A matrix metalloproteinase-responsive hydrogel system controls angiogenic peptide release for repair of cerebral ischemia/reperfusion injury

Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.

Association between Gene Polymorphisms and SNP-SNP Interactions of the Matrix Metalloproteinase 2 Signaling Pathway and the Risk of Vascular Senescence

Objective This study aimed to explore the association of single nucleotide polymorphisms(SNP)in the matrix metalloproteinase 2(MMP-2)signaling pathway and the risk of vascular senescence(VS).Methods In this cross-sectional study,between May and November 2022,peripheral venous blood of151 VS patients(case group)and 233 volunteers(control group)were collected.Fourteen SNPs were identified in five genes encoding the components of the MMP-2 signaling pathway,assessed through carotid-femoral pulse wave velocity(cf PWV),and analyzed using multivariate logistic regression.The multigene influence on the risk of VS was assessed using multifactor dimensionality reduction(MDR)and generalized multifactor dimensionality regression(GMDR)modeling.Results Within the multivariate logistic regression models,four SNPs were screened to have significant associations with VS:chemokine(C-C motif)ligand 2(CCL2)rs4586,MMP2 rs14070,MMP2rs7201,and MMP2 rs1053605.Carriers of the T/C genotype of MMP2 rs14070 had a 2.17-fold increased risk of developing VS compared with those of the C/C genotype,and those of the T/T genotype had a19.375-fold increased risk.CCL2 rs4586 and MMP-2 rs14070 exhibited the most significant interactions.Conclusion CCL2 rs4586,MMP-2 rs14070,MMP-2 rs7201,and MMP-2 rs1053605 polymorphisms were significantly associated with the risk of VS.

Long noncoding RNAs HAND2-AS1 ultrasound microbubbles suppress hepatocellular carcinoma progression by regulating the miR-873-5p/tissue inhibitor of matrix metalloproteinase-2 axis

BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found that the expression of lncRNA HAND2-AS1 was downregulated in HCC tissues,but its role in HCC progression is unclear.Ultrasound targeted microbubble destruction mediated gene transfection is a new method to overexpress genes.AIM To study the role of ultrasound microbubbles(UTMBs)mediated HAND2-AS1 in the progression of HCC,in order to provide a new reference for the treatment of HCC.METHODS In vitro,we transfected HAND2-AS1 siRNA into HepG2 cells by UTMBs,and detected cell proliferation,apoptosis,invasion and epithelial-mesenchymal transition(EMT)by cell counting kit-8 assay,flow cytometry,Transwell invasion assay and Western blotting,respectively.In addition,we transfected miR-837-5p mimic into UTMBs treated cells and observed the changes of cell behavior.Next,the UTMBs treated HepG2 cells were transfected together with miR-837-5p mimic and tissue inhibitor of matrix metalloproteinase-2(TIMP2)overexpression vector,and we detected cell proliferation,apoptosis,invasion and EMT.In vivo,we established a mouse model of subcutaneous transplantation of HepG2 cells and observed the effect of HAND2-AS1 silencing on tumor formation ability.RESULTS We found that UTMBs carrying HAND2-AS1 restricted cell proliferation,invasion,and EMT,encouraged apoptosis,and HAND2-AS1 silencing eliminated the effect of UTMBs.Additionally,miR-873-5p targets the gene HAND2-AS1,which also targets the 3’UTR of TIMP2.And miR-873-5p mimic counteracted the impact of HAND2-AS1.Further,miR-873-5p mimic solely or in combination with pcDNA-TIMP2 had been transformed into HepG2 cells exposed to UTMBs.We discovered that TIMP2 reversed the effect of miR-873-5p mimic caused by the blocked signalling cascade for matrix metalloproteinase(MMP)2/MMP9.In vivo results showed that HAND2-AS1 silencing significantly inhibited tumor formation in mice.CONCLUSION LncRNA HAND2-AS1 promotes TIMP2 expression by targeting miR-873-5p to inhibit HepG2 cell growth and delay HCC progression.

