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1.
Clin Respir J ; 14(2): 140-147, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31758867

RESUMO

INTRODUCTION: The characteristics of Allergic Bronchopulmonary Aspergillosis (ABPA) based on its radiological classification is still unclear. OBJECTIVES: To investigate the clinical significances of ABPA patients with central bronchiectasis (ABPA-CB) by different radiological classifications of mucus plugs. METHODS: ABPA-CB patients from a pulmonary hospital between 2008 and 2015 were retrospectively included and analysed. According to the chest imaging in their first visit to physician, the ABPA-CB patients were divided into two groups based on the presence of high-attenuation mucus (HAM) or low-attenuation mucus (LAM). The primary endpoint was ABPA relapse within 1 year since the glucocorticoid withdrawal. The relationship between the imaging findings and the clinical prognosis was illuminated. RESULTS: A total of 125 ABPA patients were analysed in this study. Compared to the LAM group, the HAM group presented higher blood eosinophil cells counts, higher rates of Aspergillus detection isolated in sputum and expectoration of brownish-black mucus plugs, more affected lobes and segments, poorer pulmonary function and higher rate of relapse. CONCLUSIONS: The clinical characteristics and prognosis of ABPA-CB patients are closely related to its radiological phenotype of mucus plugs in the central bronchiectasis. Clinicians should promote a diversity of personalized treatments for different patients with different radiological characteristics.

2.
J Thorac Dis ; 10(7): 4387-4395, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30174887

RESUMO

Background: Patients with community acquired pneumonia (CAP) caused by viruses can develop severe complications, which result in hospitalization and death. The purpose of this study was to analyse the aetiology, incidence, clinical characteristics, and outcomes of CAP patients with fever during non-pandemics, and then to provide theoretical basis for accurate diagnosis and treatment in CAP patients. Methods: An enrolment system was established for monitoring the CAP patients with fever. Multiplex polymerase chain reaction (mPCR) kits were used to detect 10 viruses [influenza A and B, adenovirus (ADV), respiratory syncytial virus (RSV) A and B, picornavirus, parainfluenza virus (PIV), coronavirus, human metapneumovirus (HMPV), and bocavirus]. Data on age, gender, underlying diseases, complications, laboratory indexes, and outcomes were collected by physicians. Results: This prospective study included 320 patients with fever. Among them, 23.4% were viral-positive by mPCR, with influenza virus most prominent followed by picornavirus. Strong variation in seasonal distribution was shown in viral infections, with peak months from December to February. Patients with influenza infection were likely to be taken to emergency rooms and have respiratory failure with higher creatinine kinase levels and lower white blood cell counts. Streptococcus pneumoniae followed by haemophilus influenzae were the most common bacteria in viral co-infections, which accounted for one third of virus-positive patients. Viral CAP and mixed CAP were not independent factors for death. In addition, lactate dehydrogenase (LDH) >246 IU/L [odds ratio (OR) =7.06, 95% confidence interval (CI): 2.15-23.2, P=0.001], and serum calcium <2.18 mmol/L (OR =6.67, 95% CI: 1.42-31.3, P=0.016) were associated with death. Conclusions: Viruses play an important role in CAP patients with fever, a systematic clinical, radiological and biological analysis of these patients can contribute to effective therapy that may prevent the development of CAP and improve the outcomes. The present work showed an elaborate analysis evidence of viral infection among fever CAP inpatients.

