RESUMO
Inhibition of overactivated inflammation has been demonstrated as one of the most efficient strategies for treating inflammatory diseases. In the present study, 6formyl umbelliferone (6FU) was used to evaluate its antiinflammatory effects on lipopolysaccharide (LPS)stimulated RAW 264.7 macrophages. 6FU inhibited chronic inflammatory processes, including increasing nitric oxide levels, and the expression of proinflammatory genes and producing cytokines was investigated by a nitrite assay and reverse transcriptionpolymerase chain reaction, respectively. Nitric oxide and proinflammatory cytokines, including tumor necrosis factorα, interleukin (IL)1ß and IL6 were decreased by treatment with 6FU, without cell cytotoxicity in LPSstimulated RAW 264.7 cells, which was measured by a WST1 assay. In the western blot analysis, the expression levels of phosphorylated extracellular signalregulated kinase (ERK)1/2 was downregulated in 6FUtreated cells. Furthermore, in the western blotting and immunofluorescence staining results, translocation activities of ERK1/2 and NFκB from the cytoplasm to the nucleus were suppressed, which may inhibit translation of numerous proteins associated with proinflammation, including inducible nitric oxide synthase and cyclooxygenase2. Therefore, based on these results, it was suggested that 6FU may be a potential candidate for the development of agents against chronic inflammation.
Assuntos
Anti-Inflamatórios/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , NF-kappa B/metabolismo , Umbeliferonas/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Citocinas/genética , Citocinas/metabolismo , Ativação Enzimática/efeitos dos fármacos , Lipopolissacarídeos , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/metabolismo , Fosforilação/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , Células RAW 264.7 , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Lovastatin is a 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor that is clinically used for the prevention of cardiovascular diseases. Although it has been reported that lovastatin has anti-inflammatory properties in several studies, how lovastatin regulates the inflammation is still unclear. To evaluate the effect of lovastatin on nitric oxide production (NO) in RAW264.7 macrophages, NO production assay was performed. Also, cell viability was measured to confirm cytotoxicity. Level of tumor necrosis factor-α (TNF-α) transcription was measured by reverse transcription polymerase chain reaction (RT-PCR) from total RNA in RAW264.7 cells. Western blot analysis and immunofluorescence staining were used to investigate the regulation of lovastatin on the expression, phosphorylation, and nuclear translocation of cellular proteins. The results of the present study revealed that lovastatin reduced nitric oxide production via the reduction of inducible nitric oxide synthase (iNOS) expression in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. The mRNA level of TNF-α was reduced in presence of lovastatin. In addition, lovastatin downregulated histone deacetylase 1 (HDAC1), resulting in the accumulation of acetylated histone H3 and heat shock protein 70. Furthermore, the expression of phosphoinositide 3-kinase catalytic subunits α and ß was reduced under lovastatin treatment, and the phosphorylation of Akt and mammalian target of rapamycin was consequently inhibited. Lovastatin also inhibited the phosphorylation of inhibitor of nuclear factor (NF)-κBα and the translocation of NF-κB into the nucleus. Therefore, the present study demonstrates that lovastatin inhibits the expression of pro-inflammatory mediators, including iNOS and TNF-α, through the suppression of HDAC1 expression, PI3K/Akt phosphorylation and NF-κB translocation in LPS-stimulated RAW264.7 macrophage cells.
Assuntos
Anti-Inflamatórios/administração & dosagem , Histona Desacetilase 1/genética , Inflamação/tratamento farmacológico , Lovastatina/administração & dosagem , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Histona Desacetilase 1/antagonistas & inibidores , Humanos , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/patologia , Lipopolissacarídeos/toxicidade , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Camundongos , NF-kappa B/genética , Óxido Nítrico Sintase Tipo II/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Células RAW 264.7 , Serina-Treonina Quinases TOR/genética , Fator de Necrose Tumoral alfa/genéticaRESUMO
Crohn's disease (CD) can involve any part of the gastrointestinal tract from the mouth to anus. However, gastroduodenal CD is rare with a frequency reported to range between 0.5% and 4.0%. Most patients with gastroduodenal CD have concomitant lesions in the terminal ileum or colon, but isolated gastroduodenal Crohn's disease is an extremely rare presentation of the disease accounting for less than 0.07% of all patients with CD. The symptoms of gastroduodenal CD include epigastric pain, dyspepsia, early satiety, anorexia, nausea, vomiting, and weight loss. The diagnosis of gastroduodenal CD requires a high level of clinical suspicion and can be made by comprehensive clinical evaluation. Here we report a rare case of isolated duodenal CD not confirmed by identification of granuloma on biopsy, but diagnosed by clinical evaluation.
RESUMO
This study is the first report of the antitumor activities of desmethylanhydroicaritin (DMAI) isolated from Sophora flavescens on U87MG cells. Human glioblastoma is one of the most aggressive malignant type of brain tumors and highly diffuses to around normal brain tissues. DMAI showed anti-proliferation effects on U87MG cells at the concentration of 30µM, however did not affect to HEK-293 cells. DMAI induced anti-proliferation effects via ERK/MAPK, PI3K/Akt/mTOR signal pathway and G2/M phase cell cycle arrest. DMAI led to morphological change and inhibition of filapodia formation through regulation of Rac 1 and Cdc 42. In addition, migration and invasion of U87MG cells were inhibited by DMAI via down-regulation of matrix metalloproteinase (MMP) -2 and MMP -9 expressions and activities. Our results suggest that DMAI has a potential as a therapeutic agent against glioblastoma cells.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Flavonas/farmacologia , Sophora , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz , Invasividade Neoplásica , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TORRESUMO
In order to prepare anode material for low-temperature solid oxide fuel cells (SOFCs), the mesoporous NiO-SDC was synthesized using a cationic surfactant (cetyltrimethyl-ammonium bromide; CTAB) for obtaining wide triple-phase boundary (TPB). In addition, Ni-SDC anode-supported SOFC single cells with YSZ electrolyte and LSM cathode were fabricated and the performance of single cells was evaluated at 600 °C. The microstructure of NiO-SDC was characterized by XRD, EDX, SEM, and BET, and the results showed that the mesoporous NiO-SDC with 10 nm pores could be obtained. It was found that the surface area and the electrical performance were strongly influenced by the Ni content in Ni-SDC cermets. After calcined at 600 °C, the surface area of NiO-SDC was between 90-117 m2/g at 35-45 Ni wt%, which was sufficiently high for providing large TPB in SOFC anode. The optimum Ni content for cell performance was around 45 wt% and the corresponding MPD was 0.36 W/cm2. Indeed, the mesoporous NiO-SDC cermet may be of interest for use as an anode for low-temperature SOFCs.