UNAXIS的Matrix2 DVD5／9／10生产线

Matrix2是Unaxis推出的第二代DVD5／9／10生产线,通过重新设计优化了工艺和生产步骤,使生产线有更高的产能、更长的无故障时间、更好的生产重复性和设备的可维护性。Matrix2作为生产工艺有保证的预录DVD光盘的一揽子方案,表征着有全球服务网络支持的最新的技术革新。

All-trans retinoic acid regulates the expression of MMP-2 and TGF-β2 via RDH5 in retinal pigment epithelium cells

·AIM: To investigate the effect of all-trans retinoic acid(ATRA) on retinol dehydrogenase 5(RDH5), matrix metalloproteinase-2(MMP-2) and transforming growth factor-β2(TGF-β2) transcription levels, and the effect of RDH5 on MMP-2 and TGF-β2 in retinal pigment epithelium(RPE) cells.·METHODS: After adult RPE cell line-19(ARPE-19 cells) intervened with gradient concentrations of ATRA(0-20 μmol/L) for 24h, flow cytometry was used to detect the proliferation and apoptosis of cells in each group, and quantitative realtime polymerase chain reaction(q RT-PCR) was used to detect RDH5, MMP-2 and TGF-β2 m RNA expression. Then, after ARPE-19 cells transfected with three different si RNA targets for 48h, the RDH5 knockdown efficiency of each group and expression of MMP-2 and TGF-β2 m RNA within them was detected by q RT-PCR. ·RESULTS: Flow cytometry results showed that ATRA could inhibit the proliferation of RPE cells and promote the apoptosis of RPE cells, and the difference of apoptosis was statistically significant when the ATRA concentration exceeded 5 μmol/L and compared with the normal control group(P=0.027 and P=0.031, respectively). q RT-PCR results showed that ATRA could significantly inhibit the expression level of RDH5 m RNA(P<0.001) and promote the expression of MMP-2 and TGF-β2 m RNA(P=0.03 and P<0.001, respectively) in a dose-dependent manner, especially when treated with 5 μmol/L ATRA. The knockdown efficiency of RDH5 si RNA varies with different targets, among which RDH5 si RNA-435 had the highest knockdown efficiency, i.e., more than 50% lower than that of the negative control group(P=0.02). When RDH5 was knocked down for 48h, the results of q RT-PCR showed that the expressions of MMP-2 and TGF-β2 m RNA were significantly up-regulated(P<0.001).·CONCLUSION: ATRA inhibits the expression of RDH5 and promotes MMP-2 and TGF-β2, and further RDH5 knockdown significantly upregulates MMP-2 and TGF-β2. These findings suggest that RDH5 may be involved in an epithelial-mesenchymal transition of RPE cells mediated by ATRA.

抗NXP2抗体阳性的皮肌炎1例报告并文献复习

抗核基质蛋白2(nuclear matrix protein 2,NXP2)抗体阳性的皮肌炎是特发性炎性肌病的一种,除肌无力、皮肤改变的典型表现外,还有钙质沉着、皮下水肿、严重的肌痛及吞咽困难等表现。本文报道1例具有典型临床及影像学表现、随访17个月后复查抗NXP2抗体为阴性的患者。1病例资料患者,男,27岁,因“肢体疼痛无力1月余,加重2周”于2019年6月8日就诊于我科。患者于入院1月前无明显诱因出现肢体疼痛,腰部疼痛症状明显。3周前出现肢体无力感,伴面部皮疹,鼻翼两侧为著。2周前出现全身浮肿,抬头及转颈无力,双上肢抬起费力,坐起费力,行走约50米后肌肉无力酸痛明显,伴双上肢近端、双侧髋部、双膝关节及前胸部皮疹,伴发热,化验示肌酸激酶7500 U/L,行肌电图示肌源性损害,门诊按“肌病”收至我科。患者自发病以来,饮食睡眠可,二便如常,体重增加约10千克。

N×N Clos Digital Cross-Connect Switch Using Quantum Dot Cellular Automata(QCA)

