249 AD outpatients were recruited in the current study. Skin prick tests were conducted to assess the patient's sensitization to specific allergens. FLG mutations were analyzed through comprehensive sequencing. Logistic regression analyses were conducted to determine the interactions between FLG mutations and sensitization present. The mean age of the patients was 3.5 years, and the mean age of onset of AD was 9.6 months. The mean SCORAD of the patients was 25.8. Fourteen types of mutations were identified in the FLG of 64 patients. A total of 24 (9.6 %) and 29 (11.6 %) cases were mutated with 3321delA and K4671X, respectively. Sensitization to at least one type of allergen was detected in 118 patients (47.4 %). Logistic regression analyses showed that FLG mutations presented an interaction with sensitization to peanut and did not interact with the other detected allergens among AD patients. Sensitization to peanut allergens would have an interaction with the mutation of K4671X and the combined mutations in FLG in patients with atopic dermatitis. However, sensitization to the other common allergens might not interact with FLG mutations in the development of atopic dermatitis.


Assuntos
Alérgenos/imunologia , Arachis/efeitos adversos , Dermatite Atópica/genética , Dermatite Atópica/imunologia , Proteínas de Filamentos Intermediários/genética , Hipersensibilidade a Amendoim/genética , Hipersensibilidade a Amendoim/imunologia , Adolescente , Adulto , Criança , Pré-Escolar , China , Análise Mutacional de DNA , Estudos de Associação Genética , Humanos , Imunização , Lactente , Recém-Nascido , Mutação/genética , Testes Cutâneos , Adulto Jovem
15.
Cytokine ; 56(3): 550-9, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22019000

RESUMO

Inflammation may play a major role in the pathogenesis of preeclampsia (PE). In this meta-analysis, we determined whether maternal polymorphisms and serum concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) were associated with PE. All studies investigating the associations between PE and maternal polymorphisms of TNF-α-308G/A, IL-6-174G/C, and IL-10-1082A/G or serum concentrations of TNF-α, IL-6, and IL-10 were reviewed. We found that neither maternal TNF-α-308G/A (p=0.86, odds ratio [OR]=0.98, 95% confidence interval [CI], 0.76-1.25), IL-6 174G/C (p=0.14, OR=1.23, 95% CI, 0.93-1.61), nor IL-10-1082A/G (p=0.72, OR=1.07, 95% CI, 0.75-1.52) were associated with PE. On the other hand, maternal TNF-α (p<0.00001, weighted mean difference [WMD]=19.63 pg/ml, 95% CI, 18.54-20.72 pg/ml), IL-6 (p<0.00001, WMD=6.58 pg/ml, 95% CI, 5.49-7.67 pg/ml), and IL-10 (p=0.0005, WMD=19.30 pg/ml, 95% CI, 8.42-30.17 pg/ml) concentrations were significantly higher in PE patients versus controls. Our findings strengthen the clinical evidence that PE is accompanied by exaggerated inflammatory responses, but do not support TNF-α-308G/A, IL-6-174G/C, and IL-10-1082A/G as candidate susceptibility loci in PE.


Assuntos
Interleucina-10/genética , Interleucina-6/genética , Pré-Eclâmpsia/genética , Fator de Necrose Tumoral alfa/genética , Feminino , Heterogeneidade Genética , Humanos , Interleucina-10/sangue , Interleucina-6/sangue , Polimorfismo de Nucleotídeo Único/genética , Pré-Eclâmpsia/sangue , Gravidez , Viés de Publicação , Controle de Qualidade , Fator de Necrose Tumoral alfa/sangue
16.
Sex Transm Infect ; 86(4): 292-6, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20460262

RESUMO

OBJECTIVE: To explore the risk factors underlying congenital syphilis (CS) and to build a hazards model to assess the risk of CS in offspring born to mothers with syphilis treated in gestation. METHODS: This prospective study observed 554 pregnant women with syphilis and their offspring recruited from August 2002 to May 2007 in Shenzhen Centre for Chronic Disease Control and Prevention. After treatment, all the women were followed up until the diagnosis of CS in their offspring was confirmed or denied. Comparisons were made between women bearing infants with CS and women bearing infants without CS to reveal the risk factors for CS. ORs and their 95% CI were calculated for each risk factor by using logistical regression analysis. RESULTS: Twenty-nine (5.2%) infants were diagnosed with CS. Univariable analyses showed that the reciprocal logarithm of the titre of non-treponemal antibodies in mothers (log (1/T); OR=11.18, p<0.001), gestational week (GW) at treatment (OR=1.10, p<0.001) and the interaction between these two variates (OR=1.09, p<0.001) was associated with CS. Multivariable analysis showed that only the interaction was significantly associated with CS (OR=1.09, p=0.047). CONCLUSIONS: The risk of CS could be predicted by the interaction between GW x log (1/T). Early treatment given to women with syphilis during antenatal care may be the only effective method to decrease the risk of CS.


