Objective To explore the possible effects of methyl methanesulfonate sensitive 2(MMS2)in the process of angiotensin Ⅱ inducing differentiation of neural stem cells (NSCs) into dopaminegic phenotype neurons. Methods NSCs were isolated from the brain of newborn rats and were cultured in the serum-free medium.Identification of neural precursor cells was done by Nestin immunocyt ochemical staining. Then the second generation of NSCs was divided into the following six groups: A, control; B, AⅡ; C, AT1 antagonist ZD7155; D, ZD7155+AⅡ; E, AT2 antagonist PD123319; F, PD123319+AⅡ. The detection of expression of MMS2 and TH mRNA level was done by real-time PCR. The silence of the expression of MMS2 in NSCs was brought about via the transfection of MMS2-siRNA, and then the NSCs were induced to differentiate into dopaminegic neurons. The expression of TH mRNA level in the cells of the groups after transfection was detected by real-time PCR. Results Nestin-positive cells were observed in suspended growth in the medium.Real-Time PCR revealed that the MMS2 and TH mRNA expression of group B and D were significantly higher than that of the control group(P<0.05), There was no significant difference in MMS2 and TH mRNA expression between group C, E, F and the control, respectively. Conclusion AⅡ increased the expression of MMS2 mRNA in NSCs and induced the differentiation of NSCs into DA neurons via AT2 recepter. MMS2 may play important roles in the process of angiotensin Ⅱ inducing NSCs to differentiate into dopaminergic neurons.

In coal mines, main occupational hazard is coal-mine dust, which can cause health problem including coal workers' pneumoconiosis and lung cancer. Some heat shock proteins (Hsps) have been reported as an acute response to a wide variety of stressful stimuli. Whether Hsps protect against chronic environmental coal-mine dust over years is unknown. It is also interesting to know that whether the expression of Hsp27 and Hsp70 proteins as a marker for exposure is associated risk of lung cancer among coal miners. We investigated the association between levels of Hsp27 and Hsp70 expression in lymphocytes and plasma and levels of coal-mine dust exposure in workplace or risk of lung cancer in 42 cancer-free non-coal miners, 99 cancer-free coal miners and 51 coal miners with lung cancer in Taiyuan city in China. The results showed that plasma Hsp27 levels were increased in coal miners compared to non-coal miners (P<0.01). Except high cumulative coal-mine dust exposure (OR=13.62, 95%CI=6.05-30.69) and amount of smoking higher than 24 pack-year (OR=2.72, 95% CI=1.37-5.42), the elevated levels of plasma Hsp70 (OR=13.00, 95% CI=5.14-32.91) and plasma Hsp27 (OR=2.97, 95% CI=1.40-6.32) and decreased expression of Hsp70 in lymphocytes (OR=2.36, 95% CI=1.05-5.31) were associated with increased risk of lung cancer. These findings suggest that plasma Hsp27 may be a potential marker for coal-mine dust exposure. And the expression of Hsp27 and Hsp70 levels in plasma and lymphocytes may be used as biomarkers for lung cancer induced by occupational coal-mine dust exposure.

In coal mines, main occupational hazard is coal-mine dust, which can cause health prob-lem including coal workers' pneumoconiosis and lung cancer. Some heat shock proteins (Hsps) have been reported as an acute response to a wide variety of stressful stimuli. Whether Hsps protect against chronic environmental coal-mine dust over years is unknown. It is also interesting to know that whether the expression of Hsp27 and Hsp70 proteins as a marker for exposure is associated risk of lung cancer among coal miners. We investigated the association between levels of Hsp27 and Hsp70 expression in lymphocytes and plasma and levels of coal-mine dust exposure in workplace or risk of lung cancer in 42 cancer-free non-coal miners, 99 cancer-free coal miners and 51 coal miners with lung cancer in Taiyuan city in China. The results showed that plasma Hsp27 levels were increased in coal miners compared to non-coal miners (P<0.01). Except high cumulative coal-mine dust exposure (OR= 13.62, 95%CI=6.05-30.69) and amount of smoking higher than 24 pack-year (OR=2.72, 95%CI=1.37-5.42), the elevated levels of plasma Hsp70 (OR= 13.00, 95% CI=5.14-32.91) and plasma Hsp27 (OR=2.97, 95% CI=1.40-6.32) and decreased expression of Hsp70 in lymphocytes (OR=2.36, 95% CI=1.05-5.31) were associated with increased risk of lung cancer. These findings suggest that plasma Hsp27 may be a potential marker for coal-mine dust exposure. And the expres-sion of Hsp27 and Hsp70 levels in plasma and lymphocytes may be used as biomarkers for lung can-cer induced by occupational coal-mine dust exposure.

Objective To evaluate the bioequivalence of two formulations of minocycline hydrochloride capsules administered orally after fasting administration and fed administration.Methods An open-label,randomized,two-period,self-crossover design was employed to assess the bioequivalence study.Twenty-eight healthy subjects were enrolled in both fasting and fed groups,with each period involving a single administration of either the reference formulation or the test formulation of 50 mg,separated by a washout period of 7 days.The concentration of minocycline in human plasma was determined by HPLC-MS/MS and was used for calculating pharmacokinetic parameters and evaluating the bioequivalence of the test formulation and reference formulation.Results After oral administration of test and reference formulations of minocycline under fasting condition,the Cmax Values of minocycline were(541±137)ng·mL-1 for the test formulation and(558±140)ng·mL-1for the reference formulation.The AUC0-t values were(8 347±1 986)h·ng·mL-1 for the test and(8 205±1 790)h·ng·mL-1 for the reference.The t1/2 values were(18.2±2.84)h for the test and(18.0±3.05)h for the reference.After oral administration of the test and reference formulations of minocycline under fed condition,the Cmax values of minocycline were(349±72.1)ng·mL-1 for the test and(352±73.2)ng·mL-1for the reference.The AUC0-twere(6 428±1 077)h·ng·mL-1 for the test and(6 588±1 118)h·ng·mL-1 for the reference.The t1/2values were(18.5±3.10)h for the test and(18.4±3.21)h for the reference.Under fasting condition,the 90% confidence intervals for the geometric mean ratios of Cmax,AUC0-t,and AUC0-∞ between the test and reference formulations were(90.84%,101.46% ),(95.2%,102.8% ),and(95.31%,102.71% ),respectively.Under fed conditions,the 90% confidence intervals for the geometric mean ratios of Cmax,AUC0-t,and AUC0-∞ between the test formulation and the reference formulation were(94.71%,103.42% ),(95.40%,99.83% ),and(95.79%,100.02% ),respectively.Conclusions Bioequivalence of the two minocycline formulations was demonstrated after fasting administration and fed administration in a healthy Chinese population.