Tanshinone IIA derivatives induced S-phase arrest through stabilizing c-myc G-quadruplex DNA to regulate ROS-mediated PI3K/Akt/mTOR pathway.

Herein, a derivate from tanshinone IIA, 1,6,6-trimethyl-11-phenyl-7,8,9,10-tetrahydro-6H-furo[2',3':1,2]phenanthro[3,4-d]imidazole (TA25), has been synthesized and investigated as potential inhibitor against the proliferation, migration and invasion of lung cancer cells. MTT assay and cell colony formation assay results showed that TA25 exhibits acceptable inhibitory effect against the proliferation of lung cancer A549 cells, and the value of IC50 was about 17.9 µM. This result was further confirmed by the inhibition of TA25 against the growth of xenograft lung cancer cells on zebrafish bearing tumor (A549 lung cancer cells). The results of wound-healing assay and FITC-gelatin invasion assay displayed that TA25 could inhibit the migration and invasion of lung cancer A549 cells. Moreover, the studies on the binding properties of TA25 interact with c-myc G-quadruplex DNA suggested that TA25 can bind in the G-quarter plane formed from G7, G11, G16 and G20 with c-myc G-quadruplex DNA through π-π stacking. Further study of the potential anti-cancer mechanism indicated that TA25 can induce S-phase arrest in lung cancer A549 cells, and this phenomenon resulted from the promotion of the production of reactive oxygen species and DNA damage in A549 cells under the action of TA25. Further research revealed that TA25 could inhibit the PI3K/Akt/mTOR signal pathway and increase the expression of p53 protein. Overall, TA25 can be developed into a promising inhibitor against the proliferation, migration and invasion of lung cancer cells and has potential clinical application in the near future.

Dietary patterns and hyperglycemia in a follow-up study in Nanjing city / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the association between dietary patterns and the risk of developing hyperglycemia in Nanjing.</p><p><b>METHODS</b>Using multi-stage stratified random cluster sampling, the baseline survey was conducted on local residents older than 30 years in 7 communities from 2 urban districts from June to September 2007 in Nanjing. The total eligible subjects were 3376. Excluding the 476 previously diagnosed hyperglycemia patients, 2900 non-hyperglycemia subjects were used as the baseline sample for the follow-up survey from June to September 2010. Using specially designed food frequency questionnaire (FFQ), factor analysis was applied to identify food patterns. Multivariable linear and Cox regression models were used to analyze the association between different dietary patterns and risk of hyperglycemia.</p><p><b>RESULTS</b>The follow-up rate was 72.2%, with 2093 subjects participated the follow-up survey in 3 years. Three-year cumulative incidence of hyperglycemia was 7.5% (158/2093). The incidence rate was 7.1% (62/873) for males and 7.9% (96/1220) for females, but the differences were not statistically significant (χ(2) = 0.43, P = 0.513). Five dietary patterns were identified by factor analysis: condiment, animal and plant protein, traditional healthy, sweet food and alcohol drinking. By multivariable linear regression, on average, an increase in traditional healthy pattern and sweet food pattern of 1 unit was associated with a -0.054, 0.050 mmol/L increase in fasting blood glucose, respectively, and the differences were both statistically significant (t = -2.38, 2.27, respectively, P values were both less than 0.05). By multivariable Cox regression, the pattern sweet food was positively significantly associated with hyperglycemia risk in men. The incidence of hyperglycemia was 4.7% (14/295) for the lowest tertile of the factor score (T1), and 9.7% (26/269) for the highest tertile of the factor score (T3) (T3:T1: RR = 1.88, 95%CI: 1.04 - 3.54). The pattern traditional healthy was inversely associated with hyperglycemia risk in women. The incidence of hyperglycemia was 10.7% (45/421) for T1 and 6.3% (21/335) for T3 (T3:T1: RR = 0.59, 95% CI: 0.35 - 0.99). Conversely, a statistically significant positively association was observed for the pattern alcohol drinking in women. The incidence of hyperglycemia was 8.1% (38/472) for T1 and 11.1% (33/297) for T3 (T3:T1: RR = 1.35, 95%CI: 0.84 - 2.16).</p><p><b>CONCLUSION</b>Dietary patterns are associated with hyperglycemia. The sweet food pattern is a risk factor for hyperglycemia in men. In women, healthy dietary pattern is healthy and the alcohol drinking pattern is a risk factor for hyperglycemia.</p>