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Pesquisa : B01.050.050.136 [Categoria DeCS]
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  1 / 19315 MEDLINE  
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[PMID]:29214789
[Au] Autor:Kim CW; Han JH; Wu L; Choi JY
[Ad] Endereço:Department of Otorhinolaryngology, Hallym University College of Medicine, Seoul, Korea.
[Ti] Título:microRNA-183 is Essential for Hair Cell Regeneration after Neomycin Injury in Zebrafish.
[So] Source:Yonsei Med J;59(1):141-147, 2018 Jan.
[Is] ISSN:1976-2437
[Cp] País de publicação:Korea (South)
[La] Idioma:eng
[Ab] Resumo:PURPOSE: microRNAs (miRNAs) are non-coding RNAs composed of 20 to 22 nucleotides that regulate development and differentiation in various organs by silencing specific RNAs and regulating gene expression. In the present study, we show that the microRNA (miR)-183 cluster is upregulated during hair cell regeneration and that its inhibition reduces hair cell regeneration following neomycin-induced ototoxicity in zebrafish. MATERIALS AND METHODS: miRNA expression patterns after neomycin exposure were analyzed using microarray chips. Quantitative polymerase chain reaction was performed to validate miR-183 cluster expression patterns following neomycin exposure (500 µM for 2 h). After injection of an antisense morpholino (MO) to miR-183 (MO-183) immediately after fertilization, hair cell regeneration after neomycin exposure in neuromast cells was evaluated by fluorescent staining (YO-PRO1). The MO-183 effect also was assessed in transgenic zebrafish larvae expressing green fluorescent protein (GFP) in inner ear hair cells. RESULTS: Microarray analysis clearly showed that the miR-183 cluster (miR-96, miR-182, and miR-183) was upregulated after neomycin treatment. We also confirmed upregulated expression of the miR-183 cluster during hair cell regeneration after neomycin-induced ototoxicity. miR-183 inhibition using MO-183 reduced hair cell regeneration in both wild-type and GFP transgenic zebrafish larvae. CONCLUSION: Our work demonstrates that the miR-183 cluster is essential for the regeneration of hair cells following ototoxic injury in zebrafish larvae. Therefore, regulation of the miR-183 cluster can be a novel target for stimulation of hair cell regeneration.
[Mh] Termos MeSH primário: Células Ciliadas Auditivas/fisiologia
MicroRNAs/metabolismo
Regeneração/genética
Peixe-Zebra/genética
[Mh] Termos MeSH secundário: Animais
Animais Geneticamente Modificados
Contagem de Células
Perfilação da Expressão Gênica
Regulação da Expressão Gênica/efeitos dos fármacos
Técnicas de Silenciamento de Genes
Proteínas de Fluorescência Verde/metabolismo
Células Ciliadas Auditivas/efeitos dos fármacos
Larva/efeitos dos fármacos
Larva/genética
MicroRNAs/genética
Morfolinos/farmacologia
Neomicina/toxicidade
Regeneração/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (MIRN183 microRNA, zebrafish); 0 (MicroRNAs); 0 (Morpholinos); 1404-04-2 (Neomycin); 147336-22-9 (Green Fluorescent Proteins)
[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:171208
[St] Status:MEDLINE
[do] DOI:10.3349/ymj.2018.59.1.141


  2 / 19315 MEDLINE  
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[PMID]:29382818
[Au] Autor:Sánchez-Iranzo H; Galardi-Castilla M; Minguillón C; Sanz-Morejón A; González-Rosa JM; Felker A; Ernst A; Guzmán-Martínez G; Mosimann C; Mercader N
[Ad] Endereço:Development of the Epicardium and Its Role during Regeneration Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC-ISCIII), Melchor Fernández Almagro 3, 28029, Madrid, Spain.
[Ti] Título:Tbx5a lineage tracing shows cardiomyocyte plasticity during zebrafish heart regeneration.
