Identification the key factor of pulmonary fibrosis following silica nanoparticles exposure based on bioinformatics analysis / 中华劳动卫生职业病杂志

Objective: To investigate the main mechanisms of pulmonary fibrosis following silica nanoparticles (SiNPs) exposure through constructing the macrophage-fibroblast model in vitro, which simulated the process of pulmonary fibrosis. Methods: In January 2021, human mononuclear leukemia cells (THP-1) were treated with 0, 25, 50, 100 μg/ml SiNPs for 24 h. The supernatant of THP-1 cells was collected and applied to human embryonic lung fibroblast cells (MRC-5) which divided into control and low, medium and high dose groups at the logarithmic growth stage for 24 h. MRC-5 cell viability was detected by CCK8. The hydroxyproline (Hyp), interleukin 6 (IL-6), interleukin 1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) expression were detected in the supernatants of MRC-5. The changed proteins were detected by liquid-phase mass spectrometry in high dose group. GeneCard database were applied to identity the differential pulmonary fibrosis proteins in high dose group. Gene Ontology (GO) was performed to identity the key biological process in differential pulmonary fibrosis proteins of high dose group. The String database was used to construct the protein-protein interactions (PPI) network of differential pulmonary fibrosis proteins. The APP of CytoHubba was applied to calculate the key protein of differential pulmonary fibrosis proteins in PPI network. Correlation coefficients between key differential pulmonary fibrosis proteins were calculated using Pearson correlation analysis. Western blotting was applied to detect the expression of key proteins of differential pulmonary fibrosis proteins in different groups. Results: CCK8 results showed that MRC-5 cell viability was increasing in low, medium and high dose groups compared with control group (P<0.05). The expression levels of Hyp and IL-1β in different group were increased compared with control group, the expression levels of IL-6 and TNF-α were increased in high dose group compared with control group (P<0.05). GeneCard database identified 26 differential pulmonary fibrosis proteins, which were mainly involved in extracellular matrix hydrolysis, cell inflammatory response, tissue repair, cell proliferation, inflammation response by GO analysis. The APP of CytoHubba was calculated that matrix metalloproteinase 9 (MMP9) and tissue inhibitor metalloproteinase 1 (TIMP1) played an important role in PPI network. The results of correlation analysis showed that MMP9 was correlated with the expression of matrix metalloproteinase 1 (MMP1), matrix metalloproteinase 3 (MMP3), TIMP1 and epidermal growth factor receptor (EGFR) (r=0.97, 0.98, 0.94, 0.93, P<0.05). Western blotting results showed that TIMP1 protein expression was increased in low, medium and high dose groups, while MMP9 protein expression was increased only in high dose group (P<0.05) . Conclusion: Differential expression proteins related with pulmonary fibrosis in MRC-5 cells mainly regulate biological processes of extracellular matrix hydrolysis, tissue repair, and cellular inflammation response following SiNPs exposure. MMP9 and TIMP1 may be the key proteins, which affected the fibrosis process in vitro pulmonary fibrosis model.

An in vitro study of the effect of Mycobacterium tuberculosis infection on the expression of bone destruction-related factors in osteoclasts / 中国脊柱脊髓杂志

Objectives:To establish a model of Mycobacterium tuberculosis infection of osteoclasts(OC)and explore the mechanism of Mycobacterium tuberculosis infection on OC.Methods:Peripheral blood mononuclear cells(peripheral blood mononuclear cells,PBMCs)were isolated from healthy volunteers.Receptor activator of nuclear factor-KB ligand(RANKL)and macrophage-colony stimulating factor(M-CSF)were used to make PBMCS into OC,and tartrate resistant acid phosphatase(TRAP)staining was performed on the cells.The constructed kanamycin resistant H37Rv pMV261-GFP green fluorescent strain was resuscitated and cultured with 10％oleic albumin dextrose catalase(OADC),7H9 and kanamycin containing Mycobacterium tuberculosis special liquid medium in an incubator at 37℃ until the optical density(OD)value was about 0.5 at 600nm.The OC cells cultured alone were set as the blank control group.And OC cells were also infected with Mycobacterium tuberculosis at different multiplicity of infection(MOI)for 24h,and MTT colorimetric method was used to detect cell survival rate.The MOI with the highest cell survival rate was selected as experimental MOI,and OC cells infected with H37Rv at experimental MOI were set as the experimental group.Fluorescence microscopy and Mycobacterium tuberculosis acid-fast staining were used to observe the transfection of Mycobacterium tuberculosis at the experimental MOI.Quantitative real-time PCR(qRT-PCR)was used to detect the expressions of non-receptor tyrosine kinase C-src,cathepsin K(CK),carbonic anhydrase 2(CA2),Integrin-β3 and matrix metalloproteinase-9(MMP-9).Immunohistochemistry was used to detect the expressions of P-src,CK,CA2,Integrin-β3 and MMP-9 on the cell surface.Western blot(WB)was used to detect the protein expression levels of P-src,CK,CA2,Integrin-β3,and MMP-9.Results:TRAP staining showed that more than 90％of the cells were OC after 15d of culture,which could be used for experiments.The results of MTT colorimetric assay showed that the cell survival rate was the highest when the MOI was 20:1(P＜0.05).This transfection multiplicity can be used as the concentration of experimental group.Fluorescence microscopy showed that when the transfection multiplicity ratio was 20:1,the green fluorescent Mycobacterium tuberculosis entered the OC and was successfully transfected into the OC.The results of acid-fast staining after infection of OC with Mycobacterium tuberculosis showed that when the MOI was 20:1,the acid-fast Mycobacterium tuberculosis stained red entered OC and was also successfully transfected into OC.The results of qRT-PCR,cell immunohistochemistry,and WB showed that the expressions of MMP-9,CK,C-src,CA2,and Integrin-β3 in the experimental group were higher than those in the blank control group(P＜0.05).Conclusions:Mycobacterium tuberculosis can transfect OC;Compared with the blank control group,the levels of five bone destruction factors in the experimental group transfected with OC by Mycobacterium tuberculosis were increased,suggesting that bone destruction of spinal tuberculosis may be related to this,which may provide a new exploration direction for the diagnosis and treatment of bone tuberculosis diseases.

