Base de dados : MEDLINE
Pesquisa : D13.695.578.550.650 [Categoria DeCS]
Referências encontradas : 266 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 27 ir para página                         

  1 / 266 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28696256
[Au] Autor:Han S; Zhuang H; Shumyak S; Wu J; Li H; Yang LJ; Reeves WH
[Ad] Endereço:Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Florida, Gainesville, FL 32610; and.
[Ti] Título:A Novel Subset of Anti-Inflammatory CD138 Macrophages Is Deficient in Mice with Experimental Lupus.
[So] Source:J Immunol;199(4):1261-1274, 2017 Aug 15.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Dead cells accumulating in the tissues may contribute to chronic inflammation. We examined the cause of impaired apoptotic cell clearance in human and murine lupus. Dead cells accumulated in bone marrow from lupus patients but not from nonautoimmune patients undergoing myeloablation, where they were efficiently removed by macrophages (MΦ). Impaired apoptotic cell uptake by MΦ also was seen in mice treated i.p. with pristane (develop lupus) but not mineral oil (MO) (do not develop lupus). The inflammatory response to both pristane and MO rapidly depleted resident (Tim4 ) large peritoneal MΦ. The peritoneal exudate of pristane-treated mice contained mainly Ly6C inflammatory monocytes; whereas in MO-treated mice, it consisted predominantly of a novel subset of highly phagocytic MΦ resembling small peritoneal MΦ (SPM) that expressed CD138 and the scavenger receptor Marco. Treatment with anti-Marco-neutralizing Abs and the class A scavenger receptor antagonist polyinosinic acid inhibited phagocytosis of apoptotic cells by CD138 MΦ. CD138 MΦ expressed IL-10R, CD206, and CCR2 but little TNF-α or CX3CR1. They also expressed high levels of activated CREB, a transcription factor implicated in generating alternatively activated MΦ. Similar cells were identified in the spleen and lung of MO-treated mice and also were induced by LPS. We conclude that highly phagocytic, CD138 SPM-like cells with an anti-inflammatory phenotype may promote the resolution of inflammation in lupus and infectious diseases. These SPM-like cells are not restricted to the peritoneum and may help clear apoptotic cells from tissues such as the lung, helping to prevent chronic inflammation.
[Mh] Termos MeSH primário: Lúpus Eritematoso Sistêmico/imunologia
Macrófagos Peritoneais/imunologia
Fagocitose
Sindecana-1/imunologia
[Mh] Termos MeSH secundário: Animais
Antígenos Ly/análise
Apoptose
Células da Medula Óssea/imunologia
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo
Modelos Animais de Doenças
Seres Humanos
Inflamação/imunologia
Subunidade alfa de Receptor de Interleucina-10/genética
Subunidade alfa de Receptor de Interleucina-10/imunologia
Pulmão/citologia
Pulmão/imunologia
Lúpus Eritematoso Sistêmico/induzido quimicamente
Lúpus Eritematoso Sistêmico/fisiopatologia
Macrófagos Peritoneais/efeitos dos fármacos
Macrófagos Peritoneais/patologia
Proteínas de Membrana/genética
Proteínas de Membrana/metabolismo
Camundongos
Óleo Mineral/farmacologia
Poli I/farmacologia
Receptores Imunológicos/genética
Receptores Imunológicos/metabolismo
Baço/citologia
Baço/imunologia
Sindecana-1/genética
Terpenos/farmacologia
Fator de Necrose Tumoral alfa/genética
Fator de Necrose Tumoral alfa/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Ly); 0 (Creb1 protein, mouse); 0 (Cyclic AMP Response Element-Binding Protein); 0 (Interleukin-10 Receptor alpha Subunit); 0 (Ly-6C antigen, mouse); 0 (Marco protein, mouse); 0 (Membrane Proteins); 0 (Receptors, Immunologic); 0 (Sdc1 protein, mouse); 0 (Syndecan-1); 0 (TIM-4 protein, mouse); 0 (Terpenes); 0 (Tumor Necrosis Factor-alpha); 25249-22-3 (Poly I); 26HZV48DT1 (pristane); 8020-83-5 (Mineral Oil)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170712
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1700099


  2 / 266 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28115843
[Au] Autor:Roviello GN; Vicidomini C; Costanzo V; Roviello V
[Ad] Endereço:CNR Istituto di Biostrutture e Bioimmagini, Via Mezzocannone site and Headquarters.
