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Pesquisa : A11.251.210.200 [Categoria DeCS]
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[PMID]:28467418
[Au] Autor:Khare S; Nick JA; Zhang Y; Galeano K; Butler B; Khoshbouei H; Rayaprolu S; Hathorn T; Ranum LPW; Smithson L; Golde TE; Paucar M; Morse R; Raff M; Simon J; Nordenskjöld M; Wirdefeldt K; Rincon-Limas DE; Lewis J; Kaczmarek LK; Fernandez-Funez P; Nick HS; Waters MF
[Ad] Endereço:Department of Neurology, University of Florida, Gainesville, FL, United States of America.
[Ti] Título:A KCNC3 mutation causes a neurodevelopmental, non-progressive SCA13 subtype associated with dominant negative effects and aberrant EGFR trafficking.
[So] Source:PLoS One;12(5):e0173565, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The autosomal dominant spinocerebellar ataxias (SCAs) are a diverse group of neurological disorders anchored by the phenotypes of motor incoordination and cerebellar atrophy. Disease heterogeneity is appreciated through varying comorbidities: dysarthria, dysphagia, oculomotor and/or retinal abnormalities, motor neuron pathology, epilepsy, cognitive impairment, autonomic dysfunction, and psychiatric manifestations. Our study focuses on SCA13, which is caused by several allelic variants in the voltage-gated potassium channel KCNC3 (Kv3.3). We detail the clinical phenotype of four SCA13 kindreds that confirm causation of the KCNC3R423H allele. The heralding features demonstrate congenital onset with non-progressive, neurodevelopmental cerebellar hypoplasia and lifetime improvement in motor and cognitive function that implicate compensatory neural mechanisms. Targeted expression of human KCNC3R423H in Drosophila triggers aberrant wing veins, maldeveloped eyes, and fused ommatidia consistent with the neurodevelopmental presentation of patients. Furthermore, human KCNC3R423H expression in mammalian cells results in altered glycosylation and aberrant retention of the channel in anterograde and/or endosomal vesicles. Confirmation of the absence of plasma membrane targeting was based on the loss of current conductance in cells expressing the mutant channel. Mechanistically, genetic studies in Drosophila, along with cellular and biophysical studies in mammalian systems, demonstrate the dominant negative effect exerted by the mutant on the wild-type (WT) protein, which explains dominant inheritance. We demonstrate that ocular co-expression of KCNC3R423H with Drosophila epidermal growth factor receptor (dEgfr) results in striking rescue of the eye phenotype, whereas KCNC3R423H expression in mammalian cells results in aberrant intracellular retention of human epidermal growth factor receptor (EGFR). Together, these results indicate that the neurodevelopmental consequences of KCNC3R423H may be mediated through indirect effects on EGFR signaling in the developing cerebellum. Our results therefore confirm the KCNC3R423H allele as causative for SCA13, through a dominant negative effect on KCNC3WT and links with EGFR that account for dominant inheritance, congenital onset, and disease pathology.
[Mh] Termos MeSH primário: Receptor do Fator de Crescimento Epidérmico/metabolismo
Canais de Potássio Shaw/genética
Degenerações Espinocerebelares/genética
[Mh] Termos MeSH secundário: Animais
Células CHO
Cricetinae
Cricetulus
Drosophila melanogaster
Feminino
Seres Humanos
Masculino
Linhagem
Transporte Proteico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (KCNC3 protein, human); 0 (Shaw Potassium Channels); EC 2.7.10.1 (Receptor, Epidermal Growth Factor)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180311
[Lr] Data última revisão:
180311
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0173565


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[PMID]:29380037
[Au] Autor:Miyashita N; Onozawa M; Hayasaka K; Yamada T; Migita O; Hata K; Okada K; Goto H; Nakagawa M; Hashimoto D; Kahata K; Kondo T; Kunishima S; Teshima T
[Ad] Endereço:Department of Hematology, Hokkaido University Faculty of Medicine, Graduate School of Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo, 0608638, Japan.
[Ti] Título:A novel heterozygous ITGB3 p.T720del inducing spontaneous activation of integrin αIIbß3 in autosomal dominant macrothrombocytopenia with aggregation dysfunction.