Evaluation of CT perfusion imaging parameters and serum CTRP-3,LDL-C and MMP-9 on the hemorrhage transformation after acute cerebral infarction / 中国医学装备

Objective:To explore the evaluations of computed tomography(CT)perfusion imaging parameters and serum complement C1q/tumor necrosis factor related protein-3(CTRP-3),low density lipoprotein cholesterol(LDL-C),matrix metalloproteinase-9(MMP-9)on hemorrhagic transformation(HT)after acute cerebral infarction(ACI).Methods:A total of 206 ACI patients who admitted to the People's Hospital of Jianyang from August 2019 to July 2022 were retrospectively selected as the study objects.The patients were divided into HT group(45 cases)and non-HT group(161 cases)according to whether occurred HT after intravenous thrombolysis.The CT perfusion imaging parameters[blood flow(BF),blood volume(BV),mean transit time(MTT),permeability surface(PS)],CTRP-3,LDL-C,MMP-9 were compared between two groups.Receiver operating characteristic(ROC)curve model was used to analyze the area under curve(AUC)values,sensitivities and specificities of CT perfusion imaging parameters,CTRP-3,LDL-C and MMP-9 in diagnosing HT.Results:The BF and BV of HT group were lower than those of non-HT group,while the MTT and PS of HT group were higher than those of non-HT group,and the differences were statistically significant(t=-5.941,t=-5.777,t=5.863,t=6.954,P<005),respectively.The CTRP-3 and LDL-C of HT group were respectively lower than those of non-HT group,while the MMP-9 of HT group was higher than that of non-HT group,with statistical significances(t=-3.788,t=-5.835,t=6.935,P<0.05).The ROC curve analysis showed that the AUC values of BF,BV,MTT,PS,CT comprehensive parameters,CTRP-3,LDL-C and MMP-9 were respectively 0.790,0.779,0.738,0.775,0.949,0.692,0.777 and 0.785(P<0.05).The sensitivities of them were respectively 88.90%,100.00%,53.30%,66.70%,100.00%,88.90%,66.70%and 78.60%.The specificities of them were respectively 64.60%,51.60%,91.30%,77.60%,81.40%,47.80%,78.90%and 75.80%.The differences of the AUC values between CT comprehensive parameters and CTRP-3,and between that and LDL-C,and between that and MMP-9 were significant(Z=6.202,Z=4.563,Z=3.704,P<0.05),respectively.Conclusion:CT perfusion imaging parameters,serum CTRP-3,LDL-C and MMP-9 levels have close correlation with HT after ACI.The monitoring of the change degrees of them is helpful to provide important references for predicting the occurrence of HT in ACI patients after thrombolytic therapy.

