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Sample records for matrix metalloproteinase-9 persists

  1. The serum matrix metalloproteinase-9 level is an independent predictor of recurrence after ablation of persistent atrial fibrillation

    PubMed Central

    Wu, Gang; Wang, Shun; Cheng, Mian; Peng, Bin; Liang, Jingjun; Huang, He; Jiang, Xuejun; Zhang, Lizhi; Yang, Bo; Cha, Yongmei; Jiang, Hong; Huang, Congxin

    2016-01-01

    OBJECTIVES: This study investigated whether the serum matrix metalloproteinase-9 level is an independent predictor of recurrence after catheter ablation for persistent atrial fibrillation. METHODS: Fifty-eight consecutive patients with persistent atrial fibrillation were enrolled and underwent catheter ablation. The serum matrix metalloproteinase-9 level was detected before ablation and its relationship with recurrent arrhythmia was analyzed at the end of the follow-up. RESULTS: After a mean follow-up of 12.1±7.2 months, 21 (36.2%) patients had a recurrence of their arrhythmia after catheter ablation. At baseline, the matrix metalloproteinase-9 level was higher in the patients with recurrence than in the non-recurrent group (305.77±88.90 vs 234.41±93.36 ng/ml, respectively, p=0.006). A multivariate analysis showed that the matrix metalloproteinase-9 level was an independent predictor of arrhythmia recurrence, as was a history of atrial fibrillation and the diameter of the left atrium. CONCLUSION: The serum matrix metalloproteinase-9 level is an independent predictor of recurrent arrhythmia after catheter ablation in patients with persistent atrial fibrillation. PMID:27276393

  2. Matrix Metalloproteinase-9 Regulates Neuronal Circuit Development and Excitability.

    PubMed

    Murase, Sachiko; Lantz, Crystal L; Kim, Eunyoung; Gupta, Nitin; Higgins, Richard; Stopfer, Mark; Hoffman, Dax A; Quinlan, Elizabeth M

    2016-07-01

    In early postnatal development, naturally occurring cell death, dendritic outgrowth, and synaptogenesis sculpt neuronal ensembles into functional neuronal circuits. Here, we demonstrate that deletion of the extracellular proteinase matrix metalloproteinase-9 (MMP-9) affects each of these processes, resulting in maladapted neuronal circuitry. MMP-9 deletion increases the number of CA1 pyramidal neurons but decreases dendritic length and complexity. Parallel changes in neuronal morphology are observed in primary visual cortex and persist into adulthood. Individual CA1 neurons in MMP-9(-/-) mice have enhanced input resistance and a significant increase in the frequency, but not amplitude, of miniature excitatory postsynaptic currents (mEPSCs). Additionally, deletion of MMP-9 significantly increases spontaneous neuronal activity in awake MMP-9(-/-) mice and enhances response to acute challenge by the excitotoxin kainate. Our data document a novel role for MMP-9-dependent proteolysis: the regulation of several aspects of circuit maturation to constrain excitability throughout life. PMID:26093382

  3. Correlation between matrix metalloproteinase-9 and endometriosis.

    PubMed

    Liu, Haiping; Wang, Jianye; Wang, Haiyu; Tang, Ning; Li, Yunfei; Zhang, Yan; Hao, Tianyu

    2015-01-01

    Endometrial implantation is the major cause of endometriosis (EMS). Matrix metalloproteinase (MMPs) can degrade multiple extracellular matrix and has been postulated to be related with EMC occurrence. This study thus investigated serum and ascites levels of MMP-9 in EMS patients, in an attempt to discuss the correlation between MMP-9 and EMS. A total of 100 EMS patients, including eutopic endometrium and ectopic endometrium, were recruited in this study along with hysteromyoma patients as the control group. Peripheral blood and ascites samples were collected and tested for MMP-9 levels using gelatin zymogram and enzyme-linked immunosorbent assay (ELISA). In EMS patients, MMP-9 levels in serum and ascites were 6.24 ± 0.53 mM and 38.57 ± 4.93 mM, respectively. Both of them were significantly higher than those in control group (P<0.05). Eutopic endometrium group had higher MMP-9 levels compared to those in ectopic endometrium ones (P<0.05). With advancement of disease stage, EMS patients had progressively elevated MMP-9 levels (P<0.05). Patients at proliferative stage had higher MMP-9 secretion (P<0.05). In summary, site of endometrium, clinical stage and proliferative cycle were independent risk factors for EMS. The elevation of serum and ascites MMP-9 existed in EMS patients, of which those had ectopic endometrium, advanced stage and at proliferative stage had higher MMP-9 expression. PMID:26722547

  4. Correlation between matrix metalloproteinase-9 and endometriosis

    PubMed Central

    Liu, Haiping; Wang, Jianye; Wang, Haiyu; Tang, Ning; Li, Yunfei; Zhang, Yan; Hao, Tianyu

    2015-01-01

    Endometrial implantation is the major cause of endometriosis (EMS). Matrix metalloproteinase (MMPs) can degrade multiple extracellular matrix and has been postulated to be related with EMC occurrence. This study thus investigated serum and ascites levels of MMP-9 in EMS patients, in an attempt to discuss the correlation between MMP-9 and EMS. A total of 100 EMS patients, including eutopic endometrium and ectopic endometrium, were recruited in this study along with hysteromyoma patients as the control group. Peripheral blood and ascites samples were collected and tested for MMP-9 levels using gelatin zymogram and enzyme-linked immunosorbent assay (ELISA). In EMS patients, MMP-9 levels in serum and ascites were 6.24±0.53 mM and 38.57±4.93 mM, respectively. Both of them were significantly higher than those in control group (P<0.05). Eutopic endometrium group had higher MMP-9 levels compared to those in ectopic endometrium ones (P<0.05). With advancement of disease stage, EMS patients had progressively elevated MMP-9 levels (P<0.05). Patients at proliferative stage had higher MMP-9 secretion (P<0.05). In summary, site of endometrium, clinical stage and proliferative cycle were independent risk factors for EMS. The elevation of serum and ascites MMP-9 existed in EMS patients, of which those had ectopic endometrium, advanced stage and at proliferative stage had higher MMP-9 expression. PMID:26722547

  5. Matrix Metalloproteinase-9 Production by Immortalized Human Chondrocyte Lines

    PubMed Central

    Malemud, Charles J.; Meszaros, Evan C.; Wylie, Meredith A.; Dahoud, Wissam; Skomorovska-Prokvolit, Yelenna; Mesiano, Sam

    2016-01-01

    We reported at the Keynote Forum of Immunology Summit-2015 that recombinant human (rh) TNF-α or rhIL-6 stimulated production of matrix metalloproteinase-9 (MMP-9) in the T/C28a2 and C-28/I2 human immortalized chondrocyte cell lines. Furthermore, we reported that tocilizumab (TCZ), a fully humanized monoclonal antibody which neutralizes IL-6-mediated signaling, inhibited the rhIL-6-mediated increase in the production of MMP-9. IL-6 is also a known activator of the JAK/STAT signaling pathway. In that regard, we evaluated the effect of rhIL-6 on total and phosphorylated Signal Transducer and Activator of Transcription by these chondrocyte lines which showed that whereas STAT3 was constitutively phosphorylated in T/C28a2 chondrocytes, rhIL-6 activated STAT3 in C-28/I2 chondrocytes. The finding that rhIL-6 increased the production of MMP-9 by human immortalized chondrocyte cell lines may have important implications with respect to the destruction of articular cartilage in rheumatoid arthritis and osteoarthritis. Thus, the markedly elevated level of IL-6 in rheumatoid arthritis and osteoarthritis sera and synovial fluid would be expected to generate significant MMP-9 to cause the degradation of articular cartilage extracellular matrix proteins. The finding that TCZ suppressed rhIL-6-mediated MMP-9 production suggests that TCZ, currently employed in the medical therapy of rheumatoid arthritis, could be considered as a drug for osteoarthritis.

  6. Matrix metalloproteinase 9 modulates collagen matrices and wound repair

    PubMed Central

    LeBert, Danny C.; Squirrell, Jayne M.; Rindy, Julie; Broadbridge, Elizabeth; Lui, Yuming; Zakrzewska, Anna; Eliceiri, Kevin W.; Meijer, Annemarie H.; Huttenlocher, Anna

    2015-01-01

    Acute and chronic injuries are characterized by leukocyte infiltration into tissues. Although matrix metalloproteinase 9 (Mmp9) has been implicated in both conditions, its role in wound repair remains unclear. We previously reported a zebrafish chronic inflammation mutant caused by an insertion in the hepatocyte growth factor activator inhibitor gene 1 (hai1; also known as spint1) that is characterized by epithelial extrusions and neutrophil infiltration into the fin. Here, we performed a microarray analysis and found increased inflammatory gene expression in the mutant larvae, including a marked increase in mmp9 expression. Depletion of mmp9 partially rescued the chronic inflammation and epithelial phenotypes, in addition to restoring collagen fiber organization, as detected by second-harmonic generation imaging. Additionally, we found that acute wounding induces epithelial cell mmp9 expression and is associated with a thickening of collagen fibers. Interestingly, depletion of mmp9 impaired this collagen fiber reorganization. Moreover, mmp9 depletion impaired tissue regeneration after tail transection, implicating Mmp9 in acute wound repair. Thus, Mmp9 regulates both acute and chronic tissue damage and plays an essential role in collagen reorganization during wound repair. PMID:26015541

  7. Matrix Metalloproteinase 9 Exerts Antiviral Activity against Respiratory Syncytial Virus

    PubMed Central

    Dabo, Abdoulaye J.; Cummins, Neville; Eden, Edward; Geraghty, Patrick

    2015-01-01

    Increased lung levels of matrix metalloproteinase 9 (MMP9) are frequently observed during respiratory syncytial virus (RSV) infection and elevated MMP9 concentrations are associated with severe disease. However little is known of the functional role of MMP9 during lung infection with RSV. To determine whether MMP9 exerted direct antiviral potential, active MMP9 was incubated with RSV, which showed that MMP9 directly prevented RSV infectivity to airway epithelial cells. Using knockout mice the effect of the loss of Mmp9 expression was examined during RSV infection to demonstrate MMP9’s role in viral clearance and disease progression. Seven days following RSV infection, Mmp9-/- mice displayed substantial weight loss, increased RSV-induced airway hyperresponsiveness (AHR) and reduced clearance of RSV from the lungs compared to wild type mice. Although total bronchoalveolar lavage fluid (BALF) cell counts were similar in both groups, neutrophil recruitment to the lungs during RSV infection was significantly reduced in Mmp9-/- mice. Reduced neutrophil recruitment coincided with diminished RANTES, IL-1β, SCF, G-CSF expression and p38 phosphorylation. Induction of p38 signaling was required for RANTES and G-CSF expression during RSV infection in airway epithelial cells. Therefore, MMP9 in RSV lung infection significantly enhances neutrophil recruitment, cytokine production and viral clearance while reducing AHR. PMID:26284919

  8. Plasma matrix metalloproteinase-9 response to downhill running in humans.

    PubMed

    Welsh, M C; Allen, D L; Byrnes, W C

    2014-05-01

    Matrix metalloproteinase-9 is a proteolytic enzyme capable of degrading proteins of the muscle extracellular matrix. Systemic levels of MMP-9 or its inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), have the potential to serve as blood markers of exercise-induced muscle damage. The purpose of this study was to determine if an eccentrically-dominated task, downhill running (DHR), produces changes in plasma MMP-9 or TIMP-1 and examine the relationship between MMP-9/TIMP-1 levels and indirect indicators of muscle damage. Subjects were sedentary (SED, n=12) or had a history of concentrically-biased training (CON, n=9). MMP-9 and TIMP-1 were measured before (Pre-Ex), immediately after (Post-Ex), and 1-, 2-, 4-, and 7-days post-DHR (-10°), and compared to discomfort ratings, creatine kinase activity and strength loss. At 1-day Post-Ex, discomfort increased (5.6 ± 7.8 to 45.5 ± 19.9 mm; 0-100 mm scale), strength decreased (-6.9 ± 1.6%) and CK increased (162.9 ± 177.2%). MMP-9 was modestly but significantly increased at Post-Ex in both CONC and SED (32.7 ± 33.6%) and at 4-days in SED (66.9 ± 88.1%), Individual responses were variable, however. There were no correlations between MMPs and discomfort ratings, plasma CK or strength. While plasma MMP-9 changes may be detectable in the systemic circulation after DHR, they are small and do not correspond to other markers of damage. PMID:24048912

  9. Rhubarb Antagonizes Matrix Metalloproteinase-9-induced Vascular Endothelial Permeability

    PubMed Central

    Cui, Yun-Liang; Zhang, Sheng; Tian, Zhao-Tao; Lin, Zhao-Fen; Chen, De-Chang

    2016-01-01

    Background: Intact endothelial structure and function are critical for maintaining microcirculatory homeostasis. Dysfunction of the latter is an underlying cause of various organ pathologies. In a previous study, we showed that rhubarb, a traditional Chinese medicine, protected intestinal mucosal microvascular endothelial cells in rats with metastasizing septicemia. In this study, we investigated the effects and mechanisms of rhubarb on matrix metalloproteinase-9 (MMP9)-induced vascular endothelial (VE) permeability. Methods: Rhubarb monomers were extracted and purified by a series of chromatography approaches. The identity of these monomers was analyzed by hydrogen-1 nuclear magnetic resonance (NMR), carbon-13 NMR, and distortionless enhancement by polarization transfer magnetic resonance spectroscopy. We established a human umbilical vein endothelial cell (HUVEC) monolayer on a Transwell insert. We measured the HUVEC permeability, proliferation, and the secretion of VE-cadherin into culture medium using fluorescein isothiocyanate-dextran assay, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay, and enzyme-linked immunosorbent assay, respectively, in response to treatment with MMP9 and/or rhubarb monomers. Results: A total of 21 rhubarb monomers were extracted and identified. MMP9 significantly increased the permeability of the HUVEC monolayer, which was significantly reduced by five individual rhubarb monomer (emodin, 3,8-dihydroxy-1-methyl-anthraquinone-2-carboxylic acid, 1-O-caffeoyl-2-(4-hydroxyl-O-cinnamoyl)-β-D-glucose, daucosterol linoleate, and rhein) or a combination of all five monomers (1 μmol/L for each monomer). Mechanistically, the five-monomer mixture at 1 μmol/L promoted HUVEC proliferation. In addition, MMP9 stimulated the secretion of VE-cadherin into the culture medium, which was significantly inhibited by the five-monomer mixture. Conclusions: The rhubarb mixture of emodin, 3,8-dihydroxy-1-methyl-anthraquinone-2

  10. Matrix metalloproteinase 9 level as an indicator for restenosis following cervical and intracranial angioplasty and stenting

    PubMed Central

    Liu, Jun-peng; Wang, Yin-zhou; Li, Yong-kun; Cheng, Qiong; Zheng, Zheng

    2015-01-01

    Cervical and intracranial angioplasty and stenting is an effective and safe method of reducing the risk of ischemic stroke, but it may be affected by in-stent restenosis. The present study investigated serum level of matrix metalloproteinase 9 as a predictor of restenosis after 40 patients underwent cervical and/or intracranial angioplasty and stenting. Results showed that restenosis occurred in 30% (3/10) of patients when the serum level of matrix metalloproteinase 9 at 3 days after surgery was 2.5 times higher than preoperative level. No restenosis occurred when the serum level of matrix metalloproteinase 9 at 3 days after surgery was not 2.5 times higher than preoperative level. Restenosis occurred in 12% (2/17) of patients when the serum level of matrix metalloproteinase 9 was higher than preoperative level for more than 30 days after surgery, but only occurred in 4% (1/23) of patients when the serum level of matrix metalloproteinase 9 was higher than preoperative level for less than 30 days after surgery. However, the differences observed were not statistically significant (P > 0.05). Experimental findings indicate that when the serum level of matrix metalloproteinase 9 is 2.5 times higher than preoperative level at 3 days after cervical and intracranial angioplasty and stenting, it may serve as a predictor of in-stent restenosis. PMID:26170826

  11. Genomic Organization of channel catfish, Ictalurus punctatus, matrix metalloproteinase-9-gene

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the course of studying pathogenesis of enteric septicemia of catfish, we noted that channel catfish matrix metalloproteinase-9 (MMP-9) gene was up-regulated after Edwardsiella ictaluri infection. In this study, we cloned and sequenced MMP-9 genomic DNA by using a Unversal GenomeWalker kit. The co...

  12. CLONING AND SEQUENCING OF CHANNEL CATFISH (ICTALURUS PUNCTATUS) MATRIX METALLOPROTEINASE-9

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the course of studying pathogenesis of enteric septicemia of catfish, we noted that channel catfish matrix metalloproteinase-9 (MMP-9) gene was up-regulated after Edwardsiella ictaluri infection. In this study, we cloned and sequenced using the RACE. The complete sequence of the CC MMP-9 cDNA g...

  13. Molecular Cloning, Expression and Genome Organization of Channel Catfish (Ictalurus punctatus) Matrix Metalloproteinase-9

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the course of studying pathogenesis of enteric septicemia of catfish, we noted that channel catfish matrix metalloproteinase-9 (MMP-9) gene was up-regulated after Edwardsiella ictaluri infection. In this study, we cloned, sequenced using the RACE (rapid amplification of cDNA ends) method and cha...

  14. Matrix Metalloproteinase-9 regulates neuronal circuit development and excitability

    PubMed Central

    Murase, Sachiko; Lantz, Crystal; Kim, Eunyoung; Gupta, Nitin; Higgins, Richard; Stopfer, Mark; Hoffman, Dax A.; Quinlan, Elizabeth M.

    2015-01-01

    In early postnatal development, naturally occurring cell death, dendritic outgrowth and synaptogenesis sculpt neuronal ensembles into functional neuronal circuits. Here we demonstrate that deletion of the extracellular proteinase MMP-9 affects each of these processes, resulting in maladapted neuronal circuitry. MMP-9 deletion increases the number of CA1 pyramidal neurons, but decreases dendritic length and complexity while dendritic spine density is unchanged. Parallel changes in neuronal morphology are observed in primary visual cortex, and persist into adulthood. Individual CA1 neurons in MMP-9−/− mice have enhanced input resistance and a significant increase in the frequency, but not amplitude, of miniature excitatory postsynaptic currents (mEPSCs). Additionally, deletion of MMP-9 significant increases spontaneous neuronal activity in awake MMP-9−/− mice and enhances response to acute challenge by the excitotoxin kainate. Thus MMP-9-dependent proteolysis regulates several aspects of circuit maturation to constrain excitability throughout life. PMID:26093382

  15. Environmental arsenic exposure and serum matrix metalloproteinase-9

    PubMed Central

    Burgess, Jefferey L.; Kurzius-Spencer, Margaret; O’Rourke, Mary Kay; Littau, Sally R.; Roberge, Jason; Meza-Montenegro, Maria Mercedes; Gutiérrez-Millán, Luis Enrique; Harris, Robin B.

    2014-01-01

    The objective of this study was to evaluate the relationship between environmental arsenic exposure and serum matrix metalloproteinase (MMP)-9, a biomarker associated with cardiovascular disease and cancer. In a cross-sectional study of residents of Arizona, USA (n=215) and Sonora, Mexico (n=163), drinking water was assayed for total arsenic, and daily drinking water arsenic intake estimated. Urine was speciated for arsenic and concentrations were adjusted for specific gravity. Serum was analyzed for MMP-9 using ELISA. Mixed model linear regression was used to assess the relation among drinking water arsenic concentration, drinking water arsenic intake, urinary arsenic sum of species (the sum of arsenite, arsenate, monomethylarsonic acid and dimethylarsinic acid), and MMP-9, controlling for autocorrelation within households. Drinking water arsenic concentration and intake were positively associated with MMP-9, both in crude analysis and after adjustment for gender, country/ethnicity, age, body mass index, current smoking and diabetes. Urinary arsenic sum of species was positively associated with MMP-9 in multivariable analysis only. Using Akaike’s Information Criterion, arsenic concentration in drinking water provided a better fitting model of MMP-9, than either urinary arsenic or drinking water arsenic intake. In conclusion, arsenic exposure was positively associated with MMP-9 using all three exposure metrics evaluated. PMID:23232971

  16. Huoxue Rongluo Tablet reduces matrix metalloproteinase-9 expression in infarcted brain tissue

    PubMed Central

    Zhou, Desheng; Li, Mei; Hu, Hua; Chen, Yao; Yang, Yang; Zhong, Jie; Liu, Lijuan

    2013-01-01

    Huoxue Rongluo Tablet was made of tall gastrodis tuber, dahurian angelica root, honeysuckle stem, grassleaf sweetflag rhizome, common flowering quince fruit, figwort root, red peony root and peach seed at a ratio of 3:2:6:2:3:3:3:3. Huoxue Rongluo Tablet is a well-established and common pre-scription for the treatment of cerebral infarction. In this study, a rat model of cerebral ischemia was established and the animals were intragastrically administered Huoxue Rongluo Tablet. This treat-ment reduced infarct volume, decreased matrix metalloproteinase-9 expression, and improved neurological function. Moreover, the effects of Huoxue Rongluo Tablet were better than those of buflomedil pyridoxal phosphate. These results indicate that Huoxue Rongluo Tablet is effective in treating cerebral infarction by regulating matrix metalloproteinase-9 protein expression. PMID:25206642

  17. Huoxue Rongluo Tablet reduces matrix metalloproteinase-9 expression in infarcted brain tissue.

    PubMed

    Zhou, Desheng; Li, Mei; Hu, Hua; Chen, Yao; Yang, Yang; Zhong, Jie; Liu, Lijuan

    2013-12-01

    Huoxue Rongluo Tablet was made of tall gastrodis tuber, dahurian angelica root, honeysuckle stem, grassleaf sweetflag rhizome, common flowering quince fruit, figwort root, red peony root and peach seed at a ratio of 3:2:6:2:3:3:3:3. Huoxue Rongluo Tablet is a well-established and common pre-scription for the treatment of cerebral infarction. In this study, a rat model of cerebral ischemia was established and the animals were intragastrically administered Huoxue Rongluo Tablet. This treat-ment reduced infarct volume, decreased matrix metalloproteinase-9 expression, and improved neurological function. Moreover, the effects of Huoxue Rongluo Tablet were better than those of buflomedil pyridoxal phosphate. These results indicate that Huoxue Rongluo Tablet is effective in treating cerebral infarction by regulating matrix metalloproteinase-9 protein expression. PMID:25206642

  18. Matrix Metalloproteinase-9 as a Novel Player in Synaptic Plasticity and Schizophrenia

    PubMed Central

    Lepeta, Katarzyna; Kaczmarek, Leszek

    2015-01-01

    Recent findings implicate alterations in glutamate signaling, leading to aberrant synaptic plasticity, in schizophrenia. Matrix metalloproteinase-9 (MMP-9) has been shown to regulate glutamate receptors, be regulated by glutamate at excitatory synapses, and modulate physiological and morphological synaptic plasticity. By means of functional gene polymorphism, gene responsiveness to antipsychotics and blood plasma levels MMP-9 has recently been implicated in schizophrenia. This commentary critically reviews these findings based on the hypothesis that MMP-9 contributes to pathological synaptic plasticity in schizophrenia. PMID:25837304

  19. The Matrix Metalloproteinase 9 Point-of-Care Test in Dry Eye.

    PubMed

    Lanza, Nicole L; Valenzuela, Felipe; Perez, Victor L; Galor, Anat

    2016-04-01

    Dry eye is a common, multifactorial disease currently diagnosed by a combination of symptoms and signs. However, the subjective symptoms of dry eye poorly correlate to the current gold standard for diagnostic tests, reflecting the need to develop better objective tests for the diagnosis of dry eye. This review considers the role of ocular surface matrix metalloproteinase 9 (MMP-9) in dry eye and the implications of a novel point-of-care test that measures MMP-9 levels, InflammaDry (RPS, Sarasota, FL) on choosing appropriate therapeutic treatments. PMID:26850527

  20. Regulation of matrix metalloproteinase-9 expression between gingival fibroblast cells from old and young rats

    SciTech Connect

    Kim, Su-Jung; Chung, Yong-Koo; Chung, Tae-Wook; Kim, Jeong-Ran; Moon, Sung-Kwon; Kim, Cheorl-Ho Park, Young-Guk

    2009-01-09

    Gingival fibroblast cells (rGF) from aged rats have an age-related decline in proliferative capacity compared with young rats. We investigated G1 phase cell cycle regulation and MMP-9 expression in both young and aged rGF. G1 cell cycle protein levels and activity were significantly reduced in response to interleukin-1{beta} (IL-1{beta}) stimulation with increasing in vitro age. Tumor necrosis factor-{alpha} (TNF-{alpha})-induced matrix metalloproteinase-9 (MMP-9) expression was also decreased in aged rGF in comparison with young rGF. Mutational analysis and gel shift assays demonstrated that the lower MMP-9 expression in aged rGF is associated with lower activities of transcription factors NF-{kappa}B and AP-1. These results suggest that cell cycle dysregulation and down-regulation of MMP-9 expression in rGF may play a role in gingival remodeling during in vitro aging.

  1. Complete structure, genomic organization, and expression of channel catfish (Ictalurus punctatus, Rafinesque 1818) matrix metalloproteinase-9 gene

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the course of studying pathogenesis of enteric septicemia of catfish, we noted that the channel catfish (CC) matrix metalloproteinase-9 (MMP-9) expressed sequence tag (EST) was up-regulated after early Edwardsiella ictaluri infection. In this study, the CC MMP-9 gene was cloned, sequenced and ch...

  2. Therapeutic sesamol attenuates monocrotaline-induced sinusoidal obstruction syndrome in rats by inhibiting matrix metalloproteinase-9.

    PubMed

    Periasamy, Srinivasan; Hsu, Dur-Zong; Chen, Shin-Yi; Yang, Shan-Shan; Chandrasekaran, Victor Raj Mohan; Liu, Ming-Yie

    2011-11-01

    We investigated the therapeutic effect of sesamol against monocrotaline-induced sinusoidal obstruction syndrome (SOS) in rats. Male Sprague-Dawley rats were gavaged with a single dose of monocrotaline (90 mg/kg) to induce SOS. Sesamol (5, 10, 20, and 40 mg/kg) was subcutaneously injected 24 h after monocrotaline treatment. Control rats were given saline only. Aspartate transaminase, alanine transaminase, mast cells, CD 68(+) Kupffer cells, neutrophils, myeloperoxidase, matrix metalloproteinase-9 (MMP-9), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), laminin, and collagen were assessed 48 h after monocrotaline treatment. All tested parameters, except for TIMP-1, laminin, and collagen, were significantly higher in monocrotaline-treated rats than in control rats, and, except for TIMP-1, laminin, and collagen, significantly lower in sesamol-treated rats than in monocrotaline-treated rats. In addition, liver pathology revealed that sesamol offered significant protection against SOS. We conclude that a single dose of sesamol therapeutically attenuated SOS by decreasing the recruitment of inflammatory cells, downregulating MMP-9, and upregulating TIMP-1 expression. PMID:21681587

  3. Matrix metalloproteinase-9 and vascular endothelial growth factor expression change in experimental retinal neovascularization

    PubMed Central

    Di, Yu; Nie, Qing-Zhu; Chen, Xiao-Long

    2016-01-01

    AIM To investigate the signal transduction mechanism of matrix metalloproteinase-9 (MMP-9) mediated- vascular endothelial growth factor (VEGF) expression and retinal neovascularization (RNV) in oxygen-induced retinopathy (OIR) model. METHODS C57BL/6J mice were divided into four groups: control group, OIR group, OIR control group (phosphate-buffered saline by intravitreal injection) and treated group [tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) by intravitreal injection]. OIR model was established in C57BL/6J mice exposed to 75%±2% oxygen for 5d. mRNA level and protein expression of MMP-9, TIMP-1 and VEGF were measured by real-time polymerase chain reaction and Western blotting, and located by immunohistochemistry. RESULTS Levels of MMP-9 and VEGF in retina were significantly increased in animals with OIR and OIR control group. Levels of TIMP-1 in retina was significantly reduced in animals with OIR and OIR control group. Furthermore, a significant correlation was found between MMP-9 and VEGF. Intravitreal injection of TIMP-1 significantly reduced MMP-9 and VEGF expression of the OIR mouse model (all P<0.05). CONCLUSION These results demonstrate that MMP-9-mediated up-regulation of VEGF promotes RNV in retinopathy of prematurity (ROP). TIMP-1 may be a potential target for the prevention and treatment of ROP. PMID:27366678

  4. Transcriptional Activation of Human Matrix Metalloproteinase-9 Gene Expression by Multiple Coactivators

    PubMed Central

    Zhao, Xueyan; Benveniste, Etty N.

    2008-01-01

    Summary Matrix metalloproteinase-9 (MMP-9), a proteolytic enzyme for matrix proteins, chemokines and cytokines, is a major target in cancer and autoimmune diseases since it is aberrantly upregulated. To control MMP-9 expression in pathological conditions, it is necessary to understand the regulatory mechanisms of MMP-9 expression. MMP-9 gene expression is regulated primarily at the transcriptional level. In this study, we investigated the role of multiple coactivators in regulating MMP-9 transcription. We demonstrate that multiple transcriptional coactivators are involved in MMP-9 promoter activation, including CBP/p300, PCAF, CARM1 and GRIP1. Furthermore, enhancement of MMP-9 promoter activity requires the histone acetyltransferase activity of PCAF but not that of CBP/p300, and the methyltransferase activity of CARM1. More importantly, these coactivators are not only able to activate MMP-9 promoter activity independently, but also function in a synergistic manner. Significant synergy was observed among CARM1, p300 and GRIP1, which is dependent on the interaction of p300 and CARM1 with the AD1 and AD2 domains of GRIP1, respectively. This suggests the formation of a ternary coactivator complex on the MMP-9 promoter. Chromatin immunoprecipitation assays demonstrate that these coactivators associate with the endogenous MMP-9 promoter, and that siRNA knockdown of expression of these coactivators reduces endogenous MMP-9 expression. Taken together, these studies demonstrate a new level of transcriptional regulation of MMP-9 expression by the cooperative action of coactivators. PMID:18790699

  5. Serum matrix metalloproteinase 9 (MMP9) as a biochemical marker for wasting marmoset syndrome

    PubMed Central

    YOSHIMOTO, Takuro; NIIMI, Kimie; TAKAHASHI, Eiki

    2016-01-01

    Use of the common marmoset (Callithrix jacchus) as a non-human primate experimental animal has increased in recent years. Although wasting marmoset syndrome (WMS) is one of the biggest problems in captive marmoset colonies, the molecular mechanisms, biochemical markers for accurate diagnosis and a reliable treatment remain unknown. In this study, as a first step to finding biochemical marker(s) for the accurate diagnosis of WMS, we conducted blood cell counts, including hematocrit, hemoglobin and platelets, and examined serum chemistry values, including albumin, calcium and levels of serum matrix metalloproteinase 9 (MMP9), using a colony of marmosets with and without weight loss. MMP9 is thought to be an enzyme responsible for the degradation of extracellular matrix components and participates in the pathogenesis of inflammatory conditions, such as human and murine inflammatory bowel disease, which, like WMS, are characterized histologically by inflammatory cell infiltrations in the intestines. The values of hematocrit and hemoglobin and levels of serum albumin and calcium in the WMS group were significantly decreased versus the control group. The platelet values and serum MMP9 concentrations were increased significantly in the WMS group compared with the control group. MMP9 could be a new and useful marker for the diagnosis of WMS in addition to hematocrit, hemoglobin, serum albumin and calcium. Our results also indicate that MMP9 could be a useful molecular candidate for treatment. PMID:26876041

  6. Serum matrix metalloproteinase-9 in colorectal cancer family-risk population screening

    PubMed Central

    Otero-Estévez, Olalla; Chiara, Loretta De; Rodríguez-Girondo, Mar; Rodríguez-Berrocal, Francisco Javier; Cubiella, Joaquín; Castro, Inés; Hernández, Vicent; Martínez-Zorzano, Vicenta Soledad

    2015-01-01

    Matrix metalloproteinase-9 (MMP-9) is related to tumour development and progression in colorectal cancer (CRC) and its utility as biomarker has been suggested. The aim of our study was to measure serum MMP-9 in asymptomatic first-degree relatives of CRC patients, and to analyse its diagnostic accuracy for the detection of advanced neoplasia (AN: advanced adenomas and CRC). Additionally, we compared its diagnostic capability with the most used non-invasive faecal immunochemical test (FIT). Serum MMP-9 was quantified by ELISA in 516 asymptomatic individuals that underwent a colonoscopy and a FIT. MMP-9 levels were significantly related to age and gender and therefore the concentration was corrected by these confounders. Corrected MMP-9 (cMMP-9) levels were higher in individuals with advanced adenomas (AA; p-value = 0.029) and AN (p-value = 0.056) compared to individuals with no neoplasia. Moreover, elevated cMMP-9 concentration was associated with more severe characteristics of adenomas (number of lesions, size and histology). Nevertheless, the diagnostic accuracy of cMMP-9 was considerably lower than that of FIT for identifying AA (22.64% vs. 47.17% sensitivity, 90% specificity) or AN (19.30% vs. 52.63% sensitivity, 90% specificity). According to our results, serum MMP-9 cannot be considered of utility for the diagnosis of AN in CRC family-risk population screening. PMID:26264519

  7. Longitudinal prospective study of matrix metalloproteinase-9 as a serum marker in gliomas.

    PubMed

    Iwamoto, Fabio M; Hottinger, Andreas F; Karimi, Sasan; Riedel, Elyn; Dantis, Jocelynn; Jahdi, Maryam; Panageas, Katherine S; Lassman, Andrew B; Abrey, Lauren E; Fleisher, Martin; Deangelis, Lisa M; Holland, Eric C; Hormigo, Adília

    2011-12-01

    The objective of this study was to evaluate if longitudinal measurements of serum matrix metalloproteinase-9 (MMP-9) correlated with disease status or survival in adults with gliomas. Serum samples were collected prospectively and concurrently with MRI scans at multiple time points during the course of the disease. MMP-9 levels were determined by ELISA and correlated with radiographic disease status and survival. Forty-one patients with low-grade gliomas, 105 with anaplastic gliomas, and 197 with glioblastoma enrolled in this study from August 2002 to September 2008. A total of 1,684 serum samples (97.1% of all MMP-9 samples) had a matching MRI scan. No statistically significant association was observed between levels of serum MMP-9 and radiographic disease status in low-grade gliomas (P = 0.98), anaplastic gliomas (P = 0.39) or glioblastomas (P = 0.33). Among patients with glioblastoma, longitudinal increases in MMP-9 had a weak association with shorter survival (HR = 1.1 per each doubling in MMP-9 levels, 95% CI, 1.0-1.3, P = 0.04) but they were not independently associated with survival when adjusted for age, extent of resection, and performance status. Changes in serum MMP-9 were not associated with survival in the anaplastic glioma cohort. Serum MMP-9 showed no utility in determining glioma disease status and was not a clinically relevant prognostic marker of survival. PMID:21710351

  8. Alpha1-antichymotrypsin activity correlates with and may modulate matrix metalloproteinase-9 in human acute wounds.

    PubMed

    Reiss, Matthew J; Han, Yuan-Ping; Garner, Warren L

    2009-01-01

    Matrix metalloproteinase-9 (MMP-9) plays a central role in many physiologic processes including acute and the chronic wounds. MMP-9 is not routinely expressed in healthy tissues but is promptly expressed as a proenzyme and converted into active enzyme after tissue injury. The mechanisms involved, including the activators and inhibitors for this enzyme in human tissue remain largely obscure. We recently identified alpha1-antichymotrypsin (alpha1-ACT), an acute phase factor, as a potent inhibitor controlling activation of pro-MMP-9 by human skin. The aim of this study is to establish the clinical relevance of the inhibitor in cutaneous wound healing. Fluids from acute burn blisters and conditioned media from skin explants of burn patients were analyzed. We observed that the presence pro-MMP-9 and its activation correlated with the proximity to and degree of injury. Early after trauma, massive levels of wound alpha1-ACT were associated with an absence of pro-MMP-9 activation. Conversely, the active MMP-9 occurs simultaneously with inactivation of alpha1-ACT. Our results suggest a role for alpha1-ACT as a physiologic inhibitor of MMP-9 activation in human wound healing. PMID:19660051

  9. Matrix Metalloproteinase 9 (MMP-9) Regulates Vein Wall Biomechanics in Murine Thrombus Resolution

    PubMed Central

    Nguyen, Khanh P.; McGilvray, Kirk C.; Puttlitz, Christian M.; Mukhopadhyay, Subhradip; Chabasse, Christine; Sarkar, Rajabrata

    2015-01-01

    Objective Deep venous thrombosis is a common vascular problem with long-term complications including post-thrombotic syndrome. Post-thrombotic syndrome consists of leg pain, swelling and ulceration that is related to incomplete or maladaptive resolution of the venous thrombus as well as loss of compliance of the vein wall. We examine the role of metalloproteinase-9 (MMP-9), a gene important in extracellular remodeling in other vascular diseases, in mediating thrombus resolution and biomechanical changes of the vein wall. Methods and Results The effects of targeted deletion of MMP-9 were studied in an in vivo murine model of thrombus resolution using the FVB strain of mice. MMP-9 expression and activity significantly increased on day 3 after DVT. The lack of MMP-9 impaired thrombus resolution by 27% and this phenotype was rescued by the transplantation of wildtype bone marrow cells. Using novel biomechanical techniques, we demonstrated that the lack of MMP-9 significantly decreased thrombus-induced loss of vein wall compliance. Biomechanical analysis of the contribution of individual structural components showed that MMP-9 affected the elasticity of the extracellular matrix and collagen-elastin fibers. Biochemical and histological analyses correlated with these biomechanical effects as thrombi of mice lacking MMP-9 had significantly fewer macrophages and collagen as compared to those of wildtype mice. Conclusions MMP-9 mediates thrombus-induced loss of vein wall compliance by increasing stiffness of the extracellular matrix and collagen-elastin fibers during thrombus resolution. MMP-9 also mediates macrophage and collagen content of the resolving thrombus and bone-marrow derived MMP-9 plays a role in resolution of thrombus mass. These disparate effects of MMP-9 on various aspects of thrombus illustrate the complexity of individual protease function on biomechanical and morphometric aspects of thrombus resolution. PMID:26406902

  10. Functional roles of N-linked glycosylation of human matrix metalloproteinase 9

    PubMed Central

    Duellman, Tyler; Burnett, John; Yang, Jay

    2016-01-01

    Matrix metalloproteinase-9 (MMP-9) is a secreted endoproteinase with a critical role in the regulation of the extracellular matrix and proteolytic activation of signaling molecules. Human (h)MMP-9 has two well-defined N-glycosylation sites at residues N38 and N120, however, their role has remained mostly unexplored partly because expression of the N-glycosylation-deficient N38S has been difficult due to a recently discovered SNP-dependent miRNA-mediated inhibitory mechanism. hMMP-9 cDNA encoding amino acid substitutions at residues 38 (mS38) or 120 (N120S) were created in the background of a miRNA binding site disrupted template and expressed by transient transfection. hMMP-9 harboring a single mS38 replacement secreted well, whereas N120S, or a double mS38/ N120S hMMP-9 demonstrated much reduced secretion. Imaging indicated ER-retention of the non-secreted variants and co-IP confirmed an enhanced strong interaction between the non-secreted hMMP-9s and the ER-resident protein calreticulin. Removal of N-glycosylation at residue 38 revealed an amino acid-dependent strong interaction with calreticulin likely preventing unloading of the misfolded protein from the ER chaperone down the normal secretory pathway. As with other glycoproteins, N-glycosylation strongly regulates hMMP-9 secretion. This is mediated, however, through a novel mechanism of cloaking an N-glycosylation-independent strong interaction with the ER-resident calreticulin. PMID:26207422

  11. Regulation of Matrix Metalloproteinase-9 by Epigenetic Modifications and the Development of Diabetic Retinopathy

    PubMed Central

    Zhong, Qing; Kowluru, Renu A.

    2013-01-01

    Diabetes activates retinal matrix metalloproteinase-9 (MMP-9), and MMP-9 damages the mitochondria and augments capillary cell apoptosis. Our aim is to elucidate the mechanism responsible for MMP-9 activation. Histone modifications and recruitment of the nuclear transcriptional factor-κB (p65 subunit) at the MMP-9 promoter and the activity of lysine-specific demethylase 1 (LSD1) were measured in the retina from streptozotocin-induced diabetic rats. The role of LSD1 in MMP-9 activation was investigated in isolated retinal endothelial cells transfected with LSD1 small interfering RNA (siRNA). The results were confirmed in the retina from human donors with diabetic retinopathy. Diabetes decreased histone H3 dimethyl lysine 9 (H3K9me2) and increased acetyl H3K9 (Ac-H3K9) and p65 at the retinal MMP-9 promoter. LSD1 enzyme activity and its transcripts were elevated. LSD1 siRNA ameliorated the glucose-induced decrease in H3K9me2 and increase in p65 at the MMP-9 promoter, and prevented MMP-9 activation, mitochondrial damage, and cell apoptosis. Human donors with diabetic retinopathy had similar epigenetic changes at the MMP-9 promoter. Thus, activated LSD1 hypomethylates H3K9 at the MMP-9 promoter and this frees up that lysine 9 for acetylation. Increased Ac-H3K9 facilitates the recruitment of p65, resulting in MMP-9 activation and mitochondrial damage. Thus, the regulation of LSD1 by molecular or pharmacological means has the potential to retard the development of diabetic retinopathy. PMID:23423566

  12. Simvastatin inhibits induction of matrix metalloproteinase-9 in rat alveolar macrophages exposed to cigarette smoke extract

    PubMed Central

    Kim, Sang-Eun; Thuy, Tran Thi Thanh; Lee, Ji-Hyun; Ro, Jai Youl; Bae, Young-An; Kong, Yoon; Ahn, Jee-Yin; Lee, Dong-Soon; Oh, Yeon-Mock; Lee, Sang-Do

    2009-01-01

    Matrix metalloproteinase-9 (MMP-9) may play an important role in emphysematous change in chronic obstructive pulmonary disease (COPD), one of the leading causes of mortality and morbidity worldwide. We previously reported that simvastatin, an inhibitor of HMG-CoA reductase, attenuates emphysematous change and MMP-9 induction in the lungs of rats exposed to cigarette smoke. However, it remained uncertain how cigarette smoke induced MMP-9 and how simvastatin inhibited cigarette smoke-induced MMP-9 expression in alveolar macrophages (AMs), a major source of MMP-9 in the lungs of COPD patients. Presently, we examined the related signaling for MMP-9 induction and the inhibitory mechanism of simvastatin on MMP-9 induction in AMs exposed to cigarette smoke extract (CSE). In isolated rat AMs, CSE induced MMP-9 expression and phosphorylation of ERK and Akt. A chemical inhibitor of MEK1/2 or PI3K reduced phosphorylation of ERK or Akt, respectively, and also inhibited CSE-mediated MMP-9 induction. Simvastatin reduced CSE-mediated MMP-9 induction, and simvastatin-mediated inhibition was reversed by farnesyl pyrophosphate (FPP) or geranylgeranyl pyrophosphate (GGPP). Similar to simvastatin, inhibition of FPP transferase or GGPP transferase suppressed CSE-mediated MMP-9 induction. Simvastatin attenuated CSE-mediated activation of RAS and phosphorylation of ERK, Akt, p65, IκB, and nuclear AP-1 or NF-κB activity. Taken together, these results suggest that simvastatin may inhibit CSE-mediated MMP-9 induction, primarily by blocking prenylation of RAS in the signaling pathways, in which Raf-MEK-ERK, PI3K/Akt, AP-1, and IκB-NF-κB are involved. PMID:19299917

  13. Expression analysis of Matrix Metalloproteinase-9 in epithelialized and non-epithelialized apical periodontitis lesions

    PubMed Central

    Carneiro, Everdan; Menezes, Renato; Garlet, Gustavo Pompermaier; Garcia, Roberto Brandão; Bramante, Clóvis Monteiro; Figueira, Rita; Sogayar, Mari; Granjeiro, José Mauro

    2009-01-01

    OBJECTIVE To determine the expression of matrix metalloproteinase-9 (MMP-9) in apical periodontitis lesions. STUDY DESIGN Nineteen epithelialized and eighteen non-epithelialized apical periodontitis lesions were collected after periapical surgery. After histological processing, serial sectioning, H&E staining and microscopic analysis, 10 epithelialized and 10 non-epithelialized lesions were selected for immunohistochemical analysis for MMP-9 and CD 68. At least 1/3 of each specimen was frozen at −70°C for further mRNA isolation and reverse transcription into cDNA for Real-Time-PCR procedures. The relative expression of a target gene was determined in comparison with reference genes (GAPDH, HPRT, β-actin and BCRP). RESULTS Polymorphonuclear neutrophils, macrophages and lymphocytes were stained for MMP-9 in both types of lesions, and when present, epithelial cells were also stained. The number and the ratio of MMP-9+/total cells were greater in non-epithelialized than epithelialized lesions (p=0.0001) and showed a positive correlation to CD68+/total cells (p=0.045). No significant differences were observed for MMP-9 mRNA expression between ephithelized and non-ephithelized lesions. However, when compared to healthy periapical ligaments, both types of lesions presented increased MMP-9 expression (p<0.0001). CONCLUSION The present data suggest the participation of several inflammatory cells, mainlly CD68+ cells, in the MMP-9 expression in apical periodontitis lesions. MMP-9 could be actively enroled in the ECM degradation in apical periodontitis lesions. PMID:18926740

  14. Molecular Mechanism of Transcriptional Regulation of Matrix Metalloproteinase-9 in Diabetic Retinopathy.

    PubMed

    Mishra, Manish; Flaga, Jadwiga; Kowluru, Renu A

    2016-08-01

    Increase in matrix metalloproteinase-9 (MMP-9) is implicated in retinal capillary cell apoptosis, a phenomenon which precedes the development of diabetic retinopathy. MMP-9 promoter has multiple sites for binding the transcriptional factors, including two for activator protein 1 (AP-1). The binding of AP-1, a heterodimer of c-Jun and c-Fos, is regulated by posttranslational modifications, and in diabetes, deacetylating enzyme, Sirt1, is inhibited. Our aim, is to investigate the molecular mechanism of MMP-9 transcriptional regulation in diabetes. Binding of AP-1 (c-Jun, c-Fos) at the MMP-9 promoter, and AP-1 acetylation were analyzed in retinal endothelial cells incubated in normal or high glucose by chromatin-immunoprecipitation and co-immunoprecipitation respectively. Role of AP-1 in MMP-9 regulation was confirmed by c-Jun or c-Fos siRNAs, and that of its acetylation, by Sirt1 overexpression. In vitro results were validated in the retina from diabetic mice overexpressing Sirt1, and in the retinal microvessels from human donors with diabetic retinopathy. In experimental models, AP-1 binding was increased at the proximal and distal sites of the MMP-9 promoter, and similar phenomenon was confirmed in the retinal microvessels from human donors with diabetic retinopathy. Silencing of AP-1, or overexpression of Sirt1 ameliorated glucose-induced increase in MMP-9 expression and cell apoptosis. Thus, in diabetes, due to Sirt1 inhibition, AP-1 is hyperacetylated, which increases its binding at MMP-9 promoter, and hence, activation of Sirt1 could inhibit the development of diabetic retinopathy by impeding MMP-9-mediated mitochondrial damage. J. Cell. Physiol. 231: 1709-1718, 2016. © 2015 Wiley Periodicals, Inc. PMID:26599598

  15. Attenuation of dextran sodium sulphate induced colitis in matrix metalloproteinase-9 deficient mice

    PubMed Central

    Santana, Alfredo; Medina, Carlos; Paz-Cabrera, Maria Cristina; Díaz-Gonzalez, Federico; Farré, Esther; Salas, Antonio; Radomski, Marek W; Quintero, Enrique

    2006-01-01

    AIM: To study whether matrix metalloproteinase-9 (MMP-9) is a key factor in epithelial damage in the dextran sodium sulphate (DSS) model of colitis in mice. METHODS: MMP-9-deficient and wild-type (wt) mice were given 5% DSS in drinking water for 5 d followed by recovery up to 7 d. On d 5 and 12 after induction of colitis, gelatinases, MMP-2 and MMP-9, were measured in homogenates of colonic tissue by zymography and Western blot, whereas tissue inhibitor of metalloproteinases (TIMPs) were measured by reverse zymography. The gelatinolytic activity was also determined in supernatants of polymorphonuclear leukocytes (PMN) isolated from mice blood. Moreover, intestinal epithelial cells were stimulated with TNF-α to study whether these cells were able to produce MMPs. Finally, colonic mucosal lesions were measured by microscopic examination. RESULTS: On d 5 of colitis, the activity of MMP-9 was increased in homogenates of colonic tissues (0.24 ± 0.1 vs 21.3 ± 6.4, P < 0.05) and PMN from peripheral blood in wt (0.5 ± 0.1 vs 10.4 ± 0.7, P < 0.05), but not in MMP-9-deficient animals. The MMP-9 activity was also up-regulated by TNF-α in epithelial intestinal cells (2.5 ± 0.5 vs 14.7 ± 3.0, P < 0.05). Although colitis also led to increase of TIMP-1 activity, the MMP-9/TIMP-1 balance remained elevated. Finally, in the MMP-9-deficient colitic mice both the extent and severity of intestinal epithelial injury were significantly attenuated when compared with wt mice. CONCLUSION: We conclude that DSS induced colitis is markedly attenuated in animals lacking MMP-9. This suggests that intestinal injury induced by DSS is modulated by MMP-9 and that inhibition of this gelatinase may reduce inflammation. PMID:17072979

  16. AMP-activated protein kinase suppresses matrix metalloproteinase-9 expression in mouse embryonic fibroblasts.

    PubMed

    Morizane, Yuki; Thanos, Aristomenis; Takeuchi, Kimio; Murakami, Yusuke; Kayama, Maki; Trichonas, George; Miller, Joan; Foretz, Marc; Viollet, Benoit; Vavvas, Demetrios G

    2011-05-01

    Matrix metalloproteinase-9 (MMP-9) plays a critical role in tissue remodeling under both physiological and pathological conditions. Although MMP-9 expression is low in most cells and is tightly controlled, the mechanism of its regulation is poorly understood. We utilized mouse embryonic fibroblasts (MEFs) that were nullizygous for the catalytic α subunit of AMP-activated protein kinase (AMPK), which is a key regulator of energy homeostasis, to identify AMPK as a suppressor of MMP-9 expression. Total AMPKα deletion significantly elevated MMP-9 expression compared with wild-type (WT) MEFs, whereas single knock-out of the isoforms AMPKα1 and AMPKα2 caused minimal change in the level of MMP-9 expression. The suppressive role of AMPK on MMP-9 expression was mediated through both its activity and presence. The AMPK activators 5-amino-4-imidazole carboxamide riboside and A769662 suppressed MMP-9 expression in WT MEFs, and AMPK inhibition by the overexpression of dominant negative (DN) AMPKα elevated MMP-9 expression. However, in AMPKα(-/-) MEFs transduced with DN AMPKα, MMP-9 expression was suppressed. AMPKα(-/-) MEFs showed increased phosphorylation of IκBα, expression of IκBα mRNA, nuclear localization of nuclear factor-κB (NF-κB), and DNA-binding activity of NF-κB compared with WT. Consistently, selective NF-κB inhibitors BMS345541 and SM7368 decreased MMP-9 expression in AMPKα(-/-) MEFs. Overall, our results suggest that both AMPKα isoforms suppress MMP-9 expression and that both the activity and presence of AMPKα contribute to its function as a regulator of MMP-9 expression by inhibiting the NF-κB pathway. PMID:21402702

  17. Selective Inhibition of Matrix Metalloproteinase-9 Attenuates Secondary Damage Resulting from Severe Traumatic Brain Injury

    PubMed Central

    Gooyit, Major; Chen, Shanyan; Purdy, Justin J.; Walker, Jennifer M.; Giritharan, Andrew B.; Purnell, Whitley; Robinson, Christopher R.; Shin, Dmitriy; Schroeder, Valerie A.; Suckow, Mark A.; Simonyi, Agnes; Y. Sun, Grace; Mobashery, Shahriar; Cui, Jiankun; Chang, Mayland; Gu, Zezong

    2013-01-01

    Traumatic brain injury (TBI) is a leading cause of death and long-term disability. Following the initial insult, severe TBI progresses to a secondary injury phase associated with biochemical and cellular changes. The secondary injury is thought to be responsible for the development of many of the neurological deficits observed after TBI and also provides a window of opportunity for therapeutic intervention. Matrix metalloproteinase-9 (MMP-9 or gelatinase B) expression is elevated in neurological diseases and its activation is an important factor in detrimental outcomes including excitotoxicity, mitochondrial dysfunction and apoptosis, and increases in inflammatory responses and astrogliosis. In this study, we used an experimental mouse model of TBI to examine the role of MMP-9 and the therapeutic potential of SB-3CT, a mechanism-based gelatinase selective inhibitor, in ameliorating the secondary injury. We observed that activation of MMP-9 occurred within one day following TBI, and remained elevated for 7 days after the initial insult. SB-3CT effectively attenuated MMP-9 activity, reduced brain lesion volumes and prevented neuronal loss and dendritic degeneration. Pharmacokinetic studies revealed that SB-3CT and its active metabolite, p-OH SB-3CT, were rapidly absorbed and distributed to the brain. Moreover, SB-3CT treatment mitigated microglial activation and astrogliosis after TBI. Importantly, SB-3CT treatment improved long-term neurobehavioral outcomes, including sensorimotor function, and hippocampus-associated spatial learning and memory. These results demonstrate that MMP-9 is a key target for therapy to attenuate secondary injury cascades and that this class of mechanism-based gelatinase inhibitor–with such desirable pharmacokinetic properties–holds considerable promise as a potential pharmacological treatment of TBI. PMID:24194849

  18. Broccoli and watercress suppress matrix metalloproteinase-9 activity and invasiveness of human MDA-MB-231 breast cancer cells

    SciTech Connect

    Rose, Peter . E-mail: bchpcr@nus.edu.sg; Huang, Qing; Ong, Choon Nam; Whiteman, Matt

    2005-12-01

    A high dietary intake of cruciferous vegetables has been associated with a reduction in numerous human pathologies particularly cancer. In the current study, we examined the inhibitory effects of broccoli (Brassica oleracea var. italica) and watercress (Rorripa nasturtium aquaticum) extracts on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cancer cell invasion and matrix metalloproteinase-9 activity using human MDA-MB-231 breast cancer cells. Aberrant overexpression of matrix metalloproteinases, including metalloproteinase-9, is associated with increased invasive potential in cancer cell lines. Our results demonstrate that extracts of broccoli and Rorripa suppressed TPA-induced MMP-9 activity and invasiveness in a concentration dependant manner as determined by zymographic analysis. Furthermore, fractionation of individual extracts followed by liquid chromatography mass spectroscopy analysis (LC-MS) revealed that the inhibitory effects of each vegetable were associated with the presence of 4-methysulfinylbutyl (sulforaphane) and 7-methylsulphinylheptyl isothiocyanates. Taken together, our data indicate that isothiocyanates derived form broccoli and Rorripa inhibit metalloproteinase 9 activities and also suppress the invasive potential of human MDA-MB-231 breast cancer cells in vitro. The inhibitory effects observed in the current study may contribute to the suppression of carcinogenesis by diets high in cruciferous vegetables.

  19. Melatonin Preserves Blood-Brain Barrier Integrity and Permeability via Matrix Metalloproteinase-9 Inhibition

    PubMed Central

    Alluri, Himakarnika; Wilson, Rickesha L.; Anasooya Shaji, Chinchusha; Wiggins-Dohlvik, Katie; Patel, Savan; Liu, Yang; Peng, Xu; Beeram, Madhava R.; Davis, Matthew L.; Huang, Jason H.; Tharakan, Binu

    2016-01-01

    Microvascular hyperpermeability that occurs at the level of the blood-brain barrier (BBB) often leads to vasogenic brain edema and elevated intracranial pressure following traumatic brain injury (TBI). At a cellular level, tight junction proteins (TJPs) between neighboring endothelial cells maintain the integrity of the BBB via TJ associated proteins particularly, zonula occludens-1 (ZO-1) that binds to the transmembrane TJPs and actin cytoskeleton intracellularly. The pro-inflammatory cytokine, interleukin-1β (IL-1β) as well as the proteolytic enzymes, matrix metalloproteinase-9 (MMP-9) are key mediators of trauma-associated brain edema. Recent studies indicate that melatonin a pineal hormone directly binds to MMP-9 and also might act as its endogenous inhibitor. We hypothesized that melatonin treatment will provide protection against TBI-induced BBB hyperpermeability via MMP-9 inhibition. Rat brain microvascular endothelial cells grown as monolayers were used as an in vitro model of the BBB and a mouse model of TBI using a controlled cortical impactor was used for all in vivo studies. IL-1β (10 ng/mL; 2 hours)-induced endothelial monolayer hyperpermeability was significantly attenuated by melatonin (10 μg/mL; 1 hour), GM6001 (broad spectrum MMP inhibitor; 10 μM; 1 hour), MMP-9 inhibitor-1 (MMP-9 specific inhibitor; 5 nM; 1 hour) or MMP-9 siRNA transfection (48 hours) in vitro. Melatonin and MMP-9 inhibitor-1 pretreatment attenuated IL-1β-induced MMP-9 activity, loss of ZO-1 junctional integrity and f-actin stress fiber formation. IL-1β treatment neither affected ZO-1 protein or mRNA expression or cell viability. Acute melatonin treatment attenuated BBB hyperpermeability in a mouse controlled cortical impact model of TBI in vivo. In conclusion, one of the protective effects of melatonin against BBB hyperpermeability occurs due to enhanced BBB integrity via MMP-9 inhibition. In addition, acute melatonin treatment provides protection against BBB

  20. Ablation of Matrix Metalloproteinase-9 Prevents Cardiomyocytes Contractile Dysfunction in Diabetics

    PubMed Central

    Prathipati, Priyanka; Metreveli, Naira; Nandi, Shyam Sundar; Tyagi, Suresh C.; Mishra, Paras K.

    2016-01-01

    Elevated expression and activity of matrix metalloproteinase-9 (MMP9) and decreased contractility of cardiomyocytes are documented in diabetic hearts. However, it is unclear whether MMP is involved in the regulation of contractility of cardiomyocytes in diabetic hearts. In the present study, we tested the hypothesis that MMP9 regulates contractility of cardiomyocytes in diabetic hearts, and ablation of MMP9 prevents impaired contractility of cardiomyocytes in diabetic hearts. To determine the specific role of MMP9 in cardiomyocyte contractility, we used 12–14 week male WT (normoglycemic sibling of Akita), Akita, and Ins2+∕−/MMP9−∕− (DKO) mice. DKO mice were generated by cross-breeding male Ins2+∕− Akita (T1D) with female MMP9 knockout (MMP9−∕−) mice. We isolated cardiomyocytes from the heart of the above three groups of mice and measured their contractility and calcium transients. Moreover, we determined mRNA and protein levels of sarco-endoplasmic reticulum calcium ATPase-2a (SERCA-2a), which is involved in calcium handling during contractility of cardiomyocytes in WT, Akita, and DKO hearts using QPCR, Western blotting and immunoprecipitation, respectively. Our results revealed that in Akita hearts where increased expression and activity of MMP9 is reported, the rates of shortening and re-lengthening (±dL/dt) of cardiomyocytes were decreased, time to 90% peak height and baseline during contractility was increased, rate of calcium decay was increased, and calcium transient was decreased as compared to WT cardiomyocytes. However, these changes in Akita were blunted in DKO cardiomyocytes. The molecular analyses of SERCA-2a in the hearts showed that it was downregulated in Akita as compared to WT but was comparatively upregulated in DKO. These results suggest that abrogation of MMP9 gene prevents contractility of cardiomyocytes, possibly by increasing SERCA-2a and calcium transients. We conclude that MMP9 plays a crucial role in the regulation

  1. Niclosamide suppresses migration of hepatocellular carcinoma cells and downregulates matrix metalloproteinase-9 expression

    PubMed Central

    TOMIZAWA, MINORU; SHINOZAKI, FUMINOBU; MOTOYOSHI, YASUFUMI; SUGIYAMA, TAKAO; YAMAMOTO, SHIGENORI; ISHIGE, NAOKI

    2015-01-01

    Metastasis negatively affects the prognosis of hepatocellular carcinoma (HCC). In the present study, niclosamide, which is known to suppress the proliferation of HCC cells, was investigated for possible suppressant effects on the migration of HCC cells. HLF and PLC/PRF/5 HCC cells were cultured in the presence of niclosamide. Cell proliferation was analyzed using the MTS assay. Cell migration was measured by performing a scratch assay. Expression levels of cyclin D1 and matrix metalloproteinase 9 (MMP9) were analyzed by performing revers transcription-quantitative polymerase chain reaction. Compared with the control treatment, treatment with 10 µm niclosamide suppressed the proliferation of the HLF and PRL/PRF/5 cells to 49.9±3.7 and 17.9±11.5% (P<0.05), respectively. Furthermore, compared with the control treatment, treatment with 1.0 µM niclosamide downregulated the expression of cyclin D1 to 52.4±4.4 and 23.9±5.4% (P<0.05) in the HLF and PRL/PRF/5 cells, respectively. In the scratch assay, treatment of the HLF cells with niclosamide (1.0 µm) decreased the distance of the scratched line from the growing edge to 4.6±1.0 mm compared with the 9.2±1.4 mm observed with the control treatment (P<0.05). Similarly, treatment of the PRL/PRF/5 cells with niclosamide (1.0 µm) also decreased the distance of the scratched line from the growing edge to 3.0±0.8 mm compared with the 5.5±0.9 mm observed with the control treatment (P<0.05). Further, MMP9 expression levels in the HLF cells treated with 1.0 µm niclosamide decreased to 22.4±1.76% (P<0.05) compared with those in the untreated control HLF cells. Similarly, expression level of MMP9 in the PRL/PRF/5 cells treated with 1.0 µm niclosamide deceased to 18.7±10.7% (P<0.05) compared with those in the untreated control PRL/PRF/5 cells. Overall, niclosamide downregulated the expression of MMP9 in and suppressed the migration of HCC cells. PMID:26788160

  2. Integrin αvβ6 and matrix metalloproteinase 9 correlate with survival in gastric cancer

    PubMed Central

    Lian, Pei-Long; Liu, Zhao; Yang, Guang-Yun; Zhao, Rui; Zhang, Zhao-Yang; Chen, Yue-Guang; Zhuang, Zhuo-Nan; Xu, Ke-Sen

    2016-01-01

    AIM: To investigate the expression of integrin αvβ6 and matrix metalloproteinase 9 (MMP-9), their association with prognostic factors and to assess their predictive role in gastric cancer patients. METHODS: Immunohistochemistry was used to determine the expressions of integrin αvβ6 and MMP-9 in 126 specimens from patients with primary gastric carcinoma. Associations between immunohistochemical staining and various clinic pathologic variables of tissue specimens were evaluated by the χ2 test and Fisher’s exact test. Expression correlation of αvβ6 and MMP-9 was assessed using bivariate correlation analysis. The patients were followed-up every 3 mo in the first two years and at least every 6 mo afterwards, with a median follow-up of 56 mo (ranging from 2 mo to 94 mo). Four different combinations of αvβ6 and MMP-9 levels (that is, both markers positive, both markers negative, αvβ6 positive with MMP-9 negative, and αvβ6 negative with MMP-9 positive) were evaluated for their relative effect on survival. The difference in survival curves was evaluated with a log-rank test. Survival analysis was conducted using the Kaplan-Meier survival and Cox proportional hazards model analysis. RESULTS: The expressions of integrin αvβ6 and MMP-9 were investigated in 126 cases, among which 34.92% were positive for αvβ6 expression, and 42.06% for MMP-9 expression. The expression of αvβ6 was associated with Lauren type, differentiation, N stage, and TNM stage (the P values were 0.006, 0.038, 0.016, and 0.002, respectively). While MMP-9 expression was associated with differentiation, T stage, N stage, and TNM stage (the P values were 0.039, 0.014, 0.033, and 0.008, respectively). The positive correlation between αvβ6 and MMP-9 in gastric cancer was confirmed by a correlation analysis. The Kaplan-Meier survival analysis showed that patients with expression of αvβ6 or MMP-9 alone died earlier than those with negative expression and that patients who were both αvβ6

  3. Epigenetics of Epileptogenesis-Evoked Upregulation of Matrix Metalloproteinase-9 in Hippocampus.

    PubMed

    Zybura-Broda, Katarzyna; Amborska, Renata; Ambrozek-Latecka, Magdalena; Wilemska, Joanna; Bogusz, Agnieszka; Bucko, Joanna; Konopka, Anna; Grajkowska, Wieslawa; Roszkowski, Marcin; Marchel, Andrzej; Rysz, Andrzej; Koperski, Lukasz; Wilczynski, Grzegorz M; Kaczmarek, Leszek; Rylski, Marcin

    2016-01-01

    Enhanced levels of Matrix Metalloproteinase-9 (MMP-9) have been implicated in the pathogenesis of epilepsy in humans and rodents. Lack of Mmp-9 impoverishes, whereas excess of Mmp-9 facilitates epileptogenesis. Epigenetic mechanisms driving the epileptogenesis-related upregulation of MMP-9 expression are virtually unknown. The aim of this study was to reveal these mechanisms. We analyzed hippocampi extracted from adult and pediatric patients with temporal lobe epilepsy as well as from partially and fully pentylenetetrazole kindled rats. We used a unique approach to the analysis of the kindling model results (inclusion in the analysis of rats being during kindling, and not only a group of fully kindled animals), which allowed us to separate the molecular effects exerted by the epileptogenesis from those related to epilepsy and epileptic activity. Consequently, it allowed for a disclosure of molecular mechanisms underlying causes, and not consequences, of epilepsy. Our data show that the epileptogenesis-evoked upregulation of Mmp-9 expression is regulated by removal from Mmp-9 gene proximal promoter of the two, interweaved potent silencing mechanisms-DNA methylation and Polycomb Repressive Complex 2 (PRC2)-related repression. Demethylation depends on a gradual dissociation of the DNA methyltransferases, Dnmt3a and Dnmt3b, and on progressive association of the DNA demethylation promoting protein Gadd45β to Mmp-9 proximal gene promoter in vivo. The PRC2-related mechanism relies on dissociation of the repressive transcription factor YY1 and the dissipation of the PRC2-evoked trimethylation on Lys27 of the histone H3 from the proximal Mmp-9 promoter chromatin in vivo. Moreover, we show that the DNA hydroxymethylation, a new epigenetic DNA modification, which is localized predominantly in the gene promoters and is particularly abundant in the brain, is not involved in a regulation of MMP-9 expression during the epileptogenesis in the rat hippocampus as well as in the

  4. Epigenetics of Epileptogenesis-Evoked Upregulation of Matrix Metalloproteinase-9 in Hippocampus

    PubMed Central

    Zybura-Broda, Katarzyna; Amborska, Renata; Ambrozek-Latecka, Magdalena; Wilemska, Joanna; Bogusz, Agnieszka; Bucko, Joanna; Konopka, Anna; Grajkowska, Wieslawa; Roszkowski, Marcin; Marchel, Andrzej; Rysz, Andrzej; Koperski, Lukasz; Wilczynski, Grzegorz M.; Kaczmarek, Leszek; Rylski, Marcin

    2016-01-01

    Enhanced levels of Matrix Metalloproteinase-9 (MMP-9) have been implicated in the pathogenesis of epilepsy in humans and rodents. Lack of Mmp-9 impoverishes, whereas excess of Mmp-9 facilitates epileptogenesis. Epigenetic mechanisms driving the epileptogenesis-related upregulation of MMP-9 expression are virtually unknown. The aim of this study was to reveal these mechanisms. We analyzed hippocampi extracted from adult and pediatric patients with temporal lobe epilepsy as well as from partially and fully pentylenetetrazole kindled rats. We used a unique approach to the analysis of the kindling model results (inclusion in the analysis of rats being during kindling, and not only a group of fully kindled animals), which allowed us to separate the molecular effects exerted by the epileptogenesis from those related to epilepsy and epileptic activity. Consequently, it allowed for a disclosure of molecular mechanisms underlying causes, and not consequences, of epilepsy. Our data show that the epileptogenesis-evoked upregulation of Mmp-9 expression is regulated by removal from Mmp-9 gene proximal promoter of the two, interweaved potent silencing mechanisms–DNA methylation and Polycomb Repressive Complex 2 (PRC2)-related repression. Demethylation depends on a gradual dissociation of the DNA methyltransferases, Dnmt3a and Dnmt3b, and on progressive association of the DNA demethylation promoting protein Gadd45β to Mmp-9 proximal gene promoter in vivo. The PRC2-related mechanism relies on dissociation of the repressive transcription factor YY1 and the dissipation of the PRC2-evoked trimethylation on Lys27 of the histone H3 from the proximal Mmp-9 promoter chromatin in vivo. Moreover, we show that the DNA hydroxymethylation, a new epigenetic DNA modification, which is localized predominantly in the gene promoters and is particularly abundant in the brain, is not involved in a regulation of MMP-9 expression during the epileptogenesis in the rat hippocampus as well as in the

  5. Interplay between Matrix Metalloproteinase-9, Matrix Metalloproteinase-2, and Interleukins in Multiple Sclerosis Patients

    PubMed Central

    Tamborino, Carmine; Baldi, Eleonora; Kostic, Vladimir; Drulovic, Jelena; Dujmovic, Irena

    2016-01-01

    Matrix Metalloproteases (MMPs) and cytokines have been involved in the pathogenesis of multiple sclerosis (MS). However, no studies have still explored the possible associations between the two families of molecules. The present study aimed to evaluate the contribution of active MMP-9, active MMP-2, interleukin- (IL-) 17, IL-18, IL-23, and monocyte chemotactic proteins-3 to the pathogenesis of MS and the possible interconnections between MMPs and cytokines. The proteins were determined in the serum and cerebrospinal fluid (CSF) of 89 MS patients and 92 other neurological disorders (OND) controls. Serum active MMP-9 was increased in MS patients and OND controls compared to healthy subjects (p < 0.001 and p < 0.01, resp.), whereas active MMP-2 and ILs did not change. CSF MMP-9, but not MMP-2 or ILs, was selectively elevated in MS compared to OND (p < 0.01). Regarding the MMPs and cytokines intercorrelations, we found a significant association between CSF active MMP-2 and IL-18 (r = 0.3, p < 0.05), while MMP-9 did not show any associations with the cytokines examined. Collectively, our results suggest that active MMP-9, but not ILs, might be a surrogate marker for MS. In addition, interleukins and MMPs might synergistically cooperate in MS, indicating them as potential partners in the disease process. PMID:27555667

  6. Interplay between Matrix Metalloproteinase-9, Matrix Metalloproteinase-2, and Interleukins in Multiple Sclerosis Patients.

