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Introduction: Pulpal and periradicular diseases stem from immune reactions to microbiota, causing inflammation. Limited blood supply hampers dental pulp self-healing. Managing inflammation involves eliminating bacteria and reducing proinflammatory mediators especially MMP-9, which has a significant correlation with pulpitis. s. Flavonoids like Hesperidin, Baicalein, Epigallocatechin gallate, Genistein, Icariin, and Quercetin show potential for pulp capping. Aim: This in-silico study compares various Flavonoids for their anti-inflammatory effects on MMP-9, with Chlorhexidine as a control, a known MMP-9 inhibitor. Materials and Methods: Protein and Ligand Preparation: The human MMP-9 catalytic domain (PDB ID: 4XCT) structure was retrieved, and necessary modifications were made. Flavonoids from PubChem database were prepared for docking using AutoDock Vina. A grid for docking was created, and molecular dynamics simulations were conducted using Gromacs-2019.4 with GROMOS96 force field. Trajectory analysis was performed, and MM-PBSA calculation determined binding free energies. Results: Analysis of MMP-9 and ligand interactions revealed Hesperidin's high binding affinity, forming numerous hydrogen bonds with specific amino acids. Molecular dynamics simulations confirmed stability, with RMSD, RMSF, Rg, and SASA indicating consistent complex behaviour over 100 ns. MM-PBSA calculation affirmed favourable energy contributions in MMP9-Hesperidin interactions. Conclusion: MMP-9 plays a crucial role in prognosis of pulpitis. Incorporating MMP-9 inhibitors into pulp capping agents may enhance therapeutic efficacy. Hesperidin emerges as a potent MMP-9 inhibitor, warranting further in vivo validation against other agents. [ABSTRACT FROM AUTHOR]

Abstract Background Matrix metalloproteinases-9 (MMP-9) can regulate extracellular matrix deposition in diabetic glomerular injury. However, it remains unknown whether MMP-9 is involved in the renal tubular injury. Meanwhile, neutrophil gelatinase-associated lipocalin (NGAL), defined as a biomarker of proximal tubular injury, may influence MMP-9 by forming the MMP-9/NGAL complex. The aim of this study was to investigate MMP-9 expression in proximal renal tubules and the relationship of MMP-9 and NGAL in diabetic rat model treated with Valsartan. Methods Sprague Dawley rats were randomly divided into three groups: Diabetic group, Control group, and Treated group. The diabetic rat model was established by injection of streptozotocin. Related indexes were measured at the end of the 2nd, 4th, 8th and 12th week post-modeling. Results In diabetic groups, the concentrations of MMP-9 markedly increased in the serum and urine of rats in the early stage, even before the appearance of pathological albuminuria. Markedly elevated MMP-9/NGAL complex concentrations were also tested in diabetic groups. Western blot and qPCR tests confirmed that MMP-9 expression levels in the proximal renal tubular epithelial cells of diabetic rats were significantly higher than in control groups (P

Cognitive dysfunction is one of the complications of diabetes. Unfortunately, there is no effective methods to block its progression currently. One of the pathophysiological mechanisms is synaptic protein damage and neuronal signal disruption because of glucose metabolism disorder. Dystroglycan protein, located in the post‐synaptic membrane of neurons, links the intracellular cytoskeleton with extracellular matrix. Abnormal expression of dystroglycan protein affects neuronal biological functions and leads to cognitive impairment. However, there are no relevant studies to observe the changes of β‐dystroglycan protein in diabetes rat brain and in primary neurons under high glucose exposure. Our data demonstrated the alterations of cognitive abilities in the diabetic rats; β‐dystroglycan protein degradation occurred in hippocampal and cortical tissues in diabetic rat brain. We further explored the mechanisms underlying of this phenomenon. When neurons are exposed to high glucose environment in long‐term period, microRNA‐132 (miR‐132) would be down‐regulated in neurons. Matrix Metalloproteinases‐9 (MMP‐9) mRNA, as a target of miR‐132, could be up‐regulated; higher expression and overlay activity of MMP‐9 protein could increase β‐DG protein degradation. In this way, β‐DG degradation may affect structure and functions among the synapses, which related to cognition decline. It may provide some theoretical basis for elucidating the molecular mechanism of diabetes‐induced cognitive dysfunction. [ABSTRACT FROM AUTHOR]

Objective: To investigate matrix metalloproteinases (MMP)-2 and MMP-9 inhibitory effect of Salsola komarovii Iljin, an edible halophyte with health beneficial effects. Methods: Salsola komarovii crude extracts (SKI), and solvent (n-hexane, 85% aq. MeOH, n-BuOH, and H2O) fractionated extracts of SKI were prepared. Gelatin zymography was carried out to observe MMP enzymatic activity. The release of the MMP enzymes was measured by enzyme-linked immunosorbent assay. Expression of MMPs in mRNA and protein level were investigated by polymerase chain reaction analysis and immunoblotting, respectively. Results: SKI and SKI fractions inhibited active MMP-2 and MMP-9 amount in the treated cell culture medium. Also, SKI suppressed the release of MMP-2 and MMP-9 from stimulated HT1080 human fibrosarcoma cells. Furthermore, SKI suppressed the mRNA and protein expression of MMP-2 and MMP-9. SKI fractions showed parallel effects except for H2O fraction which did not yield any significant MMP inhibitory effect. Among fractions, 85% aq. MeOH was the most active fraction to inhibit both the enzymatic effect and expression of MMP-2 and MMP-9. Conclusions: SKI may contain potential MMP release inhibitory compounds. Salsola komarovii is a promising source of compounds against MMP and could be utilized in the development of antitumor agents.

Background: Matrix metalloproteinases-9 (MMP-9) can regulate extracellular matrix deposition in diabetic glomerular injury. However, it remains unknown whether MMP-9 is involved in the renal tubular injury. Meanwhile, neutrophil gelatinase-associated lipocalin (NGAL), defined as a biomarker of proximal tubular injury, may influence MMP-9 by forming the MMP-9/NGAL complex. The aim of this study was to investigate MMP-9 expression in proximal renal tubules and the relationship of MMP-9 and NGAL in diabetic rat model treated with Valsartan.Methods: Sprague Dawley rats were randomly divided into three groups: Diabetic group, Control group, and Treated group. The diabetic rat model was established by injection of streptozotocin. Related indexes were measured at the end of the 2nd, 4th, 8th and 12th week post-modeling.Results: In diabetic groups, the concentrations of MMP-9 markedly increased in the serum and urine of rats in the early stage, even before the appearance of pathological albuminuria. Markedly elevated MMP-9/NGAL complex concentrations were also tested in diabetic groups. Western blot and qPCR tests confirmed that MMP-9 expression levels in the proximal renal tubular epithelial cells of diabetic rats were significantly higher than in control groups (P < 0.05). Correlation analysis showed that MMP-9 was positively correlated with NGAL at both protein and gene expression levels. In addition, Valsartan observably reduced tubular injury as well as MMP-9 expression in diabetic rats.Conclusions: In diabetic kidney injury, the expression of MMP-9 in the proximal renal tubular epithelial cells was significantly increased. Besides, a positive correlation was found between MMP-9 and NGAL expression, along with high levels of MMP-9/NGAL complex, which indicated that NGAL might participate in the regulation of MMP-9 expression. The administration of Valsartan may reduce this effect. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinase (MMP)-9 belongs to the zinc-dependent endopeptidase family, which is associated with important inflammatory processes and plays an important role in cell metabolism, embryonic development, and wound repair. The present study was performed using Pampus argenteus individuals fed with different feeds. The full-length cDNA of the MMP-9 gene was 2783 bp and encoded 681 amino acids. The amino acid sequence analysis of Pampus argenteus MMP-9 showed that it contained a highly conserved fibronectin type II domain and heme domain, and it was evolutionarily closely related to the MMP-9 of Seriola dumerili. Real-time PCR, western blotting, and enzyme activity assay were used to analyze the expression of MMP-9 in P. argenteus under different feeding conditions, in various tissues, and on different feeding days. The results showed that the expression of MMP-9 in group A (fed with jellyfish for the first 20 days) and B' group (fed with jellyfish for subsequent 15 days) was significantly higher than that in other groups (P < 0.05) and the expression in the kidney was significantly higher than that in other tissues (P < 0.05). The expression increased gradually with the increase in feeding time. The results suggest that MMP-9 expression is induced in P. argenteus fed with jellyfish and plays a very important role in the immune response of the body. [ABSTRACT FROM AUTHOR]

