Expression of matrix metalloproteinase-9 in nasopharyngeal carcinoma and association with Epstein-Barr virus infection

Objective: To evaluate the expression of matrix metalloproteinase-9 (MMP9) in nasopharyngeal carcinoma and the association between MMP9 and Epstein-Barr virus infection. Methods: The MMP9 expression was studied by immu-nohistochemical analysis; and Epstein-Barr virus encoded small nuclear mRNA-1(EBER-1) produced by in situ hybridization were examined in 41 nasopharyngeal carcinoma sections, and the relation between them, and the associations of MMP9 with clinical features were statistically analyzed. Results: Positive expression rate of MMP9 was 73.17%. The expression of MMP9 showed significant positive correlation with the expression of EBER-1 (γ0.483, P=0.001). There was significant association of MMP9 expression with lymph nodes metastasis and clinical stage (P<0.001), non-significant association with age, gender, pathological classification and T classification. Conclusions: The highly pronounced expression of MMP9 is associated with cervical lymph nodes metastasis. Epstein-Barr virus can enhance N     

Association of matrix metalloproteinase-9 C1562T polymorphism and coronary artery disease: a meta-analysis简

Objective

Many investigations have studied the associations between matrix metalloproteinase-9 (MMP-9) C1562T polymorphisms and coronary artery disease (CAD). However, the conclusions of these studies were inconsistent. Therefore, this study was aimed at clarifying the association between MMP-9 C1562T polymorphisms and CAD in a large-scale meta-analysis.

Methods

The PubMed and Embase databases were retrieved to collect all publications on the association between MMP-9 C1562T polymorphisms and CAD. Then the odd ratios (ORs) and 95% confidence intervals (95% CIs) for C1562T TT+TC versus CC genotype between CAD and the control groups were evaluated. Subgroup analysis was also performed according to different races. The meta-analysis was performed by Stata 10.0.

Results

Sixteen case-control studies were included in our meta-analysis, involving 11 032 CAD patients and 4628 non-CAD controls. Compared with C allele carriers, East Asian T allele carriers TT+TC had a significantly higher risk of CAD (OR=1.43; 95% CI: 1.03–1.99; P=0.031); however, there were no significant associations in Western populations (OR=1.06; 95% CI: 0.96–1.18; P=0.240) or West Asians (OR=1.13; 95% CI: 0.75–1.70; P=0.565). When further analyzing the association between C1562T polymorphisms and myocardial infarction (MI, the most serious type of CAD), the risk of TT+TC genotype versus CC genotype for MI was significantly higher for the overall (OR=1.21; 95% CI: 1.04–1.40; P=0.012) and for East Asians (OR=1.58; 95% CI: 1.26–1.97; P=0.000) but not in Western populations (OR=1.12; 95% CI: 0.99–1.26; P=0.078).

Conclusions

Our meta-analysis suggested an obvious ethnic difference in the association between MMP-9 C1562T polymorphisms and CAD. MMP-9 C1562T polymorphism was significantly related to CAD in East Asians. However, no significant associations were observed in either West Asians or Western populations.     

实验性兔脑血管痉挛血清MMP-9及VEGF的变化研究

观察血清基质金属蛋白酶-9（MMP-9）及血管内皮生长因子（VEGF）在实验性新西兰白兔蛛网膜下腔出血后的浓度变化,探讨它们与脑血管痉挛发生、发展及转归过程的关系,为临床诊断及治疗提供理论依据。实验结果表明血清MMP-9及VEGF的浓度变化可以作为预测蛛网膜下腔出血后脑血管痉挛的发作、判断其发展及预后的参考指标之一,为临床诊断与治疗提供依据。MMP-9及VEGF参与了蛛网膜下腔出血后的病理生理过程,与迟发性脑血管痉挛的发病机制有密切关系。     

Expression of MMP-9 in hepatic sinusoidal obstruction syndrome induced by Gynura segetum

