Investigation of the tissue-damaging effects and mechanisms of neutrophil-derived MMP-8 in Fusarium keratitis / 中华实验眼科杂志

Objective:To investigate the mechanism of tissue damage caused by neutrophil matrix metalloproteinase-8 (MMP-8) in Fusarium keratitis. Methods:A total of 108 male C57BL/6J SPF grade mice, 6-8 weeks old, were selected to establish a model of Fusarium keratitis (FK) in the right eyes.Corneal inflammation in mice was observed and scored under a slit lamp microscope.Based on the corneal inflammation scores, the modeling eyes were divided into 0, 12, 24, 48, and 72-hour groups post-modeling.At the corresponding time points, mice were euthanized, and corneal tissues were collected.The expressions of MMP-8, adenylate-activated protein kinase (AMPKα) and its serine 172-site phosphorylated form (p-AMPKα) proteins in corneal tissues were detected by Western blot.The neutrophil count in mice corneal tissues at each time point was determined using hematoxylin and eosin staining.The co-localization of neutrophils and MMP-8 protein in the cornea was observed by immunofluorescence staining.In the in vitro corneal collagen degradation experiment, corneal tissues were divided into MMP-8 group, buffer group, and normal saline group, which were treated with 100 μl of activated recombinant MMP-8, detection buffer, and normal saline, respectively.Hydroxyproline content in corneal tissues was determined using a hydroxyproline assay kit, and the mass fractions of hydroxyproline were compared among the groups.Peripheral blood neutrophils were isolated from human blood samples, and Fusarium spores were collected for experiments.Human neutrophils were divided into four groups, negative control group (cultured neutrophils), co-culture group (neutrophils co-cultured with spores), AICAR-treated group (neutrophils co-cultured with spores and treated with p-AMPK protein kinase activator AICAR), and compound C-treated group (neutrophils co-cultured with spores and treated with the inhibitor compound C).The MMP-8 protein expression levels in each group of human neutrophils were assessed via immunofluorescence staining.The use and care of animals complied with the ARVO statement and Regulations for the Administration of Affairs Concerning Experimental Animals.The animal experiment protocol was approved by the Animal Ethics Committee of Henan Eye Hospital (No.HNEECA-2017-04-02).One healthy adult volunteer was selected and 10 ml of peripheral venous blood was collected.The clinical study protocol was approved by the Clinical Ethics Committee of Henan Eye Hospital (No.HNEECKY-2019[16]). Results:At 24 hours post-modeling, corneal opacification was observed in the modeling eyes, and corneal perforation occurred in 72-hour post-modeling group.The corneal inflammation scores in 24, 48, and 72-hour post-modeling groups were all higher than those in 12-hour post-modeling group, and the differences were statistically significant (all at P<0.001).The relative expression levels of MMP-8 protein in the cornea were higher in 12, 24, and 48-hour post-modeling groups compared to 0-hour group, with statistically significant differences (all at P<0.001).There was a moderate positive correlation between the relative expression level of MMP-8 protein in the cornea and the inflammation scores of the modeling eye ( rs=0.50, P<0.05).In the cornea, the p-AMPKα (Thr 172)/AMPKα ratio was higher in 24, 48, and 72-hour post-modeling groups than in 0-hour group, and the differences were statistically significant (all at P<0.05).The p-AMPKα(Thr 172)/AMPKα ratio in the cornea was moderately positively correlated with the relative expression level of MMP-8 protein ( r=0.54, P<0.01).The number of neutrophils in the cornea was significantly higher in 24, 48, and 72-hour post-modeling groups than in 0-hour group, with statistically significant differences (all at P<0.001).The number of neutrophils in the cornea was strongly positively correlated with the inflammation score ( rs=0.77, P<0.001), and was moderately positively correlated with the relative expression level of MMP-8 protein ( r=0.56, P<0.05).MMP-8 protein expression in the cornea of the modeling eyes showed a high degree of co-localization with neutrophils.The hydroxyproline content in the cornea was (0.52±0.02)μg/mg, (0.51±0.03)μg/mg, and (0.27±0.02)μg/mg in buffer group, normal saline group and MMP-8 group, respectively, with a significant overall difference among them ( F=156.63, P<0.01).The corneal hydroxyproline content was lower in MMP-8 group compared to buffer and normal saline groups, and the differences were statistically significant (all at P<0.05).In the experiment involving the infection of cultured Fusarium spores with human neutrophils, the fluorescence intensity of MMP-8 expression was significantly higher in AICAR-treated group than in negative control group and compound C-treated group, with statistically significant differences (all at P<0.05). Conclusions:The MMP-8 secreted by neutrophils in mice with fungal keratitis can degrade corneal stromal collagen fibers, leading to corneal opacification or perforation.The variations in MMP-8 protein expression levels in human neutrophils may be associated with AMPK activation.