3.
Cell Death Dis ; 9(9): 885, 2018 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-30158514

RESUMO

Nucleoside diphosphate kinase 1 (NME1) is well-known as a tumor suppressor that regulates p53 function to prevent cancer metastasis and progression. However, the role of NME1 in virus-infected cells remains unknown. Here, we showed that NME1 suppresses viral replication in foot-and-mouth disease virus (FMDV)-infected cells. NME1-enhanced p53-mediated transcriptional activity and induction of interferon-inducible antiviral genes expression. FMDV infection decreased NME1 protein expression. The 2B and VP4 proteins were identified as the viral factors that induced reduction of NME1. FMDV 2B protein has a suppressive effect on host protein expression. We measured, for the first time, VP4-induced lysosomal degradation of host protein; VP4-induced degradation of NME1 through the macroautophagy pathway, and impaired p53-mediated signaling. p53 plays significant roles in antiviral innate immunity by inducing several interferon-inducible antiviral genes expression, such as, ISG20, IRF9, RIG-I, and ISG15. VP4 promoted interaction of p53 with murine double minute 2 (MDM2) through downregulation of NME1 resulting in destabilization of p53. Therefore, 5-flurouracil-induced upregulation of ISG20, IRF9, RIG-I, and ISG15 were suppressed by VP4. VP4-induced reduction of NME1 was not related to the well-characterized blocking effect of FMDV on cellular translation, and no direct interaction was detected between NME1 and VP4. The 15-30 and 75-85 regions of VP4 were determined to be crucial for VP4-induced reduction of NME1. Deletion of these VP4 regions also inhibited the suppressive effect of VP4 on NME1-enhanced p53 signaling. In conclusion, these data suggest an antiviral role of NME1 by regulation of p53-mediated antiviral innate immunity in virus-infected cells, and reveal an antagonistic mechanism of FMDV that is mediated by VP4 to block host innate immune antiviral response.


Assuntos
Antivirais/imunologia , Vírus da Febre Aftosa/imunologia , Febre Aftosa/imunologia , Regulação da Expressão Gênica/imunologia , Interferons/imunologia , Lisossomos/imunologia , Nucleosídeo NM23 Difosfato Quinases/imunologia , Proteína Supressora de Tumor p53/imunologia , Animais , Linhagem Celular , Regulação para Baixo/imunologia , Células HEK293 , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata/imunologia , Transdução de Sinais/imunologia , Regulação para Cima/imunologia , Proteínas Virais/imunologia , Replicação Viral/imunologia
4.
BMJ Open ; 8(2): e018865, 2018 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-29453299

RESUMO

OBJECTIVES: Sarcoidosis is a multisystem disease characterised by the formation of granulomas within various organs, mainly the lungs. Several studies from different countries have been undertaken to investigate sarcoidosis with extrapulmonary involvement except from China. The objective of this study is to investigate a comparative clinical analysis in patients with pulmonary sarcoidosis with and without extrapulmonary involvement from China. METHODS: Data from inpatients diagnosed with sarcoidosis at Shanghai Pulmonary Hospital (Shanghai, China) between January 2009 and December 2014 were retrospectively collected and analysed. Six hundred and thirty-six patients with biopsy-proven sarcoidosis were included in the study, including 378 isolated pulmonary sarcoidosis and 258 pulmonary sarcoidosis plus extrapulmonary involvement. RESULTS: Two hundred and fifty-eight (40.6%) patients with pulmonary sarcoidosis had extrapulmonary involvement. Extrapulmonary localisations were detected mostly in extrathoracic lymph nodes (n=147) and skin (n=86). Statistically significant differences were demonstrated between patients with pulmonary sarcoidosis plus extrapulmonary involvement and patients with isolated pulmonary sarcoidosis for fatigue (16.6%vs8.3%, P<0.05), serum ACE (SACE) levels (79.0±46.9 IU/L vs 69.7±38.7 IU/L, P<0.05), and high-resolution CT (HRCT) findings (53.8%vs46.2%, P<0.05). CONCLUSIONS: Extrapulmonary involvement is common in patients with pulmonary sarcoidosis, with the most common sites being extrathoracic lymph nodes and skin. Patients with sarcoidosis with extrapulmonary involvement are more symptomatic (fatigue), have higher SACE levels and more deteriorating HRCT findings, to which clinicians should pay attention.