Background Matrix metalloproteinases-9 (MMP-9) is a member of a large group of zincdependent endopeptidases and is essential in immune response. It plays an imperative function in pneumonia pathogenesis. We aimed to evaluate the role of MMP-9 in pediatric patients with congenital heart diseases (CHD) who gained ventilator-acquired pneumonia. //Patients and methods A total of 80 children were included, who were further divided into 30 cardiac patients with ventilator-associated pneumonia (VAP), 30 cardiac patients with pneumonias either hospital acquired or community acquired, and 20 agematched and sex-matched cardiac patients without chest infection as the control group. Assessments of white blood cell count, neutrophil count, serum C-reactive protein (CRP), and MMP-9 were done in all studied children. Results Comparison among the studied groups regarding laboratory data revealed high significant difference regarding white blood cell, neutrophil count, CRP, and MMP-9, as they were elevated among cardiac children with VAP than other groups (P=0.0001, 0.0001, 0.0001, and 0.0001, respectively). There was no significant difference between cases with acyanotic CHD and those with cyanotic CHD either with increased pulmonary blood flow or with decreased pulmonary blood flow regarding MMP-9 (P=0.2446). Conclusion MMP-9 level was significantly elevated in cardiac patients with VAP than other groups. Serum MMP-9 was more elevated among cyanotic CHD with increased pulmonary blood flow as hypoxia can lead to increased expression of MMP-9. MMP-9 was correlated with other inflammatory markers, including CRP, neutrophils count, and white blood cells, which offers it as a marker in assessing severity of pediatric pneumonia in cardiac patients. [ABSTRACT FROM AUTHOR]

To investigate the correlations between the water content of brain tissue around hematoma and the expression levels of matrix metalloproteinases-9 (MMP-9), interleukin-6 (IL-6) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in rats with intracerebral hemorrhage (ICH). 84 healthy adult male Wistar rats were randomly divided into observation group, sham-operated group and control group, with 28 rats in each group. In addition, the observation group was divided into 9 subgroups on the 1d after ICH, 9 subgroups on the 3d and 10 subgroups on the 7d. The ICH model was prepared in observation group, sham-operated group was only given empty needle puncture, while no model preparation for control group.The brain water content and MMP-9, IL-6 and TIMP-1 levels around hematoma in each group were detected and compared. The brain water content, MMP-9, IL-6 and TIMP-1 levels around hematoma in different subgroups of the observation group (1, 3 and 7 days after ICH) were compared. The relationships between brain water content around hematoma and the expression levels of MMP-9, IL-6 and TIMP-1 in ICH rats were analyzed. The water content of brain tissue around hematoma and the levels of MMP-9, IL-6 and TIMP-1 in the observation group were higher than sham operation group and the control group, the differences were statistically significant (P<0.05). The water content of brain tissue around hematoma and the levels of MMP-9, IL-6 and TIMP-1 in the 3d and 7d subgroups in the observation group were higher than those in the 1d subgroup, but the 7d subgroup were lower than that in the 3d subgroup, the differences were statistically significant (P<0.05). According to Spearman correlation analysis, the brain water content around the hematoma of ICH rats was positively correlated with the expression levels of MMP-9, IL-6 and TIMP-1 (P<0.05). The water content of brain tissue around ICH rats are positively correlated with the expression levels of MMP-9, IL-6 and TIMP-1. MMP-9, IL-6 and TIMP-1 play an important role in the occurrence and development of peripheral tissue edema after ICH [ABSTRACT FROM AUTHOR]

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Abstract Dendritic cell (DC)-based cytotoxic T lymphocyte (CTL) epitope vaccines are effective to induce CTL responses but require complex ex vivo DC preparation and epitope-loading. To take advantage of DC-based epitope vaccines without involving the ex vivo procedures, we aimed to develop carriers to directly load CTL epitopes onto DCs in vivo. Here, we first engineered a carrier consisting of a hydrophilic polypeptide, immune-tolerant elastin-like polypeptide (iTEP) and a substrate peptide of matrix metalloproteinases-9 (sMMP). The iTEP was able to solubilize CTL epitopes. CTL epitopes were connected to the carrier, iTEP-sMMP, through sMMP so that the epitopes can be cleaved from the carrier by MMP-9. iTEP-sMMP was found to release its epitope payloads in the DC culture media, which contained MMP-9 released from DCs. iTEP-sMMP allowed for the direct loading of CTL epitopes onto the surface MHC class I complexes of DCs. Importantly, iTEP-sMMP resulted in greater epitope presentation by DCs both in vitro and in vivo than a control carrier that cannot directly load epitopes. iTEP-sMMP also induced 2-fold stronger immune responses than the control carrier. To further enhance the direct epitope-loading strategy, we furnished iTEP-sMMP with an albumin-binding domain (ABD) and found the new carrier, ABD-iTEP-sMMP, had greater lymph node (LN) accumulation than iTEP-sMMP. ABD-iTEP-sMMP also resulted in greater immune responses than iTEP-sMMP by 1.5-fold. Importantly, ABD-iTEP-sMMP-delivered CTL epitope vaccine induced stronger immune responses than free CTL epitope vaccine. Taken together, these carriers utilized two physiological features of DCs to realize direct epitope-loading in vivo : the accumulation of DCs in LNs and MMP-9 released from DCs. These carriers are a potential substitute for DC-based CTL epitope vaccines. [ABSTRACT FROM AUTHOR]

In this study, inhibitory activity of 30 traditional medicinal plant extracts were examined and evaluated against MMP-9 activity by an orthogonal screening method based on an enzyme inhibition assay along with a surface plasmon resonance (SPR)-based binding assay. Five extracts exhibited reasonable inhibitory activity using inhibition assay. The most potent inhibition was found in Onopordum acanthium L. extract. Therefore, its active compound (onopordia) was isolated and identified as a new MMP-9 inhibitor. In order to evaluate binding profile of O. acanthium extract and onopordia, MMP-9 was immobilized on SPR carboxymethyldextran chip. Equilibrium constant (K D ), maximum binding capacity (R max ) and ΔG binding values for the interaction of onopordia and MMP-9 were found to be 3 nM, 1190 μRIU and −51.37 kJ/mol. Docking analysis supported the strong binding of onopordia to the MMP-9 active site. This new SPR based biosensor could represent a simple, sensitive, real time and label-free method for screening medicinal plant extracts for identifying potential MMP-9 inhibitors in short time. [ABSTRACT FROM AUTHOR]

2-Chloroethanol (2-CE) is one of the reactive metabolites of 1,2-DCE in vivo, which might contribute to brain edema formation induced by 1,2-dichloroethane (1,2-DCE) poisoning. Thus, the purpose of this study was to explore the roles of mitogen-activated protein kinase (MAPK) signal pathways in upregulation of matrix metalloproteinase-9 (MMP-9) in 2-CE exposed rat astrocytes. Expression of p38 MAPK (p38), extracellular signal regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK) and MMP-9 at both protein and gene levels in rat astrocytes were determined using western blot and real-time RT-PCR methods. The results showed that both protein and mRNA levels of MMP-9 in 2-CE exposed astrocytes significantly increased. Meanwhile, protein levels of phosphorylated p38 (p-p38), ERK1/2 (p-ERK1/2) and JNK1/2 (p-JNK1/2) in 2-CE exposed astrocytes also significantly increased. In addition, both protein and mRNA levels of MMP-9 significantly decreased in response to reduced protein levels of p-p38, p-ERK1/2 and p-JNK1/2 achieved by supplement with their specific inhibitors, indicating that activation of MAPK signal pathways might play an important role in upregulation of MMP-9 expression at the transcriptional level in 2-CE exposed astrocytes. Furthermore, since pretreatment of n-acetyl-l-cysteine (NAC), a powerful antioxidant amino acid, could attenuate the elevated levels of MMP-9, p-p38, p-ERK2 and p-JNK1/2 in 2-CE exposed astrocytes, activation of MAPK signal pathways in 2-CE exposed astrocytes could be mediated partially by reactive oxygen species (ROS), which was most likely generated in the metabolism of 2-CE.

