槐角黄酮栓抗炎、止血、抗溃疡作用的实验研究

目的:研究槐角黄酮栓的抗炎、止血、抗溃疡作用。方法:从中药槐角中提取总黄酮,与脂肪酸甘油酯混合后用热融法制成栓剂。采用小鼠耳廓肿胀法、滤纸肉芽肿法、腹腔毛细血管通透性试验和角叉菜胶致大鼠足跖肿胀法观察槐角黄酮栓的抗炎作用;通过玻璃毛细管法和断尾法测定小鼠出、凝血时间,评价槐角黄酮栓的止血效果。复制大鼠直肠损伤模型,直肠给药治疗,观察伤口愈合情况并HE染色,评价槐角黄酮栓的促愈合作用。结果:槐角黄酮栓具有明显的抗炎、抗溃疡作用,并能缩短小鼠出、凝血时间,提高直肠创面愈合率。结论:槐角黄酮栓制备工艺简单,具有较好的抗炎、止血、抗溃疡作用。     

苦剌总生物碱抗溃疡成分探讨

本实验发现苦刺总生物碱中的新成分13a-羟苦参碱(13a-hydroxymatrjne)具有对抗水浸应激性小鼠溃疡和吲哚美辛加乙醇所致小鼠溃疡,但对盐酸性大鼠溃疡和结扎门性大鼠溃疡形成无对抗作用。又发现去槐果碱后的苦刺总生物碱具有比13a-羟苦参碱更强的抗溃疡活性。     

多糖生物活性研究进展

多糖是单糖通过糖苷键连接而成的聚合物,具有广泛的生物活性。结合本实验室多年的实验研究,综述了近年来国内外多糖类成分在免疫调节、抗肿瘤、心脑血管系统疾病、抗病毒、抗氧化、抗炎、抗辐射等方面的生物活性研究状况。     

食用菌活性成分抗肿瘤作用的研究进展

食用菌因药食两用的特点被广泛研究,具有提升机体免疫,阻止和防御疾病的功能作用。不同食用菌中所含的生物活性组分不同,主要有:多糖类、蛋白类、萜类、生物碱类等,这些组分具有抗氧化、抗肿瘤、免疫调节、抗炎症反应、抗心血管疾病、抗细菌、抗辐射及抗糖尿病等功效,其中抗肿瘤作用研究居多,研究发现其分子作用机制主要通过调控细胞信号通路中相关因子表达水平抑制肿瘤细胞增殖,诱导细胞凋亡的,这为开发天然无毒性肿瘤药物制剂奠定了理论基础。针对食用菌不同生物活性组分抗肿瘤分子机制的最新研究进展展开简要综述。     

苦刺总生物碱和槐果碱的抗溃疡作用

实验发现苦刺总生物碱具有对抗水浸应激性小鼠溃疡,吲哚美辛加乙醇所致小鼠溃疡、盐酸性大鼠溃疡和结扎大鼠幽门性溃疡形成作用。但其成分之一的槐果碱仅能对抗前两种模型的溃疡形成。     

天门冬属植物的生物活性

天门冬属植物在我国民间作为常用中药历史悠久,国内外已报道该属植物具有抗肿瘤、抗氧化、抗菌、免疫促进、抗炎症、抗溃疡、抗腹泻、抗糖尿病、降血脂和止咳镇痛等诸多生物活性。此外,该属植物中存在一些强药效的单体化合物,且具有显著构效关系。天门冬属植物的生物活性研究为开发我国丰富的本属植物资源奠定了基础。     

白桦脂酸的研究进展

白桦脂酸是一种五环三萜酸,存在于多种天然植物,特别是白桦树皮中,毒性低,安全指数高。近年来发现白桦脂酸具有抗肿瘤、抗HIV、抗炎、抗菌、抗疟疾等多种生物活性,特别是在抗黑色素瘤与抗HIV方面具有突出的表现,从而引起了人们极大的研究兴趣。对白桦脂酸的来源和生物活性进行了简要综述。     