Effect and mechanism of transplantation of human amniotic epithelial cells on endometrium of uterine scar model rats / 中国比较医学杂志

Objective To investigate the effect of human amniotic epithelial cell(hAEC)transplantation on endometrium improvement and matrix metalloproteinase 8(MMP-8)and vascular endothelial growth factor(VEGF)expression in a rat model of uterine scaring.Methods The uterine scar model was established in rats that were randomly divided into model and transplantation groups with 18 rats in each group.The other 18 rats were used as the sham operation group.Rats in the transplantation group were injected with hAECs in the uterine scar,and rats in model and sham operation groups were administered the same amount of PBS.After 4 weeks,the uterine tissues of eight rats in each group were collected.Histomorphological changes and endometria fibrosis were observed by HE staining and Masson staining respectively,and the endometrial thickness and number of glands were measured.Endometrial growth and receptivity were evaluated by immunohistochemical staining of cytokeratin and integrin β3,respectively.mRNA expression of MMP-8 and VEGFA in endometrial tissues was measured by RT-qPCR.Western blot was used to measure MMP-8 and VEGFA protein expression.After 8 weeks,the remaining 10 rats in each group were used to assess gestational ability.Results The endometrial thickness,gland number,IOD value of keratin and integrin β3,relative mRNA and protein expression levels of MMP-8 and VEGFA,pregnancy rate and number of uterine embryos in model and transplantation groups were lower than those in sham operation group(P<0.05).The endometrial thickness,gland number,IOD value of keratin and integrin β3,relative mRNA and protein expression of MMP-8 and VEGFA,pregnancy rate and number of uterine embryos were higher than those in model group(P<0.05).Additionally,hAEC transplantation improved the pathological morphology of endometrial tissue in rats with uterine scaring and reduced the degree of endometrial fibrosis.Conclusions hAEC transplantation improves endometrial injury,reduces scar formation,improves endometrial receptivity,and enhances pregnancy function in model rats,which may be related to promotion of MMP-8 and VEGFA expression.

The effect of matrix metalloproteinase-8 protein on proliferation and migration of squamous cell carcinoma EC109 cells of the esophagus / 中国医师杂志

Objective:To investigate the effects of matrix metalloproteinase-8 (MMP-8) on the proliferation and migration of esophageal squamous cell carcinoma EC109 cells, and to explore its possible mechanism.Methods:Esophageal epithelial cells Het-1A and esophageal squamous cell carcinoma cell lines (EC109, CEC2, KYSE150, TE-1 cells) were cultured. Using polymerase chain reaction (PCR) experiments, MMP-8 low expression cell line EC109 cells were screened for plasmid transfection. The MMP-8 overexpression plasmid was MMP-8 overexpression group, and the empty plasmid was the empty vector group. Flow cytometry was used to screen and amplify the transfected cells, and stable transfected cells were constructed. The changes of proliferation and migration were detected by methyl thiazolyl tetrazolium (MTT) and scratch test, and the mRNA expression of proliferation and migration related genes was detected by quantitative real-time polymerase chain reaction (qRT-PCR).Results:MMP-8 expression was lowest in EC109 cells among all esophageal squamous cell carcinoma cell lines. Compared with the empty vector group, the proliferation and migration ability of MMP-8 overexpression group cells were significantly enhanced, and the mRNA expression levels of proliferation and migration related genes AKT1, RAC1, p53, epidermal growth factor receptor (EGFR), MTA1 and RARRES1 were significantly increased (all P<0.05). Conclusions:MMP-8 protein can enhance the proliferation and migration ability of esophageal squamous cell carcinoma EC109 cells. MMP-8 overexpression can promote the mRNA expression of proliferation and migration related genes, which may be related to its promotion of EC109 cell proliferation and migration.

The role of a disintegrin-like and metalloproteinase with throm bospondin typeⅠmotifs-8 in lung adenocarcinomaand its mechanism / 中国医师进修杂志

