Protection against UVB-induced damages in human dermal fibroblasts: efficacy of tricin isolated from enzyme-treated Zizania latifolia extract

This study was undertaken to determine the effects of enzyme-treated Zizania latifolia (ETZL) and of its major compound tricin on skin photo-aging and to investigate the mechanisms involved. It was found ETZL and tricin suppressed matrix metalloproteinase (MMP) production and increased type I-procollagen production in UVB-irradiated human dermal fibroblasts (HDFs). Furthermore, ETZL and tricin significantly up-regulated the expressions of the antioxidant enzymes HO-1 and SOD1, reduced UVB-induced reactive oxygen species (ROS) generation and mitogen-activated protein kinase (MAPK) induction by ROS and thereby attenuated activator protein-1 (AP-1) expression. In addition, ETZL and tricin both reduced the phosphorylations of IκBα and IKKα/ß and κB blocked the nuclear translocation of nuclear factor-κB (NF-κB) p65. These results show that ETZL have skin protective effects against UVB and suggest tricin as major efficacious material in ETZL protecting skin photoaging.     

血管生长抑素在小鼠胚泡中的调节作用

血管生长抑素（angiostatin,AS）是一种新血管生成的抑制蛋白,它可以有效抑制内皮细胞的增殖、迁移和管状形态的产生,是肿瘤转移的有效抑制剂.肿瘤转移和胚胎植入具有惊人的相似性,AS对小鼠胚胎植入是否有作用迄今尚无报道.采用体外培养、RT-PCR和蛋白质印迹等多种方法研究了AS对小鼠胚泡中血管内皮生长因子（VEGF）及其受体KDR、基质金属蛋白酶(MMPs)及其组织抑制剂(TIMPs)的影响.研究显示,AS下调了VEGF及其受体KDR、MMP-2和MMP-9的表达,而上调了TIMP-1和TIMP-2的表达.应用整合素αVβ3的特异性抑制剂Echistatin与AS共同处理胚泡,结果显示,Echistatin减弱了AS对MMP-2的下调作用及对TIMP-2的上调作用.以上结果提示：AS可能通过与整合素αVβ3相互作用调节胚泡中VEGF、MMPs和TIMPs的表达,从而影响胚泡的植入过程.     

Expressions of pathologic markers in PRP based chondrogenic differentiation of human adipose derived stem cells

Background

Optimization of the differentiation medium through using autologous factors such as PRP is of great consideration, but due to the complex, variable and undefined composition of PRP on one hand and lack of control over the absolute regulatory mechanisms in in vitro conditions or disrupted and different mechanisms in diseased tissue microenvironments in in vivo conditions on the other hand, it is complicated and rather unpredictable to get the desired effects of PRP making it inevitable to monitor the possible pathologic or undesired differentiation pathways and therapeutic effects of PRP. Therefore, in this study the probable potential of PRP on inducing calcification, inflammation and angiogenesis in chondrogenically-differentiated cells was investigated.

ADAM的遗传和进化

ADAM,又称MDC,分别是去整合蛋白和金属蛋白水解酶（a disintegrin and metalloproteinase,ADAM）及金属蛋白水解酶、去整合蛋白和富半胱氨酸（metalloproteinase/disintegrin/cysteine-rich,MDC）的英文缩写,是近几年在多细胞动物中发现的一类含信号肽区、前调控区、金属蛋白水解酶区、去整合蛋白区、富半胱氨酸区、上皮生长因子区、跨膜区和胞内区的细胞表面糖蛋白,本文简要总结了有关ADAM起源、遗传、进化和亲缘关系的研究结果。 Abstract:ADAM (a disintegrin and metalloproteinase),or named MDC (metalloproteinase/disintegrin/cysteine-rich) is a family of glycoproteins in cell surface,which was found in recent years and consists of a signal peptide,a propetide,a metalloproteinase,a disintegrin,a cysteine-rich domain,and an epidermal growth factor (EGF)-like domain,a transmembrane region,and a cytoplasmic tail.The research results about their origin,heredity,evolution and evolutionary relationship are summaried in this paper.     

Oxidative stress promotes the increase of matrix metalloproteinases-2 and -9 activities in the feto-placental unit of diabetic rats

Maternal diabetes increases the risk of congenital malformations, placental dysfunction and diseases in both the neonate and the offspring's later life. Oxidative stress has been involved in the etiology of these abnormalities. Matrix metalloproteases (MMPs), involved in multiple developmental pathways, are increased in the fetus and placenta from diabetic experimental models. As oxidants could be involved in the activation of latent MMPs, we investigated a putative relationship between MMPs activities and oxidative stress in the feto-placental unit of diabetic rats at midgestation. We found that H₂O₂ enhanced and that superoxide dismutase (SOD) reduced MMPs activities in the maternal side of the placenta and in the fetuses from control and diabetic rats. MMPs were not modified by oxidative status in the fetal side of the placenta. Lipid peroxidation was enhanced in the maternal and fetal sides of the placenta and in the fetus from diabetic rats when compared to controls, and gradually decreased from the maternal placental side to the fetus in diabetic animals. The activities of the antioxidant enzymes SOD and catalase were decreased in the maternal placental side, catalase activity was enhanced in the fetal placental side and both enzymes were increased in the fetuses from diabetic rats when compared to controls. Our data demonstrate changes in the oxidative balance and capability of oxidants to upregulate MMPs activity in the feto-placental unit from diabetic rats, a basis to elucidate links between oxidative stress and alterations in the developmental pathways in which MMPs are involved.     