溃疡分枝杆菌、溃疡分枝杆菌素与溃疡分枝杆菌毒素

1948年,MacCALLUM在澳大利亚东南沿海维多利亚一个儿童的腿部溃疡中分离到一种新的分枝杆菌,并称之为溃疡分枝杆菌（Mycobacterium ulcerans）,并证明是这种溃疡的病原菌。这种由溃疡分枝杆菌引起的皮肤感染主要存在于热带、亚热带地区,尤以西非地区更盛,具有地方性流行,现在通常称谓Bumli溃疡,中国也有发现,世界卫生组织（WHO）已组建全球Buruli溃疡行动委员会,开展对该病的防治研究,现已认为溃疡分枝杆菌感染（Bundi溃疡）是一种新发的感染病。     

人参抗疲劳作用研究进展

人参是古今著名的滋补强壮良药,药理研究、临床观察和流行病学调查,结果均证实人参具有多种生物活性。本文着重从人参抗中枢疲劳、抗自由基、调节糖代谢和乳酸代谢,以及对血红蛋白含量的影响等方面进行综述。     

具有生物活性的天然三萜化合物的研究进展

三萜类化合物是广泛存在于自然界的一类有机化合物,其中很多具有一定的生物活性。该文着重综述了近五年来具有抗炎、抗菌、抗肿瘤生物活性的天然游离三萜化合物的研究进展。     

Bioactivity and structural properties of chimeric analogs of the starfish SALMFamide neuropeptides S1 and S2

The starfish SALMFamide neuropeptides S1 (GFNSALMFamide) and S2 (SGPYSFNSGLTFamide) are the prototypical members of a family of neuropeptides that act as muscle relaxants in echinoderms. Comparison of the bioactivity of S1 and S2 as muscle relaxants has revealed that S2 is ten times more potent than S1. Here we investigated a structural basis for this difference in potency by comparing the bioactivity and solution conformations (using NMR and CD spectroscopy) of S1 and S2 with three chimeric analogs of these peptides. A peptide comprising S1 with the addition of S2's N-terminal tetrapeptide (Long S1 or LS1; SGPYGFNSALMFamide) was not significantly different to S1 in its bioactivity and did not exhibit concentration-dependent structuring seen with S2. An analog of S1 with its penultimate residue substituted from S2 (S1(T); GFNSALTFamide) exhibited S1-like bioactivity and structure. However, an analog of S2 with its penultimate residue substituted from S1 (S2(M); SGPYSFNSGLMFamide) exhibited loss of S2-type bioactivity and structural properties. Collectively, our data indicate that the C-terminal regions of S1 and S2 are the key determinants of their differing bioactivity. However, the N-terminal region of S2 may influence its bioactivity by conferring structural stability in solution. Thus, analysis of chimeric SALMFamides has revealed how neuropeptide bioactivity is determined by a complex interplay of sequence and conformation.     

Bone resorption and circulating PTH-like bioactivity in an animal model of hypercalcaemia of malignancy

An in vivo model of humoral hypercalcaemia of malignancy has been used to examine the role of circulating PTH-like bioactivity in the development of bone resorption and hypercalcaemia. After inoculation of cells from a renal carcinoma cell line into nude mice, circulating PTH-like bioactivity as measured by the sensitive renal and metatarsal cytochemical bioassays for PTH was elevated in only 18% and 53% of the mice respectively. Bone resorption was elevated in all the mice investigated irrespective of the level of PTH-like bioactivity. Thus, in this model, while the circulating PTH-like moiety is more potent when acting on bone, it did not correlate with the degree of bone resorption suggesting that it may not be the sole cause of the hypercalcaemia.     

Natural form of noncytolytic flexible human Fc as a long-acting carrier of agonistic ligand, erythropoietin

