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1.
J Cell Biochem ; 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31898364

RESUMO

The study aimed to investigate the expression and function of bladder cancer (BC) long noncoding RNAs (lncRNAs) using a high-throughput platform. High-throughput sequencing was used to compare the expression profiles of lncRNA in BC and adjacent normal tissues. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR), in situ hybridization, gene ontology, and Kyoto Encyclopedia of Genes and Genomes analysis were performed to verify differential expression of lncRNA. The effect of lncRNA overexpression on cellular proliferation, apoptosis, migration, and invasion was analyzed following the transfection of lncRNA overexpressing lentivirus into 5637 and T24 cell lines. The overexpressing cells were subcutaneously injected into nude mice to evaluate their effects on tumor growth. Tumor-associated RNA-binding proteins of lncRNA were analyzed by RNA pull-down combined with mass spectrometry. A total of 93 lncRNA genes were upregulated and 352 lncRNA genes were downregulated in the tissues of patients with BC. Of which, we investigated the function of downregulated lnc-MUC20-9. Overexpression of lnc-MUC20-9 in 5637 and T24 cells resulted in decreased tumor cell viability and cell clones, decreased migration and invasion, and increased apoptosis. Similarly, nude mice bearing lnc-MUC20-9 overexpressing tumor cells exhibited smaller tumor size and volume than that of mice bearing control cells. Mass spectrometry analysis showed that lnc-MUC20-9 binds to ROCK1, an oncogene whose expression was decreased in lnc-MUC20-9 overexpressing cells. The study revealed that lnc-MUC20-9 has the function of inhibiting tumor growth, migration, and invasion. In BC cells, lnc-MUC20-9 binds to ROCK1 and may be involved in lnc-MUC20-9-mediated tumor suppressor function, which might be potential therapeutic targets for BC.

2.
Chron Respir Dis ; 16: 1479973119843648, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31091985

RESUMO

In order to determine the validity of the International Classification of Functioning, Disability, and Health brief Core Set for Obstructive Pulmonary Disease (ICF-OPD) for the assessment of functioning and environmental factors in Chinese chronic OPD (COPD) patients, we conducted a cross-sectional study with a convenience sample of 100 COPD patients. Data were collected using common questionnaires for COPD patients (Modified British Medical Research Council Questionnaire, COPD Assessment Test, St George's Respiratory Questionnaire (SGRQ)), the Brief ICF Core Set for OPD, and the comprehensive ICF checklist. All except one category of the Brief ICF-OPD Core Set were confirmed in our evaluation of its content validity, but there is a high prevalence of problems in 8 categories that were not considered in the Brief ICF-OPD Core Set. The functioning-related components of the Brief ICF-OPD Core Set largely performed similarly to SGRQ in terms of differentiating between patients with different disease severity. Moreover, high correlations between the Brief ICF-OPD Core Set overall score and component scores with the respective SGRQ scales and moderate correlations between ICF-OPD Core Set overall score and component scores and lung function parameters. This study largely confirmed content, known group, and convergent validity of the ICF-OPD.

3.
Exp Ther Med ; 16(4): 3241-3248, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30214547

RESUMO

Oscillatory positive expiratory pressure (OPEP) devices have been utilized as an adjunct therapy to conventional chest physiotherapy (CPT) to promote the clearance of respiratory secretions in individuals with impaired ability to cough, particularly in chronic diseases. However, few studies have focused on the effectiveness of OPEP in lower respiratory tract infection. In the present study, all patients with lower respiratory tract infections hospitalized in the Department of Pulmonary and Critical Care Medicine, Ruijin Hospital (Shanghai, China) between February 2016 and July 2017 were analyzed. Daily sputum quantity and purulence were recorded on the first 7 days of physiotherapy. Oxygenation index, partial pressure carbon dioxide, white blood cell count, neutrophil percentage, C reactive protein (CRP) and procalcitonin (PCT) levels before and after CPT were compared between patients who received OPEP and patients who received mechanical percussion (MP). Sputum was collected prior to and following CPT. A total of 17 patients received OPEP, while 10 received MP. The OPEP group exhibited improved postural drainage compared with the MP group after 7 days of physiotherapy. After 7 days of CPT, patients who received OPEP also exhibited a significantly improved oxygenation index, while the oxygenation index in the MP group did not improve. The improvement of partial pressure carbon dioxide was not significantly different between groups. The OPEP group also exhibited a greater decrease in white blood cell count, neutrophil percentage and CRP levels, compared with the MP group. However, the decrease in PCT level was similar in the OPEP and MP groups. Sputum culture results revealed that the rate of negative conversion was very low in both groups. There was no difference between the two groups in terms of hospitalization outcomes. In conclusion, OPEP exhibited a greater effectiveness in draining sputum, improving oxygenation and reducing inflammatory status in patients with lower respiratory tract infections compared with MP; however, it did not promote the elimination of microbes.

