Curcumin suppresses glioblastoma cell proliferation by p-AKT/mTOR pathway and increases the PTEN expression.

BACKGROUND: Glioblastoma (GB) is the most common neoplasm in the brain. Curcumin, as a known polyphenolic compound extracted from turmeric, is a chemotherapy used in some cancer treatments in China. However, the effect of curcumin on the survivability of GB cells remains to be elucidated. METHODS: We performed a CCK8 assay to detect the viability of GB cells following treatments with curcumin and examined the migration and invasion the ability of these cells using the wound-healing and transwell invasion assays. The cell proliferation and apoptotic proteins were detected by Western blot analyses. We utilized a glioblastoma-xenograft mouse model to assess cell proliferation following curcumin treatment. RESULTS: We found that curcumin inhibited the proliferation, migration, and invasion of U251 and U87 GB cells. We detected that curcumin decreased p-AKT and p-mTOR protein expression, and promoted the apoptosis of U251 and U87 GB cells. Further, we found that curcumin promoted the PTEN and p53 expression, as the tumor suppressor genes. In addition, we administered curcumin to nude mice and found that curcumin decreased the tumor volume, caused necrosis of tumor tissue, and significantly enhanced the PTEN and p53 expression in vivo. CONCLUSIONS: These results indicated that curcumin inhibited proliferation by decreasing the p-AKT/p-mTOR pathway and promoted apoptosis by increasing the PTEN and p53 expression. Our study provided the molecular mechanisms by which curcumin inhibited glioblastoma and its targeted interventions.

Captopril Attenuates the Upregulated Connexin 43 Expression in Artery Calcification.

OBJECTIVE: Vascular calcification is commonly observed in atherosclerosis and diabetes. The renin-angiotensin II system is associated with the regulation of arterial stiffening. The aim of this study was to examine whether the angiotensin-converting enzyme inhibitors captopril attenuates artery calcification. METHODS: The rat model of arterial calcification was established by a combination of warfarin and vitamin K1. Two weeks after the induction of arterial calcification, captopril treatment was initiated. One week after captopril treatment, aortic arteries were examined to determine the calcification morphology and the connexin 43 expression. Matrix Gla protein (MGP), receptor activator of nuclear factor-κB ligand (RANKL) and extracellular regulated protein kinase (ERK) pathways were examined. RESULTS: The morphology of the calcified arteries was significantly attenuated after captopril treatment. Consistently, captopril inhibited the increased connexin 43 expression and enhanced the decreased MGP expression in calcification arteries. Furthermore, captopril enhanced the decreased SM22 expression in calcified arteries by fluorescence assay. Finally, the calcification arteries increased the p38, p-ERK and RANKL expression, which were downregulated by captopril treatment. CONCLUSIONS: We concluded that captopril attenuated the increased connexin 43 expression and enhanced the MGP and SM22 expression levels, which are associated with the inactivation of p-ERK, p38 and RANKL pathways in rat aortic arteries.

Vildagliptin and G-CSF Improved Angiogenesis and Survival after Acute Myocardial Infarction.

BACKGROUND: Myocardial infarction (MI) is one of the most important diseases that has stimulated interest in understanding cardiac function recovery. SDF-1 is a chemotactic factor and a pro-angiogenic molecule; SDF-1 degradation is inhibited by dipeptidyl peptidase-4 (DPP4) inhibitors, such as vildagliptin. We investigated whether vildagliptin affects angiogenesis in MI and improves cardiac function recovery. METHODS: We established a therapeutic strategy using vildagliptin and G-CSF treatment to improve cardiac function recovery after MI in mice. RESULTS: Vildagliptin treatment increased the myocardial homing of circulating CXCR4+ stem cells and angiogenesis. The combination of vildagliptin and G-CSF treatment attenuated cardiac remodeling and improved survival and cardiac function after MI. Vildagliptin treatment induced active SDF-1, which preserved the cardiac SDF-1-CXCR4 homing axis for MI injury. CONCLUSION: Vildagliptin and G-CSF induced stem cell mobilization and increased angiogenesis as a therapeutic strategy for improving survival and cardiac function after MI.

Time-dependent changes of autophagy and apoptosis in lipopolysaccharide-induced rat acute lung injury.

OBJECTIVES: Abnormal lung cell death including autophagy and apoptosis is the central feature in acute lung injury (ALI). To identify the cellular mechanisms and the chronology by which different types of lung cell death are activated during lipopolysaccharide (LPS)-induced ALI, we decided to evaluate autophagy (by LC3-II and autophagosome) and apoptosis (by caspase-3) at different time points after LPS treatment in a rat model of LPS-induced ALI. MATERIALS AND METHODS: Sprague-Dawley rats were randomly divided into two groups: control group and LPS group. ALI was induced by LPS intraperitoneal injection (3 mg/kg). The lung tissues were collected to measure lung injury score by histopathological evaluation, the protein expression of LC3-II and caspase-3 by Western blot, and microstructural changes by electron microscopy analysis. RESULTS: During ALI, lung cell death exhibited modifications in the death process at different stages of ALI. At early stages (1 hr and 2 hr) of ALI, the mode of lung cell death started with autophagy in LPS group and reached a peak at 2 hr. As ALI process progressed, apoptosis was gradually increased in the lung tissues and reached its maximal level at later stages (6 hr), while autophagy was time-dependently decreased. CONCLUSION: These findings suggest that activated autophagy and apoptosis might play distinct roles at different stages of LPS-induced ALI. This information may enhance the understanding of lung pathophysiology at the cellular level during ALI and pulmonary infection, and thus help optimize the timing of innovating therapeutic approaches in future experiments with this model.

Bone mesenchymal stem cells contributed to the neointimal formation after arterial injury.

OBJECTIVES: Recent findings suggest that in response to repair-to-injury bone marrow mesenchymal stem cells (BMSCs) participate in the process of angiogenesis. It is unclear what role BMSCs play in the structure of the vessel wall. In present study, we aimed to determine whether BMSCs had the capacity of endothelial cells (ECs). METHODS: BMSCs were separated and cultured. FACS and RT-PCR analysis confirmed the gene expression phenotype. The capacity of migration and adhesion and the ultrastructure of BMSCs were examined. The effect of BMSCs transplantation on the vascular repair was investigated in a murine carotid artery-injured model. RESULTS: BMSCs could express some markers and form the tube-like structure. The migration and adhesion capacity of BMSCs increased significantly after stimulated. In addition, BMSCs had the intact cell junction. In vivo the local transfer of BMSCs differentiated into neo-endothelial cells in the injury model for carotid artery and contributed to the vascular remodeling. CONCLUSION: These results showed that BMSCs could contribute to neointimal formation for vascular lesion and might be associated with the differentiation into ECs, which indicated the important therapeutic implications for vascular diseases.