[So] Source:Nat Commun;9(1):428, 2018 01 30.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:During development, mesodermal progenitors from the first heart field (FHF) form a primitive cardiac tube, to which progenitors from the second heart field (SHF) are added. The contribution of FHF and SHF progenitors to the adult zebrafish heart has not been studied to date. Here we find, using genetic tbx5a lineage tracing tools, that the ventricular myocardium in the adult zebrafish is mainly derived from tbx5a cells, with a small contribution from tbx5a SHF progenitors. Notably, ablation of ventricular tbx5a -derived cardiomyocytes in the embryo is compensated by expansion of SHF-derived cells. In the adult, tbx5a expression is restricted to the trabeculae and excluded from the outer cortical layer. tbx5a-lineage tracing revealed that trabecular cardiomyocytes can switch their fate and differentiate into cortical myocardium during adult heart regeneration. We conclude that a high degree of cardiomyocyte cell fate plasticity contributes to efficient regeneration.
[Mh] Termos MeSH primário: Ventrículos do Coração/citologia
Miocárdio/citologia
Miócitos Cardíacos/citologia
Regeneração/genética
Proteínas com Domínio T-Box/genética
Peixe-Zebra/genética
[Mh] Termos MeSH secundário: Animais
Animais Geneticamente Modificados
Diferenciação Celular
Linhagem da Célula/genética
Rastreamento de Células
Embrião não Mamífero
Regulação da Expressão Gênica no Desenvolvimento
Genes Reporter
Proteínas de Fluorescência Verde/genética
Proteínas de Fluorescência Verde/metabolismo
Ventrículos do Coração/crescimento & desenvolvimento
Ventrículos do Coração/metabolismo
Proteínas Luminescentes/genética
Proteínas Luminescentes/metabolismo
Miocárdio/metabolismo
Miócitos Cardíacos/metabolismo
Cadeias Leves de Miosina/genética
Cadeias Leves de Miosina/metabolismo
Organogênese/genética
Células-Tronco/citologia
Células-Tronco/metabolismo
Proteínas com Domínio T-Box/deficiência
Peixe-Zebra/crescimento & desenvolvimento
Peixe-Zebra/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Luminescent Proteins); 0 (Myosin Light Chains); 0 (T-Box Domain Proteins); 0 (T-box transcription factor 5); 0 (red fluorescent protein); 147336-22-9 (Green Fluorescent Proteins)
[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:180201
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02650-6


  3 / 19315 MEDLINE  
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[PMID]:29281629
[Au] Autor:Ojeda Naharros I; Gesemann M; Mateos JM; Barmettler G; Forbes A; Ziegler U; Neuhauss SCF; Bachmann-Gagescu R
[Ad] Endereço:Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
[Ti] Título:Loss-of-function of the ciliopathy protein Cc2d2a disorganizes the vesicle fusion machinery at the periciliary membrane and indirectly affects Rab8-trafficking in zebrafish photoreceptors.
[So] Source:PLoS Genet;13(12):e1007150, 2017 12.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Ciliopathies are human disorders caused by dysfunction of primary cilia, ubiquitous organelles involved in transduction of environmental signals such as light sensation in photoreceptors. Concentration of signal detection proteins such as opsins in the ciliary membrane is achieved by RabGTPase-regulated polarized vesicle trafficking and by a selective barrier at the ciliary base, the transition zone (TZ). Dysfunction of the TZ protein CC2D2A causes Joubert/Meckel syndromes in humans and loss of ciliary protein localization in animal models, including opsins in retinal photoreceptors. The link between the TZ and upstream vesicle trafficking has been little explored to date. Moreover, the role of the small GTPase Rab8 in opsin-carrier vesicle (OCV) trafficking has been recently questioned in a mouse model. Using correlative light and electron microscopy and live imaging in zebrafish photoreceptors, we provide the first live characterization of Rab8-mediated trafficking in photoreceptors in vivo. Our results support a possibly redundant role for both Rab8a/b paralogs in OCV trafficking, based on co-localization of Rab8 and opsins in vesicular structures, and joint movement of Rab8-tagged particles with opsin. We further investigate the role of the TZ protein Cc2d2a in Rab8-mediated trafficking using cc2d2a zebrafish mutants and identify a requirement for Cc2d2a in the latest step of OCV trafficking, namely vesicle fusion. Progressive accumulation of opsin-containing vesicles in the apical portion of photoreceptors lacking Cc2d2a is caused by disorganization of the vesicle fusion machinery at the periciliary membrane with mislocalization and loss of the t-SNAREs SNAP25 and Syntaxin3 and of the exocyst component Exoc4. We further observe secondary defects on upstream Rab8-trafficking with cytoplasmic accumulation of Rab8. Taken together, our results support participation of Rab8 in OCV trafficking and identify a novel role for the TZ protein Cc2d2a in fusion of incoming ciliary-directed vesicles, through organization of the vesicle fusion machinery at the periciliary membrane.
