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Cyclooxygenase (COX)-2, a multi-functional molecule, is overexpressed in hepatocellular carcinomas. In order to understand cell proliferation and its association with COX-2 in HepG2 cells in the presence of ursolic acid (UA), viili exopolysaccharides (VEPS) and Astragalus polysaccharides (APS), the cell proliferation, superoxide dismutase (SOD) and metabolic malondialdehyde (MDA) of fatty acids, COX-2, prostaglandin E2 (PGE2), as well as apoptotic morphology and rate were investigated. The results revealed that the activities of SOD, COX-2 and PGE2 were reduced, MDA was markedly decreased, apoptotic blebs were induced, and HepG2 cells were accumulated in the G1 and sub G1/apoptotic phases in test groups. The results indicated that UA, VEPS, APS and any combination of these possess anticancer properties, particularly by downregulating COX-2 expression, which may have increased internal oxidation and triggered apoptosis together with a change in internal antioxidant response elements, leading to a reduction in cell proliferation. [ABSTRACT FROM AUTHOR]

The long-term improvement of intrastriatal co-grafts with genetically engineered fibroblasts expressing tyrosine hydroxylase (TH) and glial cell line-derived neurotrophic factor (GDNF) was investigated in the present study. Two recombinant vectors, pCMV-TH and pCI-neo-GDNF, were transfected respectively into the primary fibroblasts, and their expression was further identified by in situ hybridization and immunocytochemistry. The engineered fibroblasts expressing TH, GDNF, or both were transplanted into the striatum of parkinsonian rats, and the therapeutic effects were observed for 20 weeks. Data revealed that only animals with fibroblasts expressing both TH and GDNF exhibited a stable and significant behavioral and biochemical recovery. Moreover, persistence of both TH and GDNF expression in grafts was demonstrated 20 weeks after transplantation. These results suggest that combined transplantation of fibroblasts expressing TH and GDNF can lead to long-term and remarkable therapeutic effects on parkinsonian rat model. [ABSTRACT FROM AUTHOR]

The motor behavior and levels of dopamine and its metabolites in the striatum were studied in rats that received a unilateral injection of 6-OHDA and underwent grafting of rat-derived primary fibroblasts that had been genetically modified to expresslacZand human glial cell line-derived neurotrophic factor (GDNF). Rotation behavior tests were performed each week and striatal levels of DA and its metabolites were measured every 4 weeks after grafting of fibroblasts that expressedlacZ, with or without additional transfection of the GDNF transgene. Rats grafted with GDNF-producing fibroblasts showed a significant improvement in motor behavior as determined by the rotation test, with a less pronounced reduction in the levels of dopamine and its metabolites in the striatum as compared with those in the control animals or brain parts. In addition, there was a lower decrease in the number of TH immunoreactive neurons in the substantia nigra ipsilateral to the lesion in rats with GDNF-producing fibroblasts than in rats withlacZ-expressing fibroblasts. These results support the notion that intracerebral grafting of fibroblasts that express GDNF is a potentially useful therapeutic strategy for treating Parkinson’s disease. [ABSTRACT FROM AUTHOR]