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Pesquisa : G05.360.600 [Categoria DeCS]
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  1 / 101358 MEDLINE  
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[PMID]:28461122
[Au] Autor:Werisch M; Berger U; Berendonk TU
[Ad] Endereço:Technische Universität Dresden, Department of Forest Sciences, Institute of Forest Growth and Forest Computer Sciences, Tharandt 01735, Germany. Electronic address: martin.werisch@tu-dresden.de.
[Ti] Título:Conjugative plasmids enable the maintenance of low cost non-transmissible plasmids.
[So] Source:Plasmid;91:96-104, 2017 May.
[Is] ISSN:1095-9890
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Some plasmids can be transferred by conjugation to other bacterial hosts. But almost half of the plasmids are non-transmissible. These plasmid types can only be transmitted to the daughter cells of their host after bacterial fission. Previous studies suggest that non-transmissible plasmids become extinct in the absence of selection of their encoded traits, as plasmid-free bacteria are more competitive. Here, we aim to identify mechanisms that enable non-transmissible plasmids to persist, even if they are not beneficial. For this purpose, an individual-based model for plasmid population dynamics was set up and carefully tested for structural consistency and plausibility. Our results demonstrate that non-transmissible plasmids can be stably maintained in a population, even if they impose a substantial burden on their host cells growth. A prerequisite is the co-occurrence of an incompatible and costly conjugative plasmid type, which indirectly facilitates the preservation of the non-transmissible type. We suggest that this constellation might be considered as a potential mechanism maintaining plasmids and associated antibiotic resistances. It should be investigated in upcoming laboratory experiments.
[Mh] Termos MeSH primário: Bactérias/genética
Conjugação Genética
Regulação Bacteriana da Expressão Gênica
Transferência Genética Horizontal
Modelos Estatísticos
Plasmídeos/química
[Mh] Termos MeSH secundário: Bactérias/metabolismo
Simulação por Computador
Aptidão Genética
Plasmídeos/metabolismo
Seleção Genética
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


  2 / 101358 MEDLINE  
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[PMID]:28461121
[Au] Autor:Hall JPJ; Brockhurst MA; Dytham C; Harrison E
[Ad] Endereço:Department of Animal and Plant Sciences, University of Sheffield, Sheffield S10 2TN, UK.
[Ti] Título:The evolution of plasmid stability: Are infectious transmission and compensatory evolution competing evolutionary trajectories?
[So] Source:Plasmid;91:90-95, 2017 May.
[Is] ISSN:1095-9890
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Conjugative plasmids are widespread and play an important role in bacterial evolution by accelerating adaptation through horizontal gene transfer. However, explaining the long-term stability of plasmids remains challenging because segregational loss and the costs of plasmid carriage should drive the loss of plasmids though purifying selection. Theoretical and experimental studies suggest two key evolutionary routes to plasmid stability: First, the evolution of high conjugation rates would allow plasmids to survive through horizontal transmission as infectious agents, and second, compensatory evolution to ameliorate the cost of plasmid carriage can weaken purifying selection against plasmids. How these two evolutionary strategies for plasmid stability interact is unclear. Here, we summarise the literature on the evolution of plasmid stability and then use individual based modelling to investigate the evolutionary interplay between the evolution of plasmid conjugation rate and cost amelioration. We find that, individually, both strategies promote plasmid stability, and that they act together to increase the likelihood of plasmid survival. However, due to the inherent costs of increasing conjugation rate, particularly where conjugation is unlikely to be successful, our model predicts that amelioration is the more likely long-term solution to evolving stable bacteria-plasmid associations. Our model therefore suggests that bacteria-plasmid relationships should evolve towards lower plasmid costs that may forestall the evolution of highly conjugative, 'infectious' plasmids.
