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1.
Mol Med Rep ; 21(2): 883-893, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31789407

RESUMO

Rearrangement of the mixed lineage leukemia (MLL; also known as lysine methyltransferase 2A) gene is a recurrent genomic aberration in acute myeloid leukemia (AML). MLLT3, super elongation complex subunit (AF9) is one of the most common MLL fusion partners in AML. The present study aimed to explore the aberrant expression of genes associated with the MLL­AF9 translocation and identified potential new targets for the therapy of AML with MLL­AF9 translocation. The transcriptomic and epigenetic datasets were downloaded from National Center of Biotechnology Information Gene Expression Omnibus (GEO) database. Differentially expressed genes were obtained from two independent datasets (GSE68643 and GSE73457). Gene Ontology biological process and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed using the Database for Annotation, Visualization and Integrated Discovery. MLL­AF9­associated chromatin immunoprecipitation sequencing (ChIP­Seq) data was analyzed and identified binding sites for MLL­AF9 and wild type MLL (MLL WT). The ChIP­Seq of histone modification data was downloaded from the GEO database, including histone 3 lysine 4 trimethylation (H3K4me3), histone 3 lysine 79 dimethylation (H3K79me2) and histone 3 lysine 27 acetylation (H3K27ac), was used for comparing histone modification marks between the MLL­AF9 leukemia cells and normal hematopoietic cells at MLL­AF9 and MLL WT binding sites. The differentially expressed genes with the same trend in H3K79me2, H3K27ac and H3K4me3 alteration were identified as potential MLL­AF9 direct target genes. Upon validation using RNA­Seq data from the Therapeutically Applicable Research to Generate Effective Treatments AML project, eight potential direct target genes of MLL­AF9 were identified and further confirmed in MLL­AF9 mouse model using reverse transcription­quantitative polymerase chain reaction. These genes may have a critical role in AML with MLL­AF9 translocation.

2.
Oncol Rep ; 42(6): 2426-2434, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31638261

RESUMO

RAD51, is a key homologous recombination protein that repairs DNA damage and maintains gene diversity and stability. Previous studies have demonstrated that the over­expression of RAD51 is associated with chemotherapy resistance of tumor cells to chemotherapy, and enhanced activity of DNA damage repair (DDR) systems contributes to resistance of adult T­cell leukemia­lymphoma (ATL) resistance to chemotherapy. Thus, targeting RAD51 is a potential strategy for the sensitization of ATL cells to chemotherapeutic drugs by inducing DNA damage. In general, cells can repair minor DNA damage through DDR; however, serious DNA damage may cause cell toxicity in cells which cannot be restored. In the present, down regulation of RAD51 by shRNA and imatinib sensitized Jurkat cells to etoposide by decreasing the activity of homologous recombination (HR). We found that the suppression of RAD51 by shRNA inhibited tumor cells proliferation and enhanced apoptosis of Jurkat cells after etoposide treatment. Importantly, downregulation of RAD51 by imatinib obviously increased the apoptosis of Jurkat cell after etoposide treatment. These results demonstrated that RAD51 may be of great value to as a novel target for the clinical treatment of adult T­cell leukemia­lymphoma (ATL), and it may improve the survival of leukemia patients.

3.
PLoS Negl Trop Dis ; 13(7): e0007590, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31306427

RESUMO

BACKGROUND: The entomopathogenic fungus Beauveria bassiana has been widely used to kill mosquito larvae and adults in the laboratory and field. However, its slow action of killing has hampered its widespread application. In our study, the B. bassiana fungus was genetically modified to express the Bacillus thuringiensis (Bt) toxin Cyt2Ba to improve its efficacy in killing mosquitoes. METHODOLOGY/PRINCIPAL FINDINGS: The efficacy of the wild type (WT) of B. bassiana and a transgenic strain expressing Cyt2Ba toxin (Bb-Cyt2Ba) was evaluated against larval and adult Aedes mosquitoes (Aedes aegypti and Aedes albopictus) using insect bioassays. The Bb-Cyt2Ba displayed increased virulence against larval and adult Aedes mosquitoes compared with the WT: for Ae. aegypti adults, the median lethal time (LT50) was decreased by 33% at the concentration of 1× 108 conidia/ml, 19% at 1× 107 conidia/ml and 47% at 1× 106 conidia/ml. The LT50 for Ae. albopictus adults was reduced by 20%, 23% and 29% at the same concentrations, respectively. The LT50 for Ae. aegypti larvae was decreased by 42% at 1× 107 conidia/ml and 25% at 1× 106 conidia/ml, and that for Ae. albopictus larvae was reduced by 33% and 31% at the same concentrations, respectively. In addition, infection with Bb-Cyt2Ba resulted in a dramatic reduction in the fecundity of Aedes mosquitoes. CONCLUSIONS/SIGNIFICANCE: In conclusion, our study demonstrated that the virulence of B. bassiana against mosquitoes can be significantly improved by introducing the Bt toxin gene Cyt2Ba into the genome to express the exogenous toxin in the fungus. The transgenic strain Bb-Cyt2Ba significantly reduced the survival and fecundity of Ae. aegypti and Ae. albopictus compared with the WT strain, which suggested that this recombinant B. bassiana has great potential for use in mosquito control.