Quantum dot cellular automata(QCA)technology is emerging as a future technology which designs the digital circuits at quantum levels.The tech-nology has gained popularity in terms of designing digital circuits,which occupy very less area and less power dissipation in comparison to the present comple-mentary metal oxide semiconductor(CMOS)technology.For designing the rou-ters at quantum levels with non-blocking capabilities various multi-stage networks have been proposed.This manuscript presents the design of the N×NClos switch matrix as a multistage interconnecting network using quantum-dot cellular automata technology.The design of the Clos switch matrix presented in the article uses three input majority gates(MG).To design the 4×4 Clos switch matrix,a basic 2×2 switch architecture has been proposed as a basic mod-ule.The 2×2 switching matrix(SM)design presented in the manuscript utilizes three input majority gates.Also,the 2×2 SM has been proposed usingfive input majority gates.Two different approaches(1&2)have been presented for designing 2×2 SM usingfive input majority gates.The 2×2 SM design based on three input majority gate utilizes four zone clocking scheme to allow signal transmis-sion.Although,the clocking scheme used in 2×2 SM using three input MG and in 2×2 SM approach 1 usingfive input MG is conventional.The 2×2 SM approach 2 design,utilizes the clocking scheme in which clocks can be applied by electricfield generators easily and in turn the switch element becomes physically realizable.The simulation results conclude that the 2×2 SM is suitable for designing a 4×4 Clos network.A higher order of input-output switching matrix,supporting more number of users can utilize the proposed designs.

H5N1亚型禽流感病毒M2的修饰表达及其免疫原性分析

禽流感的发生不仅会造成禽类的大量死亡,而且也严重地威胁着人类健康,接种疫苗是控制禽流感发生的主要措施之一.M2基因的保守性使其成为基因工程亚单位疫苗的目标抗原.本研究将M2基因的跨膜区删除后,构建原核表达载体pET32a-△M 2,IPTG诱导后,收获的细菌总蛋白SDS-PAGE电泳结果表明修饰的M2基因在原核表达系统中得到高效表达,表达蛋白以可溶性形式存在,Western杂交和动物免疫结果表明重组蛋白具有抗原性和免疫原性.本研究结果为利用M2重组蛋白开发具有交叉保护作用的禽流感疫苗奠定了基础.

Expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 in hepatic stellate cells during rat hepatic fibrosis and its intervention by IL-10

AIM: To investigate the expression of matrix metallopr-oteinase-2 and tissue inhibitor of metalloproteinase-1 in hepatic fibrosis and the antifibrogenic role of exogenous interleukin-10 (IL-10). METHODS: Hepatic fibrosis was induced by CCI4 administration and 60 male Sprague-Dawley rats were randomly divided into normal control group (group N, 8 rats), CCI4-induced group (group C, 28 rats) and IL-10-treated group (group I, 24 rats). At the beginning of the 7th and 11th wk, rats in each group were routinely perfused with pronase E and type IV collagenase through portal vein catheter and the suspension was centrifuged by 11% Nycodenz density gradient to isolate hepatic stellate cells (HSCs). RT-PCR was used to analyze mRNA of MMP-2 and TIMP-1 from freshly isolated cells. Densitometric data were standardized with β-actin signals. Immunocytochemistry was performed to detect MMP-2 and TIMP-1 expression in HSC cultured for 72 h. RESULTS: Compared to group N in the 7th wk, MMP-2 and TIMP-1 mRNA increased in group C (P= 0.001/0.001) and group I (P= 0.001/0.009). The level of MMP-2 and TIMP-1 mRNA in group I was significantly lower than that in group C (P= 0.001/0.001). In the 11th wk, MMP-2 mRNA in group I was still lower than that in group C (P = 0.005), but both dropped compared with that in the 7th week (P = 0.001/0.004). TIMP-1 mRNA in group I was still lower than that in group C (P= 0.001), and increased in group C (P= 0.001) while decreased in group I (P = 0.042) compared with that in the 7th wk. Same results were found by immunocytochemistry. CONCLUSION: Expression of MMP-2 and TIMP-1 is increased in hepatic fibrosis. IL-10 exhibits an antifibrogenic effect by suppressing MMP-2 and TIMP-1 expression.