Study on the analysis on the clinical effect of hyperbaric oxygen chamber in treating the postoperatively malignant brain edema of craniocerebral trauma / 中国医学装备

Objective:To study the clinical effect of NBYY-BXDR-001 hyperbaric oxygen chamber in treating the postoperatively malignant brain edema of craniocerebral trauma,and the effects of that on the levels of matrix metalloproteinase-9(MMP-9),neutrophil gelatinase-associated lipocalin(NGAL),tenascin-C(TNC)and tumor necrosis factor-ɑ(TNF-ɑ).Methods:A total of 84 patients with postoperatively malignant brain edema of craniocerebral trauma who admitted to the hospital were selected,and they were divided into an observation group(45 cases received the interventional treatment of hyperbaric oxygen within postoperative 1-3 days)and a control group(39 cases received interventional treatment of hyperbaric oxygen within postoperative 4-10 days)according to the different therapeutic times of postoperative hyperbaric oxygen.The levels of serum MMP-9,NGAL,TNC and TNF-ɑof the two groups of patients were compared.The Glasgow Coma Scale(GCS)scores and the duration of brain edema of patients before and after treatment were recorded,and the mortality rates of the two groups of patients also were recorded.Results:There was no statistically significant difference in postoperative mortality rates between the two groups.The overall efficacy of the observation group was significantly better than that of the control group,and the difference was statistically significant(Z=-2.203,P<0.05).The GCS scores of the patients of the observation group at the 1st week,2nd week,3rd week and 4th week after surgery were significantly higher than that at the 1st d after surgery,and the differences were statistically significant(t=5.236,t=5.687,t=6.354,t=6.782,P<0.05),respectively.The serum MMP-9,NGAL,TNC and TNF-ɑ levels of the two groups of patients at the 1st week,2nd week,3rd week and 4th week after surgery were significantly lower than those at the 1st day after surgery,and the differences were statistically significant(Fobservation group= 125.127,F=98.224,F=137.791,F=105.226,Fcontrol group=113.370,F=73.363,F=115.520,F=84.069,P<0.05),respectively.At the 2nd,3rd and 4th week after surgery,the GCS scores of the observation group were significantly higher than those of the control group,and the serum MMP-9,NGAL,TNC and TNF-ɑ of the observation group were significantly lower than those of the control group,and the differences were statistically significant(tMMP-9=5.689,t=6.879,t=8.253,tNGAL=8.658,t=9.657,t=8.658,tTNC=6.587,t=6.354,t=6.859,tTNF-ɑ=7.898,t=8.654,t=8.256,P<0.05),respectively.Compared with the control group,the peak time and duration of brain edema of the observation group were significantly shortened,and the differences of them between two groups were statistically significant(t=2.064,t=-2.084,P<0.05),respectively.Conclusion:Early interventional treatment of hyperbaric oxygen in patients with postoperatively malignant brain edema of craniocerebral trauma can contribute to relieve postoperative brain edema and improve the treatment effect,which is related to the adjustment of hyperbaric oxygen for serum MMP-9,NGAL,TNC and TNF-ɑ levels.

Modified Wenjingtang Affects Caspase-8， MMP-9， N-cadherin and E-cadherin in Local Microenvironment of EM Rats with Kidney Deficiency and Blood Stasis / 中国实验方剂学杂志

Objective:To investigate the therapeutic effect and mechanism of modified Wenjingtang on endometriosis （EM） rats with kidney deficiency and blood stasis. Method:Healthy non-pregnant female Sprague-Dawley （SD） rats of SPF grade were randomly divided into the blank group and experimental group. After being modeled via soaking in ice water and subcutaneous injection of epinephrine hydrochloride， the ones in the experimental group were further divided into the sham operation group and EM model group， with the former only undergoing laparotomy and the latter further receiving autologous endometrial transplant for triggering EM. The successfully modeled rats with EM due to kidney deficiency and blood stasis were randomized into the positive drug （danazol， 63 mg·kg^-1） group and low- （5 g·kg^-1）， medium- （10 g·kg^-1）， and high-dose （20 g·kg^-1） modified Wenjingtang groups. The corresponding drugs were administered by gavage， once per day， for four weeks. Then the ectopic and eutopic endometrial tissues were stained with hematoxylin-eosin （HE） to observe the histopathological changes. The protein and mRNA expression levels of cysteinyl aspartate-specific proteinase-8 （Caspase-8）， matrix metalloproteinase-9 （MMP-9）， N-cadherin， and E-cadherin were detected by immunohistochemistry （IHC）， Western blotting， and real-time polymerase chain reaction （Real-time PCR）， respectively. Result:The IHC and Western blot revealed that the protein expression levels of MMP-9 and N-cadherin in eutopic and ectopic endometrial tissues of the model group were significantly increased as compared with those in the sham operation group （<italic>P</italic><0.01）， while the levels of Caspase-8 and E-cadherin was significantly decreased （<italic>P</italic><0.01）. Compared with the model group， the danazol and low-， medium-， and high-dose modified Wenjingtang groups exhibited obviously down-regulated MMP-9 and N-cadherin protein expression in eutopic and ectopic endometrial tissues （<italic>P</italic><0.05，<italic>P</italic><0.01）， but up-regulated Caspase-8 and E-cadherin （<italic>P</italic><0.05， <italic>P</italic><0.01）. Real-time PCR uncovered that the mRNA expression levels of MMP-9 and N-cadherin in eutopic and ectopic endometrial tissues of the model group were significantly elevated as compared with those in the sham operation group （<italic>P</italic><0.01）， whereas the levels of Caspase-8 and E-cadherin significantly declined （<italic>P</italic><0.01）. The comparison with the eutopic endometrial tissue in the model group showed that the mRNA expression levels of MMP-9 and N-cadherin in the danazol group and high- and medium-dose modified Wenjingtang groups were significantly down-regulated， while those of Caspase-8 and E-cadherin were significantly up-regulated （<italic>P</italic><0.05，<italic>P</italic><0.01）. Conclusion:Modified Wenjingtang alleviates the immunosuppression and blocks the angiogenesis in EM rats with kidney deficiency and blood stasis syndrome by regulating the expression of such cytokines as Caspase-8， MMP-9， N-cadherin， and E-cadherin， thus exerting the therapeutic effect against EM. The above-mentioned micro-indicators are potential markers reflecting the disease （EM）， syndrome （kidney deficiency and blood stasis）， and pathological mechanisms （immunosuppression and angiogenesis）.