[Mh] Termos MeSH primário: Bactérias/genética
Conjugação Genética
Regulação Bacteriana da Expressão Gênica
Transferência Genética Horizontal
Modelos Estatísticos
Plasmídeos/química
[Mh] Termos MeSH secundário: Bactérias/metabolismo
Evolução Biológica
Cromossomos Bacterianos/química
Cromossomos Bacterianos/metabolismo
Aptidão Genética
Loci Gênicos
Mutagênese Insercional
Plasmídeos/metabolismo
Seleção Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


  3 / 101358 MEDLINE  
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[PMID]:27777628
[Au] Autor:Brueckner L; van Arensbergen J; Akhtar W; Pagie L; van Steensel B
[Ad] Endereço:Division of Gene Regulation, Netherlands Cancer Institute, Amsterdam, The Netherlands.
[Ti] Título:High-throughput assessment of context-dependent effects of chromatin proteins.
[So] Source:Epigenetics Chromatin;9:43, 2016.
[Is] ISSN:1756-8935
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Chromatin proteins control gene activity in a concerted manner. We developed a high-throughput assay to study the effects of the local chromatin environment on the regulatory activity of a protein of interest. The assay combines a previously reported multiplexing strategy based on barcoded randomly integrated reporters with Gal4-mediated tethering. We applied the assay to heterochromatin protein 1a (HP1a), which is mostly known as a repressive protein but has also been linked to transcriptional activation. RESULTS: Recruitment to over 1000 genomic locations revealed that HP1a is a potent repressor able to silence even highly expressing reporter genes. However, the local chromatin context can modulate HP1a function. In pericentromeric regions, HP1a-induced repression was enhanced by twofold. In regions marked by a H3K36me3-rich chromatin signature, HP1a-dependent silencing was significantly decreased. We found no evidence for an activating function of HP1a in our experimental system. Furthermore, we did not observe stable transmission of repression over mitotic divisions after loss of targeted HP1a. CONCLUSIONS: The multiplexed tethered reporter assay should be applicable to a large number of chromatin proteins and will be a useful tool to dissect combinatorial regulatory interactions in chromatin.
[Mh] Termos MeSH primário: Cromatina/metabolismo
Proteínas Cromossômicas não Histona/genética
Proteínas de Drosophila/genética
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Proteínas Cromossômicas não Histona/metabolismo
Proteínas de Drosophila/metabolismo
Drosophila melanogaster/genética
Drosophila melanogaster/metabolismo
Inativação Gênica
Histonas/metabolismo
Plasmídeos/genética
Plasmídeos/metabolismo
Elongação da Transcrição Genética
Fatores de Transcrição/genética
Fatores de Transcrição/metabolismo
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Chromatin); 0 (Chromosomal Proteins, Non-Histone); 0 (Drosophila Proteins); 0 (GAL4 protein, Drosophila); 0 (Histones); 0 (Transcription Factors)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180310
[Lr] Data última revisão:
180310
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE


  4 / 101358 MEDLINE  
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[PMID]:29442033
[Au] Autor:Xia M; Wei J; Tong K
[Ti] Título:MiR-224 promotes proliferation and migration of gastric cancer cells through targeting PAK4.
[So] Source:Pharmazie;71(8):460-464, 2016 Aug 01.
[Is] ISSN:0031-7144
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Although recent studies have shown the important role and overexpression of miR-224 in several tumors, its function in gastric cancer has not yet been defined. In the present study, we tried to confirm the result of microRNAs microarray and further investigated the functions of miR-224 in gastric cancer, and tried to find new downstream targets of miR-224. In this study, the level of miR-224 was measured in gastric cancer cells with the normal human gastric epithelial cell. The effects of miR-224 of on proliferation, migration, and target protein expression were evaluated by CCK8 assay, colony assay, transwell migration assay, western blotting. In addition, luciferase reporter plasmid was constructed to demonstrate the direct target of miR-224. Overexpression of miR-224 was detected in the gastric cancer cells, especially in SCG-7901. Exogenous miR-224 expression promoted the proliferation and migration of gastric cells and abrogating expression of miR-224 suppressed proliferation, and migration of SCG-7901 cells in vitro. Luciferase assays revealed that miR-224 directly targeted the 3'UTR of p21-activated kinase 4 (PAK4). The present study provides an experimental foundation for miR-224 as a potential tumor suppressor that may decrease PAK4 expression to inhibit gastric cancer cells and that in the future, targeting of this miRNA may provide a novel strategy for the diagnosis and treatment of patients with this lethal disease.
