雷公藤多苷联合泼尼松治疗类风湿关节炎肺间质病变的临床疗效

目的:探讨雷公藤多苷治疗类风湿关节炎(RA)肺间质病变(ILD)的临床疗效分析。方法:选取2013年12月至2016年12月右江民族医学院附属医院收治的RA-ILD患者100例作为研究对象,按照随机数字表法分为对照组和观察组,每组50例,对照组给予泼尼松治疗,观察组在此基础上给予雷公藤多苷治疗。比较2组患者临床治疗有效率、治疗前后症状评分、红细胞沉降率(ESR)、C反应蛋白(CRP)、类风湿因子(RF)水平、肺高分辨CT(HRCT)积分、用力肺活量(FVC)、第一秒钟用力呼气容积(FEV1)、FEV1/FVC、外周血基质金属蛋白酶1(MMP-1)、基质金属蛋白酶-9(MMP-9)水平变化以及不良反应的差异。结果:雷公藤多苷可明显减少RA-ILD患者的症状评分,提高临床治疗有效率,下降ESR、CRP、RF、HRCT、MMP-9水平,上调FVC、FEV1、FEV1/FVC、MMP-1。观察组和对照组不良反应发生率差异无统计学意义(P>0.05)。结论:雷公藤多苷可有效治疗RA-ILD,其作用机制可能通过MMPs介导。     

“Real life” polycyclic aromatic hydrocarbon (PAH) mixtures modulate hCG,hPL and hPLGF levels and disrupt the physiological ratio of MMP-2 to MMP-9 and VEGF expression in human placenta cell lines

Using JEG-3 and BeWo cells, we examined the effect of “real life” mixtures of polycyclic aromatic hydrocarbons (PAHs), at doses reported in maternal blood (Mix I) and in placental tissue (Mix II), on human chorionic gonadotropin (hCG), placental lactogen (hPL) and placental growth factor (hPLGF) secretion, protein expression and immunolocalization. Additionally, the action of PAH mixtures on basal and hormone-stimulated matrix metalloproteinase-2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF) protein expression was evaluated. Under basal conditions, the PAH mixtures increased hCG and decreased hPLGF levels in both cell lines, while hPL expression was stimulated in JEG-3 and inhibited in BeWo. There was no effect on the MMP-2/MMP-9 ratio or VEGF expression. In hormone-stimulated cells, PAH mixtures changed the MMP-2/MMP-9 ratio in JEG-3 cells in favor of MMP-9, while in BeWo MMP-2 was favored. The effect on VEGF expression was cell specific and dependent on the mixture. In hCG-treated cells, only Mix II inhibited VEGF expression in JEG-3 cells. Neither PAH mixtures affected this protein in BeWo cells. In hPL-treated cells, Mix I had a stimulatory effect in JEG-3 cells, while Mix II exerted an inhibitory effect in BeWo cells. In hPLGF-treated cells, Mix II decreased in JEG-3 cells, but in BeWo cells, both mixtures increased VEGF expression. Considering that the evaluated protein hormones play crucial roles in angiogenesis and neovascularization in the placenta, “real life” PAH mixtures by disrupting protein hormones levels, the MMP-2/MMP-9 ratio and VEGF expression can lead to insufficiency and many pregnancy-related disorders.     

10-MDP-钙盐形成对牙本质粘接成绩影响的评价

目的　分析10-MDP-钙盐形成对牙本质粘接成绩的影响。方法　采用酸蚀冲洗粘接模式，根据牙本质表面的处理方式和选择粘接剂的不同将牙齿随机分为以下4组（n=5）进行处理，制作牙本质/树脂粘接试件：①对照组，直接使用全酸蚀粘接剂Single bond 2(SB2)处理后粘接；②10-MDP组，使用SB2处理进行粘接前，牙本质表面以含有磷酸酯单体10-MDP的自配底涂剂预处理；③CHX组，使用SB2处理进行粘接前，先以氯己定（CHX）预处理牙本质表面;④SBU组，使用包含10-MDP的通用型粘接剂Single bond universal(SBU)处理后进行粘接。通过微拉伸测试（μTBS）测试粘接强度，以X射线衍射(XRD)、原位酶谱测试表征自配10-MDP底涂剂和两种牙本质粘接剂处理的牙本质表面，分析10-MDP-钙盐形成对牙本质粘接成绩的影响。结果　微拉伸结果显示，不同处理方式的粘接试件在24 h水储后没有表现出明显的统计学差异(P>0.1)；经过6个月的水储后，与10-MDP组和SBU组相比，对照组的微拉伸强度显著降低(P<0.05)，而CHX组的微拉伸强度没有明显变化(P>0.05)。XRD结果显示,在10-MDP组和SBU组均检测到10-MDP-钙盐形成的特征性峰，表明有10-MDP-钙盐的形成。原位酶谱结果显示，10-MDP组与SBU组之间混合层荧光强度没有明显区别，但均明显高于对照组，CHX组荧光强度低于10-MDP组与SBU组。结论　10-MDP-钙盐的形成能够保护暴露的胶原纤维不接触到MMPs而免于水解，从而增强牙本质/树脂的粘接成绩。     

Nanofiber technology in the ex vivo expansion of cord blood-derived hematopoietic stem cells

Umbilical cord blood (CB) can be used as an alternative source of hematopoietic stem cells (HSCs) for transplantation in hematological and non-hematological disorders. Despite several recognized advantages the limited cell number in CB one unit still restricts its clinical use. The success of transplantation greatly depends on the levels of total nucleated cell and CD34+ cell counts. Thus, many ex vivo strategies have been developed within the last decade in order to solve this obstacle, with more or less success, mainly determined by the degree of difficulty related with maintaining HSCs self-renewal and stemness properties after long-term expansion. Different research groups have developed very promising and diverse CB-derived HSC expansion strategies using nanofiber scaffolds. Here we review the state-of-the-art of nanofiber technology-based CB-derived HSC expansion.     

