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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 pro-inflammatory 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 MMP-9-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., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Conservative Dentistry and Endodontics.)

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.

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., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Objective : This study was designed to see if neuregulin-1β (NRG-1β) plays a protective role in spinal cord ischemia and reperfusion injury (SCII). Design : Animal research. Setting : China. Participants : NA. Interventions : Forty-eight SD rats were randomly divided into control group ( n  = 16), SCII model group ( n  = 16) and NRG-1β-treated group ( n  = 16). In control group, the abdominal aorta was isolated but not clipped. The rats in NRG-1β-treated group were treated with 10μg/kg NRG-1β during developing SCII model. Outcome Measures : Neurological scores were evaluated. At 3, 6, 12 and 24 h after the reperfusion, rats were killed. Pathological changes of spinal cord were assessed with HE staining, and immunohistochemical staining of matrix metalloproteinases-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1). MMP-9 and TIMP-1 mRNA levels were assessed using real-time PCR. Results : NRG-1β reduced the damage of SCII in the rats. The expression of MMP-9 protein and mRNA in NRG-1β treatment group was significantly lower than the model group ( P  < 0.05) at 6 h, 12 h and 24 h after the perfusion. The expression of TIMP-1 protein and mRNA in the treatment group was significantly higher than the model group at 12 h and 24 h after the perfusion. Conclusion : NRG-1β reduced the reperfusion damage in rat model of SCII, in which process MMP-9 and TIMP-1 were probably involved.

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.

Chronic asthma is associated with progressive airway remodeling, which may contribute to declining lung function. An increase in matrix metalloproteinases-9 (MMP-9)/tissue inhibitor metalloproteinase-1 (TIMP-1) may indicate airway inflammation and bronchial injury. Bronchial biopsy specimens and alveolar macrophages (AMs) were obtained from patients with asthma under regular treatment with inhaled corticosteroids or combination therapy and normal subjects ( n = 10). Asthmatics included those with a slow forced expiratory volume in one second (FEV 1 ) decline (<30 mL/year, n = 13) and those with a fast FEV 1 decline (≥30 mL/year, n = 8) in 5-year follow-up. Immunostaining expression of MMP-9 and TIMP-1 was detected in airway tissues. MMP-9 and TIMP-1 was measured from AMs cultured for 24 h. After the 5-year treatment, the methacholine airway hyperresponsiveness of the slow FEV 1 decline group was decreased, but that of the fast FEV 1 decline group was increased (PC 20 , provocative concentration causing a 20% decrease in FEV 1 , 3.12 ± 1.10 to 1.14 ± 0.34 mg/dL, p < 0.05). AMs of asthma with a fast FEV 1 decline released a higher level of MMP-9 (8.52 ± 3.53 pg/mL, p < 0.05) than those of a slow FEV 1 decline (0.99 ± 0.20 pg/mL). The MMP-9/TIMP ratio in the fast FEV 1 decline group (0.089 ± 0.032) was higher than that of the slow FEV 1 decline group (0.007 ± 0.001, p < 0.01). The annual FEV 1 decline in 5 years was proportional to the level of MMP-9 (r = 57, p < 0.01) and MMP-9/TIMP-1 ratio (r = 0.58, p < 0.01). The airways of asthma with greater yearly decline in FEV 1 showed an increased thickness of submucosa and strong expression of MMP-9. An increase in MMP-9 and MMP-9/TIMP-1 in airways or AMs could be indicators of chronic airway inflammation and contribute to a greater decline in lung function of patients with chronic asthma.

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.

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., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

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.

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.

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-9-1562T 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., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

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.

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.

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., (Copyright © 2015 Elsevier B.V. All rights reserved.)

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., (Copyright © 2015. Published by Elsevier B.V.)

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.

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.

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., (Copyright © 2014 Elsevier B.V. All rights reserved.)

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.

Acute lung injury (ALI) was one of the major complications after cardiopulmonary bypass (CPB). Matrix metalloproteinases (MMPs) play an important role in ALI following CPB. In this study, we investigated the effects of doxycycline (DOX), a potent MMP inhibitor, on MMP-9 and ALI in the rat model of CPB. 48 adult male Sprague-Dawley rats were randomized into four groups: group I (Control group, underwent cannulation + heparinization only); group II (CPB group, underwent 60-minutes of normothermic CPB); group III (Low-dose treatment group, underwent 60-minutes of normothermic CPB with DOX gavage 30 mg/kg ×1 week ahead of CPB); and group IV (High-dose treatment group, underwent 60-minutes of normothermic CPB with DOX gavage 60 mg/kg ×1 week ahead of CPB). The effects of doxycycline on ALI were determined by measuring the lung Wet/Dry ratio, the inflammation of bronchoalveolar lavage fluid (BALF) and the ultrastructural changes of the lungs. The role of doxycycline on MMP-9 was assessed by the plasma concentration, the activity and the expression in lung tissue. Our results demonstrated that the lung Wet/Dry weight ratio and the inflammatory mediators (TNF-α, IL-1β) in BALF were decreased significantly with doxycycline treatment. The lung damages were attenuated by doxycycline. The levels of plasma concentration, the activity and the expression of MMP-9 in lung tissue were suppressed with doxycycline and the effects were dose dependent. Doxycycline could suppress the expression of MMP-9 and cytokines, and improve the ALI following CPB.

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.

