Neoagarooligosaccharide Protects against Hepatic Fibrosis via Inhibition of TGF-β/Smad Signaling Pathway

Hepatic fibrosis occurs when liver tissue becomes scarred from repetitive liver injury and inflammatory responses; it can progress to cirrhosis and eventually to hepatocellular carcinoma. Previously, we reported that neoagarooligosaccharides (NAOs), produced by the hydrolysis of agar by β-agarases, have hepatoprotective effects against acetaminophen overdose-induced acute liver injury. However, the effect of NAOs on chronic liver injury, including hepatic fibrosis, has not yet been elucidated. Therefore, we examined whether NAOs protect against fibrogenesis in vitro and in vivo. NAOs ameliorated PAI-1, α-SMA, CTGF and fibronectin protein expression and decreased mRNA levels of fibrogenic genes in TGF-β-treated LX-2 cells. Furthermore, downstream of TGF-β, the Smad signaling pathway was inhibited by NAOs in LX-2 cells. Treatment with NAOs diminished the severity of hepatic injury, as evidenced by reduction in serum alanine aminotransferase and aspartate aminotransferase levels, in carbon tetrachloride (CCl₄)-induced liver fibrosis mouse models. Moreover, NAOs markedly blocked histopathological changes and collagen accumulation, as shown by H&E and Sirius red staining, respectively. Finally, NAOs antagonized the CCl₄-induced upregulation of the protein and mRNA levels of fibrogenic genes in the liver. In conclusion, our findings suggest that NAOs may be a promising candidate for the prevention and treatment of chronic liver injury via inhibition of the TGF-β/Smad signaling pathway.     

纳米药物非临床药代动力学的研究策略及关注要点

随着纳米技术的迅速发展，纳米药物的研发已成为目前药物创新的发展方向之一。纳米药物具有基于纳米结构的尺度效应，其药代动力学特征与普通药物相比存在明显差异，其药代动力学研究与普通药物相比也有其特殊性。本文着重探讨纳米药物的非临床药代动力学的研究策略及关注要点，包括受试物、体内/外试验、生物样本分析、数据评价分析等，期望为研发者提供参考。     

基于滚动摩擦作用下玉米颗粒在模拟筒仓卸料中的力链分析（网络首发、推荐阅读）

针对颗粒滚动摩擦作用对筒仓中玉米颗粒的力链空间分布进行研究，通过EDEM离散元软件建立筒仓模型与仿真玉米颗粒模型进行卸粮仿真模拟，并与筒仓卸料实验作流态对比，验证模型与仿真结果的准确性。通过对模拟仓进行切片观察和数据处理，对比分析了不同摩擦情况下力链的细观参数随时间演化规律。模拟结果表明：颗粒间摩擦系数越大，卸粮完成的最终时间越长；颗粒间滚动摩擦系数越小，颗粒由整体流转变为管状流的时间越早。对于有漏斗的筒仓来说，减小颗粒间摩擦会改变整体流和管状流之间的极限，从而增加产生管状流的面积。标准滚动摩擦系数下玉米颗粒在卸料过程中会出现起拱-塌陷效应；减小滚动摩擦，玉米颗粒卸料较稳定，未出现起拱的应力突增、以及拱塌陷的应力衰减；增大颗粒间滚动摩擦不但会增加拱效应，且出现成拱高度距离漏斗口更高。     

Combinations of Piperine with Hydroxypropyl-β-Cyclodextrin as a Multifunctional System

Piperine is an alkaloid that has extensive pharmacological activity and impacts other active substances bioavailability due to inhibition of CYP450 enzymes, stimulation of amino acid transporters and P-glycoprotein inhibition. Low solubility and the associated low bioavailability of piperine limit its potential. The combination of piperine with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) causes a significant increase in its solubility and, consequently, an increase in permeability through gastrointestinal tract membranes and the blood–brain barrier. X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR) were used to characterize interactions between piperine and HP-β-CD. The observed physicochemical changes should be combined with the process of piperine and CD system formation. Importantly, with an increase in solubility and permeability of piperine as a result of interaction with CD, it was proven to maintain its biological activity concerning the antioxidant potential (2,2-diphenyl-1-picryl-hydrazyl-hydrate assay), inhibition of enzymes essential for the inflammatory process and for neurodegenerative changes (hyaluronidase, acetylcholinesterase, butyrylcholinesterase).     

金针菇多糖对微冻大黄鱼及其鱼片品质变化的影响

为研究金针菇多糖（polysaccharide from Flammulina velutipes，FVP）对微冻大黄鱼及鱼片在贮藏期间肌原纤维蛋白性质的变化及水分分布的影响，实验分别选用0.03、0.06、0.09 g/L FVP浸渍处理大黄鱼和鱼片，以无菌水处理为对照组，分析微冻贮藏期间样品的感官指标得分、总挥发性盐基氮含量、总巯基含量、Ca2＋-ATPase活性、蛋白流变学性质以及水分迁移变化规律。结果表明：FVP可有效抑制整鱼总挥发性盐基氮含量上升和感官得分的下降；减缓整鱼及鱼片在微冻过程中总巯基含量、Ca2＋-ATPase活性下降和水分流失；此外FVP还能够延缓大黄鱼因腐败而出现的蛋白凝胶能力减弱。在本实验选取的多糖浓度范围内，0.09 g/L FVP处理组保鲜效果较强。该研究结果可为FVP用于水产品贮运保鲜提供理论参考。