4.
Saudi J Biol Sci ; 25(5): 888-894, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30108437

RESUMO

Although many strategies have been developed for non-small cell lung cancer (NSCLC), more secondary and further treatments are needed due to drug resistance or tumor recurrence. Apatinib is a novel oral antiangiogenic agent and in this study, we aim to investigate the clinical value of apatinib in heavily pretreated NSCLC. Here, we reported the characteristics, efficacy and adverse events of three patients treated with apatinib (500 mg/day). We also summarized the currently available evidence and ongoing clinical trials regarding the use of apatinib in NSCLC. Two cases of adenocarcinoma and one case of squamous cell carcinoma were treated with apatinib due to disease progression after previous treatments of chemotherapy and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). All patients responded to apatinib rapidly and underwent drug resistance shortly afterwards. The patient with squamous cell carcinoma died of hemoptysis. Other adverse events were acceptable. All previous relevant studies were compared and showed similar results but a longer progression-free survival. Additionally, ongoing clinical trials were systematically searched and listed. In conclusion, apatinib shows some efficacy in heavily treated NSCLC and generally tolerable toxicity in non-squamous NSCLC. More solid evidence will be accessible in near future.

5.
BMC Pulm Med ; 18(1): 131, 2018 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-30089474

RESUMO

BACKGROUND: Adipose-derived mesenchymal stem cell (ASCs) exerts immunomodulatory roles in asthma. However, the underlying mechanism remains unclear. The present study aimed to explore the effects and mechanisms of ASCs on chronic asthma using an ovalbumin (OVA)-sensitized asthmatic mouse model. METHODS: Murine ASCs (mASCs) were isolated from male Balb/c mice and identified by the expression of surface markers using flow cytometry. The OVA-sensitized asthmatic mouse model was established and then animals were treated with the mASCs through intratracheal delivery. The therapy effects were assessed by measuring airway responsiveness, performing immuohistochemical analysis, and examining bronchoalveolar lavage fluid (BALF). Additionally, the expression of inflammatory cytokines and lgE was detected by CHIP and ELISA, respectively. The mRNA levels of serum indices were detected using qRT-PCR. RESULTS: The mASCs grew by adherence with fibroblast-like morphology, and showed the positive expression of CD90, CD44, and CD29 as well as the negative expression of CD45 and CD34, indicating that the mASCs were successfully isolated. Administering mASCs to asthmatic model animals through intratracheal delivery reduced airway responsiveness, the number of lymphocytes (P < 0.01) and the expression of lgE (P < 0.01), IL-1ß (P < 0.05), IL-4 (P < 0.001), and IL-17F (P < 0.001), as well as increased the serum levels of IL-10 and Foxp3, and the percentage of CD4 + CD25 + Foxp3+ Tregs in the spleen, and reduced the expression of IL-17 (P < 0.05) and RORγ. CONCLUSIONS: Intratracheal administration of mASCs alleviated airway inflammation, improved airway remodeling, and relieved airway hyperresponsiveness in an OVA-sensitized asthma model, which might be associated with the restoration of Th1/Th2 cell balance by mASCs.


Assuntos
Asma/terapia , Citocinas/sangue , Pulmão/patologia , Transplante de Células-Tronco Mesenquimais , Remodelação das Vias Aéreas , Animais , Asma/induzido quimicamente , Líquido da Lavagem Broncoalveolar/citologia , Modelos Animais de Doenças , Feminino , Imunoglobulina E/sangue , Masculino , Células-Tronco Mesenquimais/citologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina , Linfócitos T Reguladores/citologia , Equilíbrio Th1-Th2
6.
Am J Transl Res ; 9(5): 2421-2428, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28559992

RESUMO

Adipose-derived mesenchymal stem cells (ADMSCs) possess immunomodulation property, yet their therapeutic potential in asthma is unclear. This study aimed to explore the effects of ADMSCs on airway hyperresponsiveness and inflammation in ovalbumin (OVA)-induced asthma models. The underlying mechanism(s) was also examined. BALB/c mice were sensitized with OVA on days 0, 7, and 14, followed by 8-week OVA challenge from day 22. ADMSCs were injected via tail vein on day 21. Animals were measured for airway responsiveness, lung pathology, IgE and cytokine levels in serum, cell composition in bronchoalveolar lavage fluid (BALF), gene expression in the lung, and regulatory T cells (Tregs). We found that delivery of ADMSCs decreased airway responsiveness and eosinophil counts in BALF and reduced infiltration of inflammatory cells and number of mucus-expressing goblet cells in the lung in OVA-challenged mice. OVA-evoked elevation of serum IgE levels and alteration of cytokine production in serum and BALF was significantly prevented by ADMSCs. In addition, administration of ADMSCs impaired the regulation of lung IL-10, Foxp3, IL-17, and RORγ expression by OVA challenge and restored the percentage of CD4+CD25+Foxp3+ Tregs in the spleen. In conclusion, ADMSCs confer protection against OVA-induced airway hyperresponsiveness and inflammation, which is associated with induction of Tregs and restoration of immune homeostasis. These findings suggest that ADMSCs may have therapeutic implications for allergic asthma.