Objective:To explore the role of a disintegrin-like and metalloproteinase with throm bospondin typeⅠmotifs-8(ADAMTS8) gene in lung adenocarcinoma and its mechanism.Methods:Selected lung adenocarcinoma data sets GSE75037 and GSE116959 and lung adenocarcinoma transcriptome data and clinical information from the TCGA database; useed R software to analyze differential genes in lung adenocarcinoma tissues, and performed GO enrichment analysis and KEGG signal pathway enrichment for differential genes set analysis; analyzed the expression of ADAMTS8 gene in lung adenocarcinoma and its correlation with patient survival and prognosis; CCK-8 experiment detects the effect of ADAMTS8 overexpression or knockdown on the proliferation of A549 cells; Western blot detected ADAMTS8 overexpression or knockdown effect on Wnt/β-catenin signaling pathway. Results:The combined analysis found that 395 genes were up-regulated in lung adenocarcinoma samples, and 716 genes were down-regulated; ADAMTS8 was under-expressed in lung adenocarcinoma tissues, and its expression level was related to tumor stage; low-expression of ADAMTS8 was associated with shorter survival time, poor prognosis, Cox regression analysis showed that ADAMTS8 can be used as an independent prognostic marker for patients with lung adenocarcinoma; CCK-8 results showed that overexpression of ADAMTS8 can inhibit the proliferation of A549 cells, knocking down ADAMTS8 can promote the proliferation of A549 cells ( P<0.05); Western blot results showed that after overexpression of ADAMTS8, the protein levels of β-catenin, cyclin D1 and c-Myc in cells were significantly reduced ( P<0.05), while knocking down ADAMTS8 could cause the protein levels of β-catenin, cyclin D1 and c-Myc in cells increased significantly ( P<0.05). Conclusions:ADAMTS8 is under-expressed in lung adenocarcinoma and can be used as an independent prognostic marker for patients. Overexpression of ADAMTS8 may inhibit the proliferation of lung adenocarcinoma cells by inhibiting the activity of Wnt/β-catenin signaling pathway.

Association between Volatile Sulfur Compounds Prevotella intermedia and Matrix Metalloproteinase-8 Expression

Abstract Objective: To determine the correlation between levels of methyl mercaptan (CH3SH) hydrogen sulfide (H2S), the proportion of Prevotella intermedia (Pi), and matrix metalloproteinase-8 (MMP-8) gene expression levels in periodontitis patients accompanied by halitosis. Material and Methods: Samples were obtained from gingival crevicular fluid (GCF) in the deepest pocket and by swabbing in the tongue coating area in patients with periodontitis presenting with halitosis (n = 23) and healthy subjects as controls (n = 7). The values of CH3SH and H2S were obtained using Oral Chroma. The proportion of Pi and MMP-8 expression levels were evaluated using PCR-RT. All the result was statistically analyzed using SPSS software. Results: The levels of CH3SH and H2S in participants with PD ≥ 6 mm showed a robust negative correlation with the proportion of P. intermedia in GCF and tongue coating. No statistically significant association was detected between CH3SH and H2S levels and MMP-8 expression levels (p>0.05). Conclusion: There is no association between CH3SH and H2S levels, the proportion of P. intermedia, and MMP-8 expression in patients with periodontitis accompanied by halitosis (AU).

Application value of spiral CT combined with a disintegrin and metalloproteinase 8, neuron-specific enolase and cytokeratin 19 fragment measurements in the clinical diagnosis of lung cancer / 中国基层医药

Objective:To investigate the application value of spiral CT combined with a disintegrin and metalloproteinase 8 (ADAM8), neuron-specific enolase (NSE) and cytokeratin 19 fragment (CYFRA21-1) measurements in the clinical diagnosis of lung cancer.Methods:Fifty patients with lung cancer who received treatment in Shanxi Rongjun Hospital from February 2018 to December 2019 were included in the lung cancer group. Fifty patients with benign lung disease who concurrently received treatment in Shanxi Rongjun Hospital were included in the benign lung disease group. Fifty 50 healthy controls who concurrently received treatment in Shanxi Rongjun Hospital were included in the control group. Serum levels of ADAM8, NSE and CYFRA211 were compared among the three groups. Three groups received spiral CT scans. ADAM8-, NSE- and CYFRA211-positive detection rates were analyzed. The receiver operating characteristic (ROC) curve was used to analyze the efficacy of different methods in the diagnosis of lung cancer. Serum ADAM8, NSE and CYFRA211 levels in patients with lung cancer at different TNM stages were compared.Results:Serum levels of ADAM8, NSE and CYFRA211 in the lung cancer and benign lung disease groups were (381.69 ± 34.82) ng/L, (255.28 ± 30.48) ng/L, (16.87 ± 3.11) μg/L, (9.27 ± 2.11) μg/L,(13.54 ± 8.10) μg/L, (3.01 ± 1.34) μg/L, respectively, which were significantly higher than those in the control group [(225.83 ± 24.19) ng/L, (7.42 ± 2.35) μg/L, (1.78 ± 1.02) μg/L, t = 5.352, 25.994, 4.142, 17.142, 5.165, 10.186, all P < 0.05]. Serum levels of ADAM8, NSE and CYFRA211 in the lung cancer group were significantly higher than those in the benign lung disease group ( t = 19.316, 14.299, 9.069, all P < 0.05). The positive detection rate of lung cancer by spiral CT combined with ADAM8, NSE and CYFRA211 measurements was 92.00%, which was significantly higher than that by spiral CT combined with a single detection ( χ2 = 7.862, 9.000, 11.422, 9.000, all P < 0.05). The ROC curve analysis revealed that the area under the ROC curve, sensitivity and specificity of the combined method were 0.916, 0.920 and 0.900, respectively, which were significantly higher than those of spiral CT combined with a single detection. Serum ADAM8, NSE and CYFRA211 levels at TNM stages III-IV were (430.18 ± 36.43) ng/L, (20.05 ± 3.49) μg/L, (15.93 ± 8.22) μg/L, respectively, which were significantly higher than those at TNM stages I-II [(314.72 ± 30.85) ng/L, (12.49 ± 2.67) μg/L, (10.25 ± 6.35) μg/L, t = 11.777, 8.312, 2.644, all P < 0.05). Conclusion:Spiral CT combined with serum ADAM8, NSE and CYFRA211 levels can greatly increase the diagnostic sensitivity and specificity of lung cancer, which is worthy of clinical application.

