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1.
Int J Biol Markers ; 34(2): 108-116, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30966849

RESUMO

BACKGROUND: The prognostic value of Stathmin 1 (STMN1) in malignant solid tumors remains controversial. Thus, we conducted this meta-analysis to summarize the potential value of STMN1 as a biomarker for predicting overall survival in patients with solid tumor. METHODS: We systematically searched eligible studies in PubMed, Web of Science, and EMBASE from the establishment date of these databases to September 2018. Hazard ratio (HR) and its 95% confidence interval (CI) was used to assess the association between STMN1 expression and overall survival. RESULTS: A total of 25 studies with 4625 patients were included in this meta-analysis. Our combined results showed that high STMN1 expression was associated with poor overall survival in solid tumors (HR = 1.85, 95% CI 1.55, 2.21). In general, our subgroup and sensitivity analyses demonstrated that our combined results were stable and reliable. However, from the results of the subgroups we found that high STMN1 expression was not related to overall survival in colorectal cancer and endometrial cancer anymore, suggesting that much caution should be taken to interpret our combined result, and more studies with large sample sizes are required to further explore the prognostic value of STMN1 expression in the specific type of tumors, especially colorectal cancer and endometrial cancer. CONCLUSIONS: STMN1 could serve as a prognostic biomarker and could be developed as a valuable therapeutic target for patients with solid tumors. However, due to the limitations of the present meta-analysis, this conclusion should be taken with caution. Further studies adequately designed are required to confirm our findings.

2.
Biosci Rep ; 39(1)2019 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-30578380

RESUMO

A consensus about the prognostic role of NIMA-related kinase 2 (NEK2) expression in various solid tumors has not been made yet. Thus, this meta-analysis aimed to systematically assess the prognostic role of NEK2 expression in patients with solid tumors. The eligible studies were identified through searching PubMed, Web of Science, and EMBASE. The hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) were used to evaluate the link between NEK2 overexpression and overall survival (OS) and disease-free survival/recurrence-free survival (DFS/RFS) of patients with solid tumors. A total of 17 studies with 4897 patients were included in this meta-analysis. Among these studies, all of them explored the association between NEK2 expression and OS of patients with solid tumors. Our pooled analysis indicated that NEK2 overexpression was significantly related to adverse OS (HR = 1.66; 95% CI: 1.38-2.00; P = 0.001). Additionally, there were six studies with 854 patients that investigated the association between NEK2 expression and DFS/RFS. Our pooled result indicated that there was a substantial relationship between NEK2 overexpression and poorer DFS/RFS (HR = 2.00; 95% CI: 1.61-2.48; P = 0.003). In conclusion, our meta-analysis indicated that NEK2 may be a useful predictor of prognosis and an effective therapeutic target in solid tumors. Nevertheless, more high-quality studies are warranted to further support our conclusions because of several limitations in our meta-analysis.


Assuntos
Biomarcadores Tumorais/genética , Quinases Relacionadas a NIMA/genética , Neoplasias/genética , Prognóstico , Intervalo Livre de Doença , Humanos , Neoplasias/patologia
3.
Opt Express ; 26(20): 25989-26002, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30469692

RESUMO

We describe a first distributed polarization analysis (DPA) system using binary polarization rotators in an optical frequency domain reflectormeter (OFDR) capable of measuring the variations of polarization states along a single-mode fiber (SMF). We demonstrate using such a DPA system to accurately measure the distance-resolved birefringence with 12 fiber loops of different radii with different birefringence values along a length of SMF and obtain a bending-induced birefringence coefficient (BBC) of 6.601 × 10-10 m2, agreeing well with the theoretically estimated value of 5.334 × 10-10 m2. To further verify the measurement accuracy, we obtain the birefringence values of the 12 fiber loops of different radii one at a time using a non-distributed polarization analysis system with an accuracy traceable to a birefringence standard made with a quartz crystal, and obtain a BBC value of 6.490 × 10-10 m2, agreeing well with our distributed measurement with a relative error of only 1.68%. In addition, we measure the residual birefringence of the SMF with both distributed and non-distributed polarization analysis systems and obtain similar results with a relative error of only 0.59%. Our experiments not only validate the performances of our DPA system, but also the first to use DPA to experimentally obtain the accurate birefringence values along the SMF and verify the theory of bending-induced birefringence. Our work further proves that such an OFDR-based DPA system is a practical tool for optical component characterization, nondestructive optical material inspection, and distributed fiber optic transversal stress sensing.