[Mh] Termos MeSH primário: Proteínas de Transporte Vesicular/genética
Proteínas de Transporte Vesicular/metabolismo
Proteínas de Peixe-Zebra/genética
Proteínas de Peixe-Zebra/metabolismo
Proteínas rab de Ligação ao GTP/metabolismo
[Mh] Termos MeSH secundário: Animais
Animais Geneticamente Modificados
Transporte Biológico
Movimento Celular
Cílios/genética
Cílios/metabolismo
Seres Humanos
Membranas/metabolismo
Opsinas/genética
Opsinas/metabolismo
Células Fotorreceptoras de Vertebrados/metabolismo
Transporte Proteico
Peixe-Zebra
Proteínas rab de Ligação ao GTP/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (CC2D2A protein, zebrafish); 0 (Opsins); 0 (Vesicular Transport Proteins); 0 (Zebrafish Proteins); EC 3.6.1.- (Rab8a protein, zebrafish); EC 3.6.1.-. (RAB8A protein, human); EC 3.6.5.2 (rab GTP-Binding Proteins)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171228
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1007150


  4 / 19315 MEDLINE  
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[PMID]:29228003
[Au] Autor:Crawley O; Giles AC; Desbois M; Kashyap S; Birnbaum R; Grill B
[Ad] Endereço:Department of Neuroscience, The Scripps Research Institute, Scripps Florida, Jupiter, Florida, United States of America.
[Ti] Título:A MIG-15/JNK-1 MAP kinase cascade opposes RPM-1 signaling in synapse formation and learning.
[So] Source:PLoS Genet;13(12):e1007095, 2017 12.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The Pam/Highwire/RPM-1 (PHR) proteins are conserved intracellular signaling hubs that regulate synapse formation and axon termination. The C. elegans PHR protein, called RPM-1, acts as a ubiquitin ligase to inhibit the DLK-1 and MLK-1 MAP kinase pathways. We have identified several kinases that are likely to form a new MAP kinase pathway that suppresses synapse formation defects, but not axon termination defects, in the mechanosensory neurons of rpm-1 mutants. This pathway includes: MIG-15 (MAP4K), NSY-1 (MAP3K), JKK-1 (MAP2K) and JNK-1 (MAPK). Transgenic overexpression of kinases in the MIG-15/JNK-1 pathway is sufficient to impair synapse formation in wild-type animals. The MIG-15/JNK-1 pathway functions cell autonomously in the mechanosensory neurons, and these kinases localize to presynaptic terminals providing further evidence of a role in synapse development. Loss of MIG-15/JNK-1 signaling also suppresses defects in habituation to repeated mechanical stimuli in rpm-1 mutants, a behavioral deficit that is likely to arise from impaired glutamatergic synapse formation. Interestingly, habituation results are consistent with the MIG-15/JNK-1 pathway functioning as a parallel opposing pathway to RPM-1. These findings indicate the MIG-15/JNK-1 pathway can restrict both glutamatergic synapse formation and short-term learning.
