1.Association of polymorphisms of estrogen receptor-? and vitamin D receptor genes with peak bone mass in Shanghai women
Jinwei HE ; Qiren HUANG ; Zhenlin ZHANG ; Yuejuan QIN ; Jinhui LU ; Miao LI ; Qi ZHOU ; Yunqiu HU ; Yujuan LIU ; Hao ZHANG
Chinese Journal of Endocrinology and Metabolism 1985;0(02):-
Objective To investigate the association of estrogen receptor-? (ER-?) and vitamin D receptor (VDR) gene polymorphisms with peak bone mass in Shanghai women. Methods The ER-? PvuⅡ and XbaⅠ genotypes and VDR ApaⅠ genotypes were determined by PCR-RFLP in 515 unrelated healthy women aged 19-40 years of Han nationality in Shanghai. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. Results Frequencies of ER-? PvuⅡ genotype PP, Pp and pp were 13.2%, 49.3% and 37.5% respectively. Frequencies of ER-? XbaⅠ genotype XX, Xx and xx were 4.7%, 40.4% and 54.9% respectively. Frequencies of VDR ApaⅠ genotype AA, Aa and aa were 5.8%, 41.9% and 52.3% respectively. Hardy-Weinberg equilibrium was evident for both ER-? and VDR gene polymorphisms. No association was found between ER-? PvuⅡ and XbaⅠ genotypes and BMD of various sites in women. Only a significant association was found between VDR ApaⅠ genotype and BMD at L 1-4(P
2.Cholesterol-tuned liposomal membrane rigidity directs tumor penetration and anti-tumor effect.
Hangyi WU ; Miaorong YU ; Yunqiu MIAO ; Shufang HE ; Zhuo DAI ; Wenyi SONG ; Yuan LIU ; Sha SONG ; Ejaj AHMAD ; Dongkai WANG ; Yong GAN
Acta Pharmaceutica Sinica B 2019;9(4):858-870
Recently, liposomes have been widely used in cancer therapeutics, but their anti-tumor effects are suboptimal due to limited tumor penetration. To solve this problem, researchers have made significant efforts to optimize liposomal diameters and potentials, but little attention has been paid to liposomal membrane rigidity. Herein, we sought to demonstrate the effects of cholesterol-tuned liposomal membrane rigidity on tumor penetration and anti-tumor effects. In this study, liposomes composed of hydrogenated soybean phospholipids (HSPC), 1,2-distearoyl--glycero-3-phosphoethanolamine--[methoxy(polyethylene glycol)-2000] (DSPE-PEG) and different concentrations of cholesterol were prepared. It was revealed that liposomal membrane rigidity decreased with the addition of cholesterol. Moderate cholesterol content conferred excellent diffusivity to liposomes in simulated diffusion medium, while excessive cholesterol limited the diffusion process. We concluded that the differences of the diffusion rates likely stemmed from the alterations in liposomal membrane rigidity, with moderate rigidity leading to improved diffusion. Next, the tumor penetration and the anti-tumor effects were analyzed. The results showed that liposomes with moderate rigidity gained excellent tumor penetration and enhanced anti-tumor effects. These findings illustrate a feasible and effective way to improve tumor penetration and therapeutic efficacy of liposomes by changing the cholesterol content, and highlight the importance of liposomal membrane rigidity.