[Ti] Título:Nucleic acid binding and other biomedical properties of artificial oligolysines.
[So] Source:Int J Nanomedicine;11:5897-5904, 2016.
[Is] ISSN:1178-2013
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:In the present study, we report the interaction of an artificial oligolysine (referred to as AOL) realized in our laboratory with targets of biomedical importance. These included polyinosinic acid (poly rI) and its complex with polycytidylic acid (poly I:C), RNAs with well-known interferon-inducing ability, and double-stranded (ds) DNA. The ability of the peptide to bind both single-stranded poly rI and ds poly I:C RNAs emerged from our circular dichroism (CD) and ultraviolet (UV) studies. In addition, we found that AOL forms complexes with dsDNA, as shown by spectroscopic binding assays and UV thermal denaturation experiments. These findings are encouraging for the possible use of AOL in biomedicine for nucleic acid targeting and oligonucleotide condensation, with the latter being a key step preceding their clinical application. Moreover, we tested the ability of AOL to bind to proteins, using serum albumin as a model protein. We demonstrated the oligolysine-protein binding by CD experiments which suggested that AOL, positively charged under physiological conditions, binds to the protein regions rich in anionic residues. Finally, the morphology characterization of the solid oligolysine, performed by scanning electron microscopy, showed different crystal forms including cubic-shaped crystals confirming the high purity of AOL.
[Mh] Termos MeSH primário: Ácidos Nucleicos/metabolismo
Peptídeos/química
Peptídeos/metabolismo
[Mh] Termos MeSH secundário: Dicroísmo Circular
DNA/química
DNA/metabolismo
Lisina
Ácidos Nucleicos/química
Poli I/química
Poli I/metabolismo
Poli I-C
Ligação Proteica
Desnaturação Proteica
RNA de Cadeia Dupla/química
RNA de Cadeia Dupla/metabolismo
Soroalbumina Bovina/química
Soroalbumina Bovina/metabolismo
Raios Ultravioleta
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Nucleic Acids); 0 (Peptides); 0 (RNA, Double-Stranded); 25249-22-3 (Poly I); 27432CM55Q (Serum Albumin, Bovine); 9007-49-2 (DNA); K3Z4F929H6 (Lysine); O84C90HH2L (Poly I-C)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170125
[St] Status:MEDLINE
[do] DOI:10.2147/IJN.S121247


  3 / 266 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:25343355
[Au] Autor:Ito M; Hayashi K; Adachi E; Minamisawa T; Homma S; Koido S; Shiba K
[Ad] Endereço:Department of Oncology, The Jikei University School of Medicine, Tokyo, Japan; Division of Protein Engineering, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
[Ti] Título:Combinatorial contextualization of peptidic epitopes for enhanced cellular immunity.
[So] Source:PLoS One;9(10):e110425, 2014.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Invocation of cellular immunity by epitopic peptides remains largely dependent on empirically developed protocols, such as interfusion of aluminum salts or emulsification using terpenoids and surfactants. To explore novel vaccine formulation, epitopic peptide motifs were co-programmed with structural motifs to produce artificial antigens using our "motif-programming" approach. As a proof of concept, we used an ovalbumin (OVA) system and prepared an artificial protein library by combinatorially polymerizing MHC class I and II sequences from OVA along with a sequence that tends to form secondary structures. The purified endotoxin-free proteins were then examined for their ability to activate OVA-specific T-cell hybridoma cells after being processed within dendritic cells. One clone, F37A (containing three MHC I and two MHC II OVA epitopes), possessed a greater ability to evoke cellular immunity than the native OVA or the other artificial antigens. The sensitivity profiles of drugs that interfered with the F37A uptake differed from those of the other artificial proteins and OVA, suggesting that alteration of the cross-presentation pathway is responsible for the enhanced immunogenicity. Moreover, F37A, but not an epitopic peptide, invoked cellular immunity when injected together with monophosphoryl lipid A (MPL), and retarded tumor growth in mice. Thus, an artificially synthesized protein antigen induced cellular immunity in vivo in the absence of incomplete Freund's adjuvant or aluminum salts. The method described here could be potentially used for developing vaccines for such intractable ailments as AIDS, malaria and cancer, ailments in which cellular immunity likely play a crucial role in prevention and treatment.