Assuntos
Aedes/microbiologia , Bacillus thuringiensis/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/toxicidade , Toxinas Bacterianas/genética , Toxinas Bacterianas/toxicidade , Beauveria/genética , Endotoxinas/genética , Endotoxinas/toxicidade , Proteínas Hemolisinas/genética , Proteínas Hemolisinas/toxicidade , Controle Biológico de Vetores/métodos , Animais , Feminino , Fertilidade , Regulação Fúngica da Expressão Gênica , Instabilidade Genômica , Larva/microbiologia , Controle de Mosquitos/métodos , Proteínas Recombinantes , Esporos Fúngicos , Virulência/genética
4.
Nat Prod Res ; : 1-5, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31232100

RESUMO

From the deep-sea-derived fungus Aspergillus candidus, one novel (1) and three known (2-4) p-terphenyl derivates were isolated. The structure of the new compound was established mainly on the basis of extensive analysis of 1D and 2D NMR data. All four isolates were tested for in vitro anti-food allergic and antitumor bioactivities. Compounds 3 and 4 showed potent antiproliferative effect against four cancer cells of Hela, Eca-109, Bel-7402, and PANC-1 with IC50 values ranging from 5.5 µM to 9.4 µM.

5.
Mol Med Rep ; 18(2): 1473-1484, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29901168

RESUMO

Long non-coding RNAs (lncRNAs) are transcripts characterized by >200 nucleotides, without validated protein production. Previous studies have demonstrated that certain lncRNAs have a critical role in the initiation and development of acute myeloid leukemia (AML). In the present study, the subtype­specific lncRNAs in AML was identified. Following the exclusion of the subtype­specific lncRNAs, the prognostic value of lncRNAs was investigated and a three­lncRNA expression­based risk score [long intergenic non­protein coding RNA 926, family with sequence similarity 30 member A and LRRC75A antisense RNA 1 (LRRC75A­AS1)] was developed for AML patient prognosis prediction by analyzing the RNA­seq data of AML patients from Therapeutically Available Research to Generate Effective Treatments (TARGET) and The Cancer Genome Atlas (TCGA) projects. In the training set obtained from TARGET, patients were divided into poor and favorable prognosis groups by the median risk score. The prognostic effectiveness of this lncRNA risk score was confirmed in the validation set obtained from TCGA by the same cut­off. Furthermore, the lncRNA risk score was identified as an independent prognostic factor in the multivariate analysis. As further verification of the independent prognostic power of the lncRNA risk score, stratified analysis was performed by a cytogenetics risk group and revealed a consistent result. The prognostic predictive ability of the risk score was compared with the cytogenetics risk group by time­dependent receiver operating characteristic curves analysis. It was revealed that the combination of the lncRNA risk score and cytogenetics risk group provided a higher prognostic value than a single prognostic factor. The present study also performed co­expression analysis to predict the potential regulatory mechanisms of these lncRNAs in a cis/trans/competing endogenous RNA manner. The results suggested that LRRC75A­AS1 was highly associated with the target genes of transcription factors tumor protein 53 and ETS variant 6. Overall, these results highlighted the use of the three­lncRNA expression­based risk score as a potential molecular biomarker to predict the prognosis in AML patients.


Assuntos
Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Leucemia Mieloide Aguda/genética , RNA Antissenso/genética , RNA Longo não Codificante/genética , Atlas como Assunto , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Cariotipagem , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , Masculino , Análise Multivariada , Prognóstico , Proteínas Proto-Oncogênicas c-ets/genética , Proteínas Proto-Oncogênicas c-ets/metabolismo , RNA Antissenso/metabolismo , RNA Longo não Codificante/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Risco , Transdução de Sinais , Análise de Sobrevida , Transcriptoma , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
6.
Org Lett ; 20(3): 660-663, 2018 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-29323495

RESUMO

A one-step methodology for the synthesis of multisubstituted quinoline-4-carboxamides was developed by simply refluxing a mixture of isatins 1 and various kinds of 1,1-enediamines 2-4 in a reaction catalyzed by NH2SO3H. As a result, a series of quinolone-4-carboxamides were produced through a novel cascade reaction mechanism. This reaction involved the formation of the quinoline ring accompanied by the formation of an amide bond in one step. Accordingly, this protocol is suitable for combinatorial and parallel syntheses of quinolone-4-carboxamide drugs or natural products.