[So] Source:Ann Hematol;97(4):629-640, 2018 Apr.
[Is] ISSN:1432-0584
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:We identified a novel heterozygous ITGB3 p.T720del mutation in a pedigree with macrothrombocytopenia exhibiting aggregation dysfunction. Platelet aggregation induced by ADP and collagen was significantly reduced, while ristocetin aggregation was normal. Integrin αIIbß3 was partially activated in a resting status, but platelet expression of αIIbß3 was downregulated. Functional analysis using a cell line showed spontaneous phosphorylation of FAK in αIIb/ß3 (p.T720del)-transfected 293T cells in suspension conditions. Abnormal cytoplasmic protrusions, membrane ruffling, and cytoplasmic localization of αIIbß3 were observed in αIIb/ß3 (p.T720del)-transfected CHO cells. Such morphological changes were reversed by treatment with an FAK inhibitor. These findings imply spontaneous, but partial, activation of αIIbß3 followed by phosphorylation of FAK as the initial mechanism of abnormal thrombopoiesis. Internalization and decreased surface expression of αIIbß3 would contribute to aggregation dysfunction. We reviewed the literature of congenital macrothrombocytopenia associated with heterozygous ITGA2B or ITGB3 mutations. Reported mutations were highly clustered at the membrane proximal region of αIIbß3, which affected the critical interaction between αIIb R995 and ß3 D723, resulting in a constitutionally active form of the αIIbß3 complex. Macrothrombocytopenia caused by a heterozygous activating mutation of ITGA2B or ITGB3 at the membrane proximal region forms a distinct entity of rare congenital thrombocytopenia.
[Mh] Termos MeSH primário: Deleção de Genes
Genes Dominantes
Heterozigoto
Integrina beta3/genética
Complexo Glicoproteico GPIIb-IIIa de Plaquetas/agonistas
Trombocitopenia/genética
[Mh] Termos MeSH secundário: Adulto
Animais
Células CHO
Cricetulus
Saúde da Família
Feminino
Células HEK293
Seres Humanos
Integrina beta3/metabolismo
Japão
Masculino
Meia-Idade
Mutagênese Sítio-Dirigida
Linhagem
Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo
Proteínas Recombinantes/metabolismo
Trombocitopenia/sangue
Trombocitopenia/metabolismo
Trombocitopenia/fisiopatologia
Adulto Jovem
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ITGB3 protein, human); 0 (Integrin beta3); 0 (Platelet Glycoprotein GPIIb-IIIa Complex); 0 (Recombinant 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:180131
[St] Status:MEDLINE
[do] DOI:10.1007/s00277-017-3214-4


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[PMID]:29357376
[Au] Autor:Li Y; Zhou C; Li J; Liu J; Lin L; Li L; Cao D; Li Q; Wang Z
[Ad] Endereço:School of Pharmaceutical Sciences, School of Pharmaceutical Sciences, Guangzhou, China.
[Ti] Título:Single domain based bispecific antibody, Muc1-Bi-1, and its humanized form, Muc1-Bi-2, induce potent cancer cell killing in muc1 positive tumor cells.
[So] Source:PLoS One;13(1):e0191024, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Muc1 is one of the most studied tumor antigens. However, antibodies or antibody-toxin conjugates against Muc1 have not shown significant efficacy for tumors with Muc1 overexpression. In this study, we employed bispecific antibody approach to target Muc1 positive tumor cells. A novel bispecific antibody, Muc1-Bi-1, was constructed by linking single domain antibodies, anti-Muc1-VHH and anti-CD16-VHH. Muc1-Bi-2, the humanized form of Muc1-Bi-1, was also constructed by grafting. Both Muc1-Bi bispecific antibodies can be efficiently expressed and purified from bacteria. In vitro, the Muc1-Bi bispecific antibodies can recruit Natural Killer (NK) cells to drive potent and specific cell killing of Muc1-overexpressing tumor cells. In xenograft model, the Muc1-Bi bispecific antibodies can suppress tumor growth in the presence of human peripheral blood mononuclear cells (PBMC). These data suggested that the single domain based Muc1-Bi may provide a valid strategy for targeting tumors with Muc1 overexpression.