Expression of periostin in gingival tissue of patients with chronic periodontitis and its clinical significance / 吉林大学学报(医学版)

Objective: To detect the expressions of periostin, matrix metalloproteinase-8 (MMP-8) and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) in gingival tissue of the patients with chronic periodontitis, and to explore the possible role of periostin in the occurrence and development of chronic periodontitis and its related biological mechanism. Methods: A total of 23 normal gingival tissues (control group) and 19 inflammatory gingival tissues (case group) were selected. The expressions of periostin, MMP-8 and TIMP-2 in gingival tissue of the patients in two groups were detected by immunohistochemical SP method. The correlation between the expressions of periositn and MMP-8 and TIMP-2 in gingival tissue of the patients in two groups were detected by Spearman analysis. Results: The positive expression rate of periostin in gingival tissue of the patients in case group was lower than that in control group (P<0. 05). The correlative analysis results demonstrated that the expression of periostin had negative relationship with the expression of MMP-8 (r=-0.51, P<0. 05) in control group, and positive relationship with the expression of TIMP-2 (r=0. 50, P<0. 05); in case group, the expression of periostin had negative relationship with the expression of MMP-8 (r=-0.482, P<0. 05), and positive relationship with the expression of TIMP-2 (r= 0.655, P<0. 05). Conclusion: Periostin can be used as a preliminary indicator for maintaining the structural stability of gingival tissue, and become a research target for periodontal tissue regeneration.

Expression of Toll-Like Receptor 4 and Matrix Metalloproteinase 8 in Gingival Crevicular Fluid in Patients with Periodontitis

Abstract Objective: To determine the expression of TLR4 and MMP8 in gingival crevicular fluid [GCF] in patients with periodontitis. Material and Methods: Clinical samples were collected from 23 gingival crevicular fluid of periodontal disease subjects (n = 14) and healthy periodontal subjects (n=9). Measurement of Clinical parameters of probing pocket depth (PPD), bleeding on probing (BOP), and clinical attachment loss (CAL) were included as diagnostic criteria. Pocket Depth (PD) and CAL were defined as present if the PPD was ≥ 4 mm and the CAL ≥ 1 mm. Expression of TLR4 and MMP8 in the gingival crevicular fluid of deep pockets (PD≥ 6mm), shallow pockets (PD 4-5 mm) and healthy periodontal sulcus (0-3 mm) were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Statistical analysis to compare the pocket was using Independent t-test and Mann-Whitney test. Correlation between mRNA expression and clinical parameters was analyzed using Spearman's correlation test Results: Expression of TLR4 was higher in shallow pockets compared to the control group, but the difference was not statistically significant (p>0.05). The expression of MMP8 was higher in shallow pockets compared to the control group, but the difference was not statistically significant (p>0.05) either. There is no significant correlation between TLR4 and MMP8 with clinical periodontal parameters Conclusion: TLR4 and MMP8 mRNA expression levels should not be used as a clinical biomarker in periodontitis diagnostic tools.