4.
PLoS One ; 12(10): e0185646, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28973001

RESUMO

BACKGROUND: Although China has paid more attention on the prevention and control of tuberculosis (TB) in schools, several unsolved questions in this field still threaten the progress of TB control. Therefore, there is an urgent need to develop a systematic and practical strategy for Chinese school TB prevention and control system. In this study, we aimed to assess the feasibility of a combined strategy named ESMPE (examination, screening, monitoring, prevention and education) that adhere to the basic principles of Chinese schools TB control strategy. METHODS: The ESMPE strategy included five sections, namely TB screening during physical examination for the school freshmen entrances, screening of close contacts, monitoring of high-risk schools, preventive treatment and TB education. The effectiveness of ESMPE strategy was evaluated from 2011 to 2016. The original data were provided by the Dalian Tuberculosis Hospital. Descriptive analysis and nonparametric tests were used for comparing statistical differences of results between different years. RESULTS: The detection rate of active pulmonary TB in school freshmen was decreased from 2011 to 2016 (χ2 = 41.941, P = 6.0551E-8). 97.22% (17,043/17,530) of close contacts experienced close contacts screening, and the secondary attack rate (SAR) of TB in schools fell by 146.35/105 from 2011 to 2012, and finally reduced to 85.57/105 in 2016. There was a significant correlation between SAR of student TB and the rate of screened close contacts (r = -0.924, P = 0.009). TB incidence of five monitored schools had a substantial decline after receiving monitoring, and this declining trend continued in 2016. Due to the TB education and advanced screening methods, the mean of diagnostic delay time in students with TB was shortened (15.71 days), while still fewer latent TB infection students received preventive treatment (30.38%). CONCLUSIONS: The ESMPE strategy has shown a favorable effect on TB prevention and control in Dalian schools. More systematic evidence is needed on the effect of this strategy in reducing the incidence of TB in schools from other settings prior to its further scaling-up in China.


Assuntos
Tuberculose/prevenção & controle , Criança , China/epidemiologia , Humanos , Incidência , Tuberculose/diagnóstico , Tuberculose/epidemiologia
5.
Int J Surg ; 44: 176-184, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28583892

RESUMO

BACKGROUNDS: Updated guidelines for surgical site infections (SSIs) suggested that chlorhexidine (CH) or povidone-iodine (PVI) product was equally appropriate to be applied in preoperative disinfection, but which one was optimal remained ambiguous. Moreover, recent studies reported inconsistent results. Thus, an updated meta-analysis was conducted to clarify the superiority of CH or PVI for prevention of SSIs in clean and clean-contaminated surgery. METHODS: From the inception to November 2016, Pubmed, Embase, and the Cochrane library were systematically searched for randomized controlled trials (RCTs) which explored preoperative antisepsis schemes (CH or PVI) for prevention of SSIs in clean and clean-contaminated surgery. Relative risks (RRs) with 95% confidence interval (CI) were calculated using random effects model. Furthermore, subgroup analysis, sensitive analysis, and trial sequential analysis (TSA) were applied to estimate whether overall pooled effect was enough credible and robust. RESULTS: Thirteen RCTs involving 6997 patients (3352 in CH and 3645 in PVI group) undergoing clean and clean-contaminated surgeries were included in our meta-analysis. Compared with PVI, preoperative CH antisepsis was associated with lower incidence of SSIs (RR, 0.70; 95%CI, 0.60-0.83, I2 = 0). Additionally, subgroup analysis, sensitive analysis, and TSA indicated that the current available evidence was reliable and robust. CONCLUSIONS: CH should be more preferentially recommended for preoperative skin preparation as compared with PVI in clean and clean-contaminated surgery.


