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1.
Int J Mol Med ; 52(4)2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37654184

RESUMO

Acute pancreatitis (AP)­associated lung injury (ALI) is a critical complication of AP. Adropin is a regulatory protein of immune metabolism. The present study aimed to explore the immunomodulatory effects of adropin on AP­ALI. For this purpose, serum samples of patients with AP were collected and the expression levels of serum adropin were detected using ELISA. Animal models of AP and adropin knockout (Adro­KO) were constructed, and adropin expression in serum and lung tissues was investigated. The levels of fibrosis and apoptosis were evaluated using hematoxylin and eosin staining, Masson's staining and immunohistochemistry of in lung tissue. M1/M2 type macrophages in the lungs were detected using immunofluorescence staining, western blot analysis and reverse transcription­quantitative PCR. As shown by the results, adropin expression was decreased in AP. In the Adro­KO + L­arginine (L­Arg) group, macrophage infiltration, fibrosis and apoptosis were increased. The expression of peroxisome proliferator­ activated receptor γ (PPARγ) was downregulated, and the macrophages exhibited a trend towards M1 polarization in the Adro­KO + L­Arg group. Adropin exogenous supplement attenuated the levels of fibrosis and apoptosis in the model of AP. Adropin exogenous supplement also increased PPARγ expression by the regulation of the phosphorylation levels, which was associated with M2 macrophage polarization. On the whole, the findings of the present study suggest that adropin promotes the M2 polarization of lung macrophages and reduces the severity of AP­ALI by regulating the function of PPARγ through the regulation of its phosphorylation level.


Assuntos
Lesão Pulmonar , Macrófagos , Animais , Masculino , Camundongos , Lesão Pulmonar/metabolismo , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pancreatite/metabolismo , PPAR gama/metabolismo , Fosforilação
2.
Int J Mol Med ; 35(3): 747-54, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25543835

RESUMO

Indian hedgehog (Ihh), one of the hedgehog gene families, is indicated in the regulation of chondrocyte differentiation. Tougu Xiaotong formula (TXF), a traditional Chinese medicinal compound, has been used for the treatment of bone and joint disease. However, the underlying molecular mechanisms of TXF on the function of bone marrow stromal cells (BMSCs) remain unclear. In the present study, the affect of TXF on proliferation and chondrogenic differentiation was investigated in primary BMSCs from four­week­old Sprague Dawley rats. The cell viability in BMSCs treated with TXF was higher compared to the untreated cells. Additionally, the percentage of G(0)/G(1) phase cells was significantly decreased, whereas that of the S phase cells was significantly increased. Furthermore, following TXF treatment, cyclin D1, cyclin­dependent kinase 4 (CDK4) and CDK6 expression in BMSCs was significantly enhanced. The results showed that TXF had no cytotoxicity to BMSCs. To explore the effect of TXF on the differentiation in BMSCs, whether TXF induced chondrogenic differentiation of BMSCs by the regulation of Ihh signaling pathway was investigated. The protein expression of Ihh, Patched and Smoothened in the induction group were significantly increased when compared to those in the control group, and the highest protein level of Ihh was in the induction group that was treated with the combination of TXF and transforming growth factor­ß1 (TGF­ß1). In addition, TXF combined with TGF­ß1 significantly induced the protein expression of cartilage oligomeric matrix protein and collagen II compared to the TGF­ß1 group. Taken together, these results indicate that TXF promotes the proliferation via accelerating the G(1)/S transition, and induces chondrogenic differentiation in BMSCs by activation of the Ihh signaling pathway in association with TGF­ß1.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Condrogênese/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Animais , Ciclo Celular/efeitos dos fármacos , Proliferação de Células , Sobrevivência Celular/efeitos dos fármacos , Ciclina D1/genética , Ciclina D1/metabolismo , Quinase 4 Dependente de Ciclina/genética , Quinase 4 Dependente de Ciclina/metabolismo , Quinase 6 Dependente de Ciclina/genética , Quinase 6 Dependente de Ciclina/metabolismo , Medicamentos de Ervas Chinesas/química , Expressão Gênica , Masculino , Células-Tronco Mesenquimais/metabolismo , Ratos , Transdução de Sinais , Fator de Crescimento Transformador beta1/metabolismo
3.
Int J Mol Med ; 34(6): 1573-80, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25339266