The analysis of matrix metalloproteinase-8 in gingival crevicular fluid and periodontal diseases

Periodontal disease, also generally called periodontitis or gum disease, is a chronic infection-induced inflammatory disease that causes tooth loss if not properly treated, and is considered as a modifying factor in systemic health. Gingival crevicular fluid (GCF) matrix metalloproteinase-8 (MMP-8) is an inflammatory marker found in periodontal pathologic conditions. Gingivitis, a nondestructive type of periodontal disease, can progress to periodontitis if left untreated. Therefore, assessing the level of MMP-8 with comfortable methods and no tissue intervention can determine the progression of the periodontal disease for a better treatment. Objective: The purpose of the present study is to determine the relationship between MMP-8 in GCF and periodontal disease. Setting and Design: This is a cross-sectional study that took place in West Sumatra, Indonesia from June to December 2013. Materials and Methods: This study involves 60 respondents who are divided into three groups based on the periodontal disease index. The samples consist of 20 healthy individuals, 20 with mild gingivitis, and 20 periodontitis initial. GCF was collected from each group. MMP8 level in GCF was tested by using ELISA technique. Statistical Analysis: Data were analyzed with SPSS version 17 Software. ANOVA test was used to determine the differences in average levels of MMP-8. Bonferroni post hoc test was used to discover which spesific means differed. Results: The level of MMP-8 is significantly different between the healthy group and mild gingivitis group, between the healthy group with mild periodontitis group, and also between groups with mild gingivitis and mild periodontitis (P < 0.05). Conclusion: The findings of this study can be used by practitioners of dentistry to establish a proper diagnosis and appropriate treatment of periodontal disease by measuring the scale of MMP-8, to prevent or to minimize further complication in periodontitis patients.

Application of minocycline in the treatment of aggressive periodontitis / 中国基层医药

Objective To study the application effect of minocycline in the treatment of aggressive periodontitis.Methods From January 2014 to January 2017,116 cases of invasive periodontitis in the People's Hospital of Panan County were selected in the research.According to the different treatment methods,the patients were divided into observation group and control group with 58 cases in each group.The control group was given basic treatment,the observation group was given minocycline on the basis of basic treatment.The levels of tumor necrosis factor α(TNF-α),interleukin-17(IL-17),matrix metalloproteinase-1(MMP-1)and matrix metalloproteinase-8(MMP-8)in the two groups were observed.The changes of gingival index(GI),periodontal exploration depth(PD),attachment loss(AL),periodontitis gingival crevicular fluid(NO)were compared.Results After treatment,the total effective rate in the observation group was 93.1％(58/54),which was significantly higher than that in the control group [80.0％(58/46)],the difference was statistically significant(χ2 =9.469,P=0.002).After treatment,the levels of TNF-α,IL-17,MMP-1,MMP-8 in the gingival crevicular fluid of the observation group were(2.98 ±0.77)ng/mL,(20.87 ± 5.34)pg/mL,(1422.45 ±175.45)pg/mL,(1341.58 ±169.56)pg/mL,respectively,which were lower than those of the control group[(3.98 ±0.99)ng/mL,(31.65 ±7.88)pg/mL,(1781.44 ±199.55)pg/mL,(1678.99 ± 185.44)pg/mL](t=6.072,8.625,10.289,10.226,P<0.05).The levels of GI,PD,AL and NO of the observation group were(1.21 ±0.38)mm,(1.51 ±0.61)mm,(2.43 ±0.39)mm,(45.78 ±8.21)μmol/L,respectively,which were lower than those of the control group [(3.31 ±0.29)mm,(4.21 ±0.89)mm,(3.59 ±0.62)mm,(64.34 ± 12.88)μmol/L](t=33.4572,19.057,12.061,9.254,all P<0.05).After treatment,the levels of TNF-α,IL-17,MMP-1 and MMP-8 in the gingival crevicular fluid of the two groups were significantly lower compared with those before treatment(observation group:t=14.590,18.885,23.019,3.789,control group: t=7.809,12.993,10.905,7.608,all P<0.05).Conclusion The use of minocycline in the treatment of invasive periodontitis can significantly reduce the levels of TNF-α,IL-17,MMP-1,MMP-8 in gingival crevicular fluid,relieve periodontal plaque,promote periodontal tissue regeneration,the clinical efficacy is good.

Clinical effects of photo-activated disinfection as an adjunctive therapy for the treatment of chronic periodontitis / 上海交通大学学报（医学版）

Objective · To investigate the clinical effects of photo-activated disinfection (PAD)-assisted non-surgical therapy on the treatment of chronic periodontitis. Methods · Eleven patients with chronic periodontitis (totally 118 selected sites) were randomly enrolled. A split-mouth self-control method was adopted. Selected sites with the probing depth (PD) of bilateral homonymous teeth ≥ 5 mm were randomly assigned to the group A (receiving scaling and root planning, SRP) and the group B (receiving SRP+ PAD). Periodontal clinical indexes, inflammation indexes, and periodontal pathogens at selected sites were examined at baseline and 6 and 12 weeks after treatment. Results · Both SRP alone and SRP+PAD improved the periodontal inflammation significantly. The positive rate of bleeding on probing (BOP) 12 weeks after treatment was remarkably lower in the group B than in the group A (37.3% vs 57.6%, P=0.042). Both SRP and SRP+PAD effectively decreased matrix metalloproteinase-8 (MMP-8) and interleukin-1β (IL-1β) levels in gingival crevicular fluid. The IL-1β levels 6 and 12 weeks after treatment were significantly lower in the group B than in the group A [(17.99±14.26) pg/mL vs (32.64±30.69) pg/mL, P=0.007; (11.37±10.25) pg/mL vs (23.85±15.55) pg/mL, P=0.000]. Both treatments decreased the ratio of P. gingivalis and F.nucleatum in total bacteria. Conclusion · PAD can serve as a potential adjunctive therapy to conventional SRP in the treatment of chronic periodontitis with better improvement of bleeding gums and control of periodontal inflammation.