7.
Polymers (Basel) ; 10(4)2018 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-30966397

RESUMO

Hydrophobic zinc oxide (ZnO) nanoparticles were produced through grafting aminopropyltriethoxysilane (APS) and oleic acid (OA), which was activated by N,N'-carbonyldiimidazole (CDI). The functional group containing ZnO nanoparticles were incorporated into unsaturated polyester (UP) resin, and their dispersibility in the UP matrix and effects on the properties of UP/ZnO nanocomposites were investigated. ZnO nanoparticles modified by APS and OA activated by CDI, (CDI⁻OA⁻APS⁻ZnO), can be homogeneously dispersed as supported by transmission electron microscopy (TEM) investigations and had been encapsulated in the UP resin. CDI⁻OA⁻APS⁻ZnO nanoparticles were embedded in the net structure of the UP composites through chemical bonds between oleic acid, styrene, and polyester resin, which significantly influence the cure reaction of UP resin and the properties of UP composites. Thermogravimetric analysis (TGA) results show that the incorporation of ZnO nanoparticles could improve the thermal stability of UP when thermal cracking temperature exceeds 365 °C. The exothermic peak and the initial temperature of cure reaction of the UP resin decreased with increasing ZnO content. The tensile strength and bending strength of UP/CDI⁻OA⁻APS⁻ZnO nanocomposites increased by 91.4% and 71.3% when 3 wt % CDI⁻OA⁻APS⁻ZnO nanoparticles was added into the composites, respectively, compared with pure UP resin.

8.
Tumour Biol ; 37(7): 8721-9, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26738868

RESUMO

Ovarian cancer is the most lethal gynecological malignancy. Patients usually have poor prognosis because of late diagnosis, relapse, and chemoresistance. It is pressing to seek novel agent for the treatment of ovarian cancer. Neferine is a bisbenzylisoquinoline alkaloid isolated from the embryos of lotus (Nelumbo nucifera). In this study, we investigated the antitumor effect of neferine on ovarian cancer cells. We found that neferine exhibited growth-inhibitory effect on human ovarian cancer cells, whereas showing less cytotoxic to non-malignant fallopian tube epithelial cells. Furthermore, we demonstrated that neferine induced autophagy and inactivated the mTOR pathway. Finally, we found that both p38 MAPK and JNK signaling pathways were activated by neferine treatment and contributed to the induction of autophagy in ovarian cancer cells. In conclusion, our findings showed that neferine induced autophagy of human ovarian cancer cells via p38 MAPK/JNK activation. Neferine may be explored as a promising antitumoral agent in ovarian cancer.


Assuntos
Autofagia/efeitos dos fármacos , Benzilisoquinolinas/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Neoplasias Ovarianas/tratamento farmacológico , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Feminino , Humanos , Nelumbo/química , Neoplasias Ovarianas/metabolismo , Extratos Vegetais/farmacologia , Serina-Treonina Quinases TOR/metabolismo
9.
Nano Lett ; 11(11): 4601-6, 2011 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-21985530

RESUMO

We report on the first controlled alternation between memory and threshold resistance switching (RS) in single Ni/NiO core-shell nanowires by setting the compliance current (I(CC)) at room temperature. The memory RS is triggered by a high I(CC), while the threshold RS appears by setting a low I(CC), and the Reset process is achieved without setting a I(CC). In combination with first-principles calculations, the physical mechanisms for the memory and threshold RS are fully discussed and attributed to the formation of an oxygen vacancy (Vo) chain conductive filament and the electrical field induced breakdown without forming a conductive filament, respectively. Migration of oxygen vacancies can be activated by appropriate Joule heating, and it is energetically favorable to form conductive chains rather than random distributions due to the Vo-Vo interaction, which results in the nonvolatile switching from the off- to the on-state. For the Reset process, large Joule heating reorders the oxygen vacancies by breaking the Vo-Vo interactions and thus rupturing the conductive filaments, which are responsible for the switching from on- to off-states. This deeper understanding of the driving mechanisms responsible for the threshold and memory RS provides guidelines for the scaling, reliability, and reproducibility of NiO-based nonvolatile memory devices.