[Mh] Termos MeSH primário: Anticorpos Biespecíficos/imunologia
Mucina-1/imunologia
[Mh] Termos MeSH secundário: Animais
Anticorpos Biespecíficos/genética
Células CHO
Linhagem Celular Tumoral
Proliferação Celular
Cricetulus
Ensaio de Imunoadsorção Enzimática
Citometria de Fluxo
Seres Humanos
Camundongos
Camundongos Endogâmicos NOD
Camundongos SCID
Neoplasias/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibodies, Bispecific); 0 (MUC1 protein, human); 0 (Mucin-1)
[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:180123
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191024


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[PMID]:29031765
[Au] Autor:Boakye YD; Groyer L; Heiss EH
[Ad] Endereço:Department of Pharmacognosy, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria.
[Ti] Título:An increased autophagic flux contributes to the anti-inflammatory potential of urolithin A in macrophages.
[So] Source:Biochim Biophys Acta;1862(1):61-70, 2018 01.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: An extract of Phyllanthus muellerianus and its constituent geraniin have been reported to exert anti-inflammatory activity in vivo. However, orally consumed geraniin, an ellagitannin, shows low bioavailability and undergoes metabolization to urolithins by gut microbiota. This study aimed at comparing geraniin and urolithin A with respect to inhibition of M1 (LPS) polarization of murine J774.1 macrophages and shedding more light on possible underlying mechanisms. METHODS: Photometric, fluorimetric as well as luminescence-based assays monitored production of reactive oxygen species (ROS) and nitric oxide (NO), cell viability or reporter gene expression. Western blot analyses and confocal microscopy showed abundance and localization of target proteins, respectively. RESULTS: Urolithin A is a stronger inhibitor of M1 (LPS) macrophage polarization (production of NO, ROS and pro-inflammatory proteins) than geraniin. Urolithin A leads to an elevated autophagic flux in macrophages. Inhibition of autophagy in M1 (LPS) macrophages overcomes the suppressed nuclear translocation of p65 (NF-kB; nuclear factor kB), the reduced expression of pro-inflammatory genes as well as the diminished NO production brought about by urolithin A. The increased autophagic flux is furthermore associated with impaired Akt/mTOR (mammalian target of rapamycin) signaling in urolithin A-treated macrophages. CONCLUSIONS AND GENERAL SIGNIFICANCE: Intestinal metabolization may boost the potential health benefit of widely consumed dietary ellagitannins, as suggested by side by side comparison of geraniin and urolithin A in M1(LPS) macrophages. Increased activity of the autophagic cellular recycling machinery aids the anti-inflammatory bioactivity of urolithin A.
[Mh] Termos MeSH primário: Anti-Inflamatórios/farmacologia
Autofagia/efeitos dos fármacos
Cumarínicos/farmacologia
Macrófagos/metabolismo
[Mh] Termos MeSH secundário: Transporte Ativo do Núcleo Celular/efeitos dos fármacos
Animais
Células CHO
Núcleo Celular/metabolismo
Cricetinae
Cricetulus
Células HEK293
Seres Humanos
Lipopolissacarídeos/toxicidade
Camundongos
Óxido Nítrico/metabolismo
Espécies Reativas de Oxigênio/metabolismo
Fator de Transcrição RelA/metabolismo
Proteínas ral de Ligação ao GTP/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents); 0 (Coumarins); 0 (Lipopolysaccharides); 0 (RELA protein, human); 0 (Reactive Oxygen Species); 0 (Transcription Factor RelA); 1143-70-0 (3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one); 31C4KY9ESH (Nitric Oxide); EC 3.6.1.- (Rala protein, mouse); EC 3.6.5.2 (ral GTP-Binding 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:171017
[St] Status:MEDLINE


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[PMID]:29291441
[Au] Autor:Otvagin VF; Nyuchev AV; Kuzmina NS; Grishin ID; Gavryushin AE; Romanenko YV; Koifman OI; Belykh DV; Peskova NN; Shilyagina NY; Balalaeva IV; Fedorov AY
[Ad] Endereço:Lobachevsky State University of Nizhny Novgorod, Gagarina Av. 23, Nizhny Novgorod 603950, Russian Federation.
