Antithrombin and Its Role in Host Defense and Inflammation

Antithrombin (AT) is a natural anticoagulant that interacts with activated proteases of the coagulation system and with heparan sulfate proteoglycans (HSPG) on the surface of cells. The protein, which is synthesized in the liver, is also essential to confer the effects of therapeutic heparin. However, AT levels drop in systemic inflammatory diseases. The reason for this decline is consumption by the coagulation system but also by immunological processes. Aside from the primarily known anticoagulant effects, AT elicits distinct anti-inflammatory signaling responses. It binds to structures of the glycocalyx (syndecan-4) and further modulates the inflammatory response of endothelial cells and leukocytes by interacting with surface receptors. Additionally, AT exerts direct antimicrobial effects: depending on AT glycosylation it can bind to and perforate bacterial cell walls. Peptide fragments derived from proteolytic degradation of AT exert antibacterial properties. Despite these promising characteristics, therapeutic supplementation in inflammatory conditions has not proven to be effective in randomized control trials. Nevertheless, new insights provided by subgroup analyses and retrospective trials suggest that a recommendation be made to identify the patient population that would benefit most from AT substitution. Recent experiment findings place the role of various AT isoforms in the spotlight. This review provides an overview of new insights into a supposedly well-known molecule.     

儿茶酚–(胺)表面化学介导的一氧化氮催化释放涂层研究

目的 在316L不锈钢(SS)表面构建原位一氧化氮(NO)催化释放涂层,使其能特异选择性地抗凝血、抑制平滑肌细胞(SMCs)增生,从而促进内皮细胞(ECs)生长。方法 在弱碱性水溶液中,选用多巴胺(DA)和己二胺(HD)为前驱体,利用多巴胺邻二苯酚结构自聚合沉膜的能力、多巴胺与己二胺的酚–(胺)表面化学,通过简单的一锅法在316L SS表面构建富氨基粘附涂层DA/HD。再通过碳二亚胺化学交联反应,共价接枝螯合Cu²⁺的1,4,7,10–四氮杂环十二烷–1,4,7,10–四羧酸(DOTA),最后获得均匀且稳定的NO催化释放涂层(命名为Cu-DOTA@DA/HD)。结果 DA/HD涂层表面的氨基密度高达22 nmol/cm²,实现了Cu-DOTA的有效固定,其NO催化释放速率可达5.2×10^–10 mol/(cm²·min)。Cu-DOTA@DA/HD涂层显著地抑制了血小板的粘附和激活,也能有效抑制血栓的形成,其表面血栓总质量由316L SS的(40.3±10.3) mg降低至(3.0±0.4) mg。...     

Importance of Kupffer Cells in the Development of Acute Liver Injuries in Mice

Kupffer cells reside within the liver sinusoid and serve as gatekeepers. They produce pro- and anti-inflammatory cytokines and other biologically important molecules upon the engagement of pattern recognition receptors such as Toll-like receptors. Kupffer cell-ablated mice established by in vivo treatment with clodronate liposomes have revealed many important features of Kupffer cells. In this paper, we review the importance of Kupffer cells in murine acute liver injuries and focus on the following two models: lipopolysaccharide (LPS)-induced liver injury, which is induced by priming with Propionibacterium acnes and subsequent challenge with LPS, and hypercoagulability-mediated acute liver failure such as that in concanavalin A (Con A)-induced hepatitis. Kupffer cells are required for LPS sensitization induced by P. acnes and are a major cellular source of interleukin-18, which induces acute liver injury following LPS challenge. Kupffer cells contribute to Con A-induced acute liver failure by initiating pathogenic, intrasinusoidal thrombosis in collaboration with sinusoidal endothelial cells. The mechanisms underlying these models may shed light on human liver injuries induced by various etiologies such as viral infection and/or abnormal metabolism.     

The Effects of Marine Carbohydrates and Glycosylated Compounds on Human Health

Marine organisms have been recognized as a valuable source of bioactive compounds with industrial and nutraceutical potential. Recently, marine-derived carbohydrates, including polysaccharides and low molecular weight glycosylated oligosaccharides, have attracted much attention because of their numerous health benefits. Moreover, several studies have reported that marine carbohydrates exhibit various biological activities, including antioxidant, anti-infection, anticoagulant, anti-inflammatory, and anti-diabetic effects. The present review discusses the potential industrial applications of bioactive marine carbohydrates for health maintenance and disease prevention. Furthermore, the use of marine carbohydrates in food, cosmetics, agriculture, and environmental protection is discussed.     