Suppression of matrix metalloproteinase-2 via RNA interference inhibits pancreatic carcinoma cell invasiveness and adhesion

AIM:To investigate the inhibitory effects of RNA interference (RNAi) on expression of matrix metalloproteinase-2 (MMP-2) gene and invasiveness and adhesion of human pancreatic cancer cell line,BxPC-3.METHODS:RNAi was performed using the vector (pGPU6)-based small interference RNA (siRNA) plasmid gene silence system to specifically knock down MMP-2 expression in pancreatic cancer cell line,BxPC-3. Four groups of different specific target sequence in coding region of MMP-2 and one non-specific sequence were chosen to construct four experimental siRNA plasmids of pGPU6-1,pGPU6-2,pGPU6-3 and pGPU6-4,and one negative control siRNA plasmid of pGPU6 (-). MMP-2 expression was measured by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Cell proliferation and apoptosis were examined by methyl thiazolyl tetrazolium (MTT) and flow cytometry,respectively. The abilities of adhesion and invasion were detected by cell adhesion assay and cell invasion assay using Transwell chambers.RESULTS:The expression of MMP-2 was inhibited and the inhibitory effects of different sequence varied. pGPU6-1 group had the most efficient inhibitory effect,followed by pGPU6-2 and pGPU6-3 groups.Invasiveness and adhesion were more significantly reduced in pGPU6-1,pGPU6-2 and pGPU6-3 groups as compared with pGPU6 (-) and blank control groups. However,no difference concerning cell proliferation and apoptosis was observed after transfection between experiment groups and control groups.CONCLUSION:RNAi against MMP-2 successfully inhibited the mRNA and protein expression of MMP-2 in the pancreatic cancer cell line,BxPC-3,leading to a potent suppression of tumor cell adhesion and invasion without affecting cell proliferation and apoptosis. These findings suggest that the RNAi approach towards MMP-2 may be an effective therapeutic strategy for the clinical management of pancreatic tumor.

Relationship between matrix metalloproteinase-2 mRNA expression and clinicopathological and urokinase-type plasminogen activator system parameters and prognosis in human gastric cancer

AIM: To investigate the relationship between matrix metalloproteinase-2 (MMP-2) mRNA expression and clinicopathologic and urokinase-type plasminogen activator (uPA) system parameter and prognosis in human gastric cancer. METHODS: Expression of MMP-2 mRNA, uPA, and uPA-R mRNA in tumor tissues and ≥5 cm adjacent normal tissues from 67 cases of gastric cancer was studied using RT-PCR and Northern blot respectively.Survival analyses were done using the Kaplan-Meier method. RESULTS: The expression rates of MMP-2 mRNA,uPA and uPA-R mRNA in tumor tissues (31%,41%,and 51%, respectively) were significantly higher than those in ≥5 cm adjacent tissues (19%, 11%, and 9%; X2=4.59,43.58, and 53.24 respectively, P<0.05,0.0001,and 0.0001, respectively). Expression of MMP-2 mRNA was significantly correlated with lymph node metastasis (metastasis: 61.9%, no metastasis: 39.1%, X2= 7.61, P<0.05),Lauren's classification of diffuse/mixed types:54.2%,intestinal type: 26.3%,X2 = 4.25, P<0.05, expression of uPA and uPA-R mRNA (uPA+: 55.1%, uPA-: 22.2% and uPA-R+: 54.9%, uPA-R-: 18.8%, X2=5.72 and 6.40 respectively, P<0.05).Kaplan-Meier survival analysis of MMP-2 mRNA expression did not show significant difference in all 67 cases, but revealed an association of the expression of MMP-2 mRNA, uPA, and uPA-R mRNA with worse prognosis (P= 0.0083, 0.0160, and 0.0094, respectively). CONCLUSION: MMP-2 may play an important role in the development of invasion and metastasis of gastric cancer.