Background and objective:Hepatic sinusoidal obstruction syndrome(HSOS) is characterized by painful hepatomegaly,ascites,increased body weight,and jaundice.Gynura segetum(Compositae),a plant widely used in Chinese traditional medicine,often leads to the development of HSOS.However,the mechanism is unclear.The aim was to study the role of matrix metalloproteinase-9(MMP-9) in the onset of HSOS induced by Gynura segetum.Methods:Twenty-five male Sprague-Dawley rats were randomly divided into two groups.Twenty were exposed to 600 mg/kg daily Gynura segetum extract solution for three weeks;five control rats were exposed to tap water alone.Liver sections were evaluated by light microscopy with a modified scoring system.Routine transmission electron microscopy(TEM) methods were used to evaluate the ultrastructual features of fixed liver tissue,and blood samples were collected to determine liver enzyme concentrations.MMP-9 expression was assessed by both immunohistochemical staining and enzyme-linked immunosorbent assay(ELISA) methods.Results:A stable and reproducible rat model of HSOS was achieved by long-term exposure to Gynura segetum extract.The treated rats presented clinical symptoms and the histopathological manifestation of HSOS,including abnormal liver enzyme concentrations(alanine aminotransferase(ALT):(84.8±13.62) vs.(167.0±72.63) U/L,P<0.05;aspartate aminotransferase(AST):(27.6±6.31) vs.(232.8±108.58) U/L,P<0.05).Hematoxylin and eosin(H&E) staining and TEM together revealed deposition of red blood cells,the damage and destruction of hepatic sinusoidal endothelial cells,collapse of hepatic sinusoids,hemorrhage of subendothelial cells,atrophy and destruction of hepatocytes,etc.Compared with controls,the expression of MMP-9 in the blood sample,the lung and liver tissues of HSOS rats was increased.Conclusions:MMP-9 may have an important role in early pathological changes of HSOS,and thus the onset of the disease.     

Correlation of matrix metalloproteinase-2, -9, tissue inhibitor-1 of matrix metalloproteinase and CD44 variant 6 in head and neck cancer metastasis

INTRODUCTIONHeadandneckcancersquamouscellcarci noma (HNSCC)isthefifthmostfrequentmalig nantneoplasmworld wide ;andischaracterizedbylocalinvasion ,disseminationtolocallymphnodeandfrequentrecurrenceattheprimarysiteoftumour.Despiteimprovementsindiagnosisandt…     

Effects of rosuvastatin on the production and activation of matrix metalloproteinase-2 and migration of cultured rat vascular smooth muscle cells induced by homocysteine

Objective: To test the influence of homocysteine on the production and activation of matrix metalloproteinase-2 (MMP-2) and tissue inhibitors of matrix metalloproteinase-2 (TIMP-2) and on cell migration of cultured rat vascular smooth muscle cells (VSMCs). Also, to explore whether rosuvastatin can alter the abnormal secretion and activation of MMP-2 and TIMP-2 and migration of VSMCs induced by homocysteine. Methods: Rat VSMCs were incubated with different concentrations of homocysteine (50–5 000 μmol/L). Western blotting and gelatin zymography were used to investigate the expressions and activities of MMP-2 and TIMP-2 in VSMCs in culture medium when induced with homocysteine for 24, 48, and 72 h. Transwell chambers were employed to test the migratory ability of VSMCs when incubated with homocysteine for 48 h. Different concentrations of rosuvastatin (10⁻⁹–10⁻⁵ mol/L) were added when VSMCs were induced with 1 000 μmol/L homocysteine. The expressions and activities of MMP-2 and TIMP-2 were examined after incubating for 24, 48, and 72 h, and the migration of VSMCs was also examined after incubating for 48 h. Results: Homocysteine (50–1 000 μmol/L) increased the production and activation of MMP-2 and expression of TIMP-2 in a dose-dependent manner. However, when incubated with 5 000 μmol/L homocysteine, the expression of MMP-2 was up-regulated, but its activity was down-regulated. Increased homocysteine-induced production and activation of MMP-2 were reduced by rosuvastatin in a dose-dependent manner whereas secretion of TIMP-2 was not significantly altered by rosuvastatin. Homocysteine (50–5 000 μmol/L) stimulated the migration of VSMCs in a dose-dependent manner, but this effect was eliminated by rosuvastatin. Conclusions: Homocysteine (50–1 000 μmol/L) significantly increased the production and activation of MMP-2, the expression of TIMP-2, and the migration of VSMCs in a dose-dependent manner. Additional extracellular rosuvastatin can decrease the excessive expression and activation of MMP-2 and abnormal migration of VSMCs induced by homocysteine.     

