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Int Immunopharmacol ; 55: 174-182, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29268189


In rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLSs) play an essential role in cartilage destruction. Aggressive migration and invasion by FLSs significantly affect RA pathology. Kaempferol has been shown to inhibit cancer cell migration and invasion. However, the effects of kaempferol on RA FLSs have not been investigated. Our study aimed to determine the effects of kaempferol on RA both in vitro and in vivo. In vitro, cell migration and invasion were measured using scratch assays and the Boyden chamber method, respectively. The cytoskeletal reorganization of RA FLSs was evaluated by immunofluorescence staining. Matrix metalloproteinase (MMP) levels were measured by real-time PCR, and protein expression levels were measured by western blotting. In vivo, the effects of kaempferol were evaluated in mice with CIA. The results showed that kaempferol reduced migration, invasion and MMP expression in RA FLSs. In addition, we demonstrated that kaempferol inhibited reorganization of the actin cytoskeleton during cell migration. Moreover, kaempferol dramatically suppressed tumor necrosis factor (TNF)-α-induced MAPK activation without affecting the expression of TNF-α receptors. We also demonstrated that kaempferol attenuated the severity of arthritis in mice with CIA. Taken together, these results suggested that kaempferol inhibits the migration and invasion of FLSs in RA by blocking MAPK pathway activation without affecting the expression of TNF-α receptors.

Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Fibroblastos/fisiologia , Quempferóis/uso terapêutico , Sinoviócitos/fisiologia , Actinas/metabolismo , Adulto , Idoso , Animais , Artrite Experimental , Movimento Celular , Células Cultivadas , Citoesqueleto/metabolismo , Feminino , Humanos , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos , Camundongos Endogâmicos DBA , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/metabolismo
Rheumatology (Oxford) ; 56(8): 1417-1427, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28431044


Objective: To explore the role of leonurine in the regulation of synovial inflammation and joint destruction inRA. Methods: Fibroblast-like synoviocytes were isolated from synovial tissue from RA patients. Pro-inflammatory cytokine and MMP expression was evaluated using real-time PCR and a cytometric bead array. Cell migration and invasion in vitro were measured using the Boyden chamber method and the scratch assay, respectively. Protein expression was measured by western blotting. Nuclear factor kappa B (NF-κB) nuclear translocation was detected by immunofluorescence. The in vivo effect of leonurine was evaluated in mice with CIA. Results: Leonurine treatment significantly decreased the production of pro-inflammatory cytokines (IL-1ß, IL-6, IL-8 and TNFα) and MMPs (MMP-1 and MMP-3) and suppressed the migration and invasion of RA fibroblast-like synoviocytes. The molecular analysis revealed that leonurine impaired TNFα-induced NF-κB signalling by inhibiting the phosphorylation and degradation of inhibitor of NF-κB alpha (IκBα) and subsequently preventing the nuclear translocation of the NF-κB p65 subunit. Leonurine also inhibited the p38 and Jun N-terminal kinase mitogen-activated protein kinases signalling pathways without affecting ERK signalling. Intraperitoneal injection of leonurine reduced synovial inflammation, joint destruction and the serum IL-1ß, IL-6 and TNFα levels in mice with CIA. Conclusion: Our findings show that leonurine reduces synovial inflammation and joint destruction in RA through the NF-κB and mitogen-activated protein kinases pathways. Leonurine has potential as a therapeutic agent for RA.

Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Ácido Gálico/análogos & derivados , Adulto , Animais , Artrite Experimental/induzido quimicamente , Artrite Experimental/metabolismo , Artrite Reumatoide/metabolismo , Citocinas/efeitos dos fármacos , Feminino , Fibroblastos/metabolismo , Ácido Gálico/farmacocinética , Humanos , Mediadores da Inflamação/metabolismo , Masculino , Metaloproteinase 1 da Matriz/efeitos dos fármacos , Metaloproteinase 3 da Matriz/efeitos dos fármacos , Camundongos , Pessoa de Meia-Idade , Proteínas Quinases Ativadas por Mitógeno/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Membrana Sinovial/efeitos dos fármacos , Sinoviócitos/efeitos dos fármacos , Sinoviócitos/patologia , Fator de Transcrição RelA/efeitos dos fármacos
Thromb Haemost ; 114(6): 1165-74, 2015 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-26422658