[Mh] Termos MeSH primário: Técnicas de Química Combinatória
Epitopos/imunologia
Imunidade Celular/imunologia
Peptídeos/imunologia
[Mh] Termos MeSH secundário: Adjuvantes Imunológicos/farmacologia
Sequência de Aminoácidos
Animais
Apresentação do Antígeno/efeitos dos fármacos
Apresentação do Antígeno/imunologia
Células Apresentadoras de Antígenos/imunologia
Proliferação Celular/efeitos dos fármacos
Células Clonais
Apresentação Cruzada/efeitos dos fármacos
Apresentação Cruzada/imunologia
Epitopos/química
Epitopos/efeitos dos fármacos
Imunidade Celular/efeitos dos fármacos
Ativação Linfocitária/efeitos dos fármacos
Ativação Linfocitária/imunologia
Camundongos
Dados de Sequência Molecular
Ovalbumina/imunologia
Peptídeos/química
Poli I/farmacologia
Polissacarídeos/farmacologia
Complexo de Endopeptidases do Proteassoma/metabolismo
Sequências Repetitivas de Aminoácidos
Receptores Depuradores Classe A/metabolismo
Linfócitos T Citotóxicos/efeitos dos fármacos
Linfócitos T Citotóxicos/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Adjuvants, Immunologic); 0 (Epitopes); 0 (Peptides); 0 (Polysaccharides); 0 (Scavenger Receptors, Class A); 25249-22-3 (Poly I); 9006-59-1 (Ovalbumin); 9072-19-9 (fucoidan); EC 3.4.25.1 (Proteasome Endopeptidase Complex)
[Em] Mês de entrada:1506
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:141025
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0110425


  4 / 266 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:25280235
[Au] Autor:Sorokin VA; Valeev VA; Usenko EL; Andrushchenko VV
[Ad] Endereço:B.I. Verkin Institute for Low Temperature Physics and Engineering, National Academy of Sciences of Ukraine , 47 Lenin Avenue, Kharkov, 61103, Ukraine.
[Ti] Título:Metallization of single-stranded polyI by Zn(2+) ions in neutral solutions.
[So] Source:J Phys Chem B;118(43):12360-5, 2014 Oct 30.
[Is] ISSN:1520-5207
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Metallization of single-stranded polyinosinic acid (polyI) by Zn(2+) ions at pH 7.0 was studied by differential UV spectroscopy at different temperatures. It was found that polyI is metallized at N7 and N1 atoms of hypoxanthine. The concentration dependence of the degree of binding of Zn(2+) ions to both N7 and N1 sites was obtained, and the corresponding binding constants were determined. Metallization of N1 occurs due to Zn(2+) substituting the imino protons and is effective not only at alkaline but also at neutral pH. This makes multistranded polyI-based systems more promising candidates for use in nanoelectronics than natural DNA sequences, metallization of which can be achieved only at alkaline pH.