康脑液对脑缺血再灌注损伤大鼠血管内皮生长因子、脑源性神经生长因子、基质金属蛋白酶表达的影响

目的：通过康脑液干预观察其对脑缺血再灌注损伤大鼠血管内皮生长因子（vascular endothelial growth factor,VEGF）、脑源性神经生长因子（brain derived neurotrophic factor,BDNF）、基质金属蛋白酶（matrix metalloproteinase-9,MMP-9）表达的影响,探讨康脑液对脑缺血再灌注损伤的保护机制.方法：将雄性SD大鼠随机分为假手术组、脑缺血再灌注模型组及康脑液28.6、14.3、7.15 g·kg-1·d-1剂量组（灌胃给药7 d）,改进Longa等线栓法制备大鼠右侧大脑中动脉阻塞（middle cerebral artery occlusion,MCAO）再灌注模型.于缺血2h后再灌注（分别于再灌注后6h、12h、24 h、72 h、7d处死大鼠）;采用TTC染色法观察大鼠的脑梗死面积;免疫组织化学法观察大鼠脑组织VEGF、BDNF、MMP-9的表达.结果：比较各组缺血再灌注24 h大鼠脑梗死灶面积,发现28.6、14.3 g·kg--1·d-1剂量组较脑缺血再灌注模型组明显减小（P＜0.05）;与脑缺血再灌注模型组相比,28.6、14.3 g·kg--1·d-1剂量组各时间点的VEGF、BDNF表达量明显上调（P＜0.01）,MMP-9表达的阳性细胞明显减少（P＜0.01）,差异有统计学意义.结论：康脑液可促进大鼠局灶性脑缺血后脑组织中VEGF,BDNF的表达,同时抑制脑内MMP-9的表达,缩小脑梗死面积,发挥对神经血管单元（neurovascular unit,NVU）的保护作用,减轻脑缺血再灌注损伤.     

Epstein-Barr virus interactions with the Bcl-2 protein family and apoptosis in human tumor cells

Epstein-Barr virus(EBV),a human gammaherpesvirus carried by more than 90% of the world’s population,is associated with malignant tumors such as Burkitt’s lymphoma(BL),Hodgkin lymphoma,post-transplant lymphoma,extra-nodal natural killer/T cell lymphoma,and nasopharyngeal and gastric carcinomas in immune-compromised patients.In the process of infection,EBV faces challenges:the host cell environment is harsh,and the survival and apoptosis of host cells are precisely regulated.Only when host cells receive sufficient survival signals may they immortalize.To establish efficiently a lytic or long-term latent infection,EBV must escape the host cell immunologic mechanism and resist host cell apoptosis by interfering with multiple signaling pathways.This review details the apoptotic pathway disrupted by EBV in EBV-infected cells and describes the interactions of EBV gene products with host cellular factors as well as the function of these factors,which decide the fate of the host cell.The relationships between other EBV-encoded genes and proteins of the B-cell leukemia/lymphoma(Bcl) family are unknown.Still,EBV seems to contribute to establishing its own latency and the formation of tumors by modifying events that impact cell survival and proliferation as well as the immune response of the infected host.We discuss potential therapeutic drugs to provide a foundation for further studies of tumor pathogenesis aimed at exploiting novel therapeutic strategies for EBV-associated diseases.     