Comparasion on Effect of Xuefu Zhuyutang and Modified Erchentang on Nonalcoholic Fatty Liver in Mice / 中国实验方剂学杂志

Objective:To compare the effect and mechanisms of modified Erchentang and Xuefu Zhuyutang on high-fat diet-induced apolipoprotein-E knockout (ApoE-/-) mice nonalcoholic fatty liver disease (NAFLD). Method:Ten C57/BL6J mice were taken as normal control group and fed with normal feed. Totally 30 ApoE-/- mice were fed with high-fat diet to establish a disease model for 4 weeks. After 4 weeks, the 30 ApoE-/- mice were divided into model group, Xuefu Zhuyutang group (hereinafter referred to as Huoxue group) and modified Erchentang group (hereinafter referred to as Huatan group) by random number table method, with 10 in each group. The normal group and the model group were intragastrically administered with normal saline. The drug-administered group was intragastrically administered at a dosage that was ten times of the adult dose, once a day, for 8 weeks. Serum and liver were collected after the end of the 12-week experiment. The serum lipid and liver function levels of each group were measured, and the liver pathological morphology was observed. Protein and mRNA expressions of liver inflammatory mediators interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), matrix metalloproteinase-9 (MMP-9), monocyte chemotactic factor-1 (MCP-1) were detected by Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR) and Western blot. Result:The results of serum lipids and liver function showed that compared with the normal group, serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in the model group were significantly increased, while serum high-density lipoprotein (HDL) was significantly reduced (P<0.01). Compared with the model group, serum TG ，LDL and ALT were significantly decreased, HDL was significantly increased in the Huoxue group (P<0.05). The serum levels of TC, TG， LDL, AST and ALT in the Huatan group were significantly decreased，HDL was significantly increased (P<0.05，P<0.01), and TG was decreased. The mice serum HDL in the Huatan group was higher than that in the Huoxue group. The serum ALT in the Huoxue group was lower than that in the Huatan group. The pathological observation showed that compared with the normal group, hepatocytes in the model group had severe steatosis with many lipid droplet vacuoles, suggesting that the mouse NAFLD model was successful. Compared with the model group, each administration group alleviated hepatocyte steatosis, with no significant difference between the two administration groups. Western blot and Real-time PCR results showed that compared with the normal group, protein and mRNA expression levels of TNF-α, IL-1β, MCP-1, and MMP-9 in the model group were significantly increased (P<0.05，P<0.01). Compared with the model group, the Huoxue group significantly down-regulated the expressions of IL-1β, MCP-1 protein and MCP-1 mRNA(P<0.05，P<0.01). The Huatan group significantly reduced the expressions of IL-1β, TNF-α, MMP-9, MCP-1 protein, TNF-α and MMP-9 mRNA(P<0.05，P<0.01). Conclusion:Modified Erchentang and Xuefu Zhuyutang can alleviate the therapeutic effect of NAFLD mice to a certain extent, modified Erchentang has a better therapeutic effect.

The role and relationship of EZH2, MMP-2 and MMP-9 in HCC invasion and metastasis / 西安交通大学学报(医学版)