    PubMed

    Trentini, Alessandro; Castellazzi, Massimiliano; Cervellati, Carlo; Manfrinato, Maria Cristina; Tamborino, Carmine; Hanau, Stefania; Volta, Carlo Alberto; Baldi, Eleonora; Kostic, Vladimir; Drulovic, Jelena; Granieri, Enrico; Dallocchio, Franco; Bellini, Tiziana; Dujmovic, Irena; Fainardi, Enrico

    2016-01-01

    Matrix Metalloproteases (MMPs) and cytokines have been involved in the pathogenesis of multiple sclerosis (MS). However, no studies have still explored the possible associations between the two families of molecules. The present study aimed to evaluate the contribution of active MMP-9, active MMP-2, interleukin- (IL-) 17, IL-18, IL-23, and monocyte chemotactic proteins-3 to the pathogenesis of MS and the possible interconnections between MMPs and cytokines. The proteins were determined in the serum and cerebrospinal fluid (CSF) of 89 MS patients and 92 other neurological disorders (OND) controls. Serum active MMP-9 was increased in MS patients and OND controls compared to healthy subjects (p < 0.001 and p < 0.01, resp.), whereas active MMP-2 and ILs did not change. CSF MMP-9, but not MMP-2 or ILs, was selectively elevated in MS compared to OND (p < 0.01). Regarding the MMPs and cytokines intercorrelations, we found a significant association between CSF active MMP-2 and IL-18 (r = 0.3, p < 0.05), while MMP-9 did not show any associations with the cytokines examined. Collectively, our results suggest that active MMP-9, but not ILs, might be a surrogate marker for MS. In addition, interleukins and MMPs might synergistically cooperate in MS, indicating them as potential partners in the disease process. PMID:27555667

  7. Anacardic acid inhibits the catalytic activity of matrix metalloproteinase-2 and matrix metalloproteinase-9.

    PubMed

    Omanakuttan, Athira; Nambiar, Jyotsna; Harris, Rodney M; Bose, Chinchu; Pandurangan, Nanjan; Varghese, Rebu K; Kumar, Geetha B; Tainer, John A; Banerji, Asoke; Perry, J Jefferson P; Nair, Bipin G

    2012-10-01

    Cashew nut shell liquid (CNSL) has been used in traditional medicine for the treatment of a wide variety of pathophysiological conditions. To further define the mechanism of CNSL action, we investigated the effect of cashew nut shell extract (CNSE) on two matrix metalloproteinases, MMP-2/gelatinase A and MMP-9/gelatinase B, which are known to have critical roles in several disease states. We observed that the major constituent of CNSE, anacardic acid, markedly inhibited the gelatinase activity of 3T3-L1 cells. Our gelatin zymography studies on these two secreted gelatinases, present in the conditioned media from 3T3-L1 cells, established that anacardic acid directly inhibited the catalytic activities of both MMP-2 and MMP-9. Our docking studies suggested that anacardic acid binds into the MMP-2/9 active site, with the carboxylate group of anacardic acid chelating the catalytic zinc ion and forming a hydrogen bond to a key catalytic glutamate side chain and the C15 aliphatic group being accommodated within the relatively large S1' pocket of these gelatinases. In agreement with the docking results, our fluorescence-based studies on the recombinant MMP-2 catalytic core domain demonstrated that anacardic acid directly inhibits substrate peptide cleavage in a dose-dependent manner, with an IC₅₀ of 11.11 μM. In addition, our gelatinase zymography and fluorescence data confirmed that the cardol-cardanol mixture, salicylic acid, and aspirin, all of which lack key functional groups present in anacardic acid, are much weaker MMP-2/MMP-9 inhibitors. Our results provide the first evidence for inhibition of gelatinase catalytic activity by anacardic acid, providing a novel template for drug discovery and a molecular mechanism potentially involved in CNSL therapeutic action. PMID:22745359

  8. Anacardic Acid Inhibits the Catalytic Activity of Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9

    PubMed Central

    Omanakuttan, Athira; Nambiar, Jyotsna; Harris, Rodney M.; Bose, Chinchu; Pandurangan, Nanjan; Varghese, Rebu K.; Kumar, Geetha B.; Tainer, John A.; Banerji, Asoke; Perry, J. Jefferson P.

    2012-01-01

    Cashew nut shell liquid (CNSL) has been used in traditional medicine for the treatment of a wide variety of pathophysiological conditions. To further define the mechanism of CNSL action, we investigated the effect of cashew nut shell extract (CNSE) on two matrix metalloproteinases, MMP-2/gelatinase A and MMP-9/gelatinase B, which are known to have critical roles in several disease states. We observed that the major constituent of CNSE, anacardic acid, markedly inhibited the gelatinase activity of 3T3-L1 cells. Our gelatin zymography studies on these two secreted gelatinases, present in the conditioned media from 3T3-L1 cells, established that anacardic acid directly inhibited the catalytic activities of both MMP-2 and MMP-9. Our docking studies suggested that anacardic acid binds into the MMP-2/9 active site, with the carboxylate group of anacardic acid chelating the catalytic zinc ion and forming a hydrogen bond to a key catalytic glutamate side chain and the C15 aliphatic group being accommodated within the relatively large S1′ pocket of these gelatinases. In agreement with the docking results, our fluorescence-based studies on the recombinant MMP-2 catalytic core domain demonstrated that anacardic acid directly inhibits substrate peptide cleavage in a dose-dependent manner, with an IC50 of 11.11 μM. In addition, our gelatinase zymography and fluorescence data confirmed that the cardol-cardanol mixture, salicylic acid, and aspirin, all of which lack key functional groups present in anacardic acid, are much weaker MMP-2/MMP-9 inhibitors. Our results provide the first evidence for inhibition of gelatinase catalytic activity by anacardic acid, providing a novel template for drug discovery and a molecular mechanism potentially involved in CNSL therapeutic action. PMID:22745359

  9. Matrix Metalloproteinase-1 and Matrix Metalloproteinase-9 in the Aqueous Humor of Diabetic Macular Edema Patients

    PubMed Central

    Choi, Jin A.; Jee, Donghyun

    2016-01-01

    Purpose To assess the concentrations of matrix metalloproteinase (MMP)-1 and MMP-9 in the aqueous humor of diabetic macular edema (DME) patients. Method The concentrations of MMP-1 and MMP-9 in the aqueous humors of 15 cataract patients and 25 DME patients were compared. DME patients were analyzed according to the diabetic retinopathy (DR) stage, diabetes mellitus (DM) duration, pan-retinal photocoagulation (PRP) treatment, recurrence within 3 months, HbA1C (glycated hemoglobin) level, and axial length. Results The concentrations of MMP-1 and MMP-9 of the DME groups were higher than those of the control group (p = 0.005 and p = 0.002, respectively). There was a significant difference in MMP-1 concentration between the mild non-proliferative diabetic retinopathy (NPDR) group and the proliferative diabetic retinopathy (PDR) group (p = 0.012). MMP-1 concentrations were elevated in PRP-treated patients (p = 0.005). There was a significant difference in MMP-9 concentrations between the mild NPDR group and the PDR group (p < 0.001), and between the moderate and severe NPDR group and the PDR group (p < 0.001). The MMP-9 concentrations in PRP treated patients, DM patients with diabetes ≥ 10 years and recurrent DME within 3months were elevated (p = 0.023, p = 0.011, and p = 0.027, respectively). In correlation analyses, the MMP-1 level showed a significant correlation with age (r = -0.48, p = 0.01,), and the MMP-9 level showed significant correlations with axial length (r = -0.59, p < 0.01) and DM duration (r = 049, p = 0.01). Conclusions Concentrations of MMP-1 and MMP-9 were higher in the DME groups than in the control group. MMP-9 concentrations also differed depending on DR staging, DM duration, PRP treatment, and degree of axial myopia. MMP-9 may be more important than MMP-1 in the induction of DM complications in eyes. PMID:27467659

  10. Overexpression of membrane sialic acid-specific sialidase Neu3 inhibits matrix metalloproteinase-9 expression in vascular smooth muscle cells

    SciTech Connect

    Moon, Sung-Kwon; Cho, Seung-Hak; Kim, Kyung-Woon; Jeon, Jae Heung; Ko, Jeong-Heon; Kim, Bo Yeon; Kim, Cheorl-Ho . E-mail: chkimbio@skku.edu

    2007-05-11

    The ganglioside-specific sialidase Neu3 has been suggested to participate in cell growth, migration, and differentiation. Recent reports suggest that sialidase may be involved in intimal thickening, an early stage in the development of atherosclerosis. However, the role of the Neu3 gene in vascular smooth muscle cells (VSMC) responses has not yet been elucidated. To determine whether a Neu3 is able to modulate VSMC growth, the effect of overexpression of the Neu3 gene on cell proliferation was examined. However, the results show that the overexpression of this gene has no effect on DNA synthesis and ERK phosphorylation in cultured VSMC in the presence of TNF-{alpha}. Because atherogenic effects need not be limited to proliferation, we decided to examine whether Neu3 exerted inhibitory effects on matrix metalloproteinase-9 (MMP-9) activity in TNF-{alpha}-induced VSMC. The expression of the Neu3 gene led to the inhibition of TNF-{alpha}-induced matrix metalloproteinase-9 (MMP-9) expression in VSMC as determined by zymography and immunoblot. Furthermore, Neu3 gene expression strongly decreased MMP-9 promoter activity in response to TNF-{alpha}. This inhibition was characterized by the down-regulation of MMP-9, which was transcriptionally regulated at NF-{kappa}B and activation protein-1 (AP-1) sites in the MMP-9 promoter. These findings suggest that the Neu3 gene represents a physiological modulator of VSMC responses that may contribute to plaque instability in atherosclerosis.

  11. The Effects of Matrix Metalloproteinase-9 on Dairy Goat Mastitis and Cell Survival of Goat Mammary Epithelial Cells

    PubMed Central

    Li, Hui; Zheng, Huiling; Li, Lihui; Shen, Xingai; Zang, Wenjuan; Sun, Yongsen

    2016-01-01

    Matrix metalloproteinase-9 (MMP-9) is a zinc-dependent enzyme, and plays a crucial role in extracellular matrix degeneration, inflammation and tissue remodeling. However, the relationship between MMP-9 and somatic cell count (SCC) in goat milk and the role of MMP-9 in the regulation of mastitis are still unknown. In this study, we found MMP-9 was predominantly expressed in the spleen, intestine and mammary gland. The SCC in goat milk was positively correlated with MMP-9 expression, and staphylococcus aureus could markedly increase MMP-9 expression in goat mammary epithelial cells (GMEC) in dosage and time dependent manner. We also demonstrated that SB-3CT, an inhibitor of MMP-9, promoted apoptosis and inhibited proliferation in GMEC. Thus, MMP-9 may emerge as an easily measurable and sensitive parameter that reflects the number of somatic cells present in milk and a regulatory factor of apoptosis in GMEC. PMID:27518717

  12. The Effects of Matrix Metalloproteinase-9 on Dairy Goat Mastitis and Cell Survival of Goat Mammary Epithelial Cells.

    PubMed

    Li, Hui; Zheng, Huiling; Li, Lihui; Shen, Xingai; Zang, Wenjuan; Sun, Yongsen

    2016-01-01

    Matrix metalloproteinase-9 (MMP-9) is a zinc-dependent enzyme, and plays a crucial role in extracellular matrix degeneration, inflammation and tissue remodeling. However, the relationship between MMP-9 and somatic cell count (SCC) in goat milk and the role of MMP-9 in the regulation of mastitis are still unknown. In this study, we found MMP-9 was predominantly expressed in the spleen, intestine and mammary gland. The SCC in goat milk was positively correlated with MMP-9 expression, and staphylococcus aureus could markedly increase MMP-9 expression in goat mammary epithelial cells (GMEC) in dosage and time dependent manner. We also demonstrated that SB-3CT, an inhibitor of MMP-9, promoted apoptosis and inhibited proliferation in GMEC. Thus, MMP-9 may emerge as an easily measurable and sensitive parameter that reflects the number of somatic cells present in milk and a regulatory factor of apoptosis in GMEC. PMID:27518717

  13. Significance of Circulating and Crevicular Matrix Metalloproteinase-9 in Rheumatoid Arthritis-Chronic Periodontitis Association

    PubMed Central

    Silosi, Isabela; Cojocaru, Manole; Foia, Lili; Boldeanu, Mihail Virgil; Petrescu, Florin; Biciusca, Viorel

    2015-01-01

    In the recent years, statistically significant associations between rheumatoid arthritis (RA) and periodontal disease have been identified. Emerging as a chronic inflammatory joint disease, RA displays various features and pathogenetic events similar to chronic periodontitis (CP). The purpose of this study was to evaluate the utility of determining systemic and crevicular levels of metalloproteinase-9 (MMP-9) as potential biomarkers for association between RA and CP. A total of fifty-six patients were included in the study. The subjects were categorized into four groups as follows: healthy-control (n = 21), active RA (n = 16), CP (n = 14), and RA-CP association (n = 12). Assessment of serum and crevicular concentrations of total MMP-9 (active and pro-MMP-9) was based on ELISA technique. The results of this study showed statistically significant differences of serum MMP-9 between patients groups and control. Serum levels of MMP-9 were similar in RA and RA-CP associated patients. Gingival crevicular fluid (GCF) recorded increased MMP-9 levels in RA-CP association subjects as compared to CP. Considering that RA-CP association is characterized by a disregulation of the inflammatory response, MMP-9 may play a role in the pathogenesis of RA-CP association. MMP-9 is therefore a sensitive tool in the diagnosis and management of patients affected by this binomial association. PMID:25821836

  14. Significance of circulating and crevicular matrix metalloproteinase-9 in rheumatoid arthritis-chronic periodontitis association.

    PubMed

    Silosi, Isabela; Cojocaru, Manole; Foia, Lili; Boldeanu, Mihail Virgil; Petrescu, Florin; Surlin, Petra; Biciusca, Viorel

    2015-01-01

    In the recent years, statistically significant associations between rheumatoid arthritis (RA) and periodontal disease have been identified. Emerging as a chronic inflammatory joint disease, RA displays various features and pathogenetic events similar to chronic periodontitis (CP). The purpose of this study was to evaluate the utility of determining systemic and crevicular levels of metalloproteinase-9 (MMP-9) as potential biomarkers for association between RA and CP. A total of fifty-six patients were included in the study. The subjects were categorized into four groups as follows: healthy-control (n = 21), active RA (n = 16), CP (n = 14), and RA-CP association (n = 12). Assessment of serum and crevicular concentrations of total MMP-9 (active and pro-MMP-9) was based on ELISA technique. The results of this study showed statistically significant differences of serum MMP-9 between patients groups and control. Serum levels of MMP-9 were similar in RA and RA-CP associated patients. Gingival crevicular fluid (GCF) recorded increased MMP-9 levels in RA-CP association subjects as compared to CP. Considering that RA-CP association is characterized by a disregulation of the inflammatory response, MMP-9 may play a role in the pathogenesis of RA-CP association. MMP-9 is therefore a sensitive tool in the diagnosis and management of patients affected by this binomial association. PMID:25821836

  15. Matrix Metalloproteinase-9 −1562C/T Gene Polymorphism Is Associated with Diabetic Nephropathy

    PubMed Central

    Feng, Shufen; Ye, Gang; Bai, Shi; Liao, Xueling; Li, Lu

    2016-01-01

    To investigate the association between the metalloproteinase-9 (MMP9) −1562C/T polymorphism and diabetic nephropathy (DN) in Han Chinese, the patients with type 2 diabetes were collected and divided into the non-DN (NDN) and DN groups; controls were recruited. Genotype and allele frequencies were assessed using polymerase chain reaction and restriction fragment length polymorphism. Results showed that SBP, DBP, HbA1c, UAER, Cr, BUN, TG, and TC were higher in the DN group compared with the control and NDN groups. SBP, HbA1c, and TC in DN patients with the TT and CT genotypes were lower than in those with CC. Compared with controls, the frequency of the T allele in the DN group was significantly lower. The MMP9 −1562C allele, SBP, Cr, BUN, TG, and TC were independent risk factors for DN. All of the above suggested that the MMP9 −1562C/T polymorphism was associated with DN in Han Chinese.

  16. Colocalisation of matrix metalloproteinase-9-mRNA and protein in human colorectal cancer stromal cells.

    PubMed Central

    Zeng, Z. S.; Guillem, J. G.

    1996-01-01

    The matrix metalloproteinases (MMPs) are perceived as essential for tumour invasion and metastases. The purpose of this study was to determine the expression and cellular localisation of the 92 kDa type IV collagenase (MMP-9) protein and mRNA in human colorectal cancer (CRC). In CRC and matched normal mucosa specimens from 26 CRC patients, Northern blot hybridisation and Western blot analyses provide convincing evidence that MMP-9 is expressed in greater quantities in CRC than in normal tissue. The MMP-9 tumour to normal mucosa fold-increase (T/N) was 9.7 +/- 7.1 (mean +/- s.d.) (P < 0.001) for RNA and 7.1 +/- 3.9 (P < 0.001) for protein. The sites of MMP-9 mRNA and protein synthesis were colocalised in tumour stroma by in situ hybridisation and immunohistochemistry in 26 CRC samples. Both MMP-9 mRNA and protein signals were strongest in the population of stromal cells concentrated at the tumour-stroma interface of an invading tumour. Furthermore, MMP-9-positive cells were identified as macrophages using an antimacrophage antibody (KP1) in serial sections from ten CRC samples. Given the persistent localisation of MMP-9-producing macrophages to the interphase between CRC and surrounding stroma, our observations suggest that MMP-9 production is controlled, in part, by tumour-stroma cell interactions. Further studies are needed to determine the in vivo regulation of MMP-9 production from infiltrating peritumour macrophages. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:8883399

  17. Matrix metalloproteinase-9 plays a role in protecting zebrafish from lethal infection with Listeria monocytogenes by enhancing macrophage migration.

    PubMed

    Shan, Ying; Zhang, Yikai; Zhuo, Xunhui; Li, Xiaoliang; Peng, Jinrong; Fang, Weihuan

    2016-07-01

    Zebrafish could serve as an alternative animal model for pathogenic bacteria in multiple infectious routes. Our previous study showed that immersion infection in zebrafish with Listeria monocytogenes did not cause lethality but induced transient expression of several immune response genes. We used an Affymetrix gene chip to examine the expression profiles of genes of zebrafish immersion-infected with L. monocytogenes. A total of 239 genes were up-regulated and 56 genes down-regulated compared with uninfected fish. Highest expression (>20-fold) was seen with the mmp-9 gene encoding the matrix metalloproteinase-9 (Mmp-9) known to degrade the extracellular matrix proteins. By morpholino knockdown of mmp-9, we found that the morphants showed rapid death with much higher bacterial load after intravenous or intraventricular (brain ventricle) infection with L. monocytogenes. Macrophages in mmp-9-knockdown morphants had significant defect in migrating to the brain cavity upon intraventricular infection. Decreased migration of murine macrophages with knockdown of mmp-9 and cd44 was also seen in transwell inserts with 8-μm pore polycarbonate membrane, as compared with the scrambled RNA. These findings suggest that Mmp-9 is a protective molecule against infection by L. monocytogenes by engaging in migration of zebrafish macrophages to the site of infection via a non-proteolytic role. Further work is required on the molecular mechanisms governing Mmp-9-driven macrophage migration in zebrafish. PMID:27068748

  18. Adiponectin inhibits oxidized low density lipoprotein-induced increase in matrix metalloproteinase 9 expression in vascular smooth muscle cells

    PubMed Central

    Saneipour, Maryam; Ghatreh-Samani, Keihan; Heydarian, Esfandiar; Farrokhi, Effat; Abdian, Narges

    2015-01-01

    BACKGROUND High expression of matrix metalloproteinase 9 (MMP9) during vascular injury and inflammation plays an important role in atherosclerotic plaque formation and rupture. In the process of atherosclerosis, oxidized low-density lipoprotein (oxLDL) upregulates MMP9 in human aortic vascular smooth muscle cells (HA/VSMCs). Adiponectin is an adipose tissue-derived hormone that has been shown to exert anti-atherogenic and anti-inflammatory effects. The aim of this study was to investigate the effect of adiponectin on MMP9 expression under pathogenic condition created by oxLDL in HA/VSMCs. METHODS In this experimental study, HA/VSMC were stimulated with oxLDL alone and in the presence of adiponectin for 24 and 48 h. The expression of MMP9 gene was determined by real-time polymerase chain reaction method. The protein level of this gene was investigated by western blotting technique. RESULTS An oxLDL increased MMP9 expression 2.16 ± 0.24- and 3.32 ± 0.25-fold after 24 and 48 h, respectively and adiponectin decreased oxLDL-induced MMP9 expression in a time-dependent manner. CONCLUSION These results show that adiponectin changes extracellular matrix by reducing MMP9 mRNA and protein, therefore, may stabilize lesions and reduce atheroma rupture. PMID:26405452

  19. Matrix metalloproteinase-9 deficiency impairs host defense mechanisms against Streptococcus pneumoniae in a mouse model of bacterial meningitis.

    PubMed

    Böttcher, Tobias; Spreer, Annette; Azeh, Ivo; Nau, Roland; Gerber, Joachim

    2003-03-01

    Matrix metalloproteinase-9 (MMP-9) appears to contribute to blood-brain barrier damage and neuronal injury in bacterial meningitis. To further explore the function of MMP-9 in meningeal inflammation, we injected 10(4) colony forming units (CFU) of a Streptoccocus pneumoniae type 3 strain into the right forebrain of MMP-9 deficient mice (MMP-9(-/-), n=16) and wild-type controls (129 x B6, n=15). The clinical course of the disease, leukocyte recruitment into the subarachnoid space and bacterial titers in the brain did not differ. Yet, clearance of the bacteria from blood (log CFU/ml 4.7 [3.8/5.4] vs. 3.6 [3.0/4.0]; P=0.005) and spleen homogenates (log CFU/ml 5.3 [4.8/5.5] vs. 4.0 [2.8/4.7]; P=0.01) was reduced in MMP-9 deficient mice. A reduced systemic bacterial clearance of MMP-9(-/-) mice was confirmed in experimental S. pneumoniae peritonitis/sepsis. This implies a compromised systemic, but not intracerebral host response against S. pneumoniae in MMP-9 deficiency. PMID:12581831

  20. Matrix metalloproteinase-9 (MMP-9) in human cerebrospinal fluid (CSF): elevated levels are primarily related to CSF cell count.

    PubMed

    Yushchenko, M; Weber, F; Mäder, M; Schöll, U; Maliszewska, M; Tumani, H; Felgenhauer, K; Beuche, W

    2000-10-01

    Matrix metalloproteinase-9 (MMP-9) was investigated by enzyme-linked immunosorbent assay (ELISA) and zymography in 111 paired CSF and serum samples from patients with various neurological disorders. In 20 patients with blood-brain barrier (BBB) impairment but normal CSF cell count, elevated levels of MMP-9 were not observed by ELISA measurement. Another 11 patients characterized in the same way, exhibited only slightly increased MMP-9 levels. In contrast, in 12 patients with intact BBB but elevated CSF cell count, MMP-9 was increased too. It was shown by the more sensitive zymography that MMP-9 increased if CSF cell count exceeded five cells per microl. Spearman rank statistics revealed that MMP-9 concentration in CSF correlated with CSF cell count (r=0.755; P<0.0001), but not with CSF/serum albumin ratio (Q(Alb)) (r=0.212; P=0.057), a measure for BBB impairment. Moreover, the CSF/serum MMP-9 ratio (Q(MMP-9)) did not correlate with Q(Alb)(r=0.192; P=0.100). By use of a Boyden chamber, in which granulocytes migrated through a reconstituted basement membrane, it was demonstrated that the MMP-9 concentration in the lower chamber correlated very significantly with the number of accumulated cells (r(2)=0.7692; P<0.0001). The meaning of the increase of MMP-9 in CSF is critically discussed. PMID:11024556

  1. Relation of dietary inorganic arsenic to serum matrix metalloproteinase-9 (MMP-9) at different threshold concentrations of tap water arsenic.

    PubMed

    Kurzius-Spencer, Margaret; Harris, Robin B; Hartz, Vern; Roberge, Jason; Hsu, Chiu-Hsieh; O'Rourke, Mary Kay; Burgess, Jefferey L

    2016-09-01

    Arsenic (As) exposure is associated with cancer, lung and cardiovascular disease, yet the mechanisms involved are not clearly understood. Elevated matrix metalloproteinase-9 (MMP-9) levels are also associated with these diseases, as well as with exposure to water As. Our objective was to evaluate the effects of dietary components of inorganic As (iAs) intake on serum MMP-9 concentration at differing levels of tap water As. In a cross-sectional study of 214 adults, dietary iAs intake was estimated from 24-h dietary recall interviews using published iAs residue data; drinking and cooking water As intake from water samples and consumption data. Aggregate iAs intake (food plus water) was associated with elevated serum MMP-9 in mixed model regression, with and without adjustment for covariates. In models stratified by tap water As, aggregate intake was a significant positive predictor of serum MMP-9 in subjects exposed to water As≤10 μg/l. Inorganic As from food alone was associated with serum MMP-9 in subjects exposed to tap water As≤3 μg/l. Exposure to iAs from food and water combined, in areas where tap water As concentration is ≤10 μg/l, may contribute to As-induced changes in a biomarker associated with toxicity. PMID:25605447

  2. Relation of dietary inorganic arsenic to serum matrix metalloproteinase-9 (MMP-9) at different threshold concentrations of tap water arsenic

    PubMed Central

    Kurzius-Spencer, Margaret; Harris, Robin B.; Hartz, Vern; Roberge, Jason; Hsu, Chiu-Hsieh; O’Rourke, Mary Kay; Burgess, Jefferey L.

    2015-01-01

    Arsenic (As) exposure is associated with cancer, lung and cardiovascular disease, yet the mechanisms involved are not clearly understood. Elevated matrix metalloproteinase-9 (MMP-9) levels are also associated with these diseases, as well as with exposure to water As. Our objective was to evaluate the effects of dietary components of inorganic As (iAs) intake on serum MMP-9 concentration at differing levels of tap water As. In a cross-sectional study of 214 adults, dietary iAs intake was estimated from 24-h dietary recall interviews using published iAs residue data; drinking and cooking water As intake from water samples and consumption data. Aggregate iAs intake (food plus water) was associated with elevated serum MMP-9 in mixed model regression, with and without adjustment for covariates. In models stratified by tap water As, aggregate intake was a significant positive predictor of serum MMP-9 in subjects exposed to water As ≤10 μg/l. Inorganic As from food alone was associated with serum MMP-9 in subjects exposed to tap water As ≤3 μg/l. Exposure to iAs from food and water combined, in areas where tap water As concentration is ≤10 μg/l, may contribute to As-induced changes in a biomarker associated with toxicity. PMID:25605447

  3. Puerarin Attenuated Early Diabetic Kidney Injury through Down-Regulation of Matrix Metalloproteinase 9 in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Zhong, Yifei; Zhang, Xianwen; Cai, Xianfan; Wang, Ke; Chen, Yiping; Deng, Yueyi

    2014-01-01

    Radix puerariae, a traditional Chinese herbal medication, has been used successfully to treat patients with early stage of diabetic nephropathy. However, the underlined mechanism of this renal protective effect has not been determined. In the current study, we investigated the effects and the mechanism of puerarin in Streptozotocin (STZ)-induced diabetic rats. We treated STZ-rats with either puerarin or losartan, an angiotensin II receptor blocker, as compared to those treated with vehicle. We found that both puerarin and losartan attenuated kidney hypertrophy, mesangial expansion, proteinuria, and podocyte foot process effacement in STZ rats. In addition, both puerarin and losartan increased expression of podocyte slit diaphragm proteins such as nephrin and podocin. Interestingly, we found that puerarin treatment induced a more pronounced suppression of oxidative stress production and S-nitrosylation of proteins in the diabetic kidneys as compared to losartan treatment. Furthermore, we found that matrix metalloproteinase-9 (MMP-9), which is known to be activated by oxidative stress and S-nitrosylation of proteins, was also suppressed more extensively by puerarin than losartan. In conclusion, these data provide for the first time the potential mechanism to support the use of puerarin in the treatment of early diabetic nephropathy. PMID:24454919

  4. Ophiopogonin-D suppresses MDA-MB-435 cell adhesion and invasion by inhibiting matrix metalloproteinase-9.

    PubMed

    Zhang, Yuanyuan; Han, Yuwei; Zhai, Kefeng; Sun, Minhui; Liu, Jihua; Yu, Boyang; Kou, Junping

    2015-07-01

    Ophiopogonin-D is one of steroidal saponins isolated from the root of the Chinese medicinal plant Ophiopogon japonicas. It has been claimed to possess anti-inflammatory and anti-oxidant properties. The present study was the first to examine the anti-tumor metastasis properties of ophiopogonin-D. An MTT assay showed that ophiopogonin-D inhibited the proliferation of MDA-MB-435 melanoma cells, and decreased invasion was demonstrated using a Transwell invasion assay. Furthermore, adhesion of MDA-MB-435 cells to human umbilical vascular endothelial cells and to fibronectin was inhibited by ophiopogonin-D. Gelatin zymography and western blot analysis showed that ophiopogonin-D inhibited the expression and secretion of matrix metalloproteinase-9 (MMP-9), but not that of MMP-2. Inhibition of phosphorylation of p38 by ophiopogonin-D indicated its inhibition of the mitogen-activated protein kinase pathway. Overall, the results suggested that ophiopogonin-D may be considered as a candidate drug for treating or preventing tumor metastasis. PMID:25816153

  5. Influence of Malondialdehyde and Matrix Metalloproteinase-9 on Progression of Carotid Atherosclerosis in Chronic Renal Disease with Cardiometabolic Syndrome

    PubMed Central

    Rašić, Senija; Rebić, Damir; Hasić, Sabaheta; Rašić, Ismar; Delić Šarac, Marina

    2015-01-01

    Objective was to assess whether the concentration of malondialdehyde (MDA) as a marker of lipid peroxidation and serum concentration of matrix metalloproteinase-9 (MMP-9) are involved in the process of atherosclerosis in chronic kidney disease (CKD) patients nondialysis-dependent and those on peritoneal dialysis (PD), both with signs of cardiometabolic syndrome (CMS). Thirty CKD and 22 PD patients were included in a study. All observed patients were divided into three subgroups depending on the degree of atherosclerotic changes in the carotid arteries (CA). Severity of atherosclerotic changes in the CA was evaluated by ultrasonography. We confirmed significantly lower level of serum MDA throughout all the stages of atherosclerosis in PD patients compared with observed CKD patients (P < 0.05) and increased serum concentration of MDA and MMP-9 with the progression of severity atherosclerotic changes in both groups of patients. The multiple regression analysis revealed that MDA and MMP-9 are significant predictors of changes in IMT-CA CKD patients (P < 0.05) and plaque score on CA in these patients (P < 0.05). The results suggest that MDA and MMP-9 could be mediators of CKD-related vascular remodeling in CMS. PMID:26538831

  6. Luteolin inhibits matrix metalloproteinase 9 and 2 in azoxymethane-induced colon carcinogenesis.

    PubMed

    Pandurangan, A K; Dharmalingam, P; Sadagopan, S K A; Ganapasam, S

    2014-11-01

    The present investigation deals with the antimetastatic role of luteolin (LUT) by inhibiting matrix metalloproteinase (MMP)-9 and -2 in azoxymethane (AOM)-induced colon carcinogenesis in Balb/C mice. Animals received AOM at a dosage of 15 mg/kg body weight intraperitoneally once a week for 3 weeks. AOM-induced mice was treated with LUT (1.2 mg of LUT/kg body weight/day orally). After the experimental period, the tumor markers such as γ-glutamyl transferase (GGT), 5' nucleotidase (5'ND), cathepsin-D (Cat-D), and carcinoembroyonic antigen (CEA) were elevated upon induction with AOM. Subsequent treatment with LUT results in the reduction of the tumor markers was recorded. The expressions of MMP-9 and MMP-2 were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence methods. The expressions of MMP-9 and MMP-2 were increased during AOM induction and upon treatment with LUT reduced the expressions. RT-PCR analysis of tissue inhibitor of matrix metalloproteinase (TIMP)-2 was limited during AOM-induced colorectal cancer (CRC). Supplementation of LUT increased the expression of TIMP-2. To conclude, LUT acts as an antimetastatic agent by suppressing MMP-9 and MMP-2 productions and upregulating TIMP-2 expression, thereby suggesting that LUT can be a chemotherapeutic agent against CRC. PMID:24532706

  7. Classically Activated Macrophages Use Stable Microtubules for Matrix Metalloproteinase-9 (MMP-9) Secretion*

    PubMed Central

    Hanania, Raed; Song Sun, He; Xu, Kewei; Pustylnik, Sofia; Jeganathan, Sujeeve; Harrison, Rene E.

    2012-01-01

    As major effector cells of the innate immune response, macrophages must adeptly migrate from blood to infected tissues. Endothelial transmigration is accomplished by matrix metalloproteinase (MMP)-induced degradation of basement membrane and extracellular matrix components. The classical activation of macrophages with LPS and IFN-γ causes enhanced microtubule (MT) stabilization and secretion of MMPs. Macrophages up-regulate MMP-9 expression and secretion upon immunological challenge and require its activity for migration during the inflammatory response. However, the dynamics of MMP-9 production and intracellular distribution as well as the mechanisms responsible for its trafficking are unknown. Using immunofluorescent imaging, we localized intracellular MMP-9 to small Golgi-derived cytoplasmic vesicles that contained calreticulin and protein-disulfide isomerase in activated RAW 264.7 macrophages. We demonstrated vesicular organelles of MMP-9 aligned along stable subsets of MTs and showed that selective modulation of MT dynamics contributes to the enhanced trafficking of MMP-9 extracellularly. We found a Rab3D-dependent association of MMP-9 vesicles with the molecular motor kinesin, whose association with the MT network was greatly enhanced after macrophage activation. Finally, we implicated kinesin 5B and 3B isoforms in the effective trafficking of MMP-9 extracellularly. PMID:22270361

  8. Matrix Metalloproteinase-9: Its Interplay with Angiogenic Factors in Inflammatory Bowel Diseases

    PubMed Central

    Gamian, Andrzej; Krzystek-Korpacka, Malgorzata

    2014-01-01

    Matrix metalloproteinase- (MMP-) 9 is one of the main metalloproteinases reported to be involved in extracellular matrix degradation and recently also in triggering of angiogenic switch in the course of inflammatory bowel diseases (IBD). The goal of our studies was to estimate in one experimental setting the levels of MMP-9 in sera of Crohn's Disease (CD) and ulcerative colitis (UC) patients and to evaluate its possible diagnostic potential in comparison with other biochemical markers and selected proinflammatory and angiogenic factors. The study group included 176 subjects (CD = 64, UC = 85, control = 27). Concentrations of serum MMP-9 were significantly higher in active than inactive forms of IBD, being higher in active UC than in active CD. Both in the case of CD and UC serum MMP-9 positively correlated with disease activity, IL-6 levels, platelet and leukocyte count, midkine, and PDGF-BB, as well as in UC with ESR and in CD with CRP, IL-1, and VEGF-A. Diagnostic accuracy of MMP-9 in distinguishing active UC from active CD was 66%, and displayed higher specificity than CRP (79.0% versus 61.6%, resp.). Evaluation of serum MMP-9 concentrations could aid in differentiation of active UC from active CD. MMP-9 correlated better with inflammatory and angiogenic parameters in CD than in UC. PMID:24803722

  9. Polymorphism, Genetic Effect and Association with Egg Production Traits of Chicken Matrix Metalloproteinases 9 Promoter

    PubMed Central

    Zhu, Guiyu; Jiang, Yunliang

    2014-01-01

    Matrix metalloproteinases (MMP) are key enzymes involved in cell and tissue remodeling during ovarian follicle development and ovulation. The control of MMP9 transcription in ovarian follicles occurs through a core promoter region (−2,400 to −1,700 bp). The aim of this study was to screen genetic variations in the core promoter region and examine MMP9 transcription regulation and reproduction performance. A single cytosine deletion/insertion polymorphism was found at −1954 C+/C−. Genetic association analysis indicated significant correlation between the deletion genotype (C−) with total egg numbers at 28 weeks (p = 0.031). Furthermore, luciferase-reporter assay showed the deletion genotype (C−) had significantly lower promoter activity than the insertion genotype (C+) in primary granulosa cells (p<0.01). Therefore, the identified polymorphism could be used for marker-assisted selection to improve chicken laying performance. PMID:25358310

  10. Airway Remodeling in Chronic Obstructive Pulmonary Disease and Asthma: the Role of Matrix Metalloproteinase-9.

    PubMed

    Grzela, Katarzyna; Litwiniuk, Malgorzata; Zagorska, Wioletta; Grzela, Tomasz

    2016-02-01

    Chronic obstructive pulmonary disease (COPD) and asthma are both associated with airflow restriction and progressive remodeling, which affect the respiratory tract. Among various biological factors involved in the pathomechanisms of both diseases, proteolytic enzymes--matrix metalloproteinases (MMPs)--play an important role, especially MMP-9. In this review, the authors discuss the current topics of research concerning the possible role of MMP-9 in both mentioned diseases. They include the analysis of protein levels, nucleotide polymorphisms of MMP-9 gene and their possible correlation with asthma and COPD. Finally, the authors refer to the studies on MMP-9 inhibition as a new perspective for increasing the effectiveness of treatment in asthma and COPD. PMID:26123447

  11. Thymocyte development in the absence of matrix metalloproteinase-9/gelatinase B

    PubMed Central

    Gounko, Natalia V.; Martens, Erik; Opdenakker, Ghislain; Rybakin, Vasily

    2016-01-01

    Matrix metalloproteinases (MMP) play critical roles in a variety of immune reactions by facilitating cell migration, and affect cell communication by processing both cytokines and cell surface receptors. Based on published data indicating that MMP-9 is upregulated upon T cell activation and also in the thymus upon the induction of negative selection, we investigated the contribution of MMP-9 into mouse T cell development and differentiation in the thymus. Our data suggest that MMP-9 deficiency does not result in major abnormalities in the development of any conventionally selected or agonist selected subsets and does not interfere with thymocyte apoptosis and clearance, and that MMP-9 expression is not induced in immature T cells at any stage of their thymic development. PMID:27432536

  12. INDUCTION BY EPIDERMOPHYTON FLOCCOSUM OF HUMAN FIBROBLAST MATRIX METALLOPROTEINASE-9 SECRETION IN VITRO.

    PubMed

    Kitisin, Thitinan; Luplertlop, Natthanej

    2015-03-01

    Skin infection from pathogenic dermatophyte, Epidermophytonfloccosum, can cause serious health complications, especially in immuno-compromised patients. Proteolytic enzymes secreted from E. floccosum are required for host tissue degradation, facilitating fungal invasion. However, little is known regarding host matrix metalloproteinase (MMP) expression during E. floccosum infection. In this study human foreskin fibroblast (HFF) cell line was used to determine MMP-9 protease activity by gelatin zymography and amount by ELISA. E. floccosum-induced HFF secretion of MMP-9 in a time dependent manner, but HFF cell viability decreased. Treatment with an MMP inhibitor (SB-3CT) caused reduction in E. floccosum-induced secreted MMP-9 and improvement in HFF cell viability. These findings indicate a possible control measure for protecting skin from E. floccosum infection. PMID:26513930

  13. Increased Expression of Intranuclear Matrix Metalloproteinase 9 in Atrophic Renal Tubules Is Associated with Renal Fibrosis

    PubMed Central

    Tsai, Jen-Pi; Liou, Jia-Hung; Kao, Wei-Tse; Wang, Shao-Chung; Lian, Jong-Da; Chang, Horng-Rong

    2012-01-01

    Background Reduced turnover of extracellular matrix has a role in renal fibrosis. Matrix metalloproteinases (MMPs) is associated with many glomerular diseases, but the histological association of MMPs and human renal fibrosis is unclear. Methods This is a retrospective study. Institutional Review Board approval was obtained for the review of patients’ medical records, data analysis and pathological specimens staining with waiver of informed consents. Specimens of forty-six patients were examined by immunohistochemical stain of MMP-9 in nephrectomized kidneys, and the association of renal expression of MMP-9 and renal fibrosis was determined. MMP-9 expression in individual renal components and fibrosis was graded as high or low based on MMP-9 staining and fibrotic scores. Results Patients with high interstitial fibrosis scores (IFS) and glomerular fibrosis scores (GFS) had significantly higher serum creatinine, lower estimated glomerular filtration rate (eGFR), and were more likely to have chronic kidney disease (CKD) and urothelial cell carcinoma. Univariate analysis showed that IFS and GFS were negatively associated with normal and atrophic tubular cytoplasmic MMP-9 expression and IFS was positively correlated with atrophic tubular nuclear MMP-9 expression. Multivariate stepwise regression indicated that MMP-9 expression in atrophic tubular nuclei (r = 0.4, p = 0.002) was an independent predictor of IFS, and that MMP-9 expression in normal tubular cytoplasm (r = −0.465, p<0.001) was an independent predictor of GFS. Conclusions Interstitial fibrosis correlated with MMP-9 expression in the atrophic tubular nuclei. Our results indicate that renal fibrosis is associated with a decline of MMP-9 expression in the cytoplasm of normal tubular cells and increased expression of MMP-9 in the nuclei of tubular atrophic renal tubules. PMID:23110201

  14. Matrix metalloproteinase-9 deletion attenuates myocardial fibrosis and diastolic dysfunction in ageing mice

    PubMed Central

    Chiao, Ying Ann; Ramirez, Trevi A.; Zamilpa, Rogelio; Okoronkwo, S. Michelle; Dai, Qiuxia; Zhang, Jianhua; Jin, Yu-Fang; Lindsey, Merry L.

    2012-01-01

    Aims Age-related diastolic dysfunction has been attributed to an increased passive stiffness, which is regulated by extracellular matrix (ECM). We recently showed that matrix metalloproteinase (MMP)-9, an ECM mediator, increases in the left ventricle (LV) with age. The aim of this study, accordingly, was to determine the role of MMP-9 in cardiac ageing. Methods and results We compared LV function in young (6–9 months), middle-aged (12–15 months), old (18–24 months) and senescent (26–34 months) wild-type (WT) and MMP-9 null mice (n ≥ 12/group). All groups had similar fractional shortenings and aortic peak velocities, indicating that systolic function was not altered by ageing or MMP-9 deletion. The mitral ratios of early to late diastolic filling velocities were reduced in old and senescent WT compared with young controls, and this reduction was attenuated in MMP-9 null mice. Concomitantly, the increase in LV collagen content was reduced in MMP-9 null mice (n = 5-6/group). To dissect the mechanisms of these changes, we evaluated the mRNA expression levels of 84 ECM and adhesion molecules by real-time qPCR (n = 6/group). The expression of pro-fibrotic periostin and connective tissue growth factor (CTGF) increased with senescence, as did transforming growth factor-β (TGF-β)-induced protein levels and Smad signalling, and these increases were blunted by MMP-9 deletion. In senescence, MMP-9 deletion also resulted in a compensatory increase in MMP-8. Conclusion MMP-9 deletion attenuates the age-related decline in diastolic function, in part by reducing TGF-β signalling-induced periostin and CTGF expression and increasing MMP-8 expression to regulate myocardial collagen turnover and deposition. PMID:22918978

  15. Associations of Matrix Metalloproteinase-9 and Tissue Inhibitory Factor-1 Polymorphisms With Parkinson Disease in Taiwan.

    PubMed

    Chen, Yi-Chun; Wu, Yih-Ru; Mesri, Mina; Chen, Chiung-Mei

    2016-02-01

    Matrix metalloproteinases (MMPs) function in the degradation of extracellular matrix and are considered to play a role in the pathogenesis of neurodegenerative diseases including Parkinson disease (PD). MMPs activities are modulated by tissue inhibitors of metalloproteinases (TIMPs). This study examined whether the genetic polymorphisms of MMP-3, gelatinase (MMP-2 and MMP-9), TIMP-2, and TIMP-1 were associated with PD in Taiwan.A total of 359 PD patients and 332 controls were enrolled. The candidate genetic variants included MMP-2 rs2285053 (-735 C > T), MMP-3 rs3025058 (-1171 5A > 6A), MMP-9 rs3918241 (-1831 T > A), rs17576 (G > A, R279Q), and rs3787268 (G > A, intron), TIMP-1 rs4898 (T > C, F124F), and TIMP-2 rs7503607 (-269 G > T). Associations were tested by logistic regression, adjusted with gender and age at onset.Minor allele frequency of TIMP-1 rs4898 (36.0%) was significantly lower in the male PD patients than in the male controls (51.2%) (χ test, P = 0.004). When adjusted with gender and age at onset, MMP-9 rs17576 AA genotype was associated with PD susceptibility in a recessive fashion (odds ratios [OR] = 2.28, 95% confidence intervals [95% CI] = 1.12-4.62, P = 0.02). In males, TIMP-1 rs4898 C allele was associated with a protective effect on PD (OR = 0.75, 95% CI = 0.60-0.94, P = 0.014). We did not find association between the examined genetic variants of MMP-2, MMP-3, and TIMP-2 and PD susceptibility.This is the first study that demonstrated a protective effect of TIMP-1 rs4898 C allele on male PD and a modest association of MMP-9 rs17576 AA genotype with PD susceptibility in the Taiwan population. Further replication is needed for confirmation. PMID:26844501

  16. Associations of Matrix Metalloproteinase-9 and Tissue Inhibitory Factor-1 Polymorphisms With Parkinson Disease in Taiwan

    PubMed Central

    Chen, Yi-Chun; Wu, Yih-Ru; Mesri, Mina; Chen, Chiung-Mei

    2016-01-01

    Abstract Matrix metalloproteinases (MMPs) function in the degradation of extracellular matrix and are considered to play a role in the pathogenesis of neurodegenerative diseases including Parkinson disease (PD). MMPs activities are modulated by tissue inhibitors of metalloproteinases (TIMPs). This study examined whether the genetic polymorphisms of MMP-3, gelatinase (MMP-2 and MMP-9), TIMP-2, and TIMP-1 were associated with PD in Taiwan. A total of 359 PD patients and 332 controls were enrolled. The candidate genetic variants included MMP-2 rs2285053 (−735 C > T), MMP-3 rs3025058 (−1171 5A > 6A), MMP-9 rs3918241 (−1831 T > A), rs17576 (G > A, R279Q), and rs3787268 (G > A, intron), TIMP-1 rs4898 (T > C, F124F), and TIMP-2 rs7503607 (−269 G > T). Associations were tested by logistic regression, adjusted with gender and age at onset. Minor allele frequency of TIMP-1 rs4898 (36.0%) was significantly lower in the male PD patients than in the male controls (51.2%) (χ2 test, P = 0.004). When adjusted with gender and age at onset, MMP-9 rs17576 AA genotype was associated with PD susceptibility in a recessive fashion (odds ratios [OR] = 2.28, 95% confidence intervals [95% CI] = 1.12–4.62, P = 0.02). In males, TIMP-1 rs4898 C allele was associated with a protective effect on PD (OR = 0.75, 95% CI = 0.60–0.94, P = 0.014). We did not find association between the examined genetic variants of MMP-2, MMP-3, and TIMP-2 and PD susceptibility. This is the first study that demonstrated a protective effect of TIMP-1 rs4898 C allele on male PD and a modest association of MMP-9 rs17576 AA genotype with PD susceptibility in the Taiwan population. Further replication is needed for confirmation. PMID:26844501

  17. Matrix Metalloproteinase-9 Is Required for Hippocampal Late-Phase Long-Term Potentiation and Memory

    PubMed Central

    Nagy, Vanja; Bozdagi, Ozlem; Matynia, Anna; Balcerzyk, Marcin; Okulski, Pawel; Dzwonek, Joanna; Costa, Rui M.; Silva, Alcino J.; Kaczmarek, Leszek; Huntley, George W.

    2015-01-01

    Matrix metalloproteinases (MMPs) are extracellular proteases that have well recognized roles in cell signaling and remodeling in many tissues. In the brain, their activation and function are customarily associated with injury or pathology. Here, we demonstrate a novel role for MMP-9 in hippocampal synaptic physiology, plasticity, and memory. MMP-9 protein levels and proteolytic activity are rapidly increased by stimuli that induce late-phase long-term potentiation (L-LTP) in area CA1. Such regulation requires NMDA receptors and protein synthesis. Blockade of MMP-9 pharmacologically prevents induction of L-LTP selectively; MMP-9 plays no role in, nor is regulated during, other forms of short-term synaptic potentiation or long-lasting synaptic depression. Similarly, in slices from MMP-9 null-mutant mice, hippocampal LTP, but not long-term depression, is impaired in magnitude and duration; adding recombinant active MMP-9 to null-mutant slices restores the magnitude and duration of LTP to wild-type levels. Activated MMP-9 localizes in part to synapses and modulates hippocampal synaptic physiology through integrin receptors, because integrin function-blocking reagents prevent an MMP-9-mediated potentiation of synaptic signal strength. The fundamental importance of MMP-9 function in modulating hippocampal synaptic physiology and plasticity is underscored by behavioral impairments in hippocampal-dependent memory displayed by MMP-9 null-mutant mice. Together, these data reveal new functions for MMPs in synaptic and behavioral plasticity. PMID:16481424

  18. Matrix Metalloproteinase-9 Mediates RSV Infection in Vitro and in Vivo

    PubMed Central

    Kong, Michele Y.F.; Whitley, Richard J.; Peng, Ning; Oster, Robert; Schoeb, Trenton R.; Sullender, Wayne; Ambalavanan, Namasivayam; Clancy, John Paul; Gaggar, Amit; Blalock, J. Edwin

    2015-01-01

    Respiratory Syncytial Virus (RSV) is an important human pathogen associated with substantial morbidity and mortality. The present study tested the hypothesis that RSV infection would increase matrix metalloproteinase (MMP)-9 expression, and that MMP-9 inhibition would decrease RSV replication both in vitro and in vivo. RSV A2 infection of human bronchial epithelial cells increased MMP-9 mRNA and protein release. Cells transfected with siRNA against MMP-9 following RSV infection had lower viral titers. In RSV infected wild-type (WT) mice, MMP-9, airway resistance and viral load peaked at day 2 post infection, and remained elevated on days 4 and 7. RSV infected MMP-9 knockout (KO) mice had decreased lung inflammation. On days 2 and 4 post inoculation, the RSV burden was lower in the MMP-9 KO mice compared to WT controls. In conclusion, our studies demonstrate that RSV infection is a potent stimulus of MMP-9 expression both in vitro and in vivo. Reduction of MMP-9 (via siRNA knockdown, and in MMP-9 KO mice) resulted in decreased viral replication. Our findings suggest MMP-9 is a potential therapeutic target for RSV disease. PMID:26264019

  19. On the structure and functions of gelatinase B/matrix metalloproteinase-9 in neuroinflammation.

    PubMed

    Vandooren, Jennifer; Van Damme, Jo; Opdenakker, Ghislain

    2014-01-01

    The blood-brain barrier (BBB) is a specific structure that is composed of two basement membranes (BMs) and that contributes to the control of neuroinflammation. As long as the BBB is intact, extravasated leukocytes may accumulate between two BMs, generating vascular cuffs. Specific matrix metalloproteinases, MMP-2 and MMP-9, have been shown to cleave BBB beta-dystroglycan and to disintegrate thereby the parenchymal BM, resulting in encephalomyelitis. This knowledge has been added to the molecular basis of the REGA model to understand the pathogenesis of multiple sclerosis, and it gives further ground for the use of MMP inhibitors for the treatment of acute neuroinflammation. MMP-9 is associated with central nervous system inflammation and occurs in various forms: monomers and multimers. None of the various neurological and neuropathologic functions of MMP-9 have been associated with either molecular structure or molecular form, and therefore, in-depth structure-function studies are needed before medical intervention with MMP-9-specific inhibitors is initiated. PMID:25410359

  20. Lung matrix metalloproteinase-9 correlates with cigarette smoking and obstruction of airflow.

    PubMed Central

    Kang, Min Jong; Oh, Yeon-Mok; Lee, Jae Cheol; Kim, Dong Gyu; Park, Myung Jae; Lee, Myung Goo; Hyun, In Gyu; Han, Sung Koo; Shim, Young-Soo; Jung, Ki-Suck

    2003-01-01

    Cigarette smoking is the most important risk factor for obstruction of airflow in chronic obstructive pulmonary disease (COPD). Matrix metalloproteinases (MMPs) or an imbalance between MMPs and their inhibitors, the tissue inhibitors of MMP (TIMPs), is considered to play a role in the pathogenesis of COPD. We investigated whether the MMPs expression or the imbalance between MMPs and TIMP-1 is associated with the amount of cigarette smoking and the FEV1 value, in the lung parenchyma of 26 subjects (6 non-smokers and 20 cigarette smokers). First, we performed zymographic analysis to identify the profile of the MMPs, which revealed gelatinolytic bands mainly equivalent to MMP-9 in the smokers. We then measured, using enzyme immunoassay, the concentrations of MMP-9 and its inhibitor, TIMP-1. Correlation analysis revealed that both the MMP-9 concentrations and the molar ratios of MMP-9 to TIMP-1 (MMP-9/TIMP-1) were correlated with the amount of cigarette smoking. Furthermore, MMP-9 concentrations were inversely correlated with FEV1. In conclusion, this study shows that MMP-9 expression in human lung parenchyma is associated with cigarette smoking and also with the obstruction of airflow, suggesting that MMP-9 may play a role in the pathogenesis of the cigarette smoke-induced obstruction of airflow known as the characteristic of COPD. PMID:14676438

  1. Investigation of RNA interference suppression of matrix metalloproteinase-9 in mouse model of atherosclerosis

    PubMed Central

    Jin, Zhe-Xiu; Xiong, Qiang; Jia, Fang; Sun, Chun-Ling; Zhu, Hong-Tao; Ke, Fu-Sheng

    2015-01-01

    Objective: To investigate the effect of RNA interference of matrix metalloproteinase (MMP)-9 on atherosclerosis on atherosclerosis in apolipoprotein E (ApoE)-/- mouse. Methods: ApoE-/- mouse strain and three cell lines (293T, NIH3T3 and Raw264.7) were used in the present study to investigate the effect of MMP-9 silencing by RNA interference. Thirty 10-week-old ApoE-/- mice were randomly assigned to a control group, lentiviruses with naked vector group and Lentiviruses-MMP-9 intervention group (n = 10). Aortic atherosclerotic plaques of the mice were stained with immunohistochemical techniques, the MMP-9 and high-sensitivity C-reactive protein levels of three groups were detected simultaneously. Expression of MMP-9 was significantly down-regulated in interference group. MMP-9 and high-sensitivity C-reactive protein levels in MMP-9 interference group were significantly lower than that of the control group. Conclusion: The expression of MMP-9 is closely related to vulnerability of atherosclerotic plaques. Silencing of MMP-9 expression acts as a positive role in maintenance of atherosclerotic plaque stability. The present study provides novel experimental insight for the treatment of vulnerable plaques in atherosclerosis. PMID:26131101

  2. Matrix metalloproteinase 9 (MMP-9) and biodegradable polymers in the engineering of a vascular construct

    NASA Astrophysics Data System (ADS)

    Sung, Hak-Joon

    The role of matrix metalloproteinase (MMP)-9 and processing conditions of biodegradable polymer scaffolds has been investigated to optimize engineering vascular constructs. For a small diameter vascular construct, uniform 10 mum thickness of highly porous scaffolds were developed using a computer-controlled knife coater and exploiting phase transition properties of salts. The comparative study of fast vs. slow degrading three-dimensional scaffolds using a fast degrading poly D, L-lactic-glycolic acid copolymer (PLGA) and a slow degrading poly e-caprolactone (PCL) indicated that fast degradation negatively affects cell viability and migration into the scaffold in vitro and in vivo, which is likely due to the fast polymer degradation mediated acidification of the local environment. MMP-9 was crucial for collagen remodeling process by smooth muscle cells (SMC). MMP-9 deficiency dramatically decreased inflammatory cell invasion as well as capillary formation within the scaffolds implanted in vivo. This study reports that the angiogenic response developed within the scaffolds in vivo was related to the presence of inflammatory response. Combinatorial polymer libraries fabricated from blended PLGA and PCL and processed at gradient annealing temperatures were utilized to investigate polymeric interactions with SMC. Surface roughness was also found to correlate with SMC adhesion. SMC aggregation, proliferation, and protein production, were highest in regions that exhibited increased surface roughness, reduced hardness, and decreased crystallinity of the PCL-rich phases. This study revealed a previously unknown processing temperature and blending compositions for two well-known polymers, which optimized SMC interactions.

  3. FOXA2 suppresses the metastasis of hepatocellular carcinoma partially through matrix metalloproteinase-9 inhibition.

    PubMed

    Wang, Jian; Zhu, Chang-Peng; Hu, Ping-Fang; Qian, Hui; Ning, Bei-Fang; Zhang, Qing; Chen, Fei; Liu, Jiao; Shi, Bin; Zhang, Xin; Xie, Wei-Fen

    2014-11-01

    The forkhead box transcription factor A2 (FOXA2) is a member of the hepatocyte nuclear factor family and plays an important role in liver development and metabolic homeostasis, but its role in the metastasis of hepatocellular carcinoma (HCC) has not been evaluated. In this study, we found that the expression of FOXA2 was decreased in 68.1% (49/72) of human HCC tissues compared with their paired non-cancerous adjacent tissues. Clinicopathological analysis revealed that reduced FOXA2 expression was correlated with aggressive characteristics (venous invasion, poor differentiation, high tumor node metastasis grade). FOXA2 level was even lower in portal vein tumor thrombus compared with primary tumor tissues and correlated with epithelial-mesenchymal transition in HCC cells. Overexpression of FOXA2 inhibited migration and invasion of Focus cells, whereas knockdown of FOXA2 in HepG2 showed the opposite effect. Moreover, upregulation of FOXA2 suppressed HCC metastasis to bone, brain and lung in two distinct mouse models. Finally, we proved that FOXA2 repressed the transcription of matrix metalloproteinase (MMP)-9 and exerted its antimetastasis effect partially through downregulation of MMP-9. In conclusion, our findings indicate that FOXA2 plays a critical role in HCC metastasis and may serve as a novel therapeutic target for HCC. PMID:25142974

  4. Matrix Metalloproteinase-9 Reduces Islet Amyloid Formation by Degrading Islet Amyloid Polypeptide*

    PubMed Central

    Aston-Mourney, Kathryn; Zraika, Sakeneh; Udayasankar, Jayalakshmi; Subramanian, Shoba L.; Green, Pattie S.; Kahn, Steven E.; Hull, Rebecca L.

    2013-01-01

    Deposition of islet amyloid polypeptide (IAPP) as amyloid is a pathological hallmark of the islet in type 2 diabetes, which is toxic to β-cells. We previously showed that the enzyme neprilysin reduces islet amyloid deposition and thereby reduces β-cell apoptosis, by inhibiting fibril formation. Two other enzymes, matrix metalloproteinase (MMP)-2 and MMP-9, are extracellular gelatinases capable of degrading another amyloidogenic peptide, Aβ, the constituent of amyloid deposits in Alzheimer disease. We therefore investigated whether MMP-2 and MMP-9 play a role in reducing islet amyloid deposition. MMP-2 and MMP-9 mRNA were present in mouse islets but only MMP-9 activity was detectable. In an islet culture model where human IAPP (hIAPP) transgenic mouse islets develop amyloid but nontransgenic islets do not, a broad spectrum MMP inhibitor (GM6001) and an MMP-2/9 inhibitor increased amyloid formation and the resultant β-cell apoptosis. In contrast, a specific MMP-2 inhibitor had no effect on either amyloid deposition or β-cell apoptosis. Mass spectrometry demonstrated that MMP-9 degraded amyloidogenic hIAPP but not nonamyloidogenic mouse IAPP. Thus, MMP-9 constitutes an endogenous islet protease that limits islet amyloid deposition and its toxic effects via degradation of hIAPP. Because islet MMP-9 mRNA levels are decreased in type 2 diabetic subjects, islet MMP-9 activity may also be decreased in human type 2 diabetes, thereby contributing to increased islet amyloid deposition and β-cell loss. Approaches to increase islet MMP-9 activity could reduce or prevent amyloid deposition and its toxic effects in type 2 diabetes. PMID:23229548

  5. Mouse model of pulmonary cavitary tuberculosis and expression of matrix metalloproteinase-9.

    PubMed

    Ordonez, Alvaro A; Tasneen, Rokeya; Pokkali, Supriya; Xu, Ziyue; Converse, Paul J; Klunk, Mariah H; Mollura, Daniel J; Nuermberger, Eric L; Jain, Sanjay K

    2016-07-01

    Cavitation is a key pathological feature of human tuberculosis (TB), and is a well-recognized risk factor for transmission of infection, relapse after treatment and the emergence of drug resistance. Despite intense interest in the mechanisms underlying cavitation and its negative impact on treatment outcomes, there has been limited study of this phenomenon, owing in large part to the limitations of existing animal models. Although cavitation does not occur in conventional mouse strains after infection with Mycobacterium tuberculosis, cavitary lung lesions have occasionally been observed in C3HeB/FeJ mice. However, to date, there has been no demonstration that cavitation can be produced consistently enough to support C3HeB/FeJ mice as a new and useful model of cavitary TB. We utilized serial computed tomography (CT) imaging to detect pulmonary cavitation in C3HeB/FeJ mice after aerosol infection with M. tuberculosis Post-mortem analyses were performed to characterize lung lesions and to localize matrix metalloproteinases (MMPs) previously implicated in cavitary TB in situ A total of 47-61% of infected mice developed cavities during primary disease or relapse after non-curative treatments. Key pathological features of human TB, including simultaneous presence of multiple pathologies, were noted in lung tissues. Optical imaging demonstrated increased MMP activity in TB lesions and MMP-9 was significantly expressed in cavitary lesions. Tissue MMP-9 activity could be abrogated by specific inhibitors. In situ, three-dimensional analyses of cavitary lesions demonstrated that 22.06% of CD11b+ signal colocalized with MMP-9. C3HeB/FeJ mice represent a reliable, economical and tractable model of cavitary TB, with key similarities to human TB. This model should provide an excellent tool to better understand the pathogenesis of cavitation and its effects on TB treatments. PMID:27482816

  6. Macrophage matrix metalloproteinase-9 mediates epithelial-mesenchymal transition in vitro in murine renal tubular cells.

    PubMed

    Tan, Thian Kui; Zheng, Guoping; Hsu, Tzu-Ting; Wang, Ying; Lee, Vincent W S; Tian, Xinrui; Wang, Yiping; Cao, Qi; Wang, Ya; Harris, David C H

    2010-03-01

    As a rich source of pro-fibrogenic growth factors and matrix metalloproteinases (MMPs), macrophages are well-placed to play an important role in renal fibrosis. However, the exact underlying mechanisms and the extent of macrophage involvement are unclear. Tubular cell epithelial-mesenchymal transition (EMT) is an important contributor to renal fibrosis and MMPs to induction of tubular cell EMT. The aim of this study was to investigate the contribution of macrophages and MMPs to induction of tubular cell EMT. The murine C1.1 tubular epithelial cell line and primary tubular epithelial cells were cultured in activated macrophage-conditioned medium (AMCM) derived from lipopolysaccharide-activated J774 macrophages. MMP-9, but not MMP-2 activity was detected in AMCM. AMCM-induced tubular cell EMT in C1.1 cells was inhibited by broad-spectrum MMP inhibitor (GM6001), MMP-2/9 inhibitor, and in AMCM after MMP-9 removal by monoclonal Ab against MMP-9. AMCM-induced EMT in primary tubular epithelial cells was inhibited by MMP-2/9 inhibitor. MMP-9 induced tubular cell EMT in both C1.1 cells and primary tubular epithelial cells. Furthermore, MMP-9 induced tubular cell EMT in C1.1 cells to an extent similar to transforming growth factor-beta. Transforming growth factor-beta-induced tubular cell EMT in C1.1 cells was inhibited by MMP-2/9 inhibitor. Our in vitro study provides evidence that MMPs, specifically MMP-9, secreted by effector macrophages can induce tubular cell EMT and thereby contribute to renal fibrosis. PMID:20075196

  7. Plasma matrix metalloproteinase-9 levels, MMP-9 gene haplotypes, and cardiovascular risk in obese subjects.

    PubMed

    Luizon, Marcelo R; Belo, Vanessa A; Fernandes, Karla S; Andrade, Vanessa L; Tanus-Santos, Jose E; Sandrim, Valeria C

    2016-06-01

    Plasma matrix metalloproteinase (MMP)-9 is a predictor of cardiovascular mortality, and MMP-9 polymorphisms affect plasma MMP-9 levels. However, no study examined whether MMP-9 haplotypes affect MMP-9 levels in obese adults. We examined whether MMP-9 polymorphisms and haplotypes are associated with obesity, and whether they affect MMP-9 levels in obese subjects. We examined the plasma levels of MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1 in 105 subjects with normal weight (controls), 100 obese subjects, and 156 obese subjects with ≥3 metabolic risk factors (MRFs). We determined genotypes for three polymorphisms: C-1562T (rs3918242), Q279R (A>G, rs17576), and R668Q (G>A, rs17577). MMP-9 levels and activity (MMP-9/TIMP-1 ratio) were higher in obese subjects than in controls (P < 0.05). However, MMP-9 levels were higher in obese subjects with ≥3 MRFs than in obese subjects (P < 0.05). Obese subjects with ≥3 MRFs carrying the GA+AA genotypes for R668Q (G>A) polymorphism had higher MMP-9 levels than subjects carrying the AA genotype (P < 0.05). The "T, G, A" haplotype was more common in both groups of obese subjects than in controls (OR 3.95 and 4.39, respectively; P < 0.01). Notably, obese subjects with ≥3 MRFs carrying the "T, G, A" haplotype had higher MMP-9 levels than subjects carrying the "C, A, G" reference haplotype (P < 0.05). The "T, G, A" haplotype was associated with an increased risk of obesity and affected MMP-9 levels in obese subjects with ≥3 MRFs. Our findings suggest that plasma MMP-9 levels and MMP-9 haplotypes may help to discriminate obese subjects at an increased cardiovascular risk. PMID:27146834

  8. Role of matrix metalloproteinase-9 in chronic kidney disease: a new biomarker of resistant albuminuria.

    PubMed

    Pulido-Olmo, Helena; García-Prieto, Concha F; Álvarez-Llamas, Gloria; Barderas, María G; Vivanco, Fernando; Aranguez, Isabel; Somoza, Beatriz; Segura, Julián; Kreutz, Reinhold; Fernández-Alfonso, María S; Ruilope, Luis M; Ruiz-Hurtado, Gema

    2016-04-01

    Resistant albuminuria, developed under adequate chronic blockade of the renin-angiotensin system, is a clinical problem present in a small number of patients with chronic kidney disease (CKD). The mechanism underlying this resistant albuminuria remains unknown. Matrix metalloproteinases (MMPs) are involved in the pathophysiology of cardiovascular and renal diseases. In the present study we tested the role of MMPs in resistant albuminuria. First we evaluated gelatinase MMP-2 and MMP-9 activity by zymography in the Munich Wistar Frömter (MWF) rat, a model of progressive albuminuria, and subsequently in patients with resistant albuminuria. Markers of oxidative stress were observed in the kidneys of MWF rats, together with a significant increase in pro-MMP-2 and active MMP-9 forms. These changes were normalized together with reduced albuminuria in consomic MWF-8(SHR) rats, in which chromosome 8 of MWF was replaced with the respective chromosome from spontaneously hypertensive rats. The MMP-2 and MMP-9 protein levels were similar in patients with normal and resistant albuminuria; however, high circulating levels of collagen IV, a specific biomarker of tissue collagen IV degradation, were observed in patients with resistant albuminuria. These patients showed a significant increase in gelatinase MMP-2 and MMP-9 activity, but only a significant increase in the active MMP-9 form quantified by ELISA, which correlated significantly with the degree of albuminuria. Although the expression of the tissue inhibitor of MMP-9 (TIMP)-1 was similar, a novel AlphaLISA assay demonstrated that the MMP-9-TIMP-1 interaction was reduced in patients with resistant albuminuria. It is of interest that oxidized TIMP-1 expression was higher in patients with resistant albuminuria. Therefore, increased circulating MMP-9 activity is associated with resistant albuminuria and a deleterious oxidative stress environment appears to be the underlying mechanism. These changes might contribute to the

  9. Hydrogen sulfide mitigates matrix metalloproteinase-9 activity and neurovascular permeability in hyperhomocysteinemic mice*

    PubMed Central

    Tyagi, Neetu; Givvimani, Srikanth; Qipshidze, Natia; Kundu, Soumi; Kapoor, Shray; Vacek, Jonathan C.; Tyagi, Suresh C.

    2010-01-01

    An elevated level of homocysteine (Hcy), known as hyperhomocysteinmia (HHcy), was associated with neurovascular diseases. At physiological levels, hydrogen sulfide (H2S) protected the neurovascular system. Because Hcy was also a precursor of hydrogen sulfide (H2S), we sought to test whether the H2S protected the brain during HHcy. Cystathionine-β-synthase heterozygous (CBS+/−) and wild type (WT) mice were supplemented with or without NaHS (30 µM/L, H2S donor) in drinking water. Blood flow and cerebral microvascular permeability in pial vessels were measured by intravital microscopy in WT, WT+NaHS, CBS−/+ and CBS−/+ + NaHS treated mice. The brain tissues were analyzed for matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) by Western blot and RT-PCR. The mRNA levels of CBS and cystathionine gamma lyase (CSE, enzyme responsible for conversion of Hcy to H2S) genes were measured by RT-PCR. The results showed a significant increase in MMP-2, MMP-9, TIMP-3 protein and mRNA in CBS (−/+) mice, while H2S treatment mitigated this increase. Interstitial localization of MMPs was also apparent through Immunohistochemistry. A decrease in protein and mRNA expression of TIMP-4 was observed in CBS (−/+) mice. Microscopy data revealed increase in permeability in CBS (−/+) mice. These effects were ameliorated by H2S and suggested that physiological levels of H2S supplementation may have therapeutic potential against HHcy-induced microvascular permeability, in part, by normalizing the MMP/TIMP ratio in the brain. PMID:19913585

  10. Mouse model of pulmonary cavitary tuberculosis and expression of matrix metalloproteinase-9

    PubMed Central

    Ordonez, Alvaro A.; Tasneen, Rokeya; Pokkali, Supriya; Xu, Ziyue; Converse, Paul J.; Klunk, Mariah H.; Mollura, Daniel J.; Nuermberger, Eric L.

    2016-01-01

    ABSTRACT Cavitation is a key pathological feature of human tuberculosis (TB), and is a well-recognized risk factor for transmission of infection, relapse after treatment and the emergence of drug resistance. Despite intense interest in the mechanisms underlying cavitation and its negative impact on treatment outcomes, there has been limited study of this phenomenon, owing in large part to the limitations of existing animal models. Although cavitation does not occur in conventional mouse strains after infection with Mycobacterium tuberculosis, cavitary lung lesions have occasionally been observed in C3HeB/FeJ mice. However, to date, there has been no demonstration that cavitation can be produced consistently enough to support C3HeB/FeJ mice as a new and useful model of cavitary TB. We utilized serial computed tomography (CT) imaging to detect pulmonary cavitation in C3HeB/FeJ mice after aerosol infection with M. tuberculosis. Post-mortem analyses were performed to characterize lung lesions and to localize matrix metalloproteinases (MMPs) previously implicated in cavitary TB in situ. A total of 47-61% of infected mice developed cavities during primary disease or relapse after non-curative treatments. Key pathological features of human TB, including simultaneous presence of multiple pathologies, were noted in lung tissues. Optical imaging demonstrated increased MMP activity in TB lesions and MMP-9 was significantly expressed in cavitary lesions. Tissue MMP-9 activity could be abrogated by specific inhibitors. In situ, three-dimensional analyses of cavitary lesions demonstrated that 22.06% of CD11b+ signal colocalized with MMP-9. C3HeB/FeJ mice represent a reliable, economical and tractable model of cavitary TB, with key similarities to human TB. This model should provide an excellent tool to better understand the pathogenesis of cavitation and its effects on TB treatments. PMID:27482816

  11. Proteolytic regulation of synaptic plasticity in the mouse primary visual cortex: analysis of matrix metalloproteinase 9 deficient mice

    PubMed Central

    Kelly, Emily A.; Russo, Amanda S.; Jackson, Cory D.; Lamantia, Cassandra E.; Majewska, Ania K.