[Mh] Termos MeSH primário: Poli I/química
Zinco/química
[Mh] Termos MeSH secundário: Concentração de Íons de Hidrogênio
Polimerização
Prótons
Soluções
Espectrofotometria Ultravioleta
Temperatura Ambiente
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Protons); 0 (Solutions); 25249-22-3 (Poly I); J41CSQ7QDS (Zinc)
[Em] Mês de entrada:1510
[Cu] Atualização por classe:141030
[Lr] Data última revisão:
141030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:141004
[St] Status:MEDLINE
[do] DOI:10.1021/jp5065903


  5 / 266 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:25057007
[Au] Autor:Epaulard O; Adam L; Poux C; Zurawski G; Salabert N; Rosenbaum P; Dereuddre-Bosquet N; Zurawski S; Flamar AL; Oh S; Romain G; Chapon C; Banchereau J; Lévy Y; Le Grand R; Martinon F
[Ad] Endereço:French Alternative Energies and Atomic Energy Commission, Division of Immuno-Virology, Institute for Emerging Diseases and Innovative Therapies, Infectious Diseases Models for Innovative Therapies Center, 92265 Fontenay-aux-Roses, France; Unité Mixte de Recherche E1, Université Paris-Sud, 91405 Orsa
[Ti] Título:Macrophage- and neutrophil-derived TNF-α instructs skin langerhans cells to prime antiviral immune responses.
[So] Source:J Immunol;193(5):2416-26, 2014 Sep 01.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Dendritic cells are major APCs that can efficiently prime immune responses. However, the roles of skin-resident Langerhans cells (LCs) in eliciting immune responses have not been fully understood. In this study, we demonstrate for the first time, to our knowledge, that LCs in cynomolgus macaque skin are capable of inducing antiviral-specific immune responses in vivo. Targeting HIV-Gag or influenza hemagglutinin Ags to skin LCs using recombinant fusion proteins of anti-Langerin Ab and Ags resulted in the induction of the viral Ag-specific responses. We further demonstrated that such Ag-specific immune responses elicited by skin LCs were greatly enhanced by TLR ligands, polyriboinosinic polyribocytidylic acid, and R848. These enhancements were not due to the direct actions of TLR ligands on LCs, but mainly dependent on TNF-α secreted from macrophages and neutrophils recruited to local tissues. Skin LC activation and migration out of the epidermis are associated with macrophage and neutrophil infiltration into the tissues. More importantly, blocking TNF-α abrogated the activation and migration of skin LCs. This study highlights that the cross-talk between innate immune cells in local tissues is an important component for the establishment of adaptive immunity. Understanding the importance of local immune networks will help us to design new and effective vaccines against microbial pathogens.
[Mh] Termos MeSH primário: HIV-1/imunologia
Glicoproteínas de Hemaglutininação de Vírus da Influenza/farmacologia
Vírus da Influenza A/imunologia
Células de Langerhans/imunologia
Pele/imunologia
Fator de Necrose Tumoral alfa/imunologia
Produtos do Gene gag do Vírus da Imunodeficiência Humana/farmacologia
[Mh] Termos MeSH secundário: Imunidade Adaptativa/efeitos dos fármacos
Imunidade Adaptativa/fisiologia
Animais
Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia
Imidazóis/farmacologia
Macaca mulatta
Macrófagos/imunologia
Neutrófilos/imunologia
Poli I/farmacologia
Produtos do Gene gag do Vírus da Imunodeficiência Humana/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Hemagglutinin Glycoproteins, Influenza Virus); 0 (Imidazoles); 0 (Tumor Necrosis Factor-alpha); 0 (gag Gene Products, Human Immunodeficiency Virus); 25249-22-3 (Poly I); V3DMU7PVXF (resiquimod)
[Em] Mês de entrada:1412
[Cu] Atualização por classe:161019
[Lr] Data última revisão:
161019
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:140725
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1303339


  6 / 266 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:24792476
[Au] Autor:Basu A; Jaisankar P; Suresh Kumar G
[Ad] Endereço:Chemistry Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700 032, India; Biophysical Chemistry Laboratory, CSIR-Indian Institute of Chemical Biology, Kolkata 700 032, India.
[Ti] Título:Interaction of 9-O-N-aryl/arylalkyl amino carbonyl methyl berberine analogs with single stranded ribonucleotides.
[So] Source:J Photochem Photobiol B;134:64-74, 2014 May 05.