We previously reported that expression of matrix metalloproteinase-9 (MMP-9) mRNA and protein was upregulated during 1,2-dichloroethane (1,2-DCE) induced brain edema in mice. We also found that the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway resulted in MMP-9 overexpression and nuclear factor-κB (NF-κB) activation in mice treated with 1,2-DCE. In this study, we further hypothesized that inflammatory reactions mediated by the p38 MAPK/ NF-κB signaling pathway might be involved in MMP-9 overexpression, blood−brain barrier (BBB) disruption and edema formation in the brain of 1,2-DCE-intoxicated mice. Our results revealed that subacute poisoning by 1,2-DCE upregulates protein levels of glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule 1 (Iba-1), interleukin-1β (IL-1β), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), inducible nitric oxide synthase (iNOS) and p-p65 in mouse brains. Pretreatment with an inhibitor against p38 MAPK attenuates these changes. Moreover, pretreatment with an inhibitor against NF-κB attenuates alterations in brain water content, pathological indications notable in brain edema, as well as mRNA and protein expression on levels of MMP-9, VCAM-1, ICAM-1, iNOS, and IL-1β, tight junction proteins (TJs), GFAP and Iba-1 in the brain of 1,2-DCE-intoxicated mice. Furthermore, pretreatment with an inhibitor against MMP-9 obstructs the decrease of TJs in the brain of 1,2-DCE-intoxicated mice. Lastly, pretreatment with an antagonist against the IL-1β receptor also attenuates changes in protein levels of p-p38 MAPK, p-p65, p-IκB, VCAM -1, ICAM-1, IL-1β, and Iba-1 in the brain of 1,2-DCE-intoxicated-mice. Taken together, findings from the current study indicate that the p38 MAPK/ NF-κB signaling pathway might be involved in the activation of glial cells, and the overproduction of proinflammatory factors, which might induce inflammatory reactions in the brain of 1,2-DCE-intoxicated mice that leads to brain edema.

Objective: To analyze the effect of tanreqing injection on the serum levels of transforming growth factor-β (TGF-β) and matrix metalloproteinases-9 (MMP-9) of patients with chronic obstructive pulmonary disease (COPD). Methods: 102 patients with COPD were divided into the control group and the observation group according to random number table method, 52 cases in each group. The control group was treated with routine therapy, and the observation group was treated with Tanreqing injection based on the control group. The serum TGF-β, MMP-9 levels, forced vital capacity (FYC). Is forced expiratory volume (FEV1), partial pressure of carbon dioxide (PaCO2), oxygen partial pressure (PaO2), CD4+, CD8+. CD4/CD8+, syndrome integral, clinical efficacy and incidence of side effects were observed and compared between the two groups. Results: After treatment, the serum TGF-β. MMP-9 levels. PaCO2 and syndrome integral of observation group were significantly lower than those of the control group, the PaO2, CD4+ FYC, FEV1, CD4/CD8+ and the clinical efficacy of observation group were obviously higher than those of the control group (P<0.05). There was no significant difference in the incidence of side effects between the two groups (P>0.05). Conclusion: Tameqing injection could effectively reduce the serum levels of TGF-β and MMP-9. and improve the arterial blood gas, lung function and immune function in treatment of patients with COPD. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of bushen wenyang liuayu treatment on semm levels of endometrial glandular epithelial cells osteopontin (OPN) and matrix metalloproteinases-9 (MMP-9) in patients with endometriosis. Methods: 92 cases with endometriosis who were treated in our hospital from April 2013 to April 2016 were selected and randomly divided into the control group and the observation group with 46 cases in each group. The patients in the control group were treated with western medicine, while the patients in the observation group were treated with bushen wenyang huayu method. Then the serum levels of OPN. MMP-9. estradiol (E2). luteinizing hormone (LH). follicle-stimulating hormone (FSH). tumor necrosis factor-a (TNF-a). interleukin-6 (IL-6). interleukin-8 (IL-8). CD3+, CD4+. CDS" and CD47CD8L the clinical efficacy and safety in the two groups were observed and compared before and after the treatment. Results: After treatment, the serum levels of OPN. MMP-9. TNF-α. DL-6. IL-8 and CD8+ in the observation group were lower than those of the control group, while the levels of CD3+, CD4+ and CD47 CD8+ were higher, and the differences were statistically significant (P<0.05). The total effective rate of the observation group was higher than that of the control group, while the incidence of adverse reactions was lower (P<0.05). Conclusion: Bushen wenyang huayu method can reduce the serum levels of OPN endometrial glandular epithelial cells and MPP-9 of patients with endometriosis. [ABSTRACT FROM AUTHOR]

Aims: Matrix metalloproteinases (MMP) have been associated with neonatal lung morbidity and MMP dysregulation contributes to the pathology of chronic and acute lung disorders. Most of the previous studies were performed in the 1 st weeks of life of the preterm newborns. There are no data on the serum levels of MMP-2, MMP-9 or tissue inhibitors of matrix metalloproteinases (TIMP-1) from preterm infants recovering from lung morbidities. We aimed to compare MMP-2, MMP-9 and TIMP-1 levels in preterm and term infants hospitalized with their first episode of wheezing. Methods: We prospectively evaluated 18 preterm infants with a history of chronic lung disease, respiratory distress syndrome or oxygen therapy and 14 age- and sex-matched term infants who were admitted for a first episode of wheezing. We quantified total serum concentrations of MMP-2, MMP-9 and TIMP-1 to assess whether these serum markers levels were associated with the first episode of wheezing in infants with a history of oxygen therapy during the neonatal period. Results: Upon hospitalization, MMP-2 and TIMP-1 levels were higher in preterm infants than in term infants. In contrast, there was no significant relationship between MMP-9 levels or the MMP-9/TIMP-1 ratio between preterm and term infants. The area under the receiver operating characteristic curve for MMP-2 was 0.70 (95% confidence interval [CI] 0.51-0.89). The area under the curve for TIMP-1 was 0.78 (95% CI 0.61-0.94). MMP-9, MMP-2 and TIMP-1 levels did not correlate with gestational age, gender or severity of wheezing. Conclusion: The negative proportion of MMP-9 to TIMP-1 that we detected in term infants was not present in preterm infants. The balance of MMP-9 to TIMP-1 may have been disrupted by lung damage in the premature infants. Overproduction of MMP-2 and TIMP-1 in the serum may be associated with the pathogenesis of wheezing in preterm infants.

Subacute poisoning of 1,2-dichloroethane (1,2-DCE) has become a serious occupational problem in China, and brain edema is its main pathological consequence, but little is known about the underlying mechanisms. As the metabolite of 1,2-DCE, 2-chloroethanol (2-CE) is more reactive, and might play an important role in the toxic effects of 1,2-DCE. In our previous studies, we found that matrix metalloproteinases-9 (MMP-9) expression was enhanced in mouse brains upon treatment with 1,2-DCE, and in rat astrocytes exposed to 2-CE. In the present study, we analyzed the association of nuclear factor kappa B (NF-κB) and activator protein-1 (AP-1) with MMP-9 overexpression in astrocytes treated with 2-CE. MMP-9, p65, c-Jun, and c-Fos were significantly upregulated by 2-CE treatment, which also enhanced phosphorylation of c-Jun, c-Fos and inhibitor of κBα (IκBα), and nuclear translocation of p65. Furthermore, inhibition of IκBα phosphorylation and AP-1 activity with the specific inhibitors could attenuate MMP-9 overexpression in the cells. On the other hand, inhibition of p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway suppressed the activation of both NF-κB and AP-1 in 2-CE-treated astrocytes. In conclusion, MMP-9 overexpression induced by 2-CE in astrocytes could be mediated at least in part through the p38 signaling pathway via activation of both NF-κB and AP-1. This study might provide novel clues for clarifying the mechanisms underlying 1,2-DCE associated cerebral edema.

Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract infections (ALRTIs). In this study, we aimed to evaluate the role of viral load, cytokines, matrix metalloproteinase 9 (MMP-9), and tissue inhibitor of metalloproteinase 1 (TIMP-1) in determining the severity of RSV disease and identify potential biomarkers of disease severity. A total of 142 patients with RSV infection (aged between 2 months and 5 years) who presented with ALRTI between December 2013 and March 2016 were enrolled. Their nasopharyngeal aspirates were subjected to RSV viral load quantification, and local cytokine levels of interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), IL-17A, interferon γ (IFN-γ), and IL-10 were determined using a cytokine bead array. The levels of MMP-9 and TIMP-1 in 109 aspirates were calculated using Quantikine ELISA. These parameters were compared for different disease severity categories. A higher viral load and increased levels of TNF-α, MMP-9, and MMP-9:TIMP-1 were associated with greater severity of disease; whereas levels of IL-17A, IFN-γ, and IFN-γ:IL-10 were associated with disease resolution. When defining the transition from non-severe to severe disease, MMP-9 had a sensitivity and specificity of 89.7% and 85.4%, respectively. Moreover, MMP-9:TIMP-1 had a sensitivity and specificity of 87.2% and 76.8%, respectively. Hence, MMP-9, MMP-9:TIMP-1, TNF-α, and IL-10 could serve as potential biomarkers for disease progression in RSV-infected children.

Objectives Matrix metalloproteinases (MMPs) play an important role in the pathogenesis of coronary artery disease (CAD). This study aims to determine the association of MMP-9 genotype polymorphisms and its serum levels with the risk of acute myocardial infarction (AMI) in Egyptian patients. Also, it evaluated their role as predictors of AMI outcome after six months follow-up. Methods Subjects included in the study were 184 patients with AMI and 180 controls. Genotyping of MMP-9-1562C > T polymorphism was carried out by PCR-based restriction digestion method. Serum MMP-9 was measured using ELIZA assay. All patients were followed for AMI complications during their hospitalization and 6 months later on. Results MMP-9-1562 T allele was more frequent in patients than in controls (OR = 1.65, 95%CI 1.09–2.15, P = 0.011). the frequency of CT + TT genotypes were higher in patients with morbidity (OR = 2.85, 95%CI 1.29–6.29, P = 0.008) and with mortality (OR = 3.21, 95%CI 1.28–8.02, P = 0.012) than in those without MI complications. Serum MMP-9 levels were significantly elevated in AMI as compared to controls and more associated with TT genotype. The impairment of LV function (ΔEF, ΔLAD, ΔE/A) was more observed in the TT genotype compared with CC genotype. Conclusions Our data suggest that MMP-9 (TT genotype) and its serum level are associated with the risk of suffering AMI in Egyptians. In addition, MMP-9 polymorphism and its level might be useful clinical biomarkers for predicting the outcome of AMI. [ABSTRACT FROM AUTHOR]

Objective To observe the effects of baicalein on the migration and invasion of human gastric carcinoma SGC7901 cells and its mechanism. Methods Human gastric carcinoma SGC7901 cells cultured in vitro were respectively treated with 20mL culture medium (control group), 50mol/L baicalein, 100mol/L baicalein, and 150mol/L baicalein for 48 hours. Wound healing and Transwell assay were used to determine the inhibitory effects of baicalein on cell migration and invasion in human gastric carcinoma SGC7901 cells respectively. The typsin activity of cells was detected by photocolorimetric method, the protein expression of active protease-activated receptor-2 (PAR-2) was detemined by Western blotting; the matrix metalloproteinases-2 (MMP-2) mRNA, matrix metalloproteinases-9 (MMP-9) mRNA expressions were measured with RT-PCR. Results Compared with those in control group, the abilities of cells migration and invasion and the typsin activity, active PAR-2, MMP-2 mRNA and MMP-9 mRNA expressions were dose-dependently decreased in three baicalein groups (P<0.01). There were obvious positive correlations among active PAR-2, MMP-2 mRNA and MMP-9 mRNA expressions (r=0.564, P<0.05; r=0.681, P<0.05). Conclusion PAR-2 activity, MMP-2 mRNA and MMP-9 mRNA expressions are closely correlated with the pathogenesis of gastric carcinoma. Active PAR-2 may play an important role in carcinoma cells migration and invasion via upregulating MMP-2 mRNA and MMP-9 mRNA expressions. Baicalein can inhibit PAR-2 activity, MMP-2 mRNA and MMP-9 mRNA expressions obviously in human gastric carcinoma SGC7901 cells, thus decreasing the carcinoma cells migration and invasion, which is closely correlated to its inhibiting effects on typsin activity. [ABSTRACT FROM AUTHOR]

Endothelin-1 (ET-1) is one of the most potent vasoconstrictors known to date. While its plasma or serum concentrations are elevated in some forms of experimental and human hypertension, this is not a consistent finding in all forms of hypertension. Matrix metalloproteinases -2 and -9 (MMP-2 and MMP-9), which degrade collagen type IV of the vascular basement membrane, are responsible for vascular remodeling, inflammation, and atherosclerotic complications, including in type 2 diabetes (T2D). In our study, we compared concentrations of ET-1, MMP-2, and MMP-9 in pre-hypertensive (PHTN) and hypertensive (HTN) T2D patients with those of healthy normotensive controls (N). ET-1, MMP-2, and MMP-9 were measured by ELISA. Concentrations of ET-1 in PHTN and N were very similar, while those in HTN were significantly higher. Concentrations of MMP-2 and MMP-9 in PHTN and HTN were also significantly higher compared to N. An interesting result in our study is that concentrations of MMP-2 and MMP-9 in HTN were lower compared to PHTN. In conclusion, we showed that increased production of ET-1 in patients with T2D can lead to long-lasting increases in blood pressure (BP) and clinical manifestation of hypertension. We also demonstrated that increased levels of MMP-2 and MMP-9 in pre-hypertensive and hypertensive patients with T2D mainly reflect the early vascular changes in extracellular matrix (ECM) turnover. [ABSTRACT FROM AUTHOR]

Following myocardial infarction (MI), the left ventricle (LV) undergoes a series of cardiac wound healing responses that involve both the stimulation of robust inflammation to clear necrotic myocytes and tissue debris and the induction of extracellular matrix (ECM) protein synthesis to generate an infarct scar. The collective changes in myocardial structure and function are termed LV remodeling, and matrix metalloproteinase- 9 (MMP-9) is a key instigator of post-MI LV remodeling. Through direct molecular effects on ECM and inflammatory protein turnover as well as indirect effects on major cell types that coordinate cardiac wound healing, namely the infiltrating leukocytes and the cardiac fibroblasts, MMP-9 coordinates multiple aspects of LV remodeling. In this review, we will discuss recent research that has expanded our understanding of post-MI LV remodeling, including recent proteomic advances focused on the ECM compartment to provide novel functional and translational insights. This overview will summarize how our understanding of MMP-9 has evolved over the last decade and will provide insight into future directions that will drive our understanding of MMP-9-directed cardiac ECM turnover in the post-MI LV. [ABSTRACT FROM AUTHOR]