    2015-01-01

    The extracellular matrix (ECM) is known to play important roles in regulating neuronal recovery from injury. The ECM can also impact physiological synaptic plasticity, although this process is less well understood. To understand the impact of the ECM on synaptic function and remodeling in vivo, we examined ECM composition and proteolysis in a well-established model of experience-dependent plasticity in the visual cortex. We describe a rapid change in ECM protein composition during Ocular Dominance Plasticity (ODP) in adolescent mice, and a loss of ECM remodeling in mice that lack the extracellular protease, matrix metalloproteinase-9 (MMP9). Loss of MMP9 also attenuated functional ODP following monocular deprivation (MD) and reduced excitatory synapse density and spine density in sensory cortex. While we observed no change in the morphology of existing dendritic spines, spine dynamics were altered, and MMP9 knock-out (KO) mice showed increased turnover of dendritic spines over a period of 2 days. We also analyzed the effects of MMP9 loss on microglia, as these cells are involved in extracellular remodeling and have been recently shown to be important for synaptic plasticity. MMP9 KO mice exhibited very limited changes in microglial morphology. Ultrastructural analysis, however, showed that the extracellular space surrounding microglia was increased, with concomitant increases in microglial inclusions, suggesting possible changes in microglial function in the absence of MMP9. Taken together, our results show that MMP9 contributes to ECM degradation, synaptic dynamics and sensory-evoked plasticity in the mouse visual cortex. PMID:26441540

  12. Matrix metalloproteinase-9 expression correlated with tumor response in patients with locally advanced rectal cancer undergoing preoperative chemoradiotherapy

    SciTech Connect

    Unsal, Diclehan . E-mail: diclehan@yahoo.com; Uner, Aytug; Akyurek, Nalan; Erpolat, Petek; Dursun, Ayse; Pak, Yucel

    2007-01-01

    Purpose: To analyze whether the expression of matrix metalloproteinases (MMPs) and their tissue inhibitors are associated with tumor response to preoperative chemoradiotherapy in rectal cancer patients. Methods and Materials: Forty-four patients who had undergone preoperative chemoradiotherapy were evaluated retrospectively. Treatment consisted of pelvic radiotherapy and two cycles of 5-fluorouracil plus leucovorin. Surgery was performed 6-8 weeks later. MMP-2, MMP-9, and tissue inhibitors of metalloproteinase-1 and -2 expression was analyzed by immunohistochemistry of the preradiation biopsy and surgical specimens. The intensity and extent of staining were evaluated separately, and a final score was calculated by multiplying the two scores. The primary endpoint was the correlation of expression with tumor response, with the secondary endpoint the effect of chemoradiotherapy on the expression. Results: Preoperative treatment resulted in downstaging in 20 patients (45%) and no clinical response in 24 (55%). The pathologic tumor response was complete in 11 patients (25%), partial in 23 (52%), and none in 10 (23%). Positive MMP-9 staining was observed in 20 tumors (45%) and was associated with the clinical nodal stage (p = 0.035) and the pathologic and clinical response (p < 0.0001). The staining status of the other markers was associated with neither stage nor response. The overall pathologic response rate was 25% in MMP-9-positive patients vs. 52% in MMP-9-negative patients (p = 0.001). None of the 11 patients with pathologic complete remission was MMP-9 positive. Conclusions: Matrix metalloproteinase-9 expression correlated with a poor tumor response to preoperative chemoradiotherapy in rectal carcinoma patients.

  13. Hypoxia reduces the output of matrix metalloproteinase-9 (MMP-9) in monocytes by inhibiting its secretion and elevating membranal association.

    PubMed

    Rahat, Michal A; Marom, Barak; Bitterman, Haim; Weiss-Cerem, Lea; Kinarty, Amalia; Lahat, Nitza

    2006-04-01

    Cellular hypoxia, characterizing tumors, ischemia, and inflammation induce recruitment of monocytes/macrophages, immobilize them at the hypoxic site, and alter their function. To migrate across the extracellular matrix and as part of their inflammatory functions, monocytes and macrophages secrete proteases, including matrix metalloproteinase-9 (MMP-9), whose expression is induced by proinflammatory cytokines [e.g., tumor necrosis factor alpha (TNF-alpha)]. We show that hypoxia (<0.3% O2 for 48 h) reduced the output of TNF-alpha-induced proMMP-9 by threefold (P < 0.01) in the U937 monocytic cell line and in primary human monocytes. TNF-alpha induced MMP-9 transcription by threefold, but no significant difference was observed in MMP-9 mRNA steady-state between normoxia and hypoxia, which inhibited the trafficking of proMMP-9 via secretory vesicles and increased the intracellular accumulation of proMMP-9 in the cells by 47% and 62% compared with normoxia (P < 0.05), as evaluated by zymography of cellular extracts and confocal microscopy, respectively. Secretion of proMMP-9 was reduced by the addition of cytochalazin B or nocodazole, which inhibits the polymerization of actin and tubulin fibers, or by the addition of the Rho kinase inhibitor Y27632, suggesting the involvement of the cytoskeleton and the Rho GTPases in the process of enzyme secretion. Furthermore, attachment of proMMP-9 to the cell membrane increased after hypoxia via its interactions with surface molecules such as CD44. In addition, the reduced migration of monocytes in hypoxia was shown to be mediated, at least partially, by secreted MMP-9. Thus, hypoxia post-translationally reduced the secreted amounts of proMMP-9 by using two mutually nonexclusive mechanisms: mostly, inhibition of cellular trafficking and to a lesser extent, attachment to the membrane. PMID:16434697

  14. Circulating Matrix Metalloproteinase-9 Is Associated with Cardiovascular Risk Factors in a Middle-Aged Normal Population

    PubMed Central

    Garvin, Peter; Nilsson, Lennart; Carstensen, John; Jonasson, Lena; Kristenson, Margareta

    2008-01-01

    Background Elevated levels of circulating matrix metalloproteinase-9 (MMP-9) have been demonstrated in patients with established coronary artery disease (CAD). The aim of this study was to analyse levels of MMP-9 in a population free from symptomatic CAD and investigate their associations with cardiovascular (CV) risk factors, including C-reactive protein (CRP). Methods A cross-sectional study was performed in a population based random sample aged 45–69 (n = 345, 50% women). MMP-9 levels were measured in EDTA-plasma using an ELISA-method. CV risk factors were measured using questionnaires and standard laboratory methods. Results Plasma MMP-9 was detectable in all participants, mean 38.9 ng/mL (SD 22.1 ng/mL). Among individuals without reported symptomatic CAD a positive association (p<0.001) was seen, for both men and women, of MMP-9 levels regarding total risk load of eight CV risk factors i.e. blood pressure, dyslipidemia, diabetes, obesity, smoking, alcohol intake, physical activity and fruit and vegetable intake. The association was significant also after adjustment for CRP, and was not driven by a single risk factor alone. In regression models adjusted for age, sex, smoking, alcohol intake and CRP, elevated MMP-9 levels were independently positively associated with systolic blood pressure (p = 0.037), smoking (p<0.001), alcohol intake (p = 0.003) and CRP (p<0.001). The correlation coefficient between MMP-9 and CRP was r = 0.24 (p<0.001). Conclusions In a population without reported symptomatic CAD, MMP-9 levels were associated with total CV risk load as well as with single risk factors. This was found also after adjustment for CRP. PMID:18335048

  15. Ablation of matrix metalloproteinase-9 gene decreases cerebrovascular permeability and fibrinogen deposition post traumatic brain injury in mice.

    PubMed

    Muradashvili, Nino; Benton, Richard L; Saatman, Kathryn E; Tyagi, Suresh C; Lominadze, David

    2015-04-01

    Traumatic brain injury (TBI) is accompanied with enhanced matrix metalloproteinase-9 (MMP-9) activity and elevated levels of plasma fibrinogen (Fg), which is a known inflammatory agent. Activation of MMP-9 and increase in blood content of Fg (i.e. hyperfibrinogenemia, HFg) both contribute to cerebrovascular disorders leading to blood brain barrier disruption. It is well-known that activation of MMP-9 contributes to vascular permeability. It has been shown that at an elevated level (i.e. HFg) Fg disrupts blood brain barrier. However, mechanisms of their actions during TBI are not known. Mild TBI was induced in wild type (WT, C57BL/6 J) and MMP-9 gene knockout (Mmp9(-/-)) homozygous, mice. Pial venular permeability to fluorescein isothiocyanate-conjugated bovine serum albumin in pericontusional area was observed 14 days after injury. Mice memory was tested with a novel object recognition test. Increased expression of Fg endothelial receptor intercellular adhesion protein-1 and formation of caveolae were associated with enhanced activity of MMP-9 causing an increase in pial venular permeability. As a result, an enhanced deposition of Fg and cellular prion protein (PrP(C)) were found in pericontusional area. These changes were attenuated in Mmp9(-/-) mice and were associated with lesser loss of short-term memory in these mice than in WT mice. Our data suggest that mild TBI-induced increased cerebrovascular permeability enhances deposition of Fg-PrP(C) and loss of memory, which is ameliorated in the absence of MMP-9 activity. Thus, targeting MMP-9 activity and blood level of Fg can be a possible therapeutic remedy to diminish vasculo-neuronal damage after TBI. PMID:24771110

  16. Ablation of matrix metalloproteinase-9 gene decreases cerebrovascular permeability and fibrinogen deposition post traumatic brain injury in mice

    PubMed Central

    Muradashvili, Nino; Benton, Richard L.; Saatman, Kathryn E.; Tyagi, Suresh C.; Lominadze, David

    2014-01-01

    Traumatic brain injury (TBI) is accompanied with enhanced matrix metalloproteinase-9 (MMP-9) activity and elevated levels of plasma fibrinogen (Fg), which is a known inflammatory agent. Activation of MMP-9 and increase in blood content of Fg (i.e. hyperfibrinogenemia, HFg) both contribute to cerebrovascular disorders leading to blood brain barrier disruption. It is well-known that activation of MMP-9 contributes to vascular permeability. It has been shown that at an elevated level (i.e. HFg) Fg disrupts blood brain barrier. However, mechanisms of their actions during TBI are not known. Mild TBI was induced in wild type (WT, C57BL/6J) and MMP-9 gene knockout (Mmp9−/−) homozygous, mice. Pial venular permeability to fluorescein isothiocyanate-conjugated bovine serum albumin (FITC-BSA) in pericontusional area was observed 14 days after injury. Mice memory was tested with a novel object recognition test. Increased expression of Fg endothelial receptor intercellular adhesion protein-1 and formation of caveolae were associated with enhanced activity of MMP-9 causing an increase in pial venular permeability. As a result, an enhanced deposition of Fg and cellular prion protein (PrPC) were found in pericontusional area. These changes were attenuated in Mmp9−/− mice and were associated with lesser loss of short-term memory in these mice than in WT mice. Our data suggest that mild TBI-induced increased cerebrovascular permeability enhances deposition of Fg-PrPC and loss of memory, which is ameliorated in the absence of MMP-9 activity. Thus, targeting MMP-9 activity and blood level of Fg can be a possible therapeutic remedy to diminish vasculo-neuronal damage after TBI. PMID:24771110

  17. The role of annexin A1 in expression of matrix metalloproteinase-9 and invasion of breast cancer cells

    SciTech Connect

    Kang, Hyereen; Ko, Jesang; Jang, Sung-Wuk

    2012-06-22

    Highlights: Black-Right-Pointing-Pointer We evaluated the effect of ANXA1 on promoting migration and invasion in MDA-MB-231 cells. Black-Right-Pointing-Pointer ANXA1 siRNA inhibits invasion and migration. Black-Right-Pointing-Pointer ANXA1 regulates MMP-9 expression and activity. Black-Right-Pointing-Pointer ANX-1 siRNA inhibits the activation of NF-{kappa}B in MDA-MB-231 cells. -- Abstract: Matrix metalloproteinase-9 (MMP-9) plays an important role in the invasion and metastasis of cancer cells. However, the regulatory mechanism of MMP-9 expression and its biological effects on breast cancer development remain obscure. In the current study, we examined the potential role of annexin A1 (ANXA1) in regulating migration and invasion in breast cancer cell lines. Both ANXA1 mRNA and protein are expressed in the highly invasive, hormone-insensitive human breast cancer cell lines MDA-MB-231 and SKBr3, but not in the hormone-responsive cell lines MCF-7 and T47D. Downregulation of ANXA1 expression with specific small interfering RNAs (ANXA1 siRNA) in MDA-MB-231 cells resulted in decreased cancer cell migration and invasion. Ablation of ANXA1 expression decreases the expression of MMP-9 at both the mRNA and protein levels and also reduces the proteolytic activity of MMP-9 in MDA-MB-231 cells. Moreover, silencing ANXA1 also decreases the transcriptional activity of MMP-9 by the suppression of nuclear factor kappa-B (NF-{kappa}B) activity. Collectively, these results indicate that ANXA1 functions as a positive regulator of MMP-9 expression and invasion of breast cancer cells through specific activation of the NF-{kappa}B signaling pathway.

  18. Elevated Plasma Matrix Metalloproteinase-9 and Its Correlations with Severity of Disease in Patients with Ventilator-Associated Pneumonia

    PubMed Central

    Li, Yia-Ting; Wang, Yao-Chen; Lee, Hsiang-Lin; Lu, Min-Chi; Yang, Shun-Fa

    2016-01-01

    Ventilator-associated pneumonia (VAP) increases patient mortality and medical expenditure, and a real-time and reliable method for the rapid diagnosis of VAP may help reduce fatal complications. Matrix metalloproteinases-9 (MMP-9) is considered significant in the pathogenesis of lung inflammation and infection. Therefore, we examined its relationship with the clinical course of VAP. This retrospective observational study recruited 30 healthy volunteers, 12 patients who used mechanical ventilation without the development of VAP (hereafter, patients without VAP), and 30 patients with a clinical diagnosis of VAP (hereafter, patients with VAP). The activity and level of plasma MMP-9 were determined through a gelatin zymography assay and ELISA. Our results report that both plasma MMP-9 activity and concentration were significantly elevated in the acute stage of patients with VAP when compared with control group and patients without VAP (p < 0.001). Subsequently, the plasma MMP-9 of patients with VAP decreased significantly after antibiotic treatment. Furthermore, plasma MMP-9 concentration was positively correlated with the clinical pulmonary infection score (r = 0.409, p = 0.007), WBCs (r = 0.620, p < 0.001), and neutrophils counts (r = 0.335, p = 0.035). In addition, plasma MMP-9 is an excellent tool for recognizing VAP when the cutoff level is set to 92.62 ng/mL (AUC = 0.863, 95% CI = 0.761 to 0.932). In conclusions, we concluded that MMP-9 levels play a role in the development of VAP and might have the potential to be applied in the development of VAP therapies. PMID:27499696

  19. Pioglitazone inhibits the expression of matrix metalloproteinase-9, a protein involved in diabetes-associated wound healing.

    PubMed

    Zhang, Jun; Huang, Xiaoyuan; Wang, Lingfeng

    2014-08-01

    Matrix metalloproteinase-9 (MMP-9) is a protein involved in diabetes-associated wound healing. The present study aimed to determine whether pioglitazone, an agonist of peroxisome proliferator-activated receptor‑γ (PPAR-γ), inhibits the expression of MMP-9. HaCaT cells at a density of 6x105 cells/well were seeded into 6-well plates in medium and were cultured for 24 h. The cells were then treated with bovine serum albumin (BSA) only or advanced glycation end‑product (AGE)-BSA (50, 100, 200, 300 or 400 µg/ml), with or without pioglitazone (0.5 or 1 µM). The effects of AGE-BSA on cell viability were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The levels of MMP-9 secreted into the medium were detected by an enzyme-linked immunosorbent assay. The mRNA and protein levels were analyzed by quantitative polymerase chain reaction (qPCR) and western blot analysis, respectively. AGEs are able to increase the level of MMP-9 mRNA in HaCaT cells and the levels of MMP-9 protein secreted into the medium. Pioglitazone (0.5 or 1 µΜ) significantly inhibited the levels of MMP-9 in the treated HaCaT cells. Pioglitazone (0.5 or 1 µΜ) also suppressed the levels of MMP-9 in the cell culture medium. Pioglitazone at concentrations of 0.5 and 1 µΜ significantly suppressed the levels of MMP-9 mRNA to 20 or 8%, respectively. These results suggest that pioglitazone is able to effectively suppress the expression of MMP-9 via a transcriptional mechanism. PMID:24890117

  20. The alterations of matrix metalloproteinase-9 in mouse brainstem during herpes simplex virus type 1-induced facial palsy.

    PubMed

    Chen, Dong; Zhang, Daogong; Xu, Lei; Han, Yuechen; Wang, Haibo

    2013-11-01

    The aim of this study is to explore the changes of matrix metalloproteinase-9 (MMP9) in the mouse brainstem during the development of facial paralysis induced by herpes simplex virus type 1 (HSV-1) and the inhibitory effect of methylprednisolone sodium succinate (MPSS) on MMP9 expression. HSV-1 was inoculated into the surface of posterior auricle of mouse to establish a paralyzed animal model. The paralyzed mice were divided randomly into three groups. In one group without any treatment, mice were killed at different time points of 6 h, 1, 2, 3, and 7 days post-induction of facial paralysis; in the other two groups, mice were injected daily with MPSS and a combination of MPSS and glucocorticoid receptor blocker (RU486) for 2 days, respectively. The expression of MMP9 in the facial nucleus of brainstem was detected by Western blot, quantitative real-time polymerase chain reaction, and immunofluorescence technique. A total of 52.07 % of mice developed unilateral facial paralysis after inoculated with HSV-1. Both mRNA and protein expression of MMP9 were present at low levels in normal facial nucleus of brainstem and were increased significantly after facial paralysis with its peak time at 2 days post-induction of facial paralysis. Expression of MMP9 of paralyzed mice was inhibited by MPSS, and the inhibition could be blocked by RU486. Our findings suggest that MMP9 in mouse brainstem is involved in the evolution of facial palsy induced by HSV-1 and may play an important role in the pathogenesis of this disease. MPSS might effectively relieve HSV-1-mediated damages by inhibitory effect on expression of MMP9 in HSV-1-induced facial paralysis. PMID:23817985

  1. Histamine induces the production of matrix metalloproteinase-9 in human astrocytic cultures via H1-receptor subtype.

    PubMed

    Patel, Aarti; Vasanthan, Vishnu; Fu, Wen; Fahlman, Richard P; MacTavish, David; Jhamandas, Jack H

    2016-05-01

    Accumulation of β-amyloid (Aβ) protein within the brain is a neuropathological hallmark of Alzheimer's disease (AD). One strategy to facilitate Aβ clearance from the brain is to promote Aβ catabolism. Matrix metalloproteinase-9 (MMP-9), a member of the family of Zn(+2)-containing endoproteases, known to be expressed and secreted by astrocytes, is capable of degrading Aβ. Histamine, a major aminergic brain neurotransmitter, stimulates the production of MMP-9 in keratinocytes through the histamine H1 receptor (H1R). In the present study, we show that histamine evokes a concentration- and calcium-dependent release of MMP-9 from human astrocytic U373 cells and primary cultures of human and rat astrocytes through the H1R subtype. Activation of H1R on astrocytes elevated intracellular levels of Ca(2+) that was accompanied by time-dependent increases in MAP kinase p44/p42 and PKC. In-cell western blots revealed dose-dependent increases in both enzymes, confirming involvement of these signal transduction pathways. We next investigated the extent of recombinant human MMP-9 (rhMMP-9) proteolytic activity on soluble oligomeric Aβ (soAβ). Mass spectrometry demonstrated time-dependent cleavage of soAβ (20 μM), but not another amyloidogenic protein amylin, upon incubation with rhMMP-9 (100 nM) at 1, 4 and 17 h. Furthermore, Western blots showed a shift in soAβ equilibrium toward lower order, less toxic monomeric species. In conclusion, both MAPK p44/p42 and PKC pathways appear to be involved in histamine-upregulated MMP-9 release via H1Rs in astrocytes. Furthermore, MMP-9 appears to cleave soAβ into less toxic monomeric species. Given the key role of histamine in MMP-9 release, this neurotransmitter may serve as a potential therapeutic target for AD. PMID:25682263

  2. Salvianolic acid B functioned as a competitive inhibitor of matrix metalloproteinase-9 and efficiently prevented cardiac remodeling

    PubMed Central

    2010-01-01

    Background Infarct-induced left ventricular (LV) remodeling is a deleterious consequence after acute myocardial infarction (MI) which may further advance to congestive heart failure. Therefore, new therapeutic strategies to attenuate the effects of LV remodeling are urgently needed. Salvianolic acid B (SalB) from Salviae mitiorrhizae, which has been widely used in China for the treatment of cardiovascular diseases, is a potential candidate for therapeutic intervention of LV remodeling targeting matrix metalloproteinase-9 (MMP-9). Results Molecular modeling and LIGPLOT analysis revealed in silico docking of SalB at the catalytic site of MMP-9. Following this lead, we expressed truncated MMP-9 which contains only the catalytic domain, and used this active protein for in-gel gelatin zymography, enzymatic analysis, and SalB binding by Biacore. Data generated from these assays indicated that SalB functioned as a competitive inhibitor of MMP-9. In our rat model for cardiac remodeling, western blot, echocardiography, hemodynamic measurement and histopathological detection were used to detect the effects and mechanism of SalB on cardio-protection. Our results showed that in MI rat, SalB selectively inhibited MMP-9 activities without affecting MMP-9 expression while no effect of SalB was seen on MMP-2. Moreover, SalB treatment in MI rat could efficiently increase left ventricle wall thickness, improve heart contractility, and decrease heart fibrosis. Conclusions As a competitive inhibitor of MMP-9, SalB presents significant effects on preventing LV structural damage and preserving cardiac function. Further studies to develop SalB and its analogues for their potential for cardioprotection in clinic are warranted. PMID:20735854

  3. Effects of atorvastatin on plasma matrix metalloproteinase-9 concentration after glial tumor resection; a randomized, double blind, placebo controlled trial

    PubMed Central

    2014-01-01

    Background Neurosurgical procedures such as craniotomy and brain tumor resection could potentially lead to unavoidable cerebral injuries. Matrix metalloproteinase-9 (MMP-9) is up-regulated in neurological injuries. Statins have been suggested to reduce MMP- 9 level and lead to neuroprotection. Atorvastatin preoperatively administered to evaluate its neuroprotective effects and outcome assessment in neurosurgical-induced brain injuries after glial tumor resection. In this prospective, randomized, double-blind, placebo-controlled trial, 42 patients undergoing glial tumor surgery randomly received 40 mg atorvastatin or placebo twice daily from seven days prior to operation and continued for a 3 weeks period. Plasma MMP-9 concentration measured 4 times, immediately before starting atorvastatin or placebo, immediately before surgery, 24 hours and two weeks after the surgery. Karnofsky performance score was assessed before first dose of atorvastatin as a baseline and 2 months after the surgery. Results Karnofsky performance scale after surgery raised significantly more in Atorvastatin group (11.43 +/- 10.62 vs. 4.00 +/- 8.21) (p = 0.03). Atorvastatin did not significantly reduce MMP-9 plasma concentration 24 hours after surgery in comparison to placebo. No statistical significance detected regarding length of hospital stay among the groups. Significant reduction in MMP-9 plasma concentration was recorded in atorvastatin group two weeks after surgery (p = 0.048). Conclusions Significant statistical differences detected with atorvastatin group regarding MMP-9 plasma concentration, clinical outcome and Karnofsky performance score. Consequently, atorvastatin use may lead to better outcome after neurosurgical procedures. PMID:24397933

  4. Association of Matrix Metalloproteinase-9 (MMP9) Variants with Primary Angle Closure and Primary Angle Closure Glaucoma

    PubMed Central

    Wiggs, Janey L.; Pasquale, Louis R.; Sun, Xinghuai; Fan, Bao Jian

    2016-01-01

    Shorter axial length observed in patients with primary angle closure glaucoma (PACG) might be due to altered matrix metalloproteinase-9 (MMP9) activity resulting in ECM remodeling during eye growth and development. This study aimed to evaluate common variants in MMP9 for association with PACG. Six tag SNPs of MMP9 were genotyped in a Chinese sample of 1,030 cases, including 572 PACG and 458 primary angle closure (PAC), and 499 controls. None of 6 SNPs were significantly associated with overall PAC/PACG (P > 0.07) or with PAC/PACG subgroups (Pc > 0.18). Meta-analysis of two non-Chinese studies revealed significant association between rs17576 and PACG (ORs = 0.56, P < 0.0001); however, meta-analysis of our dataset with 4 Chinese datasets did not replicate this association (ORs = 1.23, P = 0.29). Prior significant association for rs3918249 in one Caucasian study (OR = 0.63, P = 0.006) was not replicated in meta-analysis of 3 Chinese studies including this study (ORs = 0.91, P = 0.13). Significant heterogeneity between non-Chinese and Chinese datasets precluded overall meta-analysis for rs17576 and rs3918249 (Q = 0.001 and 0.04 respectively). rs17577 was nominally associated with PACG in one Caucasian study (OR = 1.71, P = 0.02), but not in 3 Chinese studies including our study (ORs = 1.20, P = 0.07). Overall meta-analysis revealed nominal association for rs17577 and PAC/PACG (ORs = 1.26, Pc = 0.05). Meta-analysis did not show significant association between the other SNPs and PAC/PACG (P > 0.47). The largest association study to date did not find significant association between MMP9 and PAC/PACG in Chinese; meta-analysis with other Chinese datasets did not produce significant association. In most instances combination with non-Chinese datasets was not possible except for one variant showing nominally significant association. More work is needed to define the role of MMP9 variants in PACG. PMID:27272641

  5. Cyanobacterial Microcystis aeruginosa lipopolysaccharide elicits release of superoxide anion, thromboxane B₂, cytokines, chemokines, and matrix metalloproteinase-9 by rat microglia.

    PubMed

    Mayer, Alejandro M S; Clifford, Jonathan A; Aldulescu, Monica; Frenkel, Jeffrey A; Holland, Michael A; Hall, Mary L; Glaser, Keith B; Berry, John

    2011-05-01

    Microcystis aeruginosa (M. aeruginosa) is a cosmopolitan Gram-negative cyanobacterium that may contaminate freshwater by releasing toxins, such as lipopolysaccharide (LPS) during aquatic blooms, affecting environmental and human health. The putative toxic effects of cyanobacterial LPS on brain microglia, a glial cell type that constitutes the main leukocyte-dependent source of reactive oxygen species in the central nervous system, are presently unknown. We tested the hypothesis that in vitro concentration- and time-dependent exposure to M. aeruginosa LPS strain UTCC 299 would activate rat microglia and the concomitant generation of superoxide anion (O₂⁻). After a 17-h exposure of microglia to M.aeruginosa LPS, the following concentration-dependent responses were observed: 0.1-100 ng/ml M. aeruginosa LPS enhanced O₂⁻ generation, with limited inflammatory mediator generation; 1000-10,000 ng/ml M. aeruginosa LPS caused thromboxane B₂ (TXB₂), matrix metalloproteinase-9 (MMP-9), and macrophage inflammatory protein-2 (MIP-2/CXCL2) release, concurrent with maximal O₂⁻ generation; 100,000 ng/mL M. aeruginosa LPS deactivated O₂⁻ production but maintained elevated levels of TXB₂, MMP-9, tumor necrosis factor-α (TNF-α), interleukin 1-α (IL-1α), and interleukin-6 (IL-6), macrophage inflammatory protein 1α (MIP-1α/CCL3), and MIP-2/CXCL2, with concomitant lactic dehydrogenase release. Although M. aeruginosa LPS was consistently less potent than Escherichia coli LPS, with the exception of O₂⁻, TXB₂, and MCP-1/CCL2 generation, it was more efficacious because higher levels of MMP-9, TNF-α, IL-1α, IL-6, MIP-1α/CCL3, and MIP-2/CXCL2 were produced. Our in vitro studies suggest that one or more of the inflammatory mediators released during M. aeruginosa LPS stimulation of microglia may play a critical role in the subsequent ability of microglia to generate O₂⁻. To our knowledge, this is the first experimental evidence that LPS isolated from a M

  6. Correlation between genetic polymorphism of matrix metalloproteinase-9 in patients with coronary artery disease and cardiac remodeling

    PubMed Central

    Yu, Qibin; Li, Hanmei; Li, Linlin; Wang, Shaoye; Wu, Yongbo

    2015-01-01

    Objective: To explore the correlation between genetic polymorphism of matrix metalloproteinase-9 (MMP-9) in patients with coronary artery disease (CAD) and cardiac remodeling. Methods: A total of 272 subjects who received coronary angiography in our hospital from July 2008 to September 2013 were selected, including 172 CAD patients (CAD group) and another 100 ones (control group). Both groups were subjected to MMP-9 and ultrasonic detections to determine vascular remodeling and atherosclerotic plaques. C1562G polymorphism of MMP-9 gene was detected, and correlation with vascular remodeling and atherosclerotic plaque was analyzed. Results: Serum MMP-9 level of CAD group (330.87±50.39 ng/ml) was significantly higher than that of control group (134.87±34.02 ng/ml) (P<0.05). Compared with control group, CAD group had significantly higher intima-media thickness, and significantly lower systolic peak velocity, mean systolic velocity and end-diastolic velocity (P<0.05). Total area of stenotic blood vessels was 67.34±22.98 mm2, while that of control blood vessels was 64.00±20.83 mm2. G/G, G/C and C/C genotype frequencies of MMP-9 differed significantly in the two groups (P<0.05). G and C allele frequencies of CAD group (70.9% and 29.1%) were significantly different from those of control group (50.0% and 50.0%) (P<0.05). G/G, G/C and C/C genotypes were manifested as lipid-rich, fibrous and calcified or ulcerated plaques respectively. Total area of stenotic blood vessels of G/G genotype significantly exceeded those of G/C and C/C genotypes (P<0.05), whereas the latter two had no significant differences. Conclusion: CAD promoted 1562C-G transformation of MMP-9 gene into genetic polymorphism, thus facilitating arterial remodeling and increasing unstable atherosclerotic plaques. PMID:26150861

  7. Association of Matrix Metalloproteinase-9 (MMP9) Variants with Primary Angle Closure and Primary Angle Closure Glaucoma.

    PubMed

    Chen, Xueli; Chen, Yuhong; Wiggs, Janey L; Pasquale, Louis R; Sun, Xinghuai; Fan, Bao Jian

    2016-01-01

    Shorter axial length observed in patients with primary angle closure glaucoma (PACG) might be due to altered matrix metalloproteinase-9 (MMP9) activity resulting in ECM remodeling during eye growth and development. This study aimed to evaluate common variants in MMP9 for association with PACG. Six tag SNPs of MMP9 were genotyped in a Chinese sample of 1,030 cases, including 572 PACG and 458 primary angle closure (PAC), and 499 controls. None of 6 SNPs were significantly associated with overall PAC/PACG (P > 0.07) or with PAC/PACG subgroups (Pc > 0.18). Meta-analysis of two non-Chinese studies revealed significant association between rs17576 and PACG (ORs = 0.56, P < 0.0001); however, meta-analysis of our dataset with 4 Chinese datasets did not replicate this association (ORs = 1.23, P = 0.29). Prior significant association for rs3918249 in one Caucasian study (OR = 0.63, P = 0.006) was not replicated in meta-analysis of 3 Chinese studies including this study (ORs = 0.91, P = 0.13). Significant heterogeneity between non-Chinese and Chinese datasets precluded overall meta-analysis for rs17576 and rs3918249 (Q = 0.001 and 0.04 respectively). rs17577 was nominally associated with PACG in one Caucasian study (OR = 1.71, P = 0.02), but not in 3 Chinese studies including our study (ORs = 1.20, P = 0.07). Overall meta-analysis revealed nominal association for rs17577 and PAC/PACG (ORs = 1.26, Pc = 0.05). Meta-analysis did not show significant association between the other SNPs and PAC/PACG (P > 0.47). The largest association study to date did not find significant association between MMP9 and PAC/PACG in Chinese; meta-analysis with other Chinese datasets did not produce significant association. In most instances combination with non-Chinese datasets was not possible except for one variant showing nominally significant association. More work is needed to define the role of MMP9 variants in PACG. PMID:27272641

  8. Hydrogel-Framed Nanofiber Matrix Integrated with a Microfluidic Device for Fluorescence Detection of Matrix Metalloproteinases-9.

    PubMed

    Han, Sang Won; Koh, Won-Gun

    2016-06-21

    Matrix metalloproteinases (MMPs) play a pivotal role in regulating the composition of the extracellular matrix and have a critical role in vascular disease, cancer progression, and bone disorders. This paper describes the design and fabrication of a microdevice as a new platform for highly sensitive MMP-9 detection. In this sensing platform, fluorescein isocyanate (FITC)-labeled MMP-9 specific peptides were covalently immobilized on an electrospun nanofiber matrix to utilize an enzymatic cleavage strategy. Prior to peptide immobilization, the nanofiber matrix was incorporated into hydrogel micropatterns for easy size control and handling of the nanofiber matrix. The resultant hydrogel-framed nanofiber matrix immobilizing the peptides was inserted into microfluidic devices consisting of reaction chambers and detection zones. The immobilized peptides were reacted with the MMP-9-containing solution in a reaction chamber, which resulted in the cleavage of the FITC-containing peptide fragments and subsequently generated fluorescent flow at the detection zone. As higher concentrations of the MMP-9 solution were introduced or larger peptide-immobilizing nanofiber areas were used, more peptides were cleaved, and a stronger fluorescence signal was observed. Due to the huge surface area of the nanofiber and small dimensions of the microsystem, a faster response time (30 min) and lower detection limit (10 pM) could be achieved in this study. The hydrogel-framed nanofiber matrix is disposable and can be replaced with new ones immobilizing either the same or different biomolecules for various bioassays, while the microfluidic system can be continuously reused. PMID:27214657

  9. Elevated Expression of Matrix Metalloproteinase-9 not Matrix Metalloproteinase-2 Contributes to Progression of Extracranial Arteriovenous Malformation

    PubMed Central

    Wei, Ting; Zhang, Haihong; Cetin, Neslihan; Miller, Emily; Moak, Teri; Suen, James Y.; Richter, Gresham T.

    2016-01-01

    Extracranial arteriovenous malformations (AVMs) are rare but dangerous congenital lesions arising from direct arterial-venous shunts without intervening capillaries. Progressive infiltration, expansion, and soft tissue destruction lead to bleeding, pain, debilitation and disfigurement. The pathophysiology of AVMs is not well understood. Matrix Metalloproteinases (MMPs) are thought to play an important role in pathologic processes underlying many diseases. This study investigates the expression of MMP-9 and MMP-2 in aggressive extracranial AVMs. The differential expression of MMP-9 and its regulatory factors is also examined. Herein we demonstrate that mRNA and protein expressions of MMP-9, but not MMP-2, are significantly higher in AVM tissues compared to normal tissues. The serum level of MMP-9, but not MMP-2, is also elevated in AVM patients compared to healthy controls. MMP-9/neutrophil gelatinase-associated lipocalin (NGAL) complex is also significantly increased in AVM tissues. The MMP-9/ tissue inhibitor of metalloproteases-1 (TIMP-1) complex presents as a major form detected in normal tissues. The increased and aberrant expression of MMP-9 and specific MMP-9 forms may help explain the constitutive vascular remodeling and infiltrative nature of these lesions. Specific MMP-9 inhibitors would be a promising treatment for AVMs. PMID:27075045

  10. Osthole, a natural coumarin, improves neurobehavioral functions and reduces infarct volume and matrix metalloproteinase-9 activity after transient focal cerebral ischemia in rats.

    PubMed

    Mao, Xuexuan; Yin, Wei; Liu, Mengfei; Ye, Minzhong; Liu, Peiqing; Liu, Jianxin; Lian, Qishen; Xu, Suowen; Pi, Rongbiao

    2011-04-18

    Previously we demonstrated that Osthole, a natural coumarin, protects against focal cerebral ischemia/reperfusion-induced injury in rats. In the present study, the effects of Osthole on neurobehavioral functions, infarct volume and matrix metalloproteinase-9 (MMP-9) in a rat 2h focal cerebral ischemia model were investigated. Osthole (100mg/kg per dose) was administrated intraperitoneally 30min before ischemic insult and immediately after reperfusion. Osthole treatment significantly reduced neurological deficit score and infarct volume by 38.5% and 33.8%, respectively, as compared with the untreated animals. Osthole reversed ischemia-reperfusion-induced increase in MMP-9 protein level/activity as evidenced by Western blotting and gelatin zymography. Taken together, these results for the first time demonstrate that Osthole reduces infarct volume, restores neurobehavioral functions and downregulates MMP-9 protein level/activity in ischemia/reperfused brain. PMID:21316348

  11. Roles of mitogen activated protein kinases and EGF receptor in arsenite-stimulated matrix metalloproteinase-9 production

    SciTech Connect

    Cooper, Karen L.; Myers, Terrance Alix; Rosenberg, Martina; Chavez, Miquella; Hudson, Laurie G. . E-mail: lghudson@unm.edu

    2004-11-01

    The dermatotoxicity of arsenic is well established and epidemiological studies identify an increased incidence of keratinocytic tumors (basal cell and squamous cell carcinoma) associated with arsenic exposure. Little is known about the underlying mechanisms of arsenic-mediated skin carcinogenesis, but activation of mitogen-activated protein (MAP) kinases and subsequent regulation of downstream target genes may contribute to tumor promotion and progression. In this study, we investigated activation of the extracellular signal regulated kinase (ERK) and the stress-associated kinase p38 by arsenite in HaCat cells, a spontaneously immortalized human keratinocyte cell line. Arsenite concentrations {>=}100 {mu}M stimulate rapid activation of p38 and ERK MAP kinases. However, upon extended exposure (24 h), persistent stimulation of p38 and ERK MAP kinases was detected at low micromolar concentrations of arsenite. Although ERK and p38 were activated with similar time and concentration dependence, the mechanism of activation differed for these two MAP kinases. ERK activation by arsenite was fully dependent on the catalytic activity of the epidermal growth factor (EGF) receptor and partially dependent on Src-family kinase activity. In contrast, p38 activation was independent of EGF receptor or Src-family kinase activity. Arsenite-stimulated MAP kinase signal transduction resulted in increased production of matrix metalloproteinase (MMP)-9, an AP-1 regulated gene product. MMP-9 induction by arsenite was prevented when EGF receptor or MAP kinase signaling was inhibited. These studies indicate that EGF receptor activation is a component of arsenite-mediated signal transduction and gene expression in keratinocytes and that low micromolar concentrations of arsenite stimulate key signaling pathways upon extended exposure. Stimulation of MAP kinase cascades by arsenic and subsequent regulation of genes including c-fos, c-jun, and the matrix degrading proteases may play an important

  12. Glycoursodeoxycholic acid reduces matrix metalloproteinase-9 and caspase-9 activation in a cellular model of superoxide dismutase-1 neurodegeneration.

    PubMed

    Vaz, Ana Rita; Cunha, Carolina; Gomes, Cátia; Schmucki, Nadja; Barbosa, Marta; Brites, Dora

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects mainly motor neurons (MNs). NSC-34 MN-like cells carrying the G93A mutation in human superoxide dismutase-1 (hSOD1(G93A)) are a common model to study the molecular mechanisms of neurodegeneration in ALS. Although the underlying pathways of MN failure still remain elusive, increased apoptosis and oxidative stress seem to be implicated. Riluzole, the only approved drug, only slightly delays ALS progression. Ursodeoxycholic acid (UDCA), as well as its glycine (glycoursodeoxycholic acid, GUDCA) and taurine (TUDCA) conjugated species, have shown therapeutic efficacy in neurodegenerative models and diseases. Pilot studies in ALS patients indicate safety and tolerability for UDCA oral administration. We explored the mechanisms associated with superoxide dismutase-1 (SOD1) accumulation and MN degeneration in NSC-34/hSOD1(G93A) cells differentiated for 4 days in vitro (DIV). We examined GUDCA efficacy in preventing such pathological events and in restoring MN functionality by incubating cells with 50 μM GUDCA at 0 DIV and at 2 DIV, respectively. Increased cytosolic SOD1 inclusions were observed in 4 DIV NSC-34/hSOD1(G93A) cells together with decreased mitochondria viability (1.2-fold, p < 0.01), caspase-9 activation (1.8-fold, p < 0.05), and apoptosis (2.1-fold, p < 0.01). GUDCA exerted preventive effects (p < 0.05) while also reduced caspase-9 levels when added at 2 DIV (p < 0.05). ATP depletion (2-fold, p < 0.05), increased nitrites (1.6-fold, p < 0.05) and metalloproteinase-9 (MMP-9) activation (1.8-fold, p < 0.05), but no changes in MMP-2, were observed in the extracellular media of 4 DIV NSC-34/hSOD1(G93A) cells. GUDCA inhibited nitrite production (p < 0.05) while simultaneously prevented and reverted MMP-9 activation (p < 0.05), but not ATP depletion. Data highlight caspase-9 and MMP-9 activation as key pathomechanisms in ALS and GUDCA

  13. High Levels of 17β-Estradiol Are Associated with Increased Matrix Metalloproteinase-2 and Metalloproteinase-9 Activity in Tears of Postmenopausal Women with Dry Eye

    PubMed Central

    Shen, Guanglin; Ma, Xiaoping

    2016-01-01

    Purpose. To determine the serum levels of sex steroids and tear matrix metalloproteinases (MMP) 2 and 9 concentrations in postmenopausal women with dry eye. Methods. Forty-four postmenopausal women with dry eye and 22 asymptomatic controls were enrolled. Blood was drawn and analyzed for serum levels of sex steroids and lipids. Then, the following tests were performed: tear collection, Ocular Surface Disease Index (OSDI) questionnaire, fluorescein tear film break-up time (TBUT), corneal fluorescein staining, Schirmer test, and conjunctival impression cytology. The conjunctival mRNA expression and tear concentrations of MMP-2 and MMP-9 were measured. Results. Serum 17β-estradiol levels were significantly higher in the dry eye subjects than in the controls (P = 0.03), whereas there were no significant differences in levels of testosterone, dehydroepiandrosterone sulfate (DHEA-S), and progesterone. Tear MMP-2 and MMP-9 concentrations (P < 0.001), as well as the MMP-9 mRNA expression in conjunctival samples (P = 0.02), were significantly higher in dry eye subjects than in controls. Serum 17β-estradiol levels were positively correlated with tear MMP-2 and MMP-9 concentrations and negatively correlated with Schirmer test values. Conclusions. High levels of 17β-estradiol are associated with increased matrix metalloproteinase-2 and metalloproteinase-9 activity in tears of postmenopausal women with dry eye. PMID:26904272

  14. Expression profiles of matrix metalloproteinase 9 in teleost fish provide evidence for its active role in initiation and resolution of inflammation

    PubMed Central

    Chadzinska, Magdalena; Baginski, Pawel; Kolaczkowska, Elzbieta; Savelkoul, Huub F J; Lidy Verburg-van Kemenade, B M

    2008-01-01

    Matrix metalloproteinase 9 (MMP-9) belongs to a family of zinc-dependent endopeptidases. As a consequence of its ability to cleave structural extracellular matrix molecules, mammalian MMP-9 is associated with vital inflammatory processes such as leucocyte migration and tissue remodelling and regeneration. Interestingly, MMP-9 genes have been identified in fish, but functional data are still limited and focus on the involvement of MMP-9 in embryonic development, reproduction and post-mortem tenderization. Here, we describe the involvement of MMP-9 in the innate immunity of carp. In carp, MMP-9 was most notably expressed in classical fish immune organs and in peritoneal and peripheral blood leucocytes, indicating a role of MMP-9 in immune responses. In our well-characterized zymosan-induced peritonitis model for carp, we analysed expression of the MMP-9 gene and the gelatinolytic levels of both pro- and activated forms of MMP-9. The biphasic profile of MMP-9 mRNA expression indicated involvement during the initial phase of inflammation and during the later phase of tissue remodelling. Also, in vitro stimulation of carp phagocytes with lipopolysaccharide or concanavalin A increased MMP-9 gene expression, with a peak at 24 hr. The increase of MMP-9 mRNA correlated with the peak of MMP-9 gelatinolytic level in culture supernatants. These results provide evidence for an evolutionarily conserved and relevant role of MMP-9 in the innate immune response. PMID:18557954

  15. Abnormal activation of calpain and protein kinase Cα promotes a constitutive release of matrix metalloproteinase 9 in peripheral blood mononuclear cells from cystic fibrosis patients.

    PubMed

    Averna, Monica; Bavestrello, Margherita; Cresta, Federico; Pedrazzi, Marco; De Tullio, Roberta; Minicucci, Laura; Sparatore, Bianca; Salamino, Franca; Pontremoli, Sandro; Melloni, Edon

    2016-08-15

    Matrix metalloproteinase 9 (MMP9) is physiologically involved in remodeling the extracellular matrix components but its abnormal release has been observed in several human pathologies. We here report that peripheral blood mononuclear cells (PBMCs), isolated from cystic fibrosis (CF) patients homozygous for F508del-cystic fibrosis transmembrane conductance regulator (CFTR), express constitutively and release at high rate MMP9 due to the alteration in their intracellular Ca(2+) homeostasis. This spontaneous and sustained MMP9 secretion may contribute to the accumulation of this protease in fluids of CF patients. Conversely, in PBMCs isolated from healthy donors, expression and secretion of MMP9 are undetectable but can be evoked, after 12 h of culture, by paracrine stimulation which also promotes an increase in [Ca(2+)]i. We also demonstrate that in both CF and control PBMCs the Ca(2+)-dependent MMP9 secretion is mediated by the concomitant activation of calpain and protein kinase Cα (PKCα), and that MMP9 expression involves extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) phosphorylation. Our results are supported by the fact that either the inhibition of Ca(2+) entry or chelation of [Ca(2+)]i as well as the inhibition of single components of the signaling pathway or the restoration of CFTR activity all promote the reduction of MMP9 secretion. PMID:27349634

  16. Selective Expression of Osteopontin in ALS-resistant Motor Neurons is a Critical Determinant of Late Phase Neurodegeneration Mediated by Matrix Metalloproteinase-9

    PubMed Central

    Morisaki, Yuta; Niikura, Mamiko; Watanabe, Mizuho; Onishi, Kosuke; Tanabe, Shogo; Moriwaki, Yasuhiro; Okuda, Takashi; Ohara, Shinji; Murayama, Shigeo; Takao, Masaki; Uchida, Sae; Yamanaka, Koji; Misawa, Hidemi

    2016-01-01

    Differential vulnerability among motor neuron (MN) subtypes is a fundamental feature of amyotrophic lateral sclerosis (ALS): fast-fatigable (FF) MNs are more vulnerable than fast fatigue-resistant (FR) or slow (S) MNs. The reason for this selective vulnerability remains enigmatic. We report here that the extracellular matrix (ECM) protein osteopontin (OPN) is selectively expressed by FR and S MNs and ALS-resistant motor pools, whereas matrix metalloproteinase-9 (MMP-9) is selectively expressed by FF MNs. OPN is secreted and accumulated as extracellular granules in ECM in three ALS mouse models and a human ALS patient. In SOD1G93A mice, OPN/MMP-9 double positivity marks remodeled FR and S MNs destined to compensate for lost FF MNs before ultimately dying. Genetic ablation of OPN in SOD1G93A mice delayed disease onset but then accelerated disease progression. OPN induced MMP-9 up-regulation via αvβ3 integrin in ChAT-expressing Neuro2a cells, and also induced CD44-mediated astrocyte migration and microglial phagocytosis in a non-cell-autonomous manner. Our results demonstrate that OPN expressed by FR/S MNs is involved in the second-wave neurodegeneration by up-regulating MMP-9 through αvβ3 integrin in the mouse model of ALS. The differences in OPN/MMP-9 expression profiles in MN subsets partially explain the selective MN vulnerability in ALS. PMID:27264390

  17. Selective Expression of Osteopontin in ALS-resistant Motor Neurons is a Critical Determinant of Late Phase Neurodegeneration Mediated by Matrix Metalloproteinase-9.

    PubMed

    Morisaki, Yuta; Niikura, Mamiko; Watanabe, Mizuho; Onishi, Kosuke; Tanabe, Shogo; Moriwaki, Yasuhiro; Okuda, Takashi; Ohara, Shinji; Murayama, Shigeo; Takao, Masaki; Uchida, Sae; Yamanaka, Koji; Misawa, Hidemi

    2016-01-01

    Differential vulnerability among motor neuron (MN) subtypes is a fundamental feature of amyotrophic lateral sclerosis (ALS): fast-fatigable (FF) MNs are more vulnerable than fast fatigue-resistant (FR) or slow (S) MNs. The reason for this selective vulnerability remains enigmatic. We report here that the extracellular matrix (ECM) protein osteopontin (OPN) is selectively expressed by FR and S MNs and ALS-resistant motor pools, whereas matrix metalloproteinase-9 (MMP-9) is selectively expressed by FF MNs. OPN is secreted and accumulated as extracellular granules in ECM in three ALS mouse models and a human ALS patient. In SOD1(G93A) mice, OPN/MMP-9 double positivity marks remodeled FR and S MNs destined to compensate for lost FF MNs before ultimately dying. Genetic ablation of OPN in SOD1(G93A) mice delayed disease onset but then accelerated disease progression. OPN induced MMP-9 up-regulation via αvβ3 integrin in ChAT-expressing Neuro2a cells, and also induced CD44-mediated astrocyte migration and microglial phagocytosis in a non-cell-autonomous manner. Our results demonstrate that OPN expressed by FR/S MNs is involved in the second-wave neurodegeneration by up-regulating MMP-9 through αvβ3 integrin in the mouse model of ALS. The differences in OPN/MMP-9 expression profiles in MN subsets partially explain the selective MN vulnerability in ALS. PMID:27264390

  18. The Extracellular Protease Matrix Metalloproteinase-9 Is Activated by Inhibitory Avoidance Learning and Required for Long-Term Memory

    ERIC Educational Resources Information Center

    Nagy, Vanja; Bozdagi, Ozlem; Huntley, George W.

    2007-01-01

    Matrix metalloproteinases (MMPs) are a family of extracellularly acting proteolytic enzymes with well-recognized roles in plasticity and remodeling of synaptic circuits during brain development and following brain injury. However, it is now becoming increasingly apparent that MMPs also function in normal, nonpathological synaptic plasticity of the…

  19. WW domain-containing oxidoreductase is involved in upregulation of matrix metalloproteinase 9 by Epstein-Barr virus latent membrane protein 2A.

    PubMed

    Lan, Yu-Yan; Wu, Shih-Yi; Lai, Hsiao-Ching; Chang, Nan-Shan; Chang, Fang-Hsin; Tsai, Meng-Hsuan; Su, Ih-Jen; Chang, Yao

    2013-07-12

    WW domain-containing oxidoreductase (WOX1) participates in tumor suppression and many other biologic functions, but its molecular and functional interactions with viral proteins remain largely unknown. This study reveals that WOX1 is physically associated with latent membrane protein 2A (LMP2A), an oncoprotein of Epstein-Barr virus. The molecular interaction involves the tyrosine residue 33 of WOX1 and the proline-rich motifs of LMP2A. Interestingly, endogenous WOX1 is required for some LMP2A-triggered, cancer-promoting effects, including activation of extracellular signal-regulated kinase-1/2, upregulation of matrix metalloproteinase 9 (MMP9) and promotion of cell invasion. Upon knockdown of endogenous WOX1, LMP2A-triggered MMP9 induction is restored by exogenous wild-type WOX1, but not by a WOX1 mutant defective in LMP2A binding. These results indicate that, through interaction with LMP2A, WOX1 is involved in MMP9 induction, suggesting a novel role of WOX1 in Epstein-Barr virus-associated cancer progression. PMID:23770367

  20. Paeoniflorin inhibits proliferation and induces apoptosis of human glioma cells via microRNA-16 upregulation and matrix metalloproteinase-9 downregulation.

    PubMed

    Li, Weihua; Qi, Zhonghua; Wei, Zhenqing; Liu, Siwei; Wang, Pin; Chen, Yanwei; Zhao, Yongshun

    2015-08-01

    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 μΜ 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. PMID:25954855

  1. Testis peritubular myoid cells increase their motility and express matrix-metalloproteinase 9 (MMP-9) after interaction with embryonal carcinoma cells.

    PubMed

    Moreno-Ruiz, P; Arluzea, J; Silván, U; Díez-Torre, A; Andrade, R; Bonilla, Z; Díaz-Núñez, M; Silió, M; Aréchaga, J

    2016-01-01

    Today cancer research studies have highlighted the role of the cancer-stroma interaction in the regulation of invasive processes. However, very little is known about cell-to-cell relationships between germinal cancer cells and the somatic ones belong to their close environment, particularly at early invasion stages. Here, we have studied the potential role of the seminiferous peritubular myoid cells (PTCs), as potential part of the reactive stroma, like tumor myofibroblast, in the progression of embryonal carcinoma (EC). To this end, we show results on the in vitro interactions between F9 murine embryonal carcinoma cells (EC cells) and primary cultures of murine PTCs, using contact-dependent and contact-independent 2D co-cultures. In these circumstances, when EC cells interact with PTCs they change their migratory behavior and matrix-metalloproteinase 9 (MMP-9) was up-regulated in PTCs. Additionally, among a variety of cytokines implicated in tumor-stroma cross-talk, we have examined in more detail the influence of tumor necrosis factor alpha (TNF-α). In this regard, it was observed that this cytokine induced a MMP-9 secretion by PTCs in a pattern dependent on its concentration, whereas does not increase the migration capacity of cancer cells. All together, our results provide evidence for a role played by peritubular myoid cells and cancer-cell secreted TNF- α for a change in the tumor microenvironment during the early stages of EC progression. PMID:26711538

  2. Terminalia catappa Exerts Antimetastatic Effects on Hepatocellular Carcinoma through Transcriptional Inhibition of Matrix Metalloproteinase-9 by Modulating NF-κB and AP-1 Activity.

    PubMed

    Yeh, Chao-Bin; Hsieh, Ming-Ju; Hsieh, Yih-Shou; Chien, Ming-Hsien; Lin, Pen-Yuan; Chiou, Hui-Ling; Yang, Shun-Fa

    2012-01-01

    High mortality and morbidity rates for hepatocellular carcinoma (HCC) in Taiwan primarily result from uncontrolled tumor metastasis. Previous studies have identified that Terminalia catappa leaf extracts (TCE) exert hepatoprotective, antioxidative, antiinflammatory, anticancer, and antimetastatic activities. However, the effects of TCE on HCC and the underlying molecular mechanisms of its activities have yet to be fully elucidated. The present study's findings demonstrate that TCE concentration dependently inhibits human HCC migration/invasion. Zymographic and western blot analyses revealed that TCE inhibited the activities and expression of matrix metalloproteinase-9 (MMP-9). Assessment of mRNA levels, using reverse transcriptase polymerase chain reaction (PCR) and real-time PCR, and promoter assays confirmed the inhibitory effects of TCE on MMP-9 expression in HCC cells. The inhibitory effects of TCE on MMP-9 proceeded by upregulating tissue inhibitor of metalloproteinase-1 (TIMP-1), as well as suppressing nuclear translocation and DNA binding activity of nuclear factor-kappa B (NF-κB) and activating protein-1 (AP-1) on the MMP-9 promoter in Huh7 cells. In conclusion, TCE inhibits MMP-9 expression and HCC cell metastasis and, thus, has potential use as a chemopreventive agent. Its inhibitory effects are associated with downregulation of the binding activities of the transcription factors NF-κB and AP-1. PMID:23258989

  3. Significance of Matrix Metalloproteinase 9 Expression as Supporting Marker to Cytokeratin 19 mRNA in Sentinel Lymph Nodes in Breast Cancer Patients

    PubMed Central

    Murawski, Marek; Woźniak, Marta; Duś-Szachniewicz, Kamila; Kołodziej, Paweł; Rzeszutko, Marta; Ziółkowski, Piotr

    2016-01-01

    One-step nucleic acid amplification (OSNA) detects and quantifies, with the use of a polymerase chain reaction, the presence of cytokeratin 19 mRNA in sentinel lymph nodes. The main advantage of the OSNA assay is the avoidance of second surgery in case of positive sentinel lymph node diagnosis. The objective of this study was to evaluate the significance of matrix metalloproteinase 9 expression by immunohistochemistry as supporting marker to cytokeratin 19 mRNA in sentinel lymph nodes in breast cancer patients and to relate this expression with clinicopathological data. This study was conducted on fresh sentinel lymph nodes obtained from 40 patients with tumors classified as carcinoma of no special type. The presence of metastatic cells in the slices of lymph nodes was evaluated by immunohistochemistry using antibodies for CK19 and MMP-9. Expression of CK19 and MMP-9 in lymph nodes was also confirmed by means of Western blot analysis. Results indicated that the strongest correlation with CK19 mRNA was displayed by MMP-9, CK19 (by immunohistochemistry, IHC), and nodal metastases (p < 0.001). Higher histological grading also positively correlated with CK19 mRNA, however that correlation was less significant. Since MMP-9 shows very strong correlation with CK19 mRNA in breast carcinoma of no special type metastases, expression of MMP-9 in sentinel lymph nodes should be considered as useful method whenever OSNA analysis is not available. PMID:27110764

  4. Effect of daptomycin on local interleukin-6, matrix metalloproteinase-9, and metallopeptidase inhibitor 1 in patients with MRSA-infected diabetic foot.

    PubMed

    Ambrosch, Andreas; Halevy, Daniel; Fwity, Boushra; Brin, Thomas; Lobmann, Ralf

    2014-03-01

    Infection is a major cause of the diabetic foot syndrome that is promoted by the increased burden of multiresistant germs like methicillin-resistant Staphylococcus aureus (MRSA). Maximizing positive outcome for serious MRSA infections requires an aggressive treatment approach and careful monitoring of the healing process. Therefore, we examined 8 patients with MRSA-infected diabetic foot syndrome of Wagner classification grade 2 or 3 (corresponding to the Texas classification stage 2 or 3) during antibiotic treatment with daptomycin. We documented the wound size and obtained samples of wound secretion for analyses of proinflammatory interleukin-6 (IL-6), protease (matrix metalloproteinase-9 [MMP-9]), and antiprotease (metallopeptidase inhibitor 1 [TIMP-1]) activity. During the course of anti-MRSA therapy, we observed a decrease in the concentration of local IL-6 within the first 3 days followed by a decrease of MMP-9 and an increase of TIMP-1. Finally, a reduction of wound size was documented. The present data show that efficient antimicrobial treatment with daptomycin has a number of beneficial effects on wound healing at the molecular level in MRSA-infected diabetic foot ulcers. PMID:24659622

  5. Effect of daptomycin on local interleukin-6, matrix metalloproteinase-9, and metallopeptidase inhibitor 1 in patients with MRSA-infected diabetic foot.

    PubMed

    Ambrosch, Andreas; Halevy, Daniel; Fwity, Boushra; Brin, Thomas; Lobmann, Ralf

    2013-06-01

    Infection is a major cause of the diabetic foot syndrome being aggravating by the increased burden of multiresistant germs like methicillin-resistant Staphylococcus aureus (MRSA). Maximizing positive outcome for serious MRSA infections requires an aggressive treatment approach and a careful monitoring of the healing process. Therefore, we examined 8 patients with MRSA-infected diabetic foot syndrome Wagner classification grades 2 or 3 (corresponding to the Texas classification stage 2 and 3) during antibiotic treatment with daptomycin. We documented the wound size and obtained samples of wound secretion for analyses of pro-inflammatory interleukin-6 (IL-6), protease (matrix metalloproteinase-9 [MMP-9]), and antiprotease activity (metallopeptidase inhibitor 1 [TIMP-1]). During the course of anti-MRSA therapy, a decrease in the concentration of local IL-6 within the first 3 days followed by a drop of MMP-9 and an increase of TIMP-1 was observed. Finally, a reduction of wound size could be documented. The present data show that efficient antimicrobial treatment with daptomycin leads to a number of beneficial processes at the molecular level of wound healing in MRSA-infected diabetic foot ulcers. PMID:23771610

  6. Plasma levels of mature brain-derived neurotrophic factor (BDNF) and matrix metalloproteinase-9 (MMP-9) in treatment-resistant schizophrenia treated with clozapine.

    PubMed

    Yamamori, Hidenaga; Hashimoto, Ryota; Ishima, Tamaki; Kishi, Fukuko; Yasuda, Yuka; Ohi, Kazutaka; Fujimoto, Michiko; Umeda-Yano, Satomi; Ito, Akira; Hashimoto, Kenji; Takeda, Masatoshi

    2013-11-27

    Brain-derived neurotrophic factor (BDNF) regulates the survival and growth of neurons, and influences synaptic efficiency and plasticity. Peripheral BDNF levels in patients with schizophrenia have been widely reported in the literature. However, it is still controversial whether peripheral levels of BDNF are altered in patients with schizophrenia. The peripheral BDNF levels previously reported in patients with schizophrenia were total BDNF (proBDNF and mature BDNF) as it was unable to specifically measure mature BDNF due to limited BDNF antibody specificity. In this study, we examined whether peripheral levels of mature BDNF were altered in patients with treatment-resistant schizophrenia. Matrix metalloproteinase-9 (MMP-9) levels were also measured, as MMP-9 plays a role in the conversion of proBDNF to mature BDNF. Twenty-two patients with treatment-resistant schizophrenia treated with clozapine and 22 age- and sex-matched healthy controls were enrolled. The plasma levels of mature BDNF and MMP-9 were measured using ELISA kits. No significant difference was observed for mature BDNF however, MMP-9 was significantly increased in patients with schizophrenia. The significant correlation was observed between mature BDNF and MMP-9 plasma levels. Neither mature BDNF nor MMP-9 plasma levels were associated clinical variables. Our results do not support the view that peripheral BDNF levels are associated with schizophrenia. MMP-9 may play a role in the pathophysiology of schizophrenia and serve as a biomarker for schizophrenia. PMID:24141084

  7. The Effector Protein BPE005 from Brucella abortus Induces Collagen Deposition and Matrix Metalloproteinase 9 Downmodulation via Transforming Growth Factor β1 in Hepatic Stellate Cells.

    PubMed

    Arriola Benitez, Paula Constanza; Rey Serantes, Diego; Herrmann, Claudia Karina; Pesce Viglietti, Ayelén Ivana; Vanzulli, Silvia; Giambartolomei, Guillermo Hernán; Comerci, Diego José; Delpino, María Victoria

    2016-02-01

    The liver is frequently affected in patients with active brucellosis. In the present study, we identified a virulence factor involved in the modulation of hepatic stellate cell function and consequent fibrosis during Brucella abortus infection. This study assessed the role of BPE005 protein from B. abortus in the fibrotic phenotype induced on hepatic stellate cells during B. abortus infection in vitro and in vivo. We demonstrated that the fibrotic phenotype induced by B. abortus on hepatic stellate (LX-2) cells was dependent on BPE005, a protein associated with the type IV secretion system (T4SS) VirB from B. abortus. Our results indicated that B. abortus inhibits matrix metalloproteinase 9 (MMP-9) secretion through the activity of the BPE005-secreted protein and induces concomitant collagen deposition by LX-2 cells. BPE005 is a small protein containing a cyclic nucleotide monophosphate binding domain (cNMP) that modulates the LX-2 cell phenotype through a mechanism that is dependent on the cyclic AMP (cAMP)/protein kinase A (PKA) signaling pathway. Altogether, these results indicate that B. abortus tilts LX-2 cells to a profibrogenic phenotype employing a functional T4SS and the secreted BPE005 protein through a mechanism that involves the cAMP and PKA signaling pathway. PMID:26667834

  8. Impact of 4-hydroxynonenal on matrix metalloproteinase-9 regulation in lipopolysaccharide-stimulated RAW 264.7 cells.

    PubMed

    Schrimpe-Rutledge, Alexandra C; Fong, Kim Y; Wright, David W

    2015-03-01

    Tissue degradation and leukocyte extravasation suggest proteolytic destruction of the extracellular matrix (ECM) during severe malaria. Matrix metalloproteinases (MMPs) play an established role in ECM turnover, and increased MMP-9 protein abundance is correlated with malarial infection. The malaria pigment hemozoin (Hz) is a heme detoxification biomineral that is produced during infection and associated with biologically active lipid peroxidation products such as 4-hydroxynonenal (HNE) adsorbed to its surface. Hz has innate immunomodulatory activity, and many of its effects can be reproduced by exogenously added HNE. Hz phagocytosis enhances MMP-9 expression in monocytes; thus, this study was designed to examine the ability of HNE to alter MMP-9 regulation in activated cells of macrophage lineage. Data show that treatment of lipopolysaccharide-stimulated RAW 264.7 cells with HNE increased MMP-9 secretion and activity. HNE treatment abolished the cognate tissue inhibitor of metalloproteinase-1 protein levels, further decreasing MMP-9 regulation. Phosphorylation of both p38 mitogen-activated protein kinase (MAPK) and c-Jun NH2-terminal kinase was induced by HNE, but only p38 MAPK inhibition lessened MMP-9 secretion. These results demonstrate the in vitro ability of HNE to cause MMP-9 dysregulation in an activated cell model. The findings may extend to myriad pathologies associated with lipid peroxidation and elevated MMP-9 levels leading to tissue damage. PMID:25663587

  9. c-Met identifies a population of matrix metalloproteinase 9-producing monocytes in peritumoural stroma of hepatocellular carcinoma.

    PubMed

    Zhao, Lan; Wu, Yan; Xie, Xu-Dong; Chu, Yi-Fan; Li, Jin-Qing; Zheng, Limin

    2015-11-01

    Macrophages (Mϕ) are prominent components of solid tumours and exhibit distinct phenotypes in different microenvironments. Previously, we found that tumours could alter the normal developmental process of Mϕ to trigger transient activation of monocytes in the peritumoural stroma of human hepatocellular carcinoma (HCC). In the present study, we showed that a fraction of monocytes in the peritumoural stroma, but not in HCC cancer nests, expressed surface c-Met molecules. Monocytes exposed to tumours strongly expressed c-Met proteins with kinetics similar to their activation status, and significant correlations were found between c-Met levels and HLA-DR expression on tumour-infiltrating monocytes. NF-κB-mediated autocrine TNF-α stimulated the expression of c-Met on activated monocytes, and by interacting with its ligand hepatocyte growth factor (HGF), c-Met increased the motility and matrix metalloproteinase (MMP) 9-producing capacity of tumour-associated monocytes. The intensity of c-Met expression on tumour-infiltrating monocytes was associated with high mortality and reduced survival of patients with HCC. Therefore, the expression of c-Met on activated monocytes/Mϕ may represent a novel mechanism by which a tumour actively and precisely regulates the distribution and functions of these cells to facilitate disease progression. PMID:26108200

  10. Thyroid hormone regulates adhesion, migration and matrix metalloproteinase 9 activity via αvβ3 integrin in myeloma cells.

    PubMed

    Cohen, Keren; Flint, Nir; Shalev, Shachar; Erez, Daniel; Baharal, Tal; Davis, Paul J; Hercbergs, Aleck; Ellis, Martin; Ashur-Fabian, Osnat

    2014-08-15

    Thyroid hormone (3,5,3'-triiodothyronine, T3; L-thyroxine, T4) enhances cancer cell proliferation, invasion and angiogenesis via a discrete receptor located near the RGD recognition site on αvβ3 integrin. Tetraiodothyroacetic acid (tetrac) and its nanoparticulate formulation interfere with binding of T3/T4 to the integrin. This integrin is overexpressed in multiple myeloma (MM) and other cancers. MM cells interact with αvβ3 integrin to support growth and invasion. Matrix metalloproteinases (MMPs) are a family of enzymes active in tissue remodeling and cancer. The association between integrins and MMPs secretion and action is well established. In the current study, we examined the effects of thyroid hormone on myeloma cell adhesion, migration and MMP activity. We show that T3 and T4 increased myeloma adhesion to fibronectin and induced αvβ3 clustering. In addition, the hormones induced MMP-9 expression and activation via αvβ3 and MAPK induction. Bortezomib, a standard myeloma treatment, caused a decrease in activity/quantity of MMPs and thyroid hormone opposed this effect. RGD peptide and tetrac impaired the production of MMP-9 in cell lines and in primary BM cells from myeloma patients. In conclusion, thyroid hormone-dependent regulation via αvβ3 of myeloma cell adhesion and MMP-9 production may play a role in myeloma migration and progression. PMID:25071016

  11. Eicosapentaenoic acid inhibits TNF-{alpha}-induced matrix metalloproteinase-9 expression in human keratinocytes, HaCaT cells

    SciTech Connect

    Kim, Hyeon Ho; Lee, Youngae; Eun, Hee Chul Chung, Jin Ho

    2008-04-04

    Eicosapentaenoic acid (EPA) is an omega-3 ({omega}-3) polyunsaturated fatty acid (PUFA), which has anti-inflammatory and anti-cancer properties. Some reports have demonstrated that EPA inhibits NF-{kappa}B activation induced by tumor necrosis factor (TNF)-{alpha} or lipopolysaccharide (LPS) in various cells. However, its detailed mode of action is unclear. In this report, we investigated whether EPA inhibits the expression of TNF-{alpha}-induced matrix metalloproteinases (MMP)-9 in human immortalized keratinocytes (HaCaT). TNF-{alpha} induced MMP-9 expression by NF-{kappa}B-dependent pathway. Pretreatment of EPA inhibited TNF-{alpha}-induced MMP-9 expression and p65 phosphorylation. However, EPA could not affect I{kappa}B-{alpha} phosphorylation, nuclear translocation of p65, and DNA binding activity of NF-{kappa}B. EPA inhibited TNF-{alpha}-induced p65 phosphorylation through p38 and Akt inhibition and this inhibition was IKK{alpha}-dependent event. Taken together, we demonstrate that EPA inhibits TNF-{alpha}-induced MMP-9 expression through inhibition of p38 and Akt activation.