Protective role of metalloproteinase inhibitor(AE-941) on ulcerative colitis in rats

AIM:To evaluate the protective role of AE-941,a matrix metalloproteinase(MMP) inhibitor,on ulcerative colitis(UC) in rats.METHODS:Sprague Dawley(SD) rats were randomly divided into three groups:a control group,an AE-941 treatment group,and an UC model group.Rats were sacrificed on days 7,21,or 56 following administration of treatment by enema and the disease activity index(DAI),colonic mucosa damage index(CMDI) and colonic expression of MMP-2 and MMP-9 were assessed.RESULTS:DAI and CDMI scores in the UC model group increased significantly compared to the control group at all timepoints(P < 0.001),and also increased significantly at the 21-and 56-d timepoints compared to the AE-941-treated group(DAI:21-and 56-d = 2.09 ± 0.25,1.52 ± 0.30 vs 1.55 ± 0.28,0.59 ± 0.19,respectively,P = 0.040 and 0.007,CMDI:21-and 56-d = 3.03 ± 0.42,1.60 ± 0.35 vs 2.08 ± 0.46,0.86 ± 0.37,respectively,P = 0.040 and 0.005).Furthermore,the colonic expression of MMP-2 and MMP-9 in the UC model group increased significantly compared to the control group(P < 0.001),and also increased compared to the AE-941-treated group on the 21-and 56-d timepoints(MMP-2:21-and 56-d = 0.6048 ± 0.0522,0.4163 ± 0.0330vs 0.3983 ± 0.0218,0.1093 ± 0.0072,respectively,P = 0.010;MMP-9:21-and 56-d = 0.6873 ± 0.0472,0.4328 ± 0.0257vs 0.5179 ± 0.0305,0.2673 ± 0.0210,respectively,P = 0.010 and 0.040).CONCLUSION:Expression of MMP-2 and MMP-9 increased significantly in rats with UC.AE-941 can reduce colonic mucosal damage by downregulating the expression of MMP-2 and MMP-9.

S100A4 siRNA Inhibits Human Pancreatic Cancer Cell Invasion In Vitro

Objective Pancreatic cancer is one of the most deadly cancers, which is characterized by its high metastatic potential. S100A4 is a major prometastatic protein involved in tumor invasion and metastasis which precise role in pancreatic cancer has not been fully investigated. We knocked down the S100A4 gene in the Bxpc-3 pancreatic cancer cell line via RNA interference to study the changes in cell behavior. Methods Real-time polymerase chain reaction and western blotting were used to detect mRNA and protein expression levels of S100A4, matrix metalloproteinase （MMP）-2, E-cadherin and thrombospondin （TSP）-I. Transwell chambers were used to detect the migration and invasion abilities; a cell adhesion assay was used to detect adhesion ability; colony forming efficiency was used to detect cell proliferation; flow cytometry was used to detect apoptosis. Results S100A4 mRNA expression was reduced to 17% after transfection with SIOOA4-siRNA, and protein expression had a similar trend, mRNA and protein expression of MMP-2 was reduced and that of E-cadherin and TSP-1 was elevated, indicating that S100A4 affects their expression. S100A4-silenced cells exhibited a marked decrease in migration and invasiveness and increased adhesion, whereas overall proliferation and apoptosis were not overtly altered. Conclusion S100A4 and its downstream factors play important roles in pancreatic cancer invasion, and silencing AIOOA4 can significantly contain the invasiveness of pancreatic cancer.