Assuntos
Pulmão/patologia , Sarcoidose Pulmonar/complicações , Sarcoidose Pulmonar/diagnóstico por imagem , Sarcoidose Pulmonar/fisiopatologia , Adulto , China , Estudos Transversais , Fadiga/epidemiologia , Feminino , Humanos , Pulmão/diagnóstico por imagem , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Peptidil Dipeptidase A/sangue , Estudos Retrospectivos , Pele/patologia , Tomografia Computadorizada por Raios X
5.
Cell Physiol Biochem ; 44(3): 1213-1223, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29179219

RESUMO

BACKGROUND/AIMS: Acute rejection (AR) is a major complication post renal transplantation, with no widely-accepted non-invasive biomarker. This study aimed to explore the expression profiles of long non-coding RNAs (lncRNAs) in the peripheral blood (PB) of renal transplant recipients and their potential diagnostic values. METHODS: The genome-wide lncRNA expression profiles were analyzed in 150 PB samples from pediatric and adult renal transplant (PRTx and ARTx) cohorts. The diagnostic performance of differentially expressed lncRNA was determined using receiver operator characteristic curve, with area under the curve (AUC) and 95% confidential interval (CI). Finally, a risk score was constructed with logistical regression model. RESULTS: A total of 162 lncRNAs were found differentially expressed in PRTx cohort, while 163 in ARTx cohort. Among these identified lncRNAs, 23 deregulated accordingly in both cohorts, and could distinguish AR recipients from those without AR. Finally, a risk score with two most significant lncRNAs (AF264622 and AB209021) was generated and exhibited excellent diagnostic performance in both PRTx (AUC:0.829, 95% CI:0.735-0.922) and ARTx cohorts (AUC: 0.889, 95% CI: 0.817-0.960). CONCLUSION: A molecular signature of two lncRNAs in PB could serve as a novel non-invasive biomarker for the diagnosis of AR in both pediatric and adult renal transplant recipients.


Assuntos
Rejeição de Enxerto/patologia , Transplante de Rim , RNA Longo não Codificante/sangue , Doença Aguda , Área Sob a Curva , Biomarcadores/sangue , Estudos de Coortes , Rejeição de Enxerto/genética , Rejeição de Enxerto/metabolismo , Humanos , Curva ROC , Transcriptoma , Transplante Homólogo
6.
Respir Med ; 122: 33-42, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27993289

RESUMO

Omalizumab, a humanized mAb that binds to IgE, has been an effective therapy for patients with severe allergic asthma; however, there are few clinical trials examining the efficacy of Omalizumab in patients with allergic bronchopulmonary aspergillosis (ABPA) except some case reports. To assess the clinical and immunological effects of Omalizumab in ABPA patients, we made a synthesis review of 102 cases from 30 published literature, analyzed the effects of Omalizumab therapy in ABPA and conducted subgroup analyses to determine factors that influenced the therapy endpoints. We found that Omalizumab treatment not only provided a clinically important reduction in serum IgE, exacerbation rates and steroid requirement, but also showed attenuated asthma symptoms and improved pulmonary function parameters in patients with ABPA. Moreover, further discussion was made when interpretating the results. Double-blind, randomized, placebo-controlled trials are necessary to establish the efficacy and safety of this novel therapeutic intervention for ABPA patients.


Assuntos
Antialérgicos/farmacologia , Anticorpos Monoclonais Humanizados/farmacologia , Aspergillus fumigatus/efeitos dos fármacos , Omalizumab/farmacologia , Adolescente , Adulto , Idoso , Antialérgicos/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Aspergilose Broncopulmonar Alérgica/tratamento farmacológico , Asma/tratamento farmacológico , Asma/prevenção & controle , Criança , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Omalizumab/administração & dosagem , Resultado do Tratamento
7.
J Thorac Dis ; 8(6): 1283-9, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27293848