Objective: To detect the expressions of enhancers of zeste homolog 2 (EZH2), matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in hepatocellular carcinoma (HCC) tissues, analyze the correlation of EZH2, MMP-2 and MMP-9 expressions in HCC tissues with the clinicopathological factors of HCC to explore the role of EZH2 in the invasion and migration of HCC cells and the regulatory effects of EZH2 on MMP-2 and MMP-9. Methods: The expressions of EZH2, MMP-2 and MMP-9 in HCC tissues was detected by qRT-PCR. We analyzed the relationship of EZH2, MMP-2 and MMP-9 with the clinicopathological factors of HCC. Pearson correlation was used to analyze the correlation between EZH2, MMP-2 and MMP-9 expressions in HCC tissues. SMMC-7721 HCC cell lines with down-regulated EZH2 expression were constructed by small interfering RNA transfection. Transwell assay was used to observe the effects of EZH2 on invasion and migration of SMMC-7721 cells. qRT-PCR was used to detect the regulatory effects of EZH2 on MMP-2 and MMP-9 in HCC cells. Results: EZH2, MMP-2 and MMP-9 expressions were increased in HCC tissues, and they were correlated with adverse clinicopathological factors. There was a significant correlation between the expressions of EZH2 and MMP-9 in HCC tissues. Deletion of EZH2 significantly inhibited the invasion and migration of HCC cells and inhibited MMP-9 expression in HCC cells. Conclusion: EZH2, MMP-2 and MMP-9 are all closely associated with HCC progression, and they can be potential biomarkers and therapeutic targets for HCC.

Effect of Ginsenoside Rh2 on Metastasis and Invasion of Colorectal Cancer Resistant Cells HCT116/L-OHP and Its Mechanism / 中国实验方剂学杂志

Objective:To observe effect of ginsenoside Rh2 (GRh2) on the invasion and migration of colon cancer resistant cells HCT116/L-OHP and its specific mechanism. Method:Cell counting kit-8 (CCK-8) assay was used to detect the inhibitory effect of different concentrations of GRh2 (0, 2.5, 5, 10, 20, 40 mg·L-1) on HCT116/L-OHP cell proliferation, scratch assay, Transwell assay and adhesion assay were used to detect the effects of GRh2 (0, 2.5, 5, 10 mg·L-1) on cell migration, invasion and adhesion. The protein expression levels of E-cadherin and matrix metalloproteinase-9(MMP-9) were examined by Western blot. Result:Compared with control group, GRh2(5, 10, 20, 40 mg·L-1) significantly inhibited the proliferation of HCT116/L-OHP cells in a dose-dependent manner(PP2 group (5, 10 mg·L-1) was significantly decreased (PP2 group was significantly decreased (PP2 group was significantly reduced (PP2 (10, 20, 30 mg·L-1) promoted E-cadherin protein expression (PPPConclusion:GRh2 can significantly inhibit the invasion and migration of HCT116/L-OHP in colon cancer cells, and its potential mechanism may be related to the promotion of E-cadherin and the inhibition of MMP-9 expression in a dose-dependent manner.

Clinical Efficacy of Modified Qingqi Huatan Wan in Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease with Syndrome of Phlegm-heat Obstructing Lung and Effect on Serum TNF-α, IL-8 and MMP-9 / 中国实验方剂学杂志

Objective: To explore the clinical efficacy of modified Qingqi Huatan Wan in treatment of acute exacerbation of chronic obstructive pulmonary disease (syndrome of phlegm-heat obstructing lung) and investigate its effects on serum tumor necrosis factor-alpha (TNF-α),interleukin-8(IL-8) and matrix metalloproteinase-9(MMP-9).Method: Sixty-four patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) were randomly divided into control group (32 cases) and treatment group (32 cases) by random number table.The control group was treated with routine western medicine therapy according to the guidance and disease conditions.Based on treatment in control group,patients in treatment group also received modified Qingqi Huatan Wan.The treatment course was 14 days for both groups.The scores of traditional Chinese medicine (TCM) syndrome,chronic obstructive pulmonary disease (COPD) assessment test (CAT),and modified version of the British Medical Research Council's Respiratory Questionnaire (mMRC),pulmonary function,blood gas analysis indicators,levels of serum TNF-α,IL-8 and MMP-9,clinical efficacy and safety were evaluated and compared once before treatment and 14 d after treatment.Result: The total clinical effective rate was 96.67% in treatment group,higher than 76.67% in control group (χ2=5.192,PPP1),percent of FEV1 in predicted value (FEV1%),and ratio of FEV1 to forced vital capacity (FEV1/FVC) were increased in both groups after treatment (PP2) and partial pressure of oxygen (PaO2) were increased in both groups,while partial pressure of carbon dioxide (PaCO2) was decreased (P2 and PaO2 in treatment group were higher than those in control group,while PaCO2 was lower than that in control group (Pα,IL-8 and MMP-9 were decreased in both groups (PPConclusion: Modified Qingqi Huatan Wan can control the symptoms safely and ameliorate pulmonary function,reduce the levels of serum TNF-α,IL-8,MMP-9 and inflammation in treatment of AECOPD.