Role of ADAM8 in tumor metastasis / 中国药理学通报

Tumor metastasis is one of the important biological characteristics of malignant tumor,which is closely related with the prognosis of the cancer patients.High expression of ADAM8 in varieties of tumors was revealed in many recent studies,and such aberrant expression played a crucial role in regulating of tumor metastasis.Studies showed that overexpression of ADAM8 attenuated the intercellular adhesion effect,promoted tumor angiogenesis,and enhanced the degradation of ECM as well as the releasing of cytokines.Therefore,suppression of ADAM8 may lead to inhibition of tumor metastasis,which makes ADAM8 a particular attractive target as it can be used as a prognostic indicator and a potential therapeutic target of malignant tumor.A review about the relations between ADAM8 protein′s abnormal expression and tumor occurrence was discussed in this paper,also include discussion about the mechanisms of ADAM8 protein′s disorder-induced tumor formation,as well as therapeutic strategies based on ADAM8-targeted,which may provide references for follow-up research and clinical treatment.

Expression of matrix metalloproteinase-8 in human breast cancer and its clinical significance / 肿瘤研究与临床

Objective To investigate the expression of matrix metalloproteinase-8 (MMP-8) in human breast cancers and its relationship with the clinicopathological parameters,evaluate the relevance of MMP-8 levels to metastases in breast cancer.Methods Human specimens were obtained from 50 patients with invasive ductal carcinomas,and 20 normal breast glands were enrolled.Intact clinical parameters were aviliable for all patients.The protein expression of MMP-8 was determined by immunohistocbemistry technology SP.Results The rate of MMP-8 positive breast cancer was significantly higher than that in normal breast glands [68 ％ (34/50) vs 15 ％ (3/20),P ＜ 0.05].The expression of MMP-8 showed a negative correlation with breast cancer staging.The expression of MMP-8 in stage Ⅰ was higher than that in stage Ⅱ and Ⅲ/Ⅳ[94 ％ (15/16),57 ％ (13/23),55 ％ (6/11),P ＜ 0.05].Lymph node negative patients had a higher MMP-8 expression than patients with lymph node metastases [84 ％ (21/25) vs 50 ％ (13/25),P ＜ 0.05].Conclusion MMP-8 expression is associated with human breast cancer metastases and might be involved in inhibiting metastases.

The frequency and clinical significance of intra-amniotic inflammation defined as an elevated amniotic fluid matrix metalloproteinase-8 in patients with preterm labor and low amniotic fluid white blood cell counts

OBJECTIVE: To determine the frequency and clinical significance of intra-amniotic inflammation (IAI) defined as an elevated amniotic fluid (AF) matrix metalloproteinase-8 (MMP-8) concentration in patients with preterm labor and intact membranes (PTL) and low AF white blood cell (WBC) counts. METHODS: Adverse pregnancy outcomes were compared according to the presence or absence of IAI in 220 singleton gestations who underwent amniocentesis due to PTL (gestational age or =23 ng/mL). RESULTS: IAI was present in 19% of study population. Adverse pregnancy outcomes were significantly more frequent in patients with IAI than in those without IAI (preterm birth within 5 days of amniocentesis, 88% vs. 41%; acute-HCA, 47% vs. 11%; positive AF culture, 10% vs. 2%; each for P<0.05). Patients with IAI had a significantly shorter median amniocentesis-to-delivery interval than those without IAI (7.8 hours [0.01-3,307.3 hours] vs. 310.3 hours [0.01-2,973.8 hours]; P<0.001 from survival analysis). Multiple logistic regression analysis demonstrated that only an IAI (odds ratio, 3.3; 95% confidence interval, 1.5-7.3; P<0.005) retained a statistical significance in the prediction of acute-HCA after other confounding variables were adjusted. CONCLUSION: Approximately one-fifth of patients with PTL and low AF WBC counts have an evidence of IAI and are at risk for impending preterm delivery and acute-HCA when AF MMP-8 concentration is used.

