乳酸链球菌素脂质体的研究

乳酸链球菌素是一种具有良好防腐效果的天然生物保鲜剂,但其易被水解并与食品基质发生反应,不太稳定等问题降低了其保鲜效果,而利用脂质体包埋技术可有效地解决乳酸链球菌素使用中存在的问题,本文将对乳酸链球菌素脂质体的特点及其制备的影响因素进行阐述。     

共递送姜黄素和EGCG脂质体的构建及其对神经炎症的作用

为克服姜黄素和表没食子儿茶素没食子酸酯(EGCG)两种生物活性成分在稳定性和代谢动力学方面的局限性,进一步发挥其协同抗氧化和抗炎作用,采用薄膜超声法构建共递送姜黄素和EGCG的脂质体。以粒径、PDI和电位为评价指标,分析磷脂与胆固醇质量比、磷脂与吐温80质量比、水合时间及超声时间对脂质体的影响,并通过静电吸附作用对脂质体进行乳铁蛋白和透明质酸修饰。使用脂多糖构建BV2小胶质细胞炎症模型,探讨乳铁蛋白和透明质酸修饰的共递送姜黄素和EGCG的脂质体对神经炎症的改善作用。在磷脂与胆固醇质量比为10∶1,磷脂和吐温80质量比为10∶3,水合时间40min,以及超声时间15min时,成功制备了呈均匀球形、平均粒径为(131.53±0.258)nm的共递送姜黄素和EGCG的脂质体,在乳铁蛋白体积为0.3mL,透明质酸体积为0.5mL时对脂质体进行修饰。实验结果显示,乳铁蛋白和透明质酸修饰的共递送姜黄素和EGCG的脂质体显著提高了姜黄素和EGCG的稳定性和抗氧化特性,抑制了脂多糖诱导的细胞形态的改变,恢复线粒体功能障碍,降低细胞内活性氧的产生,改善了脂多糖诱导的BV2小胶质细胞的炎症作用。研究结果旨在为进一步开发具有神经保护作用的功能食品提供新的思路。     

Controlled Liposome Delivery from Chitosan-Based Thermosensitive Hydrogel for Regenerative Medicine

This work describes the development of an injectable nanocomposite system based on a chitosan thermosensitive hydrogel combined with liposomes for regenerative medicine applications. Liposomes with good physicochemical properties are prepared and embedded within the chitosan network. The resulting nanocomposite hydrogel is able to provide a controlled release of the content from liposomes, which are able to interact with cells and be internalized. The cellular uptake is enhanced by the presence of a chitosan coating, and cells incubated with liposomes embedded within thermosensitive hydrogels displayed a higher cell uptake compared to cells incubated with liposomes alone. Furthermore, the gelation temperature of the system resulted to be equal to 32.6 °C; thus, the system can be easily injected in the target site to form a hydrogel at physiological temperature. Given the peculiar performance of the selected systems, the resulting thermosensitive hydrogels are a versatile platform and display potential applications as controlled delivery systems of liposomes for tissue regeneration.     

Cysteine 467 of the ASCT2 Amino Acid Transporter Is a Molecular Determinant of the Antiport Mechanism

The plasma membrane transporter ASCT2 is a well-known Na⁺-dependent obligatory antiporter of neutral amino acids. The crucial role of the residue C467 in the recognition and binding of the ASCT2 substrate glutamine, has been highlighted by structure/function relationship studies. The reconstitution in proteoliposomes of the human ASCT2 produced in P. pastoris is here employed to unveil another role of the C467 residue in the transport reaction. Indeed, the site-directed mutant C467A displayed a novel property of the transporter, i.e., the ability of mediating a low but measurable unidirectional transport of [³H]-glutamine. This reaction conforms to the main features of the ASCT2-mediated transport, namely the Na⁺-dependence, the pH dependence, the stimulation by cholesterol included in the proteoliposome membrane, and the specific inhibition by other common substrates of the reconstituted human ASCT2. Interestingly, the WT protein cannot catalyze the unidirectional transport of [³H]-glutamine, demonstrating an unspecific phenomenon. This difference is in favor of a structural conformational change between a WT and C467A mutant that triggers the appearance of the unidirectional flux; this feature has been investigated by comparing the available 3D structures in two different conformations, and two homology models built on the basis of hEAAT1 and GLT_Ph.     

DHA脂质体对脂代谢的改善作用

为了探究DHA脂质体对脂代谢的调节作用.首先利用游离脂肪酸诱导HepG2细胞,DHA脂质体干预后检测甘油三酯(TG),胆固醇(TC)含量,RT-PCR检测脂肪酸合成酶(FAS),固醇调节元件结合蛋白1(SREBP-1)的mRNA表达.其次将雄性C57BL/6J小鼠(6周龄)随机分为对照组(C)、模型组(M)、DHA脂乳...     

Clinically Translatable Transcrocetin Delivery Platform for Correction of Tumor Hypoxia and Enhancement of Radiation Therapy Effects

Improving the tumor reoxygenation to sensitize the tumor to radiation therapy is a cornerstone in radiation oncology. Here, the pre-clinical development of a clinically transferable liposomal formulation encapsulating trans sodium crocetinate (NP TSC) is reported to improve oxygen diffusion through the tumor environment. Early pharmacokinetic analysis of the clinical trial of this molecule performed on 37 patients orient to define the optimal fixed dosage to use in a triple-negative breast cancer model to validate the therapeutic combination of radiation therapy and NP TSC. Notably, it is reported that this formulation is non-toxic in both humans and mice at the defined fixed concentration, provides a normalization of the tumor vasculature within 72 h window after systemic injection, leads to a transient increase (50% improvement) in the tumor oxygenation, and significantly improves the efficacy of both mono-fractionated and fractionated radiation therapy treatment. Together, these findings support the introduction of a first-in-class therapeutic construct capable of tumor-specific reoxygenation without associated toxicities.