[Is] ISSN:1873-2682
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Studies on the molecular aspects of alkaloid-RNA complexation are of prime importance for the development of rational RNA targeted drug design strategies. Towards this goal, the binding aspects of three novel 9-O-N-aryl/arylalkyl amino carbonyl methyl substituted berberine analogs to four single stranded ribonucleotides, poly(G), poly(I), poly(C) and poly(U), were studied for the first time employing multifaceted biophysical tools. Absorbance and fluorescence studies revealed that these analogs bound non-cooperatively to poly(G) and poly(I) with binding affinities remarkably higher than berberine. The binding of these analogs to poly(U) and poly(C) was weaker in comparison to poly(G) and poly(I) but were one order higher in comparison to berberine. Quantum efficiency values revealed that energy transfer occurred from the RNA bases to the analogs upon complexation. The binding was dominated by large positive entropic contributions and small but favorable enthalpic contributions. Salt dependent studies established that the binding was dominated by hydrophobic forces that contributed around 90% of the total standard molar Gibbs energy. The chain length of the substitution at the 9-position was found to be critical in modulating the binding affinities. These results provide new insights into the binding efficacy of these novel berberine analogs to single stranded RNA sequences.
[Mh] Termos MeSH primário: Berberina/análogos & derivados
Ribonucleotídeos/química
[Mh] Termos MeSH secundário: Berberina/metabolismo
Sítios de Ligação
Calorimetria
Dicroísmo Circular
Conformação de Ácido Nucleico
Concentração Osmolar
Poli C/química
Poli C/metabolismo
Poli G/química
Poli G/metabolismo
Poli I/química
Poli I/metabolismo
Poli U/química
Poli U/metabolismo
Teoria Quântica
RNA/química
RNA/metabolismo
Ribonucleotídeos/metabolismo
Espectrometria de Fluorescência
Temperatura Ambiente
Termodinâmica
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Ribonucleotides); 0I8Y3P32UF (Berberine); 25191-14-4 (Poly G); 25249-22-3 (Poly I); 27416-86-0 (Poly U); 30811-80-4 (Poly C); 63231-63-0 (RNA)
[Em] Mês de entrada:1501
[Cu] Atualização por classe:140520
[Lr] Data última revisão:
140520
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140506
[St] Status:MEDLINE


  7 / 266 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:24528536
[Au] Autor:Wynant N; Santos D; Van Wielendaele P; Vanden Broeck J
[Ad] Endereço:Molecular Developmental Physiology and Signal Transduction, Department of Animal Physiology and Neurobiology, KU Leuven, Leuven, Belgium.
[Ti] Título:Scavenger receptor-mediated endocytosis facilitates RNA interference in the desert locust, Schistocerca gregaria.
[So] Source:Insect Mol Biol;23(3):320-9, 2014 Jun.
[Is] ISSN:1365-2583
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:RNA interference (RNAi) has become a widely used loss-of-function tool in eukaryotes; however, the delivery of double-stranded (ds)RNA) to the target cells remains a major challenge when exploiting the RNAi-technology. In insects, the efficiency of RNAi is highly species-dependent. Yet, the mechanism of cell entry in insects has only been characterized in a cell line of the fruit fly, Drosophila melanogaster, a species that is well known to be poorly amenable to environmental RNAi. In the present paper, we demonstrate that silencing vacuolar H-ATPase 16 (vha16) and clathrin heavy chain (clath), two components of the Clathrin-dependent endocytosis pathway, together with pharmacological inhibition of scavenger receptors with polyinosine and dextran sulphate, can significantly attenuate the highly robust RNAi response in the desert locust, Schistocerca gregaria.