Study on Association between Single Nucleotide Polymorphisms of MMP7, MMP8, MMP9 Genes and Development of Gastric Cancer and Lymph Node Metastasis / 대한소화기학회지

BACKGROUND/AIMS: Matrix metallopeptidase (MMP) is known to be involved in tumor invasion and metastasis of cancer. This study investigated the association of MMP7 rs11568818, MMP8 rs11225395, MMP9 rs17576 and rs2250889 with gastric cancer (GC) development and lymph node metastasis (LNM). METHODS: Samples were obtained from 326 chronic gastritis (CG) and 153 GC patients and genotyped by using the GoldenGate(R) method. Chi-square test was performed to identify the difference of allele distribution between each group (CG vs. GC; CG vs. with LNM GC). The associations of genotype with risk of GC and LNM were estimated by odds ratio and the 95% confidence interval was calculated by logistic regression adjusting for age and sex. RESULTS: The allele and genotype frequencies of MMP7 rs11568818, MMP8 rs11225395, MMP9 rs17576 and rs2250889 were not associated with the development of GC and LNM. CONCLUSIONS: In summary, MMP7 rs11568818, MMP8 rs11225395 MMP9 rs17576 and rs2250889 were not associated with the GC development and LNM in Korean population.

The relation of matrix metalloprotelnase-8 and breast cancer / 肿瘤研究与临床

Matrix metalloproteinase-8 (MMP-8) is a collagen which belongs to matrix metalloproteinase.Its function is that degrades collagen and be involved in inflammation.In breast cancer,the level of expression of MMP-8 is related to the invasion and metastasis of breast cancer as well as the clinical and pathological stage of breast cancer,but it is unclear on the molecular mechanism of MMP-8 in the malignant tumor.The research of expression in breast cancer prognosis of breast cancer will provide a reliable assessment of molecular marker.

The clinical role of increase of serum matrix metalloproteinase-8 concentration in patients with acute coronary syndrome / 西安交通大学学报·英文版

Objective: To study the clinical role of the variation of serum matrix metalloproteinase-8 (MMP-8) concentration in patients with acute coronary syndrome (ACS). Methods: ELISA method was adopted to detect serum MMP-8 concentration and to observe concentration's differences and features among 80 selected ACS cases (43 acute myocardial infarction and 37 unstable angina pectoris), 43 stable angina pectoris (SAP) cases and 37 control cases. And meanwhile the atherosclerosis risk factors of each case, such as age, sex, hypertension, body mass index, smoking, family history, diabetes, and hyperlipidemia were collected and analyzed as a whole. Results: First, serum MMP-8 concentration reached the highest point in ACS, and there was significant difference between SAP and control groups (P0.05). Third, Logistic regression analysis revealed that serum MMP-8 concentration might be the indicator of ACS (B=4.493, P=0.000), particularly, that of AMI (B=9.961, P=0.000). Fourth, linear correlation and linear regression analysis found that only neutrophil was likely to influence serum MMP-8 concentration (r=0.274, P=0.001). Fifth, in the diagnosis of ACS, the area under ROC curve of MMP-8 was 0.785, the sensitivity and specificity were 68.6% and 76.5%, respectively. Conclusion: 1 Serum MMP-8 concentration has close relationship with the occurrence of ACS, particularly with AMI; 2 Serum MMP-8 concentration may be one of the predicting indicators of ACS and particularly of AMI; 3 Neutrophil may be correlated with serum MMP-8 concentration; 4 MMP-8 is of somewhat valuable in diagnosing ACS.

The clinical role of increase of serum matrix metalloproteinase-8 concentration in patients with acute coronary syndrome / 药物分析学报

Objective To study the clinical role of the variation of serum matrix metalloproteinase-8 (MMP-8)concentration in patients with acute coronary syndrome (ACS). Methods ELISA method was adopted to detect serum MMP-8 concentration and to observe concentration's differences and features among 80 selected ACS cases (43 acute myocardial infarction and 37 unstable angina pectoris), 43 stable angina pectoris (SAP) cases and 37 control cases.And meanwhile the atherosclerosis risk factors of each case, such as age, sex, hypertension, body mass index, smoking,family history, diabetes, and hyperlipidemia were collected and analyzed as a whole. Results First, serum MMP-8 concentration reached the highest point in ACS, and there was significant difference between SAP and control groups (P<0.01). Second, sermn MMP-8 in AMI was much higher than that in UAP with significant difference (P<0.01). There was no difference between UAP and SAP groups (P>0.05). Third, Logistic regression analysis revealed that serum MMP-8 concentration might be the indicator of ACS (B=4.493, P=0.000), particularly, that of AMI (B=9.961,P=0.000). Fourth, linear correlation and linear regression analysis found that only neutrophil was likely to influence serum MMP-8 concentration (r=0.274, P=0.001). Fifth, in the diagnosis of ACS, the area under ROC curve of MMP-8 was 0.785, the sensitivity and specificity were 68.6% and 76.5%, respectively. Conclusion ① Serum MMP-8 concentration has close relationship with the occurrence of ACS, particularly with AMI;② Serum MMP-8 concentration may be one of the predicting indicators of ACS and particularly of AMI;③ Neutrophil may be correlated with serum MMP-8 concentration;④ MMP-8 is of somewhat valuable in diagnosing ACS.