RESUMO

BACKGROUND: Pulmonary Langerhans cell histiocytosis (PLCH) is an orphan disease in respiratory medicine, which most affects adult smokers. The purpose of this article was to discuss the clinical features, especially the radiologic features of PLCH patients during their hospitalization through a retrospective analysis on clinical data. Furthermore, the current literature was also reviewed. METHODS: Between December 2008 and June 2012, 14 patients with PLCH were assessed at Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. Among these patients, seven patients were diagnosed through tissue biopsy from the lung and one patient from enlarged cervical lymph nodes; the rest of six patients were diagnosed based on the clinical-radiological data. The data consisting of demographics, clinical presentation, smoking habits, pulmonary function tests (PFTs) and radiographic image from the medical records was analyzed retrospectively. RESULTS: The average age of patients (11 males and 3 females) was 42.79 (±13.71) years old. All male patients and one female patient had a long smoking history. The common manifestations were cough and exertional dyspnea. Spontaneous pneumothorax was found in three patients. Varieties of pulmonary shadows such as nodular, cystic, patch-like and cord-like were revealed by chest computed tomography (CT) examination. Large Langerhans cells (LCs) were discovered in biopsy tissue by immunohistochemical stains. CONCLUSIONS: PLCH is still an orphan disease and maybe related to smoking. Clinical symptoms such as cough and exertional dyspnea are non-specific. We shall pay attention to recurrent pneumothorax as clinically it is associated with PLCH. The characteristic radiological manifestation is cystic or nodular shadow in the lungs, which plays crucial roles in diagnosing PLCH.

8.
Cell Cycle ; 15(6): 850-60, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26901336

RESUMO

Foot-and-mouth disease is a highly contagious viral disease of cloven-hoofed animals that is caused by foot-and-mouth disease virus (FMDV). To replicate efficiently in vivo, FMDV has evolved methods to circumvent host antiviral defense mechanisms, including those induced by interferons (IFNs). Previous research has focused on the effect of FMDV L(pro) and 3C(pro) on type I IFNs. In this study, FMDV VP3 was found to inhibit type II IFN signaling pathways. The overexpression of FMDV VP3 inhibited the IFN-γ-triggered phosphorylation of STAT1 at Tyr701 and the subsequent expression of downstream genes. Mechanistically, FMDV VP3 interacted with JAK1/2 and inhibited the tyrosine phosphorylation, dimerization and nuclear accumulation of STAT1. FMDV VP3 also disrupted the assembly of the JAK1 complex and degraded JAK1 but not JAK2 via a lysosomal pathway. Taken together, the results reveal a novel mechanism used by which FMDV VP3 counteracts the type II IFN signaling pathways.


Assuntos
Proteínas do Capsídeo/metabolismo , Interferon gama/metabolismo , Janus Quinase 1/metabolismo , Lisossomos/metabolismo , Fator de Transcrição STAT1/metabolismo , Transdução de Sinais , Animais , Proteínas do Capsídeo/genética , Cricetulus , Regulação da Expressão Gênica , Genes Reporter , Células HEK293 , Interações Hospedeiro-Patógeno , Humanos , Interferon gama/genética , Janus Quinase 1/genética , Janus Quinase 2/genética , Janus Quinase 2/metabolismo , Luciferases/genética , Luciferases/metabolismo , Fosforilação , Ligação Proteica , Multimerização Proteica , Proteólise , Fator de Transcrição STAT1/genética , Tirosina/metabolismo
9.
Chest ; 149(2): 447-458, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26111257

RESUMO

BACKGROUND: Many epidemiologic studies have documented variable relationships between ambient particulate matter (PM) and COPD hospitalizations and mortality in cities worldwide. METHODS: Comprehensive and systematic searches were performed in the electronic reference databases (PubMed, EMBASE, Google Scholar, Ovid, and Web of Science) with specific search terms and selection criteria for relevant studies. Summary ORs and 95% CIs were calculated to evaluate the relationship between short-term exposure to PM with aerodynamic diameters ≤ 2.5 µm (PM2.5) and COPD hospitalizations and mortality. The sources of heterogeneity and the effect of potential confounders were explored using subgroup analyses. Study findings were analyzed using a random effects model and a fixed effects model in COPD hospitalizations and mortality, respectively. RESULTS: The search yielded 12 studies suitable for meta-analysis of hospitalizations and six studies suitable for the mortality meta-analysis until April 15, 2015. A 10-µg/m(3) increase in daily PM2.5 (lag days 0-7) was associated with a 3.1% (95% CI, 1.6%-4.6%) increase in COPD hospitalizations and a 2.5% (95% CI, 1.5%-3.5%) increase in COPD mortality. Significant publication bias was not found in studies focusing on the relationship between short-term PM2.5 exposure and COPD hospitalizations and mortality. CONCLUSIONS: Our combined analysis indicated that short-term exposure to a 10-µg/m(3) increment of ambient PM2.5 is associated with increased COPD hospitalizations and mortality. Further study is needed to elucidate to what extent this relationship is causal, together with other factors, and to elucidate the mechanism by which PM2.5 induces activation of cellular processes promoting COPD exacerbations.