Assuntos
Dispositivos de Armazenamento em Computador , Armazenamento e Recuperação da Informação/métodos , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Nanotecnologia/instrumentação , Níquel/química , Impedância Elétrica , Desenho de Equipamento , Análise de Falha de Equipamento
10.
Huan Jing Ke Xue ; 29(4): 849-54, 2008 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-18637327

RESUMO

Concentrations of PAHs in leaves of six dominant species in the Pearl River Delta of South China were determined with gas chromatography and mass spectrometry (GC-MS), and synchronously leaf-lipid contents, leaf areas, specific leaf areas (SLA) were measured. The characters of PAHs abundance and influence factors on them were investigated. The results show that concentrations of PAHs in pine needles are higher than those in broad-leaves remarkably, and the highest value (1034.7 ng x g(-1) in Pinus massoniana) is fivefold of the lowest (199.7 ng x g(-1) in Schima superba) . Flu, Phe, Fluo, Pyr, Chr are the main components of sigma PAHs, and the concentrations of 3-ring and 4-ring PAHs exceed 80% of the total PAHs. Significant positive correlations between the components and sigma PAHs were also detected. The PAHs contents by per lipid could reduce inter-species variance obviously, and the diversity is no more than two times (6.8 ng x mg(-1) and 2.7 ng x mg(-1), respectively). Adversely, the PAHs contents by per cm2 magnify inter-species variance, and the highest value (15.3 ng x cm(-2)) ascends to eight times of the lowest (1.9 ng x cm(-2)). Furthermore, significant positive correlation between PAHs and leaf-lipid contents was identified, as well as negative correlation between PAHs and specific leaf areas. All of these indicate that leaf-lipid contents and specific leaf areas are two significant factors which influenced PAHs contents in leaves.


Assuntos
Poluentes Atmosféricos/análise , Folhas de Planta/química , Hidrocarbonetos Policíclicos Aromáticos/análise , Árvores/química , China , Monitoramento Ambiental , Cromatografia Gasosa-Espectrometria de Massas , Lipídeos/análise , Rios , Estações do Ano , Especificidade da Espécie , Árvores/classificação
11.
Environ Pollut ; 156(2): 306-15, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18375026

RESUMO

Leaves of six main tree species from the Pearl River Delta (PRD) in Southern China were collected to identify the interspecific variability, the spatial variability and the seasonal variations of polycyclic aromatic hydrocarbons' (PAHs) concentrations, and to calculate the amount of PAHs removed by leaves. PAHs concentrations in pine needles were much higher than in broad-leaves and leaves from urban/industrial areas (Baiyunshan and Heshan) exhibited two times greater concentrations than leaves from the rural area (Dinghushan). Seasonal variations of PAHs in leaves occurred with lesser concentrations in September. Leaves in PRD scavenged 3.7+/-0.9 t PAHsy(-1), accounting for about 10% of the total amount emitted in this region. This result suggests that forests play an important role in the fate of PAHs.


Assuntos
Folhas de Planta/química , Hidrocarbonetos Policíclicos Aromáticos/análise , Poluentes do Solo/análise , Árvores/metabolismo , Poluentes Químicos da Água/análise , Acacia/metabolismo , China , Monitoramento Ambiental/métodos , Monitoramento Ambiental/estatística & dados numéricos , Eucalyptus/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Pinus/metabolismo , Rios/química , Estações do Ano , Água do Mar/química
12.
J Colloid Interface Sci ; 307(1): 215-20, 2007 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-17188285

RESUMO

Significant synergistic effects between sodium dodecylbenzene sulfonate (SDBS) and nonionic nonylphenol polyethylene oxyether, Triton X-100 (TX-100), at the oil/water interface have been investigated by experimental methods and computer simulation. The influences of surfactant concentration, salinity, and the ratio of the two surfactants on the interfacial tension were investigated by conventional interfacial tension methods. A dissipative particle dynamics (DPD) method was used to simulate the adsorption properties of SDBS and TX-100 at the oil/water interface. The experiment and simulation results indicate that ultralow (lower than 10(-3) mN m(-1)) interfacial tension can be obtained at high salinity and very low surfactant concentration. Different distributions of surfactants in the interface and the bulk solution corresponding to the change of salinity have been demonstrated by simulation. Also by computer simulation, we have observed that either SDBS or TX-100 is not distributed uniformly over the interface. Rather, the interfacial layer contains large cavities between SDBS clusters filled with TX-100 clusters. This inhomogeneous distribution helps to enhancing our understanding of the synergistic interaction of the different surfactants. The simulation conclusions are consistent with the experimental results.

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