Human IgG1 Fc has been widely used as a bioconjugate, but exhibits shortcomings, such as antibody- and complement-mediated cytotoxicity as well as decreased bioactivity, when applied to agonistic proteins. Here, we constructed a nonimmunogenic, noncytolytic and flexible hybrid Fc (hyFc) consisting of IgD and IgG4, and tested its function using erythropoietin (EPO) conjugate, EPO-hyFc. Despite low amino acid homology (20.5%) between IgD Fc and IgG4 Fc, EPO-hyFc retained "Y-shaped" structure and repeated intravenous administrations of EPO-hyFc into monkeys did not generate EPO-hyFc-specific antibody responses. Furthermore, EPO-hyFc could not bind to FcγR I and C1q in contrast to EPO-IgG1 Fc. In addition, EPO-hyFc exhibited better in vitro bioactivity and in vivo bioactivity in rats than EPO-IgG1 Fc, presumably due to the high flexibility of IgD. Moreover, the mean serum half-life of EPO-hyFc(H), a high sialic acid content form of EPO-hyFc, was approximately 2-fold longer than that of the heavily glycosylated EPO, darbepoetin alfa, in rats. More importantly, subcutaneous injection of EPO-hyFc(H) not only induced a significantly greater elevation of serum hemoglobin levels than darbepoetin alfa in both normal rats and cisplatin-induced anemic rats, but also displayed a delayed time to maximal serum level and twice final area-under-the-curve (AUC(last)). Taken together, hyFc might be a more attractive Fc conjugate for agonistic proteins/peptides than IgG1 Fc due to its capability to elongate their half-lives without inducing host effector functions and hindering bioactivity of fused molecules. Additionally, a head-to-head comparison demonstrated that hyFc-fusion strategy more effectively improved the in vivo bioactivity of EPO than the hyperglycosylation approach.     

A Colloidal Singularity Reveals the Crucial Role of Colloidal Stability for Nanomaterials In-Vitro Toxicity Testing: nZVI-Microalgae Colloidal System as a Case Study

Aggregation raises attention in Nanotoxicology due to its methodological implications. Aggregation is a physical symptom of a more general physicochemical condition of colloidal particles, namely, colloidal stability. Colloidal stability is a global indicator of the tendency of a system to reduce its net surface energy, which may be achieved by homo-aggregation or hetero-aggregation, including location at bio-interfaces. However, the role of colloidal stability as a driver of ENM bioactivity has received little consideration thus far. In the present work, which focuses on the toxicity of nanoscaled Fe° nanoparticles (nZVI) towards a model microalga, we demonstrate that colloidal stability is a fundamental driver of ENM bioactivity, comprehensively accounting for otherwise inexplicable differential biological effects. The present work throws light on basic aspects of Nanotoxicology, and reveals a key factor which may reconcile contradictory results on the influence of aggregation in bioactivity of ENMs.     

Free-radical-mediated protein inactivation and recovery during protein photoencapsulation

Photoencapsulation of protein therapeutics is very attractive for preparing biomolecule-loaded hydrogels for a variety of biomedical applications. However, detrimental effects of highly active radical species generated during photoencapsulation must be carefully evaluated to maintain efficient hydrogel cross-linking while preserving the structure and bioactivity of encapsulated biomolecules. Here, we examine the free-radical-mediated inactivation and incomplete release of proteins from photocurable hydrogels utilizing lysozyme as a conservative model system. Various protein photoencapsulation conditions were tested to determine the factors affecting lysozyme structural integrity and bioactivity. It was found that a portion of the lysozyme becomes conjugated to polymer chains at high photoinitiator concentrations and long polymerization times. We also found that the more hydrophilic photoinitiator Irgacure-2959 (I-2959, 2-hydroxy-1-[4-(hydroxyethoxy)phenyl]-2-methyl-1-propanone) causes more damage to lysozyme compared to the hydrophobic photoinitiator Irgacure-651 (I-651, 2,2-dimethoxy-2-phenylacetophenone), even though I-2959 has been previously shown to be more cytocompatible. Furthermore, while nonacrylated PEG provides only limited protection from the denaturing free radicals that are present during hydrogel curing, acrylated PEG macromers effectively preserve lysozyme structural integrity and bioactivity in the presence of either photoinitiator. Overall, these findings indicate how photopolymerization conditions (e.g., photoinitiator type and concentration, UV exposure time, etc.) must be optimized to obtain a functional hydrogel device that can preserve protein bioactivity and provide maximal protein release.     

静电纺丝纳米纤维体外释放与蛋白活性的研究

目的:通过选择不同的模型蛋白,探讨准确的研究静电纺丝纳米纤维支架的体外释放和快速的测定蛋白活性的方法.方法:通过O/W乳液法静电纺丝制备纳米纤维,并用扫描电镜对纳米纤维表面进行了表征.以GM-CSF为模型蛋白,采用ELISA双抗体夹心法考察纤维的体外释放行为;以BSA为模型蛋白,用SEC-H-PLC比较纤维制备前后蛋白的聚集情况;以β-半乳糖苷酶为模型蛋白,用ONPG法比较纤维制备前后酶的催化活性.结果:纤维表面平滑,直径均一,呈现互相连通的三维网状结构.纤维在5天内释放90％以上;纤维中回收的BSA单体比例为66.53％;β-半乳糖苷酶在纤维中的催化活性保持原活性的3.37％.结论:通过选择不同的模型蛋白,能够准确的测定静电纺丝纤维的体外释放,快速的考察纤维中的蛋白活性,对于更好的研究蛋白药物纳米纤维支架具有重要的参考价值.     

