Effect of tetramethylpyrazine on paw MMP-13 protein expression and serum VEGF,IL-17 and IL-23 levels in rats with collagen-induced arthritis

AIM：To investigate the mechanism of tetramethylpyrazine (TMP) in treating collagen-induced arthritis (CIA) in rats. METHODS：The rat model of type II collagen-induced arthritis was established and the rats were randomly divided into normal control group, CIA group and TMP treatment group. The protein expression of matrix metalloproteinase 13 (MMP-13) in paw tissues was detected by immunohistochemical staining and Western blotting. The histopathological changes of the skin in the rat paws were observed with HE staining. The levels of vascular endothelial growth factor (VEGF), interleukin 17 (IL-17) and interleukin 23 (IL-23) in the serum of CIA rats were detected by ELISA. RESULTS：Compared with CIA group, TMP at a dose of 100 mg/kg significantly reduced the weight loss in CIA rats and decreased the protein expression of MMP-13 by 31.82%. TMP also attenuated the pathological changes of the paw subcutaneous tissues. TMP obviously decreased the levels of VEGF by 33.33%, IL-17 by 27.40% and IL-23 by 33.33% in the serum. CONCLUSION：TMP significantly inhibits the development of CIA by decreasing the protein expression of MMP-13, inhibiting the inflammatory cell infiltration and vascular proliferation, and reducing the production of VEGF, IL-17 and IL-23 in CIA rats.     

Matrix Metalloproteinase Inhibitors (MMPIs) from Marine Natural Products: the Current Situation and Future Prospects

Matrix metalloproteinases (MMPs) are a family of more than twenty five secreted and membrane-bound zinc-endopeptidases which can degrade extracellular matrix (ECM) components. They also play important roles in a variety of biological and pathological processes. Matrix metalloproteinase inhibitors (MMPIs) have been identified as potential therapeutic candidates for metastasis, arthritis, chronic inflammation and wrinkle formation. Up to present, more than 20,000 new compounds have been isolated from marine organisms, where considerable numbers of these naturally occurring derivatives are developed as potential candidates for pharmaceutical application. Eventhough the quantity of marine derived MMPIs is less when compare with the MMPIs derived from terrestrial materials, huge potential for bioactivity of these marine derived MMPIs has lead to large number of researches. Saccharoids, flavonoids and polyphones, fatty acids are the most important groups of MMPIs derived from marine natural products. In this review we focus on the progress of MMPIs from marine natural products.     

The Mauve Stinger Pelagia noctiluca (Forssk?l, 1775). Distribution,Ecology, Toxicity and Epidemiology of Stings. A Review

The toxicity of Cnidaria is a subject of concern due to its influence on humans. In particular, jellyfish blooms can highly affect human economical activities, such as bathing, fishery, tourism, etc., as well as the public health. Stinging structures of Cnidaria (nematocysts) produce remarkable effects on human skin, such as erythema, swelling, burning and vesicles, and at times further severe dermonecrotic, cardio- and neurotoxic effects, which are particularly dangerous in sensitive subjects. In several zones the toxicity of jellyfish is a very important health problem, thus it has stimulated the research on these organisms; to date toxicological research on Cnidarian venoms in the Mediterranean region is not well developed due to the weak poisonousness of venoms of jellyfish and anemones living in this area. In spite of this, during last decades several problems were also caused in the Mediterranean by stinging consequent to Cnidarian blooms mainly caused by Pelagia noctiluca (Forsskål, 1775) which is known to be the most venomous Mediterranean jellyfish. This paper reviews the knowledge on this jellyfish species, particularly considering its occurrence and toxicity.     

基因Ⅳ型戊型肝炎病毒开放阅读框3表达的蛋白(pORF3)对L02细胞基质金属蛋白酶(MMP)表达的影响

为了探讨基因Ⅳ型戊型肝炎病毒开放阅读框3(ORF3)表达的蛋白(pORF3)影响靶细胞基质金属蛋白酶(MMP)表达的分子机制,试验运用蛋白芯片技术对比分析了稳定表达pEGFP-ORF3和pEGFP的L02细胞中基质金属蛋白酶表达谱,筛选出表达水平上调/下调的基质金属蛋白酶.结果表明,在稳定表达pEGFP-ORF3的L02细胞中,TIMP-1、TIMP-2和TIMP-4表达水平均降低.本试验结果为戊型肝炎病毒pORF3对L02细胞中基质金属蛋白酶相关蛋白表达影响的分子机制研究提供了理论依据.     