[Mh] Termos MeSH primário: Movimento Celular/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
MicroRNAs/uso terapêutico
Neoplasias Gástricas/patologia
Quinases Ativadas por p21/efeitos dos fármacos
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Células Epiteliais/efeitos dos fármacos
Regulação Neoplásica da Expressão Gênica
Genes Reporter/genética
Seres Humanos
MicroRNAs/genética
MicroRNAs/farmacologia
Plasmídeos/genética
Regulação para Cima
Cicatrização/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (MIRN224 microRNA, human); 0 (MicroRNAs); EC 2.7.1.11 (PAK4 protein, human); EC 2.7.11.1 (p21-Activated Kinases)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180215
[St] Status:MEDLINE
[do] DOI:10.1691/ph.2016.6580


  5 / 101358 MEDLINE  
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[PMID]:29302027
[Au] Autor:Campbell M; Watanabe T; Nakano K; Davis RR; Lyu Y; Tepper CG; Durbin-Johnson B; Fujimuro M; Izumiya Y
[Ad] Endereço:Department of Dermatology, School of Medicine, University of California Davis (UC Davis), Sacramento, CA, 95817, USA.
[Ti] Título:KSHV episomes reveal dynamic chromatin loop formation with domain-specific gene regulation.
[So] Source:Nat Commun;9(1):49, 2018 01 04.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The three-dimensional structure of chromatin organized by genomic loops facilitates RNA polymerase II access to distal promoters. The Kaposi's sarcoma-associated herpesvirus (KSHV) lytic transcriptional program is initiated by a single viral transactivator, K-Rta. Here we report the KSHV genomic structure and its relationship with K-Rta recruitment sites using Capture Hi-C analyses. High-resolution 3D viral genomic maps identify a number of direct physical, long-range, and dynamic genomic interactions. Mutant KSHV chromosomes harboring point mutations in the K-Rta responsive elements (RE) significantly attenuate not only the directly proximate downstream gene, but also distal gene expression in a domain-specific manner. Genomic loops increase in the presence of K-Rta, while abrogation of K-Rta binding impairs the formation of inducible genomic loops, decreases the expression of genes networked through the looping, and diminishes KSHV replication. Our study demonstrates that genomic architectural dynamics plays an essential role in herpesvirus gene expression.
[Mh] Termos MeSH primário: Regulação Viral da Expressão Gênica
Genoma Viral/genética
Herpesvirus Humano 8/genética
Plasmídeos/genética
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Linhagem Celular Tumoral
Cercopithecus aethiops
Seres Humanos
Transativadores/genética
Células Vero
Proteínas Virais/genética
Latência Viral/genética
Replicação Viral/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Trans-Activators); 0 (Viral Proteins)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180106
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02089-9


  6 / 101358 MEDLINE  
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[PMID]:29335211
[Au] Autor:Li PH; Jiang H; Zhang WJ; Li YL; Zhao MC; Zhou W; Zhang LY; Tang YD; Dong CZ; Huang ZS; Chen HX; Du ZY
[Ad] Endereço:Institute of Natural Medicine & Green Chemistry, School of Chemical Engineering and Light Industry, Guandong University of Technology, Guangzhou, 510006, China.
[Ti] Título:Synthesis of carbazole derivatives containing chalcone analogs as non-intercalative topoisomerase II catalytic inhibitors and apoptosis inducers.