Assuntos
Anti-Infecciosos Locais/uso terapêutico , Antissepsia/métodos , Clorexidina/uso terapêutico , Povidona-Iodo/uso terapêutico , Infecção da Ferida Cirúrgica/prevenção & controle , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
J Surg Res ; 209: 17-29, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28032555

RESUMO

BACKGROUND: European Hernia Society guidelines suggested that the evidence of mesh augmentation for the prevention of incisional hernia (IH) was weak. In addition, previous systematic reviews seldom focused on quality of life and cost-effectiveness related to mesh placement. Therefore, an updated meta-analysis was performed to clarify quality of life, cost-effectiveness, the safety, and effectiveness of mesh reinforcement in preventing the incidence of IH. METHODS: Embase, Pubmed, and the Cochrane library were searched from the inception to May 2016 without language limitation for randomized controlled trials (RCTs) which explored mesh reinforcement for the prevention of IH in patients undergoing abdominal surgeries. RESULTS: Twelve RCTs totaling 1661 patients (958 in mesh, 703 in nonmesh) were included in our study. Compared with nonmesh, mesh reinforcement can effectively decrease the incidence of IH (relative risk: 0.19; 95% CI: 0.09-0.42). Besides, mesh placement was associated with improved quality of life, a higher rate of seroma (relative risk: 1.64; 95% CI: 1.13-2.37), and longer operating time (mean difference: 17.62; 95% CI: 1.44-33.80). No difference can be found between both groups in postoperative overall morbidity, systemic postoperative morbidity, wound-related morbidity, surgical site infection, hematoma, wound disruption, postoperative mortality, and length of hospital stay. CONCLUSIONS: Prophylactic mesh reinforcement may be effective and safe to prevent the formation of IH after abdominal surgery, without impairing quality of life. Thus, preventive mesh should be routinely recommended in high-risk patients.


Assuntos
Hérnia Incisional/prevenção & controle , Telas Cirúrgicas , Análise Custo-Benefício , Humanos , Hérnia Incisional/mortalidade , Tempo de Internação , Duração da Cirurgia , Dor Pós-Operatória , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
Sci Rep ; 6: 37769, 2016 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-27883041

RESUMO

Growing evidence links environmental exposure to hexachlorocyclohexanes (HCHs) to the risk of type 2 diabetes mellitus (T2DM), and ADIPOQ that encodes adiponectin is considered as an important gene for T2DM. However, the role of ADIPOQ-HCH interaction on T2DM risk remains unclear. Thus, a paired case-control study was conducted in an East Chinese community. A total of 1446 subjects, including 723 cases and 723 controls matched on age, gender and residence, were enrolled, and 4 types of HCH isomers were measured in serum samples using GC-MS/MS. Additionally, 4 candidate ADIPOQ SNPs (rs182052, rs266729, rs6810075, and rs16861194) were genotyped by TaqMan assay, and plasma adiponectin was measured using ELISA. No associations between 4 SNPs and T2DM risk were found, but T2DM risk significantly increased with serum levels of ß-HCH (P < 0.001). Furthermore, the synergistic interaction between ß-HCH and rs182052 significantly increased T2DM risk (OR I-additive model = 2.20, OR I-recessive model = 2.13). Additionally, individuals carrying only rs182052 (A allele) with high levels of ß-HCH had significant reduction in adiponectin levels (P = 0.016). These results indicate that the interaction between rs182052 and ß-HCH might increase the risk of T2DM by jointly decreasing the adiponectin level and potentially trigger T2DM development.