Assuntos
Exposição Ambiental/efeitos adversos , Hospitalização/tendências , Modelos Teóricos , Material Particulado/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/mortalidade , Doença Pulmonar Obstrutiva Crônica/terapia , Cidades , Saúde Global , Humanos , Taxa de Sobrevida/tendências , Fatores de Tempo
10.
COPD ; 13(2): 160-6, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26488201

RESUMO

BACKGROUND: It was reported that Cathepsin E (Cat E) plays a critical role in antigen processing and in the development of pulmonary emphysema. The aim of this study was to investigate the role of Cat E and airflow limitation in the pathogenesis of COPD. METHODS: Sixty-five patients with COPD, 20 smoking control subjects without COPD and 15 non-smoking healthy control subjects were enrolled. Cat E and EIC (Elastase inhibitory capacity) expressions were measured by ELISA in sputum and serum samples and compared according to different subgroups. RESULTS: Cat E concentrations were significantly higher in patients with COPD than smoking control and non-smoking control subjects (P < 0.01). The levels of CatE were inversely correlated with FEV1% predicted in COPD patients (r = -0.95, P < 0.01). The levels of EIC were inversely positively correlated with FEV1% predicted in COPD patients (r = 0.926, P < 0.01). Levels of Cat E were also inversely correlated with the levels of EIC (r = -0.922, P < 0.01). CONCLUSIONS: Cat E contributes to the severity of airflow limitation during progression of COPD.


Assuntos
Catepsina E/biossíntese , Doença Pulmonar Obstrutiva Crônica/metabolismo , Enfisema Pulmonar/etiologia , Escarro/metabolismo , Biomarcadores/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Enfisema Pulmonar/metabolismo , Enfisema Pulmonar/fisiopatologia , Índice de Gravidade de Doença , Fumar/efeitos adversos , Escarro/citologia
11.
Oncotarget ; 6(29): 28071-83, 2015 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-26363448

RESUMO

Anti-EGFR monoclonal antibodies (mAb) such as cetuximab, panitumumab are one kind of efficacious targeted drugs in treatment of metastatic colorectal cancer (mCRC). However, only a small proportion of patients harbored wild-KRAS genotype can benefit from it. We hypothesized that personal genetic heterogeneity might be the main cause leading to obvious difference in its clinical efficacy. A retrospective study including 82 mCRC patients treated with chemotherapy plus cetuximab and a comprehensive meta-analysis containing 2831 cases within sixteen eligible studies were conducted to investigate the possible association between FCGR2A H131R and FCGR3A V158F and clinical outcome of mCRC patients treated with anti-EGFR mAb based therapy. Results of the retrospective study showed that H131R within FCGR2A or V158F within FCGR3A were not associated with clinical outcome in 82 KRAS wild chemorefractory mCRC patients in co-dominant, dominant, recessive, over-dominant, allele genetic models. However, the comprehensive meta-analysis with the largest of sample size obtained the significant result between FCGR3A V158F and PFS (FV/VV vs. FF: Ph = 0.027, MSR = 0.680, 95%CI = 0.549-0.842 in overall population; Ph = 0.12, MSR = 0.728, 95%CI = 0.648-0.818 in KRAS wild population) and OS (VV vs. FF: Ph < 0.001, MSR = 0.733, 95%CI = 0.578-0.930 in overall population). These findings indicate that KRAS wild chemorefractory mCRC individual harbored genotype FF of V158Fcan benefit from anti-EGFR mAb adjuvant therapy in terms of PFS and OS, and it may be useful genetic biomarker to predict clinical survival of mCRC individuals with anti-EGFR mAb based therapy.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Colorretais/genética , Resistencia a Medicamentos Antineoplásicos/genética , Receptores de IgG/genética , Idoso , Anticorpos Monoclonais/uso terapêutico , Cetuximab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/mortalidade , Intervalo Livre de Doença , Receptores ErbB/antagonistas & inibidores , Feminino , Genótipo , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Modelos de Riscos Proporcionais , Estudos Retrospectivos
12.
Bing Du Xue Bao ; 30(4): 456-62, 2014 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-25272603