Effects of hypoxia on expressions of human airway remodeling-associated factors in airway epithelial cells / 西安交通大学学报(医学版)

Objective To explore the mechanism of hypoxia on the expressions of airway remodeling-associated factors matrix metalloproteinase-9(MMP-9)and transforming growth factor β1(TGF-β1)in human airway epithelial cells(16HBE)under hypoxia.Methods We cultured 16HBE cells under normoxia or hypoxia (20 mL/L O2)for 6,12 and 24 hours.MMP-9 and TGF-β1with higher expression were pretreated with epidermal growth factor receptor(EGFR)inhibitor AG1478 and hypoxia-inducible factor-1α(HIF-1α)inhibitor Lificiguat (YC-1).Cell survival rate was measured by CCK-8 method.The mRNA levels of MMP-9 and TGF-β1were detected by RT-PCR.The levels of HIF-1α,MMP-9 and TGF-β1protein expressions were measured by Western blot. Results In hypoxia group,the levels of MMP-9 and TGF-β1mRNA as well as protein expressions increased compared with those in the control group(all P＜ 0.05).Pretreatment with AG1478 and YC-1 could inhibit the above-mentioned changes(P＜ 0.05).AG1478 suppressed the high expression of HIF-1α induced by hypoxia. Conclusion Hypoxia can up-regulate the expressions of airway remodeling-associated factors MMP-9 and TGF-β1 via EGFR's induction of HIF-α signaling pathway.

Association of in-stent restenosis with serum Gal-3 and MMP-9 levels / 西安交通大学学报(医学版)

Objective To investigate the relationship of galectin-3 (Gal-3)and matrix metalloproteinase-9 (MMP-9)with in-stent restenosis (ISR).Methods We consecutively recruited 434 patients who had undergone successful drug eluting stent (DES)implantation.Then we divided them into ISR group (n=41)and NO-ISR group (n=393)according to the results of coronary angiography review.Independent risk factors for ISR were found out by multivariate analysis and the two groups were matched for these factors except for Gal-3 and MMP-9 .After elim-ination of the influence of confounders,serum Gal-3 and MMP-9 were compared between the groups and their rela-tions with the severity of ISR were analyzed.Patients were grouped based on Gal-3 and MMP-9 concentrations and major adverse cardiac events (MACEs)were compared between the two groups.Results After elimination of the influence of confounders,the results showed that serum levels of Gal-3 and MMP-9 were significantly higher in ISR group than in NO-ISR group (P＜0.001).Serum levels of Gal-3 and MMP-9 increased with the increased grade of classification.Serum levels of Gal-3 and MMP-9 were obviously higher in classes Ⅲ and Ⅳ ISR than in class Ⅰ (P＜0.05).Patients with higher levels of Gal-3 and MMP-9 had a higher incidence of MACEs (P＜0.01).ISR group had a higher incidence of MACEs than NO-ISR group (P＜0.05).Conclusion Serum levels of Gal-3 and MMP-9 are correlated with ISR and its severity,and they are independent risk factors for ISR.The rate of MACEs during follow-up period was increased with the increased levels of Gal-3 and MMP-9 .

Expressions of PBK and MMP-9 and their effect on concurrent chemoradiotherapy in cervical cancer / 中华放射医学与防护杂志

Objective@#To investigate the expression of DNA damage repair factor PDZ binding kinase (PBK) and matrix metalloproteinase 9 (MMP-9) in cervical cancer and the effect on clinical outcomes of concurrent chemoradiotherapy.@*Methods@#A total of 65 cervical cancer pathological specimens were collected from January 2014 to July 2016. Immunohistochemistry was used to detect PBK and MMP-9 expression in the specimens.External irrsdeation was treated with intensity-modulated radiation therapy at a dose of 50 Gy/25 F. After 18 times of external irradiation, high-dose rate postoperative treatment was giver at a dose of 30-36 Gy/5-6 F which lasts 3-4 weeks. Weekly chemotherapy with Cisplatin(DDP) begins simultaneously at the beginning of external irradiation. DDP was administered intravenously at a dosage of 40 mg/m2 for 2 to 6 week. All patients were followed-up as routine. The relationship between clinical characteristics and prognosis of patients and the expression of PBK and MMP-9 were analyzed.@*Results@#PBK was expressed in 92.3% of tissues and MMP-9 was expressed in 69.2% of tissues. The expression of PBK was positively associated with overall survival (OS) and disease progression-free survival (PFS) of cervical cancer patients (χ2=4.324, 8.068, P<0.05). The expression of MMP-9 was related with PFS (χ2=5.134, P<0.05). Patients with PBK and MMP-9 expression suffered poor OS and PFS (χ2=5.382, 9.364, P<0.05).@*Conclusions@#PBK and MMP-9 could be a biomarker to predict the prognosis of cervical cancer.