Introduction: A consortium of metabolic risk factors accelerate the onset of diabetes, heart disease, stroke, and certain cancers. Proteolytic enzymes like matrix metalloproteinases (MMP) are regulated by a group of endogenous proteins called tissue inhibitors of metalloproteinases (TIMP). These TIMPs binds to active and alternate sites of activated MMPs and facilitate regulation. Impaired expression of MMPs may have a significant contribution in the pathogenesis of many tissues-destructive processes like tumor progression and cardiovascular and metabolic disorders., Materials and Methods: This case control study lays stress on the possible role of impaired levels of circulating MMP-2 and 9 in metabolic syndrome (MetS). The age, sex-matched 388 subjects with 190 newly diagnosed patients, and 198 healthy controls were recruited. To screen the patients with MetS, biochemical analysis of patients for impaired glucose level, hypertension, body mass index (BMI), and lipid profile was performed. The circulating level of MMP-2 and -9 in serum was analyzed by enzyme-linked immunosorbent assay (ELISA) in all patients and control., Results: All metabolic risk factors were statistically significant (P < 0.01) in patients against control group. The serum MMP-2 and -9 level was significantly higher (P < 0.001) in patients having MetS as compared with control group., Conclusions: Similar trend was observed in gender wise analysis of serum MMP level. Higher MMP level alteration observed in male patients as compared with female patients.

Although there is a growing literature describing the role of macrophages in breast cancer, the role of macrophages in inflammatory breast cancer (IBC) is unclear. The aim of present study was to isolate and characterize tumor associated macrophages of IBC and non-IBC patients and define their role in IBC. Tumor infiltrating monocytes/macrophages (CD14+ and CD68+) were measured by immunohistochemistry using specific monoclonal antibodies. Blood drained from axillary vein tributaries was collected during breast cancer surgery and the percentage of CD14+ in the total isolated leukocytes was assessed by flow cytometric analysis. CD14+ cells were separated from total leukocytes by immuno-magnetic beads technique and were cultured overnight. Media conditioned by CD14+ were collected and subjected to cytokine profiling using cytokine antibody array. Wound healing and invasion assays were used to test whether cytokines highly secreted by tumor drained macrophages induce motility and invasion of breast cancer cells. We found that macrophages highly infiltrate into carcinoma tissues of IBC patients. In addition blood collected from axillary tributaries of IBC patients is highly enriched with CD14+ cells as compared to blood collected from non-IBC patients. Cytokine profiling of CD14+ cells isolated from IBC patients revealed a significant increase in secretion of tumor necrosis factor-α; monocyte chemoattractant protein-1/CC-chemokine ligand 2; interleukin-8 and interleukin-10 as compared to CD14+ cells isolated from non-IBC patients. Tumor necrosis factor-α, interleukin-8 and interleukin-10 significantly increased motility and invasion of IBC cells in vitro. In conclusion, macrophages isolated from the tumor microenvironment of IBC patients secrete chemotactic cytokines that may augment dissemination and metastasis of IBC carcinoma cells., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

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.

Objective: To investigate the effect of promoter methylation of cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) gene and matrix metalloproteinases (MMPs) on the risk of non-alcoholic fatty liver disease (NAFLD)., Materials and Methods: CTLA-4 and MMP-9 promoter methylation were investigated using a methylation-specific polymerase chain reaction (MS-PCR) in blood samples taken from 80 NAFLD individuals and 95 healthy controls. The expression levels of CTLA-4 and MMP-9 were also assessed in 10 blood and 9 liver tissues mRNA samples from NAFLD patients. These cases were compared to the blood (n = 10) samples of healthy controls with real-time quantitative reverse transcriptase PCR., Results: No significant relationship was found for methylation of CTLA-4 and MMP-9 between cases and controls. The relative expression of CTLA-4 and MMP-9 mRNA in NAFLD was not significantly different compared to healthy control samples., Conclusion: For the first time, our outcomes indicate that the methylation status of CTLA-4 and MMP-9 genes has no significant function on the process of NAFLD.

Objective: Matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9 have been known to play an important role in secondary inflammatory reaction after spinal cord injury (SCI). The aim of this study was to investigate the expression and activity of MMP-2 and MMP-9 and to determine their relationship with disruption of endothelial blood-barrier after photochemically induced SCI in rats., Methods: Female Sprague-Dawley rats, weighing between 250 and 300 g (aged 8 weeks) received focal spinal cord ischemia by photothrombosis using Rose Bengal. Expressions and activities of MMP-2 and MMP-9 were assessed by Western blot and gelatin zymography at various times from 6 h to 7 days. Endothelial blood-barrier integrity was assessed indirectly using spinal cord water content., Results: Zymography and Western blot analysis demonstrated rapid up-regulation of MMP-9 protein levels in spinal cord after ischemic onset. Expressions and activities of MMP-9 showed a significant increased at 6 h after the photothrombotic ischemic event, and reached a maximum level at 24 h after the insult. By contrast, activated MMP-2 was not detected at any time point in either the experimental or the control groups. When compared with the control group, a significant increase in spinal cord water content was detected in rats at 24 h after photothrombotic SCI., Conclusion: Early up-regulation of MMP-9 might be correlated with increased water content in the spinal cord at 24 h after SCI in rats. Results of this study suggest that MMP-9 is the key factor involved in disruption of the endothelial blood-barrier of the spinal cord and subsequent secondary damage after photothrombotic SCI in rats.