严重烫伤早期大鼠脑内MMP-9的表达及意义

目的:探讨MMP-9与严重烫伤后血脑屏障损伤的关系.方法:健康SD大鼠随机分为正常组、假烫伤组、烫伤组,烫伤后又设3、6、12、24、48 h 5个时相点,用透射电镜观察血脑屏障超微结构变化;干温重法测脑含水量;紫外光度计检测脑EB含量;免疫组化观察脑MMP-9表达.结果:烫伤后大脑皮质的神经细胞线粒体肿胀或溶解,突触小泡减少,突触间隙增宽.脑毛细血管周围出现空泡化,内皮肿胀,基底膜厚薄不均.严重烫伤后脑含水量和EB含量明显增高,MMP-9表达升高,差别具有统计学意义(P<0.01).结论:严重烫伤后大鼠血脑屏障通透性增高与脑内MMP-9表达升高有关,提示MMP-9是严重烫伤后血脑屏障损伤的关键因素.     

Infection frequency of Epstein-Barr virus in subgingival samples from patients with different periodontal status and its correlation with clinical parameters

Objective： To detect the infection frequencies of different genotypes of Epstein-Barr virus （EBV） in subgingival samples from chronic periodontitis （CP） patients, and to discuss the correlation between infection with EBV and clinical parameters. Methods： Nested-PCR assay was used to detect EBV-1 and EBV-2 in subgingival samples from 65 CP patients, 65 gingivitis patients and 24 periodontally healthy individuals. The amplicons were further identified by restriction fragment length polymorphism analysis （RFLP） with endonucleases Afa I and Stu I. Clinical parameters mainly included bleeding on probing （BOP）, probing depth （PD）, attachment loss （AL） in six sites of the dentition. Results： In CP patients, gingivitis and periodontally healthy individuals, the infection frequencies were 47.7%, 24.6% and 16.7% for EBV-1, and 15.4%, 7.7% and 0% for EBV-2, respectively. In 2 out of the 65 CP patients co-infection of EBV-1 and EBV-2 was found. The positive rate of EBV-1 in chronic periodontitis patients was higher than that in gingivitis patients （P=-0.01） and periodontally healthy individuals （P=-0.01）. But no significant difference was shown in EBV-1 frequency between gingivitis patients and healthy individuals （P〉0.05） or in EBV-2 frequency among the three groups （P〉0.05）. In CP patients, higher mean BOP value was found in EBV-1 or EBV-2 positive patients than that in EBV negative ones （P〈0.01）, but with no statistical difference in the mean PD or AL value between EBV positive and negative patients （P〉0.05）. After initial periodontal treatment, 12 out of the 21 EBV-1 positive CP patients did not show detectable EBV-1 in subgingival samples. Conclusion： nPCR plus RFLP analysis is a sensitive, specific and stable method to detect EBV-1 and EBV-2 in subgingival samples. Subgingival infection with EBV-1 is closely associated with chronic periodontitis. Infection of EBV in subgingival samples was correlated with BOP.     

MMP-9和CD15s与胃癌血管生成的相关性研究及其临床意义

目的:探讨基质金属蛋白酶9(MMP-9)和唾液酸化Lewis X(CD15s)抗原与胃癌侵袭转移的相关性。方法:采用CD105,MMP-9,CD15s进行免疫组化S-P法染色,对47例胃癌根治性切除手术标本病理组织切片进行标记,检测CD105的微血管密度(MVD),并对MVD与MMP-9、CD15s的关系进行统计分析。结果:MMP-9、CD15s表达都呈阳性的胃癌组织微血管密度高于MMP-9和CD15s单阳性及二者均阴性的胃癌组织。结论:MMP-9高表达有利于癌组织局部浸润,CD15s高表达有利于癌细胞血行转移,MMP-9及CD15s检测对临床诊治胃癌及判断预后具有一定意义。     