7.
Respir Res ; 17(1): 85, 2016 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-27435725

RESUMO

BACKGROUND: The increasing use of silver nanoparticles (AgNPs) in consumer products is concerning. We examined the potential toxic effects when inhaled in Brown-Norway (BN) rats with a pre-inflammatory state compared to Sprague-Dawley (SD) rats. METHODS: We determined the effect of AgNPs generated from a spark generator (mass concentration: 600-800 µg/mm(3); mean diameter: 13-16 nm; total lung doses: 8 [Low] and 26-28 [High] µg) inhaled by the nasal route in both rat strains. Rats were sacrificed at day 1 and day 7 after exposure and measurement of lung function. RESULTS: In both strains, there was an increase in neutrophils in bronchoalveolar lavage (BAL) fluid at 24 h at the high dose, with concomitant eosinophilia in BN rats. While BAL inflammatory cells were mostly normalised by Day 7, lung inflammation scores remained increased although not the tissue eosinophil scores. Total protein levels were elevated at both lung doses in both strains. There was an increase in BAL IL-1ß, KC, IL-17, CCL2 and CCL3 levels in both strains at Day 1, mostly at high dose. Phospholipid levels were increased at the high dose in SD rats at Day 1 and 7, while in BN rats, this was only seen at Day 1; surfactant protein D levels decreased at day 7 at the high dose in SD rats, but was increased at Day 1 at the low dose in BN rats. There was a transient increase in central airway resistance and in tissue elastance in BN rats at Day 1 but not in SD rats. Positive silver-staining was seen particularly in lung tissue macrophages in a dose and time-dependent response in both strains, maximal by day 7. Lung silver levels were relatively higher in BN rat and present at day 7 in both strains. CONCLUSIONS: Presence of cellular inflammation and increasing silver-positive macrophages in lungs at day 7, associated with significant levels of lung silver indicate that lung toxicity is persistent even with the absence of airway luminal inflammation at that time-point. The higher levels and persistence of lung silver in BN rats may be due to the pre-existing inflammatory state of the lungs.


Assuntos
Exposição por Inalação/efeitos adversos , Pulmão/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Pneumonia/induzido quimicamente , Prata/toxicidade , Animais , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Mediadores da Inflamação/metabolismo , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/fisiopatologia , Macrófagos Alveolares/efeitos dos fármacos , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/metabolismo , Masculino , Fosfolipídeos/metabolismo , Pneumonia/imunologia , Pneumonia/metabolismo , Pneumonia/fisiopatologia , Eosinofilia Pulmonar/induzido quimicamente , Eosinofilia Pulmonar/imunologia , Eosinofilia Pulmonar/metabolismo , Proteína D Associada a Surfactante Pulmonar/metabolismo , Ratos Endogâmicos BN , Ratos Sprague-Dawley , Mecânica Respiratória/efeitos dos fármacos , Fatores de Tempo
8.
Mol Med Rep ; 12(3): 3855-3861, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25997387

RESUMO

An imbalance between metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) affects the synthesis and degradation of extracellular matrix molecules, which have an important role in the pathogenesis of pulmonary fibrosis. Lower mRNA expression levels of suppressor of cytokine signaling 1 (SOCS1) are present in fibroblasts from the lungs of pulmonary fibrosis. However, little is currently known regarding the precise role of SOCS1 has in idiopathic pulmonary fibrosis (IPF). The present study examined the expression levels of MMPs and TIMPs in A549 human epithelial lung carcinoma cells and human embryonic lung fibroblasts (HLFs) stimulated with transforming growth factor­ß1 (TGF­ß1) in conditions of deficiency and over­expression of SOCS1, by transfection with a lentivirus. Overexpression of SOCS1 in A549 cells and HLFs significantly inhibited the mRNA expression levels of MMP­1, MMP­2 and MMP­9 (P<0.05). In the A549 cells lacking SOCS1 expression, the mRNA expression levels of TIMP­1 were significantly higher compared with the control groups (P<0.01). Overexpression of SOCS1 partially reversed these changes. The expression levels of TIMP­1 in the HLFs with an overexpression of SOCS1 were decreased, as compared with the SOCS1­deficient HLFs following TGF­ß1 stimulation; however, this finding was not significant (0.24±0.01 vs. 0.53±0.02, P>0.05). The expression levels of TIMP­2 were significantly lower in the cells overexpressing SOCS1. Conversely, the mRNA expression levels of TIMP­2 were significantly higher in the SOCS1­deficient A549 cells, as compared with all of the other groups (P<0.05). TIMP­4 expression levels were elevated in the A549 cells and HLFs transfected with the SOCS1­deficient lentivirus. The expression levels of TIMP­4 were significantly lower in the groups overexpressing SOCS1, as compared with the other groups. These results suggest that SOCS1 may act as a suppressor of pulmonary fibrosis, by reducing the expression of MMPs and TIMPs. Therefore, SOCS1 may be a target for IPF treatment.