Assuntos
Adiponectina/genética , Grupo com Ancestrais do Continente Asiático/genética , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença/genética , Hexaclorocicloexano/efeitos adversos , Polimorfismo de Nucleotídeo Único/genética , Estudos de Casos e Controles , Estudos Transversais , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Risco , Espectrometria de Massas em Tandem/métodos
8.
Sci Rep ; 6: 27854, 2016 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-27291303

RESUMO

Brominated flame retardants exposure has been associated with increasing trends of diabetes and metabolic disease. Thus, the purpose of this study was to provide evidence of polybrominated diphenyl ethers (PBDEs) exposure in relation to diabetes prevalence and to reveal the potential underlying mechanism in epidemiological and animal studies. All the participants received a questionnaire, health examination, and the detection of 7 PBDE congeners in serum in two independent community-based studies from 2011 to 2012 in China. Male rats were exposed to 2,2'4,4'-tetrabromodiphenyl ether (BDE47) for 8 weeks to explore its effects on glucose homeostasis and potential mechanisms using high-throughput genomic analysis. Among the 7 congeners, BDE47 showed significant high detection rate and concentration in cases in Study I and Study II. Every tertile of BDE47 exposure significantly increased the risk of diabetes prevalence in Study I (Ptrend = 0.001) and Study II (Ptrend < 0.001). Additionally, BDE47 treatments induced hyperglycemia in rats. Furthermore, gene microarray analysis showed that diabetes pathway and three gene ontology terms involved in glucose transport were enriched. The results indicated that environmental exposure to BDE47 was associated with increased diabetes prevalence. However, further prospective and mechanistic studies are needed to the causation of diabetes in relation to BDE47.


Assuntos
Diabetes Mellitus Tipo 2/etiologia , Exposição Ambiental , Retardadores de Chama/toxicidade , Éteres Difenil Halogenados/toxicidade , Animais , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Glucose/metabolismo , Éteres Difenil Halogenados/sangue , Humanos , Hiperglicemia/etiologia , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Razão de Chances , Análise de Sequência com Séries de Oligonucleotídeos , Prevalência , Ratos , Ratos Sprague-Dawley
9.
Artigo em Inglês | MEDLINE | ID: mdl-27111156

RESUMO

Tb(3+)/Mn(2+) activated Ca3La6(SiO4)6 (CLS) phosphors were prepared by solid-state reaction method, and their photoluminescence and cathodoluminescence (CL) properties were investigated. The CLS:Tb(3+) sample shows a yellowish green emission under 377nm excitation, and the excitation spectrum reveals the excitation peaks between 340 and 390nm can match with the near-ultraviolet LED chip. Excellent thermal stability has been obtained in the CLS:Tb(3+) phosphor by studying the temperature dependence of the Tb(3+) emission intensity. By introducing Mn(2+) into CLS:Tb(3+), tunable emissions are generated due to the efficient energy transfer from Tb(3+) to Mn(2+). The CL spectrum of CLS:Tb(3+) displays that the characteristic (5)D4-(7)FJ (J=6-3) transitions of Tb(3+) are found under electron beam excitation. The above investigation results imply that the CLS:Tb(3+), Mn(2+) phosphors could have potential applications on LEDs and FEDs.