  12. Thyroid hormone regulates adhesion, migration and matrix metalloproteinase 9 activity via αvβ3 integrin in myeloma cells

    PubMed Central

    Cohen, Keren; Flint, Nir; Shalev, Shachar; Erez, Daniel; Baharal, Tal; Davis, Paul J.; Hercbergs, Aleck; Ellis, Martin; Ashur-Fabian, Osnat

    2014-01-01

    Thyroid hormone (3,5,3′-triiodothyronine, T3; L-thyroxine, T4) enhances cancer cell proliferation, invasion and angiogenesis via a discrete receptor located near the RGD recognition site on αvβ3 integrin. Tetraiodothyroacetic acid (tetrac) and its nanoparticulate formulation interfere with binding of T3/T4 to the integrin. This integrin is overexpressed in multiple myeloma (MM) and other cancers. MM cells interact with αvβ3 integrin to support growth and invasion. Matrix metalloproteinases (MMPs) are a family of enzymes active in tissue remodeling and cancer. The association between integrins and MMPs secretion and action is well established. In the current study, we examined the effects of thyroid hormone on myeloma cell adhesion, migration and MMP activity. We show that T3 and T4 increased myeloma adhesion to fibronectin and induced αvβ3 clustering. In addition, the hormones induced MMP-9 expression and activation via αvβ3 and MAPK induction. Bortezomib, a standard myeloma treatment, caused a decrease in activity/quantity of MMPs and thyroid hormone opposed this effect. RGD peptide and tetrac impaired the production of MMP-9 in cell lines and in primary BM cells from myeloma patients. In conclusion, thyroid hormone-dependent regulation via αvβ3 of myeloma cell adhesion and MMP-9 production may play a role in myeloma migration and progression. PMID:25071016

  13. Melatonin inhibits TPA-induced oral cancer cell migration by suppressing matrix metalloproteinase-9 activation through the histone acetylation

    PubMed Central

    Yeh, Chia-Ming; Lin, Chiao-Wen; Yang, Jia-Sin; Yang, Wei-En; Su, Shih-Chi; Yang, Shun-Fa

    2016-01-01

    Melatonin exerts antimetastatic effects on liver and breast cancer and also inhibits matrix metalloproteinase (MMP) activity. However, the detailed impacts and underlying mechanisms of melatonin on oral cancer cell metastasis are still unclear. This study showed that melatonin attenuated the 12-O-tetradecanoylphorbol-13-acetate-induced migration of oral cancer cell lines, HSC-3 and OECM-1. Zymography, quantitative real-time PCR, and Western blotting analyses revealed that melatonin lessened MMP-9 enzyme activity as well as the expression of MMP-9 mRNA and protein. Furthermore, melatonin suppressed the phosphorylation of the ERK1/2 signalling pathway, which dampened MMP-9 gene transcription by affecting the expression of transcriptional coactivators, such as CREB-binding protein (CREBBP) and E1A binding protein p300 (EP300), and decreasing histone acetylation in HSC-3 and OECM-1 cells. Examinations on clinical samples exhibited that MMP-9, CREBBP, and EP300 were significantly increased in oral cancer tissues. Moreover, the relative level of CREBBP was positively correlated with the expression of MMP-9 and EP300. In conclusion, we demonstrated that melatonin inhibits the motility of HSC-3 and OECM-1 cells in vitro through a molecular mechanism that involves attenuation of MMP-9 expression and activity mediated by decreased histone acetylation. PMID:26980735

  14. Orally administered betaine reduces photodamage caused by UVB irradiation through the regulation of matrix metalloproteinase-9 activity in hairless mice.

    PubMed

    Im, A-Rang; Lee, Hee Jeong; Youn, Ui Joung; Hyun, Jin Won; Chae, Sungwook

    2016-01-01

    Betaine is widely distributed in plants, microorganisms, in several types of food and in medical herbs, including Lycium chinense. The administration of 100 mg betaine/kg body weight/day is an effective strategy for preventing ultraviolet irradiation‑induced skin damage. The present study aimed to determine the preventive effects of betaine on ultraviolet B (UVB) irradiation‑induced skin damage in hairless mice. The mice were divided into three groups: Control (n=5), UVB‑treated vehicle (n=5) and UVB‑treated betaine (n=5) groups. The level of irradiation was progressively increased between 60 mJ/cm2 per exposure at week 1 (one minimal erythematous dose = 60 mJ/cm2) and 90 mJ/cm2 per exposure at week 7. The formation of wrinkles significantly increased following UVB exposure in the UVB‑treated vehicle group. However, treatment with betaine suppressed UVB‑induced wrinkle formation, as determined by the mean length, mean depth, number, epidermal thickness and collagen damage. Furthermore, oral administration of betaine also inhibited the UVB‑induced expression of mitogen‑activated protein kinase kinase (MEK), extracellular signal‑regulated kinase (ERK), and matrix metalloproteinase‑9 (MMP‑9). These findings suggested that betaine inhibits UVB‑induced skin damage by suppressing increased expression of MMP‑9 through the inhibition of MEK and ERK. PMID:26648401

  15. Deficiency of the protein-tyrosine phosphatase DEP-1/PTPRJ promotes matrix metalloproteinase-9 expression in meningioma cells.

    PubMed

    Petermann, Astrid; Stampnik, Yvonn; Cui, Yan; Morrison, Helen; Pachow, Doreen; Kliese, Nadine; Mawrin, Christian; Böhmer, Frank-D

    2015-05-01

    Brain-invasive growth of a subset of meningiomas is associated with less favorable prognosis. The molecular mechanisms causing invasiveness are only partially understood, however, the expression of matrix metalloproteinases (MMPs) has been identified as a contributing factor. We have previously found that loss of density enhanced phosphatase-1 (DEP-1, also designated PTPRJ), a transmembrane protein-tyrosine phosphatase, promotes meningioma cell motility and invasive growth in an orthotopic xenotransplantation model. We have now analyzed potential alterations of the expression of genes involved in motility control, caused by DEP-1 loss in meningioma cell lines. DEP-1 depleted cells exhibited increased expression of mRNA encoding MMP-9, and the growth factors EGF and FGF-2. The increase of MMP-9 expression in DEP-1 depleted cells was also readily detectable at the protein level by zymography. MMP-9 upregulation was sensitive to chemical inhibitors of growth factor signal transduction. Conversely, MMP-9 mRNA levels could be stimulated with growth factors (e.g. EGF) and inflammatory cytokines (e.g. TNFα). Increase of MMP-9 expression by DEP-1 depletion, or growth factor/cytokine stimulation qualitatively correlated with increased invasiveness in vitro scored as transmigration through matrigel-coated membranes. The studies suggest induction of MMP-9 expression promoted by DEP-1 deficiency, or potentially by growth factors and inflammatory cytokines, as a mechanism contributing to meningioma brain invasiveness. PMID:25672645

  16. Regulation of high glucose-mediated mucin expression by matrix metalloproteinase-9 in human airway epithelial cells.

    PubMed

    Yu, Hongmei; Yang, Juan; Xiao, Qian; Lü, Yang; Zhou, Xiangdong; Xia, Li; Nie, Daijing

    2015-04-10

    Mucus hypersecretion is the key manifestation in patients with chronic inflammatory airway diseases and mucin 5AC (MUC5AC) is a major component of airway mucus. Matrix metalloproteinases (MMP)-9, have been found to be involved in the pathogenesis of inflammatory airway diseases. Hyperglycemia has been shown to be an independent risk factor for respiratory infections. We hypothesize that high glucose (HG)-regulates MMP-9 production and MMP-9 activity through nicotinamide adenine dinucleotide phosphate (NADPH)/reactive oxygen species (ROS) cascades pathways, leading to mucin production in human airway epithelial cells (16HBE). We show that HG increases MMP-9 production, MMP-9 activity and MUC5AC expression. These effects are prevented by small interfering RNA (siRNA) for MMP-9, indicating that HG-induced mucin production is MMP-9-dependent. HG activates MMP-9 production, MMP-9 activity and MUC5AC overproduction, which is inhibited by nPG, DMSO and DPI (inhibitors of ROS and NADPH), suggesting that HG-activated mucin synthesis is mediated by NADPH/ROS in 16HBE cells. These observations demonstrate an important role for MMP-9 activated by NADPH/ROS signaling pathways in regulating HG-induced MUC5AC expression. These findings may bring new insights into the molecular pathogenesis of the infections related to diabetes mellitus and lead to novel therapeutic intervention for mucin overproduction in chronic inflammatory airway diseases. PMID:25704757

  17. Toll-like Receptor-4 Polymorphisms and Serum Matrix Metalloproteinase-9 in Newly Diagnosed Patients With Calcified Neurocysticercosis and Seizures

    PubMed Central

    Lachuriya, Gaurav; Garg, Ravindra Kumar; Jain, Amita; Malhotra, Hardeep Singh; Singh, Arvind Kumar; Jain, Bhawna; Kumar, Neeraj; Verma, Rajesh; Sharma, Praveen Kumar

    2016-01-01

    Abstract We evaluated seizure profile, Toll-like receptor (TLR)-4 polymorphisms, and serum matrix metalloproteinases (MMPs) in patients with calcified neurocysticercosis. One-hundred nine patients with calcified neurocysticercosis with newly diagnosed seizures and 109 control subjects were enrolled. TLR-4 Asp299Gly and Thr399Ile polymorphisms and serum MMP-9 levels were evaluated. The patients were followed for 1 year. Asp/Gly (P = 0.012) and Thr/Ile (P = 0.002), Gly (Asp/Gly plus Gly/Gly) (P = 0.008) and Ile (Thr/Ile plus Ile/Ile) (P = 0.003) genotypes were significantly associated with calcified neurocysticercosis compared with controls. Gly/Gly and Ile/Ile genotypes were not significantly associated (P = 0.529 for Gly/Gly, P = 0.798 for Ile/Ile) with either group. The levels of MMP-9 were higher in calcified neurocysticercosis (P =  < 0.001). The levels of MMP-9 were higher in patients with multiple calcified neurocysticercosis compared with single calcified neurocysticercosis (P =  < 0.001). Headache (P = 0.031), status epilepticus (P = 0.029), Todd paralysis (P = 0.039), lesion size >10 mm (P = 0.001), and perilesional edema (P =  < 0.001) were significantly associated with seizure recurrence. Heterozygous form Asp/Gly (P =  < 0.001) and heterozygous form Thr/Ile (P =  < 0.001) were significantly associated with seizure recurrence. The Gly (Asp/Gly plus Gly/Gly) (P =  < 0.001) and Ile (Thr/Ile plus Ile/Ile) (P =  < 0.001) genotypes were also significantly associated with seizure recurrence. Higher serum MMP-9 levels were significantly associated with seizure recurrence (P =  < 0.001). The TLR-4 gene abnormalities may trigger inflammation around calcified neurocysticercosis leading to an increase in perilesional edema and provocation of seizures. PMID:27124018

  18. A radical scavenger edaravone inhibits matrix metalloproteinase-9 upregulation and blood-brain barrier breakdown in a mouse model of prolonged cerebral hypoperfusion

    PubMed Central

    Maki, Takakuni; Liang, Anna C.; Arai, Ken

    2014-01-01

    Matrix metalloproteinase-9 (MMP-9) plays key roles in the brain pathophysiology, especially in blood-brain barrier (BBB) breakdown. Therefore, inhibiting MMP-9 activity may be a promising therapy for protecting brains in cerebrovascular diseases. Here we show that in a mouse prolonged cerebral hypoperfusion model, a clinically proven radical scavenger edaravone suppressed MMP-9 and reduced BBB damage in cerebral white matter. Prolonged cerebral hypoperfusion was induced by bilateral common carotid artery stenosis in male adult C57BL/6J mice (10 weeks old). After 7 days of cerebral hypoperfusion, white matter region (e.g. corpus callosum) exhibited significant BBB leakage, assessed by IgG staining. Correspondingly, immunostaining and western blotting showed that MMP-9 was upregulated in the white matter. Edaravone treatment (3 mg/kg, i.p. at day 0 and 3) inhibited both BBB leakage and MMP-9 increase. Under the early phase of cerebral hypoperfusion conditions, oligodendrocyte precursor cells (OPCs) mainly contribute to the MMP-9 increase, but our immunostaining data showed that very little OPCs expressed MMP-9 in the edaravone-treated animals at day 7. Therefore, in vitro studies with primary rat OPCs were conducted to examine whether edaravone would directly suppressed MMP-9 expressions in OPCs. OPC cultures were exposed to sub-lethal CoCl2 for 7 days to induce prolonged chemical hypoxic stress. Prolonged chemical hypoxic stress increased MMP-9 expression in OPCs, and radical scavenging with edaravone (10 μM for 7 days) ameliorated the increase. Taken together, our proof-of-concept study demonstrates that radical scavengers may provide a potential therapeutic approach for white matter injury by suppressing BBB damage. PMID:24820542

  19. Aliskiren attenuates bleomycin-induced pulmonary fibrosis in rats: focus on oxidative stress, advanced glycation end products, and matrix metalloproteinase-9.

    PubMed

    Abuelezz, Sally A; Hendawy, Nevien; Osman, Wesam M

    2016-08-01

    Pulmonary fibrosis is a progressive lung disorder with high mortality rate and limited successful treatment. This study was designed to assess the potential anti-oxidant and anti-fibrotic effects of aliskiren (Alsk) during bleomycin (BLM)-induced pulmonary fibrosis. Male Wistar rats were used as control untreated or treated with the following: a single dose of 2.5 mg/kg of BLM endotracheally and BLM and Alsk (either low dose 30 mg/kg/day or high dose 60 mg/kg/day), and another group was given Alsk 60 mg/kg/day alone. Alsk was given by gavage. Alsk anti-oxidant and anti-fibrotic effects were assessed. BLM significantly increased relative lung weight and the levels of lactate dehydrogenase and total and differential leucocytic count in bronchoalveolar lavage that was significantly ameliorated by high-dose Alsk treatment. As markers of oxidative stress, BLM caused a significant increase in the levels of lipid peroxides and nitric oxide accompanied with a significant decrease of superoxide dismutase and glutathione transferase enzymes. High-dose Alsk treatment restored these markers toward normal values. Alsk counteracted the overexpression of advanced glycation end products, matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinases-1 in lung tissue induced by BLM. Fibrosis assessed by measuring hydroxyproline content, which markedly increased in the BLM group, was also significantly reduced by Alsk. These were confirmed by histopathological and immunohistochemical examination which revealed that Alsk attenuates signs of pulmonary fibrosis and decreased the overexpressed MMP-9 and transforming growth factor β1. Collectively, these findings indicate that Alsk has a potential anti-fibrotic effect beside its anti-oxidant activity. PMID:27154762

  20. Sequential measurements of serum matrix metalloproteinase 9 to monitor chemotherapy responses in patients with advanced non-small-cell lung cancer

    PubMed Central

    Qiao, Xiaojuan; Zhai, Xiaoran; Wang, Jinghui; Zhao, Xiaoting; Yang, Xinjie; Lv, Jialin; Ma, Li; Zhang, Lina; Wang, Yue; Zhang, Shucai; Yue, Wentao

    2016-01-01

    Background Matrix metalloproteinase 9 (MMP-9) plays an important role in tumor invasion and metastasis, including lung cancer. However, whether variations in serum MMP-9 levels can serve as a biomarker for monitoring chemotherapy curative effect remains unclear. This study was designed to investigate the association between variations in serum MMP-9 levels and chemotherapy curative effect in patients with lung cancer. Patients and methods A total of 82 patients with advanced lung cancer were included. All newly diagnosed patients were treated with platinum-based doublet chemotherapy. Serial measurements of serum MMP-9 levels were performed by enzyme-linked immunosorbent assay. In this manner, we chose four time points to examine the association, including before chemotherapy, and 3 weeks after the beginning of the first, second, and fourth cycles of chemotherapy. Results Compared with the serum level of MMP-9 before progressive disease, patients with progressive disease had elevated serum levels of MMP-9. Compared with the previous time point of collecting specimens, the serum levels of MMP-9 in the patients with a complete response/partial response/stable disease decreased or were maintained stable. The differences of variation in serum MMP-9 levels in patients with different chemotherapy curative effects were all statistically significant after one cycle, two cycles, and four cycles (after one cycle: P<0.001; after two cycles: P<0.001; after four cycles: P=0.01). However, patients with small-cell lung cancer did not exhibit similar test results. Conclusion The variation in serum MMP-9 levels in patients with non-small-cell lung cancer during chemotherapy was closely related to chemotherapy curative effect and could be useful to monitor chemotherapy curative effect for a small portion of patients. PMID:27330309

  1. Matrix metalloproteinase-9 Gene-1562C>T Gene Polymorphism and Coronary Artery Disease in the Chinese Han Population: A Meta-Analysis of 5468 Subjects

    PubMed Central

    Li, Yan-Yan; Yang, Xin-Xing; Zhou, Yan-Hong; Gong, Ge; Geng, Hong-Yu; Kim, Hyun J.; Zhou, Chuan-Wei; Qian, Yun; Wang, Xiang-Ming; Wu, Jun

    2016-01-01

    Background: Multiple studies indicate that the matrix metalloproteinase-9 (MMP-9)-1562C>T gene polymorphism may be associated with an increased risk of coronary artery disease (CAD) in the Chinese Han population. However, a clear consensus has yet to be established. Objective and methods: A meta-analysis of 5468 subjects from 10 separate studies was performed to explore the possible relationship between the MMP-9-1562C>T gene polymorphism and CAD within the Chinese Han population. Pooled odds ratio (ORs) for the association and the corresponding 95% confidence intervals (CIs) were evaluated by a random or fixed-effect model. Results: Our analysis confirms the association between the MMP-9-1562C>T gene polymorphism and an increased risk of CAD within the Chinese Han population under allelic (OR: 1.60, 95% CI: 1.25–2.04, P = 0.0002), recessive (OR: 3.05, 95% CI: 1.67–5.56, P = 0.0003), dominant (OR: 2.23, 95% CI: 1.49–3.35, P = 0.0001), homozygous (OR: 3.41, 95% CI: 1.87–6.23, P < 0.0001), heterozygous (OR: 2.03, 95% CI: 1.40–2.93, P = 0.0002), and additive genetic models (OR: 1.78, 95% CI: 1.33–2.39, P < 0.0001). Conclusions: In the Chinese Han population, the MMP-9-1562C>T gene polymorphism is correlated with an increased risk of CAD. Therefore, Han Chinese carriers of the -1562T allele may be at an increased risk of CAD. PMID:27375491

  2. Glabridin inhibits migration and invasion by transcriptional inhibition of matrix metalloproteinase 9 through modulation of NF-κB and AP-1 activity in human liver cancer cells

    PubMed Central

    Hsieh, Ming-Ju; Lin, Chiao-Wen; Yang, Shun-Fa; Chen, Mu-Kuan; Chiou, Hui-Ling

    2014-01-01

    BACKGROUND AND PURPOSE High mortality and morbidity rates for hepatocellular carcinoma in Taiwan primarily result from uncontrolled tumour metastasis. Glabridin, a prenylated isoflavonoid of licorice (Glycyrrhiza glabra) roots, is associated with a wide range of biological properties, such as regulation of energy metabolism, oestrogenic, neuroprotective, anti-osteoporotic and skin whitening. However, the effect of glabridin on the metastasis of tumour cells has not been clarified. EXPERIMENTAL APPROACH A wound healing model and Boyden chamber assays in vitro were used to determine the effects of glabridin on the migration and invasion of human hepatocellular carcinoma (HHC) cells. Western blot analysis, gelatin zymography, real-time PCR and promoter assays were used to evaluate the inhibitory effects of glabridin on matrix metalloproteinase 9 (MMP9) expression in these cells. KEY RESULTS Glabridin significantly inhibited migration/invasion capacities of HCC cells, Huh7 and Sk-Hep-1, cell lines that have low cytotoxicity in vitro, even at high concentrations. Western blot analysis and gelatin zymography showed that glabridin inhibited the expression, activities and protein levels of MMP9 and the phosphorylation of ERK1/2 and JNK1/2. These inhibitory effects were associated with an up-regulation of tissue inhibitor of metalloproteinase-1 and a down-regulation of the transcription factors NF-κB and activator protein 1 signalling pathways. Finally, the administration of glabridin effectively suppressed the tumour formation in the hepatoma xenograft model in vivo. CONCLUSION AND IMPLICATIONS Glabridin inhibited the invasion of human HCC cells and may have potential as a chemopreventive agent against liver cancer metastasis. PMID:24641665

  3. Involvement of nitric oxide synthase in matrix metalloproteinase-9- and/or urokinase plasminogen activator receptor-mediated glioma cell migration

    PubMed Central

    2013-01-01

    Background Src tyrosine kinase activates inducible nitric oxide synthase (iNOS) and, in turn, nitric oxide production as a means to transduce cell migration. Src tyrosine kinase plays a key proximal role to control α9β1 signaling. Our recent studies have clearly demonstrated the role of α9β1 integrin in matrix metalloproteinase-9 (MMP-9) and/or urokinase plasminogen activator receptor (uPAR)-mediated glioma cell migration. In the present study, we evaluated the involvement of α9β1 integrin-iNOS pathway in MMP-9- and/or uPAR-mediated glioma cell migration. Methods MMP-9 and uPAR shRNAs and overexpressing plasmids were used to downregulate and upregulate these molecules, respectively in U251 glioma cells and 5310 glioma xenograft cells. The effect of treatments on migration and invasion potential of these glioma cells were assessed by spheroid migration, wound healing, and Matrigel invasion assays. In order to attain the other objectives we also performed immunocytochemical, immunohistochemical, RT-PCR, Western blot and fluorescence-activated cell sorting (FACS) analysis. Results Immunohistochemical analysis revealed the prominent association of iNOS with glioblastoma multiforme (GBM). Immunofluorescence analysis showed prominent expression of iNOS in glioma cells. MMP-9 and/or uPAR knockdown by respective shRNAs reduced iNOS expression in these glioma cells. RT-PCR analysis revealed elevated iNOS mRNA expression in either MMP-9 or uPAR overexpressed glioma cells. The migration potential of MMP-9- and/or uPAR-overexpressed U251 glioma cells was significantly inhibited after treatment with L-NAME, an inhibitor of iNOS. Similarly, a significant inhibition of the invasion potential of the control or MMP-9/uPAR-overexpressed glioma cells was noticed after L-NAME treatment. A prominent reduction of iNOS expression was observed in the tumor regions of nude mice brains, which were injected with 5310 glioma cells, after MMP-9 and/or uPAR knockdown. Protein expressions

  4. Hypothermic Machine Perfusion Reduced Inflammatory Reaction by Downregulating the Expression of Matrix Metalloproteinase 9 in a Reperfusion Model of Donation After Cardiac Death.

    PubMed

    Fu, Zhen; Ye, Qifa; Zhang, Yang; Zhong, Zibiao; Xiong, Yan; Wang, Yanfeng; Hu, Long; Wang, Wei; Huang, Wei; Ko, Dicken Shiu-Chung

    2016-06-01

    The exact mechanism by which hypothermic machine perfusion (HMP) improves the graft quality in kidney transplantation of donation after cardiac death (DCD) remains unclear. The aim of this study was to investigate the correlation between the expression of matrix metalloproteinase 9 (MMP-9) and inflammatory reaction in kidney ischemia-reperfusion (I/R) injury injury followed by cold storage (CS) or HMP model of DCD. New Zealand white rabbit kidneys were subjected to 35 min of warm ischemia and 1 h reperfusion, then preserved by either 1 h reperfusion (sham-operated group), 4 h CS or 4 h HMP in vivo. Kidneys were reperfused 24 h followed by further analysis. No treatment was given to rabbits in the normal control group. The expression of MMP-9, nuclear factor-κB (NF-κB), and MMP-2 mRNA were detected by real-time PCR (RT-PCR). MMP-9 was located by immunohistochemistry and immunofluorescence methods. Tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), myeloperoxidase (MPO), superoxide dismutase (SOD), and malondialdehyde (MDA) were measured by kits for each groups. Compared with the CS group, the expression of MMP-9 and NF-κB mRNA were downregulated in HMP group (P < 0.05). In contrast, expression of MMP-2 mRNA had no statistical significance between CS group and HMP group (P > 0.05). In normal control and sham-operated groups, a low level of MMP-9 expression was detected in glomeruli. However, positive signals of MMP-9 were mostly located in the tubulointerstitium and the vascular wall of CS and HMP groups. Expression of TNF-α, IL-6, MDA, and activity of MPO decreased while activity of SOD in the HMP group increased in contrast to the CS group (P < 0.05). In conclusion, inflammatory cytokines mediated MMP-9 expression through NF-κB band to MMP-9 promoter region, resulting in renal injury. Therefore, HMP reduced inflammatory reaction by downregulating the expression of MMP-9, which may be the mechanism of kidney protection in I

  5. Plasma Brain Natriuretic Peptide, Endothelin-1, and Matrix Metalloproteinase 9 Expression and Significance in Type 2 Diabetes Mellitus Patients with Ischemic Heart Disease

    PubMed Central

    Ju, Chunfang; Ye, Meixin; Li, Feng

    2015-01-01

    Background Type 2 diabetes (DMT2) combined with ischemic heart disease (IHD) promotes the occurrence and development of coronary atherosclerosis. We aimed to provide a theoretical basis for improving patient prognosis through analyzing expression of plasma brain natriuretic peptide (BNP), endothelin-1 (ET 1), and matrix metalloproteinase 9 (MMP-9). Material/Methods Enzyme-linked immunosorbent assay (ELISA) was used to detect BNP, ET-1, and MMP-9 levels in 50 patients with DMT2 only (group A), 47 patients with IHD only (group B), 43 patients with comorbid (both) IHD and DMT2 (group C), and 50 health controls (group D). Group C was further divided into single-branch lesion group, double-branch lesions group, and triple-branch lesion group according to coronary angiography, or cardiac function grade II, III, and IV group according to cardiac function, and their BNP, ET-1, and MMP-9 levels were compared. Results Compared with group D, TG, diastolic, and systolic blood pressure were all significantly elevated in groups A, B, and C. Group C exhibited obviously higher glycosylated hemoglobin than group A. Gensini score in group C was markedly higher than in group B. Compared with group D, BNP, ET-1, and MMP-9 levels were all increased in groups A, B, and C. Group C showed higher levels of BNP, ET-1, and MMP-9 than group A and B. BNP, ET-1, and MMP-9 levels in the triple-branch lesions group were higher than in the single-branch lesions group and double-branch lesions group. The cardiac function grade IV group presented higher levels of BNP, ET-1, and MMP-9 than did the grade II and III groups. BNP, ET-1, and MMP-9 showed a positive correlation to each other. Conclusions BNP, ET-1, and MMP-9 may participate in the occurrence and development of comorbid DMT2 and IHD. They are important objective indicators for evaluating severity and prognosis of patients with comorbid DMA2 and IHD. PMID:26190179

  6. Gallic acid abolishes the EGFR/Src/Akt/Erk-mediated expression of matrix metalloproteinase-9 in MCF-7 breast cancer cells.

    PubMed

    Chen, Ying-Jung; Lin, Ku-Nan; Jhang, Li-Mei; Huang, Chia-Hui; Lee, Yuan-Chin; Chang, Long-Sen

    2016-05-25

    Several studies have revealed that natural compounds are valuable resources to develop novel agents against dysregulation of the EGF/EGFR-mediated matrix metalloproteinase-9 (MMP-9) expression in cancer cells. In view of the findings that EGF/EGFR-mediated MMP-9 expression is closely related to invasion and metastasis of breast cancer. To determine the beneficial effects of gallic acid on the suppression of breast cancer metastasis, we explored the effect of gallic acid on MMP-9 expression in EGF-treated MCF-7 breast cancer cells. Treatment with EGF up-regulated MMP-9 mRNA and protein levels in MCF-7 cells. EGF treatment induced phosphorylation of EGFR and elicited Src activation, subsequently promoting Akt/NFκB (p65) and ERK/c-Jun phosphorylation in MCF-7 cells. Activation of Akt/p65 and ERK/c-Jun was responsible for the MMP-9 up-regulation in EGF-treated cells. Gallic acid repressed the EGF-induced activation of EGFR and Src; furthermore, inactivation of Akt/p65 and ERK/c-Jun was a result of the inhibitory effect of gallic acid on the EGF-induced MMP-9 up-regulation. Over-expression of constitutively active Akt and MEK1 or over-expression of constitutively active Src eradicated the inhibitory effect of gallic acid on the EGF-induced MMP-9 up-regulation. A chromosome conformation capture assay showed that EGF induced a chromosomal loop formation in the MMP-9 promoter via NFκB/p65 and AP-1/c-Jun activation. Treatment with gallic acid, EGFR inhibitor, or Src inhibitor reduced DNA looping. Taken together, our data suggest that gallic acid inhibits the activation of EGFR/Src-mediated Akt and ERK, leading to reduced levels of p65/c-Jun-mediated DNA looping and thus inhibiting MMP-9 expression in EGF-treated MCF-7 cells. PMID:27087131

  7. Immunohistochemical expression of matrix metalloproteinase-1, matrix metalloproteinase-2 and matrix metalloproteinase-9, myofibroblasts and Ki-67 in actinic cheilitis and lip squamous cell carcinoma.

    PubMed

    Bianco, Bianca C; Scotti, Fernanda M; Vieira, Daniella S C; Biz, Michelle T; Castro, Renata G; Modolo, Filipe

    2015-10-01

    Matrix metalloproteinases (MMPs), myofibroblasts (MFs) and epithelial proliferation have key roles in neoplastic progression. In this study immunoexpression of MMP-1, MMP-2 and MMP-9, presence of MFs and the epithelial proliferation index were investigated in actinic cheilitis (AC), lip squamous cell carcinoma (LSCC) and mucocele (MUC). Thirty cases of AC, thirty cases of LSCC and twenty cases of MUC were selected for immunohistochemical investigation of the proteins MMP-1, MMP-2, MMP-9, α-smooth muscle actin (α-SMA) and Ki-67. The MMP-1 expression in the epithelial component was higher in the AC than the MUC and LSCC. In the connective tissue, the expression was higher in the LSCC. MMP-2 showed lower epithelial and stromal immunostaining in the LSCC when compared to the AC and MUC. The epithelial staining for MMP-9 was higher in the AC when compared to the LSCC. However, in the connective tissue, the expression was lower in the AC compared to other lesions. The cell proliferation rate was increased in proportion to the severity of dysplasia in the AC, while in the LSCC it was higher in well-differentiated lesions compared to moderately differentiated. There were no statistically significant differences in number of MFs present in the lesions studied. The results suggest that MMPs could affect the biological behaviour of ACs and LSCCs inasmuch as they could participate in the development and progression from premalignant lesions to malignant lesions. PMID:26515234

  8. A nutrient mixture reduces the expression of matrix metalloproteinases in an animal model of spinal cord injury by modulating matrix metalloproteinase-2 and matrix metalloproteinase-9 promoter activities

    PubMed Central

    ZHANG, HONGQI; CHU, GE; PAN, CHAO; HU, JIANZHONG; GUO, CHAOFENG; LIU, JINYANG; WANG, YUXIANG; WU, JIANHUANG

    2014-01-01

    This study aimed to determine whether a novel nutrient mixture (NM), composed of lysine, ascorbic acid, proline, green tea extracts and other micronutrients, attenuates impairments induced by spinal cord injury (SCI) and to investigate the related molecular mechanisms. A mouse model of SCI was established. Thirty-two mice were divided into four groups. The sham group received vehicle only. The SCI groups were treated orally with saline (saline group), a low dose (500 μg 3 times/day) of NM (NM-LD group) or a high dose (2,000 μg 3 times/day) of NM (NM-HD group). The levels of mouse hindlimb movement were determined every day in the first week post-surgery. The protein expression levels of matrix metalloproteinase (MMP)-2 and MMP-9 were determined by western blotting. Wild-type and mutant MMP-2- and MMP-9-directed luciferase constructs were generated and their luciferase activities were determined. NM significantly facilitated the recovery of hindlimb movement of the mice in comparison to that in the saline group. The expression levels of MMP-2 in the NM-LD and NM-HD groups were decreased by ~50% compared with the saline group as indicated by western blotting results. The expression levels of MMP-9 in the NM-LD and NM-HD groups were decreased to ~25 and ~10%, respectively. These results suggest that NM significantly inhibits the expression of MMP-2 and MMP-9 proteins. Reverse transcription quantitative polymerase chain reaction results indicated that NM reduced the levels of MMP-2 and MMP-9 mRNA. Furthermore, the luciferase results indicated that site-directed mutagenesis comprising a −1306 C to T (C/T) base change in the MMP-2 promoter and a −1562 C/T base change in the MMP-9 promoter abolished the inhibitory effects of NM on MMP-2 and MMP-9 promoters. These results suggest that NM attenuates SCI-induced impairments in mice movement by negatively affecting the promoter activity of MMP-2 and MMP-9 genes and thus decreasing the expression of MMP-2 and MMP-9

  9. The Effect of Progestins on Tumor Necrosis Factor α-Induced Matrix Metalloproteinase 9 Activity and Gene Expression in Human Primary Amnion and Chorion Cells In Vitro

    PubMed Central

    Allen, Terrence K; Feng, Liping; Nazzal, Matthew; Grotegut, Chad A; Buhimschi, Irina A; Murtha, Amy P

    2015-01-01

    Background Current treatment modalities for preventing preterm premature rupture of membranes (PPROM) are limited, but progestins may play a role. Tumor necrosis factor α (TNFα) enhances matrix metalloproteinase 9 (MMP-9) gene expression and activity in fetal membranes, contributing to membrane weakening and rupture. We previously demonstrated that progestins attenuate TNFα-induced MMP-9 activity in a cytotrophoblast cell line. However, whether they have a similar effect in primary amnion and chorion cells of fetal membranes is unknown. In this study we evaluated the effect of progestins on basal and TNFα-induced MMP-9 activity and gene expression in primary chorion and amnion cells harvested from the fetal membranes of term non-laboring patients. Methods Primary amnion and chorion cells were isolated from fetal membranes obtained from term uncomplicated non-laboring patients following elective cesarean delivery (n=11). Confluent primary amnion and chorion cell cultures were both pretreated with vehicle (control), progesterone (P4), 17α-hydroxyprogesterone caproate (17P) or medroxyprogesterone acetate (MPA) at 10-6 M concentration for 6 h followed by stimulation with TNFα at 10 ng/mL for an additional 24 h. Cell cultures pretreated with the vehicle only served as the unstimulated control and the vehicle stimulated with TNFα served as the stimulated control. Both controls were assigned a value of 100 units. Cell culture medium was harvested for MMP-9 enzymatic activity quantification using gelatin zymography. Total RNA was extracted for quantifying MMP-9 gene expression using RT-qPCR. Basal MMP-9 activity and gene expression data were normalized to the unstimulated control. TNFα-stimulated MMP-9 activity and gene expression were normalized to the stimulated control. The primary outcome was the effect of progestins on TNFα-induced MMP-9 enzymatic activity in term human primary amnion and chorion cells in vitro. Secondary outcomes included the effect of

  10. Expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase (TIMP-1) in tissues with a diagnosis of childhood lymphoma.

    PubMed

    Bozkurt, Ceyhun; Ertem, Ulya; Oksal, Aysegül; Sahin, Gürses; Yüksek, Nazmiye; Birgen, Dilek

    2008-09-01

    Matrix metalloproteinases (MMP) are enzymes involved in the reconfiguration of the microenvironment by means of degrading the extracellular matrix and have more than 20 subgroups containing zinc. Proteins that serve as the inhibitors of these enzymes are called tissue inhibitors of matrix metalloproteinase (TIMP). These enzymes have been shown to be active in a wide range of processes, from wound recovery to fetus development, heart diseases, and spread of malignant diseases. The aim of this study was to investigate whether there is a relationship between the type, stage, and prognosis of childhood lymphoma subjects and matrix metalloproteinase type-9 (MMP-9) and its inhibitor, tissue inhibitor of matrix metalloproteinase type-1 (TIMP-1). Paraffin blocks of childhood patients diagnosed with non-Hodgkin lymphoma (n = 23), Hodgkin lymphoma (n = 14), or reactive lymphadenopathy (n = 12) were retrospectively immunohistochemically stained with MMP-9 and TIMP-1 stains and whether there was a relationship between the degree of staining and the type, tumor stage, and prognosis of the disease was investigated. Moderate and high degrees of MMP-9 staining were detected in 94.6% of the lymphoma patient tissues and a slight TIMP-1 staining was detected in 21.6% of the lymphoma patient tissues. No relationship was observed between the degree of these staining patterns and the type, tumor stage, and prognosis of the disease. This study indicates that the equilibrium between MMP-9 and TIMP-1 is important in lymphomas in addition to all the physiological and pathologic events although MMP-9 and the TIMP-1 staining patterns are not related to the tumor stage, prognosis, and type of the disease. Larger series of patients are needed to determine the prognostic value of MMP-9 and TIMP-1 in childhood lymphoma. PMID:18850474

  11. (±)Equol inhibits invasion in prostate cancer DU145 cells possibly via down-regulation of matrix metalloproteinase-9, matrix metalloproteinase-2 and urokinase-type plasminogen activator by antioxidant activity

    PubMed Central

    Zheng, Wei; Zhang, Yumei; Ma, Defu; Shi, Yuhui; Liu, Changqiu; Wang, Peiyu

    2012-01-01

    Exposure to soy isoflavones has been associated with low mortality of prostate cancer. In this study, we examined the effects of (±)equol and two representative isoflavones, daidzein and genistein, on migration and invasion in human prostate cancer DU145 cells. First of all, the three regents did not show significant growth inhibitive effect in DU145 cells until the treatments last for 72 h. Treatment with 5 µM, 10 µM, 50 µM (±)equol, 0.5 µM, 1 µM, 5 µM daidzein and genistein for 24 h decreased cell migration and invasion significantly. (±)equol activated phosphatase and tensin homologue deleted on chromosome ten at protein level but not mRNA level, which activated antioxidants, including superoxide dismutase and nuclear factor (erythroid-derived 2)-like 2. A reduction of malondialdehyde concentration, the product of lipid per-oxidation, was observed as well. Moreover, matrix metalloproteinase-2, matrix metalloproteinase-9, and urokinase-type plasminogen activator, the crucial members in metastasis, were down-regulated. Overall, our data indicate that (±)equol, daidzein and genistein may have significant anti-invasion effect in DU145 cells (in vitro). The effects induced by (±)equol may relate to its anti-oxidant effect mediated by phosphatase and tensin homologue deleted on chromosome ten. PMID:22798715

  12. Molecular Docking Analysis of Selected Clinacanthus nutans Constituents as Xanthine Oxidase, Nitric Oxide Synthase, Human Neutrophil Elastase, Matrix Metalloproteinase 2, Matrix Metalloproteinase 9 and Squalene Synthase Inhibitors

    PubMed Central

    Narayanaswamy, Radhakrishnan; Isha, Azizul; Wai, Lam Kok; Ismail, Intan Safinar

    2016-01-01

    Background: Clinacanthus nutans (Burm. f.) Lindau has gained popularity among Malaysians as a traditional plant for anti-inflammatory activity. Objective: This prompted us to carry out the present study on a selected 11 constituents of C. nutans which are clinacoside A–C, cycloclinacoside A1, shaftoside, vitexin, orientin, isovitexin, isoorientin, lupeol and β-sitosterol. Materials and Methods: Selected 11 constituents of C. nutans were evaluated on the docking behavior of xanthine oxidase (XO), nitric oxide synthase (NOS), human neutrophil elastase (HNE), matrix metalloproteinase (MMP 2 and 9), and squalene synthase (SQS) using Discovery Studio Version 3.1. Also, molecular physicochemical, bioactivity, absorption, distribution, metabolism, excretion, and toxicity (ADMET), and toxicity prediction by computer assisted technology analyzes were also carried out. Results: The molecular physicochemical analysis revealed that four ligands, namely clinacoside A–C and cycloclinacoside A1 showed nil violations and complied with Lipinski's rule of five. As for the analysis of bioactivity, all the 11 selected constituents of C. nutans exhibited active score (>0) toward enzyme inhibitors descriptor. ADMET analysis showed that the ligands except orientin and isoorientin were predicted to have Cytochrome P4502D6 inhibition effect. Docking studies and binding free energy calculations revealed that clinacoside B exhibited the least binding energy for the target enzymes except for XO and SQS. Isovitexin and isoorientin showed the potentials in the docking and binding with all of the six targeted enzymes, whereas vitexin and orientin docked and bound with only NOS and HNE. Conclusion: This present study has paved a new insight in understanding these 11 C. nutans ligands as potential inhibitors against XO, NOS, HNE, MMP 2, MMP 9, and SQS. SUMMARY Isovitexin and isoorientin (Clinacanthus nutans constituent) showed potentials in the docking and binding with all of the six targeted

  13. Matrix metalloproteinase-9 and -2 and tissue inhibitor of matrix metalloproteinase-2 in invasive pituitary adenomas: A systematic review and meta-analysis of case-control trials.

    PubMed

    Liu, Hong-Yan; Gu, Wei-Jun; Wang, Cheng-Zhi; Ji, Xiao-Jian; Mu, Yi-Ming

    2016-06-01

    The extracellular matrix is important for tumor invasion and metastasis. Normal function of the extracellular matrix depends on the balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). The objective of this meta-analysis was to assess the relationship between expression of MMP-9, MMP-2, and TIMP-2 and invasion of pituitary adenomas.We searched Pubmed, Embase, and the Chinese Biomedical Database up to October 2015. RevMan 5.1 software (Cochrane Collaboration, Copenhagen, Denmark) was used for statistical analysis. We calculated the standardized mean difference (SMD) for data expressed as mean ± standard deviation because of the difference in the detection method.Twenty-four studies (1320 patients) were included. MMP-9 expression was higher in the patients with invasive pituitary adenomas (IPAs) than patients with noninvasive pituitary adenomas (NIPAs) with detection methods of IHC [odds ratio (OR) = 5.48, 95% confidence interval (CI) = 2.61-11.50, P < 0.00001), and reverse transcriptase-polymerase chain reaction (SMD = 2.28, 95% CI = 0.91-3.64, P = 0.001). MMP-2 expression was also increased in patients with IPAs at the protein level (OR = 3.58, 95% CI = 1.63-7.87, P = 0.001), and RNA level (SMD = 3.91, 95% CI = 1.52-6.29, P = 0.001). Meta-analysis showed that there was no difference in TIMP-2 expression between invasive and NIPAs at the protein level (OR = 0.38, 95% CI = 0.06-2.26, P = 0.29). MMP-9 expression in prolactinomas and nonfunctioning pituitary adenomas was also no difference (OR = 1.03, 95% CI = 0.48-2.20, P = 0.95).The results indicated that MMP-9 and -2 may be correlated with invasiveness of pituitary adenomas, although their relationship with functional status of pituitary adenomas is still not clear. TIMP-2 expression in IPAs needs to be investigated further. PMID:27310993

  14. Vitamin D decreases the secretion of matrix metalloproteinase-2 and matrix metalloproteinase-9 in fibroblasts derived from Taiwanese patients with chronic rhinosinusitis with nasal polyposis.

    PubMed

    Wang, Ling-Feng; Tai, Chih-Feng; Chien, Chen-Yu; Chiang, Feng-Yu; Chen, Jeff Yi-Fu

    2015-05-01

    Vitamin D and its derivatives have modulatory effects in immunological and inflammatory responses. Such properties suggest that they might have an impact on chronic inflammatory airway diseases, including nasal polyposis. The aim of this study was to understand the role of vitamin D in chronic rhinosinusitis with nasal polyps (CRSwNP) by investigating its effect on the secretion of matrix metalloproteinase-2 (MMP-2) and MMP-9 in nasal polyp-derived fibroblasts. Two primary fibroblast cultures were established from nasal polyp tissues obtained during surgery. The nasal polyp-derived fibroblasts were stimulated with tumor necrosis factor-α (TNF-α; 10 ng/mL) for 24 hours, followed by replacement with media alone or with vitamin D derivatives (calcitriol or tacalcitol; 10μM) and incubated for another 24 hours. After the treatments, the levels of MMP-2 and MMP-9 secreted were evaluated by both enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. ELISA results revealed that TNF-α could substantially stimulate the secretion of MMP-2 (p < 0.01) and MMP-9 (p < 0.001) in nasal polyp-derived fibroblasts. More importantly, such stimulatory effect was significantly suppressed by adding calcitriol (p ≤ 0.01 for MMP-2 and p < 0.001 for MMP-9) or tacalcitol (p < 0.005 for both MMP-2 and MMP-9). The ELISA results were also confirmed by Western blot analysis. The inhibitory effect of vitamin D derivatives on MMP-2 and MMP-9 secretion could potentiate their application in pharmacotherapy of Taiwanese CRSwNP patients. PMID:25910558

  15. Novel roles of androgen receptor, epidermal growth factor receptor, TP53, regulatory RNAs, NF-kappa-B, chromosomal translocations, neutrophil associated gelatinase, and matrix metalloproteinase-9 in prostate cancer and prostate cancer stem cells.

    PubMed

    Chappell, William H; Abrams, Stephen L; Lertpiriyapong, Kvin; Fitzgerald, Timothy L; Martelli, Alberto M; Cocco, Lucio; Rakus, Dariusz; Gizak, Agnieszka; Terrian, David; Steelman, Linda S; McCubrey, James A

    2016-01-01

    Approximately one in six men will be diagnosed with some form of prostate cancer in their lifetime. Over 250,000 men worldwide die annually due to complications from prostate cancer. While advancements in prostate cancer screening and therapies have helped in lowering this statistic, better tests and more effective therapies are still needed. This review will summarize the novel roles of the androgen receptor (AR), epidermal growth factor receptor (EGFR), the EGFRvIII variant, TP53, long-non-coding RNAs (lncRNAs), microRNAs (miRs), NF-kappa-B, chromosomal translocations, neutrophil associated gelatinase, (NGAL), matrix metalloproteinase-9 (MMP-9), the tumor microenvironment and cancer stem cells (CSC) have on the diagnosis, development and treatment of prostate cancer. PMID:26525204

  16. The Subcellular Localization of Intercellular Adhesion Molecule-5 (Telencephalin) in the Visual Cortex is not Developmentally Regulated in the Absence of Matrix Metalloproteinase-9

    PubMed Central

    Kelly, Emily A.; Tremblay, Marie-Eve; Gahmberg, Carl G.; Tian, Li; Majewska, Ania K.

    2013-01-01

    The telencephalon-associated intercellular adhesion molecule 5 (Telencephalin; ICAM-5) regulates dendritic morphology in the developing brain. In vitro studies have shown that ICAM-5 is predominantly found within dendrites and immature dendritic protrusions, with reduced expression in mushroom spines, suggesting that ICAM-5 downregulation is critical for the maturation of synaptic structures. However, developmental expression of ICAM-5 has not been explored in depth at the ultrastructural level in intact brain tissue. To investigate the ultrastructural localization of ICAM-5 with transmission electron microscopy, we performed immunoperoxidase histochemistry for ICAM-5 in mouse visual cortex at postnatal day (P)14, a period of intense synaptogenesis, and at P28, when synapses mature. We observed the expected ICAM-5 expression in dendritic protrusions and shafts at both P14 and P28. ICAM-5 expression in these dendritic protrusions decreased in prevalence with developmental age to become predominantly localized to dendritic shafts by P28. To further understand the relationship between ICAM-5 and the endopeptidase metalloproteinase-9 (MMP-9), which mediates ICAM-5 cleavage following glutamate activation during postnatal development, we also explored ICAM-5 expression in MMP-9 null animals. This analysis revealed a similar expression of ICAM-5 in dendritic elements at P14 and P28; however an increased prevalence of ICAM-5 was noted in dendritic protrusions at P28 in the MMP-9 null animals, indicating that in the absence of MMP-9, there is no developmental shift in ICAM-5 subcellular localization. Our ultrastructural observations shed light on possible functions mediated by ICAM-5 and their regulation by extracellular proteases. PMID:23897576

  17. Matrix metalloproteinase-9 deficiency leads to prolonged foreign body response in the brain associated with increased IL-1β levels and leakage of the blood brain barrier

    PubMed Central

    Tian, Weiming; Kyriakides, Themis R.

    2013-01-01

    Matrix metalloproteinases (MMPs) are enzymes with specificity towards extracellular matrix (ECM) components. MMPs, especially MMP-9, have been shown to degrade components of the basal lamina and disrupt the blood-brain barrier (BBB) and thus, contribute to neuroinflammation. In the present study we examined the role of MMP-9 in the foreign body response in the brain. Millipore filters of mixed cellulose ester were implanted into the brain cortex of wild type and MMP-9 -null mice for a period of 2 d to 8 wks and the response was analyzed by histology and immunohistochemistry. We observed enhanced and prolonged neuroinflammation in MMP-9-null mice, evidenced by persistence of neutrophils, macrophages/microglia, and reactive astrocytes up to 8 wks post-implantation. In addition, blood vessel density around implants was increased in MMP-9-null mice and detection of mouse serum albumin (MSA) indicated that vessels were leaky. Immunohistochemical and western blot analyses indicated that this defect was associated with the absence of tight junction proteins zonula occludens-1 (ZO-1) and ZO-2 from vessels in proximity to implants. Analysis of brain sections and brain protein extracts revealed that the levels of the pro-inflammatory cytokine interleukin-1β (IL-1β), which is a substrate for MMP-9, were significantly higher in MMP-9-null mice at 8wks post-implantation. Collectively, our studies suggest that increased levels of IL-1β and the delayed repair of BBB are associated with prolongation of the FBR in MMP-9-null mice. PMID:19264129

  18. Neu1 sialidase and matrix metalloproteinase-9 cross-talk regulates nucleic acid-induced endosomal TOLL-like receptor-7 and -9 activation, cellular signaling and pro-inflammatory responses.

    PubMed

    Abdulkhalek, Samar; Szewczuk, Myron R

    2013-11-01

    The precise mechanism(s) by which intracellular TOLL-like receptors (TLRs) become activated by their ligands remains unclear. Here, we report a molecular organizational G-protein coupled receptor (GPCR) signaling platform to potentiate a novel mammalian neuraminidase-1 (Neu1) and matrix metalloproteinase-9 (MMP-9) cross-talk in alliance with neuromedin B GPCR, all of which form a tripartite complex with TLR-7 and -9. siRNA silencing Neu1, MMP-9 and neuromedin-B GPCR in RAW-blue macrophage cells significantly reduced TLR7 imiquimod- and TLR9 ODN1826-induced NF-κB (NF-κB-pSer(536)) activity. Tamiflu, specific MMP-9 inhibitor, neuromedin B receptor specific antagonist BIM23127, and the selective inhibitor of whole heterotrimeric G-protein complex BIM-46174 significantly block nucleic acid-induced TLR-7 and -9 MyD88 recruitment, NF-κB activation and proinflammatory TNFα and MCP-1 cytokine responses. For the first time, Neu1 clearly plays a central role in mediating nucleic acid-induced intracellular TLR activation, and the interactions involving NMBR-MMP9-Neu1 cross-talk constitute a novel intracellular TLR signaling platform that is essential for NF-κB activation and pro-inflammatory responses. PMID:23827939

  19. Anti-metastatic effect of supercritical extracts from the Citrus hassaku pericarp via inhibition of C-X-C chemokine receptor type 4 (CXCR4) and matrix metalloproteinase-9 (MMP-9).

    PubMed

    Kim, Chulwon; Kim, Dongmin; Nam, Dongwoo; Chung, Won-Seok; Ahn, Kyoo Seok; Kim, Sung-Hoon; Choi, Seung-Hoon; Shim, Bum Sang; Cho, Somi K; Ahn, Kwang Seok

    2014-09-01

    The fruit of hassaku (Citrus hassaku Hort. ex Tanaka) is locally known as phalsak in Korea. Recently, the fruit extract has been known to exhibit in vivo preventive effects against UVB-induced pigmentation, antiallergic activity, and enhancement of blood fluidity. However, the exact mechanisms of how supercritical extracts of phalsak peel (SEPS) inhibits tumor metastasis and invasion are still not fully understood. We found that SEPS could downregulate the constitutive expression of both CXCR4 and HER2 in human breast cancer MDA-MB-231 cells as compared with other cells. SEPS also suppressed matrix metalloproteinase-9 (MMP-9) expression and its enzymatic activity under non-cytotoxic concentrations. Neither proteasome inhibition nor lysosomal stabilization had any effect on the SEPS-induced decrease in CXCR4 expression. A detailed study of the underlying molecular mechanisms revealed that the regulation of the downregulation of CXCR4 was at the transcriptional level, as indicated by downregulation of mRNA expression, suppression of NF-κB activity, and inhibition of chromatin immunoprecipitation activity. Suppression of CXCR4 expression by SEPS correlated with the inhibition of CXCL12-stimulated invasion of MDA-MB-231 cells. Overall, our results indicate, for the first time, that SEPS can suppress CXCR4 and MMP-9 expressions through blockade of NF-κB activation and thus has the potential to suppress metastasis of breast cancer. PMID:24638915

  20. RhoA mediates the expression of acidic extracellular pH-induced matrix metalloproteinase-9 mRNA through phospholipase D1 in mouse metastatic B16-BL6 melanoma cells.

    PubMed

    Maeda, Toyonobu; Yuzawa, Satoshi; Suzuki, Atsuko; Baba, Yuh; Nishimura, Yukio; Kato, Yasumasa

    2016-03-01

    Solid tumors are characterized by acidic extracellular pH (pHe). The present study examined the contribution of small GTP-binding proteins to phospholipase D (PLD) activation of acidic pHe-induced matrix metalloproteinase-9 (MMP-9) production. Acidic pHe-induced MMP-9 production was reduced by C3 exoenzyme, which inhibits the Rho family of GTPases; cytochalasin D, which inhibits actin reorganization; and simvastatin, which inhibits geranylgeranylation of Rho. Small interfering RNA (siRNA) against RhoA, but not against Rac1 or Cdc42, significantly inhibited acidic pHe induction of MMP-9. Pull-down assays showed that acidic pHe increased the activated form of RhoA. Forced expression of constitutively active RhoA induced MMP-9 production, even at neutral pHe. RhoA siRNA also reduced acidic pHe induced PLD activity. Specific inhibition of PLD1 and Pld1 gene knockout significantly reduced acidic pHe-induced MMP-9 expression. In contrast, PLD2 inhibition or knockout had no effect on MMP-9 expression. These findings suggested that RhoA-PLD1 signaling is involved in acidic pHe induction of MMP-9. PMID:26782071

  1. Evaluation of physiological risk factors, oxidant-antioxidant imbalance, proteolytic and genetic variations of matrix metalloproteinase-9 in patients with pressure ulcer

    PubMed Central

    Latifa, Khlifi; Sondess, Sahli; Hajer, Graiet; Manel, Ben-Hadj-Mohamed; Souhir, Khelil; Nadia, Bouzidi; Abir, Jaballah; Salima, Ferchichi; Abdelhedi, Miled

    2016-01-01

    Pressure ulcer (PU) remains a common worldwide problem in all health care settings, it is synonymous with suffering. PU is a complex disease that is dependent on a number of interrelated factors. It involves multiple mechanisms such as physiological risk factors, chronic inflammation, oxidant–antioxidant imbalance and proteolytic attack on extracellular matrix by matrix metalloproteinases (MMP). Therefore, we propose that these wounds lead to molecular variations that can be detected by assessing biomarkers. In this study, we aimed to evaluate the major clinical elements and biological scars in Tunisian patients suffering from PU. Consistently, non-healing wound remains a challenging clinical problem. The complex challenges of the wound environment, involving nutrient deficiencies, bacterial infection, as well as the critical role played by inflammatory cells, should be considered because of their negative impact on wound healing. In addition, an imbalance between pro-oxidants and antioxidant systems seems to be more aggravated in patients with PU compared to healthy subjects. Of interest, this study provides further evidence to support a core role of the biological activity of MMP-9 in the pathogenesis of PU and indicates that the MMP9-1562 C/T (rs 3918242) functional polymorphism is associated with protection against this disease. PMID:27405842

  2. Differential Expression of Matrix Metalloproteinase-9 Gene in Wounds of Type 2 Diabetes Mellitus Cases With Susceptible -1562C>T Genotypes and Wound Severity.

    PubMed

    Singh, Kanhaiya; Agrawal, Neeraj K; Gupta, Sanjeev K; Mohan, Gyanendra; Chaturvedi, Sunanda; Singh, Kiran

    2014-05-25

    Coordinated extracellular matrix deposition is a prerequisite for proper wound healing which is mainly orchestrated by matrix metalloproteinases (MMPs). Diabetic wounds generally show compromised wound healing cascade and abnormal MMP9 concentration is one of the cause. Our group have recently shown that the polymorphism -1562 C>T in the promoter region of MMP9 gene is associated with pathogenesis of wound healing impairment in T2DM patients. In present study we have done expression profiling of MMP9 gene in the wound biopsy of DFU cases. Expression level of MMP9 mRNA was then compared with susceptible -1562 C>T genotypes (TT and CT) as well as with different grades of wounds. We also screened the promoter region of MMP9 gene to see the methylation state of CpGs present there. Our study suggests that levels of MMP9 mRNA increase significantly with the wound grades. Moreover, the MMP9 levels in diabetic wounds were also dependent on -1562 C>T polymorphism in the promoter region of MMP9. Diabetic wounds also showed a significant unmethylated status of MMP9 promoter compared to control wounds. In conclusion, The risk genotypes of -1562 C>T polymorphism along with lack of methylation of CpG sites in MMP9 gene promoter may result in altered expression of MMP9 in wounds of T2DM cases resulting into nonhealing chronic ulcers in them. PMID:24861096

  3. Evaluation of physiological risk factors, oxidant-antioxidant imbalance, proteolytic and genetic variations of matrix metalloproteinase-9 in patients with pressure ulcer.

    PubMed

    Latifa, Khlifi; Sondess, Sahli; Hajer, Graiet; Manel, Ben-Hadj-Mohamed; Souhir, Khelil; Nadia, Bouzidi; Abir, Jaballah; Salima, Ferchichi; Abdelhedi, Miled

    2016-01-01

    Pressure ulcer (PU) remains a common worldwide problem in all health care settings, it is synonymous with suffering. PU is a complex disease that is dependent on a number of interrelated factors. It involves multiple mechanisms such as physiological risk factors, chronic inflammation, oxidant-antioxidant imbalance and proteolytic attack on extracellular matrix by matrix metalloproteinases (MMP). Therefore, we propose that these wounds lead to molecular variations that can be detected by assessing biomarkers. In this study, we aimed to evaluate the major clinical elements and biological scars in Tunisian patients suffering from PU. Consistently, non-healing wound remains a challenging clinical problem. The complex challenges of the wound environment, involving nutrient deficiencies, bacterial infection, as well as the critical role played by inflammatory cells, should be considered because of their negative impact on wound healing. In addition, an imbalance between pro-oxidants and antioxidant systems seems to be more aggravated in patients with PU compared to healthy subjects. Of interest, this study provides further evidence to support a core role of the biological activity of MMP-9 in the pathogenesis of PU and indicates that the MMP9-1562 C/T (rs 3918242) functional polymorphism is associated with protection against this disease. PMID:27405842

  4. A Role for the Cavin-3/Matrix Metalloproteinase-9 Signaling Axis in the Regulation of PMA-Activated Human HT1080 Fibrosarcoma Cell Neoplastic Phenotype

    PubMed Central

    Toufaily, Chirine; Charfi, Cyndia; Annabi, Bayader; Annabi, Borhane

    2014-01-01

    Caveolae are specialized cell membrane invaginations known to regulate several cancer cell functions and oncogenic signaling pathways. Among other caveolar proteins, they are characterized by the presence of proteins of the cavin family. In this study, we assessed the impact of cavin-1, cavin-2, and cavin-3 on cell migration in a human HT-1080 fibrosarcoma model. We found that all cavin-1, -2 and -3 transcripts were expressed and that treatment with phorbol 12-myristate 13-acetate (PMA), which is known to prime cell migration and proliferation, specifically upregulated cavin-3 gene and protein expression. PMA also triggered matrix metalloproteinase (MMP)-9 secretion, but reduced the global cell migration index. Overexpression of recombinant forms of the three cavins demonstrated that only cavin-3 was able to reduce basal cell migration, and this anti-migratory effect was potentiated by PMA. Interestingly, cavin-3 overexpression inhibited PMA-induced MMP-9, while cavin-3 gene silencing led to an increase in MMP-9 gene expression and secretion. Furthermore, recombinant cavin-3 significantly prevented PMA-mediated dephosphorylation of AKT, a crucial regulator in MMP-9 transcription. In conclusion, our results demonstrate that cellular cavin-3 expression may repress MMP-9 transcriptional regulation in part through AKT. We suggest that the balance in cavin-3-to-MMP-9 expression regulates the extent of extracellular matrix degradation, confirming the tumor-suppressive role of cavin-3 in controlling the invasive potential of human fibrosarcoma cells. PMID:25520561

  5. Galangin and kaempferol suppress phorbol-12-myristate-13-acetate-induced matrix metalloproteinase-9 expression in human fibrosarcoma HT-1080 cells.

    PubMed

    Choi, Yu Jung; Lee, Young Hun; Lee, Seung-Taek

    2015-01-01

    Matrix metalloproteinase (MMP)-9 degrades type IV collagen in the basement membrane and plays crucial roles in several pathological implications, including tumorigenesis and inflammation. In this study, we analyzed the effect of flavonols on MMP-9 expression in phorbol-12-myristate-13-acetate (PMA)-induced human fibrosarcoma HT-1080 cells. Galangin and kaempferol efficiently decreased MMP-9 secretion, whereas fisetin only weakly decreased its secretion. Galangin and kaempferol did not affect cell viability at concentrations up to 30 μM. Luciferase reporter assays showed that galangin and kaempferol decrease transcription of MMP-9 mRNA. Moreover, galangin and kaempferol strongly reduce IκBα phosphorylation and significantly decrease JNK phosphorylation. These results indicate that galangin and kaempferol suppress PMA-induced MMP-9 expression by blocking activation of NF-κB and AP-1. Therefore, these flavonols could be used as chemopreventive agents to lower the risk of diseases involving MMP-9. PMID:25518925

  6. Protease Nexin-1 affects the migration and invasion of C6 glioma cells through the regulation of urokinase Plasminogen Activator and Matrix Metalloproteinase-9/2.

    PubMed

    Pagliara, Valentina; Adornetto, Annagrazia; Mammì, Maria; Masullo, Mariorosario; Sarnataro, Daniela; Pietropaolo, Concetta; Arcone, Rosaria

    2014-11-01

    Protease Nexin-1 (PN-1) or Serpine2 is a physiological regulator of extracellular proteases as thrombin and urokinase (uPA) in the brain. Besides, PN-1 is also implicated in some human cancers and further identified as a substrate for Matrix Metalloproteinase (MMP)-9, a key enzyme in tumor invasiveness. Our aim was to study the role of PN-1 in the migration and invasive potential of glioma cells, using the rat C6 glioma cell line as stable clones transfected with pAVU6+27 vector expressing PN-1 short-hairpin RNA. We find that PN-1 knockdown enhanced the in vitro migration and invasiveness of C6 cells which also showed a strong gelatinolytic activity by in situ zymography. PN-1 silencing did not alter prothrombin whereas increased uPA, MMP-9 and MMP-2 expression levels and gelatinolytic activity in a conditioned medium from stable C6 cells. Selective inhibitors for MMP-9 (Inhibitor I), MMP-2 (Inhibitor III) or exogenous recombinant PN-1 added to the culture medium of C6 silenced cells restored either the migration and invasive ability or gelatinolytic activity thus validating the specificity of PN-1 silencing strategy. Phosphorylation levels of extracellular signal-related kinases (Erk1/2 and p38 MAPK) involved in MMP-9 and MMP-2 signaling were increased in PN-1 silenced cells. This study shows that PN-1 affects glioma cell migration and invasiveness through the regulation of uPA and MMP-9/2 expression levels which contribute to the degradation of extracellular matrix during tumor invasion. PMID:25072751

  7. Matrix metalloproteinase-9 expression is enhanced in renal parietal epithelial cells of zucker diabetic Fatty rats and is induced by albumin in in vitro primary parietal cell culture.

    PubMed

    Zhang, Yuanyuan; George, Jasmine; Li, Yun; Olufade, Rebecca; Zhao, Xueying

    2015-01-01

    As a subfamily of matrix metalloproteinases (MMPs), gelatinases including MMP-2 and MMP-9 play an important role in remodeling and homeostasis of the extracellular matrix. However, conflicting results have been reported regarding their expression level and activity in the diabetic kidney. This study investigated whether and how MMP-9 expression and activity were changed in glomerular epithelial cells upon albumin overload. In situ zymography, immunostaining and Western blot for renal MMP gelatinolytic activity and MMP-9 protein expression were performed in Zucker lean and Zucker diabetic rats. Confocal microscopy revealed a focal increase in gelatinase activity and MMP-9 protein in the glomeruli of diabetic rats. Increased glomerular MMP-9 staining was mainly observed in hyperplastic parietal epithelial cells (PECs) expressing claudin-1 in the diabetic kidneys. Interestingly, increased parietal MMP-9 was often accompanied by decreased staining for podocyte markers (nephrin and podocalyxin) in the sclerotic area of affected glomeruli in diabetic rats. Additionally, urinary excretion of podocyte marker proteins was significantly increased in association with the levels of MMP-9 and albumin in the urine of diabetic animals. To evaluate the direct effect of albumin on expression and activity of MMP-9, primary cultured rat glomerular PECs were incubated with rat serum albumin (0.25 - 1 mg/ml) for 24 - 48 hrs. MMP-9 mRNA levels were significantly increased following albumin treatment. Meanwhile, albumin administration resulted in a dose-dependent increase in MMP-9 protein and activity in culture supernatants of PECs. Moreover, albumin activated p44/42 mitogen-activated protein kinase (MAPK) in PECs. Inhibition of p44/42 MAPK suppressed albumin-induced MMP-9 secretion from glomerular PECs. Taken together, we have demonstrated that an up-regulation of MMP-9 in activated parietal epithelium is associated with a loss of adjacent podocytes in progressive diabetic nephropathy

  8. Relaxin induces matrix-metalloproteinases-9 and -13 via RXFP1: induction of MMP-9 involves the PI3K, ERK, Akt and PKC-ζ pathways.

    PubMed

    Ahmad, Nisar; Wang, Wei; Nair, Remi; Kapila, Sunil

    2012-11-01

    We determined the precise role of relaxin family peptide (RXFP) receptors-1 and -2 in the regulation of MMP-9 and -13 by relaxin, and delineated the signaling cascade that contributes to relaxin's modulation of MMP-9 in fibrocartilaginous cells. Relaxin treatment of cells in which RXFP1 was silenced resulted in diminished induction of MMP-9 and -13 by relaxin, whereas overexpression of RXFP1 potentiated the relaxin-induced expression of these proteinases. Suppression or overexpression of RXFP2 resulted in no changes in the relaxin-induced MMP-9 and -13. Studies using chemical inhibitors and siRNAs to signaling molecules showed that PI3K, Akt, ERK and PKC-ζ and the transcription factors Elk-1, c-fos and, to a lesser extent, NF-κB are involved in relaxin's induction of MMP-9. Our findings provide the first characterization of signaling cascade involved in the regulation of any MMP by relaxin and offer mechanistic insights on how relaxin likely mediates extracellular matrix turnover. PMID:22835547

  9. 5-Azacytidine regulates matrix metalloproteinase-9 expression, and the migration and invasion of human fibrosarcoma HT1080 cells via PI3-kinase and ERK1/2 pathways.

    PubMed

    Yu, Seon-Mi; Kim, Song Ja

    2016-09-01

    Abnormal methylation of promoter CpG islands is one of the hallmarks of cancer cells, and is catalyzed by DNA methyltransferases. 5-azacytidine (5-aza C), a methyltransferase inhibitor, can cause demethylation of promoter regions of diverse genes. Epigenetic processes contribute to the regulation of matrix metalloproteinase (MMP) expression. However, little is known about the mechanisms and effects of 5-aza C on the invasive and migratory capacities of human fibrosarcoma HT1080 cells. In the present study, we found that 5-aza C induces MMP-9 activity, as determined by zymography. HT1080 cell proliferation was determined following 5-aza C administration by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell cycle was examined by flow cytometry. 5-aza C treatment inhibited cell proliferation without affecting cell viability. Furthermore, 5-aza C significantly promoted migration and invasion of HT1080 cells. 5-aza C treatment enhanced phosphorylation of extracellular signal-regulated kinase (ERK) and phosphoinositide (PI)3-kinase/Akt, and their inhibitors blocked MMP-9 activity induction, and cellular invasion and migration. Together, these findings suggest that promoter methylation may be one of the mechanisms modulating MMP-9 levels in HT1080 cells, and that 5-aza C-induced MMP-9 production is associated with the activation of ERK and PI3-kinase/Akt signaling pathways. PMID:27573026

  10. Matrix Metalloproteinase-9 Leads to Claudin-5 Degradation via the NF-κB Pathway in BALB/c Mice with Eosinophilic Meningoencephalitis Caused by Angiostrongylus cantonensis

    PubMed Central

    Chiu, Ping-Sung; Lai, Shih-Chan

    2013-01-01

    The epithelial barrier regulates the movement of ions, macromolecules, immune cells and pathogens. The objective of this study was to investigate the role of the matrix metalloproteinase (MMP)-9 in the degradation of tight junction protein during infection with rat nematode lungworm Angiostrongylus cantonensis. The results showed that phosphorylation of IκB and NF-κB was increased in mice with eosinophilic meningoencephalitis. Treatment with MG132 reduced the phosphorylation of NF-κB and the activity of MMP-9, indicating upregulation of MMP-9 through the NF-κB signaling pathway. Claudin-5 was reduced in the brain but elevated in the cerebrospinal fluid (CSF), implying that A. cantonensis infection caused tight junction breakdown and led to claudin-5 release into the CSF. Degradation of claudin-5 coincided with alteration of the blood-CSF barrier permeability and treatment with the MMP inhibitor GM6001 attenuated the degradation of claudin-5. These results suggested that degradation of claudin-5 was caused by MMP-9 in angiostrongyliasis meningoencephalitis. Claudin-5 could be used for the pathophysiologic evaluation of the blood-CSF barrier breakdown and tight junction disruption after infection with A. cantonensis. PMID:23505411

  11. Interferon-Gamma Increases the Ratio of Matrix Metalloproteinase-9/Tissue Inhibitor of Metalloproteinase-1 in Peripheral Monocytes from Patients with Coronary Artery Disease

    PubMed Central

    Gonzalez-Pacheco, Hector; Furuzawa-Carballeda, Janette; Gomez-Garcia, Lorena; Marquez-Velasco, Ricardo; Mejía-Domínguez, Ana María; Cossío-Aranda, Jorge; Martínez-Sánchez, Carlos; Bojalil, Rafael

    2013-01-01

    Acute coronary syndromes (ACS) may be triggered by acute infections. Systemic production of interferon gamma (IFN-γ) is induced during infection and regulates the production of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs), both important in plaque stability. This study evaluates the effect of IFN-γ on the MMPs/TIMP-1 ratio in cultured monocytes from 30 patients with stable coronary artery disease (CAD), 30 with unstable angina (UA) or non-ST-segment elevation myocardial infarction (NSTEMI), and 30 healthy blood donors. Supernatant concentrations of MMP-1, -2, -9, and TIMP-1 were measured by enzyme-linked immunoassays. Basal concentration of MMP-1 and TIMP-1 was similar between groups, while MMP-2 was higher in healthy individuals and MMP-9 in patients with UA/NSTEMI. Upon IFN-γ stimulation, MMP-9 secretion increased in all groups, while TIMP-1 decreased only in patients with CAD, which in turn result in a strikingly elevation in their mean MMP-9/TIMP-1 ratio. MMP-1/TIMP-1 and MMP-2/TIMP-1 ratios were <1.0 in basal conditions and after stimulation in all groups. Our results suggest that nonstimulated monocytes from patients with stable CAD show a similar behavior than those from healthy individuals. However, stimulation with IFN-γ induces an increase on the MMP-9/TIMP-1 ratio as high as that found in patients with ACS. Thus, it may bring biological plausibility to the association between acute infections and the development of ACS. PMID:23951304

  12. Inhibitory effect of plant-originated glycoprotein (27 kDa) on expression of matrix metalloproteinase-9 in cadmium chloride-induced BNL CL.2 cells.

