类胡萝卜素抗氧化性质的研究

类胡萝卜素有多种生物学作用，包括抑癌防衰、减低一些疾病发生。其重要原因之一是它们的生物抗氧化剂特性：猝灭^1O2、清除自由基、抑制脂类过氧化与细胞呼吸爆发的抗氧化作用。采用H2O2－NaOCl体系产生的^1O2的发光法研究^1O2的猝灭作用，脉冲辐解法研究与CCl3OO的反应，测定自由基引发的亚油酸氢过氧化物生成和脂质体过氧化产物硫代巴比妥酸反应物生成研究抑制脂质过氧化，通过依赖于鲁米诺的化学发光法与无细胞模拟体系研究对巨噬细胞呼吸爆发的影响。研究表明：类胡萝卜素通过物理过程猝灭^1O2，与CCl3OO发生反应生成加合物与自由基正离子，可抑制自由基引发的脂质过氧化，可清除巨噬细胞呼吸爆发所释放的活性氧自由基，降低细胞依赖于鲁米诺的化学发光，保护宿主细胞与组织，增强细胞免疫反应活性。     

火炬树叶的抗氧化性及其与Vc协同作用的研究

为研究火炬树叶的抗氧化性及其与Vc、柠檬酸的协同作用,本文以猪油为底物,采用高温诱导使其发生脂质过氧化反应,测定体系的过氧化值,结果表明:火炬树叶甲醇提取物可有效延缓猪油脂质过氧化反应,适量加入Vc可提高其抗氧化性。     

Construction and in vitro/in vivo evaluation of 17-allylamino-17-demethoxygeldanamycin (17AAG)-loaded PEGylated nanostructured lipid carriers

In this study, the PEGylated nanostructured lipid carriers (PEG-NLC) were constructed for the intravenous delivery of 17-allylamino-17-demethoxygeldanamycin (17AAG). 17AAG-PEG-NLC was successfully prepared by the method of emulsion evaporation at a high temperature and solidification at a low temperature using a mixture of glycerol monostearate and PEG₂₀₀₀-stearate as solid lipids, and medium-chain triglyceride as the liquid lipid. The results revealed that the morphology of the NLC was spheroidal. The particle size, zeta potential and entrapment efficiency for 17AAG-PEG-NLC were observed as 189.4?nm, ?20.2 mV and 83.42%, respectively. X-ray diffraction analysis revealed that 17AAG existed as amorphous structures in the nanoparticles. In the in vitro release study, the 17AAG from 17AAG-PEG-NLC exhibited a biphasic release pattern with burst release initially and sustained release afterwards. In addition, 17AAG-PEG-NLC showed a significantly higher in vitro antitumor efficacy and longer retention time in vivo than 17AAG solution. These results indicated that 17AAG-PEG-NLC may offer a promising alternative to the current 17AAG formulations for the treatment of solid tumors.     

Lipolysis and lipid oxidation caused by Staphylococcus xylosus 135 and Saccharomyces cerevisiae 31 isolated from Suan yu,a traditional Chinese low‐salt fermented fish

The aim of this study was to investigate the lipolysis and lipid oxidation of Staphylococcus xylosus 135 and Saccharomyces cerevisiae 31 in Suan yu. Suan yu were made inoculated with and without two strains at different stages, and model systems of emulsions were also established. Lipolysis and lipid oxidation were evaluated by determining the changes in free fatty acid (FFA) content and composition, conjugated diene (CD) value and thiobarbituric acid reactive substances (TBARS) value. The total FFA of the sample without cultures increased from 476.61 mg/100 g fat to 1413.89 mg/100 g fat after 5 weeks fermentation, while those of samples with cultures declined to 258.98 and 452.89 mg/100 g fat, respectively. On the other hand, CD and TBARS values of samples with inoculation markedly increased. In the model system, higher FFA, CD and TBARS values for the samples added with CFE were observed. This study showed that Staphylococcus xylosus 135 and Saccharomyces cerevisiae 31 made a significant contribution to lipolysis and lipid oxidation during the processing of Suan yu.     

Metronidazole-loaded nanostructured lipid carriers to improve skin deposition and retention in the treatment of rosacea