[Mh] Termos MeSH primário: Proteínas de Caenorhabditis elegans/metabolismo
Fatores de Troca do Nucleotídeo Guanina/metabolismo
Sistema de Sinalização das MAP Quinases
Proteínas Quinases Ativadas por Mitógeno/metabolismo
Proteínas Serina-Treonina Quinases/metabolismo
Sinapses/fisiologia
[Mh] Termos MeSH secundário: Animais
Animais Geneticamente Modificados
Axônios/metabolismo
Caenorhabditis elegans/genética
Caenorhabditis elegans/crescimento & desenvolvimento
Proteínas de Caenorhabditis elegans/genética
Fatores de Troca do Nucleotídeo Guanina/genética
Proteínas Quinases Ativadas por Mitógeno/genética
Mutação
Neurogênese
Neurônios/metabolismo
Terminações Pré-Sinápticas/metabolismo
Proteínas Quinases/genética
Proteínas Quinases/metabolismo
Proteínas Serina-Treonina Quinases/genética
Transdução de Sinais
Sinapses/enzimologia
Ubiquitina-Proteína Ligases/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Caenorhabditis elegans Proteins); 0 (Guanine Nucleotide Exchange Factors); 0 (RPM-1 protein, C elegans); EC 2.3.2.27 (Ubiquitin-Protein Ligases); EC 2.7.- (Protein Kinases); EC 2.7.1.- (jkk-1 protein, C elegans); EC 2.7.11.1 (Mig-15 protein, C elegans); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); EC 2.7.11.24 (JNK-1 protein, C elegans); EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171212
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1007095


  5 / 19315 MEDLINE  
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[PMID]:29353056
[Au] Autor:Noreen S; Pegoraro M; Nouroz F; Tauber E; Kyriacou CP
[Ad] Endereço:Department of Genetics and Genome Biology, University of Leicester, United Kingdom; Molecular Genetics Lab, Department of Zoology, University of Peshawar, Pakistan. Electronic address: shumailanoreen@uop.edu.pk.
[Ti] Título:Interspecific studies of circadian genes period and timeless in Drosophila.
[So] Source:Gene;648:106-114, 2018 Mar 30.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The level of rescue of clock function in genetically arrhythmic Drosophila melanogaster hosts using interspecific clock gene transformation was used to study the putative intermolecular coevolution between interacting clock proteins. Among them PER and TIM are the two important negative regulators of the circadian clock feedback loop. We transformed either the D. pseudoobscura per or tim transgenes into the corresponding arrhythmic D. melanogaster mutant (per01 or tim01) and observed >50% rhythmicity but the period of activity rhythm was either longer (D. pseudoobscura-per) or shorter than 24 h (D. pseudoobscura-tim) compared to controls. By introducing both transgenes simultaneously into double mutants, we observed that the period of the activity rhythm was rescued by the pair of hemizygous transgenes (~24 h). These flies also showed a more optimal level of temperature compensation for the period. Under LD 12:12 these flies have a D. pseudoobscura like activity profile with the absence of morning anticipation as well as a very prominent earlier evening peak of activity rhythm. These observation are consistent with the view that TIM and PER form a heterospecific coevolved module at least for the circadian period of activity rhythms. However the strength of rhythmicity was reduced by having both transgenes present, so while evidence for a coevolution between PER and TIM is observed for some characters it is not for others.
