A comparative ex vivo permeation evaluation of a novel 5-Fluorocuracil nanoemulsion-gel by topically applied in the different excised rat,goat, and cow skin

Aim of the study5-Fluorouracil (5-FU) can’t be given orally because of very low bioavailability and produces serious adverse effects. Therefore, the main objective of this research is to develop, evaluate, and comparative effects by different nanoformulations of topical application on chemoprevention of skin cancer in different types of skin.Material and methodsCastor oil (oil), Transcutol HP (surfactant), and Polyethylene glycol (PEG)–400 (co-surfactant) have taken on the basis of nonionic property and highest nanoemulsion (NE)-region. Aqueous micro titration method with ultra-sonication method (based on high energy) was used for the preparation of 5-FU-NE. Optimized-5-FU-NE was stable thermodynamically, and their characterizations was performed on the basis of globule size, zeta potential, refractive index, and viscosity. Optimized-NE has been converted into 5-FU-NE-Gel with the help of Carbopol® 934 and also performed their permeation studies in the different skins (cow, goat, and rat, ex vivo) using Logan transdermal diffusion cell (DHC-6T). Optimized-5-FU-NE and 5-FU-NE-Gel were evaluated cytotoxic studies (in vitro) on the melanoma cell lines.ResultsThe permeation of 5-FU from 5-FU-NE-Gel nanoformulation for rat skin model was 1.56 times higher than the 5-FU-NE and 12.51 times higher than the 5-FU-S for the cow and goat skin model. The values of steady state flux and permeability coefficient for 5-FU-NE-Gel of rat skin were higher i.e. 12.0244 ± 1.12 µgcm⁻²h⁻¹ and 1.2024 ± 0.073 × 10⁻² µg cm⁻²h⁻¹, respectively. Optimized-5-FU-NE and 5-FU-NE-Gel nanoformulation were found to be physically stable. SK-MEL-5 cancer cells have showed the results based on cytotoxicity studies (in vitro) that 5-FU as Optimized-5-FU-NE-Gel is much more efficacious than 5-FU-NE followed by free 5-FU. Localization of 5-FU from 5-FU-NE-Gel was higher with higher permeation in rat skin.Conclusion5-FU-NE-Gel is found to be for the better to treatment of cutaneous malignancies. It can be developed 5-FU-NE-Gel could be a promising vehicle for the skin cancer chemoprevention.     

miR-146a参与不同疾病的研究进展*

miR-146a是近年来miRNA研究的热点,其在不同物种中高度保守,并参与了各种类型疾病的发生与发展,如炎症、自身免疫性疾病、癌症与肥胖症等,其机制主要通过TLR4、MyD88、NF-κB和Akt等信号通路来发挥作用。就miR-146a在不同疾病过程中的作用及其机制进行综述,为深入研究miR-146a在各类疾病中的调节作用提供资料。     

The effects of two different types of clothing on seasonal cold acclimation of thermophysiological responses

The work described in this paper investigated the effects of two types of clothing, leaving the legs covered or uncovered, on seasonal cold acclimation in women. Experiments were carried out to observe the different thermal physiological responses between two groups of subjects, who dressed themselves in kneelength skirts or trousers during the daytime for 3 months from September to November. It was found that rectal temperatures and heart rates in the subjects wearing skirts were shifted to lower levels when the season gradually became colder. The results suggest that the clothing type worn in daily life may play a potential role in seasonal cold acclimation of thermal physiological responses in man.