Assuntos
Complicações Infecciosas na Gravidez/terapia , Sífilis Congênita/etiologia , Adolescente , Adulto , Feminino , Humanos , Recém-Nascido , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Cuidado Pré-Natal , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Sorodiagnóstico da Sífilis/métodos , Sífilis Congênita/terapia , Adulto Jovem
17.
Sex Transm Dis ; 37(1): 26-31, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19734825

RESUMO

BACKGROUND: Until now there has been no data to show the effectiveness or benefits of screening for syphilis in gravidas in China. This study was to assess the effectiveness of a program preventing mother-to-child-transmission of syphilis and to reveal factors impacting the benefit. METHODS: A cohort of 159,017 gravidas were screened for syphilis by serologic methods and infected individuals were treated with 3 injections of 2.4 million units of benzathine penicillin in Shenzhen in 2005. The pregnancy outcomes were compared for this cost-effectiveness analysis in 2 scenarios, intervention with screening and treatment versus no intervention. RESULTS: Eight hundred twenty-seven pregnant women (0.52%) were diagnosed with syphilis and treated subsequently. Of these, 200 gestations ended in miscarriage. Four babies were diagnosed with congenital syphilis; 25 neonates with low birth weight; 1 died after birth. The total cost was $636,748. On average, every $770 identified 1 infected mother. Every $4391 prevented 1 congenital syphilis; every $5135 prevented 1 low birth weight; and every $7075 prevented 1 death. One disability adjusted life year could be saved by $215. In total the program reached a benefit to cost ratio of 21.76. Sensitivity analyses revealed that this ratio was mainly impacted by the prevalence of syphilis in pregnant women and the rate of miscarriage. CONCLUSIONS: Screening for antenatal syphilis combined with intervening during gestation is highly effective in China. Reducing the percentage of spontaneous/induced abortion would be one of the most effective methods of further increasing the benefits of this screening.


Assuntos
Custos de Cuidados de Saúde , Programas de Rastreamento/economia , Cuidado Pré-Natal/economia , Sífilis Congênita/prevenção & controle , China , Análise Custo-Benefício , Feminino , Humanos , Recém-Nascido , Modelos Econométricos , Gravidez , Resultado da Gravidez
18.
Acta Derm Venereol ; 88(2): 136-8, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18311440

RESUMO

The treatment and relapse rate of genital warts are significant problems. The aim of this observational study was to assess the efficacy of holmium laser treatment of genital warts. A total of 1500 outpatients with genital human papillomavirus-induced lesions presenting from August 2002 to June 2005 were treated with holmium laser. The effects and side-effects of treatment were observed and analysed. Of this large cohort, lesions were excised at the first visit in 1488 cases. Twelve cases were treated a second or third time in the event that the lesions were too large to be removed at the first visit. The incidence of side-effects and complications after treatment with holmium laser was found to be low. Almost all warts can be excised at first treatment by holmium laser therapy with little bleeding during the treatment.


Assuntos
Condiloma Acuminado/cirurgia , Lasers de Estado Sólido/uso terapêutico , Adolescente , Adulto , Idoso , Condiloma Acuminado/patologia , Feminino , Humanos , Lasers de Estado Sólido/efeitos adversos , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/cirurgia
19.
Pediatr Dermatol ; 23(2): 114-6, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16650215

RESUMO

From July to December 2002, we collected data from 2247 vitiligo patients in order to establish the clinical and epidemiologic profile of vitiligo in China. Of these patients, 541 (24.1%) were children aged equal to or less than 12 years. Of the 541 children, 274 (50.6%) were boys and 267 (49.4%) were girls, with a mean age of 8.87 years and a mean onset age of 7.28 years. Similar to adult patients, boys and girls were affected by vitiligo with equal frequency. The most frequent age of onset was between 4 and 8 years (42.5%). The mean duration of vitiligo was 19.71 months (range: 0-132 months). The most common type of vitiligo was vitiligo vulgaris, the frequency of which was 38.1%, followed by focal vitiligo (34.6%), segmental vitiligo (19.4%), acrofacial vitiligo (7.6%), and universal vitiligo (0.4%). Segmental vitiligo had an earlier the other types. Of the 541 children with vitiligo, 60 (11.1%) had a family history, and 3 (0.6%) had more than one family member who was affected. Forty-one (7.6%) children had an associated autoimmune disease: halo nevi and alopecia areata, which were observed in 39 (7.2%) and 2 (0.4%) children, respectively.


Assuntos
Vitiligo/epidemiologia , Adulto , Idade de Início , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Inquéritos e Questionários , Vitiligo/complicações
20.
Pediatr Dermatol ; 23(1): 13-8, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16445403

RESUMO

To study the clinical and epidemiologic profile of childhood alopecia areata, we performed a survey in which a total of 226 childhood patients less than 16 years old were enrolled. Statistical analysis and heritability were performed using EPI INFO 6.0, SPSS10.0, and the Falconer method. The median age of onset was 10 years. The majority of patients (84.96%) presented with limited alopecia. The male : female ratio was 1.4:1. Boys appeared to have more severe involvement. The earlier the age of onset, the greater the severity of the disease. Sixty-seven patients (29.65%) had previous episodes of alopecia areata. Greater severity and longer duration were seen in the relapsing patients than in the primary patients. Six patients (2.65%) had an associated disease. A positive family history was reported in 25 patients (11.06%). The prevalence figures for alopecia areata in first-, second-, and third-degree relatives of the probands were 2.87%, 0.40%, and 0.13%, respectively. The heritabilities of AA in first-, second-, and third-degree relatives were 51.20%, 46.25%, and 25.65%, respectively. It can be speculated that the effect of genetic factors is important in the occurrence of this disease.


Assuntos
Alopecia em Áreas/diagnóstico , Alopecia em Áreas/epidemiologia , Adolescente , Distribuição por Idade , Idade de Início , Criança , Pré-Escolar , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Prevalência , Prognóstico , Índice de Gravidade de Doença , Distribuição por Sexo
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