[So] Source:Eur J Med Chem;145:498-510, 2018 Feb 10.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Novel topoisomerase II (Topo II) inhibitors have gained considerable interest for the development of anticancer agents. In this study, a series of carbazole derivatives containing chalcone analogs (CDCAs) were synthesized and investigated for their Topo II inhibition and cytotoxic activities. The results from Topo II mediated DNA relaxation assay showed that CDCAs could significantly inhibit the activity of Topo II, and the structure-activity relationship indicated the halogen substituent in phenyl ring play an important role in the activity. Further mechanism studies revealed that CDCAs function as non-intercalative Topo II catalytic inhibitors. Moreover, some CDCAs showed micromolar cytotoxic activities. The most potent compound 3h exhibited notable growth inhibition against four human cancer cell lines. Flow cytometric analysis revealed that compounds 3d and 3h arrested the HL-60 cells in sub G1 phase by induction of apoptosis. It was further confirmed by Annexin-V-FITC binding assay. Western blot analysis revealed that compound 3h induces apoptosis likely through the activation of caspase proteins.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Apoptose/efeitos dos fármacos
Carbazóis/farmacologia
Chalcona/farmacologia
DNA Topoisomerases Tipo II/metabolismo
Inibidores da Topoisomerase II/farmacologia
[Mh] Termos MeSH secundário: Antineoplásicos/síntese química
Antineoplásicos/química
Biocatálise
Carbazóis/síntese química
Carbazóis/química
Pontos de Checagem do Ciclo Celular/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Chalcona/química
Clivagem do DNA/efeitos dos fármacos
Relação Dose-Resposta a Droga
Ensaios de Seleção de Medicamentos Antitumorais
Células HL-60
Seres Humanos
Estrutura Molecular
Plasmídeos
Relação Estrutura-Atividade
Inibidores da Topoisomerase II/síntese química
Inibidores da Topoisomerase II/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Carbazoles); 0 (Topoisomerase II Inhibitors); 0P2197HHHN (carbazole); 5S5A2Q39HX (Chalcone); EC 5.99.1.3 (DNA Topoisomerases, Type II)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180117
[St] Status:MEDLINE


  7 / 101358 MEDLINE  
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[PMID]:29377933
[Au] Autor:Sato'o Y; Hisatsune J; Yu L; Sakuma T; Yamamoto T; Sugai M
[Ad] Endereço:Department of Bacteriology, Hiroshima University, Graduate school of Biomedical and Health Sciences, Hiroshima, Hiroshima, Japan.
[Ti] Título:Tailor-made gene silencing of Staphylococcus aureus clinical isolates by CRISPR interference.
[So] Source:PLoS One;13(1):e0185987, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Preparing the genetically modified organisms have required much time and labor, making it the rate-limiting step but CRISPR/Cas9 technology appearance has changed this difficulty. Although reports on CRISPR/Cas9 technology such as genome editing and CRISPR interference (CRISPRi) in eukaryotes increased, those in prokaryotes especially in Staphylococci were limited. Thus, its potential in the bacteriology remains unexplored. This is attributed to ecological difference between eukaryotes and prokaryotes. Here, we constructed a novel CRISPRi plasmid vector, pBACi for Staphylococcus aureus. The transformation efficiency of S. aureus was ~104 CFU/µg DNA using a vector extracted from dcm negative, which encoded one of DNA modification genes, E. coli. Further, pBACi was introduced into various clinical isolates including that not accepting the conventional temperature-sensitive vector. dcas9 in the vector was expressed throughout the growth phases of S. aureus and this vector decreased various gene mRNA expressions based on the crRNA targeting sequences and altered the knockdown strains' phenotypes. The targeted genes included various virulence and antibiotic resistant genes. Bioinformatics suggest this vector can be introduced into wide range of low-GC Gram-positive bacteria. Because this new CRISPR/Cas9-based vector can easily prepare knockdown strains, we believe the novel vector will facilitate the characterization of the function of genes from S. aureus and other Gram-positive bacteria.
[Mh] Termos MeSH primário: Técnicas de Silenciamento de Genes/métodos
Vetores Genéticos/síntese química
Staphylococcus aureus/genética
[Mh] Termos MeSH secundário: Proteínas de Bactérias/genética
Sistemas CRISPR-Cas/genética
Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas
Escherichia coli/genética
Edição de Genes
Inativação Gênica
Vetores Genéticos/genética
Genoma Bacteriano
Plasmídeos/genética
RNA Guia/genética
Infecções Estafilocócicas/genética
Staphylococcus aureus/patogenicidade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (RNA, Guide)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180130
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0185987


  8 / 101358 MEDLINE  
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[PMID]:29352308
[Au] Autor:Qian Q; You Z; Ye L; Che J; Wang Y; Wang S; Zhong B
[Ad] Endereço:College of Animal Sciences, Zhejiang University, Hangzhou, P. R. China.