Objective To clarify the mechanism of calcium alginate dressings for improving the express of wound healing by its effects on the expression of matrix metallopeptidase 9(MMP-9) in the wound tissue in diabetes rats. Methods The thirty-six male diabetic SD rats, wounded on the back(with a diameter of 20 mm) with sterile scissors, were randomized divided into two groups according to random number table: the experimental group (n=18, treated with calcium alginate dressing for 14 days) and the control group (n=18, treated with conventional gauze dressing). The wound healing rates in the two groups were obtained, HE and Masson staining methods were used to evaluate the thickness and inflammatory response of granulation tissue and level of collagen in it, meanwhile Western blotting and realtime polymerase chain reaction(RT-PCR) methods were applied to evaluate the expression of mRNA and protein of MMP-9 during the process of wound closure. The t-test and chi-square were used to test the differences between the data of the two groups. Results The wound healing rate in the experimental group was faster than that in the control group at day 8, 10,12 and 14 (χ2=8.333, 5.124, 14.047, 16.547, all P<0.05). The inflammatory response in experimental group was milder than that in control group at different periods post-operation. Significant statistical difference in thickness of granulation were found in the two groups at day 3((1476±118) vs (812±136)μm,t=6.384,P=0.003) and day 7((1369±86) vs (480±105)μm,t=11.307,P= 0.000). The level of collagen in control group were much lower than those in in experimental group at day 7 and 14 (15%±5% vs 51%±5%, 28%±5% vs 61%±5%,t=9.308, 8.196,bothP<0.05). And the mRNA expression of MMP-9 in the experimental group decreased significantly when compared with those in the control group at day 3, 7 and 14 (0.028±0.003 vs 0.037±0.004, 0.026±0.003 vs 0.033±0.003, 0.021±0.003 vs 0.030±0.002,t=3.118, 2.858, 7.003, allP<0.05). Meanwhile the protein levels of MMP-9 in the experimental group were significantly lower than those in the control group at day 3, 7, 14(t=10.595, 10.400, 12.359, all P<0.05). Conclusions Calcium alginate dressing promotes skin ulcer healing by inhibiting the expression of MMP-9 so as to reduce the degradation of collagen in diabetic SD rats. [ABSTRACT FROM AUTHOR]

Objective To observe the effect of Jiangu granulecontaining serum on themRNA expression of CA II,CK,and MMP-9 in osteoclasts,and to reveal themechanism of Jiangu granulein prevention and treatment of postmenopausal osteoporosis.Methods Matureosteoclasts wereinduced from osteoclast precursor RAW264. 7 cells with M-CSF and RANKL. Theoptimal concentration of serum intervention was detected with Alamar Bluemethod. On theseventh day of culture,thecells weretreated with 25% normal salinecontaining serum or 25% Jiangu granulecontaining serum,respectively. After 48 hours,total RNA was extracted and then reversely transcripted using RT-PCR. Real-timefluorescencequantitativeSYBR GREEN method was applied to detect CA II,CK,and MMP-9 mRNA expression. Toluidinebluestaining bonechip was used to analyzeboneresorption lacuna and area. Oxidation color method was used to detect TRAP content in culturefluid. ELISA method was used to detect CTx content in culturebonegrinding tablets. Results CA II, CK, and MMP-9 mRNA expression levels in Jiangu granulegroup weresignificantly lower than thosein normal salinegroup( P < 0.05). Boneresorption lacuna and area on grinding tablets and levels of TRAP and CTx in Jiangu granulegroup werelower than thosein normal salinegroup( P < 0.05). Conclusion Jiangu granuleinhibits CA II,CK,and MMP- 9 mRNA expression in osteoclasts effectively,reduces functional activity of osteoclasts,and inhibits resorption of bonematrix by osteoclasts. [ABSTRACT FROM AUTHOR]

Paeoniflorin is one of the active ingredients of the commonly used herbal medicine derived from Paeonia, which exhibits anticancer properties. MicroRNA-16 (miR-16) is upregulated in CD133- cells, but downregulated in CD133+ cells from glioma tissue. Matrix metalloproteinase-9 (MMP-9) expression in glioma tissue samples is significantly higher than that in healthy brain tissue samples. Therefore, miR-16 and MMP-9 expression may be associated with glioma pathogenesis. In the present study, the effects of paeoniflorin on glioma were analyzed. U87 cells were treated with paeoniflorin at 0, 5, 10 and 20 μM concentrations. The results suggested that paeoniflorin inhibited U87 cell proliferation and accelerated cell apoptosis. In the present study paeoniflorin treatment increased miR-16 expression and reduced MMP-9 protein expression in U87 cells. Additionally, the results of the present study suggested that miR-16 may regulate MMP-9 expression in miR-16-transfected U87 cells. Furthermore, anti-miR-16 antibodies were used in order to investigate the apoptotic effects of paeoniflorin on U87 cells. The results demonstrated that paeoniflorin inhibits proliferation and induces apoptosis of human glial cells, via miR-16 upregulation and MMP-9 downregulation. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To analyze the changes of adiponection (ANP) and matrix metalloproteinase-9 (MMP-9) in patients with coronary heart diseases (CHD) of different types, to investigate the correlation between these changes and stability of coronary artery plague. METHODS: Inpatients of our hospital were divided into 56 cases with acute myocardial infarction (AMI), 56 cases with unstable angina pectoris (UA), 54 cases with stable angina pectoris (SA), and 60 cases with CHD excluded by using coronary arteriongraphy as the control group. Changes of ANP and MMP-9 were determined, and the correlation was analyzed. RESULTS: 1. ANP and MMP-9 levels in CHD group were higher than those of control group (P < 0.01). 2. Serum ANP and MMP-9 levels in AMI and UA groups were significantly higher than those in control group and SA group (P <0.05). 3. MMP-9 level in AMI group was significantly higher than that in UA group (P <0.01). CONCLUSION: 1. Increased ANP and MMP-9 levels are the independent risk factors of CHD; 2. Increased levels of ANP and MMP-9 in patients with CHD suggest instability of atherosclerotic plaque. [ABSTRACT FROM AUTHOR]

Dietary deficiencies in folic acid result in elevated levels of plasma homocysteine, which has been associated with the development of dementia and other neurodegenerative disorders. Previously, we have shown that elevated levels of plasma homocysteine in mice deficient for a DNA repair enzyme, uracil–DNA glycosylase (UNG), result in neurodegeneration. The goal of this study was to evaluate how deficiencies in folic acid and UNG along with elevated levels of homocysteine affect vascular cognitive impairment, via chronic hypoperfursion in an animal model. Ung +/+ and Ung −/− mice were placed on either control (CD) or folic acid deficient (FADD) diets. Six weeks later, the mice either underwent implantation of microcoils around both common carotid arteries. Post-operatively, behavioral tests began at 3-weeks, angiography was measured after 5-weeks using MRI to assess vasculature and at completion of study plasma and brain tissue was collected for analysis. Learning impairments in the Morris water maze (MWM) were observed only in hypoperfused Ung −/− FADD mice and these mice had significantly higher plasma homocysteine concentrations. Interestingly, Ung +/+ FADD produced significant remodeling of the basilar artery and arterial vasculature. Increased expression of GFAP was observed in the dentate gyrus of Ung −/− hypoperfused and FADD sham mice. Chronic hypoperfusion resulted in increased cortical MMP-9 protein levels of FADD hypoperfused mice regardless of genotypes. These results suggest that elevated levels of homocysteine only, as a result of dietary folic acid deficiency, don’t lead to memory impairments and neurobiochemical changes. Rather a combination of either chronic hypoperfusion or UNG deficiency is required. [ABSTRACT FROM AUTHOR]