池沼公鱼抗凝血作用的试验研究

研究池沼公鱼提取物的抗凝血作用。采用体外试验观察池沼公鱼提取物对家兔离体血浆复钙时间的影响,体内试验采用断尾法测定小鼠出血时间、毛细玻管法测定小鼠凝血时间。结果表明,池沼公鱼提取物能明显延长小鼠的出血、凝血时间及家兔离体血浆复钙时间,说明池沼公鱼提取物具有抗凝血作用。     

抗凝冻酸奶的研制

为了改变酸奶货架期短,不易长期保藏,而影响酸奶的销售和发展的现状,采用不同工艺和添加食品抗凝冻剂,降低酸奶的冰点,加工出可以在0℃以下保藏的抗凝冻酸奶,而且不会影响风味、酸度和质地。试验结果表明,抗凝冻酸奶的最佳条件为:加糖量6%,接种量3.0%,发酵时间4.5h,复合抗冻剂加入量0.6%。     

岩藻聚糖硫酸酯的硫酸化修饰对其生物活性的影响

岩藻聚糖硫酸酯是一种硫酸化多糖,因其具有多种生物活性而得到广泛的研究,有研究表明岩藻聚糖硫酸酯的生物活性与其硫酸基团含量与位置息息相关。因此,对岩藻聚糖硫酸酯进行硫酸化修饰将有利于提高其生物活性。简述了硫酸基团对岩藻聚糖硫酸酯活性的影响以及岩藻聚糖硫酸酯的硫酸化方法,介绍了硫酸化修饰后的岩藻聚糖硫酸酯生物活性的变化,以期为岩藻聚糖硫酸酯硫酸化修饰的应用与发展提供理论参考。     

虾头类肝素的制备、理化性质及抗凝血活性评价

本研究以虾头为原料,通过酶解、阴离子交换树脂、醇沉的方法提取并分离纯化了虾头中的类肝素;采用乙酸纤维素薄膜电泳初步鉴定了纯化后类肝素的种类,通过紫外吸收光谱、高效凝胶渗透色谱分析其纯度和分子质量,通过傅里叶变换红外光谱分析其官能团结构,采用柱前衍生化高效液相色谱分析其单糖组成;并通过体外凝血实验研究了其抗凝血活性。结果表明：组分F1.1和F1.5的类肝素质量分数均达83%,纯度较高,分子质量分别为7.8、19.8 kDa;F1.1的电泳迁移率与硫酸软骨素相似,F1.5接近肝素标准品的迁移速率;F1.1和F1.5均具有羧基、乙酰氨基、硫酸基团等吸收峰;单糖组成为不同比例的葡萄糖醛酸、艾杜糖醛酸、N-乙酰半乳糖胺、半乳糖和岩藻糖;F1.1和F1.5通过内源凝血途径和共同凝血途径发挥抗凝血作用,其中F1.5的抗凝血活性优于F1.1,可以作为潜在的抗凝血治疗剂。     

黄花倒水莲总皂苷抗凝血和抗血栓作用及机制：基于网络药理学

目的：研究黄花倒水莲总皂苷（total saponin of Polygala fallax Hemsl,PTS）的抗凝血、抗血栓作用及机制。方法：网络药理学方法筛选分析预测出PTS可能作用的靶点及通路。利用FeCl3诱导大鼠颈总动脉血栓模型,通过染色切片结果来验证PTS的抗凝血、抗血栓作用。测定PTS对活化部分凝血活酶时间（activated partial thromboplastin time,APTT）、凝血酶时间（thrombin time,TT）、凝血酶原时间（prothrombin time,PT）的影响及凝血因子II（coagulation factor II,FII）a和辅因子X（cofactor X,FX）a活性的影响,初步确定其抗凝血作用机制。结果：PTS中皂苷A质量分数为1.673%。经网络药理学预测PTS的抗凝血作用靶点为FII和血小板活化因子受体（platelet activating factor receptor,PTAFR）。体内动物实验结果表明,血栓通胶囊组和高剂量PTS组的血栓形成抑制率分别为39.7%和47.4%,血栓面积率分别为50.69%和43.51%。体外实验结果表明,在0～2 mg/mL范围内,PTS延长人质控血浆APTT、TT所需质量浓度分别为0.36 mg/mL和0.14 mg/mL,FIIa和FΧa活力检测实验结果表明,PTS对FΧa的活力无影响,可剂量依赖性地抑制FIIa活力,其半数抑制质量浓度（half-maximal inhibitory concentration,IC50）为（85.88±12.50）μg/mL。结论：体内外实验证明,PTS具有抗血栓和抗凝血作用,抗凝血作用机制之一为抑制内源性凝血途径上FIIa的活性。