The intraluminal thrombus (ILT) of human abdominal aortic aneurysm (AAA) has been suggested to damage the underlying aortic wall, but previous work found scant activity of soluble proteases in the abluminal layer of the ILT, adjacent to the aneurysm. We hypothesised that transmembrane proteases carried by membrane microvesicles (MV) from dying cells remain active in the abluminal ILT. ILTs and AAA segments collected from 21 patients during surgical repair were assayed for two major transmembrane proteases, ADAM10 (a disintegrin and metalloprotease-10) and ADAM17. We also exposed cultured cells to tobacco smoke and assessed ADAM10 and ADAM17 expression and release on MVs. Immunohistochemistry showed abundant ADAM10 and ADAM17 protein in the ILT and underlying aneurysmal aorta. Domain-specific antibodies indicated both transmembrane and shed ADAM17. Importantly, ADAM10 and ADAM 17 in the abluminal ILT were enzymatically active. Electron microscopy of abluminal ILT and aortic wall showed MVs with ADAM10 and ADAM17. By flow cytometry, ADAM-positive microvesicles from abluminal ILT carried the neutrophil marker CD66, but not the platelet marker CD61. Cultured HL60 neutrophils exposed to tobacco smoke extract showed increased ADAM10 and ADAM17 content, cleavage of these molecules into active forms, and release of MVs carrying mature ADAM10 and detectable ADAM17. In conclusion, our results implicate persistent, enzymatically active ADAMs on MVs in the abluminal ILT, adjacent to the aneurysmal wall. The production of ADAM10- and ADAM17-positive MVs from smoke-exposed neutrophils provides a novel molecular mechanism for the vastly accelerated risk of AAA in smokers.

Proteínas ADAM/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Aneurisma da Aorta Abdominal/enzimologia , Arteriopatias Oclusivas/enzimologia , Micropartículas Derivadas de Células/enzimologia , Proteínas de Membrana/metabolismo , Fumaça/efeitos adversos , Trombose/enzimologia , Proteína ADAM10 , Proteína ADAM17 , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/análise , Aneurisma da Aorta Abdominal/epidemiologia , Aneurisma da Aorta Abdominal/etiologia , Ruptura Aórtica/enzimologia , Moléculas de Adesão Celular/análise , Indução Enzimática , Feminino , Células HL-60 , Humanos , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Neutrófilos/química , Neutrófilos/ultraestrutura , Processamento de Proteína Pós-Traducional , Risco , Fumar/efeitos adversos , Trombose/imunologia , Tabaco
Cyberpsychol Behav Soc Netw ; 16(8): 604-12, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23790359


The aim of this study was to integrate technology readiness into the expectation-confirmation model (ECM) for explaining individuals' continuance of mobile data service usage. After reviewing the ECM and technology readiness, an integrated model was demonstrated via empirical data. Compared with the original ECM, the findings of this study show that the integrated model may offer an ameliorated way to clarify what factors and how they influence the continuous intention toward mobile services. Finally, the major findings are summarized, and future research directions are suggested.

Telefone Celular/estatística & dados numéricos , Modelos Psicológicos , Adulto , Antecipação Psicológica , Atitude , Feminino , Humanos , Masculino , Tecnologia , Adulto Jovem
Inorg Chem ; 47(10): 4368-74, 2008 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-18433097


Single crystal and bulk powder samples of the quaternary lanthanum copper oxysulfides La5Cu6.33O4S7 and La5Cu6O4S7 have been prepared by means of high-temperature sealed-tube reactions and spark plasma sintering, respectively. In the structure of La 5Cu6.33O4S7, Cu atoms tie together the fluorite-like (2)infinity[La5O4S(5+)] and antifluorite-like (2) infinity[Cu6S6(5-)] layers of La5Cu6O4S7. The optical band gap, E g, of 2.0 eV was deduced from both diffuse reflectance spectra on a bulk sample of La5Cu6O4S7 and for the (010) crystal face of a La 5Cu6.33O4S7 single crystal. Transport measurements at 298 K on a bulk sample of La 5Cu 6O 4S 7 indicated p-type metallic electrical conduction with sigma electrical =2.18 S cm(-1), whereas measurements on a La 5Cu6.33O4S7 single crystal led to sigma electrical =4.5 10(-3) S cm(-1) along [100] and to semiconducting behavior. In going from La 5Cu6O4S7 to La5Cu6.33O4S7, the disruption of the (2)infinity[Cu6S6(5-)] layer and the decrease in the overall Cu(2+)(3d(9)) concentration lead to a significant decrease in the electrical conductivity.