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1.
In Vitro Cell Dev Biol Anim ; 59(6): 420-430, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37460875

RESUMO

Brevilin A (BA) is the primary component of Centipeda minima, which is widely used in Chinese traditional medicine. The anti-inflammatory and anti-tumor properties of BA have been established; however, its function in bone metabolism is not well understood. This study revealed that concentrations of BA below 1.0 µM did not inhibit the proliferation of bone marrow macrophages but did impede the differentiation and bone resorption activity of osteoclasts. Furthermore, BA suppressed the expression of osteoclast-specific genes Mmp9, Acp5, Dc-stamp, Ctsk, and Atp6v0d2. In addition, mTOR, ERK, and NFATc1 activation in bone marrow macrophages were suppressed by BA. As a whole, BA blocks the mTOR and ERK signaling pathways, which is responsible for the development and activity of osteoclasts, and the resorption of bone.


Assuntos
Reabsorção Óssea , Osteoclastos , Animais , Osteoclastos/metabolismo , Reabsorção Óssea/genética , Reabsorção Óssea/patologia , Serina-Treonina Quinases TOR/metabolismo , Ligante RANK/farmacologia , Ligante RANK/metabolismo , Fatores de Transcrição NFATC/genética , Fatores de Transcrição NFATC/metabolismo , Diferenciação Celular/genética , Osteogênese/genética
2.
J Cell Physiol ; 235(9): 5951-5961, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32026468

RESUMO

Osteoporosis is a devastating disease that features reduced bone quantity and microstructure, which causes fragility fracture and increases mortality, especially in the aged population. Due to the long-term side-effects of current drugs for osteoporosis, it is of importance to find other safe and effective medications. Ellagic acid (EA) is a phenolic compound found in nut galls, plant extracts, and fruits, and exhibits antioxidant and antineoplastic effects. Here, we showed that EA attenuated the formation and function of osteoclast dose-dependently. The underlying mechanism was further discovered by western blot, immunofluorescence assay, and luciferase assay, which elucidated that EA suppressed osteoclastogenesis and bone resorption mainly through attenuating receptor activator of nuclear factor-κB (NF-κB) ligand-induced NF-κB activation and extracellular signal-regulated kinase signaling pathways, accompanied by decreased protein expression of nuclear factor of activated T-cells calcineurin-dependent 1 and c-Fos. Moreover, EA inhibits osteoclast marker genes expression including Dc-stamp, Ctsk, Atp6v0d2, and Acp5. Intriguingly, we also found that EA treatment could significantly protect ovariectomy-induced bone loss in vivo. Conclusively, this study suggested that EA might have the therapeutic potentiality for preventing or treating osteoporosis.


Assuntos
Doenças Ósseas Metabólicas/tratamento farmacológico , Reabsorção Óssea/tratamento farmacológico , Ácido Elágico/farmacologia , Osteoporose/tratamento farmacológico , Animais , Conservadores da Densidade Óssea/farmacologia , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/genética , Doenças Ósseas Metabólicas/patologia , Reabsorção Óssea/genética , Reabsorção Óssea/patologia , Diferenciação Celular/efeitos dos fármacos , Humanos , Camundongos , NF-kappa B , Osteoclastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Osteoporose/etiologia , Osteoporose/genética , Osteoporose/patologia , Ovariectomia/efeitos adversos , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos
3.
Tumour Biol ; 39(5): 1010428317701656, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28475013

RESUMO

Our study aims to evaluate the efficacy of transcatheter arterial chemoembolization in the treatment of patients with liver metastasis using integrated 18F-fluorodeoxyglucose positron emission tomography/computed tomography. A total of 97 liver metastasis patients treated by transcatheter arterial chemoembolization were enrolled in this study. The 18F-fluorodeoxyglucose positron emission tomography/computed tomography images of liver metastasis patients were collected before and after transcatheter arterial chemoembolization treatment. The efficacy of transcatheter arterial chemoembolization for the treatment of liver metastasis was evaluated according to the revised Response Evaluation Criteria in Solid Tumors guidelines. The receiver operating characteristic curve analysis was used to determine cut-off values of 18F-fluorodeoxyglucose positron emission tomography parameters (Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean) for predicting the efficacy of transcatheter arterial chemoembolization. Progression-free survival and the incidence of postoperative complications were compared. Correlation of Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean with blood supply and lipiodol deposition in the lesion was analyzed. Among three 18F-fluorodeoxyglucose positron emission tomography parameters, the receiver operating characteristic analysis showed that Tsuvmax/Lsuvmax with a cut-off value of 3.56 was the best predictor of transcatheter arterial chemoembolization efficacy. According to the cut-off value of Tsuvmax/Lsuvmax, liver metastasis patients were divided into the Tsuvmax/Lsuvmax ≤ 3.56 and Tsuvmax/Lsuvmax > 3.56 groups. Compared with the Tsuvmax/Lsuvmax > 3.56 group, the Tsuvmax/Lsuvmax ≤ 3.56 group showed a longer progression-free survival and a lower incidence of postoperative complications. The Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean in the lesion with abundant blood supply were significantly lower than those in peripheral liver parenchyma, while the Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean in the lesion with lack of blood supply were significantly higher than those in peripheral liver parenchyma. Spearman correlation analysis indicated that lipiodol deposition in the lesion was positively correlated with the Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean. The Tsuvmax/Lsuvmax of 18F-fluorodeoxyglucose positron emission tomography/computed tomography may be a good tool for predicting the blood supply and efficacy of transcatheter arterial chemoembolization for patients with liver metastasis.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Quimioembolização Terapêutica , Neoplasias Hepáticas/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/secundário , Intervalo Livre de Doença , Óleo Etiodado/administração & dosagem , Feminino , Fluordesoxiglucose F18/uso terapêutico , Humanos , Fígado/irrigação sanguínea , Fígado/diagnóstico por imagem , Fígado/patologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/patologia , Compostos Radiofarmacêuticos/uso terapêutico
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