[Mh] Termos MeSH primário: Ritmo Circadiano/genética
Proteínas de Drosophila/genética
Drosophila/genética
Proteínas Circadianas Period/genética
[Mh] Termos MeSH secundário: Animais
Animais Geneticamente Modificados
Drosophila/classificação
Drosophila/metabolismo
Proteínas de Drosophila/classificação
Proteínas de Drosophila/metabolismo
Drosophila melanogaster/genética
Drosophila melanogaster/metabolismo
Teste de Complementação Genética
Atividade Motora/genética
Mutação
Proteínas Circadianas Period/classificação
Proteínas Circadianas Period/metabolismo
Filogenia
Especificidade da Espécie
Temperatura Ambiente
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Drosophila Proteins); 0 (PER protein, Drosophila); 0 (Period Circadian Proteins); 0 (timeless protein, Drosophila)
[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:180122
[St] Status:MEDLINE


  6 / 19315 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


  7 / 19315 MEDLINE  
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[PMID]:28451923
[Au] Autor:Tower J; Landis GN; Shen J; Choi R; Fan Y; Lee D; Song J
[Ad] Endereço:Molecular and Computational Biology Program, Department of Biological Sciences, University of Southern California, 1050 Childs Way, RRI201, Los Angeles, CA, 90089-2910, USA. jtower@usc.edu.
[Ti] Título:Mifepristone/RU486 acts in Drosophila melanogaster females to counteract the life span-shortening and pro-inflammatory effects of male Sex Peptide.
[So] Source:Biogerontology;18(3):413-427, 2017 Jun.
[Is] ISSN:1573-6768
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Males with null mutation of Sex Peptide (SP) gene were compared to wild-type males for the ability to cause physiological changes in females that could be reversed by mifepristone. Males from wild-type strains decreased median female life span by average -51%. Feeding mifepristone increased life span of these females by average +106%. In contrast, SP-null males did not decrease female life span, and mifepristone increased median life span of these females by average +14%, which was equivalent to the effect of mifepristone in virgin females (average +16%). Expression of innate immune response transgenic reporter (Drosocin-GFP) was increased in females mated to wild-type males, and this expression was reduced by mifepristone. In contrast, SP-null males did not increase Drosocin-GFP reporter expression in the female. Similarly, mating increased endogenous microbial load, and this effect was reduced or absent in females fed mifepristone and in females mated to SP-null males; no loss of intestinal barrier integrity was detected using dye-leakage assay. Reduction of microbial load by treating adult flies with doxycycline reduced the effects of both mating and mifepristone on life span. Finally, mifepristone blocked the negative effect on life span caused by transgenic expression of SP in virgin females. The data support the conclusion that the majority of the life span-shortening, immune-suppressive and pro-inflammatory effects of mating are due to male SP, and demonstrate that mifepristone acts in females to counteract these effects of male SP.
[Mh] Termos MeSH primário: Proteínas de Drosophila/fisiologia
Inflamação/fisiopatologia
Longevidade/efeitos dos fármacos
Mifepristona/farmacologia
Peptídeos/fisiologia
[Mh] Termos MeSH secundário: Animais
Animais Geneticamente Modificados
Feminino
Proteínas de Fluorescência Verde/genética
Masculino
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Drosophila Proteins); 0 (Peptides); 0 (male accessory gland peptide, Drosophila); 147336-22-9 (Green Fluorescent Proteins); 320T6RNW1F (Mifepristone)
[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:10.1007/s10522-017-9703-y


  8 / 19315 MEDLINE  
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[PMID]:28744122
[Au] Autor:Zou D; Wang W; Lei D; Yin Y; Ren P; Chen J; Yin T; Wang B; Wang G; Wang Y
[Ad] Endereço:Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, People's Republic of China.
[Ti] Título:Penetration of blood-brain barrier and antitumor activity and nerve repair in glioma by doxorubicin-loaded monosialoganglioside micelles system.
[So] Source:Int J Nanomedicine;12:4879-4889, 2017.