Expression of MMP-2 and MMP-9 in retinoblastoma and their significance

AIM: To investigate the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in retinoblastoma (Rb), and their relationships with tumor development stage. METHODS: Immunohistochemical technique was used to detect the expression of MMP-2 and MMP-9 in 41 cases of paraffin embedded Rb samples. Quantitative analysis of the expression of MMP-2 and MMP-9 was assessed by HMIAS-2000 Color Pathologic Analysis System. The differences of the expression of MMP-2 and MMP-9 in each clinical and pathological stage were analyzed statistically. RESULTS: In all the 41 Rb specimens, MMP-2 and MMP-9 expression was found in tumor cells. The expression of MMP-2 and MMP-9 was significantly higher in tumors with optic nerve invasion than in tumors without optic nerve invasion (P<0.05); the expression of MMP-2 and MMP-9 was significantly higher in tumors of extra-ocular stage than in tumors of glaucomatous stage or intra-ocular stage( P<0.05). CONCLUSION: MMP-2 and MMP-9 exist in retinoblastoma cells. The level of MMP-2 and MMP-9 is related to optic nerve invasion and clinical stage of Rb, which suggests the expression of MMP-2 and MMP-9 could be connected to the invasion and development of tumor cells. Further research is needed for deeper understanding of the biological behavior and better evaluation of the prognosis of Rb.

Correlation of RECK with Matrix Metalloproteinase-2 in Regulation of Trophoblast Invasion of Early Pregnancy

To study the role of the reversion-inducing-cysteine-rich protein with Kazal motifs （RECK） gene and matrix metalloproteinase-2 （MMP-2） in the regulation of trophoblast invasion of early pregnancy. Immunohistochemistry, Western blot and gelatin zymography were used to detect the RECK protein expression localization, expression level and MMP-2 activation level in the placental tissues harvested from 52 normal pregnant women （27 in the early pregnancy, 25 in the term pregnancy）. Immunohistochemistry showed that RECK expression was found both in villous tissues of early pregnancy group and term pregnancy group and was mainly observed in cell membrane and cytoplasm of cytotrophoblasts and syneytiotrophoblasts. RECK expression increased with gestational time. RECK expression of early pregnancy group was significantly lower than that of term pregnancy group （P〈0.05）. RECK expression was significantly lower in cellular column （CC） with invasion ability. Western blot showed that the RECK protein expression in early pregnancy group was significantly lower than that in term pregnancy （P〈0.05）. The optical density values of RECK protein expression in early pregnancy group and term pregnancy group were 1.35±0.14 and 2.68±0.26, respectively, while MMP-2 activation ratio was contrary to RECK protein expression and decreased with the gestation time （P〈0.01）. The MMP-2 activation ratios of early pregnancy group and term pregnancy group were 0.46±0.05 and 0.10±0.02, respectively. The expression of the tumor inhibitory gene RECK was positively related with the invasion ability of trophoblasts, while the invasion gene MMP-2 was negatively related with the ability. The interaction between RECK and MMP-2 may play an important role in the regulation of the trophoblast invasion in early pregnancy.

Expression of Matrix Metalloproteinase and Its Tissue Inhibitor in Haemangioma

The action mechanism of matrix metalloproteinases-2 （MMP-2） and tissue inhibitor of metalloproteinases-2 （TIMP-2） in the genesis, development and degeneration of haemangioma was investigated by detecting their expression in the tissue of haemangioma in different phases by using the immunohistochemistry. Fifty paraffin-embedded specimens of skin capillary haemangioma were collected, which were documented in the Department of Pathology, Renmin Hospital of Wuhan University from 2000 to 2006. All samples were stained by regular HE method, and proliferative cell nuclear antigen （PCNA） was tested by immunohistochemical S-P method. The samples were classified according to the Mulliken criteria and the expression pattern of PCNA. Immunohistochemical S-P method was ap- plied to detect the expression of MMP-2 and TIMP-2 in proliferative and degenerative phases of cutaneous capillary haemangioma, and in normal skin tissues. In combination with the detection of the expression of factor Ⅷ-related antigen, it was verified that in haemangioma tissues, the cells expressing MMP-2 and TIMP-2 were vascular endothelial cells. The MMP-2 and TIMP-2 expression was quantitatively analyzed by image analysis system （HPIAS-1000）, and one-way ANOVA（107） and SNK（q） test were done to analyze average absorbance （A） and positive area rate of immunohistochemically positive particles by using SPSS11.5. The results showed： （1） Among 50 samples of haemangioma, there were 26 proliferative haemangiomas, and 24 degenerative haemangiomas, respectively; （2） The expression of MMP-2 was weak in normal vascular endothelial cells, cytoplasm of connective tissues and extracellular matrix around blood vessels. The expression of MMP-2 in proliferative group was significantly higher than in degenerative group and control group （normal skin） （P〈0.05）, but there was no statistically significant difference between the latter two groups; （3） TIMP-2 was highly expressed in normal tissues, degenerative vascular endothelial cells, cytoplasm of connective tissues and extracellular matrix around blood vessels. The expression level of TIMP-2 in proliferative phase was significantly lower than in degenerative phase （P〈0.05）, and the expression of TIMP-2 in proliferative phase was significantly different from that in degenerative phase and normal tissues （P〈0.05）. It was concluded that in proliferative phase of haemangioma, MMP-2 may promote over-proliferation of endothelial cells of haemangioma, and in degenerative phase, TIMP-2 can inhibit the proliferation of endothelial cells of haemangioma. The two substances play important roles in the genesis, development and degeneration of haemangiomas.

