Dietary vitamin C and vitamin E with the risk of aortic aneurysm and dissection: A prospective population-based cohort study.

BACKGROUND AND AIMS: The associations between dietary vitamin C (VC), vitamin E (VE) intake and aortic aneurysm and dissection (AAD) remain unclear. This study aimed to prospectively investigate the associations between dietary VC and VE with the incident risk of AAD. METHODS AND RESULTS: A total of 139 477 participants of UK Biobank cohort were included in the analysis. Dietary VC and VE consumptions were acquired through a 24-h recall questionnaire. Cox proportional regression models were used to examine the associations between VC, VE intake and the risk of AAD. Incident AAD was ascertained through hospital inpatient records and death registers. During a median follow-up of 12.5 years, 962 incident AAD events were documented. Both dietary VC [adjusted hazard ratio (HR), 0.77; 95 % confidence intervals (CI), 0.63-0.93; P-trend = 0.008] and VE (adjusted HR, 0.70; 95 % CI, 0.57-0.87; P-trend = 0.002) were inversely associated with incident AAD when comparing the participants in the highest quartile with those in the lowest. In subgroup analyses, the associations were more pronounced in participants who were over 60 years old, participants with smoking history, hypertension or hyperlipidemia, who were under the high risk of AAD. CONCLUSION: Higher dietary VC and VE intakes are associated with reduced risk of AAD. Our study emphasizes the importance of diet adjustment strategies targeted on VC and VE to lower the incidence rate of AAD especially in the high-risk population.

[Effects of early life PM2.5 exposure on prefrontal cortex of offspring male rats].

Objective: To investigate the effects of PM2.5 exposure at different stages of early life on the prefrontal cortex of offspring rats. Methods: Twelve pregnant SD rats were randomly divided into four groups: Control group (CG), Maternal pregnancy exposure group (MG), Early postnatal exposure group (EP) and Perinatal period exposure group (PP), 3 rats in each group. The pregnant and offspring rats were exposed to clean air or 8-fold concentrated PM2.5. MG was exposed from gestational day (GD) 1 to GD21. EP was exposed from postnatal day (PND) 1 to PND21, and PP was exposed from GD1 to PND21. After exposure, the prefrontal cortex of 6 offspring rats in each group was analyzed. HE staining was used to observe the pathological damage in the prefrontal cortex. ELISA was employed to detect neuroinflammatory factors, and HPLC/MSC was applied to determine neurotransmitter content. Western blot and colorimetry were applied for detecting astrocyte markers and oxidative stress markers, respectively. Results: Compared with MG and CG, the pathological changes of prefrontal cortex in PP and EP were more obvious. Compared with MG and CG, the neuroinflammatory factors (IL-1, IL-6, TNF-α) in PP and EP were increased significantly (P＜0.01), the level of MT were decreased significantly (P＜0.05), and the level of oxytocin (OT) showed a downward trend; the level of neurotransmitter ACh was also increased significantly (P＜0.01). Compared with MG and CG, the GFAP level of PP and EP showed an upward trend, the level of oxidative stress index SOD in PP and EP was decreased significantly (P＜0.01), and the level of ROS was increased significantly (P＜0.01). Compared with the offspring rats of CG and MG, the CAT level of PP was decreased significantly (P＜0.01, P＜0.05). Compared with the offspring rats of CG, the CAT level of EP was decreased significantly (P＜0.05). There was no significant difference in IL-1, IL-6, TNF-α, MT, OT, ACh, GFAP, SOD, ROS and CAT levels between PP and EP, or MG and CG. Conclusion: PM2.5 exposure in early life has adverse effects on the prefrontal cortex of offspring male rats, and early birth exposure may be more sensitive.

[Progress in the studies on antitumor natural product ecteinascidin-743].

The alkaloid ecteinascidin-743, isolated from the marine tunicate Ecteinascidia turbinata, binds to DNA and induces cytotoxic effects in several tumors. The drug is being codeveloped by Pharma Mar and Ortho Biotech. In May 2001 and October 2003, it was granted orphan drug status by the European Commission for soft tissue sarcoma and ovarian cancer, respectively. This paper reviews its research progress, including chemical synthesis, in vitro studies and mechanism of action, antitumor activity in vivo, toxicity, pharmacokinetics, and clinical studies.

[Synthesis and drug resistant reversal activities of taxane-like multi-drug resistant reversal agents].

AIM: To design and synthesize a series of new taxoids with a 5-O-sidechain, and to test the multi-drug resistant reversal activity of these compound on KB/V200 cells which is 180 times more resistant to vincristine. METHODS: Using Sinenxan A as a common synthetic starting material, three different types of 5-O-sidechain molecules were synthesized through different route. For type I compounds, 14-acetoxy of Sinenxan A was selectively removed by hydrolysis, xanthation and reduction with tributyltin; A C-10-oxo group was introduced by PCC oxidation; 5-O-acetyl group was selectively removed by potassium tert-butoxide and finally the side chain was introduced by acylating with the corresponding acid. For type II compounds, 5-O-sidechain was introduced to the 5-deacetyl Sinenxan A which was obtained by selective hydrolysis with tBuOK. For type III compounds, 9-acetoxy group was introduced, then 5-OH was left free by thorough hydrolysis and reacetylation. Acylation at 5-position, the final product was obtained. Structure of the compounds have been confirmed by FABMS and 2DNMR. The activity of the compounds in vitro was tested on KB/V200 resistant cell line using MTT method. RESULTS: Nine compounds showed resistant reversal activity and enhancing the cytotoxicity of vicristine against KB/V200 cells. Compounds I2, I3, I4 restored the sensitivity of KB/V200 towards vicristine to a level of IC50 at 1 x 10(-8) mol.L-1 which is better than the positive control Verapamil. CONCLUSION: The drug resistant reversal activity of taxane derivatives can be affected by substitution at different positions and the length of side chains of Sinenxan A. It is worthy to be further studied.