利用胃癌MMP相关生物标志物预测MMP生物调节剂的活性

目的:根据疗效和安全性,MMP生物调节剂的临床试验结果成为急需探讨的问题.因为,目前为止MMP生物调节剂的临床试验是按照传统化疗方案进行,不是选择适合人群为基础.因此可预测性生物标志物的选择将对-抗MMP治疗是非常重要的.方法:在6个胃癌细胞株中MMP-2、MMP-9、MT1-MMP以及TIMP-2水平和用TIMP-2治疗之后在MT1-MMP以及MMP-2变化可做为生物标志物而被测定.做为MMP生物调节剂,Suramin和Fumagillin的药物敏感性是通过计算IC50值来测定.利用回归方程,用这些生物标志物推断对药物敏感性.最后其预测精度由ex vivo实验证实.结果:Suramin做为pro-MMP-2的特异性抑制剂.在对pro-MMP-2基础活性高的细胞群,其IC50值＜30ug/ml.相反,Fumagillin对胶原蛋白酶活性具有广谱的抑制作用.(IC50＜10-5M).通过回归分析,解释对Suramin敏感性的回归方程是40.7(pro-MMP-2),-10.0(MT1-MMP),-40.7,对Fumagillin 敏感性的回归方程是-11.5,(pro-MMP-2)-10.6(TIMP-2),+11.5.在exvivo,Suramin和Fumagillin的回归方程预测精度均为60%.结论:用生物标志物预测MMP抑制剂的敏感性已成为可能,利用生物标志物,不仅快速、安全筛选MMP抑制剂,而且通过个体化可改善治疗效果.     

Making the cut: protease-mediated regulation of angiogenesis

Angiogenesis is an integral element of normal physiologic development as well as of wound healing and a variety of pathologic conditions. Since the earliest studies of the cellular processes required for the formation of new capillaries from preexisting vessels, proteolysis has been recognized as one of the earliest and most sustained activities involved in these events. Several proteases including matrix metalloproteases (MMPs), and the closely related ADAM (a disintegrin and metalloprotease domain) and ADAMTS (a disintegrin and metalloprotease domain with thrombospondin motifs) families, as well as cysteine and serine proteases, have been implicated in this regulation. The current review addresses the contribution of these proteases in the positive and negative regulation of angiogenesis as mediated by degradation of the endothelial basement membrane and extracellular matrix proteins, release of angiogenic factors, processing of cytokines, growth factors and growth factor receptors, and the production of endogenous inhibitors.     

缺氧对肺动脉内皮细胞MMP-2、MMP-9表达的影响

目的观察缺氧对培养的猪肺动脉内皮细胞基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)的表达的影响.方法采用RT-PCR、Western blot、底物胶电泳(酶谱图)、免疫细胞化学等方法.结果肺动脉内皮细胞缺氧24h可使MMP-2的mRNA表达和蛋白分泌减少,酶活性减弱,与常氧组比较有显著性差异, MMP-9无明显变化.结论缺氧时MMP-2降低,溶解细胞外基质的能力降低,可能是缺氧性肺血管构型重组的机制之一.     

Liberation of desmosine and isodesmosine as amino acids from insoluble elastin by elastolytic proteases

The development of atherosclerotic lesions and abdominal aortic aneurysms involves degradation and loss of extracellular matrix components, such as collagen and elastin. Releases of the elastin cross-links desmosine (DES) and isodesmosine (IDE) may reflect elastin degradation in cardiovascular diseases. This study investigated the production of soluble elastin cross-linking structures by proteinases implicated in arterial diseases. Recombinant MMP-12 and neutrophil elastase liberated DES and IDE as amino acids from insoluble elastin. DES and IDE were also released from insoluble elastin exposed to monocyte/macrophage cell lines or human primary macrophages derived from peripheral blood monocytes. Elastin oxidized by reactive oxygen species (ROS) liberated more unconjugated DES and IDE than did non-oxidized elastin when incubated with MMP-12 or neutrophil elastase. These results support the exploration of free DES and IDE as biomarkers of elastin degradation.     

NPM1突变基因通过MMPs参与调控白血病细胞体外侵袭

核仁磷蛋白基因(nucleophosmin,NPM1)突变是目前急性髓系白血病(AML)中突变率最高的基因改变,在白血病的发生发展过程中发挥重要的调控作用。为探讨NPM1突变参与调控白血病髓外浸润的分子机制,将表达质粒pEGFPC1-NPM1-mA转染THP-1细胞系,筛选稳定表达NPM1突变蛋白的白血病细胞株(THP-1-mA)。利用RT-PCR及Western blot分析了THP-1-mA细胞与亲代细胞间MMP-2、MMP-9、TIMP-1、TIMP-2表达水平的差异。结果显示,具有体外高侵袭能力的THP-1-mA组细胞MMP-2的mRNA水平和蛋白水平均明显高于两对照组,而MMP-9 mRNA表达水平虽有所增高,但蛋白表达水平却明显降低。同时,与空载体转染组和未处理组细胞相比,THP-1-mA组细胞TIMP-2的mRNA水平和蛋白水平表达显著降低,差异具有统计学意义;TIMP-1表达水平无明显改变。提示MMP-2及其抑制剂TIMP-2在NPM1突变参与调控的白血病细胞髓外浸润中可能发挥重要作用。