[Ti] Título:Synthesis and biological evaluation of new water-soluble photoactive chlorin conjugate for targeted delivery.
[So] Source:Eur J Med Chem;144:740-750, 2018 Jan 20.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:A new water-soluble conjugate, consisting of a chlorin-based photosensitizing part, and a 4-arylaminoquinazoline moiety with high potential affinity to an epidermal growth factor receptors (EGFR) and vascular endothelial growth factor receptors (VEGFR), suitable for photodynamic therapy (PDT), was synthesized starting from methylpheophorbide-a in seven steps. An increased accumulation of this compound in A431 cells with high level of EGFR expression, in comparison with CHO and HeLa cells with low EGFR expression was observed. The prepared conjugate exhibits dark and photoinduced cytotoxicity at micromolar concentrations with IC /IC ratio of 11-18. In tumor-bearing mice, the conjugate preferentially accumulates in the tumor tissue.
[Mh] Termos MeSH primário: Sistemas de Liberação de Medicamentos
Fármacos Fotossensibilizantes/farmacologia
Porfirinas/farmacologia
Quinazolinas/farmacologia
[Mh] Termos MeSH secundário: Animais
Células CHO
Linhagem Celular Tumoral
Cricetulus
Relação Dose-Resposta a Droga
Células HeLa
Seres Humanos
Camundongos
Camundongos Endogâmicos BALB C
Estrutura Molecular
Fotoquimioterapia
Fármacos Fotossensibilizantes/síntese química
Fármacos Fotossensibilizantes/química
Porfirinas/química
Quinazolinas/química
Solubilidade
Relação Estrutura-Atividade
Fator A de Crescimento do Endotélio Vascular/biossíntese
Água/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Photosensitizing Agents); 0 (Porphyrins); 0 (Quinazolines); 0 (Vascular Endothelial Growth Factor A); 059QF0KO0R (Water); 2683-84-3 (chlorin)
[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:180102
[St] Status:MEDLINE


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[PMID]:28453956
[Au] Autor:Ta HT; Li Z; Hagemeyer CE; Cowin G; Zhang S; Palasubramaniam J; Alt K; Wang X; Peter K; Whittaker AK
[Ad] Endereço:Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Australia; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Australia. Electronic address: h.ta@uq.edu.au.
[Ti] Título:Molecular imaging of activated platelets via antibody-targeted ultra-small iron oxide nanoparticles displaying unique dual MRI contrast.
[So] Source:Biomaterials;134:31-42, 2017 Jul.
[Is] ISSN:1878-5905
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Magnetic resonance imaging (MRI) is a powerful and indispensable tool in medical research, clinical diagnosis, and patient care due to its high spatial resolution and non-limited penetration depth. The simultaneous use of positive and negative MRI imaging that employs the same contrast agents will significantly improve detection accuracy. Here we report the development of functional multimodal iron oxide nanoparticles for targeted MRI of atherothrombosis using a combination of chemical and biological conjugation techniques. Monodisperse, water-soluble and biocompatible ultra-small magnetic dual contrast iron oxide nanoparticles (DCIONs) were generated using a high-temperature co-precipitation route and appeared to be efficient positive and negative dual contrast agents for magnetic resonance imaging. Using a unique chemo-enzymatic approach involving copper-free click chemistry and Staphylococcus aureus sortase A enzyme conjugation, DCIONs were functionalized with single-chain antibodies (scFv) directed against activated platelets for targeting purposes. The DCIONs were also labelled with fluorescent molecules to allow for optical imaging. The antigen binding activity of the scFv was retained and resulted in the successful targeting of contrast agents to thrombosis as demonstrated in a range of in vitro and in vivo experiments. T - and T -weighted MRI of thrombi was recorded and demonstrated the great potential of dual T /T contrast iron oxide particles in imaging of cardiovascular disease.