RESUMO

Guanylate-binding protein 1 (GBP1) is an interferon induced protein, that belongs to the guany late-binding protein family. GBP1 is widely involved in anti-infection immune responses, anti-tumor activity and various biological reactions. Recent studies have proved that IFN-alpha, IFN-beta, IFN-gamma, IL1alpha, IL1beta, TNF-alpha and LPS can induce GBP1 expression; hence, the diverse biological functions of GBP1 have been gradually deduced and exploited. Many studies have been performed over recent years to understand the exact mechanisms that underlie the anti-infection and anti-tumor properties of GBP1. This review describes the molecular structure, biological activity, anti-infective properties and other functions of GBP1, in order to provide insights into the divergent roles of GBP1 in the regulation of various biological processes.


Assuntos
Proteínas de Ligação ao GTP/genética , Interferons/metabolismo , Animais , Antineoplásicos/metabolismo , Antivirais/metabolismo , Proteínas de Ligação ao GTP/química , Proteínas de Ligação ao GTP/metabolismo , Humanos , Interferons/genética
13.
Bing Du Xue Bao ; 30(2): 213-20, 2014 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-24923178

RESUMO

Reverse-genetic engineering of foot and mouth disease virus (FMDV) can improve the productivity, antigen matching, antigen stability, immune response ability, and biological safety of vaccines, so vaccine candidates with anticipated biological characteristics can be promptly achieved. Negative influence in taming of virulent strains can also be decreased or avoided. Reverse genetics not only make up for deficiencies like limitation of viral nature, low success rate, and time and energy consuming, but also realize more active designing of vaccines. Therefore, reverse genetics is significant in improving integral quality and efficiency of vaccines. In this review, we use FMDV vaccines as an example to summarize improvement in biological characteristics of virulent strains and provide a reference for related researches.


Assuntos
Vírus da Febre Aftosa/genética , Vírus da Febre Aftosa/imunologia , Febre Aftosa/prevenção & controle , Animais , Anticorpos Antivirais/imunologia , Febre Aftosa/imunologia , Febre Aftosa/virologia , Genética Reversa , Vacinas Virais/genética , Vacinas Virais/imunologia
14.
Bing Du Xue Bao ; 30(6): 704-12, 2014 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-25868287

RESUMO

RIG-I-like receptors (RLRs) belong to pattern recognition receptors, which perform significant roles in antiviral responses. RLRs can initiate a cascade of signaling transduction that induces the production of type I interferon and activates the interferon signaling pathway, ultimately resulting in antiviral responses. In the course of evolution, viruses have been constantly counteracting host immune systems to facilitate their own survival and replication, and have developed a set of antagonistic strategies. These mainly comprise elusion, disguise and attack strategies to eliminate the activation of RLRs. In virus-infected cells, RLRs recognize viral RNA and then induce antiviral responses. A better understanding of viral antagonistic strategies against RLRs will provide insights into the development of new antiviral medicines. This mini-review concludes that there are three main antagonistic strategies by which RNA viruses can counteract the activation of the RLRs pathway. It aims to provide references and insights for similar studies on viral antagonism in an array of RNA viruses.


Assuntos
RNA Helicases DEAD-box/imunologia , Vírus de RNA/imunologia , RNA de Cadeia Dupla/imunologia , RNA Viral/imunologia , Viroses/virologia , Proteína DEAD-box 58 , RNA Helicases DEAD-box/genética , Interações Hospedeiro-Patógeno , Humanos , Vírus de RNA/genética , Vírus de RNA/fisiologia , RNA de Cadeia Dupla/genética , RNA Viral/genética , Viroses/genética , Viroses/imunologia
15.
Chin Med J (Engl) ; 126(24): 4736-41, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24342321