带有组氨酸标签的蛇毒基因在毕赤酵母中的表达

[目的]通过巴斯德毕赤酵母（Pichia pastoris）表达带有组氨酸标签的蛇毒基因。[方法]利用基因重组技术,以海蛇基因为材料,通过PCR技术在N末端添加一个六聚组氨酸纯化标签,并将重组质粒导入菌株GS115,用1%甲醇诱导后,分泌表达了重组蛋白。[结果]测序结果显示该标签已成功插入,SDS-PAGE检测到分子量为28.5 kD的目的蛋白。[结论]成功表达了带有组氨酸标签的蛇毒蛋白,其具有良好的降纤活性。     

Increased expression of tissue inhibitor of metalloproteinase‐1 correlates with improved outcome in canine cutaneous mast cell tumours

Canine mast cell tumour (MCT) is a biologically heterogeneous disease. The extracellular matrix degradation promoted by matrix metalloproteinases (MMPs) has been studied in an attempt to elucidate the mechanisms involved in the biological behaviour of tumours. The aim of this study was to characterize the expression of MMP‐2 and ‐9 and tissue inhibitors of metalloproteinase (TIMP)‐1 and ‐2 in canine cutaneous MCTs and to evaluate their prognostic values. Immunohistochemical staining for MMP‐2, MMP‐9, TIMP‐2 and TIMP‐1 was performed in 46 canine cases of MCTs. TIMP‐1 expression showed an independent prognostic value for post‐surgical survival and disease‐related mortality. Dogs with MCTs showing less than 22.9% mast cell TIMP‐1 positivity were more prone to die because of the disease and had a shorter post‐surgical survival. This article suggests the involvement of TIMP‐1 in MCT progression, by contributing to a good outcome in patients with MCTs.     

Proteases as prognostic markers in human and canine cancers

The extracellular matrix (ECM) is composed of several types of proteins, which interact and form dynamic networks. These components can modulate cell behaviour and actively influence the growth and differentiation of tissues. ECM is also important in several pathological processes, such as cancer invasion and metastasis, by creating favourable microenvironments. Proteolysis in neoplastic tissues is mediated by proteinases, whose regulation involves complex interactions between neoplastic cells and non‐neoplastic stromal cells. In this review, we discuss aspects of proteinase expression and tumor behaviour in humans and dogs. Different classes of proteases are summarized, with special emphasis being placed on molecules that have been shown to correlate with prognosis, reinforcing the need for a better understanding of the regulation of this microenvironment and its influences in tumor progression and metastasis, which should significantly aid the development of improved prognosis and treatment.     

松材线虫类毒过敏原蛋白的原核表达及多克隆抗体的制备

 利用重叠延伸PCR基因合成法,按大肠杆菌偏爱密码子,合成松材线虫类毒过敏原蛋白基因（Bxvap2）,将其连接到原核表达载体pET-29b(+)上。获得的重组子转化大肠杆菌BL21(DE3)后,用IPTG进行诱导表达。SDS-PAGE分析表明,目的蛋白以可溶形式高效表达,占细菌总蛋白的33.5 %。将表达产物经Ni-NTA亲和柱纯化后进行质谱分析,结果显示纯化的蛋白为BXVAP2蛋白。用制备的BXVAP2蛋白免疫新西兰白兔制备多克隆抗体,间接ELISA测得抗体灵敏度5.4 ng·mL^-1（效价为1∶1 360 000）,为进一步研究该蛋白的组织定位及功能,明确该基因在致病过程中的作用机理奠定了基础。     

金属蛋白酶组织抑制剂在皱纹盘鲍抗弧菌免疫中的作用

由弧菌感染引起的疾病是影响鲍存活率的主要因素,实验以皱纹盘鲍为研究对象,探讨金属蛋白酶组织抑制剂(tissue inhibitor of metalloproteinase,TIMP)在皱纹盘鲍抗弧菌免疫中的功能及其与基质金属蛋白酶1 (matrix metalloproteinase 1,MMP-1)的相互作用关系....