[Mh] Termos MeSH primário: Plaquetas/fisiologia
Meios de Contraste/química
Compostos Férricos/química
Imagem por Ressonância Magnética/métodos
Nanopartículas de Magnetita/química
Patologia Molecular/métodos
[Mh] Termos MeSH secundário: Animais
Células CHO
Cricetulus
Citometria de Fluxo
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Contrast Media); 0 (Ferric Compounds); 0 (Magnetite Nanoparticles); 1K09F3G675 (ferric oxide)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE


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[PMID]:29374258
[Au] Autor:Hirata T; Mishra SK; Nakamura S; Saito K; Motooka D; Takada Y; Kanzawa N; Murakami Y; Maeda Y; Fujita M; Yamaguchi Y; Kinoshita T
[Ad] Endereço:Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, 565-0871, Japan.
[Ti] Título:Identification of a Golgi GPI-N-acetylgalactosamine transferase with tandem transmembrane regions in the catalytic domain.
[So] Source:Nat Commun;9(1):405, 2018 01 26.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Many eukaryotic proteins are anchored to the cell surface via the glycolipid glycosylphosphatidylinositol (GPI). Mammalian GPIs have a conserved core but exhibit diverse N-acetylgalactosamine (GalNAc) modifications, which are added via a yet unresolved process. Here we identify the Golgi-resident GPI-GalNAc transferase PGAP4 and show by mass spectrometry that PGAP4 knockout cells lose GPI-GalNAc structures. Furthermore, we demonstrate that PGAP4, in contrast to known Golgi glycosyltransferases, is not a single-pass membrane protein but contains three transmembrane domains, including a tandem transmembrane domain insertion into its glycosyltransferase-A fold as indicated by comparative modeling. Mutational analysis reveals a catalytic site, a DXD-like motif for UDP-GalNAc donor binding, and several residues potentially involved in acceptor binding. We suggest that a juxtamembrane region of PGAP4 accommodates various GPI-anchored proteins, presenting their acceptor residue toward the catalytic center. In summary, we present insights into the structure of PGAP4 and elucidate the initial step of GPI-GalNAc biosynthesis.
[Mh] Termos MeSH primário: Acetilgalactosamina/química
Glicosilfosfatidilinositóis/química
Complexo de Golgi/metabolismo
N-Acetilgalactosaminiltransferases/química
[Mh] Termos MeSH secundário: Acetilgalactosamina/biossíntese
Motivos de Aminoácidos
Animais
Células CHO
Domínio Catalítico
Cricetulus
Cristalografia por Raios X
Expressão Gênica
Vetores Genéticos/química
Vetores Genéticos/metabolismo
Glicosilfosfatidilinositóis/metabolismo
Complexo de Golgi/ultraestrutura
Seres Humanos
Camundongos
Camundongos Knockout
Modelos Moleculares
Mutação
N-Acetilgalactosaminiltransferases/genética
N-Acetilgalactosaminiltransferases/metabolismo
Ligação Proteica
Conformação Proteica em alfa-Hélice
Conformação Proteica em Folha beta
Domínios e Motivos de Interação entre Proteínas
Homologia Estrutural de Proteína
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Glycosylphosphatidylinositols); EC 2.4.1.- (N-Acetylgalactosaminyltransferases); EC 2.4.1.41 (polypeptide N-acetylgalactosaminyltransferase); KM15WK8O5T (Acetylgalactosamine)
[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:180128
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02799-0


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[PMID]:29324849
[Au] Autor:Lee JW; Heo W; Lee J; Jin N; Yoon SM; Park KY; Kim EY; Kim WT; Kim JY
[Ad] Endereço:Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.
[Ti] Título:The B cell death function of obinutuzumab-HDEL produced in plant (Nicotiana benthamiana L.) is equivalent to obinutuzumab produced in CHO cells.