[Ti] Título:High-efficiency production of human serum albumin in the posterior silk glands of transgenic silkworms, Bombyx mori L.
[So] Source:PLoS One;13(1):e0191507, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Human serum albumin (HSA) is an important biological preparation with a variety of biological functions in clinical applications. In this study, the mRNA of a fusion transposase derived from the pESNT-PBase plasmid and a pBHSA plasmid containing the HSA gene under the control of a fibroin light chain (FL) promoter were co-injected into fertilized eggs. Fifty-six transgenic silkworm pedigrees expressing theexogenous recombinant HSA (rHSA) in the posterior silk glands (PSGs) with stable inheritance were successfully obtained. The SDS-PAGE and Western blot results confirmed that the rHSA was secreted into the transgenic silkworm cocoon, and the rHSA could be easily extracted with phosphate-buffered saline (PBS). In our research, the isolated highest amount rHSA constituted up to 29.1% of the total soluble protein of the cocoon shell, indicating that the transgenic silkworm produced an average of 17.4 µg/mg of rHSA in the cocoon shell. The production of soluble rHSA in the PSGs by means of generating transgenic silkworms is a novel approach, whereby a large amount of virus-free and functional HSA can be produced through the simple rearing of silkworms.
[Mh] Termos MeSH primário: Bombyx/genética
Bombyx/metabolismo
Albumina Sérica Humana/biossíntese
Albumina Sérica Humana/genética
[Mh] Termos MeSH secundário: Animais
Animais Geneticamente Modificados
Bombyx/crescimento & desenvolvimento
Fibroínas/genética
Expressão Gênica
Genes de Insetos
Seres Humanos
Plasmídeos/genética
Regiões Promotoras Genéticas
Proteínas Recombinantes/biossíntese
Proteínas Recombinantes/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Recombinant Proteins); 9007-76-5 (Fibroins); ZIF514RVZR (Serum Albumin, Human)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180121
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191507


  9 / 101358 MEDLINE  
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[PMID]:28748978
[Au] Autor:Song L; Ding AX; Zhang KX; Gong B; Lu ZL; He L
[Ad] Endereço:Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Xinjiekouwai Street 19, Beijing 100875, China. luzl@bnu.edu.cn.
[Ti] Título:Degradable polyesters via ring-opening polymerization of functional valerolactones for efficient gene delivery.
[So] Source:Org Biomol Chem;15(31):6567-6574, 2017 Aug 09.
[Is] ISSN:1477-0539
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Degradable polymers as gene and drug carriers are emerging as one of the most promising types of materials in the biomedical and pharmaceutical areas. Herein, we report the synthesis of a series of block co-polyesters (B1-B6) and random co-polyesters (C1-C4) via ring-opening polymerization of tertiary amine-bearing valerolactone and alkylated valerolactone monomers. These polymers can completely inhibit the electrophoretic migrations of plasmid DNAs (pDNAs) at a w/w ratio of 2-6. The polyplexes of these polymers with pDNAs were steadily formed in a narrow range of sizes (75 to 220 nm) and could be effectively internalized into the cytoplasm. The results of transfection experiments showed that the block copolymers generally exhibited better performance than their random counterparts and the aliphatic chain lengths on the backbone of the polymers obviously affected the transfection efficiency (TE). Block copolymer B5 with n-octyl chains generated the best TE in Hek293T cells, which was 2.2 fold that of polyethylenimine (PEI) 25k under the optimal conditions. Moreover, these polymers were found to be more biocompatible compared to PEI 25k, and showed degradable properties. Our results suggest that these polymers are potentially reliable/efficient non-viral gene vectors.