10.
Int Immunopharmacol ; 22(2): 498-504, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25111852

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with high mortality and poor prognosis. Previous studies confirmed that NF-κB plays a critical role in the pathogenesis of pulmonary fibrosis and glucagon like peptide-1 (GLP-1) has a property of anti-inflammation by inactivation of NF-κB. Furthermore, the GLP-1 receptor was detected in the lung tissues. Our aim was to investigate the potential value and mechanisms of GLP-1 on BLM-induced pulmonary fibrosis in mice. Mice with BLM-induced pulmonary fibrosis were treated with or without GLP-1 administration. 28 days after BLM infusion, the number of total cells, macrophages, neutrophils, lymphocytes, and the content of TGF-ß1 in BALF were measured. Hematoxylin-eosin (HE) staining and Masson's trichrome (MT) staining were performed. The Ashcroft score and hydroxyproline content were analyzed. RT-qPCR and western blot were used to evaluate the expression of α-SMA and VCAM-1. The phosphorylation of NF-κB p65 was also assessed by western blot. DNA binding of NF-κB p65 was measured through Trans(AM) p65 transcription factor ELISA kit. GLP-1 reduced inflammatory cell infiltration and the content of TGF-ß1 in BLAF in mice with BLM injection. The Ashcroft score and hydroxyproline content were decreased by GLP-1 administration. Meanwhile, BLM-induced overexpression of α-SMA and VCAM-1 were blocked by GLP-1 treatment in mice. GLP-1 also reduced the ratio of phosphor-NF-κB p65/total-NF-κB p65 and NF-κB p65 DNA binding activity in BLM-induced pulmonary fibrosis in mice. Our data found that BLM-induced lung inflammation and pulmonary fibrosis were significantly alleviated by GLP-1 treatment in mice, possibly through inactivation of NF-κB.


Assuntos
Anti-Inflamatórios/uso terapêutico , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , NF-kappa B/antagonistas & inibidores , Fibrose Pulmonar/tratamento farmacológico , Actinas/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Antibióticos Antineoplásicos , Bleomicina , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Contagem de Células , Colágeno/metabolismo , DNA/metabolismo , Peptídeo 1 Semelhante ao Glucagon/farmacologia , Hidroxiprolina/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , Fator de Transcrição RelA/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Molécula 1 de Adesão de Célula Vascular/metabolismo
11.
Zhongguo Zhen Jiu ; 34(2): 205-8, 2014 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-24796072

RESUMO

The effectiveness and safety of acupuncture-moxibustion for the treatment of agrypnia was systematically reviewed. The clinical randomized controlled trial (RCT) of acupuncture-moxibustion for agrypnia were collected. The literature and document on acupuncture-moxibustion RCT for the treatment of agrypnia that published from January of 2001 to March of 2012 was searched with computer in PubMed, CNKI, Wanfang and VIP database. According to Cochrane Handbook 5. 1. 0, the bias risk and quality assessment were performed on every included trial and RevMan 5. 0 software was applied to make the Meta analysis. Totally 14 researches were included, involving 2662 cases. The Meta analysis showed that the differences of total effective rate between acupuncture-moxibustion and clinical routine treatment were significant [RR = 1.16, 95% CI (1.12, 1.19), Z = 9.32, P < 0.000 01]. The results indicate that total effective rate of acupuncture-moxibustion for agrypnia is obviously superior to that of clinical routine treatment, meaning clinical efficacy of acupuncture-moxibustion is served credit.


Assuntos
Terapia por Acupuntura , Ambliopia/terapia , Moxibustão , Criança , Pré-Escolar , Feminino , Humanos , Masculino
12.
Int J Cancer ; 134(7): 1539-48, 2014 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-24114584

RESUMO

Cytochrome P450 2A13 (CYP2A13), mainly expressed in human respiratory tract, is highly efficient in the metabolic activation of aflatoxin (AF) B1 (AFB1) and is assumed to play a role in human lung tumorigenesis in airborne AFB1 exposure. To validate the assumption, we exposed human bronchial epithelial (BEAS-2B) cells stably expressing CYP2A13 (B-2A13), CYP1A2 (B-1A2) and CYP2A6 (B-2A6) to 0.1-10 nM AFB1 for 30-50 passages. B-2A13 cells showed increased sensitivity to 0.1 nM AFB1-induced neoplastic transformation and the formation of tumors in nude mice were observed at passage 30 (P30) while it occurred at P50 B-1A2 cells. B-2A6, similar to vector control, showed no neoplastic transformation in this condition. Additionally, AFB1-DNA adducts and 8-OHdG significantly increased in transformed P40 B-2A13, in parallel with the upregulation of p-ATR, p-BRCA1, Mre11, Rad50 and Rad51. However, the apoptosis of P40 cells was near normal, while the expression of Bax, C-Caspase 3 and C-PARP increased passage-dependently. Inhibition of ATR (ATR siRNA or NU6027) reversely increased the apoptosis of P40 B-2A13 cells in parallel with the upregulation of Bax, C-Caspase 3 and C-PARP, suggesting that ATR plays an important role in maintaining cell survival via antiapoptosis. Additionally, activation of ATR was necessary to neoplastic transformation since blockage of ATR in P40 cells inhibited DNA damage repair response and anchorage-independent growth. Our data demonstrated that CYP2A13 played a critical role in AFB1-induced neoplastic transformation. ATR-mediated the dysfunction of apoptosis and DNA damage repair might be involved. These results help establish a linkage between airborne AFB1 and human respiratory carcinoma.