[Mh] Termos MeSH primário: Gafanhotos/genética
Interferência de RNA/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Clatrina
Sulfato de Dextrana
Endocitose
Poli I
RNA de Cadeia Dupla/metabolismo
Receptores Depuradores
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Clathrin); 0 (RNA, Double-Stranded); 0 (Receptors, Scavenger); 25249-22-3 (Poly I); 9042-14-2 (Dextran Sulfate)
[Em] Mês de entrada:1412
[Cu] Atualização por classe:140505
[Lr] Data última revisão:
140505
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140218
[St] Status:MEDLINE
[do] DOI:10.1111/imb.12083


  8 / 266 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:24010701
[Au] Autor:van Dijk R; Montenegro-Miranda PS; Riviere C; Schilderink R; ten Bloemendaal L; van Gorp J; Duijst S; de Waart DR; Beuers U; Haisma HJ; Bosma PJ
[Ad] Endereço:Department of Gastroenterology & Hepatology and Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, University of Amsterdam, 1105 BK Amsterdam, The Netherlands. r.vandijk@amc.uva.nl
[Ti] Título:Polyinosinic acid blocks adeno-associated virus macrophage endocytosis in vitro and enhances adeno-associated virus liver-directed gene therapy in vivo.
[So] Source:Hum Gene Ther;24(9):807-13, 2013 Sep.
[Is] ISSN:1557-7422
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Adeno-associated virus serotype 8 (AAV8) has been demonstrated to be effective for liver-directed gene therapy in humans. Although hepatocytes are the main target cell for AAV8, there is a loss of the viral vector because of uptake by macrophages and Kupffer cells. Reducing this loss would increase the efficacy of viral gene therapy and allow a dose reduction. The receptor mediating this uptake has not been identified; a potential candidate seems the macrophage scavenger receptor A (SR-A) that is involved in the endocytosis of, for instance, adenovirus. In this study we show that SR-A can mediate scAAV8 endocytosis and that blocking it with polyinosinic acid (poly[i]) reduces endocytosis significantly in vitro. Subsequently, we demonstrate that blocking this receptor improves scAAV-mediated liver-directed gene therapy in a model for inherited hyperbilirubinemia, the uridine diphospho-glucuronyl transferase 1A1-deficient Gunn rat. In male rats, preadministration of poly[i] increases the efficacy of a low dose (1×10¹¹ gc/kg) but not of a higher dose (3×10¹¹ gc/kg) scAAV8-LP1-UT1A1. Administration of poly[i] just before the vector significantly increases the correction of serum bilirubin in female rats. In these, the effect of poly[i] is seen by both doses but is more pronounced in the females receiving the low vector, where it also results in a significant increase of bilirubin glucuronides in bile. In conclusion, this study shows that SR-A mediates the endocytosis of AAV8 in vitro and in vivo and that blocking this receptor can improve the efficacy of AAV-mediated liver-directed gene therapy.
[Mh] Termos MeSH primário: Dependovirus/imunologia
Endocitose/efeitos dos fármacos
Macrófagos do Fígado/imunologia
Poli I/metabolismo
Receptores Depuradores Classe A/antagonistas & inibidores
[Mh] Termos MeSH secundário: Animais
Bilirrubina/sangue
Células CHO
Linhagem Celular
Cricetulus
Síndrome de Crigler-Najjar/genética
Síndrome de Crigler-Najjar/terapia
Modelos Animais de Doenças
Feminino
Terapia Genética/métodos
Vetores Genéticos
Glucuronosiltransferase/genética
Células HEK293
Hepatócitos/virologia
Seres Humanos
Macrófagos do Fígado/efeitos dos fármacos
Fígado/imunologia
Fígado/metabolismo
Masculino
Ratos
Receptores Depuradores Classe A/efeitos dos fármacos
Receptores Depuradores Classe A/metabolismo
Transdução Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Scavenger Receptors, Class A); 25249-22-3 (Poly I); EC 2.4.1.17 (Glucuronosyltransferase); RFM9X3LJ49 (Bilirubin)
[Em] Mês de entrada:1403
[Cu] Atualização por classe:130909
[Lr] Data última revisão:
130909
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130910
[St] Status:MEDLINE
[do] DOI:10.1089/hum.2013.086


  9 / 266 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:23695243
[Au] Autor:Mitkevich VA; Schulga AA; Trofimov AA; Dorovatovskii PV; Goncharuk DA; Tkach EN; Makarov AA; Polyakov KM
[Ad] Endereço:Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, ul. Vavilova 32, Moscow 119991, Russian Federation.