The objective of the present investigation was to improve the skin deposition and retention of metronidazole (MTZ) in rosacea therapy by incorporating it into nanostructured lipid carriers (NLCs). The main challenge in this endeavor was the partial hydrophilicity of MTZ, which mandated careful selection of excipients, including solid and liquid lipids, surfactants, and their ratios in combination. NLCs were produced by the phase inversion temperature method and finally converted into a gel for topical application. The prepared nanoparticles were evaluated for their particle size, zeta potential, entrapment efficiency, solid-state characteristics, surface morphology, in vitro drug release, and permeation through excised skin. The gel was additionally characterized for its pH, drug content, viscosity, and spreadability. The prepared nanoparticles were spherical in shape and of size less than 300?nm. Incorporation of judiciously chosen excipients made possible a relatively high entrapment efficiency of almost 40%. The drug release was found to be biphasic, with an initial burst release followed by sustained release up to 8?hours. In comparison to the plain drug gel, which had a tissue deposition of 11.23%, the NLC gel showed a much superior and desirable deposition of 26.41%. The lipophilic nature of the carrier, its size, and property of occlusion enabled greater amounts of drug to enter and be retained in the skin, simultaneously minimizing permeation through the skin, i.e. systemic exposure. The results of the study suggest that NLCs of anti-rosacea drugs have the potential to be used in the therapy of rosacea.     

Folate-mediated solid–liquid lipid nanoparticles for paclitaxel-coated poly(ethylene glycol)

Background: As a promising anticancer drug, severe side-effects of current clinical formulations for paclitaxel have restricted its use, developing a better technical-economical formulation for paclitaxel delivery is needed. Method: In this study, the compound of folate-poly(ethylene glycol) (PEG)-phosphatidylethanolamine was synthesized and characterized with Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. The solid-liquid lipid nanoparticle (SLLN) for paclitaxel modified with folate and poly(ethylene glycol) (folate-PEG-SLLN) was prepared and characterized. Morphology of folate-PEG-SLLN was examined by transmission electron microscopy. The particle size and zeta potential were performed by Zetapals. Encapsulation efficiency was analyzed by HPLC. The in vitro drug release of paclitaxel was investigated via membrane dialysis. The in vivo pharmacokinetics was measured with male Sprague-Dawley rats. Treatment efficiency was investigated with the mouse with sarcoma180 ascites tumor. Results: Paclitaxel loaded on the newly designed binary SLLN showed a longer and sustained in vitro releasing property. More importantly, S180 tumor-bearing mice treated with paclitaxel-loaded SLLN exhibited higher tumor inhibition rate, comparing with animals administered with paclitaxel injection alone (45.3% and 37.3%, respectively). Conclusion: The newly developed paclitaxel delivery system may have improved in vivo antitumor activity. The results demonstrated a great interest to use folate-mediated SLLN as a prospective drug delivery system for paclitaxel.     

Preparation and Evaluation of 2-(Allylthio)Pyrazine-Loaded Lipid Emulsion with Enhanced Stability and Liver Targeting

To develop 2-(allylthio)pyrazine (2-AP)-loaded lipid emulsion for parenteral administration, various lipid emulsions were prepared with soybean oil, lecithin, and other carriers using homogenization method, and their physical stabilities were investigated by measuring their droplet sizes. The pharmacokinetics and tissue distribution of 2-AP in lipid emulsion after intravenous administration to rats were evaluated compared with 2-AP in solution. 2-AP was lipophilic, sparingly water-soluble, and unstable in aqueous medium. The 2-AP-loaded lipid emulsion composed of 1% of 2-AP, 4% of soybean oil, 4% of lecithin, and 91% of water was physically and chemically stable for at least 8 weeks. It gave significantly faster clearance of 2-AP and higher affinity to the organs, especially the liver, compared with the 2-AP in solution, suggesting that it could selectively deliver 2-AP to the liver. Thus, the lipid emulsion with soybean oil and lecithin could be used as a potential dosage form with the liver-targeting property and enhanced stability of sparingly water-soluble 2-AP.     

Hereditary Prostate Cancer: Genes Related,Target Therapy and Prevention

Prostate cancer (PCa) is globally the second most diagnosed cancer type and the most common cause of cancer-related deaths in men. Family history of PCa, hereditary breast and ovarian cancer (HBOC) and Lynch syndromes (LS), are among the most important risk factors compared to age, race, ethnicity and environmental factors for PCa development. Hereditary prostate cancer (HPCa) has the highest heritability of any major cancer in men. The proportion of PCa attributable to hereditary factors has been estimated in the range of 5–15%. To date, the genes more consistently associated to HPCa susceptibility include mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2) and homologous recombination genes (BRCA1/2, ATM, PALB2, CHEK2). Additional genes are also recommended to be integrated into specific research, including HOXB13, BRP1 and NSB1. Importantly, BRCA1/BRCA2 and ATM mutated patients potentially benefit from Poly (ADP-ribose) polymerase PARP inhibitors, through a mechanism of synthetic lethality, causing selective tumor cell cytotoxicity in cell lines. Moreover, the detection of germline alterations in MMR genes has therapeutic implications, as it may help to predict immunotherapy benefits. Here, we discuss the current knowledge of the genetic basis for inherited predisposition to PCa, the potential target therapy, and the role of active surveillance as a management strategy for patients with low-risk PCa. Finally, the current PCa guideline recommendations are reviewed.