Therapeutic effect of interleukin-10 on CCI_4-induced hepatic fibrosis in rats

AIM： To study the therapeutic effect of exogenous interleuldn-10 on CCl4-induced hepatic fibrosis in rats and its passible mechanisms. METHODS： Fourty-seven SD rats were randomly divided into control group （group N） and CCl4-induced hepatic fibrosis model group （group C）. After CCl4 was given for 9 wk, the model group was divided into three groups. Rats in group H were put to death immediately, rats in group T were treated with IL-10 for another three wk and then put to death, rats in group R recovered after three weeks and were then killed. The degree of hepatic fibrosis was measured by HE staining and histological activity index （HAI）. Histological activity index （HAI）, change of collagen types Ⅰ and Ⅲ were measured by Picrosirius staining. The expression of TNF-α, HHP-2 and TIMP-1 in liver tissue was measured by S-P immunohis tochemistry.RESULTS： CCl4- induced experimental rat hepatic fibrosis model was established successfully. The degree of hepatic fibrosis was markedly lower in group T than in groups H and R, and there was no difference between the two groups. The expression of collagen types I and III was significantly suppressed in group T and was slightly suppressed in groups H and R. The positive levels of TNF-α, HHP-2 and TIHP-1 in group H increased significantly compared to those in group N （P〈0.01）. The positive signals decreased significantly in groups T and R （P〈0.01）, but positive score was significantly lower in group T than in group R （P〈 0.01）. CONCLUS10N： Exogenous IL-10 can reverse CCl4-induced hepatic fibrosis in rats. IL-10 may exert its reversible effects on hepatic fibrosis by blocking CCl4-induced inflammation, inhibiting expression of HHP-2 and TIMP-1 and promoting resolution of collagen types Ⅰ and Ⅲ.

Anti-proliferative effect of olmesartan on Tenon's capsule fibroblasts

AIM： To evaluate the inhibitive effect of olmesartan to fibroblast proliferation and the anti-scarring effect in Tenon＇s capsule, both in vitro and in vivo.· METHODS： Human primary Tenon＇s capsule fibroblasts were cultured in vitro, treated with up titrating concentrations of olmesartan. The rate of inhibition was tested with methyl thiazol tetrazolium（MTT） method.Real-time PCR was performed to analyze changes in m RNA expressions of the fibrosis-related factors： matrix metalloproteinase-2（MMP-2）, tissue inhibitor of metalloproteinase（TIMP-1,2） and proliferating cell nuclear antigen（PCNA）. Thirty rabbits were divided into5 groups（3, 7, 14, 21, and 28d）. A rabbit conjunctiva flap model was created in each eye. Olmesartan solution was injected subconjunctivally and then evaluated its anti-proliferation and anti-fibrosis effects through the histological morphology and immunohistochemistry of MMP-2 and PCNA in each group. Only the 7d group was treated with Masson＇s trichrome to compare the neovascularization in the subconjunctiva area.·RESULTS： In vitro, cultured Tenon＇s capsule human fibroblasts showed a dose dependent inhibition by olmesartan in MTT. Olmesartan reduced m RNA expressions of MMP-2 and PCNA but increased m RNA expressions of TIMP-1 and TIMP-2. In vivo, the rabbit eyes treated with olmesartan at 3rd, 7th, 14 thand 21stdays demonstrated a significant reduced expressions of MMP-2 and PCNA compared with control eye, no significant difference observed in 28 thday group. The cellular proliferation and neovascularization was suppressed by olmesartan in Masson＇s trichrome observation.·CONCLUSION： By inhibiting fibroblasts in vitro and in vivo, olmesartan prevents the proliferation and activity of fibroblasts in scar tissue formation, which might benefit glaucoma filtering surgery.

