RESUMO
Nobiletin has protective effects on cardiovascular diseases, but the mechanism is not clear. In this study, we examined whether nobiletin affects the expression of miR-590/LPL and its relative effects on lipid accumulation and pro-inflammatory cytokine secretion in human THP-1 macrophages. RT-qPCR analysis showed that nobiletin increased the expression of miR-590. Western blot analysis showed that nobiletin-suppressed LPL expression was enhanced by miR-590 mimic and abrogated by miR-590 inhibitor. Oil Red O staining and high-performance liquid chromatography assays showed that nobiletin attenuated lipid accumulation in macrophages. Treatment with nobiletin and miR-590 mimic decreased cellular lipid accumulation, whereas treatment with miR-590 inhibitor increased cellular lipid accumulation. ELISA illustrated that nobiletin alleviated pro-inflammatory cytokine secretion in macrophages as measured by, which was reduced by miR-590 mimic and increased by miR-590 inhibitor. In conclusion, nobiletin may alleviate lipid accumulation and secretion of pro-inï¬ammatory cytokines by enhancing the inhibitory effect of miR-590 on LPL expression, suggesting a promising strategy for potential drug development for atherosclerosis.
Assuntos
Flavonas/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipase Lipoproteica/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Aterosclerose/tratamento farmacológico , Aterosclerose/genética , Aterosclerose/metabolismo , Cardiotônicos/farmacologia , Citocinas/metabolismo , Regulação para Baixo/efeitos dos fármacos , Desenvolvimento de Medicamentos , Humanos , Mediadores da Inflamação/metabolismo , Lipase Lipoproteica/antagonistas & inibidores , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Células THP-1 , Regulação para Cima/efeitos dos fármacosRESUMO
SRM (selected reaction monitoring), a tandem mass spectrometry-based method characterized by high repeatability and accuracy, is an effective tool for the quantification of predetermined proteins. In this study, we built a time-scheduled dimethyl-SRM method that can provide the precise relative quantification of 92 proteins in one run. By applying this method to the Salmonella PhoP/PhoQ two-component system, we found that the expression of selected PhoP/PhoQ-activated proteins in response to Mg(2+) concentrations could be divided into two distinct patterns. For the time-course SRM experiment, we found that the dynamics of the selected PhoP/PhoQ-activated proteins could be divided into three distinct patterns, providing a new clue regarding PhoP/PhoQ activation and regulation. Moreover, the results for iron homeostasis proteins in response to Mg(2+) concentrations revealed that the PhoP/PhoQ two-component system may serve as a repressor for iron uptake proteins. And ribosomal protein levels clearly showed a response to different Mg(2+) concentrations and to time.
Assuntos
Proteínas de Bactérias/metabolismo , Biologia Computacional/métodos , Proteômica/métodos , Salmonella/metabolismo , Espectrometria de Massas em Tandem/métodos , Western Blotting , Relação Dose-Resposta a Droga , Magnésio/farmacologia , Peptídeos/metabolismo , Mapas de Interação de Proteínas/efeitos dos fármacos , Proteoma/metabolismo , Fatores de TempoRESUMO
Combining classical Kalman filter with NIR analysis technology, a new method of characteristic wavelength variable selection, namely Kalman filtering method, is presented. The principle of Kalman filter for selecting optimal wavelength variable was analyzed. The wavelength selection algorithm was designed and applied to NIR detection of soybean oil acid value. First, the PLS (partial leastsquares) models were established by using different absorption bands of oil. The 4 472-5 000 cm(-1) characteristic band of oil acid value, including 132 wavelengths, was selected preliminarily. Then the Kalman filter was used to select characteristic wavelengths further. The PLS calibration model was established using selected 22 characteristic wavelength variables, the determination coefficient R2 of prediction set and RMSEP (root mean squared error of prediction) are 0.970 8 and 0.125 4 respectively, equivalent to that of 132 wavelengths, however, the number of wavelength variables was reduced to 16.67%. This algorithm is deterministic iteration, without complex parameters setting and randomicity of variable selection, and its physical significance was well defined. The modeling using a few selected characteristic wavelength variables which affected modeling effect heavily, instead of total spectrum, can make the complexity of model decreased, meanwhile the robustness of model improved. The research offered important reference for developing special oil near infrared spectroscopy analysis instruments on next step.
RESUMO
Atopic dermatitis (AD) is among the most common skin disorders in humans. Although a variety of regimens are available for the treatment of AD, preventive approaches are limited. Recent studies have demonstrated that certain naturally-occurring herbal medicines are effective in preventing the development of AD via divergent mechanisms, such as inhibiting cytokine and chemokine expression, IgE production, inflammatory cell infiltration, histamine release, and/or enhancement of epidermal permeability barrier function. Yet, they exhibit few adverse effects. Since herbal medicines are widely available, inexpensive and generally safe, they could represent an ideal approach for preventing the development of AD, in both highly developed and developing countries.
Assuntos
Dermatite Atópica/prevenção & controle , Medicina Herbária , Animais , Quimiocinas/metabolismo , Modelos Animais de Doenças , Humanos , Imunoglobulina E/metabolismo , Inflamação/patologiaRESUMO
Although a variety of regimens are available for the treatment of atopic dermatitis (AD), severe adverse reactions and unpopular costs often limit their usage. In contrast, certain inexpensive, naturally-occurring ingredients are proven effective for AD with fewer side effects. The beneficial effects of these ingredients can be attributed to inhibition of cytokine and chemokine expression, IgE production, inflammatory cell infiltration, histamine release, and/or the enhancement of epidermal permeability barrier function. Since herbal medicines are widely available, inexpensive and generally safe, they could be valuable alternatives for the treatment of AD, particularly for those patients who are not suitable for the utilization of immune modulators. In this review, we summarize the therapeutic benefits of natural ingredients for the treatment of AD and the mechanisms of their actions.