[Is] ISSN:1178-2013
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:For the treatment of glioma and other central nervous system diseases, one of the biggest challenges is that most therapeutic drugs cannot be delivered to the brain tumor tissue due to the blood-brain barrier (BBB). The goal of this study was to construct a nanodelivery vehicle system with capabilities to overcome the BBB for central nervous system administration. Doxorubicin as a model drug encapsulated in ganglioside GM1 micelles was able to achieve up to 9.33% loading efficiency and 97.05% encapsulation efficiency by orthogonal experimental design. The in vitro study demonstrated a slow and sustainable drug release in physiological conditions. In the cellular uptake studies, mixed micelles could effectively transport into both human umbilical vein endothelial cells and C6 cells. Furthermore, biodistribution imaging of mice showed that the DiR/GM1 mixed micelles were accumulated sustainably and distributed centrally in the brain. Experiments on zebrafish confirmed that drug-loaded GM1 micelles can overcome the BBB and enter the brain. Among all the treatment groups, the median survival time of C6-bearing rats after administering DOX/GM1 micelles was significantly prolonged. In conclusion, the ganglioside nanomicelles developed in this work can not only penetrate BBB effectively but also repair nerves and kill tumor cells at the same time.
[Mh] Termos MeSH primário: Barreira Hematoencefálica/efeitos dos fármacos
Neoplasias Encefálicas/tratamento farmacológico
Doxorrubicina/farmacologia
Gangliosídeo G(M1)/química
Glioma/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Animais Geneticamente Modificados
Antibióticos Antineoplásicos/administração & dosagem
Antibióticos Antineoplásicos/farmacologia
Doxorrubicina/administração & dosagem
Doxorrubicina/farmacocinética
Sistemas de Liberação de Medicamentos/métodos
Gangliosídeos/química
Células Endoteliais da Veia Umbilical Humana
Seres Humanos
Masculino
Micelas
Regeneração Nervosa/efeitos dos fármacos
Ratos Wistar
Distribuição Tecidual
Peixe-Zebra/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibiotics, Antineoplastic); 0 (Gangliosides); 0 (Micelles); 0 (sialogangliosides); 37758-47-7 (G(M1) Ganglioside); 80168379AG (Doxorubicin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170727
[St] Status:MEDLINE
[do] DOI:10.2147/IJN.S138257


  9 / 19315 MEDLINE  
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[PMID]:28468832
[Au] Autor:Gut P; Reischauer S; Stainier DYR; Arnaout R
[Ad] Endereço:Nestlé Institute of Health Sciences, EPFL Innovation Park, Lausanne, Switzerland; Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany; and Cardiovascular Research Institute and Division of Cardiology, Department of Medicine, University of California San Francisco, San Francisco, C
[Ti] Título:LITTLE FISH, BIG DATA: ZEBRAFISH AS A MODEL FOR CARDIOVASCULAR AND METABOLIC DISEASE.
[So] Source:Physiol Rev;97(3):889-938, 2017 Jul 01.
[Is] ISSN:1522-1210
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The burden of cardiovascular and metabolic diseases worldwide is staggering. The emergence of systems approaches in biology promises new therapies, faster and cheaper diagnostics, and personalized medicine. However, a profound understanding of pathogenic mechanisms at the cellular and molecular levels remains a fundamental requirement for discovery and therapeutics. Animal models of human disease are cornerstones of drug discovery as they allow identification of novel pharmacological targets by linking gene function with pathogenesis. The zebrafish model has been used for decades to study development and pathophysiology. More than ever, the specific strengths of the zebrafish model make it a prime partner in an age of discovery transformed by big-data approaches to genomics and disease. Zebrafish share a largely conserved physiology and anatomy with mammals. They allow a wide range of genetic manipulations, including the latest genome engineering approaches. They can be bred and studied with remarkable speed, enabling a range of large-scale phenotypic screens. Finally, zebrafish demonstrate an impressive regenerative capacity scientists hope to unlock in humans. Here, we provide a comprehensive guide on applications of zebrafish to investigate cardiovascular and metabolic diseases. We delineate advantages and limitations of zebrafish models of human disease and summarize their most significant contributions to understanding disease progression to date.