Ki-67在肝细胞肝癌中的表达及其临床意义

[目的]探讨抗增殖核蛋白的单克隆抗体(Ki-67)在肝细胞肝癌(HCC)中的表达情况及临床意义.[方法]采用免疫组织化学方法检测51例HCC病人术后存档的石蜡标本中Ki-67的表达情况.[结果]HCC中Ki-67阳性表达率58.8％.Ki-67表达阳性率与肿瘤大小、门脉癌栓和肿瘤分级相关,与肝硬化、病灶数目、包膜、AFP及HBsAg不相关,Ki-67阳性表达组HCC病人术后无瘤生存期均显著低于阴性表达组.[结论]Ki-67对HCC的浸润转移均起促进作用,是HCC预后的重要标志物.     

Preparation and in vitro studies of microencapsulated cells releasing human tissue inhibitor of metalloproteinase-2

Objective: To prepare microencapsulated cells releasing human tissue inhibitor of metalloproteinase-2 (TIMP-2), and investigate their biological characteristics in vitro. Methods: Chinese hamster ovary (CHO) cells were stably transfected with a human TIMP-2 expression vector, encapsulated in barium alginate microcapsules and cultured in vitro. Morphological appearance of the microcapsules was observed under a light microscope. Cell viability was assessed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Enzyme linked immunosorbent assay (ELISA) and reverse zymography were used to confirm the release of biologically active TIMP-2 from the microcapsules. Cryopreservation study of the microencapsulated cells was carried out using dimethyl sulfoxide (DMSO) as preservative agent. Results: The microcapsules appeared like a sphere with diameter of 300–600 μm. The surface of the capsule wall was clearly smooth. The microencapsulated cells survived well and kept proliferating over the 6 weeks observed. No significant difference in TIMP-2 secretion was found between encapsulated and unencapsulated cells. Reverse zymography confirmed the bioactivity of MMP (matrix metalloproteinase) inhibition of TIMP-2. The cryopreservation process did not damage the microcapsule morphology nor the viability of the cells inside. Conclusion: Microencapsulated engineered CHO cells survive at least 6 weeks after preparation in vitro, and secrete bioactive TIMP-2 freely from the microcapsules.     

Preparation and in vitro studies of microencapsulated cells releasing human tissue inhibitor of metalloproteinase-2

INTRODUCTION Cell encapsulation in biocompatible and semipermeable polymeric membranes is an effective method for immunoprotection, regardless of the type of recipient (allograft, xenograft, etc.). The semipermeable nature of the membrane prevents high molecular weight molecules, antibodies and other immunologic moieties from coming into contact with the encapsulated cells and destroying them as foreign invaders, but permits the entry of nutrients and oxy- gen and the exit of therapeutic p…     

肺和食道鳞状细胞癌中P27基因蛋白的表达

目的探讨肺和食道鳞状细胞癌中P27基因蛋白的表达状况.方法收集手术切除鳞癌标本63例,10%中性甲醛固定,石蜡切片,厚度5μm.超敏型S-P免疫组织化学染色.结果P27在鳞状细胞癌中总阳性率39.68%,在肺和食道中阳性率分别为36.00%和42.15%.在高、中分化组阳性率为36.00%,低分化组阳性率为53.85%.结论鳞癌组织中P27阳性表达与分化程度及是否转移的相关性有深入研究的必要.     

Use of flow cytometry to investigate the cytokine response pattern in infants with respiratory syncytial virus infection and bronchiolitis

