Int J Med Sci
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Osteoarthritis (OA) is a common joint disease characterized by degradation and inflammation of cartilage extracellular matrix. We aimed to evaluate the protective effect of Caragana sinica root (CSR) on interleukin (IL)-1β-stimulated rat chondrocytes and a monosodium iodoacetate (MIA)-induced model of OA. In vitro, cell viability of CSR-treated chondrocytes was measured by MTT assay. ⋯ In vivo, CSR and Indomethacin inhibited the production of inflammatory mediators, MMPs and degradation of ECM in MIA-induced model of OA. In addition, CSR improved the severity of OA. Taken together, these results suggest CSR is a potential therapeutic active agent in the treatment of OA.
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Obesity associates with macrophage accumulation in adipose tissue where these infiltrating cells interact with adipocytes and contribute to the systemic chronic metabolic inflammation present in immunometabolic diseases. Tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) are two of the main enzymes of catecholamines (CA) synthesis. Adipocytes and macrophages produce, secrete and respond to CA, but the regulation of their synthesis in the interplay between immune and metabolic systems remains unknown. ⋯ Mediators released by macrophages seem to equally affect CA production by adipocytes, while adipocytes secretome preferentially affect AD production by macrophages. CA synthesis seems to be more determinant in early stages of adipogenic differentiation. Our results suggest that CA are key signaling molecules in the regulation of immune-metabolic crosstalk within the adipose tissue.
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Salinomycin (Sal) is a recently identified anti-tumor drug for treating several types of solid tumor; however, its effects on the migratory and invasive properties of non-small cell lung cancer (NSCLC) remain unclear. This study investigated the inhibitory effect underlying mechanisms of Salon transforming growth factor-β1 (TGF-β1)-induced epithelial-to-mesenchymal transition (EMT) and cell migration. Sal solidly blocked cell migration and invasion enhancement by TGF-β1-induced EMT, through recovering E-cadherin loss and suppressing mesenchymal markers induction, as well as TGF-β1-mediated AMPK/SIRT signaling activity upregulation. ⋯ Next we demonstrated that the MMP-2 and MMP-9 knockdown can act synergistically with Sal to inhibit TGF-β1-induced EMT. Moreover, treatment of PMA of MMP activator increased TGF-β1-induced MMP-2 and MMP-9, even with Sal. Our results demonstrate that Sal suppresses TGF-β1-induced EMT by downregulating MMP-2 and MMP-9 through the AMPK/SIRT pathway, thereby inhibiting lung cancer cell migration and invasion.
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Patients with type 2 diabetes mellitus (T2DM) have a high risk of fracture and experience poor bone healing. In recent years, bone mesenchymal stem cells (BMSCs) and endothelial progenitor cells (EPCs) have become the most commonly used cells in cell therapy and tissue engineering. In this study, we found that high glucose levels had a negative effect on the differentiation of BMSCs and EPCs. ⋯ The results showed that cells cultured with VEGF had a stronger actin cytoskeleton and a greater amount of nuclear and total YAP than cells cultured without VEGF. Taken together, our results indicate that co-culture with EPCs could promote the osteogenesis of BMSCs partially via VEGF. Furthermore, YAP and F-actin play important roles in this process.
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Raddeanin A (RA), an oleanane-type triterpenoid saponin derived from Anemone raddeana Regel, has been found to suppress the viability and metastasis of several cancers, including GBM, through various signaling pathways. However, the mechanisms underlying the anti-GBM properties of RA have not been fully elucidated. Epithelial to mesenchymal transition (EMT) and angiogenesis are important for the genesis and progression of GBM. ⋯ Finally, we demonstrated that RA inhibited tumor growth and prolonged survival time in an intracranial U87 xenograft mouse model. Similar to the results in vitro, RA downregulated the expression of β-catenin, EMT makers and VEGF, and decreased vessel density in vivo. In summary, our results demonstrated that RA repressed GBM via downregulating β-catenin-mediated EMT and angiogenesis both in vitro and in vivo.