Anneal and Concentration Effect on PL Properties of Sol-Gel Derived Eu^(3+) Doped SiO_2 Glass

Eu3+ doped SiO2 nano-crystalline glasses were prepared by sol-gel method. The broad peak of XRD pattern indicates an amorphous SiO2 matrix. The affection of anneal time and anneal temperatures on photoluminescence (PL) properties of SiO2 glass under different Eu doping concentration were studied systematically. It is found that the optimized anneal time is about 3 h. The excitation spectra of 2% Eu3+ doped SiO2 glass powder were measured under various anneal temperatures, and the optimized anneal temperature is observed around 700℃. The fluorescence-quenching effect can be observed in the emission spectra when the annealing temperature exceeds 700℃. The emission spectra of different molar ratio dopants were measured at an annealed temperature of 500℃, and the concentration-quenching phenomenon has also been observed in SiO2 glass powder when the molar ratio of Eu3+ ion exceeds 3% . The result shows that the PL intensity approaches its maximum when the molar ratio of Eu3+ ions in the sample is about 3% . In addition, a comparatively stronger emission spectrum at wavelength of 703 nm which is corresponding to the energy transition 5D0→7F4 of Eu ions is also obtained.

Effects of angiopoietin-1 on attachment and metastasis of human gastric cancer cell line BGC-823

AIM： To evaluate the effects of angiopoietin-1 （Ang-1） on adhesion of gastric cancer cell line BGC-823 and expression of integrin β1, CD44V6, urokinase-type plasminogen activator （uPA） and matrix metalloproteinase-2 （MMP-2）. METHODS： BGC-823 cells were transfected transiently with adenovirus-Ang-1 （Ad-Ang-1）. Cells transfected transiently with adenovirus-green fluorescent protein （Ad-GFP） and untransfected cells were used as a negative and blank control group, respectively. The cell adhesion rate between cell and extracellular matrix （ECM） was determined by cell adhesion assay. To investigate whether Ang-1 could reinforce gastric carcinoma metastasis, we performed migration and invasion assays in BGC-823 cells. The mRNA and protein expression of integrin β1, CD44V6, uPA and MMP-2 were detected by reverse transcription polymerase chain reaction and Western blotting, respectively. The expression of integrin β1 and CD44V6 was measured by immunohistochemistry. RESULTS： BGC-823 cells were transfected successfully. The adhesion rate increased significantly in the Ad-Ang-1 group （P 〈 0.05）. The Ad-Ang-1-transfected group had a significant increase in migration and invasion compared with that of the mock-transfected and Ad-GFP groups. The mRNA and protein expression of integrin β1, CD44V6, uPA and MMP-2 in the Ad- Ang-1 group was higher than that in the Ad-GFP and blank control groups （P 〈 0.05）. Compared with mocktransfected and Ad-GFP groups, integrin 131 and CD44V6 expression intensity greatly increased （P 〈 0.05）. CONCLUSION： Transfection of Ang-1 into human gastric cancer cell line BGC-823 can significantly increase expression of integrin β1 and CD44V6, by which cell adhesion and metastasis to the ECM are promoted.