Int J Med Sci
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Di-(2-ethylhexyl) phthalate (DEHP) that is one of the most commonly used phthalates in manufacturing plastic wares regulates tumorigenesis. Thymosin beta-4 (TB4), an actin-sequestering protein, has been reported as a novel regulator to form primary cilia that are antenna-like organelles playing a role in various physiological homeostasis and pathological development including tumorigenesis. Here, we investigated whether DEHP affects tumor growth via primary cilium (PC) formation via the axis of TB4 gene expression and the production of reactive oxygen species (ROS). ⋯ TB4 overexpression enhanced PC formation and DEHP-induced tumor growth. Taken together, data demonstrate that DEHP-induced tumor growth might be controlled by PC formation via TB4-H2O2 axis. Therefore, it suggests that TB4 could be a novel bio-marker to expect the risk of DEHP on tumor growth.
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A functional p53 protein plays an important role in killing tumor cells. Previous studies showed that chemotherapeutic drug, paclitaxel (PTX), showed anti-tumor activity through inducing G2/M arrest and apoptosis by targeting microtubules in tumor cells. However, PTX was not sensitive to p53-inactivated papillary thyroid carcinoma (PTC) cells by inducing G2/M arrest only. ⋯ There was high level of p53 in rAd-p53-treated PTC cells. rAd-p53 + PTX increased the level of p21, p-ATM and γ-H2AX and decreased the level of Cyclin D1/E1, suggesting p53 activated p21 which negatively regulated cyclins to induce S arrest response to DNA damage in PTC cells. rAd-p53 + PTX increased the levels of cleaved-PARP-1, cleaved -Caspase 3, and BAX and decreased the level of BCL-XL, suggesting p53 regulates the expression of BAX/BCL-XL to mediate DNA damage-induced apoptosis in PTC cells. Furthermore, rAd-p53 + PTX showed significant tumor inhibition in TPC-1 xenograft model, with an inhibitory rate of 79.39%. TUNEL assay showed rAd-p53 + PTX induced notable apoptosis in tumor tissues. rAd-p53 showed good sensitization of PTX in vitro and in vivo through inducing DNA damage induced-apoptosis indicated p53-dependent apoptosis was essential for the antitumor effect of PTX in PTC.
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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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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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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.