RESUMO
Liposcelis bostrychophila, commonly known as booklouse, is an important stored-product pest worldwide. Studies have demonstrated that booklices have developed resistance to several insecticides. In this study, an integument esterase gene, LbEST-inte4, with upregulated expression, was characterized in L. bostrychophila. Knockdown of LbEST-inte4 resulted in a substantial increase in the booklice susceptibility to malathion. Overexpression of LbEST-inte4 in Drosophila melanogaster significantly enhanced its malathion tolerance. Molecular modeling and docking analysis suggested potential interactions between LbEST-inte4 and malathion. When overexpressed LbEST-inte4 in Sf9 cells, a notable elevation in esterase activity and malathion tolerance was observed. HPLC analysis indicated that the LbEST-inte4 enzyme could effectively degrade malathion. Taken together, the upregulated LbEST-inte4 appears to contribute to malathion tolerance in L. bostrychophila by facilitating the depletion of malathion. This study elucidates the molecular mechanism underlying malathion detoxification and provides the foundations for the development of effective prevention and control measures against psocids.
Assuntos
Esterases , Proteínas de Insetos , Insetos , Inseticidas , Malation , Animais , Drosophila melanogaster , Esterases/metabolismo , Esterases/genética , Esterases/química , Inativação Metabólica , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Proteínas de Insetos/química , Insetos/efeitos dos fármacos , Resistência a Inseticidas/genética , Inseticidas/metabolismo , Inseticidas/química , Inseticidas/farmacologia , Malation/metabolismo , Malation/química , Malation/toxicidade , Malation/farmacologiaRESUMO
A chemical investigation on the fruiting bodies of Ganoderma lucidum led to the isolation and identification of five undescribed ergosteroids including two des-D-steroids (3 and 4) and one rare 6/6/7/5-fused carbon skeletal ergosterol (5) along with one 19-nor labdane-type diterpenoid (6). Their structures including their absolute configurations, were assigned by spectroscopic methods, ECD calculations, and X-ray diffraction analysis. In addition, the anti-inflammatory activities of all the isolates were evaluated. The results indicated that compound 1 can significantly down-regulate the protein expression of iNOS and COX-2 at 20 µM in LPS- stimulated RAW264.7 cells.
Assuntos
Diterpenos , Ergosterol , Reishi , Camundongos , Diterpenos/farmacologia , Diterpenos/química , Diterpenos/isolamento & purificação , Animais , Células RAW 264.7 , Reishi/química , Ergosterol/farmacologia , Ergosterol/análogos & derivados , Ergosterol/química , Ergosterol/isolamento & purificação , Estrutura Molecular , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/antagonistas & inibidores , Ciclo-Oxigenase 2/metabolismo , Relação Estrutura-Atividade , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Relação Dose-Resposta a Droga , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Regulação para Baixo/efeitos dos fármacosRESUMO
Ganoderma lucidum, known as the "herb of spiritual potency", is used for the treatment and prevention of various diseases, but the responsible constituents for its therapeutic effects are largely unknown. For the purpose of obtaining insight into the chemical and biological profiling of meroterpenoids in G. lucidum, various chromatographic approaches were utilized for the title fungus. As a result, six undescribed meroterpenoids, chizhienes A-F (1-6), containing two pairs of enantiomers (4 and 5), were isolated. Their structures were identified using spectroscopic and computational methods. In addition, the anti-inflammatory activities of all the isolates were evaluated by Western blot analysis in LPS-induced macrophage cells (RAW264.7), showing that 1 and 3 could dose dependently inhibit iNOS but not COX-2 expression. Further, 1 and 3 were found to inhibit nitric oxide (NO) production using the Greiss reagent test. The current study will aid in enriching the structural and biological diversity of Ganoderma-derived meroterpenoids.