In vitro pro ⁃ angiogenic activity of Echinococcus granulosus hydatid cysts from experimentally infected mice / 中国血吸虫病防治杂志

@#To preliminarily study the pro⁃angiogenic activity of Echinococcus granulosus hydatid cysts against hu⁃ man umbilical vein endothelial cells in vitro and the transcriptional level of potential pro⁃angiogenic factors. Methods The hydatid cysts and protoscolex derived from experimentally infected mice were collected and cultured in vitro，then the human umbilical vein endothelial cells were stimulated by the supernatant and cyst fluid respectively，and the angiogenesis was observed and analyzed through a microscope and the angiogenesis mode of the software NIH Image J. Meanwhile，the mouse homologous proteins of matrix metalloproteinase⁃9（MMP⁃9）and high mobility group box B1（HMGB1）were identified in E. granulosus genome through sequence alignment，and their transcriptional levels in the cyst wall and protoscolex were analyzed. Results The culture supernatant of hydatid cysts significantly promoted human umbilical vein endothelial cells into tubes（F = 73.03，P < 0.001），the transcriptions of MMP⁃9 and HMGB1 were detected in the cyst wall and protoscolex，and the transcriptional level of MMP⁃9 was higher in protoscolex（t = -11.65，P < 0.001），while the level of HMGB1 was higher in hydatid cysts（t = 6.43，P = 0.003）. Conclusion Some parasite⁃derived pro⁃angiogenic molecules may exist in the supernatant of E. granulosus hydatid cysts，while further researches are required into their exact mechanisms.

Assessing the Role of Matrix Metalloproteinase-9 in Rheumatoid Arthritis / 现代检验医学杂志

Objective To assess the role of Matrix Metalloproteinase-9 (MMP-9)in rheumatoid arthritis (RA).Methods Peripheral blood from 45 RA patients and 28 healthy individuals (HV)were collected to detect RF and hs-CRP by immuno-turbidimetry,ESR by westergren method and MMP-9 by ELISA.The correlation was analysed between MMP-9 and RF, ESR or hs-CRP,respectively,by pearson correlation analysis.Results Levels of RF,ESR,hs-CRP and MMP-9 were signifi-cantly higher in RA patients than HV group (t=3.93~5.96,P<0.001),respectively.RF high titer patients or patients with a high inflammation response showed a higher MMP-9 levels than the RF low titer or slight inflammation patients (P<0.05).MMP-9 was positively correlated to RF,ESR and hs-CRP in RA patients(P<0.05),respectively.Conclusion MMP-9 maybe a sensitive tool in the diagnosis and management of RA patients.

Association between the -1562 C/T polymorphism in the MMP-9 promoter and phenotype of esophageal squamous cell carcinoma in northern Chinese population / 药物分析学报

Objective To conduct a case-control study on the association of the nucleotide polymorphisms in the promoter region of the matrix metalloproteinase-9 (MMP-9) gene with phenotype of esophageal cancer. Methods All subjects were unrelated residents in northern regions of China. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was used to determine the MMP-9 genotypes. Results The overall distribution of genotypes in the patients was not different from that in the controls (OR=0.77, 95% CI=0.45-1.34; P=0.36). There were no significant differences between the patients and the control subjects in terms of the distributions of sex and age, smoking status, alcohol dependence, pickled diet status, or history of environmental exposure. The patients were further examined with stratifications by age, sex, grade, depth of tumor invasion, lymphatic invasion, venous invasion and TNM staging. The results showed no pronounced association among the stratifications. Conclusion There is no significant association between the MMP-9 single nucleotide polymorphism genotypes and phenotype of esophageal cancer.

Association between the -1562 C/T polymorphism in the MMP-9 promoter and phenotype of esophageal squamous cell carcinoma in northern Chinese population / 西安交通大学学报·英文版

Objective: To conduct a case-control study on the association of the nucleotide polymorphisms in the promoter region of the matrix metalloproteinase-9 (MMP-9) gene with phenotype of esophageal cancer. Methods: All subjects were unrelated residents in northern regions of China. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was used to determine the MMP-9 genotypes. Results: The overall distribution of genotypes in the patients was not different from that in the controls (OR = 0.77, 95% CI = 0.45-1.34; P = 0.36). There were no significant differences between the patients and the control subjects in terms of the distributions of sex and age, smoking status, alcohol dependence, pickled diet status, or history of environmental exposure. The patients were further examined with stratifications by age, sex, grade, depth of tumor invasion, lymphatic invasion, venous invasion and TNM staging. The results showed no pronounced association among the stratifications. Conclusion: There is no significant association between the MMP-9 single nucleotide polymorphism genotypes and phenotype of esophageal cancer.