[So] Source:PLoS One;13(1):e0191075, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Plants have attracted attention as bio-drug production platforms because of their economical and safety benefits. The preliminary efficacy of ZMapp, a cocktail of antibodies produced in N. benthamiana (Nicotiana benthamiana L.), suggested plants may serve as a platform for antibody production. However, because the amino acid sequences of the Fab fragment are diverse and differences in post-transcriptional processes between animals and plants remain to be elucidated, it is necessary to confirm functional equivalence of plant-produced antibodies to the original antibody. In this study, Obinutuzumab, a third generation anti-CD20 antibody, was produced in N. benthamiana leaves (plant-obinutuzumab) and compared to the original antibody produced in glyco-engineered Chinese hamster ovary (CHO) cells (CHO-obinutuzumab). Two forms (with or without an HDEL tag) were generated and antibody yields were compared. The HDEL-tagged form was more highly expressed than the non-HDEL-tagged form which was cleaved in the N-terminus. To determine the equivalence in functions of the Fab region between the two forms, we compared the CD20 binding affinities and direct binding induced cell death of a CD20-positive B cells. Both forms showed similar CD20 binding affinities and direct cell death of B cell. The results suggested that plant-obinutuzumab was equivalent to CHO-obinutuzumab in CD20 binding, cell aggregation, and direct cell death via binding. Therefore, our findings suggest that Obinutuzumab is a promising biosimilar candidate that can be produced efficiently in plants.
[Mh] Termos MeSH primário: Anticorpos Monoclonais Humanizados/farmacologia
Antineoplásicos Imunológicos/farmacologia
Linfócitos B/citologia
Morte Celular
Tabaco/genética
[Mh] Termos MeSH secundário: Animais
Células CHO
Cricetinae
Cricetulus
Epitopos/imunologia
Citometria de Fluxo
Folhas de Planta/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibodies, Monoclonal, Humanized); 0 (Antineoplastic Agents, Immunological); 0 (Epitopes); O43472U9X8 (obinutuzumab)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180112
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191075


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[PMID]:29394011
[Au] Autor:Saladino R; Chiocchini U; Botta G; Delfino M; Conigliaro R; Mosesso P
[Ti] Título:Free radical scavenging capacity and protective effect of natural substances in peloids from the thermal spring pool Bagnaccio (Viterbo, Italy).
[So] Source:J Cosmet Sci;67(2):71-92, 2016 Mar-Apr.
[Is] ISSN:1525-7886
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Natural peloids from sulfurous thermal springs are largely used in cosmetic and pelotherapy for the treatment of different dermatological conditions, including skin aging, dermatitis, and other eczemas. The beneficial effects are correlated to mineralogical and other thermal properties, as well as to the presence of natural substances with specific antioxidant activity. Few data are available for the comparison between natural peloids and synthetic (i.e., artificially maturated) muds. In this context, the natural substances and antioxidant activity of natural white mud (WM) and dark mud (DM) peloids from the sulfurous thermal spring pool Bagnaccio (Viterbo, Italy) have been studied in detail to evaluate possible relationships between physicochemical properties and therapeutic effect. A large panel of natural substances in WM and DM were characterized for the first time by ³¹P-nuclear magnetic resonance and gas chromatography associated to mass spectrometry analysis. Polar fractions of WM and DM peloids were characterized by the presence of several bioactive natural compounds, showing high antioxidant activity and DNA protective effect, as evaluated by 2,2-diphenyl-1-picrylhydrazyl assay, and hydrogen peroxide­induced DNA breakage in the alkaline comet assay. The antioxidant activity and DNA protective effect could be attributed to radical scavenging rather than a modulatory effect on the induced DNA repair, and are of order of intensity higher than that reported for synthetic muds.
