Dermal absorption and hydrolysis of methylparaben in different vehicles through intact and damaged skin: Using a pig-ear model in vitro

Currently, there is a trend to reduce of parabens use due to concern about the safety of their unmetabolised forms. This paper focused on dermal absorption rate and effectiveness of first-pass biotransformation of methylparaben (MP) under in-use conditions of skincare products. 24-h exposure of previously frozen intact and tapestripped (20 strips) pig-ear skin to nine vehicles containing 0.1% MP (AD, applied dose of 10 μg/cm²), resulted in 2.0–5.8%AD and 2.9–7.6%AD of unmetabolised MP, and 37.0–73.0%AD and 56.0–95.0%AD of p-hydroxybenzoic acid, respectively, in the receptor fluid. The absorption rate of MP was higher from emulsions than from hydrogels, from enhancer-containing vehicles than from enhancer-free vehicles, and when skin was damaged. Experiments confirmed that the freezing of pig-ear skin slightly reduces hydrolysis of MP.After 4-h exposure of intact freshly excised and intact frozen stored skin, amount of <LOQ-2.3%AD and 2.3–3.3%AD unmetabolised MP, respectively, were found in the receptor fluid. Taking into account the number of useful properties of MP, but also the potential of systemic availability of unmetabolised MP, we consider that MP is more suitable for preserving rinse-off topical products than for leave-on products. Risk of systemic absorption of parabens should also be explored via the skin with damaged barrier.     

髓母细胞瘤组织MEF2C表达与预后相关性分析

目的：探讨肌细胞增强因子2C（myoeyte enhancer factor2C，MEF2C）表达情况与髓母细胞瘤患者预后的关系。方法：选取3家三级甲等医院2001-01—01—2007—12-31病理确诊的髓母细胞瘤患者56例，其中泰安市中心医院12例．齐鲁医院26例，山东省立医院18例；对照组脑组织取自泰安市中心医院2010-01-01-2010—12—3112例非肿瘤脑外伤患者。免疫组织化学法检测56例髓母细胞瘤患者肿瘤组织和12例非肿瘤患者脑组织中MEF2C的表达；收集髓母细胞瘤患者临床资料，应用统计学方法对髓母细胞瘤患者进行生存分析。结果：髓母细胞瘤患者肿瘤组织MEF2C相对高表达率为53．6％（30／56），非肿瘤患者脑组织MEF2C相对高表达率为0（0／12），两组比较差异有统计学意义，χ2=11．50，P=0．001；肿瘤患者肿瘤组织MEF2C相对高表达组与相对低表达组间生存时间的差异有统计学意义，χ2=4．34，P=0．037。MEF2C相对高表达（p=0．023）、肿瘤转移（P=0．042）与患者3年生存率降低显著有关，而患者性别、年龄、肿瘤大小、肿瘤部位与患者3年生存率无关，P值均〉0．05。结论：MEF2C在患者肿瘤组织中的高表达可降低患者3年生存率，是患者预后不良的危险因素之一。     

Chitosan-based mucoadhesive gel for oral mucosal toluidine blue O delivery: The influence of a non-ionic surfactant

Photodynamic therapy (PDT) has been successfully employed in the treatment of oral cancer. Toluidine blue O (TBO) is a photosensitizer (PS) that has exhibited remarkable photocytotoxicity in a variety of tumour cells; however, its physicochemical properties, as well as the physicochemical properties of oral mucosa, prevent the drug from reaching the target site at a therapeutic concentration.The aim of this study was to evaluate the influence of Tween 80^® (TW), which has shown potential as a penetration enhancer, on the mucosal retention of TBO for the PDT of oral cancer. 4% Chitosan-based mucoadhesive gels (CH gels) containing or not 5%TW were prepared (both containing 1%TBO), and their physicochemical properties (pH, rheology and mucoadhesion), TBO in vitro release profiles and TBO in vitro mucosal retention were evaluated. In vivo mucosal penetration studies of TBO followed by laser exposition were also carried out.The results showed that 4%CH gels containing 5%TW and 1%TBO have adequate mucoadhesive and rheological properties for oral mucosa use, although they present a slightly acid pH. TBO release studies showed that TW reduces TBO release, but it prolongs TBO release and increases TBO retention in the mucosa. In vivo studies showed that 4%CH gels containing 5%TW and 1%TBO cause an increase in the number of apoptotic cell, after laser exposition.In summary, 4%CH gels containing 5%TW may be a promising vehicle to optimize the penetration of TBO in oral mucosa and to improve the PDT response for the treatment of oral cancer.     

Advances in understanding the molecular basis of the first steps in color vision

Serving as one of our primary environmental inputs, vision is the most sophisticated sensory system in humans. Here, we present recent findings derived from energetics, genetics and physiology that provide a more advanced understanding of color perception in mammals. Energetics of cis–trans isomerization of 11-cis-retinal accounts for color perception in the narrow region of the electromagnetic spectrum and how human eyes can absorb light in the near infrared (IR) range. Structural homology models of visual pigments reveal complex interactions of the protein moieties with the light sensitive chromophore 11-cis-retinal and that certain color blinding mutations impair secondary structural elements of these G protein-coupled receptors (GPCRs). Finally, we identify unsolved critical aspects of color tuning that require future investigation.     

The polycomb group protein enhancer of zeste 2 is a novel therapeutic target for cervical cancer

Enhancer of zeste 2 (EZH2), a polycomb histone methyltransferase, is overexpressed in various cancers, including cervical cancer. Gene expression analysis revealed that increased expression of EZH2 is associated with cervical cancer progression, particularly the progression to invasive squamous cell carcinoma. Enhancer of zeste 2 is known to trimethylate lysine 27 on histone H3, leading to gene silencing that contributes to the progression of tumours into a more aggressive form of cancer. However, the specific molecular mechanisms by which EZH2 contributes to the development of cervical cancer remain largely unknown. Recently, an EZH2 inhibitor was reported to selectively inhibit trimethylated lysine 27 on histone H3 and to reactivate silenced genes in cancer cells. In this study, we found that GSK343 (a specific inhibitor of EZH2 methyltransferase) induces phenotypic reprogramming of cancer cells from mesenchymal to epithelial cells, reducing proliferation and cell motility and blocking the invasion of cervical cancer cell lines both in vitro and in vivo. Treatment with the EZH2 inhibitor led to increased levels of the epithelial marker E‐cadherin and decreased levels of mesenchymal markers such as N‐cadherin and vimentin. The observed reprogramming is associated with restrained cervical cancer progression and provides direct evidence in support of EZH2 as a therapeutic target.