High folate intake contributes to the risk of large for gestational age birth and obesity in male offspring.

Folate supplementation is recommended before and during early pregnancy to prevent neural tube defects, but the effect of red blood cell (RBC) folate on large for gestational age (LGA) is still unknown. We performed a nested case-control study including 542 LGA cases and 1,084 appropriate for gestational age (AGA) controls to examine the association of RBC folate concentrations with risk of LGA. Then, male offspring of dams fed basic folic acid (2 mg/kg, control) or 10-fold folic acid (20 mg/kg, HFol) diet before and during pregnancy were used to explore the effect of high folate intake on birth weight and long-term effects. We observed higher RBC folate concentrations in the cases compared to controls (p = 0.039). After adjustment for maternal age, BMI at enrollment, gestational weeks at enrollment, gestational weeks at delivery and infant gender, higher RBC folate levels were significantly associated with increased risk of LGA (Ptrend = 0.003). Interestingly, male offspring of HFol dams showed the higher birth weight, elevated levels of post loading blood glucose at 9 and 13 weeks post-weaning and increased triglyceride (TG) and total cholesterol (TC) levels at 17 weeks post-weaning. Furthermore, we observed that high folate intake increased the proliferation and differentiation of adipose cells. Our results suggest that maternal high folate intake confers the risk of LGA birth and accelerates the development of obesity in male offspring.

1,25(OH)2D3 deficiency increases TM40D tumor growth in bone and accelerates tumor-induced bone destruction in a breast cancer bone metastasis model.

Breast cancer is one of the most common malignancies and bone is the commonest site of distant metastases. Evidences indicate that adequate supply of vitamin D will decrease the morbidity and mortality of breast cancer. However, the main role of vitamin D deficiency in breast cancer bone metastases remains unclear. In this study, the relationship between vitamin D and breast cancer bone metastases were evaluated. Results showed that 1,25(OH)2D3 can not only inhibit the proliferation, migration and invasion of breast cancer cell TM40D in vitro, but also attenuate the breast cancer cell TM40D-induced bone destruction in vivo, whose underlying mechanism was at least partially through decreasing the number of the osteoclasts. To our knowledge, this is the first to use 1-alpha-hydroxylase [1α(OH)ase] knockout mice which characterized vitamin D deficiency to establish the breast cancer bone metastases model. Based on this model, we also found that vitamin D deficiency will accelerate the osteolytic lesions, and 1,25(OH)2D3 supplement will restrain osteolytic lesions. Therefore, these findings suggest that vitamin D has the potential capacity to be a therapeutic agent for the breast cancer bone metastases.

Targeted imaging and induction of apoptosis of drug-resistant hepatoma cells by miR-122-loaded graphene-InP nanocompounds.

BACKGROUND: Currently, graphene oxide has attracted growing attention as a drug delivery system due to its unique characteristics. Furthermore, utilization of microRNAs as biomarkers and therapeutic strategies would be particularly attractive because of their biological mechanisms and relatively low toxicity. Therefore, we have developed functionalized nanocompounds consisted of graphene oxide, quantum dots and microRNA, which induced cancer cells apoptosis along with targeted imaging. RESULTS: In the present study, we synthesized a kind of graphene-P-gp loaded with miR-122-InP@ZnS quantum dots nanocomposites (GPMQNs) that, in the presence of glutathione, provides controlled release of miR-122. The miR-122 actively targeted liver tumor cells and induced their apoptosis, including drug-resistant liver tumor cells. We also explored the near-infrared fluorescence and potential utility for targeting imaging of InP@ZnS quantum dots. To further understand the molecular mechanism of GPMQNs-induced apoptosis of drug-resistant HepG2/ADM hepatoma cells, the relevant apoptosis proteins and signal pathways were explored in vitro and in vivo. Furthermore, near-infrared GPMQNs, which exhibited reduced photon scattering and auto-fluorescence, were applied for tumor imaging in vivo to allow for deep tissue penetration and three-dimensional imaging. CONCLUSION: In conclusion, techniques using GPMQNs could provide a novel targeted treatment for liver cancer, which possessed properties of targeted imaging, low toxicity, and controlled release.

[Systematic review of shenfu injection for septic shock].

To assess the efficacy and safety of Shenfu injection for septic shock. All clinical studies of Shenfu injection for septic shock were searched from Cochrane library, Medline, EMbase, CBM, CNKI, Wanfang and VIP. Quality assessment and information extraction were done by two independent screening. The quality of the included documents was evaluated by the Cochrane Collaboration's tool for assessing risk of bias and allocation concealment. Revman 5. 1. 4 software was used for data analysis. A total of 6 randomized controlled trials were included (499 patients), in which, 6 studies did not mention allocation concealment, blind and loss-up information. Meta-analysis showed that the Shenfu injection group was better than the conventional treatment group in SBP (OR = 9.00, 95% Cl [3.89, 14.11]; OR = 20.28, 95% Cl [16.46, 24.10], respectively) and DBP (OR = 11.25, 95% Cl [7.65, 14.85]; OR = 8.17, 95% Cl [5.21, 11.13], respectively); in improving shock symptom (OR = 4.60, 95% Cl [1.88, 11.28]; OR = 0.88, 95% Cl [0.16, 4.87]; OR = 1.02, 95% Cl [0.27, 3.93]; OR = 1.65, 95% Cl [0.42, 6.42]) and reducing HR (OR = -29.71, 95% Cl [-40.51, -18.91]; OR = -18.00, 95% Cl [-27.16, -8.84]), (OR = 8.00, 95% Cl [1.96, 14.04]), there was inconsistency between the two groups; the Shenfu injection group showed no advantage in MAP (OR = -0.10, 95% Cl [-2.34, 2.14]) and CI (OR = 0.00, 95% Cl [- 1.24, 1.24]). ADR/AE information of Shenfu injection was not fully reported. This study may exist publication bias. Shenfu injection on the basis of conventional treatment can improve blood pressure of the treatment of septic shock; we can not get a positive conclusion in improving shock symptom and HR. Also, due to the sample size of included studies were small and of lower quality, conclusions above still need high-qualitied randomized, double-blind, controlled trials be confirmed.