[Mh] Termos MeSH primário: Alcaloides/farmacologia
Depuradores de Radicais Livres/farmacologia
Hidrocarbonetos Aromáticos/farmacologia
Fenóis/farmacologia
Terpenos/farmacologia
[Mh] Termos MeSH secundário: Alcaloides/química
Alcaloides/isolamento & purificação
Alcanos/química
Alcanos/isolamento & purificação
Alcanos/farmacologia
Alcenos/química
Alcenos/isolamento & purificação
Alcenos/farmacologia
Animais
Compostos de Bifenilo/antagonistas & inibidores
Compostos de Bifenilo/química
Células CHO
Linhagem Celular Tumoral
Sobrevivência Celular/efeitos dos fármacos
Ensaio Cometa
Cricetulus
DNA/efeitos dos fármacos
Depuradores de Radicais Livres/química
Depuradores de Radicais Livres/isolamento & purificação
Fontes Termais
Seres Humanos
Hidrocarbonetos Aromáticos/química
Hidrocarbonetos Aromáticos/isolamento & purificação
Peróxido de Hidrogênio/antagonistas & inibidores
Peróxido de Hidrogênio/química
Itália
Espectroscopia de Ressonância Magnética
Camundongos
Terapia por Lama
Fenóis/química
Fenóis/isolamento & purificação
Picratos/antagonistas & inibidores
Picratos/química
Terpenos/química
Terpenos/isolamento & purificação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Alkaloids); 0 (Alkanes); 0 (Alkenes); 0 (Biphenyl Compounds); 0 (Free Radical Scavengers); 0 (Hydrocarbons, Aromatic); 0 (Phenols); 0 (Picrates); 0 (Terpenes); 9007-49-2 (DNA); BBX060AN9V (Hydrogen Peroxide); DFD3H4VGDH (1,1-diphenyl-2-picrylhydrazyl)
[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:180203
[St] Status:MEDLINE


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[PMID]:29198882
[Au] Autor:Sekiguchi K; Ogawa E; Kurohane K; Konishi H; Mochizuki N; Manabe K; Imai Y
[Ad] Endereço:Laboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422-8526, Japan.
[Ti] Título:Adjuvant effect of short chain triacylglycerol tributyrin on a mouse contact hypersensitivity model.
[So] Source:Toxicol Lett;284:56-62, 2018 Mar 01.
[Is] ISSN:1879-3169
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Little attention has been paid to chemicals that can enhance hypersensitivity caused by other chemicals. We have demonstrated that phthalate esters with short chain alcohols enhance fluorescein isothiocyanate (FITC)-induced contact hypersensitivity (CHS) in a mouse model. Furthermore, phthalate esters with such an enhancing effect were found to activate transient receptor potential ankyrin 1 (TRPA1) cation channels, which are expressed on a part of sensory neurons, using a TRPA1-expressing cell line. In this study, we examined these activities of esters comprising glycerol and a short chain fatty acid, i.e. dibutyrin and tributyrin. We carried out chemical synthesis of dibutyrin isomers. Each dibutyrin isomer weakly activated TRPA1 and slightly enhanced skin sensitization to FITC. Unexpectedly, TRPA1 activation and enhancement of FITC-CHS were much more evident in the presence of tributyrin. Mechanistically, tributyrin induced increased dendritic cell trafficking from the skin to draining lymph nodes. Tributyrin enhanced interferon-γ (IFN-γ) production by draining lymph nodes, while its effect on interleukin-4 (IL-4) production was relatively less prominent. These results suggested that tributyrin concomitantly caused TRPA1 activation and an adjuvant effect on FITC-CHS.
[Mh] Termos MeSH primário: Adjuvantes Imunológicos/toxicidade
Dermatite de Contato/imunologia
Canal de Cátion TRPA1/metabolismo
Triglicerídeos/toxicidade
[Mh] Termos MeSH secundário: Adjuvantes Imunológicos/administração & dosagem
Animais
Células CHO
Movimento Celular/efeitos dos fármacos
Cricetulus
Células Dendríticas/efeitos dos fármacos
Dermatite de Contato/metabolismo
Modelos Animais de Doenças
Feminino
Fluoresceína-5-Isotiocianato/administração & dosagem
Fluoresceína-5-Isotiocianato/toxicidade
Seres Humanos
Interferon gama/metabolismo
Interleucina-4/metabolismo
Linfonodos/efeitos dos fármacos
Linfonodos/imunologia
Camundongos Endogâmicos BALB C
Pele/efeitos dos fármacos
Pele/imunologia
Triglicerídeos/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adjuvants, Immunologic); 0 (TRPA1 Cation Channel); 0 (Triglycerides); 207137-56-2 (Interleukin-4); 82115-62-6 (Interferon-gamma); I223NX31W9 (Fluorescein-5-isothiocyanate); S05LZ624MF (tributyrin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171205
[St] Status:MEDLINE



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