Objective: To investigate the cytokine response pattern (IL-4/IFN-γ) in infants with RSV infections and bronchiolitis during the acute phase. Methods: Four-color flow cytometry was used to measure intracellular IL-4 and IFN-γ expressions in peripheral blood CD3+ and CD8+ lymphocytes from RSV-infected and bronchiolitis infants. Serum IL-4 and IFN-γ levels were also determined. Results: RSV-infected and bronchiolitis infants showed no statistical differences from not-RSV-infected or pneumonia infants and control in the frequency of IL-4 and IFN-γ expressions in CD3+CD8- lymphocytes, showed no obvious Th1/Th2 imbalance, while IFN-γ was expressed much more frequently in CD3+CD8+ lymphocytes. Systematically, RSV-infected and bronchiolitis infants showed much lower levels of serum IL-4 and IL-4/IFN-γ ratios and much higher serum IFN-γ levels than control. However, there were no statistical differences in the above three indices between RSV-infected and not-RSV infected infants or between bronchiolitis and pneumonia infants, except that bronchiolitis infants had a higher level of serum IFN-γ than pneumonia infants statistically. Conclusions: There is no type-2 cytokine response predominance in the acute phase of RSV infection and bronchiolitis. IL-4 production is suppressed and IFN-γ production upregulated, the latter being most prominent in bronchiolitis infants.     

MMP-2在膀胱癌和阴茎癌中表达的比较

目的 :探讨基质金属蛋白酶 (matrixmetalloprotein .ase - 2MMP - 2 )在膀胱癌和阴茎癌中的表达及意义。方法 :采用免疫组化法对MMP - 2在 4 2例膀胱癌和 4 5例阴茎癌中的表达进行研究。结果 :MMP - 2在膀胱癌中的阳性表达率为 2 8.5 7% (12 / 4 2 ) ,在阴茎癌中的阳性表达率为 5 7.78% (2 6 / 4 5 ) ;在膀胱移行细胞癌和腺癌中的阳性率分别为 2 3.6 8% (9/ 38)、75 .0 0 % (3/ 4 ) ,两者比较有显著性差异 (P <0 .0 1)。在阴茎癌高分化组阳性率为 4 5 .16 % ,中分化组阳性率为 85 .7% ,两组比较有显著性差异 (P <0 .0 5 )。结论 :MMP - 2在移行上皮癌与鳞状上皮癌中均有表达 ,其在鳞癌中的表达高于移行细胞癌 ,腺癌细胞的高表达提示腺癌细胞的浸润性高于移行细胞癌。     

育龄期功能失调性子宫出血女性子宫内膜组织中MMP-9、TIMP-1的表达变化与意义

目的:研究育龄期功能失调性子宫出血患者子宫内膜局部MMP-9、TIMP-1的表达变化。方法:采用免疫组化S-P法检测35例育龄期功能失调性子宫出血患者及20例正常月经健康女性排卵后期(即对照组)子宫内膜MMP-9、TIMP-1的表达情况。结果:育龄期功血女性以排卵型为主(30/35),其子宫内膜组织中MMP-9在出血部位的表达显著高于正常部位及对照组(P<0.05),TIMP-1在出血部位的表达显著低于正常部位及对照组(P<0.05),有统计学意义。结论:子宫内膜局部MMP-9与TIMP-1失衡与育龄期功血的发生有关。     

RhoC和MMP-9蛋白在结直肠癌中的表达及意义

探讨RhoC和基质金属蛋白酶-9(MMP-9)蛋白在结直肠癌发生发展中的作用。选取新鲜结直肠癌标本作为实验组,正常新鲜结肠粘膜组织作为对照组,应用流式细胞术分别检测RhoC和MMP-9的表达,检测其在不同临床病理特征之间的关系。结果表明,RhoC和MMP-9在结直肠癌组织中高表达(P<0.05),且其表达均与Dukes分期、浸润深度及炎细胞浸润相关(P<0.05),MMP-9的表达与结直肠癌的淋巴结转移密切相关(P<0.05),RhoC和MMP-9在结直肠癌中的表达呈正相关(r=0.3430,P=0.0420)。流式细胞术联合检测RhoC和MMP-9蛋白的表达有望成为判断预后的重要指标。     

Clinical characteristics of critical patients with pandemic influenza A (H1N1) virus infection in Chengdu, China

Objective  

The critical illness of pandemic influenza A (H1N1) virus infection may be associated with relatively poor outcomes. The objective of this study is to describe clinical features and factors associated with the deaths of critical patients.