RESUMO

BACKGROUND: Decorin is a small leucine-rich proteoglycan and it plays an important role in regulation of cell growth and migration in various tumor cell lines. Decorin was found down-regulated in non-small cell lung cancer tissue and may be involved in regulation of lung cancer development. METHODS: In this study, lentivirus-mediated RNA interference and over expression were employed to change the expression levels of decorin in lung cancer A549 cells. We tested the cell cycle of A549 cells and the expression of transforming growth factor (TGF)-ß, cyclin D1, epidermal growth factor receptor (EGFR), P53, and P21. RESULTS: We found that up-regulation of decorin could inhibit proliferation, block cell cycle at G1 and decrease invasive activity of A549 cells. Moreover, we also show that up-regulation of decorin induced significant decreases of TGF-ß1, cyclin D1 expression, phosphorylation of EGFR, and increases of P53 and P21 expression. Opposite results were observed in A549 cells with down-regulation of decorin. CONCLUSION: Our results suggest that decorin is a key regulator involved in proliferation and migration of A549 cells.


Assuntos
Movimento Celular/fisiologia , Decorina/metabolismo , Ciclo Celular/genética , Ciclo Celular/fisiologia , Movimento Celular/genética , Proliferação de Células , Ciclina D1/genética , Ciclina D1/metabolismo , Decorina/genética , Receptores ErbB/genética , Receptores ErbB/metabolismo , Humanos , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Células Tumorais Cultivadas
16.
PLoS One ; 8(9): e74381, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24058556

RESUMO

BACKGROUND: The widespread use of clopidogrel alone or in combination with aspirin may result in gastrointestinal mucosal injury, clinically represented as recurrent ulceration and bleeding complications. Our recent work suggested that clopidogrel significantly induced human gastric epithelial cell (GES-1) apoptosis and disrupted gastric mucosal barrier, and that a p38 MAPK inhibitor could attenuate such injury. However, their exact mechanisms are largely unknown. METHODS: The GES-1 cells were used as a model system, the effects of clopidogrel on the whole gene expression profile were evaluated by human gene expression microarray and gene ontology analysis, changes of the mRNA and protein expression were determined by real-time PCR and Western blot analysis, and cell viability and apoptosis were measured by MTT assay and flow cytometry analysis, respectively. RESULTS: Gene microarray analysis identified 79 genes that were differentially expressed (P<0.05 and fold-change >3) when cells were treated with or without clopidogrel. Gene ontology analysis revealed that response to stress and cell apoptosis dysfunction were ranked in the top 10 cellular events being affected, and that the major components of endoplasmic reticulum stress-mediated apoptosis pathway - CHOP and TRIB3- were up-regulated in a concentration- and time-dependent manner when cells were treated with clopidogrel. Pathway analysis demonstrated that multiple MAPK kinases were phosphorylated in clopidogrel-treated GES-1 cells, but that only SB-203580 (a p38-specific MAPK inhibitor) attenuated cell apoptosis and CHOP over-expression, both of which were induced by clopidogrel. CONCLUSIONS: Increased endoplasmic reticulum stress response is involved in clopidogrel-induced gastric mucosal injury, acting through p38 MAPK activation.


Assuntos
Apoptose/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Estômago/patologia , Ticlopidina/análogos & derivados , Apoptose/genética , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Clopidogrel , Análise por Conglomerados , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Estresse do Retículo Endoplasmático/genética , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/enzimologia , Perfilação da Expressão Gênica , Humanos , Imidazóis/farmacologia , Anotação de Sequência Molecular , Análise de Sequência com Séries de Oligonucleotídeos , Piridinas/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Ticlopidina/farmacologia , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
17.
World J Gastroenterol ; 19(23): 3658-64, 2013 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-23801869