RESUMO

Chondrocyte apoptosis activated by the mitochondrial-dependent signaling pathway plays a crucial role in the cartilage degeneration of osteoarthritis. Duhuo Jisheng decoction (DHJSD), a herbal formula from traditional Chinese medicine, has been widely used for treating osteoarthritis (OA). However, the molecular mechanisms behind the therapeutic effect of DHJSD remain to be elucidated. In the present study, the effects of DHJSD on the mitochondrial-dependent signaling pathway in sodium nitroprussiate (SNP)-induced chondrocyte apoptosis were investigated. Chondrocytes, from the knee articular cartilage of Sprague Dawley rats, were identified by type II collagen immunohistochemistry. The chondrocytes, stimulated with or without SNP to induce apoptosis, were treated by DHJSD for various concentrations and times. The viability of SNP-induced chondrocytes treated with DHJSD was enhanced compared to SNP-induced chondrocytes in a dose- and time-dependent manner, as assessed by the MTT assay. The apoptosis of SNP-induced chondrocytes treated by DHJSD was significantly decreased compared to SNP-induced chondrocyte, as shown by 4',6-diamidino-2-phenylindole and Annexin V/propidium iodide staining. The mitochondrial membrane potential (∆Ψm) of SNP-induced chondrocytes treated by DHJSD was significantly decreased compared to SNP-induced chondrocyte, as shown by JC-1 staining. To understand the mechanism, the mRNA and protein levels of Bax, B-cell lymphoma 2 (Bcl-2), caspase-9 and caspase-3 were detected by reverse transcription­polymerase chain reaction and western blot analysis, respectively. In SNP-induced chondrocyte treated by DHJSD, the Bcl-2 expression was increased, whereas the expression of Bax, caspase-9 and caspase-3 was decreased compared to SNP-induced chondrocyte. Taken together, these results indicated that DHJSD inhibits the apoptosis of SNP-induced chondrocyte by the mitochondrial-dependent apoptotic pathway, and this may partly explain its therapeutic efficacy for OA.


Assuntos
Apoptose/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Mitocôndrias/efeitos dos fármacos , Nitroprussiato/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Western Blotting , Cartilagem Articular/citologia , Caspase 3/genética , Caspase 3/metabolismo , Caspase 9/genética , Caspase 9/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Condrócitos/citologia , Condrócitos/metabolismo , Colágeno Tipo II/metabolismo , Relação Dose-Resposta a Droga , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/fisiologia , Doadores de Óxido Nítrico/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
4.
Int J Mol Med ; 32(6): 1329-36, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24129747

RESUMO

Bauhinia championi (Benth.) Benth. polysaccharides (BCBPs), extracted from Bauhinia championi (Benth.) Benth., which has been used in traditional Chinese medicine (TCM) for the treatment of osteoarthritis (OA), are the bioactive constituents of Bauhinia championi (Benth.) rattan. However, the molecular mechanisms responsible for their effects on OA are poorly understood. The Wnt/ß-catenin signaling pathway plays an important role in the proliferation of chondrocytes. In the present study, the effects of BCBPs on Wnt/ß-catenin signaling in chondrocytes were investigated. BCBPs were obtained by hot-water extraction and identified by the modified high performance liquid chromatography (HPLC) method. Chondrocytes were isolated from the knees of Sprague­Dawley rats and identified by type II collagen immunohistochemistry. The chondrocytes were treated with or without BCBPs for 48 h. Cell viability was evaluated by MTT assay. The mRNA and protein levels of Wnt-4, ß-catenin, Frizzled-2, glycogen synthase kinase (GSK)-3ß, cyclin D1 and collagen II were detected by western blot analysis and reverse transcription PCR (RT-PCR), respectively. We found that the BCBPs contained at least seven monosaccharides, including D-mannose, rhamnose, D-(+) glucuronic acid, D-(+) galacturonic acid, D-glucose, galactose and arabinose. The cell viability of the chondrocytes treated with 50, 100 and 200 µg/ml BCBPs was significantly higher than that of the chondroctyes in the control group (treated with 0 µg/ml BCBPs). Furthermore, compared with the control group, the mRNA and protein expression of Wnt-4, ß-catenin, Frizzled-2 and cyclin D1 in the BCBP-treated groups markedly increased, whereas the mRNA and protein expression of GSK-3ß significantly decreased. Of note, the dose of 100 µg/ml BCBPs was more effective than the dose of 50 µg/ml BCBPs and 200 µg/ml BCBPs. In addition, we found that treatment with BCBPs upregulated the protein levels of collagen II in the chondrocytes. These results indicate that BCBPs upregulate Wnt/ß-catenin signaling, thus promoting chondrocyte proliferation.


Assuntos
Bauhinia/química , Condrócitos/metabolismo , Polissacarídeos/farmacologia , Regulação para Cima/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Forma Celular/efeitos dos fármacos , Forma Celular/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Condrócitos/citologia , Condrócitos/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Regulação para Cima/genética , Via de Sinalização Wnt/genética
5.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 29(4): 645-9, 2012 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-23016408

RESUMO

EEG Synchronization is considered the conformity of the brain functional areas. Advanced brain function requires many nervous systems with a specific function in relevant brain regions (areas) to achieve integration and coordination at different levels. In this paper, a new method for phase synchronization analysis-Mutually Approximate Entropy is proposed to process different frequency band of EEG signal during audio-visual stimulation and get Similar results with the method of Synchronization Index and Mutual Information Entropy. This showed that the Mutually Approximate Entropy can lead to a good indication of the phase synchronization between two leads. The paper also explored the brain reaction zone by the results of the phase synchronization analysis. The research work lays the foundation for the brain-computer interface design.


Assuntos
Córtex Auditivo/fisiologia , Encéfalo/fisiologia , Sincronização de Fases em Eletroencefalografia/fisiologia , Processamento de Sinais Assistido por Computador , Córtex Visual/fisiologia , Estimulação Acústica , Entropia , Humanos , Estimulação Luminosa
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