Triptolide upregulates NGF synthesis in rat astrocyte cultures.

Triptolide (T10), an extract from the traditional Chinese herb, Tripterygium wilfordii Hook F (TWHF), has been shown to attenuate the rotational behavior induced by D: -amphetamine and prevent the loss of dopaminergic neurons in the substantia nigra in rat models of Parkinson's disease. To examine if the neuroprotective effect is mediated by its stimulation of production of neurotrophic factors from astrocytes, we investigated the effect of T10 on synthesis and release of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) in rat astrocyte cultures. T10 did not affect the synthesis and release of either BDNF or GDNF. However, it significantly increased NGF mRNA expression. It also increased both intracellular NGF and NGF level in culture medium. These results indicate that the neuroprotective effect of T10 might be mediated, at least in part, via a stimulation of the production and release of NGF in astrocytes.

[Influencing factors of pulmonary dysfunction in coal worker's pneumoconiosis].

OBJECTIVE: To investigate the possible influencing factors of pulmonary dysfunction in coal worker's pneumoconiosis (CWP). METHODS: A total of 141 patients with CWP and 200 control miners with similar exposure histories but without apparent pulmonary disease or inflammation were interviewed with the detailed questionnaires (including histories of coal dust-exposure, smoking habits, alcohol consumption, protective mask uses, et al). Lung function examinations were performed at the same time. Predicted formula of lung function index were established by the local healthy residents characters and the pulmonary dysfunction was classified by the ratios between tested and predicted values. RESULTS: All parameters of lung function were significantly lower in CWP cases when compared with that of control miners and the healthy controls (P < 0.05). The main types of pulmonary dysfunction were restrictive and mixed ventilation disorders in CWP patients. The factors such as the category of CWP, the mask worn, the smoking quantity and exposure to coal mine dust were included in the unconditional logistic regression model. CONCLUSIONS: The category of CWP, the usage of mask, the smoking and long duration exposure to coal mine dust may be the main possible influencing factors of pulmonary dysfunction of CWP. Influencing factor analyses were given to inform choice of pertinence preventive measures.

Doxycycline-regulated co-expression of GDNF and TH in PC12 cells.

Current gene therapy models for Parkinson's disease (PD) have adapted two treatment strategies. One is to restore dopamine (DA) production by delivering the genes of DA-synthesizing enzymes such as tyrosine hydroxylase (TH) to the striatum to relieve motor symptoms of PD. Another is to block or slow down progressive degenerative changes by delivering neurotrophic factors such as glial cell line-derived neurotrophic factor (GDNF) to protect the remained neurons. To test the assumption that the combination of the two strategies may have a compound or synergistic effect, we had constructed tetracycline-inducible (tet-off) AAV vector carrying GDNF and TH. After co-transfection of PC12 cells with this vector and the inducer plasmid, the expression of GDNF and TH protected these cells from 1-methyl-4-phenyl-pyridinium-induced injury, and significantly increased the content of dopamine in GDNF/TH-expressing cells compared with the control. Furthermore, mRNA expression of GDNF and TH could be effectively and reversibly regulated by doxycycline (Dox) and the function of GDNF and TH could be repressed by Dox. These results suggest that the tet-off AAV vector carrying GDNF and TH may be a useful tool for gene therapy in the treatment of PD.