Assuntos
Fibrose Pulmonar/enzimologia , Proteínas Supressoras da Sinalização de Citocina/fisiologia , Linhagem Celular Tumoral , Expressão Gênica , Regulação Enzimológica da Expressão Gênica , Humanos , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Proteína 1 Supressora da Sinalização de Citocina , Inibidor Tecidual de Metaloproteinase-2/genética , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Inibidores Teciduais de Metaloproteinases/genética , Inibidores Teciduais de Metaloproteinases/metabolismo
9.
Chin Med J (Engl) ; 126(23): 4403-8, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24286397

RESUMO

BACKGROUND: Interleukin-13 (IL-13) has been implicated to be responsible for recruitment of inflammatory cells from the blood to the lung, regulation of matrix metalloproteinase and induction of mucin production and secretion in chronic obstructive pulmonary disease (COPD). We determined plasma IL-13 levels in patients with COPD and investigated its association with common polymorphisms of IL-13 gene in a case-control study. METHODS: We genotyped 160 cases and 175 control subjects in a local hospital using Mass-Array(TM) Technology Platform then tested the association of four SNPs in IL-13 (rs1295685, rs1800925, rs1881457, rs20541) with COPD, and then determined plasma IL-13 levels in patients with COPD and controls. RESULTS: Association was found between IL-13 gene SNPs (rs20541 and rs1800925) and an increased risk of COPD. By linkage disequilibrium (LD) analysis, two blocks (rs1881457 and rs1800925; rs20541 and rs1295685) were found. The risk of COPD was found associated with the IL-13 gene polymorphism among southern Chinese Han population. Plasma IL-13 level was increased in COPD patients compared with controls. CONCLUSIONS: The polymorphism of the IL-13 gene is associated with an increased risk of COPD in southern Chinese Han population. Plasma IL-13 levels were found elevated in patients with COPD.


Assuntos
Interleucina-13/genética , Doença Pulmonar Obstrutiva Crônica/genética , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Genótipo , Haplótipos/genética , Humanos , Desequilíbrio de Ligação/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética
10.
Mol Med Rep ; 6(3): 631-8, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22736055

RESUMO

The risk of developing chronic obstructive pulmonary disease (COPD) is partially determined by genetic and environmental factors. Many published candidate gene studies show conflicting results due to ethnic differences and sample sizes. The number of these studies carried out in Chinese populations is small. To investigate candidate genes and haplotypes for susceptibility to COPD in a southern Han Chinese population, we performed genotyping of DNA samples in 200 COPD patients and 250 control subjects by analyzing 54 single-nucleotide polymorphisms (SNPs) in 23 genes associated with the development of COPD and/or pulmonary function identified by genome-wide association studies (GWAS). We also performed linkage disequilibrium (LD) and haplotype analysis according to the results of genotyping. The frequencies of the SNP [rs3749893 of testis­specific protein Y-encoded-like 4 (TSPYL-4) gene] G allele and SNP [rs1052443 of 5'-nucleotidase domain containing 1 (NT5DC1) gene] A allele were significantly higher in the cases studied compared to the control subjects (P=0.032, P<0.05, OR=0.692, 95% CI 0.495­0.970; P=0.0205, P<0.05, OR=0.670, 95% CI 0.477-0.941, respectively). Results showed that two blocks of SNPs (rs1052443 and rs3749893; rs11155242 and rs6937121) had sufficient precision to allow construction of a haplotype block. We constructed the TSPYL-4 and NT5DC1 haplotypes of the cases and controls, but no significant difference between the two groups was found. rs3749893 A allele of TSPYL-4 and rs1052443 C allele of NT5DC1 were associated with a protective effect against the deterioration of pulmonary function. In conclusion, TSPYL-4 and NT5DC1 gene polymorphisms are associated with susceptibility to COPD and pulmonary function.


Assuntos
5'-Nucleotidase/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Doença Pulmonar Obstrutiva Crônica/genética , Proteínas de Plasma Seminal/genética , 5'-Nucleotidase/metabolismo , Adulto , Idoso , Alelos , Frequência do Gene , Estudo de Associação Genômica Ampla , Genótipo , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Proteínas de Plasma Seminal/metabolismo
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