RESUMO

AIM: To investigate the expression patterns of long non-coding RNAs (lncRNAs) in gastric cancer. METHODS: Two publicly available human exon arrays for gastric cancer and data for the corresponding normal tissue were downloaded from the Gene Expression Omnibus (GEO). We re-annotated the probes of the human exon arrays and retained the probes uniquely mapping to lncRNAs at the gene level. LncRNA expression profiles were generated by using robust multi-array average method in affymetrix power tools. The normalized data were then analyzed with a Bioconductor package linear models for microarray data and genes with adjusted P-values below 0.01 were considered differentially expressed. An independent data set was used to validate the results. RESULTS: With the computational pipeline established to re-annotate over 6.5 million probes of the Affymetrix Human Exon 1.0 ST array, we identified 136053 probes uniquely mapping to lncRNAs at the gene level. These probes correspond to 9294 lncRNAs, covering nearly 76% of the GENCODE lncRNA data set. By analyzing GSE27342 consisting of 80 paired gastric cancer and normal adjacent tissue samples, we identified 88 lncRNAs that were differentially expressed in gastric cancer, some of which have been reported to play a role in cancer, such as LINC00152, taurine upregulated 1, urothelial cancer associated 1, Pvt1 oncogene, small nucleolar RNA host gene 1 and LINC00261. In the validation data set GSE33335, 59% of these differentially expressed lncRNAs showed significant expression changes (adjusted P-value < 0.01) with the same direction. CONCLUSION: We identified a set of lncRNAs differentially expressed in gastric cancer, providing useful information for discovery of new biomarkers and therapeutic targets in gastric cancer.


Assuntos
Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica , RNA Longo não Codificante/genética , Neoplasias Gástricas/genética , Biologia Computacional , Mineração de Dados , Bases de Dados de Ácidos Nucleicos , Éxons , Perfilação da Expressão Gênica/métodos , Humanos , Modelos Lineares , Estadiamento de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos , Reprodutibilidade dos Testes , Neoplasias Gástricas/patologia
19.
Ai Zheng ; 27(4): 337-42, 2008 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-18423116

RESUMO

BACKGROUND & OBJECTIVE: Vincristine (VCR)-resistant gastric cancer cell line SGC7901/VCR is a typical multidrug resistant (MDR) cell line with high expression of P-glycoprotein (P-gp). However, verapamil (VRP), the inhibitor of P-gp, can not totally reverse the drug resistance, indicating that additional mechanisms must contribute to the MDR phenotype. Our previous study showed that sorcin, a calcium-binding protein, is significantly up-regulated in SGC7901/VCR cells. This study was to explore the role of sorcin in the development of MDR in human gastric cancer cell line SGC7901. METHODS: The full length sorcin cDNA was isolated by reverse transcription-polymerase chain reaction (RT-PCR). The FLAG-sorsin-pcDNA3.1 plasmid was constructed and transfected into SGC7901 cells. The mRNA and protein levels of sorcin in stable clones were detected by RT-PCR and Western blot. The sensitivity of SGC7901 cells to chemotherapeutic drugs was detected using MTT assay. Then sorcin-transfected SGC7901 cells (SGC-F-Sor) were transfected with sorcin antisense oligonucleotides (ASO). The VCR-sensitivity of SGC7901 cells was determined by MTT assay. RESULTS: The full-length sorcin cDNA (616 bp) was amplified by RT-PCR. The FLAG-sorsin-pcDNA3.1 plasmid was constructed successfully. The mRNA and protein levels of sorcin were up-regulated in SGC-F-Sor cells. Overexpression of sorcin produced 8.87 folds of VCR-resistance, 6.13 folds of adriamycin (ADM)-resistance, 6.67 folds of taxol-resistance, and 2.80 folds of 5-fluorouracil (5-FU)-resistance. However, when SGC-F-Sor cells were transfected with sorcin ASO, down-regulation of sorcin expression and increased sensitivity to VCR were observed. CONCLUSIONS: Overexpression of sorcin could induce low level of MDR in SGC7901 cells, indicating that sorcin is associated with MDR of SGC7901 cells. Sorcin maybe be a target of MDR reversal in gastric cancer cells.


Assuntos
Proteínas de Ligação ao Cálcio/fisiologia , Neoplasias Gástricas/tratamento farmacológico , Proteínas de Ligação ao Cálcio/análise , Proteínas de Ligação ao Cálcio/genética , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Humanos , RNA Mensageiro/análise , Neoplasias Gástricas/patologia
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