    PubMed

    Lee, Jin; Lim, Kye-Taek

    2011-12-01

    Cadmium is very harmful to the environment and to human beings because of its long lifetime. The toxicity of cadmium as an industrial pollutant and a food contaminant, and as one of the major components in cigarette smoke is well known. Cadmium can cause a number of lesions in many organs, such as the kidney, the lung, the liver, the brain, the blood system. However, the mechanism of toxicity of cadmium is not yet clear. Also, it has been well known as human carcinogen which is indirectly caused inflammation-mediated hepatocarcinoma. In the present study it was demonstrated that glycoprotein (27 kDa) isolated from Gardenia jasminoides Ellis (GJE) protects BNL CL.2 cells from expression of inflammation-related factors stimulated by cadmium chloride (10 μM). Intracellular ROS and intracellular Ca(2+) using fluorescence, activities of activator protein (AP)-1, cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-9, and arachidonic acid (AA) using immunoblot analysis or radioactivity were evaluated. The results obtained from this experiment indicated that GJE glycoprotein (100 μg/mL) inhibits the production of intracellular ROS, and intracellular Ca(2+) mobilization. Also, it significantly suppressed inflammatory factors [expression of AP-1 (c-Jun and c-Fos), arachidonic acid, COX-2, and MMP-9]. Taken together, these findings suggest that GJE glycoprotein might be used for protection of inflammation caused by cadmium ion as one of natural compounds. PMID:21924884

  13. Non-thermal plasma inhibits human cervical cancer HeLa cells invasiveness by suppressing the MAPK pathway and decreasing matrix metalloproteinase-9 expression

    PubMed Central

    Li, Wei; Yu, K. N.; Bao, Lingzhi; Shen, Jie; Cheng, Cheng; Han, Wei

    2016-01-01

    Non-thermal plasma (NTP) has been proposed as a novel therapeutic method for anticancer treatment. However, the mechanism underlying its biological effects remains unclear. In this study, we investigated the inhibitory effect of NTP on the invasion of HeLa cells, and explored the possible mechanism. Our results showed that NTP exposure for 20 or 40 s significantly suppressed the migration and invasion of HeLa cells on the basis of matrigel invasion assay and wound healing assay, respectively. Moreover, NTP reduced the activity and protein expression of the matrix metalloproteinase (MMP)-9 enzyme. Western blot analysis indicated that NTP exposure effectively decreased phosphorylation level of both ERK1/2 and JNK, but not p38 MAPK. Furthermore, treatment with MAPK signal pathway inhibitors or NTP all exhibited significant depression of HeLa cells migration and MMP-9 expression. The result showed that NTP synergistically suppressed migration and MMP-9 expression in the presence of ERK1/2 inhibitor and JNK inhibitor, but not p38 MAPK inhibitor. Taken together, these findings suggested that NTP exposure inhibited the migration and invasion of HeLa cells via down-regulating MMP-9 expression in ERK1/2 and JNK signaling pathways dependent manner. These findings provide hints to the potential clinical research and therapy of NTP on cervical cancer metastasis. PMID:26818472

  14. Non-thermal plasma inhibits human cervical cancer HeLa cells invasiveness by suppressing the MAPK pathway and decreasing matrix metalloproteinase-9 expression

    NASA Astrophysics Data System (ADS)

    Li, Wei; Yu, K. N.; Bao, Lingzhi; Shen, Jie; Cheng, Cheng; Han, Wei

    2016-01-01

    Non-thermal plasma (NTP) has been proposed as a novel therapeutic method for anticancer treatment. However, the mechanism underlying its biological effects remains unclear. In this study, we investigated the inhibitory effect of NTP on the invasion of HeLa cells, and explored the possible mechanism. Our results showed that NTP exposure for 20 or 40 s significantly suppressed the migration and invasion of HeLa cells on the basis of matrigel invasion assay and wound healing assay, respectively. Moreover, NTP reduced the activity and protein expression of the matrix metalloproteinase (MMP)-9 enzyme. Western blot analysis indicated that NTP exposure effectively decreased phosphorylation level of both ERK1/2 and JNK, but not p38 MAPK. Furthermore, treatment with MAPK signal pathway inhibitors or NTP all exhibited significant depression of HeLa cells migration and MMP-9 expression. The result showed that NTP synergistically suppressed migration and MMP-9 expression in the presence of ERK1/2 inhibitor and JNK inhibitor, but not p38 MAPK inhibitor. Taken together, these findings suggested that NTP exposure inhibited the migration and invasion of HeLa cells via down-regulating MMP-9 expression in ERK1/2 and JNK signaling pathways dependent manner. These findings provide hints to the potential clinical research and therapy of NTP on cervical cancer metastasis.

  15. Citrate Synthase Is a Novel In Vivo Matrix Metalloproteinase-9 Substrate That Regulates Mitochondrial Function in the Postmyocardial Infarction Left Ventricle

    PubMed Central

    de Castro Brás, Lisandra E.; Cates, Courtney A.; DeLeon-Pennell, Kristine Y.; Ma, Yonggang; Iyer, Rugmani Padmanabhan; Halade, Ganesh V.; Yabluchanskiy, Andriy; Fields, Gregg B.; Weintraub, Susan T.

    2014-01-01

    Abstract Aim: To evaluate the role of matrix metalloproteinase (MMP)-9 deletion on citrate synthase (CS) activity postmyocardial infarction (MI). Results: We fractionated left ventricle (LV) samples using a differential solubility-based approach. The insoluble protein fraction was analyzed by mass spectrometry, and we identified CS as a potential intracellular substrate of MMP-9 in the MI setting. CS protein levels increased in the insoluble fraction at day 1 post-MI in both genotypes (p<0.05) but not in the noninfarcted remote region. The CS activity decreased in the infarcted tissue of wild-type (WT) mice at day 1 post-MI (p<0.05), but this was not observed in the MMP-9 null mice, suggesting that MMP-9 deletion helps to maintain the mitochondrial activity post-MI. Additionally, inflammatory gene transcription was increased post-MI in the WT mice and attenuated in the MMP-9 null mice. MMP-9 cleaved CS in vitro, generating an ∼20 kDa fragment. Innovation: By applying a sample fractionation and proteomics approach, we were able to identify a novel MMP-9-related altered mitochondrial metabolic activity early post-MI. Conclusion: Our data suggest that MMP-9 deletion improves mitochondrial function post-MI. Antioxid. Redox Signal. 21, 1974–1985. PMID:24382150

  16. Involvement of Matrix Metalloproteinase-9 in Amyloid-β 1–42–Induced Shedding of the Pericyte Proteoglycan NG2

    PubMed Central

    Schultz, Nina; Nielsen, Henrietta M.; Minthon, Lennart; Wennström, Malin

    2014-01-01

    Abstract Deposition of amyloid-β (Aβ) 1–42, the major component of senile plaques characteristic of Alzheimer disease, affects brain microvascular integrity and causes blood-brain barrier dysfunction, increased angiogenesis, and pericyte degeneration. To understand the cellular events underlying Aβ1–42 effects on microvascular alterations, we investigated whether different aggregation forms of Aβ1–42 affect shedding of the pericyte proteoglycan NG2 and whether they affect proteolytic cleavage mediated by matrix metalloproteinase (MMP)-9. We found decreased levels of soluble NG2, total MMP-9, and MMP-9 activity in pericyte culture supernatants in response to fibril-enriched preparations of Aβ1–42. Conversely, oligomer-enriched preparations of Aβ1–42 increased soluble NG2 levels in the supernatants. This increase was ablated by the MMP-9/MMP-2 inhibitor SB-3CT. There was also a trend toward increased MMP-9 activity observed after oligomeric Aβ1–42 exposure. Our results, demonstrating an Aβ1–42 aggregation-dependent effect on levels of NG2 and MMP-9, support previous studies showing an impact of Aβ1–42 on vascular integrity and thereby add to our understanding of mechanisms behind the microvascular changes commonly found in patients with Alzheimer disease. PMID:24918635

  17. Enzyme-Treated Asparagus Extract Attenuates Hydrogen Peroxide-Induced Matrix Metalloproteinase-9 Expression in Murine Skin Fibroblast L929 Cells.

    PubMed

    Shirato, Ken; Takanari, Jun; Ogasawara, Junetsu; Sakurai, Takuya; Imaizumi, Kazuhiko; Ohno, Hideki; Kizaki, Takako

    2016-05-01

    Enzyme-treated asparagus extract (ETAS) exerts a wide variety of beneficial biological actions including facilitating anti-cortisol stress and neurological anti-aging responses. However, the anti-skin aging effects of ETAS remain to be elucidated. Reactive oxygen species (ROS) play pivotal roles in skin aging. Increased ROS levels in fibroblasts in response to ultraviolet irradiation activate c-Jun N-terminal kinase (JNK) and its downstream transcription factor activator protein-1 (AP-1), and the resultant gene expression of matrix metalloproteinase (MMP) isoforms accelerates collagen breakdown in the dermis. Therefore, we explored whether ETAS has anti-skin aging effects by attenuating the oxidative stress responses in fibroblasts. Simultaneous treatment of murine skin L929 fibroblasts with hydrogen peroxide (H2O2) and either ETAS or dextrin showed that ETAS significantly suppressed H2O2-induced expression of MMP-9 mRNA as measured by real-time polymerase chain reaction. ETAS also clearly suppressed H2O2-stimulated phosphorylation of c-Jun (AP-1 subunit) and JNK as determined by Western blot. However, ETAS did not affect the increased amounts of carbonyl proteins in response to H2O2, also as determined by Western blotting. These results suggest that ETAS diminishes cellular responsiveness to ROS but does not scavenge ROS. Thus, ETAS has the potential to prevent skin aging through attenuating the oxidative stress responses in dermal fibroblasts. PMID:27319149

  18. Plasma Matrix Metalloproteinase-9 Levels Predict First-Time Coronary Heart Disease: An 8-Year Follow-Up of a Community-Based Middle Aged Population

    PubMed Central

    Garvin, Peter; Jonasson, Lena; Nilsson, Lennart; Falk, Magnus; Kristenson, Margareta

    2015-01-01

    Background The enzyme in matrix metalloproteinase (MMP)-9 has been suggested to be an important determinant of plaque degradation. While several studies have shown elevated levels in patients with coronary heart disease, results in prospective population based studies evaluating MMP-9 in relation to first time coronary events have been inconclusive. As of today, there are four published studies which have measured MMP-9 in serum and none using plasma. Measures of MMP-9 in serum have been suggested to have more flaws than measures in plasma. Aim To investigate the independent association between plasma levels of MMP-9 and first-time incidence of coronary events in an 8-year follow-up. Material and Methods 428 men and 438 women, aged 45–69 years, free of previous coronary events and stroke at baseline, were followed-up. Adjustments were made for sex, age, socioeconomic position, behavioral and cardiovascular risk factors, chronic disease at baseline, depressive symptoms, interleukin-6 and C-reactive protein. Results 53 events were identified during a risk-time of 6 607 person years. Hazard ratio (HR) for MMP-9 after adjustment for all covariates were HR = 1.44 (1.03 to 2.02, p = 0.033). Overall, the effect of adjustments for other cardiovascular risk factors was low. Conclusion Levels of plasma MMP-9 are independently associated with risk of first-time CHD events, regardless of adjustments. These results are in contrast to previous prospective population-based studies based on MMP-9 in serum. It is essential that more studies look at MMP-9 levels in plasma to further evaluate the association with first coronary events. PMID:26389803

  19. Nitric oxide attenuates matrix metalloproteinase-9 production by endothelial cells independent of cGMP- or NFκB-mediated mechanisms.

    PubMed

    Meschiari, Cesar A; Izidoro-Toledo, Tatiane; Gerlach, Raquel F; Tanus-Santos, Jose E

    2013-06-01

    Cardiovascular diseases involve critical mechanisms including impaired nitric oxide (NO) levels and abnormal matrix metalloproteinase (MMP) activity. While NO downregulates MMP expression in some cell types, no previous study has examined whether NO downregulates MMP levels in endothelial cells. We hypothesized that NO donors could attenuate MMP-9 production by human umbilical vein endothelial cells (HUVECs) as a result of less NFκB activation or cyclic GMP (cGMP)-mediated mechanisms. We studied the effects of DetaNONOate (10-400 μM) or SNAP (50-400 μM) on phorbol 12-myristate 13-acetate (PMA; 10 nM)-induced increases in MMP-9 activity (by gel zymography) or concentrations (by ELISA) as well as on a tissue inhibitor of MMPs' (TIMP)-1 concentrations (by ELISA) in the conditioned medium of HUVECs incubated for 24 h with these drugs. We also examined whether the irreversible inhibitor of soluble guanylyl cyclase ODQ modified the effects of SNAP or whether 8-bromo-cGMP (a cell-permeable analog of cGMP) influenced PMA-induced effects on MMP-9 expression. Total and phospho-NFκB p65 concentrations were measured in HUVEC lysates to assess NFκB activation. Both NO donors attenuated PMA-induced increases in MMP-9 activity and concentrations without significantly affecting TIMP-1 concentrations. This effect was not modified by ODQ, and 8-bromo-cGMP did not affect MMP-9 concentrations. While PMA increased phospho-NFκB p65 concentrations, SNAP had no influence on this effect. In conclusion, this study shows that NO donors may attenuate imbalanced MMP expression and activity in endothelial cells independent of cGMP- or NFκB-mediated mechanisms. Our results may offer an important pharmacological strategy to approach cardiovascular diseases. PMID:23456480

  20. Matrix metalloproteinase-2 and metalloproteinase-9 activities are associated with blood-brain barrier dysfunction in an animal model of severe sepsis.

    PubMed

    Dal-Pizzol, Felipe; Rojas, Hugo Alberto; dos Santos, Emilia Marcelina; Vuolo, Francieli; Constantino, Larissa; Feier, Gustavo; Pasquali, Matheus; Comim, Clarissa M; Petronilho, Fabrícia; Gelain, Daniel Pens; Quevedo, João; Moreira, José Cláudio Fonseca; Ritter, Cristiane

    2013-08-01

    There is no description on the mechanisms associated with blood-brain barrier (BBB) disruption during sepsis development. Thus, we here determined changes in permeability of the BBB in an animal model of severe sepsis and the role of matrix metalloproteinase (MMP)-2 and MMP-9 in the dysfunction of the BBB. Sepsis was induced in Wistar rats by cecal ligation and perforation. BBB permeability was assessed using the Evans blue dye method. The content of MMP-2 and MMP-9 in the cerebral microvessels was determined by western blot. The activity of MMP-2 and MMP-9 was determined using zymography. An inhibitor of MMP-2 and MMP-9 or specific inhibitors of MMP-2 or MMP-9 were administered to define the role of MMPs on BBB permeability, brain inflammatory response, and sepsis-induced cognitive alterations. The increase of BBB permeability is time-related to the increase of MMP-9 and MMP-2 in the microvessels, both in cortex and hippocampus. Using an MMP-2 and MMP-9 inhibitor, or specific MMP-2 or MMP-9 inhibitors, the increase in the permeability of the BBB was reversed. This was associated with lower brain levels of interleukin (IL)-6 and lower oxidative damage. In contrast, only the inhibition of both MMP-9 and MMP-2 was able to improve acute cognitive alterations associated with sepsis. In conclusion, MMP-2 and MMP-9 activation seems to be a major step in BBB dysfunction, but BBB dysfunction seems not to be associated with acute cognitive dysfunction during sepsis development. PMID:23479197

  1. Perioperative time course of matrix metalloproteinase-9 (MMP-9), its tissue inhibitor TIMP-1 & S100B protein in carotid surgery

    PubMed Central

    Nagy, Bálint; Woth, Gábor; Mérei, Ákos; Nagy, Lilla; Lantos, János; Menyhei, Gábor; Bogár, Lajos; Mühl, Diána

    2016-01-01

    Background & objectives: Ischaemic stroke is a life burdening disease for which carotid endarterectomy (CEA) is considered a gold standard intervention. Pro-inflammatory markers like matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) and S-100 Beta (S100B) may have a role in the early inflammation and cognitive decline following CEA. This study was aimed to describe the perioperative time courses and correlations between of MMP-9, TIMP-1 and S100B following CEA. Methods: Fifty four patients scheduled for CEA were enrolled. Blood samples were collected at four time points, T1: preoperative, T2: 60 min after cross-clamp release, T3: first postoperative morning, T4: third postoperative morning. Twenty atherosclerotic patients were included as controls. Plasma MMP-9, TIMP-1 and S100B levels were estimated by ELISA. Results: TIMP-1 was decreased significantly in the CEA group (P<0.01). Plasma MMP-9 was elevated and remained elevated from T1-4 in the CEA group (P<0.05) with a marked elevation in T3 compared to T1 (P<0.05). MMP-9/TIMP-1 was elevated in the CEA group and increased further by T2 and T3 (P<0.05). S100B was elevated on T2 and decreased on T3-4 compared to T1. Interpretation & conclusions: Our study provides information on the dynamic changes of MMP-9-TIMP-1 system and S100B in the perioperative period. Preoperative reduction of TIMP-1 might be predictive for shunt requirement but future studies are required for verification. PMID:27121520

  2. Osthole inhibits the invasive ability of human lung adenocarcinoma cells via suppression of NF-κB-mediated matrix metalloproteinase-9 expression.

    PubMed

    Kao, Shang-Jyh; Su, Jen-Liang; Chen, Chi-Kuan; Yu, Ming-Chih; Bai, Kuan-Jen; Chang, Jer-Hua; Bien, Mauo-Ying; Yang, Shun-Fa; Chien, Ming-Hsien

    2012-05-15

    The induction of matrix metalloproteinase (MMP)-9 is particularly important for the invasiveness of various cancer cells. Osthole, a natural coumarin derivative extracted from traditional Chinese medicines, is known to inhibit the proliferation of a variety of tumor cells, but the effect of osthole on the invasiveness of tumor cells is largely unknown. This study determines whether and by what mechanism osthole inhibits invasion in CL1-5 human lung adenocarcinoma cells. Herein, we found that osthole effectively inhibited the migratory and invasive abilities of CL1-5 cells. A zymographic assay showed that osthole inhibited the proteolytic activity of MMP-9 in CL1-5 cells. Inhibition of migration, invasion, and MMP2 and/or MMP-9 proteolytic activities was also observed in other lung adenocarcinoma cell lines (H1299 and A549). We further found that osthole inhibited MMP-9 expression at the messenger RNA and protein levels. Moreover, a chromatin immunoprecipitation assay showed that osthole inhibited the transcriptional activity of MMP-9 by suppressing the DNA binding activity of nuclear factor (NF)-κB in the MMP-9 promoter. Using reporter assays with point-mutated promoter constructs further confirmed that the inhibitory effect of osthole requires an NF-κB binding site on the MMP-9 promoter. Western blot and immunofluorescence assays demonstrated that osthole inhibited NF-κB activity by inhibiting IκB-α degradation and NF-κB p65 nuclear translocation. In conclusion, we demonstrated that osthole inhibits NF-κB-mediated MMP-9 expression, resulting in suppression of lung cancer cell invasion and migration, and osthole might be a potential agent for preventing the invasion and metastasis of lung cancer. PMID:22503731

  3. Distinct pattern of matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 mRNA expression in human colorectal cancer and liver metastases.

    PubMed Central

    Zeng, Z. S.; Guillem, J. G.

    1995-01-01

    The matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are perceived as essential for tumour invasion and metastasis. In the present study, we compare the topographical pattern of MMP-9 and TIMP-1 expression in colorectal cancer and liver metastasis by in situ hybridisation. TIMP-1 mRNA was detected in all 26 colorectal cancers examined, while only 18 out of 26 (69.2%) were positive for MMP-9. Both MMP-9 and TIMP-1 mRNA were observed in all ten liver metastases but were absent in three adenomas and in all normal colonic mucosa and liver. There was no association between MMP-9 or TIMP-1 mRNA expression and degree of differentiation or size of Tumours. MMP-9 and TIMP-1 mRNA were similarly observed in the peritumour stroma cells rather than in tumour cells themselves. MMP-9 mRNA positive cells were round and identified as macrophages by immunostaining with an anti-macrophage antibody (KP1), while TIMP-1, mRNA was detected in spindle-shaped stromal cells. In liver metastases, MMP-9 localised within peritumour stroma or at the interface between the tumour stroma and normal liver, whereas TIMP-1 mRNA was located throughout the malignant tumour stroma. Our data demonstrate a distinct pattern of MMP-9 and TIMP-1 mRNA expression in colorectal cancer and liver metastases suggesting distinct cellular origins as well as separate patterns of regulation. Images Figure 1 Figure 2 Figure 4 Figure 5 Figure 6 PMID:7669564

  4. Inhibition of MDA-MB-231 breast cancer cell migration and invasion activity by andrographolide via suppression of nuclear factor-κB-dependent matrix metalloproteinase-9 expression.

    PubMed

    Zhai, Zanjing; Qu, Xinhua; Li, Haowei; Ouyang, Zhengxiao; Yan, Wei; Liu, Guangwang; Liu, Xuqiang; Fan, Qiming; Tang, Tingting; Dai, Kerong; Qin, An

    2015-02-01

    Breast cancer is one of the most common types of cancer worldwide. The majority of patients with cancer succumb to the disease as a result of distant metastases (for example, in the bones), which cause severe complications. Despite advancements in breast cancer treatment, chemotherapeutic outcomes remain far from satisfactory, prompting a search for effective natural agents with few side‑effects. Andrographolide (AP), a natural diterpenoid lactone isolated from Andrographis paniculata, inhibits cancer cell growth. The current study aimed to examine the effect of AP on breast cancer cell proliferation, survival and progression in vitro and also its inhibitory activity on breast cancer bone metastasis in vivo. To achieve this, CCK8, flow cytometry, migration, invasion, western blot, PCR and luciferase reporter assay analyses were performed in vitro as well as establishing intratibial xenograft model of breast cancer bone metastasis in vivo. The results demonstrated that AP inhibits the migration and invasion of the MBA‑MD‑231 aggressive breast cancer cell line at non‑lethal concentrations, in addition to suppressing proliferation and inducing apoptosis at high concentrations in vitro. In vivo, AP significantly inhibited the growth of tumors planted in bone and attenuated cancer‑induced osteolysis. Tartrate‑resistant acid phosphatase staining revealed osteoclast activation in tumor‑bearing mice and AP was observed to attenuate this activation. The anti‑tumor activity of AP in vitro and in vivo correlates with the downregulation of the nuclear factor κB signaling pathway and the inhibition of matrix metalloproteinase‑9 expression levels. These results indicate that AP may be an effective anti‑tumor agent for the treatment of breast cancer bone metastasis. PMID:25374279

  5. Osthole inhibits the invasive ability of human lung adenocarcinoma cells via suppression of NF-κB-mediated matrix metalloproteinase-9 expression

    SciTech Connect

    Kao, Shang-Jyh; Su, Jen-Liang; Chen, Chi-Kuan; Yu, Ming-Chih; Bai, Kuan-Jen; Chang, Jer-Hua; Bien, Mauo-Ying; Yang, Shun-Fa; Chien, Ming-Hsien

    2012-05-15

    The induction of matrix metalloproteinase (MMP)-9 is particularly important for the invasiveness of various cancer cells. Osthole, a natural coumarin derivative extracted from traditional Chinese medicines, is known to inhibit the proliferation of a variety of tumor cells, but the effect of osthole on the invasiveness of tumor cells is largely unknown. This study determines whether and by what mechanism osthole inhibits invasion in CL1-5 human lung adenocarcinoma cells. Herein, we found that osthole effectively inhibited the migratory and invasive abilities of CL1-5 cells. A zymographic assay showed that osthole inhibited the proteolytic activity of MMP-9 in CL1-5 cells. Inhibition of migration, invasion, and MMP2 and/or MMP-9 proteolytic activities was also observed in other lung adenocarcinoma cell lines (H1299 and A549). We further found that osthole inhibited MMP-9 expression at the messenger RNA and protein levels. Moreover, a chromatin immunoprecipitation assay showed that osthole inhibited the transcriptional activity of MMP-9 by suppressing the DNA binding activity of nuclear factor (NF)-κB in the MMP-9 promoter. Using reporter assays with point-mutated promoter constructs further confirmed that the inhibitory effect of osthole requires an NF-κB binding site on the MMP-9 promoter. Western blot and immunofluorescence assays demonstrated that osthole inhibited NF-κB activity by inhibiting IκB-α degradation and NF-κB p65 nuclear translocation. In conclusion, we demonstrated that osthole inhibits NF-κB-mediated MMP-9 expression, resulting in suppression of lung cancer cell invasion and migration, and osthole might be a potential agent for preventing the invasion and metastasis of lung cancer. -- Highlights: ► Osthole treatment inhibits lung adenocarcinoma cells migration and invasion. ► Osthole reduces the expression and proteolytic activity of MMP-9. ► Osthole inhibits MMP-9 transcription via suppression of NF-κB binding activity. ► Osthole

  6. Effects of resveratrol and genistein on nuclear factor-κB, tumor necrosis factor-α and matrix metalloproteinase-9 in patients with chronic obstructive pulmonary disease

    PubMed Central

    LIU, XIAO-JU; BAO, HAI-RONG; ZENG, XIAO-LI; WEI, JUN-MING

    2016-01-01

    Chronic airway inflammation and airway remodeling are the major pathophysiological characteristics of chronic obstructive pulmonary disease (COPD). Resveratrol and genistein have been previously demonstrated to have anti-inflammatory and antioxidative properties. The present study aimed to measure the inhibitory effects of resveratrol and genistein on tumor necrosis factor (TNF)-α and matrix metalloproteinase (MMP)-9 concentration in patients with COPD. Lymphocytes were isolated from the blood of 34 patients with COPD and 30 healthy subjects, then randomly divided into the following four treatment groups: Control, dexamethasone (0.5 µmol/l), resveratrol (12.5 µmol/l) and genistein (25 µmol/l) groups. After 1 h of treatment, 100 µl lymphocytes were collected for nuclear factor (NF)-κB immunocytochemical staining. After 48 h treatment, the supernatant of the lymphocytes was collected for analysis of TNF-α and MMP-9 concentration levels. The percentage of lymphocytes with positive nuclear NF-κB expression was analyzed by immunocytochemical staining. The concentration levels of TNF-α and MMP-9 were measured using radioimmunoassay and enzyme-linked immunosorbent assay, respectively. The present study demonstrated that the percentage of NF-κB-positive cells, and the levels of TNF-α and MMP-9 in lymphocytes from patients with COPD patients were significantly higher compared with healthy subjects. Additionally, there were positive correlations between the percentage of NF-κB-positive cells, and the concentration levels of TNF-α and MMP-9 in patients with COPD. All three factors were significantly reduced in lymphocytes treated with resveratrol and genistein, and the inhibitory effects of resveratrol on NF-κB, TNF-α and MMP-9 were more potent than the effects of genistein. In conclusion, resveratrol and genistein may inhibit the NF-κB, TNF-α and MMP-9-associated pathways in patients with COPD. It is suggested that resveratrol and genistein may be potential

  7. Adventitial transplantation of blood outgrowth endothelial cells in porcine haemodialysis grafts alleviates hypoxia and decreases neointimal proliferation through a matrix metalloproteinase-9-mediated pathway—a pilot study

    PubMed Central

    Hughes, Deborah; Fu, Alex A.; Puggioni, Alessandra; Glockner, James F.; Anwer, Bilal; McGuire, Antonio M.; Mukhopadhyay, Debabrata; Misra, Sanjay

    2009-01-01

    Purpose. We hypothesized that adventitial transplantation of blood outgrowth endothelial cells (BOEC) to the vein-to-graft anastomosis of polytetrafluoroethylene grafts will reduce neointimal hyperplasia by reducing hypoxia inducible factor-1α (HIF-1α), by increasing angiogenesis in a porcine model of chronic renal insufficiency with haemodialysis polytetrafluoroethylene grafts. Because matrix metalloproteinases (MMPs) have been shown to be involved with angiogenesis, the expression of MMPs and their inhibitors was determined. Methods. Chronic renal insufficiency was created by subtotal renal infarction and 28 days later, arteriovenous PTFE grafts were placed bilaterally from the carotid artery to the jugular vein. Autologous blood outgrowth endothelial cells labeled with Lac Z were transplanted to the adventitia of the vein-to-graft anastomosis using polyglycolic acid scaffolding and scaffolding only to other side (control). Animals were killed 14 days later and vessels were explanted from the vein-to-graft anastomosis of both sides and underwent immunohistochemical analysis, western blotting and zymography for HIF-1α, MMP-2, MMP-9, TIMP-1 and TIMP-2. BOEC were also made hypoxic and normoxic for 12, 24 and 48 h to determine protein expression for MMPs and TIMPs. Results. Under hypoxia, BOEC significantly increased the expression of pro MMP-2 by 12 h and TIMP-2 by 24 h when compared to normoxic cells (P < 0.05). Transplantation of BOEC resulted in a significant decrease in both HIF-1α and intima-to-media ratio with a significant increase in both pro and active MMP-9 when compared to control vessels (P < 0.05). MMP-9 activity was localized to the neointima of the transplanted vessels by immunohistochemistry. There was increased CD31 density with engraftment of BOEC cells into the neointima of both the transplanted vessels compared to controls (P = NS). Conclusion. Transplantation of BOEC resulted in a significant decrease in intimal hyperplasia and HIF-1α with

  8. NADPH oxidase/ROS-dependent PYK2 activation is involved in TNF-α-induced matrix metalloproteinase-9 expression in rat heart-derived H9c2 cells

    SciTech Connect

    Yang, Chuen-Mao; Lee, I-Ta; Hsu, Ru-Chun; Chi, Pei-Ling; Hsiao, Li-Der

    2013-10-15

    TNF-α plays a mediator role in the pathogenesis of chronic heart failure contributing to cardiac remodeling and peripheral vascular disturbances. The implication of TNF-α in inflammatory responses has been shown to be mediated through up-regulation of matrix metalloproteinase-9 (MMP-9). However, the detailed mechanisms of TNF-α-induced MMP-9 expression in rat embryonic-heart derived H9c2 cells are largely not defined. We demonstrated that in H9c2 cells, TNF-α induced MMP-9 mRNA and protein expression associated with an increase in the secretion of pro-MMP-9. TNF-α-mediated responses were attenuated by pretreatment with the inhibitor of ROS (N-acetyl-L-cysteine, NAC), NADPH oxidase [apocynin (APO) or diphenyleneiodonium chloride (DPI)], MEK1/2 (U0126), p38 MAPK (SB202190), JNK1/2 (SP600125), NF-κB (Bay11-7082), or PYK2 (PF-431396) and transfection with siRNA of TNFR1, p47{sup phox}, p42, p38, JNK1, p65, or PYK2. Moreover, TNF-α markedly induced NADPH oxidase-derived ROS generation in these cells. TNF-α-enhanced p42/p44 MAPK, p38 MAPK, JNK1/2, and NF-κB (p65) phosphorylation and in vivo binding of p65 to the MMP-9 promoter were inhibited by U0126, SB202190, SP600125, NAC, DPI, or APO. In addition, TNF-α-mediated PYK2 phosphorylation was inhibited by NAC, DPI, or APO. PYK2 inhibition could reduce TNF-α-stimulated MAPKs and NF-κB activation. Thus, in H9c2 cells, we are the first to show that TNF-α-induced MMP-9 expression is mediated through a TNFR1/NADPH oxidase/ROS/PYK2/MAPKs/NF-κB cascade. We demonstrated that NADPH oxidase-derived ROS generation is involved in TNF-α-induced PYK2 activation in these cells. Understanding the regulation of MMP-9 expression and NADPH oxidase activation by TNF-α on H9c2 cells may provide potential therapeutic targets of chronic heart failure. - Highlights: • TNF-α induces MMP-9 secretion and expression via a TNFR1-dependent pathway. • TNF-α induces ROS/PYK2-dependent MMP-9 expression in H9c2 cells. • TNF

  9. NADPH oxidase/ROS-dependent PYK2 activation is involved in TNF-α-induced matrix metalloproteinase-9 expression in rat heart-derived H9c2 cells.

    PubMed

    Yang, Chuen-Mao; Lee, I-Ta; Hsu, Ru-Chun; Chi, Pei-Ling; Hsiao, Li-Der

    2013-10-15

    TNF-α plays a mediator role in the pathogenesis of chronic heart failure contributing to cardiac remodeling and peripheral vascular disturbances. The implication of TNF-α in inflammatory responses has been shown to be mediated through up-regulation of matrix metalloproteinase-9 (MMP-9). However, the detailed mechanisms of TNF-α-induced MMP-9 expression in rat embryonic-heart derived H9c2 cells are largely not defined. We demonstrated that in H9c2 cells, TNF-α induced MMP-9 mRNA and protein expression associated with an increase in the secretion of pro-MMP-9. TNF-α-mediated responses were attenuated by pretreatment with the inhibitor of ROS (N-acetyl-l-cysteine, NAC), NADPH oxidase [apocynin (APO) or diphenyleneiodonium chloride (DPI)], MEK1/2 (U0126), p38 MAPK (SB202190), JNK1/2 (SP600125), NF-κB (Bay11-7082), or PYK2 (PF-431396) and transfection with siRNA of TNFR1, p47(phox), p42, p38, JNK1, p65, or PYK2. Moreover, TNF-α markedly induced NADPH oxidase-derived ROS generation in these cells. TNF-α-enhanced p42/p44 MAPK, p38 MAPK, JNK1/2, and NF-κB (p65) phosphorylation and in vivo binding of p65 to the MMP-9 promoter were inhibited by U0126, SB202190, SP600125, NAC, DPI, or APO. In addition, TNF-α-mediated PYK2 phosphorylation was inhibited by NAC, DPI, or APO. PYK2 inhibition could reduce TNF-α-stimulated MAPKs and NF-κB activation. Thus, in H9c2 cells, we are the first to show that TNF-α-induced MMP-9 expression is mediated through a TNFR1/NADPH oxidase/ROS/PYK2/MAPKs/NF-κB cascade. We demonstrated that NADPH oxidase-derived ROS generation is involved in TNF-α-induced PYK2 activation in these cells. Understanding the regulation of MMP-9 expression and NADPH oxidase activation by TNF-α on H9c2 cells may provide potential therapeutic targets of chronic heart failure. PMID:23774252

  10. Evaluation of New Diagnostic Biomarkers in Pediatric Sepsis: Matrix Metalloproteinase-9, Tissue Inhibitor of Metalloproteinase-1, Mid-Regional Pro-Atrial Natriuretic Peptide, and Adipocyte Fatty-Acid Binding Protein

    PubMed Central

    Alqahtani, Mashael F.; Smith, Craig M.; Weiss, Scott L.; Dawson, Susan; Ralay Ranaivo, Hantamalala; Wainwright, Mark S.

    2016-01-01

    Elevated plasma concentrations of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), mid-regional pro-atrial natriuretic peptide (mrProANP), and adipocyte fatty-acid-binding proteins (A-FaBPs) have been investigated as biomarkers for sepsis or detection of acute neurological injuries in adults, but not children. We carried out a single-center, prospective observational study to determine if these measures could serve as biomarkers to identify children with sepsis. A secondary aim was to determine if these biomarkers could identify children with neurologic complications of sepsis. A total of 90 patients ≤ 18 years-old were included in this study. 30 with severe sepsis or septic shock were compared to 30 age-matched febrile and 30 age-matched healthy controls. Serial measurements of each biomarker were obtained, beginning on day 1 of ICU admission. In septic patients, MMP9-/TIMP-1 ratios (Median, IQR, n) were reduced on day 1 (0.024, 0.004–0.174, 13), day 2 (0.020, 0.002–0.109, 10), and day 3 (0.018, 0.003–0.058, 23) compared with febrile (0.705, 0.187–1.778, 22) and healthy (0.7, 0.4–1.2, 29) (p< 0.05) controls. A-FaBP and mrProANP (Median, IQR ng/mL, n) were elevated in septic patients compared to control groups on first 2 days after admission to the PICU (p <0.05). The area under the curve (AUC) for MMP-9/TIMP-1 ratio, mrProANP, and A-FaBP to distinguish septic patients from healthy controls were 0.96, 0.99, and 0.76, respectively. MMP-9/TIMP-1 ratio was inversely and mrProANP was directly related to PIM-2, PELOD, and ICU and hospital LOS (p<0.05). A-FaBP level was associated with PELOD, hospital and ICU length of stay (p<0.05). MMP-9/TIMP-1 ratio associated with poor Glasgow Outcome Score (p<0.05). A-FaBP levels in septic patients with neurological dysfunction (29.3, 17.2–54.6, 7) were significantly increased compared to septic patients without neurological dysfunction (14.6, 13.3–20.6, 11). MMP-9/TIMP-1 ratios

  11. Robust design of some selective matrix metalloproteinase-2 inhibitors over matrix metalloproteinase-9 through in silico/fragment-based lead identification and de novo lead modification: Syntheses and biological assays.

    PubMed

    Adhikari, Nilanjan; Halder, Amit K; Mallick, Sumana; Saha, Achintya; Saha, Kishna D; Jha, Tarun

    2016-09-15

    Broad range of selectivity possesses serious limitation for the development of matrix metalloproteinase-2 (MMP-2) inhibitors for clinical purposes. To develop potent and selective MMP-2 inhibitors, initially multiple molecular modeling techniques were adopted for robust design. Predictive and validated regression models (2D and 3D QSAR and ligand-based pharmacophore mapping studies) were utilized for estimating the potency whereas classification models (Bayesian and recursive partitioning analyses) were used for determining the selectivity of MMP-2 inhibitors over MMP-9. Bayesian model fingerprints were used to design selective lead molecule which was modified using structure-based de novo technique. A series of designed molecules were prepared and screened initially for inhibitions of MMP-2 and MMP-9, respectively, as these are designed followed by other MMPs to observe the broader selectivity. The best active MMP-2 inhibitor had IC50 value of 24nM whereas the best selective inhibitor (IC50=51nM) showed at least 4 times selectivity to MMP-2 against all tested MMPs. Active derivatives were non-cytotoxic against human lung carcinoma cell line-A549. At non-cytotoxic concentrations, these inhibitors reduced intracellular MMP-2 expression up to 78% and also exhibited satisfactory anti-migration and anti-invasive properties against A549 cells. Some of these active compounds may be used as adjuvant therapeutic agents in lung cancer after detailed study. PMID:27452283

  12. Helicobacter pylori-elicited induction in gastric mucosal matrix metalloproteinase-9 (MMP-9) release involves ERK-dependent cPLA2 activation and its recruitment to the membrane-localized Rac1/p38 complex.

    PubMed

    Slomiany, B L; Slomiany, A

    2016-06-01

    Matrix metalloproteinases (MMPs) are a family of endopeptidases implicated in a wide rage of degenerative and inflammatory diseases, including Helicobacter pylori-associated gastritis, and gastric and duodenal ulcer. As gastric mucosal inflammatory responses to H. pylori are characterized by the rise in MMP-9 production, as well as the induction in mitogen-activated protein kinase (MAPK) and Rac1 activation, we investigated the role of Rac1/MAPK in the processes associated with the release of MMP-9. We show that H. pylori LPS-elicited induction in gastric mucosal MMP-9 release is associated with MAPK, ERK and p38 activation, and occurs with the involvement of Rac1 and cytosolic phospholipase A2 (cPLA2). Further, we demonstrate that the LPS-induced MMP-9 release requires ERK-mediated phosphorylation of cPLA2 on Ser(505) that is essential for its membrane localization with Rac1, and that this process necessitates p38 participation. Moreover, we reveal that the activation and membrane translocation of p38 to the Rac1-GTP complex plays a pivotal role in cPLA2-dependent enhancement in MMP-9 release. Hence, our findings provide a strong evidence for the role of ERK/cPLA2 and Rac1/p38/cPLA2 cascade in H. pylori LPS-induced up-regulation in gastric mucosal MMP-9 release. PMID:26886372

  13. Apocynum venetum leaf extract attenuates disruption of the blood-brain barrier and upregulation of matrix metalloproteinase-9/-2 in a rat model of cerebral ischemia-reperfusion injury.

    PubMed

    Xiang, Jun; Lan, Rui; Tang, Yu-Ping; Chen, Yi-Ping; Cai, Ding-Fang

    2012-08-01

    We investigated the neuroprotective effects of Apocynum venetum leaf extract (AVLE) on a rat model of cerebral ischemia-reperfusion injury and explored the underlying mechanisms. Rats were randomly divided into five groups: sham, ischemia-reperfusion, AVLE125, AVLE250, and AVLE500. Cerebral ischemia was induced by 1.5 h of occlusion of the middle cerebral artery. Cerebral infarct area was measured by tetrazolium staining at 24 and 72 h after reperfusion, and neurological function was evaluated at 24, 48 and 72 h after reperfusion. Pathological changes on the ultrastructure of the blood-brain barrier (BBB) were observed by transmission electron microscopy. BBB permeability was assessed by detecting leakage of Evan's blue (EB) dye in brain tissue. The expression and activities of matrix metalloproteinase (MMP)-9/-2 were measured by western blot analyses and gelatin zymography at 24 h after reperfusion. AVLE (500 mg/kg/day) significantly reduced cerebral infarct area, improved recovery of neurological function, relieved morphological damage to the BBB, reduced water content and EB leakage in the brain, and downregulated the expression and activities of MMP-9/-2. These findings suggest that AVLE protects against cerebral ischemia-reperfusion-induced injury by alleviating BBB disruption. This action may be due to its inhibitory effects on the expression and activities of MMP-9/-2. PMID:22592643

  14. Role of protein kinase D2 phosphorylation on Tyr in modulation by ghrelin of Helicobacter pylori-induced up-regulation in gastric mucosal matrix metalloproteinase-9 (MMP-9) secretion.

    PubMed

    Slomiany, B L; Slomiany, A

    2016-06-01

    Matrix metalloproteinas-9 (MMP-9) is a glycosylated endopeptidase associated with host reaction to microbial endotoxins and also characterizes gastric mucosal inflammatory response to H. pylori infection. Here, we report on the factors involved in gastric mucosal MMP-9 secretion in response to H. pylori LPS, and the effect of hormone, ghrelin. We show that both the LPS-elicited induction in MMP-9 secretion and also the modulatory influence of ghrelin occur at the level of MMP-9 processing between the endoplasmic reticulum (ER) and Golgi. Further, we demonstrate that the LPS effect is associated with up-regulation in the activation of Arf1, a small GTPase of the ADP-ribosylation factor family, and the recruitment and phosphorylation of protein kinase D2 (PKD2), involved in the secretory cargo processing in the Golgi. Moreover, we reveal that the LPS-induced up-regulation in MMP-9 secretion is reflected in a marked increase in PKCδ-mediated PKD2 phosphorylation on Ser, while the modulatory effect of ghrelin is manifested by the SFK-PTKs-dependent phosphorylation of PKD2 on Tyr. Thus, our findings demonstrate the role of Arf1/PKD2 in mediation of H. pylori LPS-induced up-regulation in gastric mucosal MMP-9 secretion and suggest the modulatory mechanism of ghrelin action. PMID:27209313

  15. A Lindera obtusiloba Extract Blocks Calcium-/Phosphate-Induced Transdifferentiation and Calcification of Vascular Smooth Muscle Cells and Interferes with Matrix Metalloproteinase-2 and Metalloproteinase-9 and NF-κB.

    PubMed

    Freise, Christian; Kim, Ki Young; Querfeld, Uwe

    2015-01-01

    Vascular calcifications bear the risk for cardiovascular complications and have a high prevalence among patients with chronic kidney disease. Central mediators of vascular calcifications are vascular smooth muscle cells (VSMC). They transdifferentiate into a synthetic/osteoblast-like phenotype, which is induced, for example, by elevated levels of calcium and phosphate (Ca/P) due to a disturbed mineral balance. An aqueous extract from Lindera obtusiloba (LOE) is known to exert antifibrotic and antitumor effects or to interfere with the differentiation of preadipocytes. Using murine and rat VSMC cell lines, we here investigated whether LOE also protects VSMC from Ca/P-induced calcification. Indeed, LOE effectively blocked Ca/P-induced calcification of VSMC as shown by decreased VSMC mineralization and secretion of alkaline phosphatase. In parallel, mRNA expression of the calcification markers osterix and osteocalcin was reduced. Vice versa, the Ca/P-induced loss of the VSMC differentiation markers alpha smooth muscle actin and smooth muscle protein 22-alpha was rescued by LOE. Further, LOE blocked Ca/P-induced mRNA expressions and secretions of matrix metalloproteinases-2/-9 and activation of NF-κB, which are known contributors to vascular calcification. In conclusion, LOE interferes with the Ca/P-induced transdifferentiation/calcification of VSMC. Thus, LOE should be further analysed regarding a potential complementary treatment option for cardiovascular diseases including vascular calcifications. PMID:26294927

  16. Recruitment of Matrix Metalloproteinase-9 (MMP-9) to the Fibroblast Cell Surface by Lysyl Hydroxylase 3 (LH3) Triggers Transforming Growth Factor-β (TGF-β) Activation and Fibroblast Differentiation*

    PubMed Central

    Dayer, Cynthia; Stamenkovic, Ivan

    2015-01-01

    Solid tumor growth triggers a wound healing response. Similar to wound healing, fibroblasts in the tumor stroma differentiate into myofibroblasts (also referred to as cancer-associated fibroblasts) primarily, but not exclusively, in response to transforming growth factor-β (TGF-β). Myofibroblasts in turn enhance tumor progression by remodeling the stroma. Among proteases implicated in stroma remodeling, matrix metalloproteinases (MMPs), including MMP-9, play a prominent role. Recent evidence indicates that MMP-9 recruitment to the tumor cell surface enhances tumor growth and invasion. In the present work, we addressed the potential relevance of MMP-9 recruitment to and activity at the surface of fibroblasts. We show that recruitment of MMP-9 to the fibroblast cell surface occurs through its fibronectin-like (FN) domain and that the molecule responsible for the recruitment is lysyl hydroxylase 3 (LH3). Functional assays suggest that both pro- and active MMP-9 trigger α-smooth muscle actin expression in cultured fibroblasts, reflecting myofibroblast differentiation, possibly as a result of TGF-β activation. Moreover, the recombinant FN domain inhibited both MMP-9-induced TGF-β activation and α-smooth muscle actin expression by displacing MMP-9 from the fibroblast cell surface. Together our results uncover LH3 as a new docking receptor of MMP-9 on the fibroblast cell surface and demonstrate that the MMP-9 FN domain is essential for the interaction. They also show that the recombinant FN domain inhibits MMP-9-induced TGF-β activation and fibroblast differentiation, providing a potentially attractive therapeutic reagent toward attenuating tumor progression where MMP-9 activity is strongly implicated. PMID:25825495

  17. Embelin Inhibits Invasion and Migration of MDA-MB-231 Breast Cancer Cells by Suppression of CXC Chemokine Receptor 4, Matrix Metalloproteinases-9/2, and Epithelial-Mesenchymal Transition.

    PubMed

    Lee, Hanwool; Ko, Jeong-Hyeon; Baek, Seung Ho; Nam, Dongwoo; Lee, Seok Geun; Lee, Junhee; Yang, Woong Mo; Um, Jae-Young; Kim, Sung-Hoon; Shim, Bum Sang; Ahn, Kwang Seok

    2016-06-01

    Embelin (EB) is a benzoquinone derivative isolated from Embelia ribes Burm plant. Recent scientific evidence shows that EB induces apoptosis and inhibits migration and invasion in highly metastatic human breast cancer cells. However, the exact mechanisms of EB in tumor metastasis and invasion have not been fully elucidated. Here, we investigated the underlying mechanisms of antimetastatic activities of EB in breast cancer cells. The EB downregulated the chemokine receptor 4 (CXCR4) as well as matrix metalloproteinase (MMP)-9/2 expression and upregulated the tissue inhibitor of metalloproteinase 1 expression in MDA-MB-231 cells under noncytotoxic concentrations but not in MCF-7 cells. Additionally, EB inhibited the CXC motif chemokine ligand 12 induced invasion and migration activities of MDA-MB-231 cells. A detailed study of underlying mechanisms revealed that the regulation of the downregulation of CXCR4 was at the transcriptional level, as indicated by the downregulation of mRNA expression and suppression of nuclear factor-kappa B (NF-κB) activation. It further reduced the binding of NF-κB to the CXCR4 promoter. Besides, EB downregulated mesenchymal marker proteins (neural cadherin and vimentin) and concurrently upregulated epithelial markers (epithelial cadherin and occludin). Overall, these findings suggest that EB can abrogate breast cancer cell invasion and metastasis by suppression of CXCR4, MMP-9/2 expressions, and inhibition of epithelial-mesenchymal transition and thus may have a great potential to suppress metastasis of breast cancer. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27030214

  18. Japanese encephalitis virus induces matrix metalloproteinase-9 expression via a ROS/c-Src/PDGFR/PI3K/Akt/MAPKs-dependent AP-1 pathway in rat brain astrocytes

    PubMed Central

    2012-01-01

    Background Japanese encephalitis virus (JEV) infection is a major cause of acute encephalopathy in children, which destroys central nervous system (CNS) cells, including astrocytes and neurons. Matrix metalloproteinase (MMP)-9 has been shown to degrade components of the basal lamina, leading to disruption of the blood-brain barrier (BBB) and to contribute to neuroinflammatory responses in many neurological diseases. However, the detailed mechanisms of JEV-induced MMP-9 expression in rat brain astrocytes (RBA-1 cells) are largely unclear. Methods In this study, the effect of JEV on expression of MMP-9 was determined by gelatin zymography, western blot analysis, RT-PCR, and promoter assay. The involvement of AP-1 (c-Jun and c-Fos), c-Src, PDGFR, PI3K/Akt, and MAPKs in these responses were investigated by using the selective pharmacological inhibitors and transfection with siRNAs. Results Here, we demonstrate that JEV induces expression of pro-form MMP-9 via ROS/c-Src/PDGFR/PI3K/Akt/MAPKs-dependent, AP-1 activation in RBA-1 cells. JEV-induced MMP-9 expression and promoter activity were inhibited by pretreatment with inhibitors of AP-1 (tanshinone), c-Src (PP1), PDGFR (AG1296), and PI3K (LY294002), and by transfection with siRNAs of c-Jun, c-Fos, PDGFR, and Akt. Moreover, JEV-stimulated AP-1 activation was inhibited by pretreatment with the inhibitors of c-Src, PDGFR, PI3K, and MAPKs. Conclusion From these results, we conclude that JEV activates the ROS/c-Src/PDGFR/PI3K/Akt/MAPKs pathway, which in turn triggers AP-1 activation and ultimately induces MMP-9 expression in RBA-1 cells. These findings concerning JEV-induced MMP-9 expression in RBA-1 cells imply that JEV might play an important role in CNS inflammation and diseases. PMID:22251375

  19. Effect of a short-term in vitro exposure to the marine toxin domoic acid on viability, tumor necrosis factor-alpha, matrix metalloproteinase-9 and superoxide anion release by rat neonatal microglia

    PubMed Central

    Mayer, Alejandro MS; Hall, Mary; Fay, Michael J; Lamar, Peter; Pearson, Celeste; Prozialeck, Walter C; Lehmann, Virginia KB; Jacobson, Peer B; Romanic, Anne M; Uz, Tolga; Manev, Hari

    2001-01-01

    Background The excitatory amino acid domoic acid, a glutamate and kainic acid analog, is the causative agent of amnesic shellfish poisoning in humans. No studies to our knowledge have investigated the potential contribution to short-term neurotoxicity of the brain microglia, a cell type that constitutes circa 10% of the total glial population in the brain. We tested the hypothesis that a short-term in vitro exposure to domoic acid, might lead to the activation of rat neonatal microglia and the concomitant release of the putative neurotoxic mediators tumor necrosis factor-α (TNF-α), matrix metalloproteinases-2 and-9 (MMP-2 and -9) and superoxide anion (O2-). Results In vitro, domoic acid [10 μM-1 mM] was significantly neurotoxic to primary cerebellar granule neurons. Although neonatal rat microglia expressed ionotropic glutamate GluR4 receptors, exposure during 6 hours to domoic acid [10 μM-1 mM] had no significant effect on viability. By four hours, LPS (10 ng/mL) stimulated an increase in TNF-α mRNA and a 2,233 % increase in TNF-α protein In contrast, domoic acid (1 mM) induced a slight rise in TNF-α expression and a 53 % increase (p < 0.01) of immunoreactive TNF-α protein. Furthermore, though less potent than LPS, a 4-hour treatment with domoic acid (1 mM) yielded a 757% (p < 0.01) increase in MMP-9 release, but had no effect on MMP-2. Finally, while PMA (phorbol 12-myristate 13-acetate) stimulated O2- generation was elevated in 6 hour LPS-primed microglia, a similar pretreatment with domoic acid (1 mM) did not prime O2- release. Conclusions To our knowledge this is the first experimental evidence that domoic acid, at in vitro concentrations that are toxic to neuronal cells, can trigger a release of statistically significant amounts of TNF-α and MMP-9 by brain microglia. These observations are of considerable pathophysiological significance because domoic acid activates rat microglia several days after in vivo administration. PMID:11686853

  20. Tumor Necrosis Factor-α-induced Proteolytic Activation of Pro-matrix Metalloproteinase-9 by Human Skin Is Controlled by Down-regulating Tissue Inhibitor of Metalloproteinase-1 and Mediated by Tissue-associated Chymotrypsin-like Proteinase*

    PubMed Central

    Han, Yuan-Ping; Nien, Yih-Dar; Garner, Warren L.

    2008-01-01

    The proteolytic activation of pro-matrix metalloproteinase (MMP)-9 by conversion of the 92-kDa precursor into an 82-kDa active form has been observed in chronic wounds, tumor metastasis, and many inflammation-associated diseases, yet the mechanistic pathway to control this process has not been identified. In this report, we show that the massive expression and activation of MMP-9 in skin tissue from patients with chronically unhealed wounds could be reconstituted in vitro with cultured normal human skin by stimulation with transforming growth factor-β and tumor necrosis factor (TNF)-α. We dissected the mechanistic pathway for TNF-α induced activation of pro-MMP-9 in human skin. We found that proteolytic activation of pro-MMP-9 was mediated by a tissue-associated chymotrypsin-like proteinase, designated here as pro-MMP-9 activator (pM9A). This unidentified activator specifically converted pro-MMP-9 but not pro-MMP-2, another member of the gelatinase family. The tissue-bound pM9A was steadily expressed and not regulated by TNF-α, which indicated that the cytokine-mediated activation of pro-MMP-9 might be regulated at the inhibitor level. Indeed, the skin constantly secreted tissue inhibitor of metalloproteinase-1 at the basal state. TNF-α, but not transforming growth factor-β, down-regulated this inhibitor. The TNF-α-mediated activation of pro-MMP-9 was tightly associated with down-regulation of tissue inhibitor of metalloproteinase-1 in a dose-dependent manner. To establish this linkage, we demonstrate that the recombinant tissue inhibitor of metalloproteinase-1 could block the activation of pro-MMP-9 by either the intact skin or skin fractions. Thus, these studies suggest a novel regulation for the proteolytic activation of MMP-9 in human tissue, which is mediated by tissue-bound activator and controlled by down-regulation of a specific inhibitor. PMID:12004062

  1. Low-energy laser irradiation facilitates the velocity of tooth movement and the expressions of matrix metalloproteinase-9, cathepsin K, and alpha(v) beta(3) integrin in rats.

    PubMed

    Yamaguchi, Masaru; Hayashi, Masami; Fujita, Shouji; Yoshida, Takamasa; Utsunomiya, Tadahiko; Yamamoto, Hirotsugu; Kasai, Kazutaka

    2010-04-01

    It has previously been reported that low-energy laser irradiation stimulated the velocity of tooth movement via the receptor activator of nuclear factor kappa B (RANK)/RANK ligand and the macrophage colony-stimulating factor/its receptor (c-Fms) systems. Matrix metalloproteinase (MMP)-9, cathepsin K, and alpha(v) beta(3) [alpha(v)beta3] integrin are essential for osteoclastogenesis; therefore, the present study was designed to examine the effects of low-energy laser irradiation on the expression of MMP-9, cathepsin K, and alpha(v)beta3 integrin during experimental tooth movement. Fifty male, 6-week-old Wistar strain rats were used in the experiment. A total force of 10g was applied to the rat molars to induce tooth movement. A Ga-Al-As diode laser was used to irradiate the area around the moving tooth and, after 7 days, the amount of tooth movement was measured. To determine the amount of tooth movement, plaster models of the maxillae were made using a silicone impression material before (day 0) and after tooth movement (days 1, 2, 3, 4, and 7). The models were scanned using a contact-type three-dimensional (3-D) measurement apparatus. Immunohistochemical staining for MMP-9, cathepsin K, and integrin subunits of alpha(v)beta3 was performed. Intergroup comparisons of the average values were conducted with a Mann-Whitney U-test for tooth movement and the number of tartrate-resistant acid phosphatase (TRAP), MMP-9, cathepsin K, and integrin subunits of alpha(v)beta3-positive cells. In the laser-irradiated group, the amount of tooth movement was significantly greater than that in the non-irradiated group at the end of the experiment (P < 0.05). Cells positively stained with TRAP, MMP-9, cathepsin K, and integrin subunits of alpha(v)beta3 were found to be significantly increased in the irradiated group on days 2-7 compared with those in the non-irradiated group (P < 0.05). These findings suggest that low-energy laser irradiation facilitates the velocity of tooth

  2. 5-azacytidine induces anoikis, inhibits mammosphere formation and reduces metalloproteinase 9 activity in MCF-7 human breast cancer cells.

    PubMed

    Chang, Hsueh-Wei; Wang, Hui-Chun; Chen, Chiau-Yi; Hung, Ting-Wei; Hou, Ming-Feng; Yuan, Shyng-Shiou F; Huang, Chih-Jen; Tseng, Chao-Neng

    2014-01-01

    Cancer stem cells are a subset of cancer cells that initiate the growth of tumors. Low levels of cancer stem cells also exist in established cancer cell lines, and can be enriched in serum-free tumorsphere cultures. Since cancer stem cells have been reported to be resilient to common chemotherapeutic drugs in comparison to regular cancer cells, screening for compounds selectively targeting cancer stem cells may provide an effective therapeutic strategy. We found that 5-azacytidine (5-AzaC) selectively induced anoikis of MCF-7 in suspension cultures with an EC₅₀ of 8.014 µM, and effectively inhibited tumorsphere formation, as well as the migration and matrix metalloproteinases-9 (MMP-9) activity of MCF-7 cells. Furthermore, 5-AzaC and radiation collaboratively inhibited MCF-7 tumorsphere formation at clinically relevant radiation doses. Investigating the underlying mechanism may provide insight into signaling pathways crucial for cancer stem cell survival and pave the way to novel potential therapeutic targets. PMID:24633350

  3. Serum concentrations of metalloproteinase 2, metalloproteinase 9 and granzyme B in contact eczema patients

    PubMed Central

    Żbikowska-Gotz, Magdalena; Czajkowski, Rafał; Bartuzi, Zbigniew

    2013-01-01

    Introduction Contact eczema is a common skin condition with complex etiology, variable clinical presentation and lengthy therapy duration. The mechanism of contact eczema is complex, since it is affected by multiple inflammatory mediators. Aim To assess concentrations of metalloproteinase 2 (MMP-2), metalloproteinase 9 (MMP-9) and granzyme B (GzmB) in patients with contact eczema. Material and methods Seventy patients with contact eczema and 30 healthy persons as controls were included in the study. In all subjects, MMP-2, MMP-9 and GzmB were determined using ELISA immunoassay. In study group patients, concentrations were assayed in periods of disease exacerbation and remission. Obtained results were analyzed statistically. Results Mean MMP-2 and GzmB concentrations were found to be significantly higher in the study group than in the control group. Mean MMP-2, MMP-9 and GzmB levels were also statistically significantly higher during skin lesion relapse compared to contact eczema remission periods. Conclusions The presented paper demonstrates that MMP-2, MMP-9 and GzmB are good markers of contact eczema exacerbations. PMID:24278051

  4. Expression and activation of matrix metalloproteinases in wounds: modulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+.

    PubMed

    Siméon, A; Monier, F; Emonard, H; Gillery, P; Birembaut, P; Hornebeck, W; Maquart, F X

    1999-06-01

    We investigated the expression and activation of matrix metalloproteinases in a model of experimental wounds in rats, and their modulation by glycyl-L-histidyl-L-lysine-Cu(II), a potent activator of wound repair. Wound chambers were inserted under the skin of Sprague-Dawley rats and received serial injections of either 2 mg glycyl-L-histidyl-L-lysine-Cu(II) or the same volume of saline. The wound fluid and the neosynthetized connective tissue deposited in the chambers were collected and analyzed for matrix metalloproteinase expression and/or activity. Interstitial collagenase increased progressively in the wound fluid throughout the experiment. Glycyl-L-histidyl-L-lysine-Cu(II) treatment did not alter its activity. Matrix metalloproteinase-9 (gelatinase B) and matrix metalloproteinase-2 (gelatinase A) were the two main gelatinolytic activities expressed during the healing process. Pro-matrix metalloproteinase (pro-form of matrix metalloproteinase)-9 was strongly expressed during the early stages of wound healing (day 3). In the wound fluid, it decreased rapidly and disappeared after day 18, whereas in the wound tissue, matrix metalloproteinase-9 expression persisted in the glycyl-L-histidyl-L-lysine-Cu(II) injected chamber until day 22. Pro-matrix metalloproteinase-2 was expressed at low levels at the beginning of the healing process, increased progressively until day 7, then decreased until day 18. Activated matrix metalloproteinase-2 was present in wound fluid and wound tissue. It increased until day 12, then decreased progressively. Glycyl-L-histidyl-L-lysine-Cu(II) injections increased pro-matrix metalloproteinase-2 and activated matrix metalloproteinase-2 during the later stages of healing (days 18 and/or 22). These results demonstrate that various types of matrix metalloproteinases are selectively expressed or activated at the various periods of wound healing. Glycyl-L-histidyl-L-lysine-Cu(II) is able to modulate their expression and might significantly alter

  5. Impact of micronised purified flavonoid fraction on increased malondialdehyde and decreased metalloproteinase-2 and metalloproteinase-9 levels in varicocele: outcome of an experimentally induced varicocele.

    PubMed

    Dogan, F; Armagan, A; Oksay, T; Akman, T; Aylak, F; Bas, E

    2014-05-01

    To analyse the levels of an indirect marker of ROS-induced lipid peroxidation [i.e. malondialdehyde (MDA)] in both testes and the levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and matrix metalloproteinase inhibitor-1 (TIMP-1) in the left testis after induction of varicocele and investigated the impact of micronised purified flavonoid fraction (MPFF) on these markers. Forty-nine adolescent (6-week-old) male Wistar rats were included in this study. The rats were divided into seven groups as follows:Group-1, control; Group-2, sham; Group-3, left varicocele-induced; Group-4, varicocele + varicocelectomy + MPFF-treated (for 4 weeks); Group-5, varicocele + MPFF-treated (for 8 weeks); Group-6, varicocele-induced and 4 weeks later, MPFF-treated (for 4 weeks); and Group-7, varicocele + varicocelectomy. MDA was measured in the tissues of both testes using the thiobarbituric acid reactivity method. The ELISA method was used for the quantification of MMP-2, MMP-9 and TIMP-1 in the left testicular tissue. The levels of MDA were significantly higher in the varicocele group than in the other groups. The MDA levels in the left testicular tissues of Group-7 were significantly higher than those of Group 4 (P = 0.03). In the varicocele group, the MMP-2 and MMP-9 levels decreased, whereas the levels of TIMP-1 increased. The tissue levels of MMP-2 in Groups 4, 5 and 7 were significantly higher than those in Group 1 (P < 0.05). PMID:23550531

  6. Dependency of Experimental Autoimmune Encephalomyelitis Induction on MOG35-55 Properties Modulating Matrix Metalloproteinase-9 and Interleukin-6.

    PubMed

    Seo, Ji-Eun; Hasan, Mahbub; Han, Joon-Seung; Kim, Nak-Kyoon; Lee, Ji Eun; Lee, Kang Mi; Park, Ju-Hyung; Kim, Ho Jun; Son, Junghyun; Lee, Jaeick; Kwon, Oh-Seung

    2016-04-01

    Experimental autoimmune encephalomyelitis (EAE) is commonly induced with myelin oligodendrocyte glycoprotein (MOG)35-55; occasionally, EAE is not well induced despite MOG35-55 immunization. To confirm that EAE induction varies with difference in MOG35-55 properties, we compared three MOG35-55 from different commercial sources, which are MOG-A, MOG-B, and MOG-C. The peptides induced EAE disease with 100, 40, and 20 % incidence, respectively. Compared with others, MOG-A showed higher peptide purity (99.2 %) and content (92.2 %) and presented a sheet shape with additional sodium and chloride chemical elements. In MOG-A-treated group, MMP-9 activity and IL-6 levels were considerably higher than the other groups in CNS tissues, and significantly increased VCAM-1, IFN-γ, and decreased IL-4 were also shown compared to MOG-B- and/or MOG-C-treated group. In conclusion, the immunological and toxicological changes by the difference in MOG35-55 properties modulate EAE induction, and MOG35-55 which affects MMP-9 activity and IL-6 levels may be the most effective EAE-inducing antigen. This study can be potentially applied by researchers using MOG35-55 peptide and manufacturers for MOG35-55 synthesis. PMID:26464215

  7. Inhibition of matrix metalloproteinase-9 activity by doxycycline ameliorates RANK ligand-induced osteoclast differentiation in vitro and in vivo

    SciTech Connect

    Franco, Gilson C.N.; Nakanishi, Tadashi; Ohta, Kouji; Rosalen, Pedro L.; Groppo, Francisco C.; Bartlett, John D.; Stashenko, Philip; Taubman, Martin A.; Kawai, Toshihisa

    2011-06-10

    Tetracycline antibiotics, including doxycycli/e (DOX), have been used to treat bone resorptive diseases, partially because of their activity to suppress osteoclastogenesis induced by receptor activator of nuclear factor kappa B ligand (RANKL). However, their precise inhibitory mechanism remains unclear. Therefore, the present study examined the effect of Dox on osteoclastogenesis signaling induced by RANKL, both in vitro and in vivo. Although Dox inhibited RANKL-induced osteoclastogenesis and down-modulated the mRNA expression of functional osteoclast markers, including tartrate-resistant acid phosphatase (TRAP) and cathepsin K, Dox neither affected RANKL-induced MAPKs phosphorylation nor NFATc1 gene expression in RAW264.7 murine monocytic cells. Gelatin zymography and Western blot analyses showed that Dox down-regulated the enzyme activity of RANKL-induced MMP-9, but without affecting its protein expression. Furthermore, MMP-9 enzyme inhibitor also attenuated both RANKL-induced osteoclastogenesis and up-regulation of TRAP and cathepsin K mRNA expression, indicating that MMP-9 enzyme action is engaged in the promotion of RANKL-induced osteoclastogenesis. Finally, Dox treatment abrogated RANKL-induced osteoclastogenesis and TRAP activity in mouse calvaria along with the suppression of MMP9 enzyme activity, again without affecting the expression of MMP9 protein. These findings suggested that Dox inhibits RANKL-induced osteoclastogenesis by its inhibitory effect on MMP-9 enzyme activity independent of the MAPK-NFATc1 signaling cascade.

  8. Decreased levels of metalloproteinase-9 and angiogenic factors in skin lesions of patients with psoriatic arthritis after therapy with anti-TNF-α

    PubMed Central

    Cordiali-Fei, Paola; Trento, Elisabetta; D'Agosto, Giovanna; Bordignon, Valentina; Mussi, Anna; Ardigò, Marco; Mastroianni, Antonio; Vento, Antonella; Solivetti, Francesco; Berardesca, Enzo; Ensoli, Fabrizio

    2006-01-01

    Background Inflammation represents an early and key event in the development of both the cutaneous psoriasis and psoriatic arthritis. Compelling evidences indicate that the production of TNF-α plays a central role in psoriasis by sustaining the inflammatory process in the skin as well as in the joints. Among the multiple effects produced by TNF-α on keratinocytes, the induction of matrix metalloproteinase-9 (MMP-9), a collagenase implicated in joint inflammatory arthritis which acts as an angiogenesis promoting factor, might represent a key mechanism in the pathogenesis of the disease. Aims of the present study were to investigate a) the role of MMP-9 in the development of psoriasis by assessing the presence of MMP-9 in lesional skin and in sera of psoriatic patients; b) the association of MMP-9 with the activity of the disease; c) the relationship between MMP-9 and TNF-α production. Methods Eleven psoriatic patients, clinically presenting joint symptoms associated to the cutaneous disease, were included in a therapeutic protocol based on the administration of anti-TNF-α monoclonal antibody (Infliximab). Sera and skin biopsies were collected before treatment and after 6 weeks of therapy. Tissues were kept in short term cultures and production soluble mediators such as TNF-α, MMP-9, MMP-2, VEGF and E-Selectin, which include angiogenic molecules associated to the development of plaque psoriasis, were measured in the culture supernatants by immunoenzymatic assays (ng/ml or pg/ml per mg of tissue). MMP-9 concentrations were also measured in the sera. The cutaneous activity of disease was evaluated by the Psoriasis Area and Severity Index (PASI). Results Clinical and laboratory assessment indicated that all but one patients had a significant improvement of the PASI score after three months of therapy. The clinical amelioration was associated to a significant decrease of MMP-9 (P = 0.017), TNF-α (P = 0.005) and E-selectin (P = 0.018) levels, spontaneously released

  9. Analysis of the persistence of enteric markers in sewage polluted water on a solid matrix and in liquid suspension.

    PubMed

    Brooks, Yolanda; Aslan, Asli; Tamrakar, Sushil; Murali, Bharathi; Mitchell, Jade; Rose, Joan B

    2015-06-01

    Addressing the persistence of bacterial indicators using qPCR and their respective DNA targets under various conditions is a critical part of risk assessment for water quality monitoring. The goal of this study was to examine the persistence of fecal indicator bacteria (FIB) via Escherichia coli uidA, enterococci 23S rDNA and Bacteroides thetataiotaomicron 1,6 alpha mannanase from cells attached to a solid matrix and in suspension. Raw sewage (10% vol/vol) was seeded into autoclaved river water with half of the sample volume in suspension and the other half was filtered onto membranes and stored at 4°, 27° and 37°C for up to 28 days. At various time points, DNA from cells was extracted, markers were quantified, and were fit to linear and non-linear models (first order exponential, biphasic (double) exponential, two-staged, log-logistic, and Gompertz 3-parameter). First order and biphasic exponential models fit 73% of the experimental data. Persistence increased significantly when the cells were stored in an attached state (p < 0.001). Increasing temperature had an inverse effect on persistence for the cells in suspension. Bacterial cells could be stored on a solid matrix at 4°, 27° and 37 °C for up to 27, 18, and 3 days, respectively, with <90% decay. The least stable indicator at 4°, 27° and 37 °C was B. thetataiotaomicron in suspension with T90 = 9.6, 1.8, and 1.1 days, respectively. The most persistent indicator was enterococci, with T90 > 28 days in an attached state at all temperatures. PMID:25835590

  10. Relative contribution of DNAPL dissolution and matrix diffusion to the long-term persistence of chlorinated solvent source zones

    NASA Astrophysics Data System (ADS)

    Seyedabbasi, Mir Ahmad; Newell, Charles J.; Adamson, David T.; Sale, Thomas C.

