Assuntos
Receptores de Antígenos de Linfócitos T , Humanos , Idoso , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/genética , Linfócitos T/imunologia , Masculino , Feminino , Envelhecimento/imunologia , Envelhecimento/genética , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Análise da Expressão Gênica de Célula ÚnicaRESUMO
T cells play an important role in the onset and progression of systemic lupus erythematosus (SLE), and the biases in T cell receptor beta variable (TRBV) region families and complementarity determining region three (CDR3) composition in SLE patients and mouse models have been widely reported. However, the relationship between the composition and variation in the TCR ß-chain CDR3 repertoire and SLE has not been established. Here, we compared and analyzed the thymic and splenic TCR ß-chain CDR3 mRNA sequences by Roche 454 high-throughput sequencing from MRL/lpr mice at different ages. Our results indicate that diversity in the TCR CDR3 repertoire from the thymus and spleen from MRL/lpr mouse was significantly decreased with increased age (disease progression) and showed a bias in usage of common TRBV and TRBJ families. The N1 region insertions in the highly expressed CDR3s significantly increased with disease progression. This study provides a new perspective for studying SLE with progression of disease in clonal level of TCR, which may provide a basis for studying the mechanism of the MRL/lpr autoreactive T cells response and tailor an individualized treatment targeting these T cells.
Assuntos
Doenças Autoimunes/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Baço/imunologia , Timo/imunologia , Fatores Etários , Animais , Doenças Autoimunes/genética , Doenças Autoimunes/patologia , Regiões Determinantes de Complementaridade/genética , Regiões Determinantes de Complementaridade/imunologia , Humanos , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/patologia , Camundongos , Camundongos Endogâmicos MRL lpr , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Baço/patologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/patologia , Timo/patologiaRESUMO
Bioassay-directed fractionation of the stem bark extract of Erythrina variegata L. has resulted in the isolation of three new isoflavones: 5,4'-dihydroxy-8-(3,3-dimethylallyl)-2''-methoxyisopropylfurano[4,5:6,7]isoflavone (1), 5,7,4'-trihydroxy-6-(3,3-dimethylallyloxiranylmethyl)isoflavone (2), 5,4'-dihydroxy-8-(3,3-dimethylallyl)-2''-hydroxymethyl-2''-methylpyrano[5,6:6,7]isoflavone (3) and a new isoflavanone, 5,4'-dihydroxy-2'-methoxy-8-(3,3-dimethylallyl)-2'',2''-dimethylpyrano[5,6:6,7]isoflavanone (4) together with seven known compounds, euchrenone b10 (5), isoerysenegalensein E (6), wighteone (7), laburnetin (8), lupiwighteone (9), erythrodiol (10), and oleanolic acid (11). The structures were determined on the basis of spectroscopic analyses and chemical evidence. The effect of these compounds on the proliferation of rat osteogenic sarcoma (UMR106) is also reported.
Assuntos
Proliferação de Células/efeitos dos fármacos , Erythrina/química , Isoflavonas/farmacologia , Casca de Planta/química , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Isoflavonas/química , Isoflavonas/isolamento & purificação , Estrutura Molecular , Osteossarcoma/patologia , Plantas Medicinais , Ratos , Células Tumorais CultivadasRESUMO
A new ellagic acid derivative (1) was isolated from the branches of Combretum yunnanensis, and its structure was assigned as 4-(4' '-O-acetyl-alpha-rhamnopyranosyl)ellagic acid by analysis of its spectral data. Total synthesis of 1 was achieved by the glycosylation of 3,3'-di-O-benzylellagic acid (5) with 4-O-acetyl-2,3-di-O-benzyl-l-rhamnose (4) as a key reaction, and the absolute configuration of 1 was determined. Compound 1 showed weak inhibitory activity against the growth of various tumor cells and inhibited HIV-1 protease.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Combretum/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Ácido Elágico/isolamento & purificação , Inibidores da Protease de HIV/isolamento & purificação , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Doxorrubicina/farmacologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Ácido Elágico/análogos & derivados , Ácido Elágico/química , Ácido Elágico/farmacologia , Inibidores da Protease de HIV/química , Inibidores da Protease de HIV/farmacologia , Concentração Inibidora 50 , Leucemia P388 , Camundongos , Estrutura Molecular , Ressonância Magnética Nuclear BiomolecularRESUMO
Two novel triterpenoid saponins with insulin-like activity, termed assamicin I and II, were isolated from the roots of Aesculus assamica Griff. and their structures were characterized as 1 and 2, respectively. They inhibited release of free fatty acids from epinephrine-treated rat adipocytes and enhanced glucose uptake into 3T3-L1 adipocytes.