Structure-activity relationships of synthetic progestins in a yeast-based in vitro androgen bioassay

The recent identification of tetrahydrogestrinone (THG), a non-marketed designer androgen used for sports doping but previously undetectable by established mass spectrometry-based urine drug screens, and its production by a facile chemical modification of gestrinone has raised concerns about the risks of developing designer androgens from numerous marketed progestins. We therefore have used yeast-based in vitro androgen and progesterone bioassays to conduct a structure-activity study assessing the intrinsic androgenic potential of commercially available progestins and their derivatives, to identify those compounds or structures with the highest risk of forming a basis for such misapplication. Progestins had a wide range of androgenic bioactivity that was not reliably predicted for individual steroids by their progestin bioactivity. 17alpha-Hydroxyprogesterone and 19-norprogesterone derivatives with their bulky 17beta-substituents were strong progestins but generally weak androgens. 17alpha-Ethynylated derivatives of testosterone, 19-nortestosterone and 18-methyl-19-nortestosterone such as gestrinone, ethisterone, norethisterone and norgestrel had the most significant intrinsic androgenicity of all the commercially marketed progestins. Facile chemical modification of the 17alpha-ethynyl group of each of these progestins produces 17alpha-methyl, ethyl and allyl derivatives, including THG and norbolethone, which further enhanced androgenic bioactivity. Thus by using the rapid and sensitive yeast bioassay we have screened a comprehensive set of progestins and associated structures and identified the ethynylated testosterone, 19-nortestosterone and 18-methyl-19-nortestosterone derivatives as possessing the highest risk for abuse and potential for conversion to still more potent androgens. By contrast, modern progestins such as progesterone, 17alpha-hydroxyprogesterone and 19-norprogesterone derivatives had minimal androgenic bioactivity and pose low risk.     

荔枝的活性功能及主要功能物质研究进展

荔枝是药食兼用水果,传统中医和民间一直用其滋补身体,是广东省最主要的经济作物水果,对其农业和经济发展具有重要作用。但长期以来其物质基础和作用机制不清楚,且国内荔枝发展绝大部分还限于粗放的农产品加工,对其附加价值认识不充分,严重限制了荔枝产品的开发和产业的升级。近年来国内外对荔枝的活性功能及主要功能物质研究较为活跃。本文从荔枝果皮、果核、果肉、花方面综述了荔枝的抗氧化、抗辐射和保护肝脏等主要活性,并对其酚类等主要活性物质的提取分离方法及其组成、化学结构和含量等进行了全面梳理归纳,旨在为荔枝功能食品及副产品的精深加工提供依据。     

倍半萜类化合物生理活性研究进展

倍半萜是一类由１５个碳组成骨架的萜类化合物,在自然办是分布广泛;骨架结构不同,生理活性也多种多样。本文综述了倍半萜类化合物及其衍生物的一些生理活性研究进展,如抗肿瘤、抗菌、抗病毒、抗疟、对肝脏、血脂等方面的状况。     

白细胞介素－2第17和20位残基在结构功能中的重要性研究

用基因定位突变法,将白细胞介素－２（ＩＬ－２）分子中１７Ｌｅｕ和２０Ａｓｐ进行一系列突变,并测定各突变体生物活性与空间结构的变化。分析结果表明１７Ｌｅｕ突变为Ａｓｐ时,ＩＬ－２的空间结构无明显变化。生物活性却显著下降;２０Ａｓｐ突变为Ｌｅｕ,以及１７Ｌｅｕ与２０Ａｓｐ对调后,均导致ＩＬ－２的空间结构发生变化,并严重影响其生物活性。上述结果说明１７Ｌｅｕ突变为Ａｓｐ后对活性的影响并非由空间结构变化所引起,而与残基本身性质有关：１７Ｌｅｕ与２０Ａｓｐ这两个重要的残基,必须位于各自特定的空间位置,才能发挥其生物作用。