RESUMEN
Osteoporosis is the most widespread metabolic bone disease characterized by decreased bone mass and bone quality, and its diagnosis and treatment remains challenging. To date, medicinal plants have received increasing attention from researchers for researching effective and less toxic therapeutic ingredients, including polysaccharide, to treat osteoporosis. The present study aims to evaluate the osteoprotective effects of a polysaccharide (EBP) from Epimedium brevicornum in glucocorticoid-induced osteoporosis in vitro and investigate the underlying mechanism. EBP (25 and 100 µg/ml) pretreatment could significantly prevent decreased cell proliferation of osteoblasts (OBs) treated only with 100 µM of dexamethasone (Dex) via induction of apoptosis. The osteoblastic differentiation of EBP pretreatment on OBs at early and later phase was further confirmed by the increased alkaline phosphatase (ALP) activity and calcium content, respectively. Meanwhile, the increased expression of cleaved caspase-3 and Bax, as well as a decrease of Bcl-2 and the phosphorylation of PI3K, Akt and mTOR protein in Dex-treated OBs were totally reversed by EBP pretreatment. Moreover, the protein expression of Lrp-5, ß-catenin, Runx2 and Osx were significantly up-regulated in the presence of EBP pretreatment. In conclusion, these results demonstrated that EBP pretreatment may be a potential therapeutic agent for patients with glucocorticoid-induced osteoporosis (GIO).
Asunto(s)
Fraccionamiento Químico , Epimedium/química , Osteogénesis/efectos de los fármacos , Polisacáridos/aislamiento & purificación , Polisacáridos/farmacología , Apoptosis/efectos de los fármacos , Biomarcadores , Calcio/metabolismo , Diferenciación Celular/efectos de los fármacos , Proliferación Celular , Fraccionamiento Químico/métodos , Humanos , Estructura Molecular , Peso Molecular , Osteoporosis/tratamiento farmacológico , Fosfatidilinositol 3-Quinasas/metabolismo , Polisacáridos/química , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
Considering the poor medical conditions in some regions of China, this paper attempts to develop a simple and easy way to extract and process the bone features of blurry medical images and improve the diagnosis accuracy of osteoporosis as much as possible. After reviewing the previous studies on osteoporosis, especially those focusing on texture analysis, a convexity optimization model was proposed based on intra-class dispersion, which combines texture features and shape features. Experimental results show that the proposed model boasts a larger application scope than Lasso, a popular feature selection method that only supports generalized linear models. The research findings ensure the accuracy of osteoporosis diagnosis and enjoy good potentials for clinical application.
Asunto(s)
Interpretación de Imagen Asistida por Computador , Lentes , Microscopía , Osteoporosis/diagnóstico , Osteoporosis/patología , Algoritmos , Animales , Modelos Animales de Enfermedad , Femenino , Interpretación de Imagen Asistida por Computador/métodos , Microscopía/instrumentación , Microscopía/métodos , Distribución Aleatoria , Ratas Sprague-Dawley , Sensibilidad y Especificidad , Tibia/patología , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Hypoxia is a well-known factor in the promotion of apoptosis, which contributes to the development of numerous cardiac diseases, such as heart failure and myocardial infarction. Inhibiting apoptosis is an important therapeutic strategy for the treatment of related heart diseases caused by ischemia/hypoxic injury. Previous studies have demonstrated that BAG3 plays an important role in cardiomyocyte apoptosis and survival. However, the role of BAG3 in hypoxia-induced cardiomyocyte apoptosis remains to be clarified. Here, we demonstrate that BAG3 is induced by hypoxia stimuli in cultured cardiomyocytes. METHODS: BAG3 expression level was measured in H9c2 cells treated with hypoxia for 48 h. Cell proliferation and apoptosis were tested using MTT assay and Annexin V FITC-PI staining assay, respectively. The mRNA or protein expression level of BAG3, LC3-I, LC3-II, Atg5, NF-x03BA;B p65 and phosphorylated NF-x03BA;B p65 were assessed by qRT-PCR and western blot assay, respectively. Resluts: Overexpression of BAG3 inhibited cell apoptosis and promoted proliferation in hypoxia-injured H9c2 cells. Furthermore, autophagy and NF-x03BA;B were activated by BAG3 overexpression, and the NF-x03BA;B inhibitor PDTC could inhibit the activation of autophagy induced by BAG3 overexpression. In addition, the autophagy inhibitor 3-MA partly impeded the inhibitory effect of BAG3 on hypoxia-induced cardiomyocyte apoptosis. CONCLUSION: these results suggested that overexpression of BAG3 promoted cell proliferation and inhibited apoptosis by activating autophagy though the NF-x03BA;B signaling pathway in hypoxia-injured cardiomyocytes.