    2012-06-01

    The relative contribution of dense non-aqueous phase liquid (DNAPL) dissolution versus matrix diffusion processes to the longevity of chlorinated source zones was investigated. Matrix diffusion is being increasingly recognized as an important non-DNAPL component of source behavior over time, and understanding the persistence of contaminants that have diffused into lower permeability units can impact remedial decision-making. In this study, a hypothetical DNAPL source zone architecture consisting of several different sized pools and fingers originally developed by Anderson et al. (1992) was adapted to include defined low permeability layers. A coupled dissolution-diffusion model was developed to allow diffusion into these layers while in contact with DNAPL, followed by diffusion out of these same layers after complete DNAPL dissolution. This exercise was performed for releases of equivalent masses (675 kg) of three different compounds, including chlorinated solvents with solubilities ranging from low (tetrachloroethene (PCE)), moderate (trichloroethene (TCE)) to high (dichloromethane (DCM)). The results of this simple modeling exercise demonstrate that matrix diffusion can be a critical component of source zone longevity and may represent a longer-term contributor to source longevity (i.e., longer time maintaining concentrations above MCLs) than DNAPL dissolution alone at many sites. For the hypothetical TCE release, the simulation indicated that dissolution of DNAPL would take approximately 38 years, while the back diffusion from low permeability zones could maintain the source for an additional 83 years. This effect was even more dramatic for the higher solubility DCM (97% of longevity due to matrix diffusion), while the lower solubility PCE showed a more equal contribution from DNAPL dissolution vs. matrix diffusion. Several methods were used to describe the resulting source attenuation curves, including a first-order decay model which showed that half-life of

  11. Implications of matrix diffusion on 1,4-dioxane persistence at contaminated groundwater sites.

    PubMed

    Adamson, David T; de Blanc, Phillip C; Farhat, Shahla K; Newell, Charles J

    2016-08-15

    Management of groundwater sites impacted by 1,4-dioxane can be challenging due to its migration potential and perceived recalcitrance. This study examined the extent to which 1,4-dioxane's persistence was subject to diffusion of mass into and out of lower-permeability zones relative to co-released chlorinated solvents. Two different release scenarios were evaluated within a two-layer aquifer system using an analytical modeling approach. The first scenario simulated a 1,4-dioxane and 1,1,1-TCA source zone where spent solvent was released. The period when 1,4-dioxane was actively loading the low-permeability layer within the source zone was estimated to be <3years due to its high effective solubility. While this was approximately an order-of-magnitude shorter than the loading period for 1,1,1-TCA, the mass of 1,4-dioxane stored within the low-permeability zone at the end of the simulation period (26kg) was larger than that predicted for 1,1,1-TCA (17kg). Even 80years after release, the aqueous 1,4-dioxane concentration was still several orders-of-magnitude higher than potentially-applicable criteria. Within the downgradient plume, diffusion contributed to higher concentrations and enhanced penetration of 1,4-dioxane into the low-permeability zones relative to 1,1,1-TCA. In the second scenario, elevated 1,4-dioxane concentrations were predicted at a site impacted by migration of a weak source from an upgradient site. Plume cutoff was beneficial because it could be implemented in time to prevent further loading of the low-permeability zone at the downgradient site. Overall, this study documented that 1,4-dioxane within transmissive portions of the source zone is quickly depleted due to characteristics that favor both diffusion-based storage and groundwater transport, leaving little mass to treat using conventional means. Furthermore, the results highlight the differences between 1,4-dioxane and chlorinated solvent source zones, suggesting that back diffusion of 1

  12. Dietary Fatty Acids from Leaves of Clerodendrum Volubile Induce Cell Cycle Arrest, Downregulate Matrix Metalloproteinase-9 Expression, and Modulate Redox Status in Human Breast Cancer.

    PubMed

    Erukainure, Ochuko L; Zaruwa, Moses Z; Choudhary, M Iqbal; Naqvi, S Asma; Ashraf, Nadia; Hafizur, Rahman M; Muhammad, Aliyu; Ebuehi, Osaretin A T; Elemo, Gloria N

    2016-01-01

    The antiproliferative effect of the fatty acid components of Clerodendrum volubile leaves as well as its antioxidant effect on MCF-7 and MDA-MB-231 human breast cancer cell lines were investigated. Fatty acids extracted from C. volubile leaf oil were subjected to gas chromatography mass spectrometry (GCMS) analysis. The cells were cultured and treated with the fatty acids for 48 h, after which the antiproliferation effect was ascertained via MTT assay and cell viability analysis using BD fluorescence activated cells sorting (FACS) Calibur. Cell cycle was analyzed by flow cytometry on FACS Calibur. Western blotting was used in determining expression of proteins in the cell lines. The treated cell lines were assessed for reduced glutathione level, catalase, superoxide dismutase, and lipid peroxidation. The fatty acids significantly inhibited cell proliferation, arrested G0/G1 phase, downregulated the expression of MMP-9, and attenuated oxidative stress in of MCF-7 cell lines but had little or no effect on MDA-MB-231 cell lines. These results indicate the therapeutic potential of the fatty acids components of the leaves of C. volubile on human breast cancer, which may be explored further in drug development. PMID:27043182

  13. INHALED COMPLEX COMBUSTION EMISSIONS UPREGULATE TRANSCRIPTION AND ACTIVITY OF SYSTEMATIC MATRIX METALLOPROTEINASE-9 (MMP9): EVIDENCE IN MURINE AND HUMAN MODELS

    EPA Science Inventory

    Air pollution is associated with acute and chronic adverse human health effects related to atherosclerotic pathologies. MMP9 has a crucial role in the progression and ultimate degradation of vascular lesions and polymorphisms of MMP9 are highly associated with increased incidenc...

  14. Testes-specific protease 50 promotes cell invasion and metastasis by increasing NF-kappaB-dependent matrix metalloproteinase-9 expression.

    PubMed

    Song, Z B; Ni, J-S; Wu, P; Bao, Y L; Liu, T; Li, M; Fan, C; Zhang, W J; Sun, L G; Huang, Y X; Li, Y X

    2015-01-01

    The high mortality in breast cancer is often associated with metastatic progression in patients. Previously we have demonstrated that testes-specific protease 50 (TSP50), an oncogene overexpressed in breast cancer samples, could promote cell proliferation and tumorigenesis. However, whether TSP50 also has a key role in cell invasion and cancer metastasis, and the mechanism underlying the process are still unclear. Here we found that TSP50 overexpression greatly promoted cell migration, invasion, adhesion and formation of the stellate structures in 3D culture system in vitro as well as lung metastasis in vivo. Conversely, TSP50 knockdown caused the opposite changes. Mechanistic studies revealed that NF-κB signaling pathway was required for TSP50-induced cell migration and metastasis, and further results indicated that TSP50 overexpression enhanced expression and secretion of MMP9, a target gene of NF-κB signaling. In addition, knockdown of MMP9 resulted in inhibition of cell migration and invasion in vitro and lung metastasis in vivo. Most importantly, immunohistochemical staining of human breast cancer samples strongly showed that the coexpression of TSP50 and p65 as well as TSP50 and MMP9 were correlated with increased metastasis and poor survival. Furthermore, we found that some breast cancer diagnosis-associated features such as tumor size, tumor grade, estrogen receptors (ER) and progesterone receptors (PR) levels, were correlated well with TSP50/p65 and TSP50/MMP9 expression status. Taken together, this work identified the TSP50 activation of MMP9 as a novel signaling mechanism underlying human breast cancer invasion and metastasis. PMID:25811800

  15. Combined Neuroform Intracranial Stent and Bioactive Matrix Detachable Coil for Embolization of a Broad-Necked Persistent Primitive Trigeminal Artery Aneurysm

    PubMed Central

    Zhao, Q.P.; Li, T.L.; Duan, C.Z.; Chen, G.Z.

    2005-01-01

    Summary We report a patient with a wide-necked aneurysm arising at the bifurcation of the right internal carotid artery and the persistent primitive trigeminal artery (PPTA) treated successfully by Matrix detachable coil occlusion and assisted by a Neuroform intracranial stent. First, a Neuroform self-expanding intracranial stent was delivered via a 5-F Guider Softtip XP and placed as desired, then the aneurysm dome was embolized with two Matrix detachable coils through the interstices of the stent. The aneurysm was 80% occluded angiographically and the parent artery was patent. DSA imaging six months after the procedure showed the aneurysm to be obliterated at angiography and the neck tissue thickness of the aneurysm to be increased, but the parent artery diameter was not impacted. We describe the case in detail and discuss our preliminary experience of using the Neuroform stent and Matrix detachable coils for the treatment of a PPTA wide-necked aneurysm. PMID:20584437

  16. Unexpected persistence on habitat islands: genetic signatures reveal dispersal of a eucalypt-dependent marsupial through a hostile pine matrix.

    PubMed

    Taylor, Andrea C; Tyndale-Biscoe, Hugh; Lindenmayer, David B

    2007-07-01

    Several factors contribute to the extinction of populations in fragmented habitat but key ones include habitat loss and disruptions to connectivity. Aspects of the ecology of greater gliders (Petauroides volans), along with observations of their response to native forest clearance at a site in southeastern Australia, lead to the prediction in the 1960s that the species would not persist in the replacement exotic pine plantation. However, 35 years later, the species was observed in many remnant native vegetation patches retained within the plantation boundary, albeit at a lower occupancy rate than at matched continuous forest control sites. To determine the role of patch connectivity in persistence of P. volans in remnants, we employed 12 microsatellite markers to genotype individuals from 11 remnants, three contemporary nearby continuous native eucalypt forest sites and a sample collected during native vegetation clearance at the site in the 1960s. Patch samples retained substantially more genetic diversity than expected under an isolation model, suggesting that patches have experienced some immigration. Five putative patch immigrants--two from sampled sites 1- and 7-km distant, and three from unresolved or unsampled localities--were identified via genetic parentage and population assignment analyses. Patch populations displayed varying levels of admixture in Bayesian genetic structure analyses, with the oldest and most geographically isolated ones showing the least admixture, suggesting they have experienced relatively little immigration. Evidence of at least some immigration into patches may explain why P. volans has persisted contrary to expectation in heavily fragmented habitat. PMID:17594437

  17. Liver functions in silica-exposed workers in Egypt: possible role of matrix remodeling and immunological factors

    PubMed Central

    Zawilla, Nermin; Taha, Fatma; Ibrahim, Yasser

    2014-01-01

    Background: Brick manufacturing constitutes an important industrial sector in Egypt with considerable exposure to silica. Objectives: We aimed for evaluating hepatic functions in silica-exposed workers in the clay brick industry, and the possible role of matrix remodeling and immunological factors. Methods: A case–control study, 87 workers as exposed and 45 as control subjects. Questionnaire, clinical examination, and laboratory investigations: liver functions, matrix metalloproteinase-9, immunoglobulins G and E, and anti-liver kidney microsomal antibody. Results: In the exposed workers, mean levels of liver functions, matrix metalloproteinase-9 (MMP-9), and IgG and IgE were significantly higher. In the silicotic subgroup the mean level of GGT was almost twice the level in the non-silicotic subjects. Logistic regression showed that abnormal GGT and ALT were associated with production workers. Conclusion: Workers in the clay brick industry showed evidence of liver disease that could be related to matrix remodeling. PMID:24999850

  18. Persistent Biomechanical Alterations After ACL Reconstruction Are Associated With Early Cartilage Matrix Changes Detected by Quantitative MR

    PubMed Central

    Amano, Keiko; Pedoia, Valentina; Su, Favian; Souza, Richard B.; Li, Xiaojuan; Ma, C. Benjamin

    2016-01-01

    Background: The effectiveness of anterior cruciate ligament (ACL) reconstruction in preventing early osteoarthritis is debated. Restoring the original biomechanics may potentially prevent degeneration, but apparent pathomechanisms have yet to be described. Newer quantitative magnetic resonance (qMR) imaging techniques, specifically T1ρ and T2, offer novel, noninvasive methods of visualizing and quantifying early cartilage degeneration. Purpose: To determine the tibiofemoral biomechanical alterations before and after ACL reconstruction using magnetic resonance imaging (MRI) and to evaluate the association between biomechanics and cartilage degeneration using T1ρ and T2. Study Design: Cohort study; Level of evidence, 2. Methods: Knee MRIs of 51 individuals (mean age, 29.5 ± 8.4 years) with unilateral ACL injuries were obtained prior to surgery; 19 control subjects (mean age, 30.7 ± 5.3 years) were also scanned. Follow-up MRIs were obtained at 6 months and 1 year. Tibial position (TP), internal tibial rotation (ITR), and T1ρ and T2 were calculated using an in-house Matlab program. Student t tests, repeated measures, and regression models were used to compare differences between injured and uninjured sides, observe longitudinal changes, and evaluate correlations between TP, ITR, and T1ρ and T2. Results: TP was significantly more anterior on the injured side at all time points (P < .001). ITR was significantly increased on the injured side prior to surgery (P = .033). At 1 year, a more anterior TP was associated with elevated T1ρ (P = .002) and T2 (P = .026) in the posterolateral tibia and with decreased T2 in the central lateral femur (P = .048); ITR was associated with increased T1ρ in the posteromedial femur (P = .009). ITR at 6 months was associated with increased T1ρ at 1 year in the posteromedial tibia (P = .029). Conclusion: Persistent biomechanical alterations after ACL reconstruction are related to significant changes in cartilage T1ρ and T2 at 1 year

  19. Cell Persistence of Allogeneic Keratinocytes and Fibroblasts Applied in a Fibrin Matrix to Acute, Full Thickness Wounds

    PubMed Central

    Dickerson, Jaime E.; Planz, John V.; Reece, Barry T.; Weedon, Kathy A.; Kirkpatrick, Sandy D.; Slade, Herbert B.

    2013-01-01

    HP802-247 is a living cell suspension of cultured allogeneic growth-arrested human male keratinocytes and fibroblasts (1:9 ratio), intended for spray application to chronic wounds. In this study, a small wound was created on the arms of 28 healthy female volunteers (3-mm punch), followed by a single application of HP802-247. At each subsequent week for 8 weeks, a punch excision of the wounds was performed on a cohort of three subjects. Excised specimens were analyzed for allogeneic fibroblast and keratinocyte DNA determined by Y-chromosome short-tandem repeats using PCR amplification followed by capillary electrophoresis, a method with estimated sensitivity of 1 male cell in a background of 8,000 female cells. A complete haplotype attributable to HP802-247 fibroblasts was detected in three of three samples at 1 week, with one partial and one complete fibroblast haplotype detected at 2 weeks, and one partial keratinocyte haplotype detected at 3 weeks postapplication. The findings indicate that HP802-247 can be expected to persist in an acute wound bed for up to 2 weeks postapplication. PMID:26858859

  20. Synergistic upregulation of metalloproteinase-9 by growth factors and inflammatory cytokines: an absolute requirement for transcription factor NF-kappa B.

    PubMed

    Bond, M; Fabunmi, R P; Baker, A H; Newby, A C

    1998-09-11

    Matrix metalloproteinase (MMPs) enzymes are implicated in matrix remodelling during proliferative inflammatory processes including wound healing. We report here synergistic upregulation of MMP-9 protein and mRNA by platelet-derived growth factor (PDGF) or basic fibroblast growth factor (bFGF) in combination with interleukin-1alpha (IL-1alpha) or tumour necrosis factor-alpha (TNF-alpha) in primary rabbit and human dermal fibroblasts. The synergistic interaction between growth factors and cytokines implies that basement membrane remodelling is maximal physiologically when both are present together. The signalling pathways mediating this synergistic regulation are not understood, although analysis of the MMP-9 promoter has identified an essential proximal AP-1 element and an upstream nuclear factor kappa-B (NF-kappaB) site. Using electromobility shift assays, binding to the AP-1 site was only slightly increased by growth factors and cytokines. NF-kappaB binding was rapidly induced by IL-1alpha or TNF-alpha but was neither induced nor potentiated by bFGF or PDGF. Neither AP-1 nor NF-kappaB was therefore sufficient on its own for synergistic regulation. Using a recently developed adenovirus that overexpresses the inhibitory subunit, IkappaB alpha, we demonstrated an absolute requirement for NF-kappaB in upregulation of MMP-9. Activation of NF-kappaB binding by inflammatory cytokines was therefore necessary but not sufficient for synergistic upregulation of MMP-9. PMID:9755853

  1. Epidermal Growth Factor–induced Enhancement of Glioblastoma Cell Migration in 3D Arises from an Intrinsic Increase in Speed But an Extrinsic Matrix- and Proteolysis-dependent Increase in Persistence

    PubMed Central

    Kim, Hyung-Do; Guo, Tiffany W.; Wu, Angela P.; Wells, Alan; Gertler, Frank B.

    2008-01-01

    Epidermal growth factor (EGF) receptor-mediated cell migration plays a vital role in invasion of many tumor types. EGF receptor ligands increase invasiveness in vivo, but it remains unclear how consequent effects on intrinsic cell motility behavior versus effects on extrinsic matrix properties integrate to result in net increase of translational speed and/or directional persistence of migration in a 3D environment. Understanding this convolution is important for therapeutic targeting of tumor invasion, as key regulatory pathways for intrinsic versus extrinsic effects may not be coincident. Accordingly, we have undertaken a quantitative single-cell imaging study of glioblastoma cell movement in 3D matrices and on 2D substrata across a range of collagen densities with systematic variation of protease-mediated matrix degradation. In 3D, EGF induced a mild increase in cell speed and a strong increase in directional persistence, the latter depending heavily on matrix density and EGF-stimulated protease activity. In contrast, in 2D, EGF induced a similarly mild increase in speed but conversely a decrease in directional persistence (both independent of protease activity). Thus, the EGF-enhanced 3D tumor cell migration results only partially from cell-intrinsic effects, with override of cell-intrinsic persistence decrease by protease-mediated cell-extrinsic reduction of matrix steric hindrance. PMID:18632979

  2. In vitro studies to show sequestration of matrix metalloproteinases by silver-containing wound care products.

    PubMed

    Walker, Michael; Bowler, Philip G; Cochrane, Christine A

    2007-09-01

    Excess or "uncontrolled" proteinase activity in the wound bed has been implicated as one factor that may delay or compromise wound healing. One proteinase group--matrix metalloproteinases--includes collagenases, elastase, and gelatinases and can be endogenous (cell) or exogenous (bacterial) in origin. A study was conducted to assess the ability of five silver-containing wound care products to reduce a known matrix metalloproteinase supernatant concentration in vitro. Four silver-containing wound dressings (a carboxy-methyl cellulose, a nanocrystalline, a hydro-alginate, and a collagen/oxidized regenerated cellulose composite dressing), along with a 0.5% aqueous silver nitrate [w/v] solution and controls for matrix metalloproteinase-2 and matrix metalloproteinase-9 sourced from ex vivo dermal tissue and blood monocytes, respectively, were used. Extracts were separated and purified using gelatine-Sepharose column chromatography and dialysis and polyacrylamide gel electrophoretic zymography was used to analyze specific matrix metalloproteinase activity. All dressings and the solution were shown to sequester both matrix metalloproteinases. The silver-containing carboxy-methyl cellulose dressing showed significantly greater sequestration for matrix metalloproteinase-2 at 6 and 24 hours (P< 0.001) compared to the other treatments. For matrix metalloproteinase-9, both the carboxy-methyl cellulose dressing and the oxidized regenerated cellulose dressing achieved significant sequestration when compared to the other treatments at 24 hours (P <0.001), which was maintained to 48 hours (P < 0.001). Results from this study show that silver-containing dressings are effective in sequestering matrix metalloproteinase-2 and -9 and that this can be achieved without a sacrificial protein (eg, collagen). Although the varying ability of wound dressings to sequester matrix metalloproteinases has been shown in vitro, further in vivo evidence is required to confirm these findings. PMID

  3. Monocytes increase human cardiac myofibroblast-mediated extracellular matrix remodeling through TGF-β1.

    PubMed

    Mewhort, Holly E M; Lipon, Brodie D; Svystonyuk, Daniyil A; Teng, Guoqi; Guzzardi, David G; Silva, Claudia; Yong, V Wee; Fedak, Paul W M

    2016-03-15

    Following myocardial infarction (MI), cardiac myofibroblasts remodel the extracellular matrix (ECM), preventing mechanical complications. However, prolonged myofibroblast activity leads to dysregulation of the ECM, maladaptive remodeling, fibrosis, and heart failure (HF). Chronic inflammation is believed to drive persistent myofibroblast activity; however, the mechanisms are unclear. We assessed the influence of peripheral blood monocytes on human cardiac myofibroblast activity in a three-dimensional (3D) ECM microenvironment. Human cardiac myofibroblasts isolated from surgical biopsies of the right atrium and left ventricle were seeded into 3D collagen matrices. Peripheral blood monocytes were isolated from healthy human donors and cocultured with myofibroblasts. Monocytes increased myofibroblast activity measured by collagen gel contraction (baseline: 57.6 ± 5.9% vs. coculture: 65.2 ± 7.1% contraction; P < 0.01) and increased local ECM remodeling quantified by confocal microscopy. Under coculture conditions that allow indirect cellular interaction via paracrine factors but prevent direct cell-cell contact, monocytes had minimal effects on myofibroblast activity (17.9 ± 11.1% vs. 6.4 ± 7.0% increase, respectively; P < 0.01). When cells were cultured under direct contact conditions, multiplex analysis of the coculture media revealed an increase in the paracrine factors TGF-β1 and matrix metalloproteinase 9 compared with baseline (122.9 ± 10.1 pg/ml and 3,496.0 ± 190.4 pg/ml, respectively, vs. 21.5 ± 16.3 pg/ml and 183.3 ± 43.9 pg/ml; P < 0.001). TGF-β blockade abolished the monocyte-induced increase in cardiac myofibroblast activity. These data suggest that direct cell-cell interaction between monocytes and cardiac myofibroblasts stimulates TGF-β-mediated myofibroblast activity and increases remodeling of local matrix. Peripheral blood monocyte interaction with human cardiac myofibroblasts stimulates myofibroblast activity through release of TGF-β1

  4. Photon-gated persistent spectral hole burning by electron transfer from a doped donor to an acceptor branched to a host polymer matrix

    NASA Astrophysics Data System (ADS)

    Suzuki, H.; Nishi, T.; Shimada, T.; Hiratsuka, H.

    1993-01-01

    Two-color photon-gated persistent spectral hole burning (PSHB) via donor-acceptor electron transfer is reported in systems where the acceptor, 10-chloroanthracene, was intentionally branched to a side chain of the poly(methylmethacrylate) (PMMA) host polymer while the donor, metal-free tetraphenylporphine, was dispersed in the polymer. The systems, which had an acceptor concentration of up to 10-1 M, were prepared without aggregation of the acceptor. Spectral holes were burnt in the Qx(0,0) absorption band of the donor when the systems were simultaneously irradiated with a frequency-selective excitation (duration: 500 ps; energy: 200 nJ/cm2) and a gating excitation (wavelength: 514.5 nm; duration: 33 ms; energy: 14 μJ/cm2). The difference absorption spectrum between the unburned absorption spectrum and one recorded after photon-gated PSHB has confirmed that the hole formation mechanism is donor-acceptor electron transfer from a photoexcited donor to a ground-state branched acceptor. The thermal stability of burnt holes measured with a temperature cycling experiment increased when the acceptor was branched into PMMA. The effect of acceptor branching on the PSHB characteristics is discussed with reference to those for an acceptor-doped system.

  5. [Persistent diarrhea

    PubMed

    Andrade, J A; Moreira, C; Fagundes Neto, U

    2000-07-01

    INTRODUCTION: Persistent diarrhea has high impact on infantile morbidity and mortality rates in developing countries. Several studies have shown that 3 to 20% of acute diarrheal episodes in children under 5 years of age become persistent. DEFINITION: Persistent diarrhea is defined as an episode that lasts more than 14 days. ETIOLOGY: The most important agents isolated in persistent diarrhea are: Enteropathogenic E. coli (EPEC), Salmonella, Enteroaggregative E. coli (EAEC), Klebisiella and Cryptosporidium. CLINICAL ASPECTS: In general, the clinical characteristics of patients with persistent diarrhea do not change with the pathogenic agent. Persistent diarrhea seems to represent the final result of a several insults a infant suffers that predisposes to a more severe episode of diarrhea due to a combination of host factors and high rates of enviromental contamination. Therefore, efforts should be made to promptly treat all episodes of diarrhea with apropriate follow-up. THERAPY: The aim of the treatment is to restore hydroelectrolytic deficits and to replace losses until the diarrheal ceases. It is possible in the majority of the cases, using oral rehydration therapy and erly an appropriate type of diet. PREVENTION: It is imperative that management strategies also focus on preventive aspects. The most effective diarrheal prevention strategy in young infants worldwide is promotion of exclusive breast feeding. PMID:14676915

  6. Semibiotic Persistence

    NASA Astrophysics Data System (ADS)

    Prothmann, C.; Zauner, K.-P.

    From observation, we find four different strategies to successfully enable structures to persist over extended periods of time. If functionally relevant features are very large compared to the changes that can be effectuated by entropy, the functional structure itself has a high enough probability to erode only slowly over time. If the functionally relevant features are protected from environmental influence by sacrificial layers that absorb the impinging of the environment, deterioration can be avoided or slowed. Loss of functionality can be delayed, even for complex systems, by keeping alternate options for all required components available. Biological systems also apply information processing to actively counter the impact of entropy by mechanisms such as self-repair. The latter strategy increases the overall persistence of living systems and enables them to maintain a highly complex functional organisation during their lifetime and over generations. In contrast to the other strategies, information processing has only low material overhead. While at present engineered technology is far from achieving the self-repair of evolved systems, the semibiotic combination of biological components with conventionally engineered systems may open a path to long-term persistence of functional devices in harsh environments. We review nature's strategies for persistence, and consider early steps taken in the laboratory to import such capabilities into engineered architectures.

  7. Metalloproteinase-9 contributes to inflammatory glia activation and nigro-striatal pathway degeneration in both mouse and monkey models of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism.

    PubMed

    Annese, V; Herrero, María-Trinidad; Di Pentima, M; Gomez, A; Lombardi, L; Ros, C M; De Pablos, V; Fernandez-Villalba, E; De Stefano, Maria Egle

    2015-03-01

    Inflammation is a predominant aspect of neurodegenerative diseases, manifested by glia activation and expression of pro-inflammatory mediators. Studies on animal models of Parkinson's disease (PD) suggest that sustained neuroinflammation exacerbates degeneration of the dopaminergic (DA) nigro-striatal pathway. Therefore, insights into the inflammatory mechanisms of PD may help the development of novel therapeutic strategies against this disease. As extracellular matrix metalloproteinases (MMPs) could be major players in the progression of Parkinsonism, we investigated, in the substantia nigra and striatum of mice acutely injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), changes in mRNA expression, protein levels, and cell localization of MMP-9. This protease is mainly neuronal, but early after MPTP injection its mRNA and protein levels, as well as the number of MMP-9-expressing microglia and astrocytes, increase concomitantly to a prominent inflammation. Neuroinflammation and MMP-9(+) glia begin to decline within 2 weeks, although protein levels remain higher than control, in association with a partial recovery of DA nigro-striatal circuit. Comparable quantitative studies on MMP-9 knock-out mice, show a significant decrease in both glia activation and loss of DA neurons and fibers, with respect to wild-type. Moreover, in a parallel study on chronically MPTP-injected macaques, we observed that perpetuation of inflammation and high levels of MMP-9 are associated to DA neuron loss. Our data suggest that MMP-9 released by injured neurons favors glia activation; glial cells in turn reinforce their reactive state via autocrine MMP-9 release, contributing to nigro-striatal pathway degeneration. Specific modulation of MMP-9 activity may, therefore, be a strategy to ameliorate harmful inflammatory outcomes in Parkinsonism. PMID:24558048

  8. The Influence of Autologous Bone Marrow Stem Cell Transplantation on Matrix Metalloproteinases in Patients Treated for Acute ST-Elevation Myocardial Infarction

    PubMed Central

    Furenes, Eline Bredal; Opstad, Trine Baur; Solheim, Svein; Lunde, Ketil; Arnesen, Harald; Seljeflot, Ingebjørg

    2014-01-01

    Background. Matrix metalloproteinase-9 (MMP-9), regulated by tissue inhibitor of metalloproteinase-9 (TIMP-1) and the extracellular matrix metalloproteinase inducer (EMMPRIN), contributes to plaque instability. Autologous stem cells from bone marrow (mBMC) treatment are suggested to reduce myocardial damage; however, limited data exists on the influence of mBMC on MMPs. Aim. We investigated the influence of mBMC on circulating levels of MMP-9, TIMP-1, and EMMPRIN at different time points in patients included in the randomized Autologous Stem-Cell Transplantation in Acute Myocardial Infarction (ASTAMI) trial (n = 100). Gene expression analyses were additionally performed. Results. After 2-3 weeks we observed a more pronounced increase in MMP-9 levels in the mBMC group, compared to controls (P = 0.030), whereas EMMPRIN levels were reduced from baseline to 2-3 weeks and 3 months in both groups (P < 0.0001). Gene expression of both MMP-9 and EMMPRIN was reduced from baseline to 3 months. MMP-9 and EMMPRIN were significantly correlated to myocardial injury (CK: P = 0.005 and P < 0.001, resp.) and infarct size (SPECT: P = 0.018 and P = 0.008, resp.). Conclusion. The results indicate that the regulation of metalloproteinases is important during AMI, however, limited influenced by mBMC. PMID:25294955

  9. Endocytosis of collagen by hepatic stellate cells regulates extracellular matrix dynamics

    PubMed Central

    Bi, Yan; Mukhopadhyay, Dhriti; Drinane, Mary; Ji, Baoan; Li, Xing; Cao, Sheng

    2014-01-01

    Hepatic stellate cells (HSCs) generate matrix, which in turn may also regulate HSCs function during liver fibrosis. We hypothesized that HSCs may endocytose matrix proteins to sense and respond to changes in microenvironment. Primary human HSCs, LX2, or mouse embryonic fibroblasts (MEFs) [wild-type; c-abl−/−; or Yes, Src, and Fyn knockout mice (YSF−/−)] were incubated with fluorescent-labeled collagen or gelatin. Fluorescence-activated cell sorting analysis and confocal microscopy were used for measuring cellular internalization of matrix proteins. Targeted PCR array and quantitative real-time PCR were used to evaluate gene expression changes. HSCs and LX2 cells endocytose collagens in a concentration- and time-dependent manner. Endocytosed collagen colocalized with Dextran 10K, a marker of macropinocytosis, and 5-ethylisopropyl amiloride, an inhibitor of macropinocytosis, reduced collagen internalization by 46%. Cytochalasin D and ML7 blocked collagen internalization by 47% and 45%, respectively, indicating that actin and myosin are critical for collagen endocytosis. Wortmannin and AKT inhibitor blocked collagen internalization by 70% and 89%, respectively, indicating that matrix macropinocytosis requires phosphoinositide-3-kinase (PI3K)/AKT signaling. Overexpression of dominant-negative dynamin-2 K44A blocked matrix internalization by 77%, indicating a role for dynamin-2 in matrix macropinocytosis. Whereas c-abl−/− MEF showed impaired matrix endocytosis, YSF−/− MEF surprisingly showed increased matrix endocytosis. It was also associated with complex gene regulations that related with matrix dynamics, including increased matrix metalloproteinase 9 (MMP-9) mRNA levels and zymographic activity. HSCs endocytose matrix proteins through macropinocytosis that requires a signaling network composed of PI3K/AKT, dynamin-2, and c-abl. Interaction with extracellular matrix regulates matrix dynamics through modulating multiple gene expressions including MMP-9

  10. Plasma matrix metalloproteinases in neonates having surgery for congenital heart disease

    PubMed Central

    Joffe, Ari R.; Schulz, Christina; Rosychuk, Rhonda J.; Dyck, John; Rebeyka, Ivan M.; Ross, David B.; Schulz, Richard; Cheung, Po-Yin

    2009-01-01

    During cardiopulmonary-bypass matrix-metalloproteinases released may contribute to ventricular dysfunction. This study was to determine plasma matrix-metalloproteinases in neonates after cardiopulmonary-bypass and their relation to post-operative course. A prospective observational study included 18 neonates having cardiac surgery. Plasma matrix-metalloproteinases-2 and 9 activities were measured by gelatin-zymography pre-operatively, on starting cardiopulmonarybypass, 7–8 min after aortic cross-clamp release, and 1h, 4h, 24h, and 3d after cardiopulmonary-bypass. Plasma concentrations of their tissue inhibitors 1 and 2 were determined by enzyme-linked immunosorbent assay. Cardiac function was assessed by serial echocardiography. Paired t-tests and Wilcoxon tests were used to assess temporal changes, and linear correlation with simultaneous clinical and cardiac function parameters were assessed using Pearson's product-moment correlation coefficient. Plasma matrix-metalloproteinases activities and their tissue inhibitor concentrations decreased during cardiopulmonary-bypass. Matrix-metalloproteinase-2 plasma activity increased progressively starting 1h after cardiopulmonarybypass and returned to pre-operative levels at 24h. Matrix-metalloproteinase-9 plasma activity increased significantly after release of aortic cross-clamp, peaked 7–8min later, and returned to baseline at 24h. Plasma tissueinhibitor 1 and 2 concentrations increased 1h after cardiopulmonary-bypass. Cardiac function improved from 4h to 3d after surgery (p<0.05). There was no evidence of significant correlations between matrix-metalloproteinases or their inhibitors and cardiac function, inotrope scores, organ dysfunction scores, ventilation days, or hospital days. The temporal profile of plasma matrix-metalloproteinases and their inhibitors after cardiopulmonary-bypass in neonates are similar to adults. In neonates, further study should determine whether circulating matrix-metalloproteinases are

  11. Response: persistent perplexities.

    PubMed

    Radin, M J

    2001-09-01

    This response to the preceding five articles highlights the stubborn persistence of the philosophical perplexities surrounding commodification in the realm of medicine and biotechnology. PMID:11700685

  12. Induction of matrix metalloproteinase activation cascades based on membrane-type 1 matrix metalloproteinase: associated activation of gelatinase A, gelatinase B and collagenase 3.

    PubMed Central

    Cowell, S; Knäuper, V; Stewart, M L; D'Ortho, M P; Stanton, H; Hembry, R M; López-Otín, C; Reynolds, J J; Murphy, G

    1998-01-01

    SW1353 chondrosarcoma cells cultured in the presence of interleukin-1, concanavalin A or PMA secreted procollagenase 3 (matrix metalloproteinase-13). The enzyme was detected in the culture medium by Western blotting using a specific polyclonal antibody raised against recombinant human procollagenase 3. Oncostatin M enhanced the interleukin-1-induced production of procollagenase 3, whereas interleukin-4 decreased procollagenase 3 synthesis. The enzyme was latent except when the cells had been treated with concanavalin A, when a processed form of 48 kDa, which corresponds to the active form, was found in the culture medium and collagenolytic activity was detected by degradation of 14C-labelled type I collagen. The concanavalin A-induced activation of procollagenase 3 coincided with the processing of progelatinase A (matrix metalloproteinase-2) by the cells, as measured by gelatin zymography. In addition, progelatinase B (matrix metalloproteinase-9) was activated when gelatinase A and collagenase 3 were in their active forms. Concanavalin A treatment of SW1353 cells increased the amount of membrane-type-1 matrix metalloproteinase protein in the cell membranes, suggesting that this membrane-bound enzyme participates in an activation cascade involving collagenase 3 and the gelatinases. This cascade was effectively inhibited by tissue inhibitors of metalloproteinases-2 and -3. Tissue inhibitor of metalloproteinases-1, which is a much weaker inhibitor of membrane-type 1 matrix metalloproteinase than tissue inhibitors of metalloproteinases-2 and -3 [Will, Atkinson, Butler, Smith and Murphy (1996) J. Biol. Chem. 271, 17119-17123], was a weaker inhibitor of the activation cascade. PMID:9531484

  13. Matrix superpotentials

    NASA Astrophysics Data System (ADS)

    Nikitin, Anatoly G.; Karadzhov, Yuri

    2011-07-01

    We present a collection of matrix-valued shape invariant potentials which give rise to new exactly solvable problems of SUSY quantum mechanics. It includes all irreducible matrix superpotentials of the generic form W=kQ+\\frac{1}{k} R+P, where k is a variable parameter, Q is the unit matrix multiplied by a real-valued function of independent variable x, and P and R are the Hermitian matrices depending on x. In particular, we recover the Pron'ko-Stroganov 'matrix Coulomb potential' and all known scalar shape invariant potentials of SUSY quantum mechanics. In addition, five new shape invariant potentials are presented. Three of them admit a dual shape invariance, i.e. the related Hamiltonians can be factorized using two non-equivalent superpotentials. We find discrete spectrum and eigenvectors for the corresponding Schrödinger equations and prove that these eigenvectors are normalizable.

  14. Nrf2 null enhances UVB-induced skin inflammation and extracellular matrix damages.

    PubMed

    Saw, Constance Lay Lay; Yang, Anne Yuqing; Huang, Mou-Tuan; Liu, Yue; Lee, Jong Hun; Khor, Tin Oo; Su, Zheng-Yuan; Shu, Limin; Lu, Yaoping; Conney, Allan H; Kong, Ah-Ng Tony

    2014-01-01

    Nrf2 plays a critical role in defending against oxidative stress and inflammation. We previously reported that Nrf2 confers protection against ultraviolet-B (UVB)-induced inflammation, sunburn reaction, and is involved in sulforaphane-mediated photo-protective effects in the skin. In this study, we aimed to demonstrate the protective role of Nrf2 against inflammation-mediated extracellular matrix (ECM) damage induced by UVB irradiation. Ear biopsy weights were significantly increased in both Nrf2 wild-type (Nrf2 WT) and knockout (Nrf2 KO) mice one week after UVB irradiation. However, these weights increased more significantly in KO mice compared to WT mice, suggesting a greater inflammatory response in KO mice. In addition, we analyzed the protein expression of numerous markers, including macrophage inflammatory protein-2 (MIP-2), pro-matrix metalloproteinase-9 (MMP-9), and p53. p53, a regulator of DNA repair, was overexpressed in Nrf2 KO mice, indicating that the absence of Nrf2 led to more sustained DNA damage. There was also more substantial ECM degradation and increased inflammation in UVB-irradiated Nrf2 KO mice compared to UVB-irradiated WT mice. Furthermore, the protective effects of Nrf2 in response to UVB irradiation were mediated by increased HO-1 protein expression. Collectively, our results show that Nrf2 plays a key role in protecting against UVB irradiation and that the photo-protective effect of Nrf2 is closely related to the inhibition of ECM degradation and inflammation. PMID:25228981

  15. Sodium hydrosulfide prevents myocardial dysfunction through modulation of extracellular matrix accumulation and vascular density.

    PubMed

    Pan, Li-Long; Wang, Xian-Li; Wang, Xi-Ling; Zhu, Yi-Zhun

    2014-01-01

    The aim was to examine the role of exogenous hydrogen sulfide (H2S) on cardiac remodeling in post-myocardial infarction (MI) rats. MI was induced in rats by ligation of coronary artery. After treatment with sodium hydrosulfide (NaHS, an exogenous H2S donor, 56 μM/kg·day) for 42 days, the effects of NaHS on left ventricular morphometric features, echocardiographic parameters, heme oxygenase-1 (HO-1), matrix metalloproteinases-9 (MMP-9), type I and type III collagen, vascular endothelial growth factor (VEGF), CD34, and α-smooth muscle actin (α-SMA) in the border zone of infarct area were analyzed to elucidate the protective mechanisms of exogenous H2S on cardiac function and fibrosis. Forty-two days post MI, NaHS-treatment resulted in a decrease in myocardial fibrotic area in association with decreased levels of type I, type III collagen and MMP-9 and improved cardiac function. Meanwhile, NaHS administration significantly increased cystathionine γ-lyase (CSE), HO-1, α-SMA, and VEGF expression. This effect was accompanied by an increase in vascular density in the border zone of infarcted myocardium. Our results provided the strong evidences that exogenous H2S prevented cardiac remodeling, at least in part, through inhibition of extracellular matrix accumulation and increase in vascular density. PMID:25514418

  16. Persistent depressive disorder

    MedlinePlus

    PDD; Chronic depression; Depression - chronic ... The exact cause of persistent depressive disorder (PDD) is unknown. It tends to run in families. PDD occurs more often in women. Most people with PDD will also ...

  17. Persistent depressive disorder

    MedlinePlus

    The exact cause of persistent depressive disorder (PDD) is unknown. It tends to run in families. PDD occurs more often in women. Most people with PDD will also have an episode of major depression at some point in their lives. ...

  18. Persistent heap Management library

    Energy Science and Technology Software Center (ESTSC)

    2012-01-17

    PERM is a C library for persistent heap management and is intended for use with a dynamic-memory allocator (e.g. malloc, free). The PERM memory allocator replaces the standard C dynamic memory allocation functions with compatible versions that provide persistent memory to application programs. Memory allocated with the PERM allocatory will persist between program invocations after a call to a checkpoint function. This function essentially saves the state of the heap and registered global variables tomore » a file which may reside in flash memory or other node local storage. A few other functions are also provided by the library to manage checkpoint files. Global variables in an application can be marked persistent and be included in a checkpoint by using a compiler attribute defined as PERM. The PERM checkpoint methof is not dependent on the programming model ans works with distributed memory or shared memory programs.« less

  19. Persistent heap Management library

    SciTech Connect

    2012-01-17

    PERM is a C library for persistent heap management and is intended for use with a dynamic-memory allocator (e.g. malloc, free). The PERM memory allocator replaces the standard C dynamic memory allocation functions with compatible versions that provide persistent memory to application programs. Memory allocated with the PERM allocatory will persist between program invocations after a call to a checkpoint function. This function essentially saves the state of the heap and registered global variables to a file which may reside in flash memory or other node local storage. A few other functions are also provided by the library to manage checkpoint files. Global variables in an application can be marked persistent and be included in a checkpoint by using a compiler attribute defined as PERM. The PERM checkpoint methof is not dependent on the programming model ans works with distributed memory or shared memory programs.

  20. Sync Matrix

    Energy Science and Technology Software Center (ESTSC)

    2004-12-31

    Sync Matrix provides a graphic display of the relationships among all of the response activities of each jurisdiction. This is accomplished through software that organizes and displays the activities by jurisdiction, function, and time for easy review and analysis. The software can also integrate the displays of multiple jurisdictions to allow examination of the total response.

  1. Melting of persistent double-stranded polymers

    NASA Astrophysics Data System (ADS)

    Rahi, Sahand Jamal; Hertzberg, Mark Peter; Kardar, Mehran

    2008-11-01

    Motivated by recent DNA-pulling experiments, we revisit the Poland-Scheraga model of melting a double-stranded polymer. We include distinct bending rigidities for both the double-stranded segments and the single-stranded segments forming a bubble. There is also bending stiffness at the branch points between the two segment types. The transfer matrix technique for single persistent chains is generalized to describe the branching bubbles. Properties of spherical harmonics are then exploited in truncating and numerically solving the resulting transfer matrix. This allows efficient computation of phase diagrams and force-extension curves (isotherms). While the main focus is on exposition of the transfer matrix technique, we provide general arguments for a reentrant melting transition in stiff double strands. Our theoretical approach can also be extended to study polymers with bubbles of any number of strands, with potential applications to molecules such as collagen.

  2. Persistence and financial markets

    NASA Astrophysics Data System (ADS)

    Jain, S.

    2007-09-01

    The persistence phenomenon is studied in a financial context by using a novel mapping of the time evolution of the values of shares in a portfolio onto Ising spins. The method is applied to historical data from the London Financial Times Stock Exchange 100 index (FTSE 100) over an arbitrarily chosen period. By following the time dependence of the spins, we find evidence for a power law decay of the proportion of shares that remain either above or below their ‘starting’ values. As a result, we estimate a persistence exponent for the underlying financial market to be ≈0.5. Preliminary results from computer simulations on persistence in the economic dynamics of a toy model appear to reproduce the behaviour observed in real markets.

  3. Why Do Delusions Persist?

    PubMed Central

    Corlett, Philip R.; Krystal, John H.; Taylor, Jane R.; Fletcher, Paul C.

    2009-01-01

    Delusions are bizarre and distressing beliefs that characterize certain mental illnesses. They arise without clear reasons and are remarkably persistent. Recent models of delusions, drawing on a neuroscientific understanding of learning, focus on how delusions might emerge from abnormal experience. We believe that these models can be extended to help us understand why delusions persist. We consider prediction error, the mismatch between expectancy and experience, to be central. Surprising events demand a change in our expectancies. This involves making what we have learned labile, updating and binding the memory anew: a process of memory reconsolidation. We argue that, under the influence of excessive prediction error, delusional beliefs are repeatedly reconsolidated, strengthening them so that they persist, apparently impervious to contradiction. PMID:19636384

  4. Degradation of MSCRAMM target macromolecules in VLU slough by Lucilia sericata chymotrypsin 1 (ISP) persists in the presence of tissue gelatinase activity.

    PubMed

    Pritchard, David I; Brown, Alan P

    2015-08-01

    Venous leg ulcer slough is unpleasant to the patient and difficult to manage clinically. It harbours infection, also preventing wound management materials and dressings from supporting the underlying viable tissues. In other words, slough has significant nuisance value in the tissue viability clinic. In this study, we have sought to increase our knowledge of slough by building upon a previous but limited analysis of this necrotic tissue. In particular, slough has been probed using Western blotting for the presence of proteins with the capacity to engage microbial surface components recognising adhesive matrix macromolecules. Although the samples were difficult to resolve, we detected fibrinogen, fibronectin, IgG, collagen, human serum albumin and matrix metalloproteinase-9. Furthermore, the effect of a maggot-derived debridement enzyme, chymotrypsin 1 on macromolecules in slough was confirmed across seven patient samples. The effect of chymotrypsin 1 on slough confirms our thesis that this potential debridement enzyme could be effective in removing slough along with its associated bacteria, given its observed resistance to intrinsic gelatinase activity. In summary, we believe that the data provide scientists and clinicians with further insights into the potential molecular interactions between bacteria, wound tissue and Lucilia sericata in a clinically problematic yet scientifically interesting wound ecosystem. PMID:23834475

  5. A Very Persistent Mistake

    ERIC Educational Resources Information Center

    McClelland, J. A. G.

    2011-01-01

    Articulated bodies with an internal energy source require to be coupled to an external mass in order to accelerate themselves but the typical text book assertion that the net force is provided by the external mass is not correct. Arguments are presented demonstrating that the assertion is incorrect and reasons are suggested for the persistence of…

  6. Retention and Persistence Data.

    ERIC Educational Resources Information Center

    Sanford, Timothy R.

    Two studies are combined with an introductory section: one is "Persistence to Graduation for Freshmen Entering the University of North Carolina at Chapel Hill, 1967-75," by Timothy Sanford, and the second is "Freshman, Transfer, Professional, Masters, and Doctoral Student Retention at the University of North Carolina at Chapel Hill," by Paul D.…

  7. The Persistence of PCBs.

    ERIC Educational Resources Information Center

    Boyle, Robert H.; Highland, Joseph H.

    1979-01-01

    PCB's are one of the most persistent chemicals ever introduced into the environment by man. From very early in their history of manufacture PCB's were suspected of being hazardous to health, but public awareness of the hazard was slow in coming. (RE)

  8. Skip Regulates TGF- β 1-Induced Extracellular Matrix Degrading Proteases Expression in Human PC-3 Prostate Cancer Cells.

    PubMed

    Villar, Victor; Kocic, Jelena; Santibanez, Juan F

    2013-01-01

    Purpose. To determine whether Ski-interacting protein (SKIP) regulates TGF- β 1-stimulated expression of urokinase-type plasminogen activator (uPA), matrix metalloproteinase-9 (MMP-9), and uPA Inhibitor (PAI-1) in the androgen-independent human prostate cancer cell model. Materials and Methods. PC-3 prostate cancer cell line was used. The role of SKIP was evaluated using synthetic small interference RNA (siRNA) compounds. The expression of uPA, MMP-9, and PAI-1 was evaluated by zymography assays, RT-PCR, and promoter transactivation analysis. Results. In PC-3 cells TGF- β 1 treatment stimulated uPA, PAI-1, and MMP-9 expressions. The knockdown of SKIP in PC-3 cells enhanced the basal level of uPA, and TGF- β 1 treatment inhibited uPA production. Both PAI-1 and MMP-9 production levels were increased in response to TGF- β 1. The ectopic expression of SKIP inhibited both TGF- β 1-induced uPA and MMP-9 promoter transactivation, while PAI-1 promoter response to the factor was unaffected. Conclusions. SKIP regulates the expression of uPA, PAI-1, and MMP-9 stimulated by TGF- β 1 in PC-3 cells. Thus, SKIP is implicated in the regulation of extracellular matrix degradation and can therefore be suggested as a novel therapeutic target in prostate cancer treatment. PMID:23766912

  9. Persistent fetal circulation.

    PubMed

    Saucier, P H

    1980-01-01

    A review of persistent fetal circulation, which involves the presence of a right to left extrapulmonary shunt that is sustained into neonatal life, is presented. Clinical signs exhibited by the infant often resemble those of respiratory distress. Treatment is accomplished with hyperventilation and/or pharmacologically with tolazoline which, in addition to the usual attention to the overall condition of the infant, requires intensive monitoring by the nurse. PMID:6898712

  10. Persistent interface fluid syndrome.

    PubMed

    Hoffman, Richard S; Fine, I Howard; Packer, Mark

    2008-08-01

    We present an unusual case of persistent interface fluid that would not resolve despite normal intraocular pressure and corneal endothelial replacement with Descemet-stripping endothelial keratoplasty. Dissection, elevation, and repositioning of the laser in situ keratomileusis flap were required to resolve the interface fluid. Circumferential corneal graft-host margin scar formation acting as a mechanical strut may have been the cause of the intractable interface fluid. PMID:18655997

  11. Persistent fetal circulation

    PubMed Central

    D’cunha, Chrysal; Sankaran, Koravangattu

    2001-01-01

    Persistent fetal circulation (PFC), also known as persistent pulmonary hypertension of the newborn, is defined as postnatal persistence of right-to-left ductal or atrial shunting, or both in the presence of elevated right ventricular pressure. It is a relatively rare condition that is usually seen in newborns with respiratory distress syndrome, overwhelming sepsis, meconium and other aspiration syndromes, intrauterine hypoxia and ischemia, and/or neonatal hypoxia and ischemia. This condition causes severe hypoxemia, and, as a result, has significant morbidity and mortality. Improved antenatal and neonatal care; the use of surfactant; continuous monitoring of oxygenation, blood pressure and other vital functions; and early recognition and intervention have made this condition even more rare. In modern neonatal intensive care units, anticipation and early treatment of PFC and its complications in sick newborns are commonplace. Thus, severe forms of PFC are only seen on isolated occasions. Consequently, it is even more imperative to revisit PFC compared with the time when there were occasional cases of PFC seen in neonatal intensive care units, and to discuss evolving treatment and management issues that pertain to this syndrome. PMID:20084150

  12. RA-XII inhibits tumour growth and metastasis in breast tumour-bearing mice via reducing cell adhesion and invasion and promoting matrix degradation

    PubMed Central

    Leung, Hoi-Wing; Zhao, Si-Meng; Yue, Grace Gar-Lee; Lee, Julia Kin-Ming; Fung, Kwok-Pui; Leung, Ping-Chung; Tan, Ning-Hua; Lau, Clara Bik-San

    2015-01-01

    Cancer cells acquire invasive ability to degrade and adhere to extracellular matrix (ECM) and migrate to adjacent tissues. This ultimately results metastasis. Hence, the present study investigated the in vitro effects of cyclopeptide glycoside, RA-XII on cell adhesion, invasion, proliferation and matrix degradation, and its underlying mechanism in murine breast tumour cells, 4T1. The effect of RA-XII on tumour growth and metastasis in 4T1-bearing mice was also investigated. Our results showed that RA-XII inhibited tumour cell adhesion to collagen, fibronectin and laminin, RA-XII also reduced the expressions of vascular cell adhesion molecule, intracellular adhesion molecule and integrins, and integrin binding. In addition, RA-XII significantly inhibited breast tumour cell migration via interfering cofilin signaling and chemokine receptors. The activities of matrix metalloproteinase-9 and urokinase-type of plasminogen activator, and the expressions of ECM-associated proteinases were attenuated significantly by RA-XII. Furthermore, RA-XII induced G1 phase arrest and inhibited the expressions of cyclins and cyclin-dependent kinases. RA-XII inhibited the expressions of molecules in PI3K/AKT, NF-kappaB, FAK/pSRC, MAPK and EGFR signaling. RA-XII was also shown to have anti-tumour, anti-angiogenic and anti-metastatic activities in metastatic breast tumour-bearing mice. These findings strongly suggested that RA-XII is a potential anti-metastatic agent for breast cancer. PMID:26592552

  13. Persistence of brucellosis in pastoral systems.

    PubMed

    Racloz, V; Schelling, E; Chitnis, N; Roth, F; Zinsstag, J

    2013-04-01

    Regarded as a highly contagious, zoonotic disease with worldwide distribution, brucellosis is endemic in many countries and settings and is responsible for a considerable economic and health-related burden. Limited information is available on the persistence and prevalence of brucellosis in pastoral communities, due to the difficulty in gathering information and to their mobility. However, since these communities are economically and culturally dependent on livestock, it is important to further determine the cause of persistent disease and develop possible methods for its management. The two main objectives of this paper are to review the literature, identifying various epidemiological and social factors that affect the persistence of brucellosis in pastoral ecosystems, and determine prevalence estimates within these communities. The general trend of the summarised studies indicates low-level, relatively stable transmission of brucellosis in pastoral areas, when compared to transmission in intensive and semi-intensive peri-urban production systems. A formal mathematical analysis can be undertaken using matrix models or coupled differential equations. This allows an examination of the various conditions under which the number of diseased, infected or exposed animals remains stable. The authors examined an existing mathematical differential equation model for brucellosis in Mongolia for its equilibrium conditions and found it reasonably robust, though clearly more data are needed to estimate threshold densities for brucellosis transmission in other regions of the world. However, the results indicate the importance of livestock demographic determinants for brucellosis persistence. The paper concludes that brucellosis remains largely persistent in pastoral areas of the world, despite (varying) control efforts. Plans to control brucellosis in pastoral settings should include ecological considerations, such as sustaining ecosystem services in pastoral areas. This

  14. Learning's "Weak" Link to Persistence

    ERIC Educational Resources Information Center

    Wolniak, Gregory C.; Mayhew, Matthew J.; Engberg, Mark E.

    2012-01-01

    This study advances the understanding of college persistence by examining five dimensions of student learning in relation to second-year persistence. Two of the five dimensions of learning were found to be significant predictors of persistence, and each was moderated by social integration. (Contains 5 tables and 1 figure.)

  15. Persistence of Salmonid Redds

    NASA Astrophysics Data System (ADS)

    Buffington, J. M.; Buxton, T.; Fremier, A. K.; Hassan, M. A.; Yager, E.

    2013-12-01

    The construction of redds by spawning salmonids modifies fluvial processes in ways that are beneficial to egg and embryo survival. Redd topography induces hyporheic flow that oxygenates embryos incubating within the streambed and creates form drag that reduces bed mobility and scour of salmonid eggs. Winnowing of fine material during redd construction also coarsens the streambed, increasing bed porosity and hyporheic flow and reducing bed mobility. In addition to the biological benefits, redds may influence channel morphology by altering channel hydraulics and bed load transport rates depending on the size and extent of redds relative to the size of the channel. A key question is how long do the physical and biological effects of redds last? Field observations indicate that in some basins redds are ephemeral, with redd topography rapidly erased by subsequent floods, while in other basins, redds can persist for years. We hypothesize that redd persistence is a function of basin hydrology, sediment supply, and characteristics of the spawning fish. Hydrology controls the frequency and magnitude of bed mobilizing flows following spawning, while bed load supply (volume and caliber) controls the degree of textural fining and consequent bed mobility after spawning, as well as the potential for burial of redd features. The effectiveness of flows in terms of their magnitude and duration depend on hydroclimate (i.e., snowmelt, rainfall, or transitional hydrographs), while bed load supply depends on basin geology, land use, and natural disturbance regimes (e.g., wildfire). Location within the stream network may also influence redd persistence. In particular, lakes effectively trap sediment and regulate downstream flow, which may promote long-lived redds in stream reaches below lakes. These geomorphic controls are modulated by biological factors: fish species (size of fish controls size of redds and magnitude of streambed coarsening); life history (timing of spawning and

  16. Systems for persistent surveillance

    NASA Astrophysics Data System (ADS)

    Lewis, Keith

    2011-09-01

    The requirements for a persistent wide-area surveillance system are discussed in the context of evolving military operations. Significant emphasis has been placed on the development of new sensing technologies to meet the challenges posed by asymmetric threats. Within the UK, the Electro-Magnetic Remote Sensing Defence Technology Centre (EMRS DTC) has supported the research and development of new capabilities including radio-frequency (RF) and electro-optic (EO) systems, as well as work on sensor exploitation, with a goal of developing solutions for enhancing situational awareness. This activity has been supported by field trials to determine the efficacy of competing technologies in relation to realistic threat scenarios.

  17. Persistence of airline accidents.

    PubMed

    Barros, Carlos Pestana; Faria, Joao Ricardo; Gil-Alana, Luis Alberiko

    2010-10-01

    This paper expands on air travel accident research by examining the relationship between air travel accidents and airline traffic or volume in the period from 1927-2006. The theoretical model is based on a representative airline company that aims to maximise its profits, and it utilises a fractional integration approach in order to determine whether there is a persistent pattern over time with respect to air accidents and air traffic. Furthermore, the paper analyses how airline accidents are related to traffic using a fractional cointegration approach. It finds that airline accidents are persistent and that a (non-stationary) fractional cointegration relationship exists between total airline accidents and airline passengers, airline miles and airline revenues, with shocks that affect the long-run equilibrium disappearing in the very long term. Moreover, this relation is negative, which might be due to the fact that air travel is becoming safer and there is greater competition in the airline industry. Policy implications are derived for countering accident events, based on competition and regulation. PMID:20618386

  18. Persistent Genital Arousal Disorder

    PubMed Central

    Aswath, Manju; Pandit, Lakshmi V.; Kashyap, Karthik; Ramnath, Raguram

    2016-01-01

    Persistent genital arousal disorder (PGAD) is a phenomenon, in which afflicted women experience spontaneous genital arousal, unresolved by orgasms and triggered by sexual or nonsexual stimuli, eliciting stress. The current case is a 40-year-old female who experienced such orgasms for about a month. Physical examination, investigations, and psychological testing were noncontributory. Carbamazepine (600 mg) was discontinued due to a lack of response. She improved significantly with supportive therapy. Various neuropsychological conditions, pelvic pathology, medications, etc., have been associated with this disorder. Pharmacologic strategies have included the use of antidepressants, antipsychotics, mood stabilizers, and analgesics. Validation, psycho-education, identifying triggers, distraction techniques, and pelvic massage have been tried. Living with PGAD is very demanding. There is a lack of understanding of the problem, shame, and hesitation to seek help. The syndrome has been recently described, and understanding is still evolving. PMID:27570347

  19. Acute and persistent diarrhea.

    PubMed

    Grimwood, Keith; Forbes, David A

    2009-12-01

    Socially disadvantaged Indigenous infants and children living in western industrialized countries experience high rates of infectious diarrhea, no more so than Aboriginal children from remote and rural regions of Northern Australia. Diarrheal disease, poor nutrition, and intestinal enteropathy reflect household crowding, inadequate water and poor sanitation and hygiene. Acute episodes of watery diarrhea are often best managed by oral glucose-electrolyte solutions with continuation of breastfeeding and early reintroduction of feeding. Selective use of lactose-free milk formula, short-term zinc supplementation and antibiotics may be necessary for ill children with poor nutrition, persistent symptoms, or dysentery. Education, high standards of environmental hygiene, breastfeeding, and immunization with newly licensed rotavirus vaccines are all needed to reduce the unacceptably high burden of diarrheal disease encountered in young children from Indigenous communities. PMID:19962025

  20. Caliber-Persistent Artery

    PubMed Central

    Costa, Sabrina Araújo Pinho; Ruiz, Marcelo Martinson; Kaba, Shajadi Pardo; Florezi, Giovanna Piacenza; Lemos Júnior, Celso Augusto; Witzel, Andréa Lusvarghi

    2015-01-01

    Caliber-persistent artery (CPLA) of the lip is a common vascular anomaly in which a main arterial branch extends to the surface of the mucous tissue with no reduction in its diameter. It usually manifests as pulsatile papule, is easily misdiagnosed, and is observed more frequently among older people, suggesting that its development may involve a degenerative process associated with aging; CPLA is also characterized by the loss of tone of the adjacent supporting connective tissue. Although the diagnosis is clinical, high-resolution Doppler ultrasound is a useful noninvasive tool for evaluating the lesion. This report describes the case of a 58-year-old male patient who complained of a lesion of the lower lip with bleeding and recurrent ulceration. The patient was successfully treated in our hospital after a diagnosis of CPLA and is currently undergoing a clinical outpatient follow-up with no complaints. PMID:26448884

  1. Epigenetic regulation of persistent pain

    PubMed Central

    Bai, Guang; Ren, Ke; Dubner, Ronald

    2014-01-01

    Persistent or chronic pain is tightly associated with various environmental changes and linked to abnormal gene expression within cells processing nociceptive signaling. Epigenetic regulation governs gene expression in response to environmental cues. Recent animal model and clinical studies indicate that epigenetic regulation plays an important role in the development/maintenance of persistent pain and, possibly the transition of acute pain to chronic pain, thus shedding light in a direction for development of new therapeutics for persistent pain. PMID:24948399

  2. Hybrid matrix fiber composites

    DOEpatents

    Deteresa, Steven J.; Lyon, Richard E.; Groves, Scott E.

    2003-07-15

    Hybrid matrix fiber composites having enhanced compressive performance as well as enhanced stiffness, toughness and durability suitable for compression-critical applications. The methods for producing the fiber composites using matrix hybridization. The hybrid matrix fiber composites include two chemically or physically bonded matrix materials, whereas the first matrix materials are used to impregnate multi-filament fibers formed into ribbons and the second matrix material is placed around and between the fiber ribbons that are impregnated with the first matrix material and both matrix materials are cured and solidified.

  3. Isolated persistent hypermethioninemia.

    PubMed Central

    Mudd, S H; Levy, H L; Tangerman, A; Boujet, C; Buist, N; Davidson-Mundt, A; Hudgins, L; Oyanagi, K; Nagao, M; Wilson, W G

    1995-01-01

    New information has been obtained on 30 patients with isolated persistent hypermethioninemia, most of them previously unreported. Biopsies to confirm the presumptive diagnosis of partially deficient activity of ATP: L-methionine S-adenosyltransferase (MAT; E.C.2.5.1.6) in liver were not performed on most of these patients. However, none showed the clinical findings or the extreme elevations of serum folate previously described in other patients with isolated hypermethioninemia considered not to have hepatic MAT deficiency. Patients ascertained on biochemical grounds had no neurological abnormalities, and 27/30 had IQs or Bayley development-index scores within normal limits or were judged to have normal mental development. Methionine transamination metabolites accumulated abnormally only when plasma methionine concentrations exceeded 300-350 microM and did so more markedly after 0.9 years of age. Data were obtained on urinary organic acids as well as plasma creatinine concentrations. Patterns of inheritance of isolated hypermethioninemia were variable. Considerations as to the optimal management of this group of patients are discussed. PMID:7573050

  4. Metabolic aspects of bacterial persisters

    PubMed Central

    Prax, Marcel; Bertram, Ralph

    2014-01-01

    Persister cells form a multi-drug tolerant subpopulation within an isogenic culture of bacteria that are genetically susceptible to antibiotics. Studies with different Gram negative and Gram positive bacteria have identified a large number of genes associated with the persister state. In contrast, the revelation of persister metabolism has only been addressed recently. We here summarize metabolic aspects of persisters, which includes an overview about the bifunctional role of selected carbohydrates as both triggers for the exit from the drug tolerant state and metabolites which persisters feed on. Also alarmones as indicators for starvation have been shown to influence persister levels via different signaling cascades involving the activation of toxin-antitoxin systems and other regulatory factors. Finally, recent data obtained by 13C-isotopolog profiling demonstrated an active amino acid anabolism in Staphylococcus aureus cultures challenged with high drug concentrations. Understanding the metabolism of persister cells poses challenges but also paves the way for the development of anti-persister compounds. PMID:25374846

  5. Multidimensional persistence in biomolecular data

    PubMed Central

    Xia, Kelin; Wei, Guo-Wei

    2015-01-01

    Persistent homology has emerged as a popular technique for the topological simplification of big data, including biomolecular data. Multidimensional persistence bears considerable promise to bridge the gap between geometry and topology. However, its practical and robust construction has been a challenge. We introduce two families of multidimensional persistence, namely pseudo-multidimensional persistence and multiscale multidimensional persistence. The former is generated via the repeated applications of persistent homology filtration to high dimensional data, such as results from molecular dynamics or partial differential equations. The latter is constructed via isotropic and anisotropic scales that create new simiplicial complexes and associated topological spaces. The utility, robustness and efficiency of the proposed topological methods are demonstrated via protein folding, protein flexibility analysis, the topological denoising of cryo-electron microscopy data, and the scale dependence of nano particles. Topological transition between partial folded and unfolded proteins has been observed in multidimensional persistence. The separation between noise topological signatures and molecular topological fingerprints is achieved by the Laplace-Beltrami flow. The multiscale multidimensional persistent homology reveals relative local features in Betti-0 invariants and the relatively global characteristics of Betti-1 and Betti-2 invariants. PMID:26032339

  6. Multidimensional persistence in biomolecular data.

    PubMed

    Xia, Kelin; Wei, Guo-Wei

    2015-07-30

    Persistent homology has emerged as a popular technique for the topological simplification of big data, including biomolecular data. Multidimensional persistence bears considerable promise to bridge the gap between geometry and topology. However, its practical and robust construction has been a challenge. We introduce two families of multidimensional persistence, namely pseudomultidimensional persistence and multiscale multidimensional persistence. The former is generated via the repeated applications of persistent homology filtration to high-dimensional data, such as results from molecular dynamics or partial differential equations. The latter is constructed via isotropic and anisotropic scales that create new simiplicial complexes and associated topological spaces. The utility, robustness, and efficiency of the proposed topological methods are demonstrated via protein folding, protein flexibility analysis, the topological denoising of cryoelectron microscopy data, and the scale dependence of nanoparticles. Topological transition between partial folded and unfolded proteins has been observed in multidimensional persistence. The separation between noise topological signatures and molecular topological fingerprints is achieved by the Laplace-Beltrami flow. The multiscale multidimensional persistent homology reveals relative local features in Betti-0 invariants and the relatively global characteristics of Betti-1 and Betti-2 invariants. PMID:26032339

  7. Antibiotic induced bacterial lysis provides a reservoir of persisters.

    PubMed

    Podlesek, Zdravko; Butala, Matej; Šakanović, Aleksandra; Žgur-Bertok, Darja

    2016-04-01

    In a genetically uniform bacterial population a small subset of antibiotic-susceptible cells enter an antibiotic tolerant state and are hence referred to as persisters. These have been proposed to be rare phenotypic variants with several stochastically activated independent parallel processes. Here we show an overlooked phenomenon, bacterial tolerance of extraordinary high levels of ampicillin due to encasement of viable cells by an antibiotic induced network of cell debris. This matrix shields the entrapped cells from contact with the bacteriolytic β-lactam antibiotic ampicillin and may be an underlying cause of notable variations in the level of ampicillin tolerant persisters as well as of considerable medical significance. Disruption of the matrix leads to the rapid elimination of hidden survivors, revealing their metabolically active state. PMID:26821377

  8. Energy landscapes and persistent minima

    NASA Astrophysics Data System (ADS)

    Carr, Joanne M.; Mazauric, Dorian; Cazals, Frédéric; Wales, David J.

    2016-02-01

    We consider a coarse-graining of high-dimensional potential energy landscapes based upon persistences, which correspond to lowest barrier heights to lower-energy minima. Persistences can be calculated efficiently for local minima in kinetic transition networks that are based on stationary points of the prevailing energy landscape. The networks studied here represent peptides, proteins, nucleic acids, an atomic cluster, and a glassy system. Minima with high persistence values are likely to represent some form of alternative structural morphology, which, if appreciably populated at the prevailing temperature, could compete with the global minimum (defined as infinitely persistent). Threshold values on persistences (and in some cases equilibrium occupation probabilities) have therefore been used in this work to select subsets of minima, which were then analysed to see how well they can represent features of the full network. Simplified disconnectivity graphs showing only the selected minima can convey the funnelling (including any multiple-funnel) characteristics of the corresponding full graphs. The effect of the choice of persistence threshold on the reduced disconnectivity graphs was considered for a system with a hierarchical, glassy landscape. Sets of persistent minima were also found to be useful in comparing networks for the same system sampled under different conditions, using minimum oriented spanning forests.

  9. Persistence, resistance, resonance

    NASA Astrophysics Data System (ADS)

    Tsadka, Maayan

    form of musical consumption and experience. The three pieces draw lines connecting different aspects of persistence, resistance, and resonance.

  10. Asthma: mechanisms of disease persistence and progression.

    PubMed

    Cohn, Lauren; Elias, Jack A; Chupp, Geoffrey L

    2004-01-01

    When asthma is diagnosed, eosinophilic inflammation and airway remodeling are established in the bronchial airways and can no longer be separated as cause and effect because both processes contribute to persistence and progression of disease, despite anti-inflammatory therapy. Th2 cells are continually active in the airways, even when disease is quiescent. IL-13 is the key effector cytokine in asthma and stimulates airway fibrosis through the action of matrix metalloproteinases on TGF-beta and promotes epithelial damage, mucus production, and eosinophilia. The production of IL-13 and other Th2 cytokines by non-T cells augments the inflammatory response. Inflammation is amplified by local responses of the epithelium, smooth muscle, and fibroblasts through the production of chemokines, cytokines, and proteases. Injured cells produce adenosine that enhances IL-13 production. We review human and animal data detailing the cellular and molecular interactions in established allergic asthma that promote persistent disease, amplify inflammation, and, in turn, cause disease progression. PMID:15032597

  11. Persistent Neuropathic Pain Influences Persistence Behavior in Rats

    PubMed Central

    Kniffin, Tracey C.; Danaher, Robert J.; Westlund, Karin N.; Ma, Fei; Miller, Craig S.; Carlson, Charles R.

    2016-01-01

    Aims To determine whether self-regulation can be studied successfully in a rodent model and whether persistent facial pain influences self-regulatory behavior. Methods Thirty male Sprague-Dawley rats, divided into two groups, (1) chronic constriction injury of the infraorbital nerve (CCI-ION) and (2) naïve, were used in a two-part behavioral paradigm of self-regulation. This paradigm consisted of both a cued go/no-go task (part one) and a persistence trial (part two). All animals were acclimated and trained for a period of 4 weeks prior to the experimental manipulation and then tested for a total of 5 weeks following experimental manipulation. Results were analyzed with t tests, one-way analysis of variance, and two-way, repeated measures analysis of variance. Results CCI-ION surgery induced significant mechanical hypersensitivity of the ipsilateral whisker pad that began 3 weeks postsurgery and persisted through the duration of the experiment (P < .001). At weeks 4 and 5 post–experimental manipulation, naïve animals demonstrated a significant decrease in lever presses during the persistence task (P < .05) compared to baseline, whereas CCI-ION animals did not (P = .55). Conclusion These results suggest that persistent pain influences behavioral regulation and that animals experiencing persistent pain may have difficulty adapting to environmental demands. PMID:25905537

  12. On-line screening of matrix metalloproteinase inhibitors by capillary electrophoresis coupled to ESI mass spectrometry.