Assuntos
Aflatoxina B1/toxicidade , Hidrocarboneto de Aril Hidroxilases/genética , Brônquios/efeitos dos fármacos , Brônquios/enzimologia , Transformação Celular Neoplásica/efeitos dos fármacos , Aflatoxina B1/farmacocinética , Animais , Apoptose/efeitos dos fármacos , Hidrocarboneto de Aril Hidroxilases/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia/genética , Brônquios/patologia , Caspase 3/genética , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Sistema Enzimático do Citocromo P-450/genética , Adutos de DNA/efeitos dos fármacos , Reparo do DNA , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/enzimologia , Células Epiteliais/patologia , Humanos , Camundongos , Camundongos Nus , Poli(ADP-Ribose) Polimerases/genética , Regulação para Cima/efeitos dos fármacos , Proteína X Associada a bcl-2/genética
13.
Arch Toxicol ; 87(9): 1697-707, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23907605

RESUMO

Cytochrome P450 2A13 (CYP2A13) is an extrahepatic enzyme that mainly expresses in human respiratory system, and it is reported to mediate the metabolic activation of aflatoxin B1. Due to the structural similarity, AFG1 is predicted to be metabolized by CYP2A13. However, the role of CYP2A13 in metabolic activation of AFG1 is unclear. In present study, human bronchial epithelial cells that stably express CYP2A13 (B-2A13) were used to conduct the effects of AFG1 on cytotoxicity, apoptosis, DNA damages, and their response protein expression. Low concentrations of AFG1 induced significant cytotoxicity and apoptosis, which was consistent with the increased expressions of pro-apoptotic proteins, such as C-PARP and C-caspase-3. In addition, AFG1 increased 8-OHdG and γH2AX in the nuclies and induced S phase arrest and DNA damage in B-2A13 cells, and the proteins related to DNA damage responses, such as ATM, ATR, Chk2, p53, BRCA1, and γH2AX, were activated. All the above effects were inhibited by nicotine (a substrate of CYP2A13) or 8-MOP (an inhibitor of CYP enzymes), confirming that CYP2A13 mediated the AFG1-induced cytotoxicity and DNA damages. Collectively, our findings first demonstrate that CYP2A13 might be an efficient enzyme in metabolic activation of AFG1 and helps provide a new insight into adverse effects of AFG1 in human respiratory system.


Assuntos
Aflatoxinas/metabolismo , Hidrocarboneto de Aril Hidroxilases/metabolismo , Brônquios/metabolismo , Mucosa Respiratória/metabolismo , Aflatoxina B1/agonistas , Aflatoxina B1/metabolismo , Aflatoxina B1/toxicidade , Aflatoxinas/agonistas , Aflatoxinas/toxicidade , Apoptose/efeitos dos fármacos , Hidrocarboneto de Aril Hidroxilases/antagonistas & inibidores , Hidrocarboneto de Aril Hidroxilases/genética , Transporte Biológico/efeitos dos fármacos , Biotransformação , Brônquios/citologia , Brônquios/efeitos dos fármacos , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Clonais , Dano ao DNA , Desoxiguanosina/agonistas , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Histonas/agonistas , Histonas/metabolismo , Humanos , Interferência de RNA , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Mucosa Respiratória/citologia , Mucosa Respiratória/efeitos dos fármacos , Fase S/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Especificidade por Substrato
14.
FEBS Lett ; 587(18): 3032-7, 2013 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-23892074