Immediate Postnatal Concentrations of Metalloproteinase-8 in the Tracheal Aspirates and the Development of Atypical Chronic Lung Disease of Prematurity

PURPOSE: Matrix metalloproteinase-8 (MMP-8) is an endoproteinase which degrades extracellular matrix and basement membrane. As early pulmonary inflammation is known to play a key role in the development of chronic lung disease (CLD), we tested the hypothesis that preterm infants who develop CLD have higher concentrations of MMP-8 in the tracheobronchial aspirates (TA) within 24 hours after birth than those who do not develop CLD. METHODS: A retrospective cohort study was done in 70 preterm infants delivered and admitted to the neonatal intensive care unit of Seoul National University Children's Hospital. TA MMP-8 concentrations were measured by ELISA. All patients were categorized into two groups according to the presence of respiratory distress syndrome (RDS). Multiple logistic regression analysis was done to assess the risk factors of CLD. RESULTS: CLD was diagnosed in 46 patients (65.7%). There were no statistically significant differences in the TA MMP-8 concentrations between CLD (+) and CLD (-)group among whole and RDS (+) groups. But in RDS (-)group, TA MMP-8 higher in CLD (+) group than in CLD (-)group. These differences persisted significantly after adjustments for the effects of gestational age at birth and histologic chorioamnionitis [P<0.050, Odds ratio: 4.720, 95% CI: 1.004-22.196]. The diagnostic indices of MMP-8 concentrations (cutoff, 7.94 ng/mL) as a predictor of development of CLD in RDS (-)group were: sensitivity of 82.4%, specificity of 77.8%, positive predictive value of 87.5%, and negative predictive value of 70.0%. CONCLUSION: There was a strong association between increased levels of TA MMP-8 and development of CLD in RDS (-)group. We propose that TA MMP-8 concentrations within 24 hours after birth may be a significant predictor of later development ofatypical CLD.

The Relationship Among Umbilical Cord Plasma Matrix Metalloproteinase-8 and Interleukin-6 Concentration, Funisitis, Amniotic Fluid Infection and Neonatal Outcome / 대한산부인과학회잡지

OBJECTIVE: The purpose of this study was to determine whether funisitis is associated with changes in the umbilical cord plasma concentration of interleukin-6 (IL-6) and matrix metalloproteinase-8 (MMP-8), microbial invasion of the amniotic cavity and neonatal outcome. METHODS: The relationship among the presence of funisitis, IL-6 and MMP-8 concentrations in umbilical cord plasma at birth, the results of amniotic fluid culture performed within 5 days of birth was examined in 83 consecutive singleton births (20-35 weeks' gestation). Funisitis was diagnosed in the presence of neutrophil infiltration into the umbilical vessel wall or Wharton's jelly. The IL-6 and MMP-8 concentration was measured with a specific immunoassay. Amniocentesis was performed in 47 patients within 5 days of birth. RESULTS: (1) Funisitis was present in 21.7% of patients. (2) Patients with funisitis had a significant higher cord plasma IL-6 concentration, but had no significant difference in cord plasma MMP-8 concentration. (3) Clinical chorioamnionitis was more common in patients with funisitis than those without funisitis. (4) A cord plasma IL-6 > 6.34 pg/ml had a sensitivity of 77.8% and a specificity of 75.4% in the identification of funisitis. (5) No correlation between cord blood plasma IL-6 concentration and MMP-8 concentration was found. (6) There was no significant correlation between gestational age at birth and cord blood plasma MMP-8 concentrations, but there appeared to be a trend to increase of cord plasma MMP-8 concentrations as gestational ages at birth were increased. (7) Neonates with congenital sepsis had a significantly higher cord plasma IL-6 and MMP-8 concentration than those without congenital sepsis. CONCLUSION: In patient with funisitis, umbilical cord plasma IL-6 concentrations were higher than those without funisitis, but umbilical cord plasma MMP-8 concentrations had no significant difference in each group. The umbilical cord plasma IL-6 and MMP-8 can be useful as a predictor of the occurrence of congenital sepsis in preterm infant.