[Mh] Termos MeSH primário: DNA/administração & dosagem
Técnicas de Transferência de Genes
Lactonas/química
Plasmídeos/administração & dosagem
Poliésteres/química
[Mh] Termos MeSH secundário: DNA/genética
Vetores Genéticos/administração & dosagem
Vetores Genéticos/genética
Células HEK293
Seres Humanos
Lactonas/síntese química
Plasmídeos/genética
Poliésteres/síntese química
Polimerização
Transfecção/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Lactones); 0 (Polyesters); 9007-49-2 (DNA)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170728
[St] Status:MEDLINE
[do] DOI:10.1039/c7ob00822h


  10 / 101358 MEDLINE  
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[PMID]:28449719
[Au] Autor:Bongard N; Lapuente D; Windmann S; Dittmer U; Tenbusch M; Bayer W
[Ad] Endereço:Institute for Virology, University Hospital Essen, University Duisburg-Essen, Virchowstr. 179, 45147, Essen, Germany.
[Ti] Título:Interference of retroviral envelope with vaccine-induced CD8 T cell responses is relieved by co-administration of cytokine-encoding vectors.
[So] Source:Retrovirology;14(1):28, 2017 Apr 27.
[Is] ISSN:1742-4690
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Retroviral envelope (Env) proteins are known to exhibit immunosuppressive properties, which become apparent not only in retroviral infections, but also in gene-based immunizations using retroviral immunogens, where envelope interferes with the induction of CD8 T cell responses towards another, simultaneously or subsequently delivered, immunogen. RESULTS: In the Friend retrovirus mouse model, immunization with a plasmid encoding the Friend murine leukemia virus (F-MuLV) Leader-Gag protein resulted in induction of a strong GagL -specific CD8 T cell response, while the response was completely abrogated by co-immunization with an F-MuLV Env-encoding plasmid. In order to overcome this interference of retroviral envelope, we employed plasmids encoding the cytokines interleukin (IL) 1ß, IL2, IL12, IL15, IL21, IL28A or granulocyte-macrophage colony-stimulating factor (GM-CSF) as genetic adjuvants. Co-application of plasmids encoding IL2, IL12, IL21, IL28A and especially GM-CSF rescued the induction of GagL -specific CD8 T cells in mice vaccinated with FV Leader-Gag and Env. Mice that were immunized with plasmids encoding Leader-Gag and Env and the cytokines IL1ß, IL12, IL15, IL28A or GM-CSF, but not Leader-Gag and Env without any cytokine, showed significantly reduced viral loads upon a high-dose Friend virus challenge infection. CONCLUSIONS: Our data demonstrate the potency of cytokine-encoding vectors as adjuvants and immune modulators in composite vaccines for anti-retroviral immunization.
[Mh] Termos MeSH primário: Linfócitos T CD8-Positivos/imunologia
Citocinas/genética
Vírus da Leucemia Murina de Friend/imunologia
Vacinas de DNA/imunologia
Proteínas do Envelope Viral/imunologia
Vacinas Virais/imunologia
[Mh] Termos MeSH secundário: Adjuvantes Imunológicos
Animais
Citocinas/imunologia
Feminino
Vírus da Leucemia Murina de Friend/genética
Produtos do Gene gag/genética
Produtos do Gene gag/imunologia
Vetores Genéticos
Imunização
Imunomodulação
Interleucina-15/genética
Interleucina-15/imunologia
Interleucina-2/genética
Interleucina-2/imunologia
Camundongos
Camundongos Endogâmicos BALB C
Plasmídeos
Infecções por Retroviridae/imunologia
Vacinas de DNA/administração & dosagem
Proteínas do Envelope Viral/genética
Proteínas do Envelope Viral/metabolismo
Carga Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adjuvants, Immunologic); 0 (Cytokines); 0 (Gene Products, gag); 0 (Interleukin-15); 0 (Interleukin-2); 0 (Vaccines, DNA); 0 (Viral Envelope Proteins); 0 (Viral Vaccines)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1186/s12977-017-0352-7



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