    PubMed

    Wang, Xu; Dou, Zhiying; Yuan, Yaozuo; Man, Shuli; Wolfs, Kris; Adams, Erwin; Van Schepdael, Ann

    2013-07-01

    Capillary electrophoresis (CE) with the use of mass spectrometry (MS) has been considered as a unique tool for microscale enzyme assay and inhibitor screening. In this study, matrix metalloproteinase-9 (MMP-9) was selected as target enzyme due to its important role in tumor invasion and metastasis. In order to define the optimal MS parameters, a two level half fraction factorial experimental design was performed. A background electrolyte consisting of 20mM ammonium acetate (pH 6.8) and a sheath liquid of water-methanol (50:50, v/v) containing 0.05% formic acid at a flow rate of 4μl/min were selected. This system was operated in the positive ion mode with a detection-limit of 10nM for the MMP reaction product and provided 60 folds enhancement of sensitivity by using selected reaction monitoring detection compared with MS full scan mode, which significantly increased the detectability of the system and therefore reduced the enzyme reaction time in both off-line and in-line mode. Both electrophoretically mediated microanalysis and pressure mediated microanalysis combined with MS detection were investigated for MMP inhibitor screening. Good repeatability (RSD of peak area and migration time were lower than 5.0%) and linearity (R(2)>0.996) were obtained for both in-capillary approaches. Several tetracycline antibiotics and natural products were selected to test the system. The results indicated an agreement on the ranking of inhibitory potency for both in-capillary approaches. PMID:23727866

  13. A matrix lower bound

    SciTech Connect

    Grcar, Joseph F.

    2002-02-04

    A matrix lower bound is defined that generalizes ideas apparently due to S. Banach and J. von Neumann. The matrix lower bound has a natural interpretation in functional analysis, and it satisfies many of the properties that von Neumann stated for it in a restricted case. Applications for the matrix lower bound are demonstrated in several areas. In linear algebra, the matrix lower bound of a full rank matrix equals the distance to the set of rank-deficient matrices. In numerical analysis, the ratio of the matrix norm to the matrix lower bound is a condition number for all consistent systems of linear equations. In optimization theory, the matrix lower bound suggests an identity for a class of min-max problems. In real analysis, a recursive construction that depends on the matrix lower bound shows that the level sets of continuously differential functions lie asymptotically near those of their tangents.

  14. Immunomodulation by Persistent Organic Pollutants

    EPA Science Inventory

    Persistent organic pollutants (POPs) are widely distnbuted in the environment, are resistant to degradation, and increase in concentration (biomagnify) in the food chain. Concentrations in apical predators may be tens to hundreds of times greater than concentrations in their pref...

  15. Object-oriented persistent homology

    NASA Astrophysics Data System (ADS)

    Wang, Bao; Wei, Guo-Wei

    2016-01-01

    Persistent homology provides a new approach for the topological simplification of big data via measuring the life time of intrinsic topological features in a filtration process and has found its success in scientific and engineering applications. However, such a success is essentially limited to qualitative data classification and analysis. Indeed, persistent homology has rarely been employed for quantitative modeling and prediction. Additionally, the present persistent homology is a passive tool, rather than a proactive technique, for classification and analysis. In this work, we outline a general protocol to construct object-oriented persistent homology methods. By means of differential geometry theory of surfaces, we construct an objective functional, namely, a surface free energy defined on the data of interest. The minimization of the objective functional leads to a Laplace-Beltrami operator which generates a multiscale representation of the initial data and offers an objective oriented filtration process. The resulting differential geometry based object-oriented persistent homology is able to preserve desirable geometric features in the evolutionary filtration and enhances the corresponding topological persistence. The cubical complex based homology algorithm is employed in the present work to be compatible with the Cartesian representation of the Laplace-Beltrami flow. The proposed Laplace-Beltrami flow based persistent homology method is extensively validated. The consistence between Laplace-Beltrami flow based filtration and Euclidean distance based filtration is confirmed on the Vietoris-Rips complex for a large amount of numerical tests. The convergence and reliability of the present Laplace-Beltrami flow based cubical complex filtration approach are analyzed over various spatial and temporal mesh sizes. The Laplace-Beltrami flow based persistent homology approach is utilized to study the intrinsic topology of proteins and fullerene molecules. Based on a

  16. Effects of caffeic acid phenethyl ester on matrix molecules and angiogenetic and anti-angiogenetic factors in gastric cancer cells cultured on different substrates.

    PubMed

    Kosova, F; Kurt, F O; Olmez, E; Tuğlu, I; Arı, Z

    2016-01-01

    Migration, invasion, metastasis and angiogenesis associated with cancer depend on the surrounding microenvironment. Angiogenesis, the growth of new capillaries, is a regulator of cancer growth and a useful target for cancer therapy. We examined matrix protein interactions in a gastric cancer cell culture that was treated with different doses of caffeic acid (3,4-dihydroxycinnamic acid) phenethyl ester (CAPE). We also investigated the relations among the levels of vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), endostatin (ES) and trombospondin-1 (TSP-1). Cytotoxity of CAPE was measured using the 3-(4,5-dmethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. We examined the behavior of cells on laminin and collagen I coated surfaces in response to the angiogenic effect of these matrix molecules. We examined the protein alterations of these matrix molecules immunohistochemically and measured the levels of VEGF, MMP-9, ES and TSP-1 using the ELISA test. We showed that application of CAPE to the gastric cancer cell line on tissue culture plastic, laminin and collagen I significantly decreased the VEGF and MMP-9 protein levels. We found that TSP-1 levels were increased significantly in the gastric cancer cells after application of CAPE. The protein levels of gastric cancer cells also were increased significantly when tissue was cultured on laminin and collagen I. Application of CAPE to cells on laminin or collagen I coated surfaces significantly increased all of the proteins except ES. ES levels were increased on the collagen I covered surfaces, but the laminin surface decreased the levels of ES significantly. We demonstrated the beneficial effect of CAPE on a gastric cancer cell line including inhibition of proliferation and induction of some proteins that might be related to decreased angiogenesis. PMID:26523612

  17. Carbonate fuel cell matrix

    DOEpatents

    Farooque, M.; Yuh, C.Y.

    1996-12-03

    A carbonate fuel cell matrix is described comprising support particles and crack attenuator particles which are made platelet in shape to increase the resistance of the matrix to through cracking. Also disclosed is a matrix having porous crack attenuator particles and a matrix whose crack attenuator particles have a thermal coefficient of expansion which is significantly different from that of the support particles, and a method of making platelet-shaped crack attenuator particles. 8 figs.

  18. Carbonate fuel cell matrix

    DOEpatents

    Farooque, Mohammad; Yuh, Chao-Yi

    1996-01-01

    A carbonate fuel cell matrix comprising support particles and crack attenuator particles which are made platelet in shape to increase the resistance of the matrix to through cracking. Also disclosed is a matrix having porous crack attenuator particles and a matrix whose crack attenuator particles have a thermal coefficient of expansion which is significantly different from that of the support particles, and a method of making platelet-shaped crack attenuator particles.

  19. Pseudomonas biofilm matrix composition and niche biology

    PubMed Central

    Mann, Ethan E.; Wozniak, Daniel J.

    2014-01-01

    Biofilms are a predominant form of growth for bacteria in the environment and in the clinic. Critical for biofilm development are adherence, proliferation, and dispersion phases. Each of these stages includes reinforcement by, or modulation of, the extracellular matrix. Pseudomonas aeruginosa has been a model organism for the study of biofilm formation. Additionally, other Pseudomonas species utilize biofilm formation during plant colonization and environmental persistence. Pseudomonads produce several biofilm matrix molecules, including polysaccharides, nucleic acids, and proteins. Accessory matrix components shown to aid biofilm formation and adaptability under varying conditions are also produced by pseudomonads. Adaptation facilitated by biofilm formation allows for selection of genetic variants with unique and distinguishable colony morphology. Examples include rugose small-colony variants and wrinkly spreaders (WS), which over produce Psl/Pel or cellulose, respectively, and mucoid bacteria that over produce alginate. The well-documented emergence of these variants suggests that pseudomonads take advantage of matrix-building subpopulations conferring specific benefits for the entire population. This review will focus on various polysaccharides as well as additional Pseudomonas biofilm matrix components. Discussions will center on structure–function relationships, regulation, and the role of individual matrix molecules in niche biology. PMID:22212072

  20. Activation of matrix metalloproteinase in dorsal hippocampus drives improvement in spatial working memory after intra-VTA nicotine infusion in rats.

    PubMed

    Shu, Hui; Zheng, Guo-qing; Wang, Xiaona; Sun, Yanyun; Liu, Yushan; Weaver, John Michael; Shen, Xianzhi; Liu, Wenlan; Jin, Xinchun

    2015-10-01

    The hippocampus receives dopaminergic projections from the ventral tegmental area (VTA) and substantia nigra. These inputs appear to provide a modulatory signal that influences hippocampus-dependent behaviors. Enhancements in working memory performance have been previously reported following acute smoking/nicotine exposure. However, the underlying mechanism remains unclear. This study investigated the effects of nicotine on spatial working memory (SWM) and the mechanisms involved. Delayed alternation T-maze task was used to assess SWM. In situ and gel gelatin zymography were used to detect matrix metalloproteinase-9 (MMP-9) in SWM. Systemic or local (intra-VTA) administration of nicotine significantly improves SWM, which was accompanied by increased MMP-9 activity in dorsal hippocampus (dHPC). Intra-dHPC administration of MMP inhibitor FN-439 abolished the memory enhancement induced by intra-VTA nicotine infusion. FN-439 had no effect on locomotor behavior. Our data suggest that intra-VTA nicotine infusion activates MMP-9 in dHPC to improve SWM in rats. PMID:26263395

  1. Matrix differentiation formulas

    NASA Technical Reports Server (NTRS)

    Usikov, D. A.; Tkhabisimov, D. K.

    1983-01-01

    A compact differentiation technique (without using indexes) is developed for scalar functions that depend on complex matrix arguments which are combined by operations of complex conjugation, transposition, addition, multiplication, matrix inversion and taking the direct product. The differentiation apparatus is developed in order to simplify the solution of extremum problems of scalar functions of matrix arguments.

  2. Matrix with Prescribed Eigenvectors

    ERIC Educational Resources Information Center

    Ahmad, Faiz

    2011-01-01

    It is a routine matter for undergraduates to find eigenvalues and eigenvectors of a given matrix. But the converse problem of finding a matrix with prescribed eigenvalues and eigenvectors is rarely discussed in elementary texts on linear algebra. This problem is related to the "spectral" decomposition of a matrix and has important technical…

  3. Cytokines and persistent viral infections.

    PubMed

    Beltra, Jean-Christophe; Decaluwe, Hélène

    2016-06-01

    Intracellular pathogens such as the human immunodeficiency virus, hepatitis C and B or Epstein-Barr virus often cause chronic viral infections in humans. Persistence of these viruses in the host is associated with a dramatic loss of T-cell immune response due to functional T-cell exhaustion. Developing efficient immunotherapeutic approaches to prevent viral persistence and/or to restore a highly functional T-cell mediated immunity remains a major challenge. During the last two decades, numerous studies aimed to identify relevant host-derived factors that could be modulated to achieve this goal. In this review, we focus on recent advances in our understanding of the role of cytokines in preventing or facilitating viral persistence. We concentrate on the impact of multiple relevant cytokines in T-cell dependent immune response to chronic viral infection and the potential for using cytokines as therapeutic agents in mice and humans. PMID:26907634

  4. Nanocrystal doped matrixes

    DOEpatents

    Parce, J. Wallace; Bernatis, Paul; Dubrow, Robert; Freeman, William P.; Gamoras, Joel; Kan, Shihai; Meisel, Andreas; Qian, Baixin; Whiteford, Jeffery A.; Ziebarth, Jonathan

    2010-01-12

    Matrixes doped with semiconductor nanocrystals are provided. In certain embodiments, the semiconductor nanocrystals have a size and composition such that they absorb or emit light at particular wavelengths. The nanocrystals can comprise ligands that allow for mixing with various matrix materials, including polymers, such that a minimal portion of light is scattered by the matrixes. The matrixes of the present invention can also be utilized in refractive index matching applications. In other embodiments, semiconductor nanocrystals are embedded within matrixes to form a nanocrystal density gradient, thereby creating an effective refractive index gradient. The matrixes of the present invention can also be used as filters and antireflective coatings on optical devices and as down-converting layers. Processes for producing matrixes comprising semiconductor nanocrystals are also provided. Nanostructures having high quantum efficiency, small size, and/or a narrow size distribution are also described, as are methods of producing indium phosphide nanostructures and core-shell nanostructures with Group II-VI shells.

  5. Non-Persisting Student Follow-Up.

    ERIC Educational Resources Information Center

    Willett, Lynn H.

    A survey was conducted to determine the characteristics and opinions of the non-persisting students at Moraine Valley Community College. A random sample of 500 non-persisting students was selected, with equal numbers of full-time and part-time ex-students. Separate questionnaires were used for non-persisting full-time and non-persisting part-time…

  6. Computational Methods to Model Persistence.

    PubMed

    Vandervelde, Alexandra; Loris, Remy; Danckaert, Jan; Gelens, Lendert

    2016-01-01

    Bacterial persister cells are dormant cells, tolerant to multiple antibiotics, that are involved in several chronic infections. Toxin-antitoxin modules play a significant role in the generation of such persister cells. Toxin-antitoxin modules are small genetic elements, omnipresent in the genomes of bacteria, which code for an intracellular toxin and its neutralizing antitoxin. In the past decade, mathematical modeling has become an important tool to study the regulation of toxin-antitoxin modules and their relation to the emergence of persister cells. Here, we provide an overview of several numerical methods to simulate toxin-antitoxin modules. We cover both deterministic modeling using ordinary differential equations and stochastic modeling using stochastic differential equations and the Gillespie method. Several characteristics of toxin-antitoxin modules such as protein production and degradation, negative autoregulation through DNA binding, toxin-antitoxin complex formation and conditional cooperativity are gradually integrated in these models. Finally, by including growth rate modulation, we link toxin-antitoxin module expression to the generation of persister cells. PMID:26468111

  7. Persistence Length of Stable Microtubules

    NASA Astrophysics Data System (ADS)

    Hawkins, Taviare; Mirigian, Matthew; Yasar, M. Selcuk; Ross, Jennifer

    2011-03-01

    Microtubules are a vital component of the cytoskeleton. As the most rigid of the cytoskeleton filaments, they give shape and support to the cell. They are also essential for intracellular traffic by providing the roadways onto which organelles are transported, and they are required to reorganize during cellular division. To perform its function in the cell, the microtubule must be rigid yet dynamic. We are interested in how the mechanical properties of stable microtubules change over time. Some ``stable'' microtubules of the cell are recycled after days, such as in the axons of neurons or the cilia and flagella. We measured the persistence length of freely fluctuating taxol-stabilized microtubules over the span of a week and analyzed them via Fourier decomposition. As measured on a daily basis, the persistence length is independent of the contour length. Although measured over the span of the week, the accuracy of the measurement and the persistence length varies. We also studied how fluorescently-labeling the microtubule affects the persistence length and observed that a higher labeling ratio corresponded to greater flexibility. National Science Foundation Grant No: 0928540 to JLR.

  8. Visual Persistence and Adult Dyslexia.

    ERIC Educational Resources Information Center

    Winters, Roberta L.; And Others

    1989-01-01

    Visual persistence was investigated in adults with and without dyslexia in order to determine whether dyslexic adults demonstrate problems similar to those found in childhood dyslexia. Results showed that sensitivity of dyslexic adults was impaired when parts of a test stimulus were presented to adjacent retinal areas, suggesting that under…

  9. Blood Persistent Organic Pollutants Level

    EPA Science Inventory

    This indicator describes the presence of a subset of persistent organic pollutants (POPs) in the blood of the U.S. population from 1999 to 2002. Some POPs have been linked to adverse health effects such as cancer and nervous system disorders. Three broad classes of POPs are in...

  10. Kaposi's Sarcoma Herpesvirus Genome Persistence.

    PubMed

    Juillard, Franceline; Tan, Min; Li, Shijun; Kaye, Kenneth M

    2016-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) has an etiologic role in Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. These diseases are most common in immunocompromised individuals, especially those with AIDS. Similar to all herpesviruses, KSHV infection is lifelong. KSHV infection in tumor cells is primarily latent, with only a small subset of cells undergoing lytic infection. During latency, the KSHV genome persists as a multiple copy, extrachromosomal episome in the nucleus. In order to persist in proliferating tumor cells, the viral genome replicates once per cell cycle and then segregates to daughter cell nuclei. KSHV only expresses several genes during latent infection. Prominent among these genes, is the latency-associated nuclear antigen (LANA). LANA is responsible for KSHV genome persistence and also exerts transcriptional regulatory effects. LANA mediates KSHV DNA replication and in addition, is responsible for segregation of replicated genomes to daughter nuclei. LANA serves as a molecular tether, bridging the viral genome to mitotic chromosomes to ensure that KSHV DNA reaches progeny nuclei. N-terminal LANA attaches to mitotic chromosomes by binding histones H2A/H2B at the surface of the nucleosome. C-terminal LANA binds specific KSHV DNA sequence and also has a role in chromosome attachment. In addition to the essential roles of N- and C-terminal LANA in genome persistence, internal LANA sequence is also critical for efficient episome maintenance. LANA's role as an essential mediator of virus persistence makes it an attractive target for inhibition in order to prevent or treat KSHV infection and disease. PMID:27570517

  11. Biofilm Matrix Proteins

    PubMed Central

    Fong, Jiunn N. C.; Yildiz, Fitnat H.

    2015-01-01

    Proteinaceous components of the biofilm matrix include secreted extracellular proteins, cell surface adhesins and protein subunits of cell appendages such as flagella and pili. Biofilm matrix proteins play diverse roles in biofilm formation and dissolution. They are involved in attaching cells to surfaces, stabilizing the biofilm matrix via interactions with exopolysaccharide and nucleic acid components, developing three-dimensional biofilm architectures, and dissolving biofilm matrix via enzymatic degradation of polysaccharides, proteins, and nucleic acids. In this chapter, we will review functions of matrix proteins in a selected set of microorganisms, studies of the matrix proteomes of Vibrio cholerae and Pseudomonas aeruginosa, and roles of outer membrane vesicles and of nucleoid-binding proteins in biofilm formation. PMID:26104709

  12. Automatic switching matrix

    DOEpatents

    Schlecht, Martin F.; Kassakian, John G.; Caloggero, Anthony J.; Rhodes, Bruce; Otten, David; Rasmussen, Neil

    1982-01-01

    An automatic switching matrix that includes an apertured matrix board containing a matrix of wires that can be interconnected at each aperture. Each aperture has associated therewith a conductive pin which, when fully inserted into the associated aperture, effects electrical connection between the wires within that particular aperture. Means is provided for automatically inserting the pins in a determined pattern and for removing all the pins to permit other interconnecting patterns.

  13. Persistent homology analysis of protein structure, flexibility and folding

    PubMed Central

    Xia, Kelin; Wei, Guo-Wei

    2014-01-01

    Proteins are the most important biomolecules for living organisms. The understanding of protein structure, function, dynamics and transport is one of most challenging tasks in biological science. In the present work, persistent homology is, for the first time, introduced for extracting molecular topological fingerprints (MTFs) based on the persistence of molecular topological invariants. MTFs are utilized for protein characterization, identification and classification. The method of slicing is proposed to track the geometric origin of protein topological invariants. Both all-atom and coarse-grained representations of MTFs are constructed. A new cutoff-like filtration is proposed to shed light on the optimal cutoff distance in elastic network models. Based on the correlation between protein compactness, rigidity and connectivity, we propose an accumulated bar length generated from persistent topological invariants for the quantitative modeling of protein flexibility. To this end, a correlation matrix based filtration is developed. This approach gives rise to an accurate prediction of the optimal characteristic distance used in protein B-factor analysis. Finally, MTFs are employed to characterize protein topological evolution during protein folding and quantitatively predict the protein folding stability. An excellent consistence between our persistent homology prediction and molecular dynamics simulation is found. This work reveals the topology-function relationship of proteins. PMID:24902720

  14. Intermediate disturbance in experimental landscapes improves persistence of beetle metapopulations.

    PubMed

    Govindan, Byju N; Feng, Zhilan; DeWoody, Yssa D; Swihart, Robert K

    2015-03-01

    Human-dominated landscapes often feature patches that fluctuate in suitability through space and time, but there is little experimental evidence relating the consequences of dynamic patches for species persistence. We used a spatially and temporally dynamic metapopulation model to assess and compare metapopulation capacity and persistence for red flour beetles (Tribolium castaneum) in experimental landscapes differentiated by resource structure, patch dynamics (destruction and restoration), and connectivity. High connectivity increased the colonization rate of beetles, but this effect was less pronounced in heterogeneous relative to homogeneous landscapes. Higher connectivity and faster patch dynamics increased extinction rates in landscapes. Lower connectivity promoted density-dependent emigration. Heterogeneous landscapes containing patches of different carrying capacity enhanced landscape-level occupancy probability. The highest metapopulation capacity and persistence was observed in landscapes with heterogeneous patches, low connectivity, and slow patch dynamics. Control landscapes with no patch dynamics exhibited rapid declines in abundance and approached extinction due to increased adult mortality in the matrix, higher pupal cannibalism by adults, and extremely low rates of exchange between remaining habitable patches. Our results highlight the role of intermediate patch dynamics, intermediate connectivity, and the nature of density dependence of emigration for persistence of species in heterogeneous landscapes. Our results also demonstrate the importance of incorporating local dynamics into the estimation of metapopulation capacity for conservation planning. PMID:26236869

  15. Persistence of uranium emission in laser-produced plasmas

    SciTech Connect

    LaHaye, N. L.; Harilal, S. S. Diwakar, P. K.; Hassanein, A.

    2014-04-28

    Detection of uranium and other nuclear materials is of the utmost importance for nuclear safeguards and security. Optical emission spectroscopy of laser-ablated U plasmas has been presented as a stand-off, portable analytical method that can yield accurate qualitative and quantitative elemental analysis of a variety of samples. In this study, optimal laser ablation and ambient conditions are explored, as well as the spatio-temporal evolution of the plasma for spectral analysis of excited U species in a glass matrix. Various Ar pressures were explored to investigate the role that plasma collisional effects and confinement have on spectral line emission enhancement and persistence. The plasma-ambient gas interaction was also investigated using spatially resolved spectra and optical time-of-flight measurements. The results indicate that ambient conditions play a very important role in spectral emission intensity as well as the persistence of excited neutral U emission lines, influencing the appropriate spectral acquisition conditions.

  16. Matrix cracking in ceramic-matrix composites

    SciTech Connect

    Danchaivijit, S.; Shetty, D.K. . Dept. of Materials Science and Engineering)

    1993-10-01

    Matrix cracking in ceramic-matrix composites with unbonded frictional interface has been studied using fracture mechanics theory. The critical stress for extension of a fiber-bridged crack has been analyzed using the stress-intensity approach. The analysis uses a new shear-lag formulation of the crack-closure traction applied by the bridging fibers based on the assumption of a constant sliding friction stress over the sliding length of the fiber-matrix interface. The new formulation satisfies two required limiting conditions: (a) when the stress in the bridging fiber approaches the far-field applied stress, the crack-opening displacement approaches a steady-state upper limit that is in agreement with the previous formulations; and (b) in the limit of zero crack opening, the stress in the bridging fiber approaches the far-field fiber stress. This lower limit of the bridging stress is distinctly different from the previous formulations. For all other conditions, the closure traction is a function of the far-field applied stress in addition to the local crack-opening displacement, the interfacial sliding friction stress, and the material properties. Numerical calculations using the stress-intensity approach indicate that the critical stress for crack extension decreases with increasing crack length and approaches a constant steady-state value for large cracks. The steady-state matrix-cracking stress agrees with a steady-state energy balance analysis applied to the continuum model, but it is slightly less than the matrix-cracking stress predicted by such theories of steady-state cracking as that of Aveston, Cooper, and Kelly. The origin of this difference and a method for reconciliation of the two theoretical approaches are discussed.

  17. Global persistence in directed percolation

    NASA Astrophysics Data System (ADS)

    Oerding, K.; van Wijland, F.

    1998-08-01

    We consider a directed percolation process at its critical point. The probability that the deviation of the global order parameter with respect to its average has not changed its sign between 0 and t decays with t as a power law. In space dimensions 0305-4470/31/34/004/img5 the global persistence exponent 0305-4470/31/34/004/img6 that characterizes this decay is 0305-4470/31/34/004/img7 while for d<4 its value is increased to first order in 0305-4470/31/34/004/img8. Combining a method developed by Majumdar and Sire with renormalization group techniques we compute the correction to 0305-4470/31/34/004/img6 to first order in 0305-4470/31/34/004/img10. The global persistence exponent is found to be a new and independent exponent. Finally we compare our results with existing simulations.

  18. Persistence and the Nikkei Index

    NASA Astrophysics Data System (ADS)

    Jain, S.; Yamano, T.

    2007-12-01

    The persistence phenomenon is studied in the Japanese financial market by using a novel mapping of the time evolution of the values of shares in a portfolio onto Ising spins. The method is applied to historical end of day data from the Japanese stock market over an arbitrarily chosen period. By studying the time dependence of the spins, we find clear evidence for a power law decay of the proportion of shares that remain either above or below their "starting" values. The results are compared with those resulting from data from the London market, where there is evidence of a distinctive double power law. Preliminary results from the Japanese market indicate similar behavior. We estimate a long time persistence exponent for the underlying financial markets to be 0.5.

  19. Persistent Monitoring Platforms Final Report

    SciTech Connect

    Bennett, C L

    2007-02-22

    This project was inspired and motivated by the need to provide better platforms for persistent surveillance. In the years since the inception of this work, the need for persistence of surveillance platforms has become even more widely appreciated, both within the defense community and the intelligence community. One of the most demanding technical requirements for such a platform involves the power plant and energy storage system, and this project concentrated almost exclusively on the technology associated with this system for a solar powered, high altitude, unmanned aircraft. An important realization for the feasibility of such solar powered aircraft, made at the outset of this project, was that thermal energy may be stored with higher specific energy density than for any other known practical form of rechargeable energy storage. This approach has proved to be extraordinarily fruitful, and a large number of spin-off applications of this technology were developed in the course of this project.

  20. MATRIX AND VECTOR SERVICES

    Energy Science and Technology Software Center (ESTSC)

    2001-10-18

    PETRA V2 provides matrix and vector services and the ability construct, query, and use matrix and vector objects that are used and computed by TRILINOS solvers. It provides all basic matr5ix and vector operations for solvers in TRILINOS.

  1. Matrix metalloproteinases and epileptogenesis.

    PubMed

    Ikonomidou, Chrysanthy

    2014-12-01

    Matrix metalloproteinases are vital drivers of synaptic remodeling in health and disease. It is suggested that at early stages of epileptogenesis, inhibition of matrix metalloproteinases may help ameliorate cell death, aberrant network rewiring, and neuroinflammation and prevent development of epilepsy. PMID:26567100

  2. Transfer function matrix

    NASA Technical Reports Server (NTRS)

    Seraji, H.

    1987-01-01

    Given a multivariable system, it is proved that the numerator matrix N(s) of the transfer function evaluated at any system pole either has unity rank or is a null matrix. It is also shown that N(s) evaluated at any transmission zero of the system has rank deficiency. Examples are given for illustration.

  3. Persistent Patterns in Accretion Disks

    SciTech Connect

    Amin, Mustafa A.; Frolov, Andrei V.; /KIPAC, Menlo Park

    2006-04-03

    We present a set of new characteristic frequencies associated with accretion disks around compact objects. These frequencies arise from persistent rotating patterns in the disk that are finite in radial extent and driven purely by the gravity of the central body. Their existence depends on general relativistic corrections to orbital motion and, if observed, could be used to probe the strong gravity region around a black hole. We also discuss a possible connection to the puzzle of quasi-periodic oscillations.

  4. Time rate collision matrix

    SciTech Connect

    Stoenescu, M.L.; Smith, T.M.

    1980-02-01

    The collision integral terms in Boltzmann equation are reformulated numerically leading to the substitution of the multiple integrals with a multiplicative matrix of the two colliding species velocity distribution functions which varies with the differential collision cross section. A matrix of lower rank may be constructed when one of the distribution functions is specified, in which case the matrix elements represent kinetic transition probabilities in the velocity space and the multiplication of the time rate collision matrix with the unknown velocity distribution function expresses the time rate of change of the distribution. The collision matrix may be used to describe the time evolution of systems in nonequilibrium conditions, to evaluate the rate of momentum and energy transfer between given species, or to generate validity criteria for linearized kinetic equations.

  5. Grassmann matrix quantum mechanics

    NASA Astrophysics Data System (ADS)

    Anninos, Dionysios; Denef, Frederik; Monten, Ruben

    2016-04-01

    We explore quantum mechanical theories whose fundamental degrees of freedom are rectangular matrices with Grassmann valued matrix elements. We study particular models where the low energy sector can be described in terms of a bosonic Hermitian matrix quantum mechanics. We describe the classical curved phase space that emerges in the low energy sector. The phase space lives on a compact Kähler manifold parameterized by a complex matrix, of the type discovered some time ago by Berezin. The emergence of a semiclassical bosonic matrix quantum mechanics at low energies requires that the original Grassmann matrices be in the long rectangular limit. We discuss possible holographic interpretations of such matrix models which, by construction, are endowed with a finite dimensional Hilbert space.

  6. Matrix Remodeling in Pulmonary Fibrosis and Emphysema.

    PubMed

    Kulkarni, Tejaswini; O'Reilly, Philip; Antony, Veena B; Gaggar, Amit; Thannickal, Victor J

    2016-06-01

    Pulmonary fibrosis and emphysema are chronic lung diseases characterized by a progressive decline in lung function, resulting in significant morbidity and mortality. A hallmark of these diseases is recurrent or persistent alveolar epithelial injury, typically caused by common environmental exposures such as cigarette smoke. We propose that critical determinants of the outcome of the injury-repair processes that result in fibrosis versus emphysema are mesenchymal cell fate and associated extracellular matrix dynamics. In this review, we explore the concept that regulation of mesenchymal cells under the influence of soluble factors, in particular transforming growth factor-β1, and the extracellular matrix determine the divergent tissue remodeling responses seen in pulmonary fibrosis and emphysema. PMID:26741177

  7. Dealing with Persistent Pain in Older Adults

    MedlinePlus

    ... Pain Management Related Documents PDF Dealing with Persistent Pain in Later Life Download Join our e-newsletter! Resources Dealing with Persistent Pain in Older Adults Tools and Tips Printer-friendly ...

  8. Bilateral persistent pupillary membranes associated with cataract

    PubMed Central

    Ahmad, Syed Shoeb; Binson, Caroline; Lung, Chong Ka; Ghani, Shuaibah Abdul

    2011-01-01

    Summary Exuberant persistent pupillary membranes (PPM) are rare in adult eyes. We report the case of a 53-year-old man diagnosed with bilateral, profuse, persistent pupillary membranes and unilateral cataract. PMID:23362401

  9. Divergence in sink contributions to population persistence

    EPA Science Inventory

    Population sinks present unique conservation challenges. The loss of animals in sinks can compromise persistence. Conversely, sinks can bolster population sizes, improving viability. To assess the contribution of sinks to regional persistence, we simulated the removal of sink hab...

  10. High Persister Mutants in Mycobacterium tuberculosis.

    PubMed

    Torrey, Heather L; Keren, Iris; Via, Laura E; Lee, Jong Seok; Lewis, Kim

    2016-01-01

    Mycobacterium tuberculosis forms drug-tolerant persister cells that are the probable cause of its recalcitrance to antibiotic therapy. While genetically identical to the rest of the population, persisters are dormant, which protects them from killing by bactericidal antibiotics. The mechanism of persister formation in M. tuberculosis is not well understood. In this study, we selected for high persister (hip) mutants and characterized them by whole genome sequencing and transcriptome analysis. In parallel, we identified and characterized clinical isolates that naturally produce high levels of persisters. We compared the hip mutants obtained in vitro with clinical isolates to identify candidate persister genes. Genes involved in lipid biosynthesis, carbon metabolism, toxin-antitoxin systems, and transcriptional regulators were among those identified. We also found that clinical hip isolates exhibited greater ex vivo survival than the low persister isolates. Our data suggest that M. tuberculosis persister formation involves multiple pathways, and hip mutants may contribute to the recalcitrance of the infection. PMID:27176494

  11. High Persister Mutants in Mycobacterium tuberculosis

    PubMed Central

    Torrey, Heather L.; Keren, Iris; Via, Laura E.; Lee, Jong Seok; Lewis, Kim

    2016-01-01

    Mycobacterium tuberculosis forms drug-tolerant persister cells that are the probable cause of its recalcitrance to antibiotic therapy. While genetically identical to the rest of the population, persisters are dormant, which protects them from killing by bactericidal antibiotics. The mechanism of persister formation in M. tuberculosis is not well understood. In this study, we selected for high persister (hip) mutants and characterized them by whole genome sequencing and transcriptome analysis. In parallel, we identified and characterized clinical isolates that naturally produce high levels of persisters. We compared the hip mutants obtained in vitro with clinical isolates to identify candidate persister genes. Genes involved in lipid biosynthesis, carbon metabolism, toxin-antitoxin systems, and transcriptional regulators were among those identified. We also found that clinical hip isolates exhibited greater ex vivo survival than the low persister isolates. Our data suggest that M. tuberculosis persister formation involves multiple pathways, and hip mutants may contribute to the recalcitrance of the infection. PMID:27176494

  12. MOOCs and Persistence: Definitions and Predictors

    ERIC Educational Resources Information Center

    Evans, Brent J.; Baker, Rachel B.

    2016-01-01

    The chapter argues for redefining the term "persistence" as it relates to MOOCs and considers how different measures produce different results in the research; it closes with a review of research on persistence in MOOCs.

  13. Persistence and Attrition at San Juan College.

    ERIC Educational Resources Information Center

    Moore, Nelle

    A project was undertaken at San Juan College, in New Mexico, to examine findings from several studies of student persistence and retention to shed light on factors influencing persistence at the college. The project took into account several definitions of persistence, including re-enrollment in the subsequent semester (semester to semester),…

  14. Persistence-Retention. Snapshot™ Report, Spring 2014

    ERIC Educational Resources Information Center

    National Student Clearinghouse, 2014

    2014-01-01

    This snapshot report provides information on student persistence and retention rates for Spring 2014. Data is presented in tabular format on the following: (1) First-Year Persistence and Retention Rates by Starting Enrollment Intensity (all institutional sectors); (2) First-Year Persistence and Retention Rates by Age at College Entry (all…

  15. Persistence-Retention. Snapshot™ Report, Spring 2015

    ERIC Educational Resources Information Center

    National Student Clearinghouse, 2015

    2015-01-01

    This Snapshot Report offers information on student persistence and retention rates for 2009-2013. It offers data on the following: (1) First-Year Persistence and Retention Rates for Students Who Start College at Four-Year Private Nonprofit Institutions; (2) First-Year Persistence and Retention Rates for Students Who Start College at Four-Year…

  16. Intent to Persist at Religiously Affiliated Universities

    ERIC Educational Resources Information Center

    Sansom, J. Mel

    2012-01-01

    The purpose of the secondary data analysis was to examine the attributes of students who intend to persist at the same religiously affiliated institution. The review of literature indicated that persistence has been studied extensively, but there has been only limited investigation of persistence focused on religiously affiliated institutions. The…

  17. Does Motivation Affect Performance via Persistence?

    ERIC Educational Resources Information Center

    Vollmeyer, Regina; Rheinberg, Falko

    2000-01-01

    Studied the relationships among motivation, persistence, and performance in a sample of 51 German college students. Path analysis showed that initial motivation influenced persistence but that the relationship between persistence and performance was disrupted because learners with more knowledge stopped sooner. (SLD)

  18. The Extraction of Information From Visual Persistence

    ERIC Educational Resources Information Center

    Erwin, Donald E.

    1976-01-01

    This research sought to distinguish among three concepts of visual persistence by substituting the physical presence of the target stimulus while simultaneously inhibiting the formation of a persisting representation. Reportability of information about the stimuli was compared to a condition in which visual persistence was allowed to fully develop…

  19. A Grounded Theory of Adult Student Persistence

    ERIC Educational Resources Information Center

    Capps, Rosemary

    2010-01-01

    This grounded theory study investigates adult student persistence at a community college. Student persistence in college is a prerequisite for degree achievement, which correlates with higher earnings and overall better quality of life. Persistence rates remain low for adult students, who combine their college endeavors with responsibilities to…

  20. Hybrid matrix amplifier

    DOEpatents

    Martens, J.S.; Hietala, V.M.; Plut, T.A.

    1995-01-03

    The present invention comprises a novel matrix amplifier. The matrix amplifier includes an active superconducting power divider (ASPD) having N output ports; N distributed amplifiers each operatively connected to one of the N output ports of the ASPD; and a power combiner having N input ports each operatively connected to one of the N distributed amplifiers. The distributed amplifier can included M stages of amplification by cascading superconducting active devices. The power combiner can include N active elements. The resulting (N[times]M) matrix amplifier can produce signals of high output power, large bandwidth, and low noise. 6 figures.

  1. Hybrid matrix amplifier

    DOEpatents

    Martens, Jon S.; Hietala, Vincent M.; Plut, Thomas A.

    1995-01-01

    The present invention comprises a novel matrix amplifier. The matrix amplifier includes an active superconducting power divider (ASPD) having N output ports; N distributed amplifiers each operatively connected to one of the N output ports of the ASPD; and a power combiner having N input ports each operatively connected to one of the N distributed amplifiers. The distributed amplifier can included M stages of amplification by cascading superconducting active devices. The power combiner can include N active elements. The resulting (N.times.M) matrix amplifier can produce signals of high output power, large bandwidth, and low noise.

  2. Transforming growth factor-β1 and extracellular matrix protease expression in the uterosacral ligaments of patients with and without pelvic organ prolapse

    PubMed Central

    Leegant, Ava; Zuckerwise, Lisa C.; Downing, Keith; Brouwer-Visser, Jurriaan; Zhu, Changcheng; Cossio, Maria Jose; Strube, Felix; Xie, Xianhong; Banks, Erika; Huang, Gloria S

    2015-01-01

    Objectives This study was undertaken to evaluate the expression of transforming growth factor-β1 (TGF-β1) and matrix metalloproteinase 9 (MMP-9), key regulators of the extracellular matrix composition, in the uterosacral ligaments (USL) of women with pelvic organ prolapse compared with controls. Methods Under IRB approval, USL samples were obtained from women undergoing vaginal hysterectomy for stage two or greater pelvic organ prolapse (cases, n=21) and from women without pelvic organ prolapse undergoing vaginal hysterectomy for benign indications (controls, n=19). Hematoxylin and eosin and trichrome staining were performed on the USL sections, and the distribution of smooth muscle and fibrous tissue quantified. Immunohistochemical staining was performed using anti-TGF-β1 and anti-MMP-9 antibodies. The expression of TGF-β1 and MMP-9 was evaluated by the pathologist, who was blinded to all clinical data. Results TGF-β1 expression positively correlated with MMP-9 expression (R=0.4, P=0.01). The expression of TGF-β1 and MMP-9 were similar in subjects with pelvic organ prolapse versus controls. There was a significant increase in fibrous tissue (P=0.008), and a corresponding decrease in smooth muscle (P=0.03), associated with increasing age. TGF-β1 expression, but not MMP-9 expression, also significantly increased with age (P=0.02). Discussion Although our study uncovered age-related alterations in USL composition and TGF-β1 expression, there was no difference in the expression of TGF-β1 or MMP-9 in the subjects with pelvic organ prolapse versus controls. PMID:25185601

  3. Measurement matrix optimization method based on matrix orthogonal similarity transformation

    NASA Astrophysics Data System (ADS)

    Pan, Jinfeng

    2016-05-01

    Optimization of the measurement matrix is one of the important research aspects of compressive sensing theory. A measurement matrix optimization method is presented based on the orthogonal similarity transformation of the information operator's Gram matrix. In terms of the fact that the information operator's Gram matrix is a singular symmetric matrix, a simplified orthogonal similarity transformation is deduced, and thus the simplified diagonal matrix that is orthogonally similar to it is obtained. Then an approximation of the Gram matrix is obtained by letting all the nonzero diagonal entries of the simplified diagonal matrix equal their average value. Thus an optimized measurement matrix can be acquired according to its relationship with the information operator. Results of experiments show that the optimized measurement matrix compared to the random measurement matrix is less coherent with dictionaries. The relative signal recovery error also declines when the proposed measurement matrix is utilized.

  4. On Persistence in Multiobjective Oligopoly

    NASA Astrophysics Data System (ADS)

    Ahmed, E.; Hegazi, A. S.; El-Hafez, A. T. Abd

    Multiobjective oligopoly models are constructed. The objective of th e first two models are to maximize profits and to maximize sales. In the third model, the objectives are to maximize profits and to minimize risk. Giving more weight to risk minimization decreased the profits. In all the three models, we found that the weight of the profit maximization has to be higher than a given threshold. Sufficient conditions for persistence of some multiobjective oligopolies are derived. Again, they require that the weight of profit maximization to be higher than certain value.

  5. Metal Matrix Composites

    SciTech Connect

    Hunt, Warren; Herling, Darrell R.

    2004-02-01

    Metal matrix composites have found selected application in areas that can cost-effectively capitalize on improvements in specific stiffness, specific strength, fatigue resistance, wear resistance, and coefficient of thermal expansion. Metal matrix composites comprise a relatively wide range of materials defined by the metal matrix, reinforcement type, and reinforcement geometry. In the area of the matrix, most metallic systems have been explored, including aluminum, beryllium, magnesium, titanium, iron, nickel, cobalt, and silver. However, aluminum is by far the most preferred. For reinforcements, the materials are typically ceramics, which provide a very beneficial combination of stiffness, strength, and relatively low density. Candidate reinforcement materials include SiC, Al2O3, B4C, TiC, TiB2, graphite, and a number of other ceramics. In addition, metallic materials such as tungsten and steel fibers have been considered.

  6. Pesticide-Exposure Matrix

    Cancer.gov

    The "Pesticide-exposure Matrix" was developed to help epidemiologists and other researchers identify the active ingredients to which people were likely exposed when their homes and gardens were treated for pests in past years.

  7. The Hill Interaction Matrix

    ERIC Educational Resources Information Center

    Hill, William Fawcett

    1971-01-01

    Leadership style, group composition, and group development are simultaneously quantified through the use of the matrix. It represents an attempt to objectify the art of group therapy. Comment by Richard C. Rank follows. (Author)

  8. Matrix computations in MACSYMA

    NASA Technical Reports Server (NTRS)

    Wang, P. S.

    1977-01-01

    Facilities built into MACSYMA for manipulating matrices with numeric or symbolic entries are described. Computations will be done exactly, keeping symbols as symbols. Topics discussed include how to form a matrix and create other matrices by transforming existing matrices within MACSYMA; arithmetic and other computation with matrices; and user control of computational processes through the use of optional variables. Two algorithms designed for sparse matrices are given. The computing times of several different ways to compute the determinant of a matrix are compared.

  9. Optical coherency matrix tomography

    PubMed Central

    Kagalwala, Kumel H.; Kondakci, H. Esat; Abouraddy, Ayman F.; Saleh, Bahaa E. A.

    2015-01-01

    The coherence of an optical beam having multiple degrees of freedom (DoFs) is described by a coherency matrix G spanning these DoFs. This optical coherency matrix has not been measured in its entirety to date—even in the simplest case of two binary DoFs where G is a 4 × 4 matrix. We establish a methodical yet versatile approach—optical coherency matrix tomography—for reconstructing G that exploits the analogy between this problem in classical optics and that of tomographically reconstructing the density matrix associated with multipartite quantum states in quantum information science. Here G is reconstructed from a minimal set of linearly independent measurements, each a cascade of projective measurements for each DoF. We report the first experimental measurements of the 4 × 4 coherency matrix G associated with an electromagnetic beam in which polarization and a spatial DoF are relevant, ranging from the traditional two-point Young’s double slit to spatial parity and orbital angular momentum modes. PMID:26478452

  10. Persistent Homology for The Quantitative Prediction of Fullerene Stability

    PubMed Central

    Xia, Kelin; Feng, Xin; Tong, Yiying; Wei, Guo Wei

    2014-01-01

    Persistent homology is a relatively new tool often used for qualitative analysis of intrinsic topological features in images and data originated from scientific and engineering applications. In this paper, we report novel quantitative predictions of the energy and stability of fullerene molecules, the very first attempt in employing persistent homology in this context. The ground-state structures of a series of small fullerene molecules are first investigated with the standard Vietoris-Rips complex. We decipher all the barcodes, including both short-lived local bars and long-lived global bars arising from topological invariants, and associate them with fullerene structural details. By using accumulated bar lengths, we build quantitative models to correlate local and global Betti-2 bars respectively with the heat of formation and total curvature energies of fullerenes. It is found that the heat of formation energy is related to the local hexagonal cavities of small fullerenes, while the total curvature energies of fullerene isomers are associated with their sphericities, which are measured by the lengths of their long-lived Betti-2 bars. Excellent correlation coefficients (> 0.94) between persistent homology predictions and those of quantum or curvature analysis have been observed. A correlation matrix based filtration is introduced to further verify our findings. PMID:25523342

  11. Persistent brain network homology from the perspective of dendrogram.

    PubMed

    Lee, Hyekyoung; Kang, Hyejin; Chung, Moo K; Kim, Bung-Nyun; Lee, Dong Soo

    2012-12-01

    The brain network is usually constructed by estimating the connectivity matrix and thresholding it at an arbitrary level. The problem with this standard method is that we do not have any generally accepted criteria for determining a proper threshold. Thus, we propose a novel multiscale framework that models all brain networks generated over every possible threshold. Our approach is based on persistent homology and its various representations such as the Rips filtration, barcodes, and dendrograms. This new persistent homological framework enables us to quantify various persistent topological features at different scales in a coherent manner. The barcode is used to quantify and visualize the evolutionary changes of topological features such as the Betti numbers over different scales. By incorporating additional geometric information to the barcode, we obtain a single linkage dendrogram that shows the overall evolution of the network. The difference between the two networks is then measured by the Gromov-Hausdorff distance over the dendrograms. As an illustration, we modeled and differentiated the FDG-PET based functional brain networks of 24 attention-deficit hyperactivity disorder children, 26 autism spectrum disorder children, and 11 pediatric control subjects. PMID:23008247

  12. Persistent Currents and Quantum Critical Phenomena in Mesoscopic Physics

    NASA Astrophysics Data System (ADS)

    Zelyak, Oleksandr

    In this thesis, we study persistent currents and quantum critical phenomena in the systems of mesoscopic physics. As an introduction in Chapter 1 we familiarize the reader with the area of mesoscopic physics. We explain how mesoscopic systems are different from quantum systems of single atoms and molecules and bulk systems with an Avogadro number of elements. We also describe some important mesoscopic phenomena. One of the mathematical tools that we extensively use in our studies is Random Matrix Theorty. This theory is not a part of standard physics courses and for educational purposes we provide the basics of Random Matrix Theory in Chapter 2. In Chapter 3 we study the persistent current of noninteracting electrons in quantum billiards. We consider simply connected chaotic Robnik-Berry quantum billiard and its annular analog. The electrons move in the presence of a point-like magnetic flux at the center of the billiard. For the simply connected billiard, we find a large diamagnetic contribution to the persistent current at small flux, which is independent of the flux and is proportional to the number of electrons (or equivalently the density since we keep the area fixed). The size of this diamagnetic contribution is much larger than the previously studied mesoscopic fluctuations in the persistent current in the simply connected billiard. This behavior of persistent current can ultimately be traced to the response of the angular-momentum l = 0 levels (neglected in semiclassical expansions) on the unit disk to a point-like flux at its center. We observe the same behavior for the annular billiard when the inner radius is much smaller than the outer one. We also find that the usual fluctuating persistent current and Anderson-like localization due to boundary scattering are seen when the annulus tends to a one-dimensional ring. We explore the conditions for the observability of this phenomenon. In Chapter 4 we study quantum critical phenomena in a system of two

  13. Human Granulocyte Macrophage Colony-Stimulating Factor Enhances Antibiotic Susceptibility of Pseudomonas aeruginosa Persister Cells.

    PubMed

    Choudhary, Geetika S; Yao, Xiangyu; Wang, Jing; Peng, Bo; Bader, Rebecca A; Ren, Dacheng

    2015-01-01

    Bacterial persister cells are highly tolerant to antibiotics and cause chronic infections. However, little is known about the interaction between host immune systems with this subpopulation of metabolically inactive cells, and direct effects of host immune factors (in the absence of immune cells) on persister cells have not been studied. Here we report that human granulocyte macrophage-colony stimulating factor (GM-CSF) can sensitize the persister cells of Pseudomonas aeruginosa PAO1 and PDO300 to multiple antibiotics including ciprofloxacin, tobramycin, tetracycline, and gentamicin. GM-CSF also sensitized the biofilm cells of P. aeruginosa PAO1 and PDO300 to tobramycin in the presence of biofilm matrix degrading enzymes. The DNA microarray and qPCR results indicated that GM-CSF induced the genes for flagellar motility and pyocin production in the persister cells, but not the normal cells of P. aeruginosa PAO1. Consistently, the supernatants from GM-CSF treated P. aeruginosa PAO1 persister cell suspensions were found cidal to the pyocin sensitive strain P. aeruginosa PAK. Collectively, these findings suggest that host immune factors and bacterial persisters may directly interact, leading to enhanced susceptibility of persister cells to antibiotics. PMID:26616387

  14. Human Granulocyte Macrophage Colony-Stimulating Factor Enhances Antibiotic Susceptibility of Pseudomonas aeruginosa Persister Cells

    PubMed Central

    Choudhary, Geetika S.; Yao, Xiangyu; Wang, Jing; Peng, Bo; Bader, Rebecca A.; Ren, Dacheng

    2015-01-01

    Bacterial persister cells are highly tolerant to antibiotics and cause chronic infections. However, little is known about the interaction between host immune systems with this subpopulation of metabolically inactive cells, and direct effects of host immune factors (in the absence of immune cells) on persister cells have not been studied. Here we report that human granulocyte macrophage-colony stimulating factor (GM-CSF) can sensitize the persister cells of Pseudomonas aeruginosa PAO1 and PDO300 to multiple antibiotics including ciprofloxacin, tobramycin, tetracycline, and gentamicin. GM-CSF also sensitized the biofilm cells of P. aeruginosa PAO1 and PDO300 to tobramycin in the presence of biofilm matrix degrading enzymes. The DNA microarray and qPCR results indicated that GM-CSF induced the genes for flagellar motility and pyocin production in the persister cells, but not the normal cells of P. aeruginosa PAO1. Consistently, the supernatants from GM-CSF treated P. aeruginosa PAO1 persister cell suspensions were found cidal to the pyocin sensitive strain P. aeruginosa PAK. Collectively, these findings suggest that host immune factors and bacterial persisters may directly interact, leading to enhanced susceptibility of persister cells to antibiotics. PMID:26616387

  15. Persistent Pneumonia in an Infant

    PubMed Central

    Padilla, Kristen; Logan, Latania; Codispoti, Christopher; Jones, Carolyn

    2015-01-01

    A 4-month-old boy with past medical history of eczema presented with fever and cough; a chest radiograph showed lung consolidation, and he was initially treated with amoxicillin for presumed community-acquired pneumonia. After several days, his fever persisted. He was also profoundly anemic. Antibiotic coverage was broadened because of the concern for resistant organisms; he began to improve and was discharged from the hospital. However, at 5 months of age, his fever returned, and he continued to demonstrate lung consolidation on chest radiograph. Additionally, he had lost weight and continued to be anemic. Splenic cysts were noted on abdominal ultrasound. He was diagnosed with an unusual etiology for his pneumonia and improved with the appropriate therapy. An underlying immunodeficiency was suspected, but initial testing was nondiagnostic. At 12 months of age, he presented with another infection, and the final diagnosis was made. PMID:26122810

  16. Long-persistence blue phosphors

    NASA Technical Reports Server (NTRS)

    Yen, William M. (Inventor); Jia, Weiyi (Inventor); Lu, Lizhu (Inventor); Yuan, Huabiao (Inventor)

    2000-01-01

    This invention relates to phosphors including long-persistence blue phosphors. Phosphors of the invention are represented by the general formula: MO . mAl.sub.2 O.sub.3 :Eu.sup.2+,R.sup.3+ wherein m is a number ranging from about 1.6 to about 2.2, M is Sr or a combination of Sr with Ca and Ba or both, R.sup.3+ is a trivalent metal ion or trivalent Bi or a mixture of these trivalent ions, Eu.sup.2+ is present at a level up to about 5 mol % of M, and R.sup.3+ is present at a level up to about 5 mol % of M. Phosphors of this invention include powders, ceramics, single crystals and single crystal fibers. A method of manufacturing improved phosphors and a method of manufacturing single crystal phosphors are also provided.

  17. Persistent nicorandil induced oral ulceration

    PubMed Central

    Healy, C M; Smyth, Y; Flint, S R

    2004-01-01

    Four patients with nicorandil induced ulceration are described, and the literature on the subject is reviewed. Nicorandil induced ulcers are very painful and distressing for patients. Clinically they appear as large, deep, persistent ulcers that have punched out edges. They are poorly responsive to topical steroids and usually require alteration of nicorandil treatment. The ulceration tends to occur at high doses of nicorandil and all four cases reported here were on doses of 40 mg per day or greater. In these situations reduction of nicorandil dose may be sufficient to promote ulcer healing and prevent further recurrence. However, nicorandil induced ulcers have been reported at doses as low as 10 mg daily and complete cessation of nicorandil may be required. PMID:15201264

  18. Persistent homology and string vacua

    NASA Astrophysics Data System (ADS)

    Cirafici, Michele

    2016-03-01

    We use methods from topological data analysis to study the topological features of certain distributions of string vacua. Topological data analysis is a multi-scale approach used to analyze the topological features of a dataset by identifying which homological characteristics persist over a long range of scales. We apply these techniques in several contexts. We analyze {N}=2 vacua by focusing on certain distributions of Calabi-Yau varieties and Landau-Ginzburg models. We then turn to flux compactifications and discuss how we can use topological data analysis to extract physical information. Finally we apply these techniques to certain phenomenologically realistic heterotic models. We discuss the possibility of characterizing string vacua using the topological properties of their distributions.

  19. Tendon Functional Extracellular Matrix

    PubMed Central

    Screen, H.R.C.; Birk, D.E.; Kadler, K.E.; Ramirez, F; Young, M.F.

    2015-01-01

    This article is one of a series, summarising views expressed at the Orthopaedic Research Society New Frontiers in Tendon Research Conference. This particular article reviews the three workshops held under the “Functional Extracellular Matrix” stream. The workshops focused on the roles of the tendon extracellular matrix, such as performing the mechanical functions of tendon, creating the local cell environment and providing cellular cues. Tendon is a complex network of matrix and cells, and its biological functions are influenced by widely-varying extrinsic and intrinsic factors such as age, nutrition, exercise levels and biomechanics. Consequently, tendon adapts dynamically during development, ageing and injury. The workshop discussions identified research directions associated with understanding cell-matrix interactions to be of prime importance for developing novel strategies to target tendon healing or repair. PMID:25640030

  20. Matrix interdiction problem

    SciTech Connect

    Pan, Feng; Kasiviswanathan, Shiva

    2010-01-01

    In the matrix interdiction problem, a real-valued matrix and an integer k is given. The objective is to remove k columns such that the sum over all rows of the maximum entry in each row is minimized. This combinatorial problem is closely related to bipartite network interdiction problem which can be applied to prioritize the border checkpoints in order to minimize the probability that an adversary can successfully cross the border. After introducing the matrix interdiction problem, we will prove the problem is NP-hard, and even NP-hard to approximate with an additive n{gamma} factor for a fixed constant {gamma}. We also present an algorithm for this problem that achieves a factor of (n-k) mUltiplicative approximation ratio.

  1. Persistent primitive trigeminal artery: a review.

    PubMed

    Azab, Waleed; Delashaw, Johnny; Mohammed, Mohammed

    2012-01-01

    The trigeminal artery is the largest of the fetal carotid-basilar anastomotic arteries, and it persists for the longest embryonic period. The artery usually involutes after the development of the posterior communicating artery. The exact causes of persistence of this primitive vessel into adulthood are not completely clear. Angiographic and anatomical descriptions of the various persistent trigeminal artery (PTA) configurations and their relation to the remainder of the cerebrovascular tree and the other surrounding structures have been reported. Persistent trigeminal artery can be associated with many other vascular anomalies and disorders including aneurysms, arteriovenous malformations and carotid-cavernous fistulae. A thorough understanding of the anatomical and angiographic features of this persistent embryonic arterial channel is of utmost importance when making therapeutic decisions and embarking on surgical or endovascular intervention for any pertinent pathological condition. We review the embryology, angiographic features, microsurgical anatomy and associated vascular anomalies and disorders of the persistent trigeminal artery. PMID:22843453

  2. A Historical Perspective on Bacterial Persistence.

    PubMed

    Verstraeten, Natalie; Knapen, Wouter; Fauvart, Maarten; Michiels, Jan

    2016-01-01

    Bactericidal antibiotics quickly kill the majority of a bacterial population. However, a small fraction of cells typically survive through entering the so-called persister state. Persister cells are increasingly being viewed as a major cause of the recurrence of chronic infectious disease and could be an important factor in the emergence of antibiotic resistance. The phenomenon of persistence was first described in the 1940s, but remained poorly understood for decades afterwards. Only recently, a series of breakthrough discoveries has started to shed light on persister physiology and the molecular and genetic underpinnings of persister formation. We here provide an overview of the key studies that have paved the way for the current boom in persistence research, with a special focus on the technological and methodological advances that have enabled this progress. PMID:26468095

  3. Complex matrix model duality

    SciTech Connect

    Brown, T. W.

    2011-04-15

    The same complex matrix model calculates both tachyon scattering for the c=1 noncritical string at the self-dual radius and certain correlation functions of operators which preserve half the supersymmetry in N=4 super-Yang-Mills theory. It is dual to another complex matrix model where the couplings of the first model are encoded in the Kontsevich-like variables of the second. The duality between the theories is mirrored by the duality of their Feynman diagrams. Analogously to the Hermitian Kontsevich-Penner model, the correlation functions of the second model can be written as sums over discrete points in subspaces of the moduli space of punctured Riemann surfaces.

  4. Matrixed business support comparison study.

    SciTech Connect

    Parsons, Josh D.

    2004-11-01

    The Matrixed Business Support Comparison Study reviewed the current matrixed Chief Financial Officer (CFO) division staff models at Sandia National Laboratories. There were two primary drivers of this analysis: (1) the increasing number of financial staff matrixed to mission customers and (2) the desire to further understand the matrix process and the opportunities and challenges it creates.

  5. Dualities in Persistent (Co)Homology

    SciTech Connect

    de Silva, Vin; Morozov, Dmitriy; Vejdemo-Johansson, Mikael

    2011-09-16

    We consider sequences of absolute and relative homology and cohomology groups that arise naturally for a filtered cell complex. We establishalgebraic relationships between their persistence modules, and show that they contain equivalent information. We explain how one can use the existingalgorithm for persistent homology to process any of the four modules, and relate it to a recently introduced persistent cohomology algorithm. Wepresent experimental evidence for the practical efficiency of the latter algorithm.

  6. Matrix Synthesis and Characterization

    NASA Technical Reports Server (NTRS)

    1984-01-01

    The role of NASA in the area of composite material synthesis; evaluation techniques; prediction analysis techniques; solvent-resistant tough composite matrix; resistance to paint strippers; acceptable processing temperature and pressure for thermoplastics; and the role of computer modeling and fiber interface improvement were discussed.

  7. The Acrosomal Matrix.

    PubMed

    Foster, James A; Gerton, George L

    2016-01-01

    The acrosome, a single exocytotic vesicle on the head of sperm, has an essential role in fertilization, but the exact mechanisms by which it facilitates sperm-egg interactions remain unresolved. The acrosome contains dozens of secretory proteins that are packaged into the forming structure during spermatogenesis; many of these proteins are localized into specific topographical areas of the acrosome, while others are more diffusely distributed. Acrosomal proteins can also be biochemically classified as components of the acrosomal matrix, a large, relatively insoluble complex, or as soluble proteins. This review focuses on recent findings using genetically modified mice (gene knockouts and transgenic "green acrosome" mice) to study the effects of eliminating acrosomal matrix-associated proteins on sperm structure and function. Some gene knockouts produce infertile phenotypes with obviously missing, specific activities that affect acrosome biogenesis during spermatogenesis or interfere with acrosome function in mature sperm. Mutations that delete some components produce fertile phenotypes with subtler effects that provide useful insights into acrosomal matrix function in fertilization. In general, these studies enable the reassessment of paradigms to explain acrosome formation and function and provide novel, objective insights into the roles of acrosomal matrix proteins in fertilization. The use of genetically engineered mouse models has yielded new mechanistic information that complements recent, important in vivo imaging studies. PMID:27194348

  8. Matrix Embedded Organic Synthesis

    NASA Astrophysics Data System (ADS)

    Kamakolanu, U. G.; Freund, F. T.

    2016-05-01

    In the matrix of minerals such as olivine, a redox reaction of the low-z elements occurs. Oxygen is oxidized to the peroxy state while the low-Z-elements become chemically reduced. We assign them a formula [CxHyOzNiSj]n– and call them proto-organics.

  9. Constructing the matrix

    NASA Astrophysics Data System (ADS)

    Elliott, John

    2012-09-01

    As part of our 'toolkit' for analysing an extraterrestrial signal, the facility for calculating structural affinity to known phenomena must be part of our core capabilities. Without such a resource, we risk compromising our potential for detection and decipherment or at least causing significant delay in the process. To create such a repository for assessing structural affinity, all known systems (language parameters) need to be structurally analysed to 'place' their 'system' within a relational communication matrix. This will need to include all known variants of language structure, whether 'living' (in current use) or ancient; this must also include endeavours to incorporate yet undeciphered scripts and non-human communication, to provide as complete a picture as possible. In creating such a relational matrix, post-detection decipherment will be assisted by a structural 'map' that will have the potential for 'placing' an alien communication with its nearest known 'neighbour', to assist subsequent categorisation of basic parameters as a precursor to decipherment. 'Universal' attributes and behavioural characteristics of known communication structure will form a range of templates (Elliott, 2001 [1] and Elliott et al., 2002 [2]), to support and optimise our attempt at categorising and deciphering the content of an extraterrestrial signal. Detection of the hierarchical layers, which comprise intelligent, complex communication, will then form a matrix of calculations that will ultimately score affinity through a relational matrix of structural comparison. In this paper we develop the rationales and demonstrate functionality with initial test results.

  10. The energetic and chemical fingerprints of persistent soil organic carbon

    NASA Astrophysics Data System (ADS)

    Barré, Pierre; Plante, Alain F.; Cécillon, Lauric; Lutfalla, Suzanne; Baudin, François; Bernard, Sylvain; Christensen, Bent T.; Fernandez, Jose M.; Houot, Sabine; Kätterer, Thomas; Macdonald, Andy; van Oort, Folkert; Le Guillou, Corentin; Chenu, Claire

    2016-04-01

    A better understanding of soil organic carbon (SOC) persistence is needed to better predict SOC vulnerability to global change. The absence of convincing physical or chemical procedures to define, characterize or isolate relatively labile versus persistent SOC pools makes the study of persistent SOC difficult. Long-term bare fallow (LTBF) experiments, in which C inputs have been stopped for several decades, provide a unique opportunity to study persistent SOC without the inherent artefacts induced by extraction procedures, the hypothesis being that SOC is gradually enriched in persistent C with time as labile components decompose. We determined the evolution of thermal and chemical characteristics of bulk SOC in five LTBF experiments across Europe: Askov (DK), Grignon (FR), Rothamsted (UK), Ultuna (SW) and Versailles (FR), using a multi-technique approach involving Rock-Eval pyrolysis, thermogravimetry and differential scanning calorimetry (TG-DSC), mid-infrared diffuse reflectance spectroscopy (DRIFT-MIRS), and Near Edge X-Ray Absorption Fine Structure (NEXAFS). Results of Rock-Eval and TG analyses showed that the temperature needed to combust the SOC increased with bare fallow duration at all sites. Conversely, SOC energy density (in mJ mg-1 C) measured by DSC decreased with bare fallow duration. Rock-Eval pyrolysis results showed that hydrogen index (HI) tended to decrease with bare fallow duration whereas the oxygen index (OI) did not show consistent trends across sites. NEXAFS signals presented little differences and were dominated by carboxyl peak. Nonetheless, NEXAFS results showed a trend of increasing carboxyl groups and decreasing ketone and amide groups with bare fallow duration. Due to the mineral matrix, only a reduced part of the DRIFT-MIRS signals has been used. We observed that the bulk chemistry of aliphatic SOC (CH3 vs. CH2 functional groups) showed different trends for the different sites. Our results showed that in spite of the heterogeneity of

  11. A PILOT STUDY OF CHILDREN'S TOTAL EXPOSURE TO PERSISTENT PESTICIDES AND OTHER PERSISTENT ORGANIC POLLUTANTS (CTEPP)

    EPA Science Inventory

    The Pilot Study of Children's Total Exposure to Persistent Pesticides and Other Persistent Organic Pollutants (CTEPP) investigated the aggregate exposures of 257 preschool children and their primary adult caregivers to pollutants commonly detected in their everyday environments. ...

  12. Genetic Mapping of Persistence in Tetraploid Alfalfa

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Persistence is a critical trait for alfalfa, yet the genetics of this trait is poorly understood. Herein, we characterize an F1 alfalfa population derived from the cross between the two cultivated alfalfa subpecies for persistence in three production seasons at Ames and Nashua, Iowa locations and o...

  13. Persistence of Grazed Red Clover Varieties

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Historically, red clover (Trifolium pratense) has been limited by its lack of stand persistence in hay and grazed systems compared to other small-seeded forage legumes. Breeding over the past 50 years has extended red clover persistence in a hay management system to four years. This study examined g...

  14. Long Persistent Light Emitting Diode Indicators

    ERIC Educational Resources Information Center

    Jia, Dongdong; Ma, Yiwei; Hunter, D. N.

    2007-01-01

    An undergraduate laboratory was designed for undergraduate students to make long persistent light emitting diode (LED) indicators using phosphors. Blue LEDs, which emit at 465 nm, were characterized and used as an excitation source. Long persistent phosphors, SrAl[subscript 2]O[subscript 4]:Eu[superscript 2+],Dy[superscript 3+] (green) and…

  15. Supplemental Instruction: Supporting Persistence in Barrier Courses

    ERIC Educational Resources Information Center

    Bronstein, Susan B.

    2008-01-01

    Courses that interfere with undergraduate students' persistence are barriers that appear all along the undergraduate continuum. Supplemental Instruction (SI) may contribute to students' achievement in a barrier course and, therefore, to their persistence in their academic program. The purpose of this single-case descriptive study was to explore…

  16. Personality Characteristics in Relation to College Persistence

    ERIC Educational Resources Information Center

    Johnson, Duane E.

    1970-01-01

    Scales of the Minnesota Counseling Inventory (MCI) were used to compare persisters with nonpersisters. All four comparisons involving the Conformity scale and two of four comparisons involving the Family Relationships scale demonstrated significant differences. Persisters scored lower than nonpersisters on all comparisons involving the Conformity…

  17. Counseling on Campus: Client Persistence and Progress

    ERIC Educational Resources Information Center

    Lucas, Margaretha S.

    2012-01-01

    Two related studies addressed college students' persistence and progress in psychotherapy. In Study 1, using emotional health variables assessed at intake, students who persisted in counseling and demonstrated clinical improvement were compared with those who either did not return for their first session or who did return but stopped before…

  18. Paths correlation matrix.

    PubMed

    Qian, Weixian; Zhou, Xiaojun; Lu, Yingcheng; Xu, Jiang

    2015-09-15

    Both the Jones and Mueller matrices encounter difficulties when physically modeling mixed materials or rough surfaces due to the complexity of light-matter interactions. To address these issues, we derived a matrix called the paths correlation matrix (PCM), which is a probabilistic mixture of Jones matrices of every light propagation path. Because PCM is related to actual light propagation paths, it is well suited for physical modeling. Experiments were performed, and the reflection PCM of a mixture of polypropylene and graphite was measured. The PCM of the mixed sample was accurately decomposed into pure polypropylene's single reflection, pure graphite's single reflection, and depolarization caused by multiple reflections, which is consistent with the theoretical derivation. Reflection parameters of rough surface can be calculated from PCM decomposition, and the results fit well with the theoretical calculations provided by the Fresnel equations. These theoretical and experimental analyses verify that PCM is an efficient way to physically model light-matter interactions. PMID:26371930

  19. Hypercube matrix computation task

    NASA Technical Reports Server (NTRS)

    Calalo, Ruel H.; Imbriale, William A.; Jacobi, Nathan; Liewer, Paulett C.; Lockhart, Thomas G.; Lyzenga, Gregory A.; Lyons, James R.; Manshadi, Farzin; Patterson, Jean E.

    1988-01-01

    A major objective of the Hypercube Matrix Computation effort at the Jet Propulsion Laboratory (JPL) is to investigate the applicability of a parallel computing architecture to the solution of large-scale electromagnetic scattering problems. Three scattering analysis codes are being implemented and assessed on a JPL/California Institute of Technology (Caltech) Mark 3 Hypercube. The codes, which utilize different underlying algorithms, give a means of evaluating the general applicability of this parallel architecture. The three analysis codes being implemented are a frequency domain method of moments code, a time domain finite difference code, and a frequency domain finite elements code. These analysis capabilities are being integrated into an electromagnetics interactive analysis workstation which can serve as a design tool for the construction of antennas and other radiating or scattering structures. The first two years of work on the Hypercube Matrix Computation effort is summarized. It includes both new developments and results as well as work previously reported in the Hypercube Matrix Computation Task: Final Report for 1986 to 1987 (JPL Publication 87-18).