The human matrix metalloproteinases (MMPs) are importantly involved in aneurysm formation. Since the clinical manifestations in Behçet disease (BD) include aneurysm formation among major symptoms, polymorphisms in MMP-9 might be associated with BD susceptibility. The aim of the current case–control study was to investigate the association of four single nucleotide polymorphisms (SNPs) in MMP-9 gene: -1562 C/T, 2003 G/A (R668Q), 836 A/G (Q279R) and 1721 C/G (R574P) with BD risk in the Tunisian population. The distribution of MMP-9 gene polymorphisms was analyzed by polymerase chain-reaction (PCR) and restriction fragment length polymorphism (RFLP) for 240 BD patients and 288 controls. Our study indicated that the MMP-9 -1562 C/T polymorphism (rs3918242) was not associated with BD risk. We found a significant association of the MMP-9 2003 G/A (rs17577) with an increased susceptibility to BD. However, the MMP-9 1721 C/G polymorphism (rs2250889) had a protective role against the development of BD. Subgroup analysis based on stratification by gender revealed that the MMP-9 2003 G/A polymorphism was associated with a highly significant BD risk in women's group (G vs. A: P = 0.0000001). However, the MMP-9 836 A/G polymorphism had a protective role in men's group (G vs. A: P = 0.00043). The MMP-9 1721 C/G polymorphism was associated with a protective effect in both men and women groups (CG + GG vs. CC: P = 0.04 and P = 0.0002, respectively). The haplotype analysis did not show any association with BD risk. A significant difference in the MMP-9 serum levels were observed in the patient subgroup with ocular lesions manifestations. [ABSTRACT FROM AUTHOR]

The present report investigated the correlation between the expression levels of matrix metalloproteinase (MMP)-9 in gastric carcinoma patients and the clinicopathological characteristics. Forty-five samples of gastric carcinoma and distal gastric mucosa tissue, and 10 samples of healthy gastric mucosa tissue were analyzed using semi-quantitative polymerase chain reaction, as well as immunohistochemical and hematoxylin and eosin staining. MMP-9 protein levels in serum samples from the same patients were quantified by enzyme-linked immunosorbent assay. The present report identified that MMP-9 expression was markedly higher in the gastric carcinoma tissue (86.67%) than in the adjacent healthy tissue (10.00%). A positive association was identified between the level of MMP-9 protein expression and the depth of cancer invasion (P<0.05). Furthermore, the preoperative serum levels of the MMP-9 protein in the gastric carcinoma tissue were correlated with the tumor-node-metastasis stage and occurrence of lymph node metastasis (P<0.01). Data from the present report indicates that MMP-9 may be key in gastric carcinoma malignancy, and implies that MMP-9 may serve as a novel biomarker in the diagnosis and prognosis of gastric carcinoma. [ABSTRACT FROM AUTHOR]

The effect of Artesunate on anti-hepatic fibrosis was discovered by our team for the first time. In order to investigate the effect of Artesunate on hepatic fibrosis induced by Bovine serum albumin (BSA) in rats and understand the initiatory mechanism of its effect, several experiments were conducted in this assay. HE staining and Masson׳s Trichrome staining were employed in observation of morphological changes. The content of hydroxyproline in the hepatic tissue was determined by using an acid hydrolyzation method. In addition, the expression of Matrix metalloproteinase-13 (MMP-13) and type I collagen were tested by western blotting respectively. The expression of Matrix metalloproteinase-2(MMP-2), Matrix metalloproteinase-9 (MMP-9) were determined by Gelatin Zymography Assay. Also, we use immunohistochemical studies to measure the expression of α-SMA. The final results indicated that Artesunate could dramatically attenuate the extent of hepatic fibrosis showed by histopathological sections of hepatic tissues, significantly decrease the content of hydroxyproline and efficiently inhibit the protein expression of MMP-2, MMP-9, α-SMA and type I collagen. Artesunate could as well promote the expression of MMP-13 at the same time. In conclusion, the results not only suggested that Artesunate could ameliorate hepatic fibrosis, but also suggested the anti-fibrogenic mechanisms of Artesunate might be associated with inhibiting the activation of HSCs, decreasing the expression of MMP-2, MMP-9 and increasing the expression of MMP-13.These results would bring new insights for the treatment for hepatic fibrosis. [ABSTRACT FROM AUTHOR]

Background: Matrix metalloproteinases (MMP)-8 is increased in smokers with chronic periodontitis (CP). The levels of MMP- 9 have not been assessed in the periodontal tissues of smokers. Therefore, the aim of this study is to estimate the concentrations of MMP-8 and -9 in the gingival crevicular fluid (GCF) of smokers and non-smokers with CP. Materials and Methods: Plaque, bleeding on probing, probing pocket depth, and attachment level were assessed in 60 subjects who were equally divided into three groups. Group A consisted of smokers with CP, Group B - non-smokers with CP and Group C - periodontally healthy subjects. The concentrations of MMP-8 and -9 were determined from GCF samples by using enzyme-linked immunosorbent assay. Results: A highly significant difference (P < 0.0001) was found in the MMP-9 concentration between the Groups A (27.56 ± 2.87 ng/ml) and B (17.16 ± 1.74 ng/ml) and between Groups A and C (14.13 ± 2.87 ng/ml). A significant difference (P < 0.002) was also found between the Groups B and C. A highly significant difference (P < 0.0001) in MMP-8 concentration was found between the A (68.96 ± 20.53 ng/ml) and C (7.05 ± 0.75 ng/ml) and also between Groups B (56.97 ± 12.70 ng/ml) and C. The difference in MMP-8 concentration between A and B was not statistically significant. Conclusion: Our findings of significantly elevated MMP-9 than MMP-8 from the diseased sites in smokers imply that MMP-9 is more significantly related to the increased periodontal destruction seen among smokers with CP. [ABSTRACT FROM AUTHOR]

Objective: To explore the effect of sequential treatment with glucocorticoid and tumor necrosis factor-alpha inhibitors in patients with Takayasu arteritis (TA). Materials and Methods: In five patients with TA, the effects of the sequential treatment with prednisone for 5-7 months and then with adalimumab (ADA) + methotrexate (MTX) or infliximab + MTX, or with ADA only, for 12 months on both clinical and laboratory findings were evaluated. Results: All treatments improved both symptoms and laboratory parameters without the development of side-effects. Conclusions: It was hypothesized that MMP-9 and neutrophil gelatinase-associated lipocalin could be markers of the response to the treatments. [ABSTRACT FROM AUTHOR]

AIMS: Matrix metalloproteinases (MMP) have been associated with neonatal lung morbidity and MMP dysregulation contributes to the pathology of chronic and acute lung disorders. Most of the previous studies were performed in the 1st weeks of life of the preterm newborns. There are no data on the serum levels of MMP-2, MMP-9 or tissue inhibitors of matrix metalloproteinases (TIMP-1) from preterm infants recovering from lung morbidities. We aimed to compare MMP-2, MMP-9 and TIMP-1 levels in preterm and term infants hospitalized with their first episode of wheezing. METHODS: We prospectively evaluated 18 preterm infants with a history of chronic lung disease, respiratory distress syndrome or oxygen therapy and 14 age- and sex-matched term infants who were admitted for a first episode of wheezing. We quantified total serum concentrations of MMP-2, MMP-9 and TIMP-1 to assess whether these serum markers levels were associated with the first episode of wheezing in infants with a history of oxygen therapy during the neonatal period. RESULTS: Upon hospitalization, MMP-2 and TIMP-1 levels were higher in preterm infants than in term infants. In contrast, there was no significant relationship between MMP-9 levels or the MMP-9/TIMP-1 ratio between preterm and term infants. The area under the receiver operating characteristic curve for MMP-2 was 0.70 (95% confidence interval [CI] 0.51-0.89). The area under the curve for TIMP-1 was 0.78 (95% CI 0.61-0.94). MMP-9, MMP-2 and TIMP-1 levels did not correlate with gestational age, gender or severity of wheezing. CONCLUSION: The negative proportion of MMP-9 to TIMP-1 that we detected in term infants was not present in preterm infants. The balance of MMP-9 to TIMP-1 may have been disrupted by lung damage in the premature infants. Overproduction of MMP-2 and TIMP-1 in the serum may be associated with the pathogenesis of wheezing in preterm infants. [ABSTRACT FROM AUTHOR]