Recent advances in understanding the roles of matrix metalloproteinases in tumour invasion and metastasis

This review aims to provide an overview of recent developments regarding the roles of MMPs in tumour invasion and metastasis. Much of the mortality burden belonging to cancer relates to its ability to invade adjacent tissue and form metastases at distant sites. This would not be possible without remodelling of the ECM, a process which is enabled by the functions of MMPs. Recent studies provide a better understanding of the importance of the biophysical nature of the ECM, how this influences cancer cell motility, and how MMPs act to modify matrix stiffness. The regulation of MMPs and the role of immune cell generated MMPs has also become better understood. All of this provides a framework for the therapeutic targeting of MMPs and recent advances in the development of selective MMPs inhibitors are also reviewed. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

牙龈卟啉单胞菌膜泡对牙龈上皮细胞MMPs基因表达的影响

目的:探讨牙龈卟啉单胞菌膜泡对牙龈上皮细胞基质金属蛋白酶(MMPs)基因表达的影响,揭示牙龈卟啉单胞菌在牙周炎中的致病作用.方法:以Real-time RT-PCR法检测牙龈卟啉单胞菌膜泡刺激下牙龈上皮细胞MMP-1和MMP-3的mRNA表达水平.结果:牙龈卟啉单胞菌膜泡显著地上调MMP-1和MMP-3 mRNA表达水平.结论:牙龈卟啉单胞菌诱导牙龈上皮细胞发生细胞炎症反应,可能是牙周炎发生、发展的重要因素.     

The anti-MMP activity of benzalkonium chloride

Objective

This study evaluated the ability of benzalkonium chloride (BAC) to bind to dentine and to inhibit soluble recombinant MMPs and bound dentine matrix metalloproteinases (MMPs).

Methods

Dentine powder was prepared from extracted human molars. Half was left mineralized; the other half was completely demineralized. The binding of BAC to dentine powder was followed by measuring changes in the supernatant concentration using UV spectrometry. The inhibitory effects of BAC on rhMMP-2, -8 and -9 were followed using a commercially available in vitro proteolytic assay. Matrix-bound endogenous MMP-activity was evaluated in completely demineralized beams. Each beam was either dipped into BAC and then dropped into 1 mL of a complete medium (CM) or they were placed in 1 mL of CM containing BAC for 30 days. After 30 days, changes in the dry mass of the beams or in the hydroxyproline (HYP) content of hydrolysates of the media were quantitated as indirect measures of matrix collagen hydrolysis by MMPs.

Results

Demineralized dentine powder took up 10-times more BAC than did mineralized powder. Water rinsing removed about 50% of the bound BAC, whilst rinsing with 0.5 M NaCl removed more than 90% of the bound BAC. BAC concentrations 0.5 wt% produced 100% inhibition of soluble recombinant MMP-2, -8 or -9, and inhibited matrix-bound MMPs between 55 and 66% when measured as mass loss or 76-81% when measured as solubilization of collagen peptide fragments.

Conclusions

BAC is effective at inhibiting both soluble recombinant MMPs and matrix-bound dentine MMPs in the absence of resins.     

Different expression profiles of the lysyl oxidases and matrix metalloproteinases in human ACL fibroblasts after co-culture with synovial cells

Purposes The anterior cruciate ligament (ACL) has poor functional healing response. The synovial tissue surrounding ACL ligament might be a major regulator of the microenvironment in the joint cavity after ACL injury, thus affecting the repair process. Using transwell co-culture, this study explored the direct influence of human synovial cells (HSCs) on ACL fibroblasts (ACLfs) by characterizing the differential expression of the lysyl oxidase family (LOXs) and matrix metalloproteinases (MMP-1, ?2, ?3), which facilitate extracellular matrix (ECM) repair and degradation, respectively. Methods The mRNA expression levels of LOXs and MMP-1, ?2, ?3 were analyzed by semi-quantitative PCR and quantitative real-time PCR. The protein expression levels of LOXs and MMP-1, ?2, ?3 were detected by western blot. Results We found that co-culture resulted in an increase in the mRNAs of LOXs in normal ACLfs and differentially regulated the expression of MMPs. Then we applied 12% mechanical stretch on ACLfs to induce injury and found the mRNA expression levels of LOXs in injured ACLfs were decreased in the co-culture group relative to the mono-culture group. Conversely, the mRNA expression levels of MMPs in injured ACLfs were promoted in the co-culture group compared with the mono-culture group. At translational level, we found that LOXs were lower while MMPs were highly expressed in the co-culture group compared to the mono-culture group. Conclusions The co-culture of ACLfs and HSCs, which mimicked the cell-to-cell contact in a micro-environment, could contribute to protein modulators for wound healing, inferring the potential reason for the poor self-healing of injured ACL.