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1.
Oncol Rep ; 41(4): 2453-2463, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30816477

RESUMO

Deoxypodophyllotoxin (DPT) is a natural chemical that has been demonstrated to inhibit cellular viability and motility in various cancer cell types. Although previous studies have indicated that programmed cell death and cell cycle arrest are involved in the suppression of glioma development by DPT, the underlying mechanism has not been fully explored. Different methods were used to the elucidate the mechanisms of DPT that inhibit the malignant behavior of glioma cells. Cellular viability was assessed by MTT assay. Relative protein and mRNA expression levels were detected by western blot analysis and reverse transcription­quantitative polymerase chain reaction analyses, respectively. Cell cycle distribution and the apoptosis rate were detected by flow cytometry. Hochest 33258 staining was also performed to detect apoptosis. Transwell assays without and with Matrigel were used to assess migration and invasion abilities, respectively. It was determined that DPT suppressed cellular viability by inducing cell cycle arrest at the G1/S phase by targeting the phosphatidylinositol 4,5­bisphosphate 3­kinase (PI3K)/RAC­α serine/threonine­protein kinase (Akt)­cyclin­dependent kinase inhibitor 1­cyclin­dependent kinase 2/cyclin E signaling cascades. Additionally, DPT significantly enhanced apoptosis by attenuating the PI3K/Akt­mediated suppression of Bcl­2­associated agonist of cell death expression, which was accompanied by an increased apoptosis regulator BAX/apoptosis regulator Bcl­2 ratio. Furthermore, DPT downregulated the invasiveness of glioma cells by hindering PI3K/Akt­matrix metalloproteinase (MMP)9/MMP2 signaling pathways. In conclusion, DPT effectively inhibited the expression of PI3K and downregulated PI3K/Akt­mediated signaling pathways to prevent glioblastoma progression.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Glioblastoma/tratamento farmacológico , Podofilotoxina/análogos & derivados , Transdução de Sinais/efeitos dos fármacos , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose/efeitos dos fármacos , Astrócitos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioblastoma/patologia , Humanos , Invasividade Neoplásica/patologia , Invasividade Neoplásica/prevenção & controle , Fosfatidilinositol 3-Quinases/metabolismo , Podofilotoxina/farmacologia , Podofilotoxina/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sequiviridae/química
2.
Gene ; 698: 82-91, 2019 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-30825599

RESUMO

Differential co-expression is a cutting-edge approach to analyze gene expression data and identify both shared and divergent expression patterns. The availability of high-throughput gene expression datasets and efficient computational approaches have unfolded the opportunity to a systems level understanding of functional genomics of different stresses with respect to plants. We performed the meta-analysis of the available microarray data for reoviridae and sequiviridae infection in rice with the aim to identify the shared gene co-expression profile. The microarray data were downloaded from ArrayExpress and analyzed through a modified Weighted Gene Co-expression Network Analysis (WGCNA) protocol. WGCNA clustered the genes based on the expression intensities across the samples followed by identification of modules, eigengenes, principal components, topology overlap, module membership and module preservation. The module preservation analysis identified 4 modules; salmon (638 genes), midnightblue (584 genes), lightcyan (686 genes) and red (562 genes), which are highly preserved in both the cases. The networks in case of reoviridae infection showed neatly packed clusters whereas, in sequiviridae, the clusters were loosely connected which is due to the differences in the correlation values. We also identified 83 common transcription factors targeting the hub genes from all the identified modules. This study provides a coherent view of the comparative aspect of the expression of common genes involved in different virus infections which may aid in the identification of novel targets and development of new intervention strategy against the virus.


Assuntos
Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica de Plantas/genética , Oryza/genética , Biologia Computacional/métodos , Redes Reguladoras de Genes/genética , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Reoviridae/patogenicidade , Infecções por Reoviridae/genética , Sequiviridae/patogenicidade , Transcriptoma/genética , Viroses/genética
3.
Arch Virol ; 154(5): 899-907, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19350366

RESUMO

The order Picornavirales includes several plant viruses that are currently classified into the families Comoviridae (genera Comovirus, Fabavirus and Nepovirus) and Sequiviridae (genera Sequivirus and Waikavirus) and into the unassigned genera Cheravirus and Sadwavirus. These viruses share properties in common with other picornavirales (particle structure, positive-strand RNA genome with a polyprotein expression strategy, a common replication block including type III helicase, a 3C-like cysteine proteinase and type I RNA-dependent RNA polymerase). However, they also share unique properties that distinguish them from other picornavirales. They infect plants and use specialized proteins or protein domains to move through their host. In phylogenetic analysis based on their replication proteins, these viruses form a separate distinct lineage within the picornavirales branch. To recognize these common properties at the taxonomic level, we propose to create a new family termed "Secoviridae" to include the genera Comovirus, Fabavirus, Nepovirus, Cheravirus, Sadwavirus, Sequivirus and Waikavirus. Two newly discovered plant viruses share common properties with members of the proposed family Secoviridae but have distinct specific genomic organizations. In phylogenetic reconstructions, they form a separate sub-branch within the Secoviridae lineage. We propose to create a new genus termed Torradovirus (type species, Tomato torrado virus) and to assign this genus to the proposed family Secoviridae.