[Ti] Título:Structure and functional studies of the ribonuclease binase Glu43Ala/Phe81Ala mutant.
[So] Source:Acta Crystallogr D Biol Crystallogr;69(Pt 6):991-6, 2013 Jun.
[Is] ISSN:1399-0047
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Ribonuclease from Bacillus intermedius (binase) is a small basic protein with antitumour activity. The three-dimensional structure of the binase mutant form Glu43Ala/Phe81Ala was determined at 1.98 Å resolution and its functional properties, such as the kinetic parameters characterizing the hydrolysis of polyinosinic acid and cytotoxicity towards Kasumi-1 cells, were investigated. In all crystal structures of binase studied previously the characteristic dimer is present, with the active site of one subunit being blocked owing to interactions within the dimer. In contrast to this, the new mutant form is not dimeric in the crystal. The catalytic efficiency of the mutant form is increased 1.7-fold and its cytotoxic properties are enhanced compared with the wild-type enzyme.
[Mh] Termos MeSH primário: Endorribonucleases/química
Endorribonucleases/genética
Proteínas Mutantes/química
Proteínas Mutantes/genética
Poli I/metabolismo
[Mh] Termos MeSH secundário: Bacillus/química
Bacillus/enzimologia
Bacillus/genética
Catálise
Linhagem Celular Tumoral
Sobrevivência Celular/efeitos dos fármacos
Endorribonucleases/metabolismo
Seres Humanos
Cinética
Modelos Moleculares
Mutagênese
Proteínas Mutantes/metabolismo
Difração de Raios X
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Mutant Proteins); 25249-22-3 (Poly I); EC 3.1.- (Endoribonucleases); EC 3.1.27.1 (ribonuclease T(2))
[Em] Mês de entrada:1310
[Cu] Atualização por classe:130522
[Lr] Data última revisão:
130522
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130523
[St] Status:MEDLINE
[do] DOI:10.1107/S0907444913004046


  10 / 266 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:23187479
[Au] Autor:Chen YD; Fuh AY; Cheng KT
[Ad] Endereço:Department of Photonics, National Cheng Kung University, Tainan 701, Taiwan.
[Ti] Título:Optically and thermally controllable light scattering based on dye-doped liquid crystals in poly(N-vinylcarbazole) films-coated liquid crystal cell.
[So] Source:Opt Express;20(24):26252-60, 2012 Nov 19.
[Is] ISSN:1094-4087
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:This paper presents the optically controllable light scattering based on dye-doped liquid crystals (DDLCs) in a cell, whose substrates are coated with poly(N-vinylcarbazole) (PVK) films. The optical control mechanism is the light-induced dissolution of PVK in DDLCs, which reforms the disordered LC distribution into multiple and micron-sized LC domains. The induced thermal effect on the process is investigated in detail. Scanning electron microscopy images are obtained to show the surface structures of the produced PVK films. The generated scattering can be switched back to the original one by particular thermally induced phase separation. Results indicate that the light-induced thermal effect and photoisomerization lead to the dissolution of PVK in DDLCs. Finally, scattering mode light shutter with different transmission is successfully achieved by illuminating the cell under various light intensities.
[Mh] Termos MeSH primário: Corantes/química
Cristalização/métodos
Luz
Cristais Líquidos/química
Fotoquímica/métodos
Poli I
Espalhamento de Radiação
[Mh] Termos MeSH secundário: Corantes/efeitos da radiação
Desenho de Equipamento
Glicocálix
Temperatura Alta
Seres Humanos
Isomerismo
Lasers
Cristais Líquidos/efeitos da radiação
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Coloring Agents); 25249-22-3 (Poly I); 68777-95-7 (poly If)
[Em] Mês de entrada:1305
[Cu] Atualização por classe:121128
[Lr] Data última revisão:
121128
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:121129
[St] Status:MEDLINE
[do] DOI:10.1364/OE.20.026252



página 1 de 27 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde