RESUMO
Osteoarthritis is a chronic degenerative disease based on the degeneration and loss of articular cartilage. Inflammation and aging play an important role in the destruction of the extracellular matrix, in which microRNA (miRNA) is a key point, such as miRNA-34a-5p. Upregulation of miRNA-34a-5p was previously reported in a rat OA model, and its inhibition significantly suppressed interleukin (IL)-1ß-induced apoptosis in rat chondrocytes. However, Oxidative stress caused by reactive oxygen species (ROS) can exacerbate the progression of miRNA regulated OA by mediating inflammatory processes. Thus, oxidative stress effects induced via tert-butyl hydroperoxide (tBHP) in human chondrocytes were assessed in the current research by evaluating mitochondrial ROS production, mitochondrial cyclooxygenase (COX) activity, and cell apoptosis. We also analyzed the activities of antioxidant enzymes including glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD). Additionally, inflammatory factors, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, IL-8, and IL-24, which contribute to OA development, were detected by enzyme-linked immunosorbent assay (ELISA). The results of this study indicated that miR-34a-5p/silent information regulator 1 (SIRT1)/p53 axis was involved in the ROS-induced injury of human chondrocytes. Moreover, dual-luciferase assay revealed that SIRT1 expression was directly regulated by miR-34a-5p, indicating the presence of a positive feedback loop in the miR-34a-5p/SIRT1/p53 axis that plays an important role in cell survival. However, ROS disrupted the miR-34a-5p/SIRT1/p53 axis, leading to the development of OA, and articular injection of SIRT1 agonist, SRT1720, in a rat model of OA effectively ameliorated OA progression in a dose-dependent manner. Our study confirms that miRNA-34a-5p could participate in oxidative stress responses caused by ROS and further regulate the inflammatory process via the SIRT1/p53 signaling axis, ultimately affecting the onset of OA, thus providing a new treatment strategy for clinical treatment of OA.
RESUMO
OBJECTIVE: To investigate the CT manifestations of thymic carcinoid and assess the diagnostic value of CT for this disease. METHODS: CT and clinical findings of 5 patients (4 males and 1 female, average age 41 years) with histologically confirmed thymic carcinoid were retrospectively analyzed. RESULTS: The clinical findings of the 5 patients showed no specificity, and none of the patients presented with carcinoid syndrome. The tumors were relatively large (mean size on the largest planar of 11.7 cm x 7.6 cm) with heterogeneous density, and showed necrosis or cystic degeneration in the tumor. The lesions showed uneven enhancement in contrast-enhanced imaging and displayed linear enhancement of the blood vessels in the tumors in 3 cases with unclear tumor margins. The adjacent major vessels were displayed in 4 cases (the superior vena cava in 2 and brachiocephalic vein in 4 cases), and 5 showed mediastinal and/or root of the neck lymphatic metastasis. None of the cases have lung or other site metastasis. CONCLUSION: The CT findings of the thymic carcinoid have some characteristics, and can be helpful in the diagnosis.