Assuntos
Filogenia , Vírus de Plantas/classificação , Vírus de RNA/classificação , Genoma Viral , Vírus de Plantas/genética , Vírus de RNA/genética , RNA Viral/genética , Secoviridae/classificação , Secoviridae/genética , Análise de Sequência de RNA , Sequiviridae/classificação , Sequiviridae/genética
4.
Arch Virol ; 149(7): 1459-65, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15221545

RESUMO

The sequences of the 3'-terminal 1306 and 2160 nucleotides of RNAs 1 and 2 of a virus serologically related to Satsuma dwarf virus (SDV) from Hyuganatsu ( Citrus tamurana Hort. ex Tan.) were determined, respectively. We found that the partial RNA-dependent RNA polymerase region in RNA1 and the coat proteins (CPs) region in RNA2 of the virus tentatively named Hyuganatsu virus (HV) have 78.3-84.0% and 76.9-80.7% amino acid sequence identities to those of known SDV-related viruses (SDV-RVs), i.e., SDV, Citrus mosaic virus, and Navel orange infectious mottling virus. Sequence analyses show that HV is classifiable as a new SDV-RV species.


Assuntos
RNA Viral/química , Sequiviridae/classificação , Sequiviridae/genética , Sequência de Aminoácidos , Proteínas do Capsídeo/química , Proteínas do Capsídeo/genética , Citrus/virologia , Genes Virais , Dados de Sequência Molecular , Filogenia , RNA Viral/isolamento & purificação , RNA Polimerase Dependente de RNA/química , RNA Polimerase Dependente de RNA/genética , Alinhamento de Sequência , Análise de Sequência de RNA , Homologia de Sequência , Sequiviridae/isolamento & purificação , Proteínas Virais/química , Proteínas Virais/genética
5.
Virus Genes ; 23(1): 45-52, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11556400

RESUMO

Satsuma dwarf virus (SDV) and two closely related viruses, Citrus mosaic (CiMV), and Naval orange infectious mottling (NIMV), seriously affect citrus varieties grown in Japan and East Asia. All three viruses have icosahedral particles built of two proteins encapsidating two single-stranded genomic RNAs. The natural mode of transmission of these SDV-like viruses is unknown, and they were previously placed among tentative members of the family Comoviridae. Recently, a complete genome of SDV was sequenced, and its replication-related proteins were found only distantly related to those of viruses from the family Comoviridae (Iwanami T., Kondo Y., and Karasev A.V. J Gen Virol 80, 793-797, 1999). Here we present a partial genome sequence for another SDV-like virus, NIMV, and a thorough phylogenetic analysis of the gene products encoded by SDV, CiMV, and NIMV to assess their relationships with picorna-like viruses infecting plants, insects, and vertebrates. The RdRp's of SDV-like viruses form a new lineage, separate from members of Como- and Sequiviridae families. Phylogenetic analysis suggests that SDV-like viruses may represent a new family of plant picorna-like viruses. Sequence analysis of the capsid proteins (CPs) encoded by the SDV-like viruses revealed a region of similarity to CPs of animal calici- and picornaviruses that encompasses the structural core of the eight-strand beta-barrel characteristic of picornaviral CPs. These data suggest that SDV and related bipartite viruses evolved separately from the viruses in the family Comoviridae and that the split of an ancestor, monopartite picorna-like virus genome might have occurred more than once.


Assuntos
Evolução Molecular , Vírus de Plantas/genética , Vírus de RNA/genética , Sequência de Aminoácidos , Animais , Genoma Viral , Humanos , Dados de Sequência Molecular , Filogenia , Picornaviridae , Vírus de Plantas/classificação , Vírus de Plantas/fisiologia , Vírus de RNA/classificação , Vírus de RNA/fisiologia , RNA Viral , Secoviridae/classificação , Secoviridae/genética , Homologia de Sequência de Aminoácidos , Sequiviridae/classificação , Sequiviridae/genética , Proteínas Virais/genética , Replicação Viral
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