Assuntos
Ganoderma , Reishi , Reishi/química , Ganoderma/química , Anti-Inflamatórios/farmacologia , Linhagem Celular , Macrófagos , Estrutura MolecularRESUMO
Previous studies have suggested an association between preoperative plasma fibrinogen and D-dimer levels and prognosis in patients with non-small cell lung cancer (NSCLC) who underwent surgery. In this study, we evaluate the value of pre- and post-operative plasma fibrinogen and D-dimer levels and changes in the levels of the two markers between before and after operation in predicting tumor recurrence and metastasis in NSCLC patients who undergoing radical surgery. One hundred and eighty-four patients with I-IIIA NSCLC were enrolled in this study, and plasma fibrinogen and D-dimer levels were measured in these patients before and after surgery, respectively. The results showed that pre- and post-operative plasma fibrinogen and D-dimer levels were significantly higher in NSCLC patients than in control group. Pre- and post-operative plasma fibrinogen and D-dimer positivities were significantly correlated with tumor recurrence (P = 0.020 and P = 0.001 for fibrinogen, and P = 0.027 and P = 0.001 for D-dimer). Moreover, there was a significant link between the decrease in fibrinogen and D-dimer levels after surgery and tumor recurrence (P = 0.014 and P = 0.018). Patients with pre- and post-operative fibrinogen and D-dimer positivities had a shorter disease-free survival (DFS) than those without (P = 0.002 and P < 0.001 for fibrinogen, and P = 0.003 and P = 0.001 for D-dimer). Multivariate Cox regression analyses revealed that pre- and post-operative fibrinogen and D-dimer positivities were independent predictors for unfavorable DFS. Our results indicate that pre- and post-operative plasma fibrinogen and D-dimer levels may be useful biomarkers in predicting tumor recurrence and metastasis for patients who undergo curative surgery.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fibrinogênio/análise , Neoplasias Pulmonares/patologia , Adulto , Idoso , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Intervalo Livre de Doença , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Fibrinogênio/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Período Pós-Operatório , Valor Preditivo dos Testes , Período Pré-Operatório , Prognóstico , Modelos de Riscos ProporcionaisRESUMO
The purpose of this prospective study was to evaluate the prognostic and predictive value of survivin mRNA-circulating tumor cells (CTCs) in peripheral blood of patients with advanced non-small cell lung cancer (NSCLC) who received first-line chemotherapy. Blood samples were collected from 78 patients with stage IIIB and IV NSCLC before (C0) and after 1 cycle (C1) and 3 cycles (C3) of chemotherapy. Survivin mRNA-CTCs were detected by real-time quantitative-PCR and correlated with treatment response and survival. The results showed that the presence of survivin mRNA-CTCs before and during chemotherapy was associated with histology type, tumor stage, and number of sites of metastasis. Moreover, the detection of survivin mRNA-CTCs after 1 and 3 cycles of chemotherapy was significantly associated with imaging response to treatment. Patients with positivity for survivin mRNA-CTCs at C0, C1, and C3 time points had significantly shorter progressive-free survival (PFS) and overall survival (OS) compared with patients without. Multivariate analysis using a Cox proportional hazards model revealed that the presence of survivin mRNA-CTCs after one and three chemotherapy cycles was a significant independent factor for worse PFS and OS. In conclusion, the detection of survivin mRNA-CTCs before and during chemotherapy is a prognostic and predictive factor correlated with poor PFS and OS in patients with advanced NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Proteínas Inibidoras de Apoptose/genética , Neoplasias Pulmonares/patologia , RNA Mensageiro/análise , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Células Neoplásicas Circulantes , SurvivinaRESUMO
The aim of this study was to assess the prognostic value of EpCAM/MUC1 mRNA-positive circulating tumor cells (CTCs) in patients with non-small cell lung cancer (NSCLC). The presence of EpCAM/MUC1 mRNA-positive CTCs was evaluated in 74 NSCLC patients before the initiation of any therapy, from which 61 patients with surgical resection of tumor were also evaluable for EpCAM/MUC1 mRNA-positive CTC analysis after surgery, by quantitative real-time PCR assay. Sixty patients with benign lung disease (BLD) entered this study as controls. The results showed that blood levels of EpCAM and MUC1 mRNA in NSCLC patients before and after surgery were significantly higher than those in BLD patients (P = 0.001 and P = 0.015, respectively, for EpCAM; P = 0.003 and P = 0.026, respectively, for MUC1), and the levels of the two gene mRNA in NSCLC patients significantly decreased after surgery (P = 0.025 and P = 0.033, respectively). Disease recurrence significantly increased in NSCLC patients with EpCAM/MUC1 mRNA-positive CTC preoperation and postoperation (P = 0.004 and P = 0.001, respectively). Disease-free survival and overall survival significantly reduced in patients with EpCAM/MUC1 mRNA-positive CTC preoperation and postoperation (P = 0.012 and P = 0.002, respectively, for preoperation; both P < 0.001 for postoperation). Multivariate analysis demonstrated that the presence of EpCAM/MUC1 mRNA-positive CTCs before and after surgery was an independent factor associated with disease recurrence. In conclusion, the detection of EpCAM/MUC1 mRNA-positive CTCs in the blood before and after surgery is useful for predicting a poor prognosis in NSCLC patients who undergo curative surgery.
Assuntos
Antígenos de Neoplasias/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Moléculas de Adesão Celular/sangue , Mucina-1/sangue , Células Neoplásicas Circulantes , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Intervalo Livre de Doença , Molécula de Adesão da Célula Epitelial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/sangueRESUMO
OBJECTIVE: To investigate the association of Malassezia furfur with chronic urticaria in the crew members of ships. METHODS: A comparative mycological study of 126 crew members of ships with chronic urticaria and 45 normal control subjects was carried out. The 82 urticaria patients identified as positive for Malassezia furfur were divided into groups A and B to receive treatment with antihistaminics (group A) and antihistaminics combined with 2% ketoconazole shampoo(group A). RESULTS: The carrier rates of Malassezia furfur were significantly higher in urticaria patients than in the normal control subjects (P<0.01), but in view of the case ratios of the final cure or improvement, no significant difference was observed between the two groups by the end of the treatment courses (P>0.05). But 6 to 8 weeks from the end of the treatment course, better therapeutic effect was noted in group B (P<0.01), with higher rate of negative Malassezia furfur findings (P<0.01). CONCLUSION: Malassezia furfur may play an important role in the prevalence of chronic urticaria among the crew members, and anti-fungal treatment may produce better long-term therapeutic effect.