Background: Although connective tissue growth factor (CTGF) has been demonstrated to contribute to the formation of atherosclerotic plaques, its divergent effects on atherosclerosis have been proposed. It is unclear if blocking the activity of CTGF may prevent the development of atherosclerosis. Methods: We established a rat carotid artery atherosclerotic model which recapitulates the early-stage atherosclerotic lesion and highly expresses CTGF. We blocked CTGF expression in atherosclerotic lesion by injecting a neutralizing anti-CTGF antibody and knocked-down CTGF expression in vascular smooth muscle cells (VSMCs) using a CTGF siRNA. Results: Blocking the activity of CTGF extensively prevented the increase in arterial stenosis rate, intima area, and tunica media, along with significant suppression of MMP-2, MMP-9, and phospho-Akt proteins in the areas of atherosclerotic lesions. CTGF siRNA suppressed the growth and migration of VSMCs in vitro. Conclusions: CTGF contributes significantly to the development of early-stage atherosclerosis. Blocking the activity of CTGF is capable of preventing the development of early-stage atherosclerosis through a mechanism involving the inactivation of Akt and suppression of MMP-2 and MMP-9. Our result suggests a novel strategy to the prevention of atherosclerosis. [ABSTRACT FROM AUTHOR]

Inflammatory damage plays a pivotal role in cerebral ischemia and may represent a target for treatment. Pigment epithelium-derived factor (PEDF) is proven to possess neuroprotective property. But there is little known about the intrinsic PEDF after cerebral ischemia. This study evaluated the time course expression of the intrinsic PEDF and its underlying regulation mechanisms after cerebral ischemia. Male Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion. Telmisartan (PPARγ agonist) and GW9662 (PPARγ antagonist) were systemically administered to explore the effect on PPARγ, PEDF, NF-κB and MMP-9 expression at 24 h after cerebral ischemia by western blot and qRT-PCR. The neurological deficits, brain water content and infarct volume were measured. Compared with normal group, the expressions of PEDF and PPARγ decreased, and the expression of NF-κB and MMP-9 increased at early stage after ischemia ( P < 0.05). Compared with the vehicle group, the decrease of PEDF and PPARγ was significantly up-regulated and the increase of NF-κB and MMP-9 was down-regulated by telmisartan at 24 h ( P < 0.05). The neurological deficits, brain water content and infarct volume were dramatically alleviated by telmisartan ( P < 0.05). Telmisartan's effects were reversed by GW9662 co-administration ( P < 0.05). The expression of intrinsic PEDF was down-regulated at the early stage of cerebral ischemia. The protective effects of intrinsic PEDF by activating PPARγ pathway may be one of the strategic targets for cerebral ischemic therapies. [ABSTRACT FROM AUTHOR]

Abstract: Matrix metalloproteinase-9 (MMP-9) is involved in tissue remodeling or neural plasticity in various clinical states (e.g. inflammation, neuropathic pain). We focused on the effect of MMP-9 on development of morphine tolerance after repeated morphine treatment. To develop morphine tolerance, mice were given morphine (10mg/kg; s.c.) once daily for 5days. The antinociceptive effect of morphine was measured by the tail flick method. Development of morphine tolerance was significantly inhibited by daily treatment of the non-specific MMP inhibitor GM6001 (5μg/mouse, i.c.v.). A MMP-9 inhibitor (5μg/mouse, i.c.v.) partially, yet significantly, inhibited the development of morphine tolerance. Intrathecal treatment of a MMP-9 inhibitor did not affect morphine tolerance. In MMP-9(−/−) mice, the development of morphine tolerance was partially, yet significantly, inhibited compared with wild-type mice. MMP-9 protein expression levels in the midbrain gradually increased 12h to 24h after morphine treatment on day 1, but were unchanged on days 3–5. In the spinal cord, MMP-9 protein expression levels were unchanged. In gelatin zymography analyses, MMP-9 activity in the midbrain gradually increased 12 to 24h after morphine treatment. Increment in MMP-9 activity in the midbrain was also observed on days 3–5. Our findings suggest that persistent MMP-9 activation observed after the transient increment in MMP-9 expression from the early phase of morphine treatment may contribute to the development of morphine tolerance. [Copyright &y& Elsevier]

Abstract: Cardiac fibroblasts play the key role in cardiac function and matrix metalloproteinases-9 (MMP-9) is a well known contributor to the development of myocardial remodeling. However, the direct regulation of MMP-9 on the function of cardiac fibroblasts and the underlying mechanism are far from elucidation. In the present research, recombinant protein encoding catalytic domain of MMP-9 (MMP-9 CD) was constructed and the function of neonatal cardiac fibroblasts was investigated by cell proliferation assay, migration assay, picrosirius red assay, multiplex cytokine assay and fibroblast phenotype detection. 200nM MMP-9 CD stimulated cardiac fibroblasts migration (169.4±22.5% versus 100±0%, p <0.01), increased collagen synthesis (1.5±0.2 fold, p <0.05), up-regulated the secretion of ICAM (574.0±40.1 versus 268.5±8.6pg/ml, p <0.01), TNF-α (192.6±11.0 versus 14.4±1.8pg/ml, p <0.001), IL-6 (1500.9±70.2 versus 323.4±40.6pg/ml, p <0.001) and sVCAM-1 (30.3±4.3 versus 7.0±0.1pg/ml, p <0.05) and down-regulated VEGF (436.5±148.9 versus 1034.3±28.1pg/ml, p <0.05) significantly with modest effects on proliferation. Accompanying with these regulations, transition of fibroblasts to myofibroblast was confirmed by immunofluorescent stain of α-smooth muscle actin (α-SMA) with MMP-9 CD treatment. Furthermore, salvianolic acid B (SalB) inhibited the effects of MMP-9 CD significantly. In conclusion, our results provide evidence for a direct influence of MMP-9 on cardiac fibroblast migration, collagen and cytokine secretion, which can be attenuated by SalB. [Copyright &y& Elsevier]

Purpose: To investigate the effects of pyrrolidine dithiocarbamate (PDTC), a nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) inhibitor, on the expression of matrix metalloproteinases (MMP) and MMP-mediated apoptosis in retinal ganglion cells (RGCs) following the transection of the optic nerve (ON) in rats. Materials and Methods: The ON of adult male Sprague-Dawley rats was transected. The expression of MMP-2, MMP-9, and NF-κB was measured by Western blot analysis and immunohistochemical analysis following transection. In situ zymography was also performed to localize gelatinolytic activity in the retinas. PDTC was injected intravitreally immediately following transection of the ON to evaluate the effect on the expression of NF-κB and MMP as well as its anti-apoptotic effect and neuroprotective effect on RGCs. Results: Significant up-regulation of MMP-9, and NF-κB was observed 7 days post-transection; however, this was not observed for MMP-2. PDTC at concentrations of 0.5 mM suppressed the up-regulation of MMP-9 and NF-κB, inhibiting gelatinolytic activity in the RGC layer. Meanwhile, far fewer apoptotic RGCs were detected and more surviving RGCs were preserved in PDTC-treated retinas 7 days post-transection compared to retinas in the control group. However, this kind of neuroprotective effect was not significant at 14 days post-transection. Conclusions: This study demonstrated that PDTC, mediated in part through the down-regulation of MMP-9, could contribute to delaying the death of RGCs following transection of the ON. [ABSTRACT FROM AUTHOR]

Genetic variations and the expression profile of matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) are involved in the invasion and metastasis of colorectal cancer. The gene profiles of TIMP2 and MMP were assayed from 333 colorectal cancer using polymerase chain reaction-restriction fragment length polymorphism. TIMP2-418*G/* G, TIMP2 303* G/* G and MMP9-1562*C/* C were more frequent in patients than in controls ( P = 0.020, P < 0.0001 and P < 0.044, respectively). Frequency of TIMP2-418* G/* G was higher in patients with metastasis than in those without metastasis, and that of TIMP2 303* G/* G was higher in patients with rectal cancer than in those with colon cancer ( P = 0.008 and P = 0.022, respectively). TIMP2-303* A/* A and MMP2-1575* G/* G were less frequent in patients than in controls ( P = 0.001 and P = 0.005, respectively). The TIMP2-418* G303* G haplotype was more frequent ( P < 0.0001) and MMP2-1575* G-735* C haplotype was less frequent in patients than in controls ( P = 0.005). Specific single-nucleotide polymorphism in TIMP2 and MMP appeared to be associated with tumorigenesis and biological behavior in colorectal cancer, which is expected be further verified in a larger cohort in the future. [ABSTRACT FROM AUTHOR]