Effects of (-)-Epigallocatechin-3-gallate on Brain Infarction and the Activity Change of Matrix Metalloproteinase-9 Induced by Middle Cerebral Artery Occlusion in Mice

Matrix metalloproteinases (MMPs) can degrade a wide range of extracellular matrix components. It has been reported that MMP-9 are activated after focal ischemia in experimental animals. (-)-Epigallocatechin-3-gallate (EGCG), a major constituent of green tea polyphenols, is a potent free radical scavenger and reduces the neuronal damage caused by oxygen free radicals. And it has been known that EGCG could reduce the infarction volume in focal brain ischemia and inhibit MMP-9 activity. To delineate the relationship between the anti-ischemic action and the MMP-9-inhibiting action of EGCG, we investigated the effect of EGCG on brain infarction and the activity of matrix metalloproteinase-9 induced by permanent middle cerebral artery occlusion (pMCAO) in ICR mice. EGCG (40 mg/kg, i.p. 15~30 min prior to MCAO) significantly decreased infarction volume at 24 hr after MCAO. GM 6001 (50 mg/kg, i.p. 15~30 min prior to MCAO), a MMP inhibitor, also significantly reduced infarction volume. In zymogram, MMP-9 activities began to increase at ipsilateral cortex at 2 hr after MCAO, and the increments of MMP-9 activities were attenuated by EGCG treatment. Western blot for MMP-9 also showed patterns similar to that of zymogram. These findings demonstrate that the anti-ischemic action of EGCG in mouse focal cerebral ischemia involves its inhibitory effect on MMP-9.

Implication of Changes of Serum C-Reaction Protein and Matrix Metalloproteinase-9 in Patients with Acute Coronary Syndrome in Nursing / 中国康复理论与实践

@#ObjectiveTo explore the changes of serum high sensitive C-reaction protein (HS-CRP) and matrix metalloproteinase-9 (MMP-9) in patients with acute coronary syndrome (ACS) and their effects in nursing.Methods103 ACS patients, including 56 cases of unstable angina (UA)) and 47 cases of acute myocardial infarction (AMI), and other 40 persons (no abnormal results in coronary artery angiography, selected as control group) were examined for serum levels of HS-CRP and MMP-9. The difference among the groups was analyzed.ResultsThe HS-CRP levels of UA group, AMI group and control group were (3.87± 0.76 )g/L, (4.12 ±0.67)g/L and (1.67±0.38)g/L respectively; MMP-9 were (113.25±7.76)ng/ml, (193.09±25.87)ng/ml and (42.05±3.81)ng/ml respectively. The concentrations of HS-CRP and MMP-9 of ACS patients were significatly higher than those of the control group (P<0.01).ConclusionThe changes of HS-CRP and MMP-9 concentrations of ACS patients are remarkable, and may be as the markers to instruct nursing works.

Effect of Batroxobin on focal cerebral ischemia and reperfusion injury in streptozotocin-induced diabetic rats / 中国康复理论与实践

@#ObjectiveTo observe the effect of Batroxobin and Urokinase on brain of diabetic rats following focal cerebral ischemia and reperfusion injury. To investigate the preventive mechanism of Batroxobin following focal cerebral ischemia and reperfusion injury in diabetic rats after thrombolysis therapy.MethodsDiabetic rat was induced by administrating streptozotocin intraperitoneally. Rat model of focal cerebral ischemia and reperfusion injury induced by intraluminal filament occlusion of middle cerebral artery(MCA) that removed 2h later was used. Batroxobin and Urokinase were administrated intravenously in different groups. Infarct volume,cerebral hemorrhage and matrix metalloproteinase (MMP)-2,MMP-9 were detected at 2h,24h,48h after ischemia and reperfusion injury.ResultsThe significant decrease of infarct volume were observed in Batroxobin and Urokinase groups. There were 5 rats observed cerebral hemorrhage in Urokinase group and no cerebral hemorrhage in Batroxobin group. The number of MMP-2 and MMP-9 positive cells in Batroxobin and Batroxobin Urokinase groups decreased compared with saline and Urokinase groups. ConclusionBatroxobin can decrease the infarct volume significantly without the complication of cerebral hemorrhage after ischemia and reperfusion injury in diabetic rats, which maybe relate to down regulation of the expression of MMP-2 and MMP-9.

The change of matrix metalloproteinase-9 early expression after cerebral ischemia-reperfusion injury / 中国康复理论与实践

@#ObjectiveTo explore the relationship of the expression of matrix metalloproteinase-9 (MMP-9) and the infarction area after transient focal cerebral ischemia and reperfusion.MethodsModels of transient focal ischemia of MCA in rats were built by placing an intraluminal suture and the neurologic deficit score, lesion area and MMP-9 expression were analyzed.ResultsThe expression of MMP-9 and the infarction area were positive correlation, but there is no correlation between the neurologic deficit score and the MMP-9 expression.ConclusionAfter cerebral ischemia-reperfusion the MMP-9 expression is upregulated. The study suggests that MMP-9 may be involved in infarction lesion.