[Mh] Termos MeSH primário: Doenças Cardiovasculares/genética
Descoberta de Drogas/métodos
Doenças Metabólicas/genética
Peixe-Zebra/genética
[Mh] Termos MeSH secundário: Animais
Animais Geneticamente Modificados
Fármacos Cardiovasculares/farmacologia
Doenças Cardiovasculares/tratamento farmacológico
Doenças Cardiovasculares/metabolismo
Doenças Cardiovasculares/fisiopatologia
Modelos Animais de Doenças
Predisposição Genética para Doença
Seres Humanos
Doenças Metabólicas/tratamento farmacológico
Doenças Metabólicas/metabolismo
Doenças Metabólicas/fisiopatologia
Fenótipo
Especificidade da Espécie
Peixe-Zebra/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Cardiovascular Agents)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1152/physrev.00038.2016


  10 / 19315 MEDLINE  
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[PMID]:28468884
[Au] Autor:Gardner CL; Sun C; Luke T; Raviprakash K; Wu H; Jiao JA; Sullivan E; Reed DS; Ryman KD; Klimstra WB
[Ad] Endereço:University of Pittsburgh Center for Vaccine Research, Pittsburgh, Pennsylvania, USA.
[Ti] Título:Antibody Preparations from Human Transchromosomic Cows Exhibit Prophylactic and Therapeutic Efficacy against Venezuelan Equine Encephalitis Virus.
[So] Source:J Virol;91(14), 2017 Jul 15.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Venezuelan equine encephalitis virus (VEEV) is a mosquito-borne RNA virus that causes low mortality but high morbidity rates in humans. In addition to natural outbreaks, there is the potential for exposure to VEEV via aerosolized virus particles. There are currently no FDA-licensed vaccines or antiviral therapies for VEEV. Passive immunotherapy is an approved method used to protect individuals against several pathogens and toxins. Human polyclonal antibodies (PAbs) are ideal, but this is dependent upon serum from convalescent human donors, which is in limited supply. Non-human-derived PAbs can have serious immunoreactivity complications, and when "humanized," these antibodies may exhibit reduced neutralization efficiency. To address these issues, transchromosomic (Tc) bovines have been created, which can produce potent neutralizing human antibodies in response to hyperimmunization. In these studies, we have immunized these bovines with different VEEV immunogens and evaluated the protective efficacy of purified preparations of the resultant human polyclonal antisera against low- and high-dose VEEV challenges. These studies demonstrate that prophylactic or therapeutic administration of the polyclonal antibody preparations (TcPAbs) can protect mice against lethal subcutaneous or aerosol challenge with VEEV. Furthermore, significant protection against unrelated coinfecting viral pathogens can be conferred by combining individual virus-specific TcPAb preparations. With the globalization and spread or potential aerosol release of emerging infectious diseases, it will be critical to develop platforms that are able to produce therapeutics in a short time frame. By using a transchromosomic (Tc) bovine platform, it is theoretically possible to produce antigen-specific highly neutralizing therapeutic polyclonal human antibody (TcPAb) preparations in 6 months or less. In this study, we demonstrate that Tc bovine-derived Venezuelan equine encephalitis virus (VEEV)-specific TcPAbs are highly effective against VEEV infection that mimics not only the natural route of infection but also infection via aerosol exposure. Additionally, we show that combinatorial TcPAb preparations can be used to treat coinfections with divergent pathogens, demonstrating that the Tc bovine platform could be beneficial in areas where multiple infectious diseases occur contemporaneously or in the case of multipathogen release.
[Mh] Termos MeSH primário: Animais Geneticamente Modificados
Anticorpos Antivirais/administração & dosagem
Vírus da Encefalite Equina Venezuelana/imunologia
Encefalomielite Equina Venezuelana/prevenção & controle
Encefalomielite Equina Venezuelana/terapia
Imunização Passiva
[Mh] Termos MeSH secundário: Animais
Anticorpos Antivirais/isolamento & purificação
Bovinos
Modelos Animais de Doenças
Seres Humanos
Camundongos
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Viral)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE



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