RESUMO

Previous microarray analyses revealed that LMO4 is expressed in 3T3-L1 preadipocytes, however, its roles in adipogenesis are unknown. In the present study, using RT-PCR sequencing and quantitative real-time RT-PCR, we confirmed that LMO4 gene is expressed in 3T3-L1 preadipocytes and its expression peaks at the early stage of 3T3-L1 preadipocyte differentiation. Further analyses showed that LMO4 knockdown decreased the proliferation of 3T3-L1 preadipocytes, and attenuated the differentiation of 3T3-L1 preadipocytes, as evidenced by reduced lipid accumulation and down-regulation of PPARγ gene expression. Collectively, our findings indicate that LMO4 is a novel modulator of adipogenesis.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Adipócitos/metabolismo , Adipogenia/genética , Regulação da Expressão Gênica , Proteínas com Domínio LIM/genética , PPAR gama/genética , Células 3T3-L1 , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adipócitos/citologia , Animais , Sequência de Bases , Diferenciação Celular , Proliferação de Células , Proteínas com Domínio LIM/metabolismo , Camundongos , Dados de Sequência Molecular , PPAR gama/metabolismo , Transdução de Sinais
15.
Arch Toxicol ; 87(8): 1557-67, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23640034

RESUMO

Several persistent organic pollutants are reported to be potentially associated with the risk of human diabetes that has become rapidly epidemic in China currently. 2,2',3,3',4,4',5,5',6,6'-decabromodiphenyl ether (BDE209) is commercially most important both in the production and in the use of polybrominated diphenyl ethers (PBDEs). It might bioaccumulate in wildlife and human and is the only PBDEs mixture still used today. In the present study, male adult rats treated with BDE209 (0, 0.05, 1, and 20 mg/kg) for 8 weeks were used to explore the effects of BDE209 on glucose homeostasis and possible mechanisms; 0.05 mg/kg of BDE209 induced dose-related hyperglycemia. Then, we performed the full-genome gene expression microarrays, gene ontology analysis, and pathway analysis in this group and control. BDE209 induced 1,257 liver gene transcript changes, and 18 canonical pathways were significantly enriched. Four of them were involved in immune diseases, including autoimmune thyroid disease, graft-versus-host disease, allograft rejection, and type I diabetes mellitus (T1MD), which was confirmed by the decrease in serum insulin. Subsequently, gene act network and gene co-expression network found that some MHC molecules and TNF-α were involved in T1DM pathway, which was then confirmed by the increase in serum TNF-α. Additionally, reduced glutathione and superoxide dismutase in plasma indicated that oxidative damage might partly contribute to BDE209-induced hyperglycemia. The results of this study provide some new experimental evidence that the exposure to high levels of BDE209 may contribute to the onset of diabetes in human populations. Further work needs to be done to confirm this link.


Assuntos
Glucose/metabolismo , Éteres Difenil Halogenados/toxicidade , Fígado/efeitos dos fármacos , Fígado/fisiologia , Animais , Diabetes Mellitus Tipo 1/genética , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Hiperglicemia/induzido quimicamente , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Fígado/metabolismo , Masculino , Redes e Vias Metabólicas/efeitos dos fármacos , Redes e Vias Metabólicas/genética , Análise em Microsséries , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
16.
Toxicol Appl Pharmacol ; 270(2): 114-21, 2013 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-23602888