Abstract: Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, has recently been shown to possess antitumor activity in various cancer cells. However, the effects of DHA in preventing the invasion of cancer cells have not been studied. In the present study, we investigated the inhibitory effects of DHA on tumor invasion and migration and the possible mechanisms involved using human fibrosarcoma HT-1080 cells. DHA reduced PMA-induced activation of MMP-9 and MMP-2 and further inhibited cell invasion and migration. DHA suppressed PMA-enhanced expression of MMP-9 protein, mRNA, and transcriptional activity through suppressing NF-κB and AP-1 activation without changing the level of tissue inhibitor of metalloproteinase (TIMP)-1. DHA also reduced PMA-enhanced MMP-2 expression by suppressing membrane-type 1 MMP (MT1-MMP), but did not alter TIMP-2 levels. DHA-inhibited PMA-induced NF-κB and c-Jun nuclear translocation, which are upstream of PMA-induced MMP-9 expression and invasion. Furthermore, DHA strongly repressed the PMA-induced phosphorylation of Raf/ERK and JNK, which are dependent on the PKCα pathway. In conclusion, we demonstrated that the anti-invasive effects of DHA may occur through inhibition of PKCα/Raf/ERK and JNK phosphorylation and reduction of NF-κB and AP-1 activation, leading to down-regulation of MMP-9 expression. The data presented show that DHA is an effective anti-metastatic agent that functions by down-regulating MMP-9 gene expression. [Copyright &y& Elsevier]

The purpose of this study was to explore the inhibiting role of MMP-9 gene silence in the invasive ability and growth of laryngeal squamous cell carcinoma (LSCC) by lentivirus mediated RNA interference. MMP-9-RNAi-lentivirus and the control lentivirus (GFP-lentivirus) were transfected into Hep-2 cells. Gelatin zymography showed the proteins expression of MMP-9 were knockdown in the MMP-9 siRNA transfected Hep-2 cells. The invasive activity and viability of MMP-9 siRNA treated Hep-2 cells were decreased than the control cells measured with modified Boyden chamber assay and MTT assay. In animal experiment, 20 nude mice bearing Hep-2 cell tumor were randomly separated into the experimental and the control groups. The former were intratumorally injected with MMP-9-RNAi-lentivirus, and the later were injected with equivalent dose of GFP-lentivirus. Results showed the average weight and volume of tumor in MMP-9-RNAi-lentivirus treated group were significantly lower than those in the control group (P < .01). The protein expressions of MMP-9 were downregulated in tumors of MMP-9-RNAi-lentivirus treatment. The PCNA index was obviously lower in the tumors of treated group than that in the control group (P < .01). These results suggest that MMP-9 gene silence by lentivirus mediated RNA interference can inhibit invasion and growth of LSCC. [ABSTRACT FROM AUTHOR]

Abstract: Angiotensin II (AngII) is widely recognized as a critical regulator of the development of atherosclerosis. Matrix metalloproteinases (MMPs) are thought to participate in plaque destabilization through degradation of the extracellular matrix. In the present study, we investigated the potential mechanism of AngII-induced MMP-9 expression in vascular smooth muscle cells (VSMC). AngII upregulated the expression of MMP-9 significantly in VSMC obtained from rat aorta. RNAi-mediated knockdown of p65 and losartan, an inhibitor of AngII receptors subtype-1 (AT1), could abolish AngII-induced MMP-9 expression. In addition, AngII induced the NF-κB binding activity via AT1 and AT2 receptors in VSMC, and AngII-induced activation of NF-κB is not associated with significant downregulation of IκB. In summary, this study demonstrates that AngII stimulates NF-κB nuclear translocation in VSMC via AT1 and AT2. AngII increases the expression of MMP-9 in VSMC, and AT1 and NF-κB pathways have an important role in this response. [Copyright &y& Elsevier]

Objective. The T cell co-stimulatory factors CD28 and CTLA-4 and their ligands CD80 and CD86 occur as receptors on T cells and antigen-presenting cells and also in soluble forms in the circulation. We determined the levels of soluble co-stimulatory molecules in patients with abdominal aortic aneurysm (AAA) and normal individuals. We further correlated these soluble co-stimulatory molecules to other clinical parameters of importance such as age of the patient, presence of hypertension, size of the aneurysm and levels of matrix metalloproteinases-9 and C-reactive protein. Design, setting, subjects. This case-control study was designed to quantify the circulating levels of soluble co-stimulatory molecules by an in-house enzyme linked immunosorbent assay. A total of 314 subjects participated in the study including 100 patients and 214 normal controls. The statistical analysis was performed by Mann–Whitney test and Spearman's correlation rank test. Results. Our results show increased plasma levels of sCD28, sCD86 ( P = 0.0001) and decreased plasma levels of sCTLA-4 ( P = 0.0018) in the patients compared with normal individuals. The levels of these factors were not related to the age of the patient, size of aneurysm or levels of C-reactive protein in plasma. There was, however, a significant inverse relationship between the concentrations of sCTLA-4 and sCD80 with matrix metalloproteinase-9. Conclusions. We suggest that soluble co-stimulatory molecules serve as biomarkers for the estimation of immune activation in AAA patients. [ABSTRACT FROM AUTHOR]

Glycosylation of proteins has profound consequences on the activities of macromolecules and their interactions with inhibitors/substrates. Matrix metalloproteinase-9 (MMP-9, also known as gelatinase B) is a member of the MMP family of zinc-dependent endopeptidases, with critical functions in both physiological and pathological processes. MMP-9, a glycosylated MMP, is implicated in inflammation, angiogenesis and tumor metastasis. We have determined by the use of mass spectrometry that of the three possible N-glycosylation sites in human MMP-9 only two are glycosylated. The N-glycosylation sites are at asparagines in positions 38 and 120, the first site within the propeptide domain of the zymogenic form (pro-MMP-9) of the enzyme and the second in the catalytic domain. The chemical nature of the sugar attachments to both these sites was determined by mass spectrometry. Both N-glycosylation sites have NeuAcα(1,2)-Galβ(1,4)-GlcNAcβ(1,2)-Manα(1,3)-[NeuAcα(1,2)-Galβ(1,4)-GlcNAcβ(1,2)-Manα(1,6)-]Manβ(1,4)-GlcNAcβ(1,4)-[Fucα(1,6)-]GlcNAcβ oligosaccharide chains. A computational model of glycosylated pro-MMP-9 was generated and it was studied by dynamics simulations [Copyright &y& Elsevier]

Objective To explore the potential role of transforming growth factor-β (TGF-β) and matrix metalloproteinases (MMPs) in its occurrence and development of arterial calcification. Methods Sixty male SD rats were randomly divided into the control group and experimental group, with 30 rats in each group. Rats in the experimental group were injected vitamin D3 with a dose of 500 000 U/(kg· d) subcutaneously for 3 consecutive days , which was in order to induce the arterial calcification in rat models. The same dose of 5% glucose without vitamin D3 was injected into the rats of two groups subcutaneously. Using Von Kossa staining to observe the degree of tissue calcification of the rats, and using real-time fluorescent quantitative PCR to determinate the expression of mRNA of TGF-β and MMPs in the two groups. Results The degree of calcification and the mRNA expression of TGF-β and MMPs in the experimental group were significantly higher than those of the control group (all P<0.05). Conclusion The TGF-β and MMPs may contribute to the formation of arterial calcification. [ABSTRACT FROM AUTHOR]