RESUMO
Postmenopausal osteoporosis (PMOP) is a major health problem affecting millions of women worldwide. PMOP patients are often accompanied by abnormal accumulation of bone marrow adipose tissue (BMAT). BMAT is a critical regulator of bone homeostasis, and an increasing BMAT volume is negatively associated with bone mass reduction or fracture. BMAT regulates bone metabolism via adipokines, cytokines and the immune system, but the specific mechanisms are largely unknown. This review emphasizes the impact of estrogen deficiency on bone homeostasis and BMAT expansion, and the mechanism by which BMAT regulates PMOP, providing a promising strategy for targeting BMAT in preventing and treating PMOP.
Assuntos
Tecido Adiposo , Medula Óssea , Osteoporose Pós-Menopausa , Humanos , Tecido Adiposo/metabolismo , Feminino , Densidade Óssea , Adipocinas/metabolismo , Estrogênios/metabolismo , Osso e Ossos/metabolismo , Animais , Citocinas/metabolismo , HomeostaseRESUMO
Mitochondrial dysfunction is one of the triggers for obesity-induced neuron apoptosis. Thinned young apple is getting more attention on account of the extensive biological activities because of rich polyphenols and polysaccharides. However, the neuroprotective effect of thinned young apple powder (YAP) is still unclear. The aim of the present study was to investigate the preventive effect of YAP on obesity-induced neuronal apoptosis. C57BL/6J male mice were divided into 5 groups, control (CON), high fat diet (HFD), HFD + orlistat (ORL), HFD + low-dose young apple powder (LYAP) and HFD + high-dose young apple powder (HYAP) groups and intervened for 12 weeks. It was found that the YAP effectively reduced body weight gain. Importantly, the levels of pro-apoptosis protein were lower in LYAP and HYAP groups than the HFD group, such as Bak/Bcl2 and cleaved caspase3/caspase3. Pathway analysis based on untargeted metabolomics suggested that YAP alleviated obesity-induced neuronal apoptosis by three main metabolic pathway including arginine metabolism, citrate cycle (TCA cycle) and glutathione metabolism. Meanwhile, YAP improved the protein expression of mitochondrial respiratory chain complex, maintained the homeostasis of TCA cycle intermediates, protected the balance of mitochondrial dynamics and alleviated lipid accumulation. In addition, the levels of several antioxidants in cerebral cortex were higher in HYAP group than the HFD group like superoxide dismutase (SOD) and catalase (CAT). In summary, YAP supplementation suppressed neuronal apoptosis in the cerebral cortex of HFD-induced obesity mice by improving mitochondrial function and inhibiting oxidative stress.
Assuntos
Malus , Camundongos , Masculino , Animais , Pós/farmacologia , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Mitocôndrias/metabolismo , Estresse Oxidativo , Dieta Hiperlipídica/efeitos adversos , Apoptose , Córtex Cerebral/metabolismoRESUMO
Glioblastoma multiforme (GBM) is the most aggressive brain cancer with a poor prognosis. Therefore, the correlative molecular markers and molecular mechanisms should be explored to assess the occurrence and treatment of glioma.WB and qPCR assays were used to detect the expression of CXCL5 in human GBM tissues. The relationship between CXCL5 expression and clinicopathological features was evaluated using logistic regression analysis, Wilcoxon symbolic rank test, and Kruskal-Wallis test. Univariate, multivariate Cox regression and Kaplan-Meier methods were used to assess CXCL5 and other prognostic factors of GBM. Gene set enrichment analysis (GSEA) was used to identify pathways associated with CXCL5. The correlation between CXCL5 and tumor immunoinfiltration was investigated using single sample gene set enrichment analysis (ssGSEA) of TCGA data. Cell experiments and mouse subcutaneous transplanted tumor models were used to evaluate the role of CXCL5 in GBM. WB, qPCR, immunofluorescence, and immunohistochemical assays showed that CXCL5 expression was increased in human GBM tissues. Furthermore, high CXCL5 expression was closely related to poor disease-specific survival and overall survival of GBM patients. The ssGSEA suggested that CXCL5 is closely related to the cell cycle and immune response through PPAR signaling pathway. GSEA also showed that CXCL5 expression was positively correlated with macrophage cell infiltration level and negatively correlated with cytotoxic cell infiltration level. CXCL5 may be associated with the prognosis and immunoinfiltration of GBM.