RESUMO

Cytochrome P450 2A13 (CYP2A13) mainly expresses in human respiratory system and mediates the metabolic activation of aflatoxin B1 (AFB1). Our previous study suggested that CYP2A13 could increase the cytotoxic and apoptotic effects of AFB1 in immortalized human bronchial epithelial cells (BEAS-2B). However, the role of CYP2A13 in AFB1-induced DNA damage is unclear. Using BEAS-2B cells that stably express CYP2A13 (B-2A13), CYP1A2 (B-1A2), and CYP2A6 (B-2A6), we compared their effects in AFB1-induced DNA adducts, DNA damage, and cell cycle changes. BEAS-2B cells that were transfected with vector (B-vector) were used as a control. The results showed that AFB1 (5-80 nM) dose- and time-dependently induced DNA damage in B-2A13 cells. AFB1 at 10 and 80nM significantly augmented this effect in B-2A13 and B-1A2 cells, respectively. B-2A6 cells showed no obvious DNA damage, similar to B-vector cells and the vehicle control. Similarly, compared with B-vector, B-1A2 or B-2A6 cells, B-2A13 cells showed more sensitivity in AFB1-induced γH2AX expression, DNA adduct 8-hydroxy-deoxyguanosine formation, and S-phase cell-cycle arrest. Furthermore, AFB1 activated the proteins related to DNA damage responses, such as ATM, ATR, Chk2, p53, BRCA1, and H2AX, rather than the proteins related to DNA repair. These effects could be almost completely inhibited by 100 µM nicotine (a substrate of CYP2A13) or 1 µM 8-methoxypsoralen (8-MOP; an inhibitor of CYP enzyme). Collectively, these findings suggest that CYP2A13 plays an important role in low-concentration AFB1-induced DNA damage, possibly linking environmental airborne AFB1 to genetic injury in human respiratory system.


Assuntos
Aflatoxina B1/toxicidade , Hidrocarboneto de Aril Hidroxilases/metabolismo , Brônquios/efeitos dos fármacos , Adutos de DNA/metabolismo , Dano ao DNA , Aflatoxina B1/metabolismo , Hidrocarboneto de Aril Hidroxilases/antagonistas & inibidores , Brônquios/enzimologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/enzimologia , Humanos , Immunoblotting , Metoxaleno/farmacologia , Microscopia Confocal , Nicotina/farmacologia
17.
Sheng Wu Gong Cheng Xue Bao ; 27(8): 1215-24, 2011 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-22097811

RESUMO

We constructed transgenic chicken bioreactor vector, driven by chicken ovalbumin promoter, lentiviral vector and cytomegalovirus (CMV) promoter control vector encoding green fluorescent protein (GFP) and luciferase (Luc) as reporter genes. The three vectors were used to transfect or infect chicken primary oviduct epithelial cells, embryo fibroblasts cells, mouse 3T3-L1 preadipocytes cells and bovine mammary epithelial cells. High efficient and specific expression vector for transgenic chicken bioreactor was determined by detecting fluorescence and luciferase activity. Reporter gene analysis showed that chicken ovalbumin promoter expression vector was not cell type-specific in these four different cells. Additionally, luciferase reporter analysis illustrated that the chicken ovalbumin promoter activity was over 100 times lower than that of the CMV promoter in four different cells. Both of these two reporter genes were expressed in those four different cells infected by lentiviral expression vectors. Similarly, the GFP reached the similar expression level in cells infected by lentivirus and cells transfected with CMV promoter plasmid vectors when the multiplicity of infection was 20. In conclusion, the transgenic chicken bioreactor vector under the control of chicken ovalbumin promoter was not highly efficient and cell type-specific. However, the efficient expression and extensiveness oflentiviral vector could be used for studying chicken oviduct bioreactor.


Assuntos
Animais Geneticamente Modificados , Galinhas/genética , Vetores Genéticos/genética , Ovalbumina/genética , Oviductos/metabolismo , Células 3T3-L1 , Animais , Bovinos , Citomegalovirus/genética , Citomegalovirus/metabolismo , Células Epiteliais/citologia , Feminino , Proteínas de Fluorescência Verde/genética , Lentivirus/genética , Lentivirus/metabolismo , Luciferases/genética , Camundongos , Oviductos/citologia , Regiões Promotoras Genéticas/genética , Transfecção
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