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.     

低压静电场辅助冷冻对竹笋品质的影响

为研究低压静电场辅助冷冻对竹笋冻结特性的影响，以冻结曲线、硬度、水分损失率、水分迁移、冰晶形态和组织微观结构为指标，探究低压静电场辅助冷冻（－35 ℃）和普通冷冻（－35 ℃）条件下竹笋品质的变化规律。结果表明：低压静电场辅助冷冻提高了冻结效率，改变了冰晶形态及分布，减轻了组织微观结构破损程度，改善了解冻汁液流失情况。与静电板间距10、20、30、40 cm处的冷冻竹笋解冻后水分损失率分别为14.16%、12.58%、9.73%、10.44%，显著低于对照组（21.01%）（P＜0.05），硬度分别为461.19、507.48、496.65 g和455.31 g，显著高于对照组（350.70 g）（P＜0.05）。低场核磁共振分析结果表明，在低压静电场辅助冷冻下竹笋解冻后汁液流失减少，扫描电子显微镜观察结果显示，竹笋纤维排列整齐，组织微观结构保持较好。低压静电场辅助冷冻可有效改善竹笋品质，可为利用低压静电场进行果蔬的冷冻贮藏和冷链运输提供参考。     

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。     

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。     

Role of the HSP70 Co-Chaperone SIL1 in Health and Disease

Cell surface and secreted proteins provide essential functions for multicellular life. They enter the endoplasmic reticulum (ER) lumen co-translationally, where they mature and fold into their complex three-dimensional structures. The ER is populated with a host of molecular chaperones, associated co-factors, and enzymes that assist and stabilize folded states. Together, they ensure that nascent proteins mature properly or, if this process fails, target them for degradation. BiP, the ER HSP70 chaperone, interacts with unfolded client proteins in a nucleotide-dependent manner, which is tightly regulated by eight DnaJ-type proteins and two nucleotide exchange factors (NEFs), SIL1 and GRP170. Loss of SIL1′s function is the leading cause of Marinesco-Sjögren syndrome (MSS), an autosomal recessive, multisystem disorder. The development of animal models has provided insights into SIL1′s functions and MSS-associated pathologies. This review provides an in-depth update on the current understanding of the molecular mechanisms underlying SIL1′s NEF activity and its role in maintaining ER homeostasis and normal physiology. A precise understanding of the underlying molecular mechanisms associated with the loss of SIL1 may allow for the development of new pharmacological approaches to treat MSS.