  20. Degradomics of matrix metalloproteinases in inflammatory diseases.

    PubMed

    Dufour, Antoine

    2015-01-01

    Organisms have evolved to react to stress, tissue damage and pathogen invasion to assure their survival. Leukocytes are the primary responders and they regulate repair, immune defense and inflammation with the aid of a wide variety of other cells (e.g. epithelial, fibroblasts). To assure proper responses, a plethora of proteins are involved including signaling molecules, chemokines and proteases to orchestrate a step-by-step reaction. Inflammation is an essential biological process, however, when it persists, it can lead to various diseases that are challenging to heal or cure. The technologies and techniques covered in this book chapter can be applied to study all proteases and their inhibitors although will be centered on the matrix metalloproteinases (MMPs). It will focus on the proteolysis performed by MMPs, their various beneficial and detrimental effects in inflammation and the novel methods to study their roles on human diseases. PMID:25961692

  1. Extracellular matrix fluctuations during early embryogenesis

    PubMed Central

    Szabó, A; Rupp, P A; Rongish, B J; Little, C D; Czirók, A

    2011-01-01

    Extracellular matrix (ECM) movements and rearrangements were studied in avian embryos during early stages of development. We show that the ECM moves as a composite material, whereby distinct molecular components as well as spatially separated layers exhibit similar displacements. Using scanning wide field and confocal microscopy we show that the velocity field of ECM displacement is smooth in space and that ECM movements are correlated even at locations separated by several hundred micrometers. Velocity vectors, however, strongly fluctuate in time. The autocorrelation time of the velocity fluctuations is less than a minute. Suppression of the fluctuations yields a persistent movement pattern that is shared among embryos at equivalent stages of development. The high resolution of the velocity fields allows a detailed spatio-temporal characterization of important morphogenetic processes, especially tissue dynamics surrounding the embryonic organizer (Hensen’s node). PMID:21750366

  2. Standard Errors for Matrix Correlations.

    ERIC Educational Resources Information Center

    Ogasawara, Haruhiko

    1999-01-01

    Derives the asymptotic standard errors and intercorrelations for several matrix correlations assuming multivariate normality for manifest variables and derives the asymptotic standard errors of the matrix correlations for two factor-loading matrices. (SLD)

  3. On matrix model formulations of noncommutative Yang-Mills theories

    SciTech Connect

    Azeyanagi, Tatsuo; Hirata, Tomoyoshi; Hanada, Masanori

    2008-11-15

    We study the stability of noncommutative spaces in matrix models and discuss the continuum limit which leads to the noncommutative Yang-Mills theories. It turns out that most noncommutative spaces in bosonic models are unstable. This indicates perturbative instability of fuzzy R{sup D} pointed out by Van Raamsdonk and Armoni et al. persists to nonperturbative level in these cases. In this sense, these bosonic noncommutative Yang-Mills theories are not well-defined, or at least their matrix model formulations studied in this paper do not work. We also show that noncommutative backgrounds are stable in a supersymmetric matrix model deformed by a cubic Myers term, though the deformation itself breaks supersymmetry.

  4. Laboratory diagnosis of persistent human chlamydial infection

    PubMed Central

    Puolakkainen, Mirja

    2013-01-01

    Diagnostic assays for persistent chlamydial infection are much needed to conduct high-quality, large-scale studies investigating the persistent state in vivo, its disease associations and the response to therapy. Yet in most studies the distinction between acute and persistent infection is based on the interpretation of the data obtained by the assays developed to diagnose acute infections or on complex assays available for research only and/or difficult to establish for clinical use. Novel biomarkers for detection of persistent chlamydial infection are urgently needed. Chlamydial whole genome proteome arrays are now available and they can identify chlamydial antigens that are differentially expressed between acute infection and persistent infection. Utilizing these data will lead to the development of novel diagnostic assays. Carefully selected specimens from well-studied patient populations are clearly needed in the process of translating the proteomic data into assays useful for clinical practice. Before such antigens are identified and validated assays become available, we face a challenge of deciding whether the persistent infection truly induced appearance of the proposed marker or do we just base our diagnosis of persistent infection on the presence of the suggested markers. Consequently, we must bear this in mind when interpreting the available data. PMID:24381934

  5. Persistent Bloodstream Infection with Kocuria rhizophila Related to a Damaged Central Catheter

    PubMed Central

    Becker, Karsten; Mérens, Audrey; Ferroni, Agnès; Dubern, Béatrice; Vu-Thien, Hoang

    2012-01-01

    A case of persistent bloodstream infection with Kocuria rhizophila related to a damaged central venous catheter in a 3-year-old girl with Hirschsprung's disease is reported. The strain was identified as K. rhizophila by 16S rRNA gene sequencing and matrix-assisted laser desorption ionization–time of flight mass spectrometry. Arbitrarily primed PCR analysis showed a clonal strain. The repeated septic episodes were resolved with the catheter repair. PMID:22259211

  6. Giant persistent photoconductivity in rough silicon nanomembranes.

    PubMed

    Feng, Ping; Mönch, Ingolf; Harazim, Stefan; Huang, Gaoshan; Mei, Yongfeng; Schmidt, Oliver G

    2009-10-01

    This paper reports the observation of giant persistent photoconductivity from rough Si nanomembranes. When exposed to light, the current in p-type Si nanomembranes is enhanced by roughly 3 orders of magnitude in comparison with that in the dark and can persist for days at a high conductive state after the light is switched off. An applied gate voltage can tune the persistent photocurrent and accelerate the response to light. By analyzing the band structure of the devices and the surfaces through various coatings, we attribute the observed effect to hole-localized regions in Si nanomembranes due to the rough surfaces, where light can activate the confined holes. PMID:19637888

  7. Gasoline on hands: preliminary study on collection and persistence.

    PubMed

    Darrer, Melinda; Jacquemet-Papilloud, Joëlle; Delémont, Olivier

    2008-03-01

    The identification of an arsonist remains one of the most difficult challenges a fire investigation has to face. Seeking and detection of traces of gasoline could provide a valuable information to link a suspect with an arson scene where gasoline was used to set-up the fire. In this perspective, a first study was undertaken to evaluate a simple, fast and efficient method for collecting gasoline from hands, and to assess its persistence over time. Four collection means were tested: PVC, PE and Latex gloves, as well as humidified filter paper. A statistical assessment of the results indicates that Latex and PVC gloves worn for about 20 min, as well as paper filter rubbed on hands, allow an efficient collection of gasoline applied to hands. Due to ease of manipulation and to a reduced amount of volatile compounds detected from the matrix, PVC gloves were selected for the second set of experiments. The evaluation of the persistence of gasoline on hands was then carried out using two initial quantities (500 and 1000 microl). Collection was made with PVC gloves after 0, 30 min, 1, 2 and 4h, on different volunteers. The results show a common tendency of massive evaporation of gasoline during the first 30 min: a continued but non-linear decrease was observed along different time intervals. The results of this preliminary study are in agreement with other previous researches conducted on the detection of flammable liquid residues on clothes, shoes and skin. PMID:17714900

  8. On the Matrix Exponential Function

    ERIC Educational Resources Information Center

    Hou, Shui-Hung; Hou, Edwin; Pang, Wan-Kai

    2006-01-01

    A novel and simple formula for computing the matrix exponential function is presented. Specifically, it can be used to derive explicit formulas for the matrix exponential of a general matrix A satisfying p(A) = 0 for a polynomial p(s). It is ready for use in a classroom and suitable for both hand as well as symbolic computation.

  9. The cellulose resource matrix.

    PubMed

    Keijsers, Edwin R P; Yılmaz, Gülden; van Dam, Jan E G

    2013-03-01

    The emerging biobased economy is causing shifts from mineral fossil oil based resources towards renewable resources. Because of market mechanisms, current and new industries utilising renewable commodities, will attempt to secure their supply of resources. Cellulose is among these commodities, where large scale competition can be expected and already is observed for the traditional industries such as the paper industry. Cellulose and lignocellulosic raw materials (like wood and non-wood fibre crops) are being utilised in many industrial sectors. Due to the initiated transition towards biobased economy, these raw materials are intensively investigated also for new applications such as 2nd generation biofuels and 'green' chemicals and materials production (Clark, 2007; Lange, 2007; Petrus & Noordermeer, 2006; Ragauskas et al., 2006; Regalbuto, 2009). As lignocellulosic raw materials are available in variable quantities and qualities, unnecessary competition can be avoided via the choice of suitable raw materials for a target application. For example, utilisation of cellulose as carbohydrate source for ethanol production (Kabir Kazi et al., 2010) avoids the discussed competition with easier digestible carbohydrates (sugars, starch) deprived from the food supply chain. Also for cellulose use as a biopolymer several different competing markets can be distinguished. It is clear that these applications and markets will be influenced by large volume shifts. The world will have to reckon with the increase of competition and feedstock shortage (land use/biodiversity) (van Dam, de Klerk-Engels, Struik, & Rabbinge, 2005). It is of interest - in the context of sustainable development of the bioeconomy - to categorize the already available and emerging lignocellulosic resources in a matrix structure. When composing such "cellulose resource matrix" attention should be given to the quality aspects as well as to the available quantities and practical possibilities of processing the

  10. Biofilm formation by enteric pathogens and its role in plant colonization and persistence

    PubMed Central

    Yaron, Sima; Römling, Ute

    2014-01-01

    The significant increase in foodborne outbreaks caused by contaminated fresh produce, such as alfalfa sprouts, lettuce, melons, tomatoes and spinach, during the last 30 years stimulated investigation of the mechanisms of persistence of human pathogens on plants. Emerging evidence suggests that Salmonella enterica and Escherichia coli, which cause the vast majority of fresh produce outbreaks, are able to adhere to and to form biofilms on plants leading to persistence and resistance to disinfection treatments, which subsequently can cause human infections and major outbreaks. In this review, we present the current knowledge about host, bacterial and environmental factors that affect the attachment to plant tissue and the process of biofilm formation by S. enterica and E. coli, and discuss how biofilm formation assists in persistence of pathogens on the plants. Mechanisms used by S. enterica and E. coli to adhere and persist on abiotic surfaces and mammalian cells are partially similar and also used by plant pathogens and symbionts. For example, amyloid curli fimbriae, part of the extracellular matrix of biofilms, frequently contribute to adherence and are upregulated upon adherence and colonization of plant material. Also the major exopolysaccharide of the biofilm matrix, cellulose, is an adherence factor not only of S. enterica and E. coli, but also of plant symbionts and pathogens. Plants, on the other hand, respond to colonization by enteric pathogens with a variety of defence mechanisms, some of which can effectively inhibit biofilm formation. Consequently, plant compounds might be investigated for promising novel antibiofilm strategies. PMID:25351039

  11. The persistent stereotype: children's images of scientists

    NASA Astrophysics Data System (ADS)

    Emens McAdam, Janice

    1990-03-01

    Through their reading children learn to regard scientists as eccentrics. It is shown that this stereotype has persisted for over thirty years and affects many adult attitudes. Some methods of breaking the author-reader cycle are suggested.

  12. Helicobacter and Salmonella Persistent Infection Strategies

    PubMed Central

    Monack, Denise M.

    2013-01-01

    Some host-adapted bacterial pathogens are capable of causing persistent infections in humans. For example, Helicobacter pylori inhabits the human gastric mucosa and persistence can be lifelong. Salmonella enterica serovar Typhi causes systemic infections that involve colonization of the reticuloendothelial system and some individuals become lifelong carriers. In this review, I compare and contrast the different lifestyles of Helicobacter and Salmonella within the host and the strategies they have evolved to persist in mammalian hosts. Persistently infected carriers serve as the reservoirs for these pathogens, and the carrier state is an essential feature that is required for survival of the bacteria within a restricted host population. Therefore, investigating the chronic carrier state should provide insight into bacterial survival strategies, as well as new therapeutic approaches for treatments. PMID:24296347

  13. Persisters-as elusive as ever.

    PubMed

    Kaldalu, Niilo; Hauryliuk, Vasili; Tenson, Tanel

    2016-08-01

    Persisters-a drug-tolerant sub-population in an isogenic bacterial culture-have been featured throughout the last decade due to their important role in recurrent bacterial infections. Numerous investigations detail the mechanisms responsible for the formation of persisters and suggest exciting strategies for their eradication. In this review, we argue that the very term "persistence" is currently used to describe a large and heterogeneous set of physiological phenomena that are functions of bacterial species, strains, growth conditions, and antibiotics used in the experiments. We caution against the oversimplification of the mechanisms of persistence and urge for a more rigorous validation of the applicability of these mechanisms in each case. PMID:27262568

  14. Teen Birth Rates Drop, But Disparities Persist

    MedlinePlus

    ... Features Teen Birth Rates Drop, But Disparities Persist Language: English Español (Spanish) Recommend on Facebook Tweet Share Compartir The feature you selected is no longer available. In 10 seconds you will be automatically redirected to the CDC. ...

  15. Stimuli, Reinforcers, and the Persistence of Behavior

    ERIC Educational Resources Information Center

    Nevin, John A.

    2009-01-01

    This article reviews evidence from basic and translational research with pigeons and humans suggesting that the persistence of operant behavior depends on the contingency between stimuli and reinforcers, and considers some implications for clinical interventions. (Contains 4 figures.)

  16. Demystifying the persistent pneumothorax: role of imaging.

    PubMed

    Chaturvedi, Apeksha; Lee, Steven; Klionsky, Nina; Chaturvedi, Abhishek

    2016-06-01

    Evaluation for pneumothorax is an important indication for obtaining chest radiographs in patients who have had trauma, recent cardiothoracic surgery or are on ventilator support. By definition, a persistent pneumothorax constitutes ongoing bubbling of air from an in situ chest drain, 48 h after its insertion. Persistent pneumothorax remains a diagnostic dilemma and identification of potentially treatable aetiologies is important. These may be chest tube related (kinks or malposition), lung parenchymal disease, bronchopleural fistula, or rarely, oesophageal-pleural fistula. Although radiographs remain the mainstay for diagnosis and follow up of pneumothorax, computed tomography (CT) is increasingly being used for problem solving. Aetiology of persistent air leak determines the optimal treatment. For some, a simple repositioning of the chest tube/drain may suffice; others may require surgery. In this pictorial review, we will briefly describe the physiology of pneumothorax, discuss imaging features of identifiable causes for persistent pneumothorax and provide a brief overview of treatment options. Specific aetiology of a persistent air leak may often not be immediately discernible, and will need to be carefully sought. Accurate interpretation of imaging studies can expedite diagnosis and facilitate prompt treatment. Key points • Persistent pneumothorax is defined as a leak persisting for more than 2 days.• Radiographs can identify chest-tube-related causes of pneumothorax.• CT is the most useful test to identify other causes.• Penetrating thoracic injury can cause fistulous communication resulting in a persistent pneumothorax.• Discontinuity of visceral pleura identified by CT may indicate a bronchopleural fistula. PMID:27100907

  17. Persistence of the Lower Stratospheric Polar Vortices

    NASA Technical Reports Server (NTRS)

    Waugh, Darryn W.; Randel, William J.; Pawson, Steven; Newman, Paul A.; Nash, Eric R.

    1999-01-01

    The persistence of the Arctic and Antarctic lower stratospheric vortices is examined over the period 1958 to 1998. Three different vortex-following diagnostics (two using potential vorticity and one based solely on the zonal winds) are compared, and shown to give very similar results for the break up date. The variability in the timing of the breakup of each vortex is qualitatively the same: there are large interannual variations together with smaller decadal-scale variations and there is a significant increase in the persistence since the mid-1980s (all variations are larger for the Arctic vortex). Also, in both hemispheres there is a high correlation between the persistence and the strength and coldness of the spring vortex, with all quantities having the same interannual and decadal variability. However, there is no such correlation between the persistence and the characteristics of the mid-winter vortex. In the northern hemisphere there is also a high correlation between the vortex persistence and the upper tropospheric/lower stratospheric eddy heat flux averaged over the two months prior to the breakup. This indicates that the variability in the wave activity entering the stratosphere over late-winter to early-spring plays a key role in the variability of the vortex persistence (and spring polar temperatures) on both interannual and decadal time scales. However, the decadal variation in the Arctic vortex coldness and persistence for the 1990's falls outside the range of natural variability, while this is not the case for the eddy heat flux. This suggests that the recent increase in vortex persistence is not due solely to changes in the wave activity entering the stratosphere.

  18. Persistent homology analysis of phase transitions

    NASA Astrophysics Data System (ADS)

    Donato, Irene; Gori, Matteo; Pettini, Marco; Petri, Giovanni; De Nigris, Sarah; Franzosi, Roberto; Vaccarino, Francesco

    2016-05-01

    Persistent homology analysis, a recently developed computational method in algebraic topology, is applied to the study of the phase transitions undergone by the so-called mean-field XY model and by the ϕ4 lattice model, respectively. For both models the relationship between phase transitions and the topological properties of certain submanifolds of configuration space are exactly known. It turns out that these a priori known facts are clearly retrieved by persistent homology analysis of dynamically sampled submanifolds of configuration space.

  19. Persistent and Recurrent Clostridium difficile Colitis

    PubMed Central

    Cole, Shola A.; Stahl, Thomas J.

    2015-01-01

    Clostridium difficile infection (CDI) is the most frequent cause of nosocomial diarrhea. It has become a significant dilemma in the treatment of patients, and causes increasing morbidity that, in extreme cases, may result in death. Persistent and recurrent disease hamper attempts at eradication of this infection. Escalating levels of treatment and novel therapeutics are being utilized and developed to treat CDI. Further trials are warranted to definitively determine what protocols can be used to treat persistent and recurrent disease. PMID:26034401

  20. Circularly Polarized Persistent Room-Temperature Phosphorescence from Metal-Free Chiral Aromatics in Air.

    PubMed

    Hirata, Shuzo; Vacha, Martin

    2016-04-21

    Circularly polarized room-temperature phosphorescence (RTP) with persistent emission characteristics was observed from metal-free chiral binaphthyl structures. Enantiomers of the binaphthyl compounds doped into an amorphous hydroxylated steroid matrix produced blue fluorescence and yellow persistent RTP in air. The lifetime and quantum yield of the yellow persistent RTP were 0.67 s and 2.3%, respectively. The dissymmetry factors of circular dichroism (CD) in the first absorption band, circularly polarized fluorescence (CPF), and circularly polarized persistent RTP were |1.1 × 10(-3)|, |4.5 × 10(-4)|, and |2.3 × 10(-3)|, respectively. A comparison between the experimental data and calculations by time-dependent density functional theory for transient CD spectra confirmed that the binaphthyl conformations in the lowest singlet excited state (S1) and the lowest triplet state (T1) were different. The large difference in the dissymmetry factors for the CPF and the circularly polarized persistent RTP was likely caused by this conformational change between S1 and T1. PMID:27058743

  1. Ceramic matrix and resin matrix composites: A comparison

    NASA Technical Reports Server (NTRS)

    Hurwitz, Frances I.

    1987-01-01

    The underlying theory of continuous fiber reinforcement of ceramic matrix and resin matrix composites, their fabrication, microstructure, physical and mechanical properties are contrasted. The growing use of organometallic polymers as precursors to ceramic matrices is discussed as a means of providing low temperature processing capability without the fiber degradation encountered with more conventional ceramic processing techniques. Examples of ceramic matrix composites derived from particulate-filled, high char yield polymers and silsesquioxane precursors are provided.

  2. Ceramic matrix and resin matrix composites - A comparison

    NASA Technical Reports Server (NTRS)

    Hurwitz, Frances I.

    1987-01-01

    The underlying theory of continuous fiber reinforcement of ceramic matrix and resin matrix composites, their fabrication, microstructure, physical and mechanical properties are contrasted. The growing use of organometallic polymers as precursors to ceramic matrices is discussed as a means of providing low temperature processing capability without the fiber degradation encountered with more conventional ceramic processing techniques. Examples of ceramic matrix composites derived from particulate-filled, high char yield polymers and silsesquioxane precursors are provided.

  3. Light cone matrix product

    SciTech Connect

    Hastings, Matthew B

    2009-01-01

    We show how to combine the light-cone and matrix product algorithms to simulate quantum systems far from equilibrium for long times. For the case of the XXZ spin chain at {Delta} = 0.5, we simulate to a time of {approx} 22.5. While part of the long simulation time is due to the use of the light-cone method, we also describe a modification of the infinite time-evolving bond decimation algorithm with improved numerical stability, and we describe how to incorporate symmetry into this algorithm. While statistical sampling error means that we are not yet able to make a definite statement, the behavior of the simulation at long times indicates the appearance of either 'revivals' in the order parameter as predicted by Hastings and Levitov (e-print arXiv:0806.4283) or of a distinct shoulder in the decay of the order parameter.

  4. Google matrix of Twitter

    NASA Astrophysics Data System (ADS)

    Frahm, K. M.; Shepelyansky, D. L.

    2012-10-01

    We construct the Google matrix of the entire Twitter network, dated by July 2009, and analyze its spectrum and eigenstate properties including the PageRank and CheiRank vectors and 2DRanking of all nodes. Our studies show much stronger inter-connectivity between top PageRank nodes for the Twitter network compared to the networks of Wikipedia and British Universities studied previously. Our analysis allows to locate the top Twitter users which control the information flow on the network. We argue that this small fraction of the whole number of users, which can be viewed as the social network elite, plays the dominant role in the process of opinion formation on the network.

  5. Hyaluronan: A Matrix Component

    NASA Astrophysics Data System (ADS)

    Rügheimer, Louise

    2008-09-01

    The glucosaminoglycan hyaluronan is a key component of the extracellular matrix. It is a large, negatively charged molecule that can act as an ion exchange reservoir for positive ions. Hyaluronan is involved in renomedullary water handling through its water-binding capacity. In the renal medulla, the main source for hyaluronan production is the renomedullary interstitial cells. Hyaluronan synthases are found in the inner part of the plasma membrane and polymerize hyaluronan chains which are extruded into the extracellular space. Hyaluronidases are a family of enzymes involved in the degradation of hyaluronan. They have a wide range of properties, including differences in size, inhibitor sensitivities, catalytic mechanisms, substrate specificities and pH optima.

  6. Mixed Mode Matrix Multiplication

    SciTech Connect

    Meng-Shiou Wu; Srinivas Aluru; Ricky A. Kendall

    2004-09-30

    In modern clustering environments where the memory hierarchy has many layers (distributed memory, shared memory layer, cache,...), an important question is how to fully utilize all available resources and identify the most dominant layer in certain computations. When combining algorithms on all layers together, what would be the best method to get the best performance out of all the resources we have? Mixed mode programming model that uses thread programming on the shared memory layer and message passing programming on the distributed memory layer is a method that many researchers are using to utilize the memory resources. In this paper, they take an algorithmic approach that uses matrix multiplication as a tool to show how cache algorithms affect the performance of both shared memory and distributed memory algorithms. They show that with good underlying cache algorithm, overall performance is stable. When underlying cache algorithm is bad, superlinear speedup may occur, and an increasing number of threads may also improve performance.

  7. Matrix membranes and integrability

    SciTech Connect

    Zachos, C.; Fairlie, D.; Curtright, T.

    1997-06-01

    This is a pedagogical digest of results reported in Curtright, Fairlie, {ampersand} Zachos 1997, and an explicit implementation of Euler`s construction for the solution of the Poisson Bracket dual Nahm equation. But it does not cover 9 and 10-dimensional systems, and subsequent progress on them Fairlie 1997. Cubic interactions are considered in 3 and 7 space dimensions, respectively, for bosonic membranes in Poisson Bracket form. Their symmetries and vacuum configurations are explored. Their associated first order equations are transformed to Nahm`s equations, and are hence seen to be integrable, for the 3-dimensional case, by virtue of the explicit Lax pair provided. Most constructions introduced also apply to matrix commutator or Moyal Bracket analogs.

  8. Herbicide Persistence in Seawater Simulation Experiments.

    PubMed

    Mercurio, Philip; Mueller, Jochen F; Eaglesham, Geoff; Flores, Florita; Negri, Andrew P

    2015-01-01

    Herbicides are detected year-round in marine waters, including those of the World Heritage listed Great Barrier Reef (GBR). The few previous studies that have investigated herbicide persistence in seawater generally reported half-lives in the order of months, and several studies were too short to detect significant degradation. Here we investigated the persistence of eight herbicides commonly detected in the GBR or its catchments in standard OECD simulation flask experiments, but with the aim to mimic natural conditions similar to those found on the GBR (i.e., relatively low herbicide concentrations, typical temperatures, light and microbial communities). Very little degradation was recorded over the standard 60 d period (Experiment 1) so a second experiment was extended to 365 d. Half-lives of PSII herbicides ametryn, atrazine, diuron, hexazinone and tebuthiuron were consistently greater than a year, indicating high persistence. The detection of atrazine and diuron metabolites and longer persistence in mercuric chloride-treated seawater confirmed that biodegradation contributed to the breakdown of herbicides. The shortest half-life recorded was 88 d for growth-regulating herbicide 2,4-D at 31°C in the dark, while the fatty acid-inhibitor metolachlor exhibited a minimum half-life of 281 d. The presence of moderate light and elevated temperatures affected the persistence of most of the herbicides; however, the scale and direction of the differences were not predictable and were likely due to changes in microbial community composition. The persistence estimates here represent some of the first appropriate data for application in risk assessments for herbicide exposure in tropical marine systems. The long persistence of herbicides identified in the present study helps explain detection of herbicides in nearshore waters of the GBR year round. Little degradation of these herbicides would be expected during the wet season with runoff and associated flood plumes

  9. Characterization of Bacillus anthracis Persistence In Vivo

    PubMed Central

    Jenkins, Sarah A.; Xu, Yi

    2013-01-01

    Pulmonary exposure to Bacillus anthracis spores initiates inhalational anthrax, a life-threatening infection. It is known that dormant spores can be recovered from the lungs of infected animals months after the initial spore exposure. Consequently, a 60-day course antibiotic treatment is recommended for exposed individuals. However, there has been little information regarding details or mechanisms of spore persistence in vivo. In this study, we investigated spore persistence in a mouse model. The results indicated that weeks after intranasal inoculation with B. anthracis spores, substantial amounts of spores could be recovered from the mouse lung. Moreover, spores of B. anthracis were significantly better at persisting in the lung than spores of a non-pathogenic Bacillus subtilis strain. The majority of B. anthracis spores in the lung were tightly associated with the lung tissue, as they could not be readily removed by lavage. Immunofluorescence staining of lung sections showed that spores associated with the alveolar and airway epithelium. Confocal analysis indicated that some of the spores were inside epithelial cells. This was further confirmed by differential immunofluorescence staining of lung cells harvested from the infected lungs, suggesting that association with lung epithelial cells may provide an advantage to spore persistence in the lung. There was no or very mild inflammation in the infected lungs. Furthermore, spores were present in the lung tissue as single spores rather than in clusters. We also showed that the anthrax toxins did not play a role in persistence. Together, the results suggest that B. anthracis spores have special properties that promote their persistence in the lung, and that there may be multiple mechanisms contributing to spore persistence. PMID:23750280

  10. Herbicide Persistence in Seawater Simulation Experiments

    PubMed Central

    Mercurio, Philip; Mueller, Jochen F.; Eaglesham, Geoff; Flores, Florita; Negri, Andrew P.

    2015-01-01

    Herbicides are detected year-round in marine waters, including those of the World Heritage listed Great Barrier Reef (GBR). The few previous studies that have investigated herbicide persistence in seawater generally reported half-lives in the order of months, and several studies were too short to detect significant degradation. Here we investigated the persistence of eight herbicides commonly detected in the GBR or its catchments in standard OECD simulation flask experiments, but with the aim to mimic natural conditions similar to those found on the GBR (i.e., relatively low herbicide concentrations, typical temperatures, light and microbial communities). Very little degradation was recorded over the standard 60 d period (Experiment 1) so a second experiment was extended to 365 d. Half-lives of PSII herbicides ametryn, atrazine, diuron, hexazinone and tebuthiuron were consistently greater than a year, indicating high persistence. The detection of atrazine and diuron metabolites and longer persistence in mercuric chloride-treated seawater confirmed that biodegradation contributed to the breakdown of herbicides. The shortest half-life recorded was 88 d for growth-regulating herbicide 2,4-D at 31°C in the dark, while the fatty acid-inhibitor metolachlor exhibited a minimum half-life of 281 d. The presence of moderate light and elevated temperatures affected the persistence of most of the herbicides; however, the scale and direction of the differences were not predictable and were likely due to changes in microbial community composition. The persistence estimates here represent some of the first appropriate data for application in risk assessments for herbicide exposure in tropical marine systems. The long persistence of herbicides identified in the present study helps explain detection of herbicides in nearshore waters of the GBR year round. Little degradation of these herbicides would be expected during the wet season with runoff and associated flood plumes

  11. Persistent Scatterer Interferometry Using SENTINEL-1 Data

    NASA Astrophysics Data System (ADS)

    Crosetto, M.; Monserrat, O.; Devanthéry, N.; Cuevas-González, M.; Barra, A.; Crippa, B.

    2016-06-01

    This paper is focused on deformation monitoring using a Persistent Scatterer Interferometry technique and the interferometric SAR data acquired by the Sentinel-1 satellite of the European Space Agency. The first part of the paper describes the procedure used to process and analyze Sentinel-1 interferometric SAR data. Two main approaches are described. The first one is a simplified Persistent Scatterer Interferometry approach that exploits two key properties of the Sentinel-1 data: the high coherence of the 12-day interferograms and the reduced orbital tube. The second approach is a full Persistent Scatterer Interferometry approach, where a more sophisticate data treatment is employed. The second part of the paper illustrates the results obtained with the two processing approaches. Two case studies are described. The first one concerns landslide detection and monitoring. In this case, the simplified Persistent Scatterer Interferometry approach was used. The second one regards the deformation monitoring of an urban area. In this case, a full Persistent Scatterer Interferometry approach was used.

  12. Dry season streamflow persistence in seasonal climates

    NASA Astrophysics Data System (ADS)

    Dralle, David N.; Karst, Nathaniel J.; Thompson, Sally E.

    2016-01-01

    Seasonally dry ecosystems exhibit periods of high water availability followed by extended intervals during which rainfall is negligible and streamflows decline. Eventually, such declining flows will fall below the minimum values required to support ecosystem functions or services. The time at which dry season flows drop below these minimum values (Q*), relative to the start of the dry season, is termed the "persistence time" (). The persistence time determines how long seasonal streams can support various human or ecological functions during the dry season. In this study, we extended recent work in the stochastic hydrology of seasonally dry climates to develop an analytical model for the probability distribution function (PDF) of the persistence time. The proposed model accurately captures the mean of the persistence time distribution, but underestimates its variance. We demonstrate that this underestimation arises in part due to correlation between the parameters used to describe the dry season recession, but that this correlation can be removed by rescaling the flow variables. The mean persistence time predictions form one example of the broader class of streamflow statistics known as crossing properties, which could feasibly be combined with simple ecological models to form a basis for rapid risk assessment under different climate or management scenarios.

  13. Persistent Pain and Sensory Abnormalities after Abdominoplasty

    PubMed Central

    Finnerup, Kenneth; Andresen, Sven R.; Nikolajsen, Lone; Finnerup, Nanna B.

    2015-01-01

    Background: Persistent postsurgical pain is a well-recognized problem after a number of common surgical procedures, such as amputation, thoracotomy, and inguinal hernia repair. Less is known about persistent pain after cosmetic surgical procedures. We, therefore, decided to study the incidence and characteristics of persistent pain after abdominoplasty, which is one of the most frequent cosmetic surgical procedures. Methods: In September 2014, a link to a web-based questionnaire was mailed to 217 patients who had undergone abdominoplasty between 2006 and 2014 at the Department of Plastic Surgery, Aalborg University Hospital, Denmark. The questionnaire included questions about pain and sensory abnormalities located to the abdominal skin, and physical and psychological function; patient satisfaction with surgery was rated on a 4-point scale. Results: One hundred seventy patients answered the questionnaire. Fourteen patients (8.2%) reported pain within the past 7 days related to the abdominoplasty. Abnormal abdominal skin sensation was common and reported by 138 patients (81%). Sensory hypersensitivity was associated with the presence of persistent pain. Satisfaction with the procedure was reported by 149 (88%) patients. The majority of patients reported improvement on all physical and psychological factors. Patients with pain were more often disappointed with the surgery and unwilling to recommend the surgery. Conclusions: Overall, patients were satisfied with the procedure, although abnormal abdominal skin sensation was common. However, there is a risk of developing persistent neuropathic pain after abdominoplasty, and patients should be informed about this before surgery. PMID:26893986

  14. On persistence interfaces for scientific data stores

    SciTech Connect

    Malon, D.M.; May, E.N.

    1996-02-09

    A common dilemma among builders of large scientific data stores is whether to use a lightweight object persistence manager or a genuine object-oriented database. There are often good reasons to consider each of these strategies; a few are described in this paper. Too often, however, electing to use a lightweight approach has meant programming to an interface that is entirely different than that expected by commercial object-oriented databases. With the emergence of object database standards, it is possible to provide an interface to persistence managers that does not needlessly inhibit coexistence with (and, perhaps, eventual migration to) object-oriented databases. This paper describes an implementation of a substantial subset of the ODMG-93[1]C++ specification that allows clients to use many of today`s lightweight object persistence managers through an interface that conforms to the ODMG standard. We also describe a minimal interface that persistence software should support in order to provide persistence services for ODMG implementations.

  15. Persistent agents in Axelrod's social dynamics model

    NASA Astrophysics Data System (ADS)

    Reia, Sandro M.; Neves, Ubiraci P. C.

    2016-01-01

    Axelrod's model of social dynamics has been studied under the effect of external media. Here we study the formation of cultural domains in the model by introducing persistent agents. These are agents whose cultural traits are not allowed to change but may be spread through local neighborhood. In the absence of persistent agents, the system is known to present a transition from a monocultural to a multicultural regime at some critical Q (number of traits). Our results reveal a dependence of critical Q on the occupation probability p of persistent agents and we obtain the phase diagram of the model in the (p,Q) -plane. The critical locus is explained by the competition of two opposite forces named here barrier and bonding effects. Such forces are verified to be caused by non-persistent agents which adhere (adherent agents) to the set of traits of persistent ones. The adherence (concentration of adherent agents) as a function of p is found to decay for constant Q. Furthermore, adherence as a function of Q is found to decay as a power law with constant p.

  16. A matrix model for WZW

    NASA Astrophysics Data System (ADS)

    Dorey, Nick; Tong, David; Turner, Carl

    2016-08-01

    We study a U( N) gauged matrix quantum mechanics which, in the large N limit, is closely related to the chiral WZW conformal field theory. This manifests itself in two ways. First, we construct the left-moving Kac-Moody algebra from matrix degrees of freedom. Secondly, we compute the partition function of the matrix model in terms of Schur and Kostka polynomials and show that, in the large N limit, it coincides with the partition function of the WZW model. This same matrix model was recently shown to describe non-Abelian quantum Hall states and the relationship to the WZW model can be understood in this framework.

  17. The Childrens Total Exposure to Persistent Pesticides and Other Persistent Organic Pollutants (CTEPP) Study

    EPA Science Inventory

    The Children's Total Exposure to Persistent Pesticides and Other Persistent Pollutant (CTEPP) study was one of the largest aggregate exposure studies of young children in the United States. The CTEPP study examined the exposures of about 260 preschool children and their primary a...

  18. The Childrens Total Exposure to Persistent Pesticides and Other Persistent Organic Pollutants (CTEPP) Study -- Ohio

    EPA Science Inventory

    The Children's Total Exposure to Persistent Pesticides and Other Persistent Pollutant (CTEPP) study was one of the largest aggregate exposure studies of young children in the United States. The CTEPP study examined the exposures of about 260 preschool children and their primary a...

  19. THE CHILDRENS TOTAL EXPOSURE TO PERSISTENT PESTICIDES AND OTHER PERSISTENT ORGANIC POLLUTANTS (CTEPP) STUDY -- NORTH CAROLINA

    EPA Science Inventory

    The Children's Total Exposure to Persistent Pesticides and Other Persistent Pollutant (CTEPP) study was one of the largest aggregate exposure studies of young children in the United States. The CTEPP study examined the exposures of about 260 preschool children and their primary a...

  20. Contrasting persistence strategies in Salmonella and Mycobacterium

    PubMed Central

    McKinney, John D.

    2009-01-01

    Summary Long-term survival of persistent bacterial pathogens in mammalian hosts critically depends on their ability to avoid elimination by innate and adaptive immune responses. The persistent human pathogens that cause typhoid fever and tuberculosis exemplify alternative strategies for survival in the host: immune evasion and immune adaptation, respectively. Salmonella enterica serotype Typhi evades host innate immune responses and inflammation by expressing factors that interfere with its detection as a Gram-negative bacterium, enabling persistent colonization of an immunologically privileged niche, the gallbladder. In contrast, Mycobacterium tuberculosis has adapted to survive within phagocytic cells, which typically eliminate invading microbes, by deploying stress resistance mechanisms that counteract the harsh environment of the phagolysosome. PMID:20056478

  1. Persistent Structures in the Turbulent Boundary Layer

    NASA Technical Reports Server (NTRS)

    Palumbo, Dan; Chabalko, Chris

    2005-01-01

    Persistent structures in the turbulent boundary layer are located and analyzed. The data are taken from flight experiments on large commercial aircraft. An interval correlation technique is introduced which is able to locate the structures. The Morlet continuous wavelet is shown to not only locates persistent structures but has the added benefit that the pressure data are decomposed in time and frequency. To better understand how power is apportioned among these structures, a discrete Coiflet wavelet is used to decompose the pressure data into orthogonal frequency bands. Results indicate that some structures persist a great deal longer in the TBL than would be expected. These structure contain significant power and may be a primary source of vibration energy in the airframe.

  2. Persistent hydrogen bonding in polymorphic crystal structures.

    PubMed

    Galek, Peter T A; Fábián, László; Allen, Frank H

    2009-02-01

    The significance of hydrogen bonding and its variability in polymorphic crystal structures is explored using new automated structural analysis methods. The concept of a chemically equivalent hydrogen bond is defined, which may be identified in pairs of structures, revealing those types of bonds that may persist, or not, in moving from one polymorphic form to another. Their frequency and nature are investigated in 882 polymorphic structures from the Cambridge Structural Database. A new method to compare conformations of equivalent molecules is introduced and applied to derive distinct subsets of conformational and packing polymorphs. The roles of chemical functionality and hydrogen-bond geometry in persistent interactions are systematically explored. Detailed structural comparisons reveal a large majority of persistent hydrogen bonds that are energetically crucial to structural stability. PMID:19155561

  3. Persistence and predictability in a perfect model

    NASA Technical Reports Server (NTRS)

    Schubert, Siegfried D.; Suarez, Max J.; Schemm, Jae-Kyung

    1992-01-01

    A realistic two-level GCM is used to examine the relationship between predictability and persistence. Predictability is measured by the average divergence of ensembles of solutions starting from perturbed initial conditions, and persistence is defined in terms of the autocorrelation function based on a single long-term model integration. The average skill of the dynamical forecasts is compared with the skill of simple persistence-based statistical forecasts. For initial errors comparable in magnitude to present-day analysis errors, the statistical forecast loses all skill after about one week, reflecting the lifetime of the lowest frequency fluctuations in the model. Large ensemble mean dynamical forecasts would be expected to remain skillful for about 3 wk. The disparity between the skill of the statistical and dynamical forecasts is greater for the higher frequency modes, which have little memory beyond 1 d, yet remain predictable for about 2 wk. The results are analyzed in terms of two characteristic time scales.

  4. Matrix market: a web resource for test matrix collection

    SciTech Connect

    Boisvert, R.F.; Pozo, R.; Remington, K.; Barrett, R.F.; Dongarra, J.J. /

    1996-05-30

    We describe a repository of data for the testing of numerical algorithms and mathematical software for matrix computations. The repository is designed to accommodate both dense and sparse matrices, as well as software to generate matrices. It has been seeded with the well known Harwell-Boeing sparse matrix collection. The raw data files have been augmented with an integrated World Wide Web interface which describes the matrices in the collection quantitatively and visually, For example, each matrix has a Web page which details its attributes, graphically depicts its sparsity pattern, and provides access to the matrix itself in several formats. In addition, a search mechanism is included which allows retrieval of matrices based on a variety of attributes, such as type and size, as well as through free-text search in abstracts. The URL is http://math.nist.gov/MatrixMarket.

  5. High Energy Radiation Induced Activation of COX-2 and MMP-9 is Mediated by NF-kappaB

    NASA Astrophysics Data System (ADS)

    Rolle, G.; Munyu, S.; Jejelowo, O. A.; Sodipe, A.; Shishodia, S.

    2010-04-01

    Space radiation is a known carcinogen, and astronauts are exposed to high-energy radiation. In this study, we demonstrate that high-energy radiation activates cylooxygenase-2 and matrix metalloproteinase-9 through the NF-kB pathway.

  6. Glass matrix armor

    DOEpatents

    Calkins, Noel C.

    1991-01-01

    An armor system which utilizes glass. A plurality of constraint cells are mounted on a surface of a substrate, which is metal armor plate or a similar tough material, such that the cells almost completely cover the surface of the substrate. Each constraint cell has a projectile-receiving wall parallel to the substrate surface and has sides which are perpendicular to and surround the perimeter of the receiving wall. The cells are mounted such that, in one embodiment, the substrate surface serves as a sixth side or closure for each cell. Each cell has inside of it a plate, termed the front plate, which is parallel to and in contact with substantially all of the inside surface of the receiving wall. The balance of each cell is completely filled with a projectile-abrading material consisting of glass and a ceramic material and, in certain embodiments, a polymeric material. The glass may be in monolithic form or particles of ceramic may be dispersed in a glass matrix. The ceramic material may be in monolithic form or may be in the form of particles dispersed in glass or dispersed in said polymer.

  7. Hypercube matrix computation task

    NASA Technical Reports Server (NTRS)

    Calalo, R.; Imbriale, W.; Liewer, P.; Lyons, J.; Manshadi, F.; Patterson, J.

    1987-01-01

    The Hypercube Matrix Computation (Year 1986-1987) task investigated the applicability of a parallel computing architecture to the solution of large scale electromagnetic scattering problems. Two existing electromagnetic scattering codes were selected for conversion to the Mark III Hypercube concurrent computing environment. They were selected so that the underlying numerical algorithms utilized would be different thereby providing a more thorough evaluation of the appropriateness of the parallel environment for these types of problems. The first code was a frequency domain method of moments solution, NEC-2, developed at Lawrence Livermore National Laboratory. The second code was a time domain finite difference solution of Maxwell's equations to solve for the scattered fields. Once the codes were implemented on the hypercube and verified to obtain correct solutions by comparing the results with those from sequential runs, several measures were used to evaluate the performance of the two codes. First, a comparison was provided of the problem size possible on the hypercube with 128 megabytes of memory for a 32-node configuration with that available in a typical sequential user environment of 4 to 8 megabytes. Then, the performance of the codes was anlyzed for the computational speedup attained by the parallel architecture.

  8. Hybridized polymer matrix composites

    NASA Technical Reports Server (NTRS)

    House, E. E.; Hoggatt, J. T.; Symonds, W. A.

    1980-01-01

    The extent to which graphite fibers are released from resin matrix composites that are exposed to fire and impact conditions was determined. Laboratory simulations of those conditions that could exist in the event of an aircraft crash and burn situation were evaluated. The effectiveness of various hybridizing concepts in preventing this release of graphite fibers were also evaluated. The baseline (i.e., unhybridized) laminates examined were prepared from commercially available graphite/epoxy, graphite/polyimide, and graphite/phenolic materials. Hybridizing concepts investigated included resin fillers, laminate coatings, resin blending, and mechanical interlocking of the graphite reinforcement. The baseline and hybridized laminates' mechanical properties, before and after isothermal and humidity aging, were also compared. It was found that a small amount of graphite fiber was released from the graphite/epoxy laminates during the burn and impact conditions used in this program. However, the extent to which the fibers were released is not considered a severe enough problem to preclude the use of graphite reinforced composites in civil aircraft structure. It also was found that several hybrid concepts eliminated this fiber release. Isothermal and humidity aging did not appear to alter the fiber release tendencies.

  9. Emergency Response Synchronization Matrix

    Energy Science and Technology Software Center (ESTSC)

    1999-06-01

    An emergency response to a disaster is complex, requiring the rapid integration, coordination, and synchronization of multiple levels of governmental and non-governmental organizations from numerous jurisdictions into a unified community response. For example, a community’s response actions to a fixed site hazardous materials incident could occur in an area extending from an on-site storage location to points 25 or more miles away. Response actions are directed and controlled by local governments and agencies situated withinmore » the response area, as well as by state and federal operaticns centers quite removed from the area of impact. Time is critical and the protective action decision-making process is greatly compressed. The response community must carefully plan and coordinate response operations in order to have confidence that they will be effectively implemented when faced with the potentially catastrophic nature of such releases. A graphical depiction of the entire response process via an emergency response synchronization matrix is an effective tool in optimizing the planning, exercising, and implementation of emergency plans. This system—based approach to emergency planning depicts how a community organizes its response tasks across space and time in relation to hazard actions. It provides the opportunity to make real—time adjustments as necessary for maximizing the often limited resources in protecting area residents. A response must involve the entire community and must not be limited by individual jurisdictions and organizations acting on their own without coordination, integration, and synchronization.« less

  10. Chronic Bacterial Pathogens: Mechanisms of Persistence

    PubMed Central

    Byndloss, Mariana X.; Tsolis, Renee M

    2015-01-01

    Summary Many bacterial pathogens can cause acute infections that are cleared with onset of adaptive immunity, however a subset of these pathogens can establish persistent, and sometimes lifelong infections. While bacteria causing chronic infections are phylogenetically diverse, they share common features in their interactions with the host that enable a protracted period of colonization. This chapter will compare the persistence strategies of two chronic pathogens from the Proteobacteria, Brucella abortus, and Salmonella enterica serovar Typhi (S. Typhi) to consider how these two pathogens, which are very different at the genomic level, can utilize common strategies to evade immune clearance to cause chronic intracellular infections of the mononuclear phagocyte system. PMID:27227304

  11. Trigeminal neuralgia and persistent trigeminal artery.

    PubMed

    Conforti, Renata; Parlato, Raffaele Stefano; De Paulis, Danilo; Cirillo, Mario; Marrone, Valeria; Cirillo, Sossio; Moraci, Aldo; Parlato, Ciro

    2012-12-01

    We report a case of trigeminal neuralgia caused by persistent trigeminal artery (PTA) associated with asymptomatic left temporal cavernoma. Our patient presented unstable blood hypertension and the pain of typical trigeminal neuralgia over the second and third divisions of the nerve in the right side of the face. The attacks were often precipitated during physical exertion. MRI and Angio-MRI revealed the persistent carotid basilar anastomosis and occasionally left parietal cavernoma. After drug treatment of blood hypertension, spontaneous recovery of neuralgia was observed and we planned surgical treatment of left temporal cavernoma. PMID:22246457

  12. Amnestically Induced Persistence in Random Walks

    NASA Astrophysics Data System (ADS)

    Cressoni, J. C.; da Silva, Marco Antonio Alves; Viswanathan, G. M.

    2007-02-01

    We study how the Hurst exponent α depends on the fraction f of the total time t remembered by non-Markovian random walkers that recall only the distant past. We find that otherwise nonpersistent random walkers switch to persistent behavior when inflicted with significant memory loss. Such memory losses induce the probability density function of the walker’s position to undergo a transition from Gaussian to non-Gaussian. We interpret these findings of persistence in terms of a breakdown of self-regulation mechanisms and discuss their possible relevance to some of the burdensome behavioral and psychological symptoms of Alzheimer’s disease and other dementias.

  13. Infection persistence time of Aedes breeding habitats

    NASA Astrophysics Data System (ADS)

    Bicout, D. J.; Chalvet-Monfray, K.; Sabatier, P.

    2002-03-01

    The Aedes mosquito species are capable of maintaining the circulation of viruses only by the strategy of transovarial transmission and diapause of eggs. It is found that when the transovarial transmission is inhibited, the survival time of the presence of viruses in a given mosquito habitat is limited from above by the eggs lifetime. In contrast, when the transovarial transmission is turned on, the infection persistence time may largely exceed both the eggs lifetime and flooding period depending upon the production rate of infected eggs. We present a simple model allowing the derivation of analytical expressions of the infection persistence time.

  14. Nicotine replacement therapies: patient safety and persistence

    PubMed Central

    Ferguson, Stuart G; Shiffman, Saul; Gitchell, Joseph G

    2011-01-01

    Nicotine replacement therapy (NRT) has become a central part of the treatment of nicotine dependence. However, NRT’s potential efficacy is limited to some extent by patient adherence and persistence. Here we review the relationship between NRT compliance and adherence, and overall treatment outcome. We then examine the factors that likely impact on treatment compliance and persistence, with a special focus on users’ perceptions of treatment safety and efficacy as possible mediators. Potential clinical strategies for improving suboptimal medication use are also discussed. PMID:22915971

  15. Persistent migraine aura in an adolescent girl.

    PubMed

    Bruen, Robin; Peng, Si Liang; Perreault, Sebastien; Major, Philippe; Ospina, Luis H

    2013-08-01

    A 14-year-old girl presented with a prolonged migraine visual aura of several weeks' duration. Symptoms gradually resolved over a 6-week period, with no recurrence of visual aura over a 20-month follow-up period. Although there is significant overlap between the features of stereotypical and persistent migraine auras, or "visual snow," the latter tend to be unformed and can occupy the entire visual field of both eyes. To our knowledge, this phenomenon has been reported only twice before in children. Recognition of its features will allow the pediatric ophthalmologist to differentiate persistent visual aura from visual hallucinations. PMID:23871134

  16. Ceramic matrix composite article and process of fabricating a ceramic matrix composite article

    DOEpatents

    Cairo, Ronald Robert; DiMascio, Paul Stephen; Parolini, Jason Robert

    2016-01-12

    A ceramic matrix composite article and a process of fabricating a ceramic matrix composite are disclosed. The ceramic matrix composite article includes a matrix distribution pattern formed by a manifold and ceramic matrix composite plies laid up on the matrix distribution pattern, includes the manifold, or a combination thereof. The manifold includes one or more matrix distribution channels operably connected to a delivery interface, the delivery interface configured for providing matrix material to one or more of the ceramic matrix composite plies. The process includes providing the manifold, forming the matrix distribution pattern by transporting the matrix material through the manifold, and contacting the ceramic matrix composite plies with the matrix material.

  17. Synthetic Division and Matrix Factorization

    ERIC Educational Resources Information Center

    Barabe, Samuel; Dubeau, Franc

    2007-01-01

    Synthetic division is viewed as a change of basis for polynomials written under the Newton form. Then, the transition matrices obtained from a sequence of changes of basis are used to factorize the inverse of a bidiagonal matrix or a block bidiagonal matrix.

  18. How to Study a Matrix

    ERIC Educational Resources Information Center

    Jairam, Dharmananda; Kiewra, Kenneth A.; Kauffman, Douglas F.; Zhao, Ruomeng

    2012-01-01

    This study investigated how best to study a matrix. Fifty-three participants studied a matrix topically (1 column at a time), categorically (1 row at a time), or in a unified way (all at once). Results revealed that categorical and unified study produced higher: (a) performance on relationship and fact tests, (b) study material satisfaction, and…

  19. Distribution of the transfer matrix in disordered wires

    NASA Astrophysics Data System (ADS)

    Ancliff, M.

    2016-07-01

    A closed expression is derived for the probability distribution of the transfer matrix for a particle moving in one-dimension with delta-correlated, weak disorder. The change in the distribution as a function of wire length is described by a diffusion equation on the {SU}(1,1) group, which is solved through the decomposition of the regular representation into irreducible components. The expression generalizes a number of well-known results, including the distributions of the transmission coefficient and local density of states. As an application, the average single energy-level contribution to the persistent current in a flux threaded ring is derived.

  20. Persistent ion beam induced conductivity in zinc oxide nanowires

    SciTech Connect

    Johannes, Andreas; Niepelt, Raphael; Gnauck, Martin; Ronning, Carsten

    2011-12-19

    We report persistently increased conduction in ZnO nanowires irradiated by ion beam with various ion energies and species. This effect is shown to be related to the already known persistent photo conduction in ZnO and dubbed persistent ion beam induced conduction. Both effects show similar excitation efficiency, decay rates, and chemical sensitivity. Persistent ion beam induced conduction will potentially allow countable (i.e., single dopant) implantation in ZnO nanostructures and other materials showing persistent photo conduction.

  1. Matrix Metalloproteinase-3 (MMP-3) Is an Endogenous Activator of the MMP-9 Secreted by Placental Leukocytes: Implication in Human Labor

    PubMed Central

    Flores-Pliego, Arturo; Espejel-Nuñez, Aurora; Castillo-Castrejon, Marisol; Meraz-Cruz, Noemi; Beltran-Montoya, Jorge; Zaga-Clavellina, Veronica; Nava-Salazar, Sonia; Sanchez-Martinez, Maribel; Vadillo-Ortega, Felipe; Estrada-Gutierrez, Guadalupe

    2015-01-01

    Background The activity of matrix degrading enzymes plays a leading role in the rupture of the fetal membranes under normal and pathological human labor, and matrix metalloproteinase-9 (MMP-9) it is considered a biomarker of this event. To gain further insight into local MMP-9 origin and activation, in this study we analyzed the contribution of human placental leukocytes to MMP-9 secretion and explored the local mechanisms of the pro-enzyme activation. Methods Placental blood leukocytes were obtained from women at term gestation without labor and maintained in culture up to 72 h. MMP-9 activity in the culture supernatants was determined by zymography and using a specific substrate. The presence of a potential pro-MMP-9 activator in the culture supernatants was monitored using a recombinant biotin-labeled human pro-MMP-9. To characterize the endogenous pro-MMP-9 activator, MMP-1, -3, -7 and -9 were measured by multiplex assay in the supernatants, and an inhibition assay of MMP-9 activation was performed using an anti-human MMP-3 and a specific MMP-3 inhibitor. Finally, production of MMP-9 and MMP-3 in placental leukocytes obtained from term pregnancies with and without labor was assessed by immunofluorescence. Results Placental leukocytes spontaneously secreted pro-MMP-9 after 24 h of culture, increasing significantly at 48 h (P≤0.05), when the active form of MMP-9 was detected. Culture supernatants activated the recombinant pro-MMP-9 showing that placental leukocytes secrete the activator. A significant increase in MMP-3 secretion by placental leukocytes was observed since 48 h in culture (P≤0.05) and up to 72 h (P≤0.001), when concentration reached its maximum value. Specific activity of MMP-9 decreased significantly (P≤0.005) when an anti-MMP-3 antibody or a specific MMP-3 inhibitor were added to the culture media. Placental leukocytes from term labor produced more MMP-9 and MMP-3 compared to term non-labor cells. Conclusions In this work we confirm that

  2. Study Circle Guide: Adult Student Persistence

    ERIC Educational Resources Information Center

    National Center for the Study of Adult Learning and Literacy (NCSALL), 2006

    2006-01-01

    This study circle was created by the National Center for the Study of Adult Learning and Literacy (NCSALL). The study circle is part of NCSALL's efforts to help connect research and practice in the field of adult basic education and adult literacy. The Adult Student Persistence Study Circle is one of a series of study circles that NCSALL has…

  3. Inchworm, Inchworm: Persistent Problems in Reading Education.

    ERIC Educational Resources Information Center

    McCullough, Constance M., Ed.

    The papers in this volume represent thoughts about the state of the art of teaching reading (with an emphasis on persistent problems) of many recognized authorities in the field of reading education. Eight of the articles were originally presented at a joint Reading Hall of Fame and International Reading Association (IRA) symposium at the IRA…

  4. TOXICITY PERSISTENCE IN PRICKLY PEAR CREEK, MONTANA

    EPA Science Inventory

    Instream toxicity tests using the larval fathead minnow Pimephales promelas and the cladoceran Ceriodaphnia reticulata were conducted on Prickly Pear Creek, Montana waters to study toxicity persistence in a stream. The toxicity source was Spring Creek, a tributary of Prickly Pear...

  5. The Enigmatic Persistence of Anorexia Nervosa

    PubMed Central

    Walsh, B. Timothy

    2014-01-01

    Objective In this review, based on recent advances in cognitive neuroscience, the author presents a formulation in which the marked persistence of anorexia nervosa can be usefully understood as a well-ingrained maladaptive habit. Method The author reviewed the relevant literature on the development and course of anorexia nervosa and interpreted critical features in light of developments in cognitive neuroscience. Results Anorexia nervosa is a well characterized disorder with remarkable persistence both across history and among affected individuals. Food restriction, the salient behavioral feature of the disorder, often begins innocently but gradually takes on a life of its own. Over time, it becomes highly entrenched and resistant to change through either psychological or pharmacological treatment. Cognitive neuroscience has described two related but distinct processes that underlie the acquisition of new patterns of behavior, namely, action-outcome and stimulus-response learning. It is likely that both processes are engaged in the development of anorexia nervosa and that stimulus-response learning (that is, habit formation) is critical to the persistence of the dieting behavior. Conclusions The formulation of the dieting behavior characteristic of anorexia nervosa as a well-entrenched habit provides a basis for understanding the striking persistence of this disorder. This model helps explain the resistance of anorexia nervosa to interventions that have established efficacy in related disorders and implies that addressing the dieting behavior is critical, especially early in the course of the illness, before it has become ingrained. PMID:23429750

  6. Persistence of Ebola Virus in Sterilized Wastewater

    PubMed Central

    2015-01-01

    In the wake of the ongoing 2014/2015 Ebola virus outbreak, significant questions regarding the appropriate handling of Ebola virus-contaminated liquid waste remain, including the persistence of Ebola virus in wastewater. To address these uncertainties, we evaluated the persistence of Ebola virus spiked in sterilized domestic sewage. The viral titer decreased approximately 99% within the first test day from an initial viral titer of 106 TCID50 mL–1; however, it could not be determined if this initial rapid decrease was due to aggregation or inactivation of the viral particles. The subsequent viral titer decrease was less rapid, and infectious Ebola virus particles persisted for all 8 days of the test. The inactivation constant (k) was determined to be −1.08 (2.1 days for a 90% viral titer decrease). Due to experimental conditions, we believe these results to be an upper bound for Ebola virus persistence in wastewater. Wastewater composition is inherently heterogeneous; subsequently, we caution that interpretation of these results should be made within a holistic assessment, including the effects of wastewater composition, dilution, and potential exposure routes within wastewater infrastructure. While it remains unknown if Ebola virus may be transmitted via wastewater, these data demonstrate a potential exposure route to infectious Ebola virus via wastewater and emphasize the value of a precautionary approach to wastewater handling in an epidemic response. PMID:26523283

  7. Persistence in eye movement during visual search

    NASA Astrophysics Data System (ADS)

    Amor, Tatiana A.; Reis, Saulo D. S.; Campos, Daniel; Herrmann, Hans J.; Andrade, José S.

    2016-02-01

    As any cognitive task, visual search involves a number of underlying processes that cannot be directly observed and measured. In this way, the movement of the eyes certainly represents the most explicit and closest connection we can get to the inner mechanisms governing this cognitive activity. Here we show that the process of eye movement during visual search, consisting of sequences of fixations intercalated by saccades, exhibits distinctive persistent behaviors. Initially, by focusing on saccadic directions and intersaccadic angles, we disclose that the probability distributions of these measures show a clear preference of participants towards a reading-like mechanism (geometrical persistence), whose features and potential advantages for searching/foraging are discussed. We then perform a Multifractal Detrended Fluctuation Analysis (MF-DFA) over the time series of jump magnitudes in the eye trajectory and find that it exhibits a typical multifractal behavior arising from the sequential combination of saccades and fixations. By inspecting the time series composed of only fixational movements, our results reveal instead a monofractal behavior with a Hurst exponent , which indicates the presence of long-range power-law positive correlations (statistical persistence). We expect that our methodological approach can be adopted as a way to understand persistence and strategy-planning during visual search.

  8. Persistence in eye movement during visual search

    PubMed Central

    Amor, Tatiana A.; Reis, Saulo D. S.; Campos, Daniel; Herrmann, Hans J.; Andrade, José S.

    2016-01-01

    As any cognitive task, visual search involves a number of underlying processes that cannot be directly observed and measured. In this way, the movement of the eyes certainly represents the most explicit and closest connection we can get to the inner mechanisms governing this cognitive activity. Here we show that the process of eye movement during visual search, consisting of sequences of fixations intercalated by saccades, exhibits distinctive persistent behaviors. Initially, by focusing on saccadic directions and intersaccadic angles, we disclose that the probability distributions of these measures show a clear preference of participants towards a reading-like mechanism (geometrical persistence), whose features and potential advantages for searching/foraging are discussed. We then perform a Multifractal Detrended Fluctuation Analysis (MF-DFA) over the time series of jump magnitudes in the eye trajectory and find that it exhibits a typical multifractal behavior arising from the sequential combination of saccades and fixations. By inspecting the time series composed of only fixational movements, our results reveal instead a monofractal behavior with a Hurst exponent , which indicates the presence of long-range power-law positive correlations (statistical persistence). We expect that our methodological approach can be adopted as a way to understand persistence and strategy-planning during visual search. PMID:26864680

  9. The Persistent Madness of Greek Hazing.

    ERIC Educational Resources Information Center

    Ruffins, Paul

    1998-01-01

    Origins and persistent reasons for college sorority and fraternity hazing, particularly in black organizations, are examined, including desire for domination, links to childhood abuse, and homoeroticism. The influences of tradition, peer pressure, the need to belong, and desire for solidarity are also considered. Reviews recent research on the…

  10. The role of persistence in chemical evaluations.

    PubMed

    Mackay, Donald; Hughes, Dianne M; Romano, M Luisa; Bonnell, Mark

    2014-10-01

    The initial stage in the assessment and priority setting of chemicals for their potential to cause harm to humans and the environment is usually a hazard assessment employing metrics for persistence, bioaccumulation, and inherent toxicity. This hazard assessment is followed, when necessary, by the more demanding task of risk assessment. Hazard assessment of data and processes influencing persistence are discussed, leading to a number of suggestions for more effective evaluation. These include 1) an initial focus on accurate data for intensive chemical partitioning and reaction half-life properties that are universally applicable as distinct from extensive properties that can be included later on a location-specific basis; 2) separate treatments of near-field and far-field exposures; 3) a focus on persistence and its effect on levels of exposure, especially for substances for which "time to exposure" is less than "time to degradation" and have been termed "pseudo-persistent." We show that "continuously present" is a better descriptor of this concern. Case studies illustrate and support these suggestions. Data on the intensive properties and on exposure pathways are best combined in evaluative multimedia mass balance models that can provide a clear depiction of the likely chemical fate, exposure routes, and levels. The information generated by the mass balance models can serve to justify and direct a full risk assessment that includes region-specific information on chemical quantities, estimates of exposure, and potential for adverse effects. PMID:24753402

  11. PERSISTENT, BIOACCUMULATIVE, AND TOXIC POLLUTANTS (PBTS)

    EPA Science Inventory

    Article describes the class of compounds known as persistent, bioaccumulative, and toxic pollutants (known as PBTs), including the mechanisms responsible for ability to build up the food chain and for causing adverse health effects and ecosystem damage. Exposure to numerous PBTs ...

  12. Paradoxical Understandings Regarding Adult Undergraduate Persistence

    ERIC Educational Resources Information Center

    Kasworm, Carol E.

    2014-01-01

    Historically, characteristics of student persistence and graduation completion were most often linked to strategies which honored the full-time residential younger undergraduate. Adult students have been viewed as high-risk and typically problematic students for continuous enrollment and degree completion. This article explores the key paradoxical…

  13. Anger Expression and Persistence in Young Children

    ERIC Educational Resources Information Center

    He, Jie; Xu, Qinmei; Degnan, Kathryn Amey

    2012-01-01

    This study investigated anger expression during toy removal (TR) in 92 young Chinese children, two to five years of age, and its relations to their persistence in responding to obstacles during two challenging tasks with highly desirable goals [TR and locked box (LB)] and one challenging task with a less desirable goal [impossible perfect circles…

  14. Persistence of Problematic Sexual Behaviors in Children

    ERIC Educational Resources Information Center

    Levesque, Mireille; Bigras, Marc; Pauze, Robert

    2012-01-01

    The purpose of this study was to identify personal and family predictors and correlates of persistence of problematic sexual behaviors (PSB) in children. Participants were the families of 49 children (ages 4-11 years) referred by Child Protective Services in 4 administrative districts of Quebec. Caregivers completed interviews and questionnaires…

  15. Persistence of Value-Driven Attentional Capture

    ERIC Educational Resources Information Center

    Anderson, Brian A.; Yantis, Steven

    2013-01-01

    Stimuli that have previously been associated with the delivery of reward involuntarily capture attention when presented as unrewarded and task-irrelevant distractors in a subsequent visual search task. It is unknown how long such effects of reward learning on attention persist. One possibility is that value-driven attentional biases are plastic…

  16. RISK CHARACTERIZATION OF PERSISTENT NEUROTOXIC CONTAMINANTS

    EPA Science Inventory

    Neurotoxicity is an adverse change in structure or function of the central and/or peripheral nervous system following exposure to a chemical, physical, or biological agent. Thousands of chemicals have been estimated to have neurotoxic potential. Many persistent and bioaccumulat...

  17. High School Economic Composition and College Persistence

    ERIC Educational Resources Information Center

    Niu, Sunny X.; Tienda, Marta

    2013-01-01

    Using a longitudinal sample of Texas high school seniors of 2002 who enrolled in college within the calendar year of high school graduation, we examine variation in college persistence according to the economic composition of their high schools, which serves as a proxy for unmeasured high school attributes that are conductive to postsecondary…

  18. Prerequisites for Persistence in Distance Education

    ERIC Educational Resources Information Center

    Ekstrand, Britten

    2013-01-01

    In the last two decades, distance education has grown worldwide and is now established as a reliable educational method. Accompanying this development, questions about low rates of student persistence have come to interest governments, institutions, and university management. This article is based on an original local study at a university in…

  19. Persistent Marriage Regimes in Changing Times

    ERIC Educational Resources Information Center

    Fussell, Elizabeth; Palloni, Alberto

    2004-01-01

    Marriage among women in Latin America occurs early in life and is nearly universal in spite of the social and economic changes and instability in the region. We use demographic measures to illustrate the precociousness, persistence, and universality of marriage during the past 50 years. We argue that marriage is central to social life because…

  20. The persistence length of adsorbed dendronized polymers.

    PubMed

    Grebikova, Lucie; Kozhuharov, Svilen; Maroni, Plinio; Mikhaylov, Andrey; Dietler, Giovanni; Schlüter, A Dieter; Ullner, Magnus; Borkovec, Michal

    2016-07-21

    The persistence length of cationic dendronized polymers adsorbed onto oppositely charged substrates was studied by atomic force microscopy (AFM) and quantitative image analysis. One can find that a decrease in the ionic strength leads to an increase of the persistence length, but the nature of the substrate and of the generation of the side dendrons influence the persistence length substantially. The strongest effects as the ionic strength is being changed are observed for the fourth generation polymer adsorbed on mica, which is a hydrophilic and highly charged substrate. However, the observed dependence on the ionic strength is much weaker than the one predicted by the Odijk, Skolnik, and Fixman (OSF) theory for semi-flexible chains. Low-generation polymers show a variation with the ionic strength that resembles the one observed for simple and flexible polyelectrolytes in solution. For high-generation polymers, this dependence is weaker. Similar dependencies are found for silica and gold substrates. The observed behavior is probably caused by different extents of screening of the charged groups, which is modified by the polymer generation, and to a lesser extent, the nature of the substrate. For highly ordered pyrolytic graphite (HOPG), which is a hydrophobic and weakly charged substrate, the electrostatic contribution to the persistence length is much smaller. In the latter case, we suspect that specific interactions between the polymer and the substrate also play an important role. PMID:27353115

  1. Persistence of Salmonella typhimurium on Fabrics

    PubMed Central

    Wilkoff, Lee J.; Westbrook, Louise; Dixon, Glen J.

    1969-01-01

    The persistence of Salmonella typhimurium (V-31) on wool blanket, wool gabardine, cotton sheeting, cotton knit jersey, cotton terry cloth, and cotton wash-and-wear fabrics was studied. Three methods of exposure were employed to contaminate the fabrics: direct contact, aerosol, and a lyophilized mixture of bacteria and dust having a high content of textile fibers. After contamination, the fabrics were held in 35 or 78% relative humidity at 25 C. The persistence time of S. typhimurium on fabrics held in 35% relative humidity was substantially longer when the fabrics were contaminated by direct contact or by exposure to dust containing bacteria than when contaminated by exposure to aerosolized cultures. Viable bacterial populations persisted for 24 weeks at relatively high population densities on swatches of wool gabardine, cotton sheeting, cotton knit jersey, and cotton terry cloth exposed by direct contact and held in a humidity of 35%. In 78% humidity, bacterial populations persisted on the fabrics for relatively shorter periods of time regardless of the mode of contamination or fabric type. This organism retained its virulence for Swiss mice after being recovered from wool gabardine swatches held 8 weeks in humidities of 35 or 78% and from cotton terry cloth swatches held 6 weeks in the same humidities. Images PMID:4896883

  2. Persistence in eye movement during visual search.

    PubMed

    Amor, Tatiana A; Reis, Saulo D S; Campos, Daniel; Herrmann, Hans J; Andrade, José S

    2016-01-01

    As any cognitive task, visual search involves a number of underlying processes that cannot be directly observed and measured. In this way, the movement of the eyes certainly represents the most explicit and closest connection we can get to the inner mechanisms governing this cognitive activity. Here we show that the process of eye movement during visual search, consisting of sequences of fixations intercalated by saccades, exhibits distinctive persistent behaviors. Initially, by focusing on saccadic directions and intersaccadic angles, we disclose that the probability distributions of these measures show a clear preference of participants towards a reading-like mechanism (geometrical persistence), whose features and potential advantages for searching/foraging are discussed. We then perform a Multifractal Detrended Fluctuation Analysis (MF-DFA) over the time series of jump magnitudes in the eye trajectory and find that it exhibits a typical multifractal behavior arising from the sequential combination of saccades and fixations. By inspecting the time series composed of only fixational movements, our results reveal instead a monofractal behavior with a Hurst exponent , which indicates the presence of long-range power-law positive correlations (statistical persistence). We expect that our methodological approach can be adopted as a way to understand persistence and strategy-planning during visual search. PMID:26864680

  3. The Myth of Persistence of Vision Revisited.

    ERIC Educational Resources Information Center

    Anderson, Joseph; Anderson, Barbara

    1993-01-01

    Argues that "persistence of vision" myth (the succession of still images perceived as continuous motion) has a place in the history of film scholarship but can no longer be given currency in film theory. Suggests replacement of the concept of the passive viewer implied by the myth by an enlightened understanding of how viewers actually interface…

  4. Registered Nurse Persistence in Baccalaureate Education

    ERIC Educational Resources Information Center

    Krov, Kathleen Nadler

    2010-01-01

    There is a need to increase the number of baccalaureate prepared registered nurses to safely meet the complex healthcare needs of citizens of the United States. Since there is no research on the characteristics of registered nurse students persisting in baccalaureate education, this quantitative descriptive case study was designed to identify the…

  5. Characteristics of Learning Disabilities Persisting into Adolescence.

    ERIC Educational Resources Information Center

    Whyte, Lillian A.

    1984-01-01

    Describes characteristics of learning disabled teenagers. Describes results of a study of 331 secondary students who completed a self-report inventory showing that childhood learning disability characteristics persist into adolescence, most seriously in the areas of visual perception, fine motor skills, and the ability to write and make spatial…

  6. The Persistence of African American College Men

    ERIC Educational Resources Information Center

    Beale, Tyson J.

    2010-01-01

    This study explored the family dynamics of persistent African American college men. These students were typical Black males, not those pre-categorized as high-achieving or unprepared for college. The stories of participants revealed their strength, ambition, and intentions to successfully gain a baccalaureate degree. In general Black males are…

  7. Persistent Fifth Aortic Arch with Coarctation

    PubMed Central

    Kim, Sue Hyun; Choi, Eun-Suk; Cho, Sungkyu; Kim, Woong-Han

    2016-01-01

    Persistent fifth aortic arch (PFAA) is a rare congenital anomaly of the aortic arch frequently associated with other cardiovascular anomalies, such as tetralogy of Fallot and aortic arch coarctation or interruption. We report the case of a neonate with PFAA with coarctation who successfully underwent surgical repair. PMID:26889445

  8. Persistence of Change: Fume Hood Campaign Lessons

    ERIC Educational Resources Information Center

    Feder, Elah; Robinson, Jennifer; Wakefield, Sarah

    2012-01-01

    Purpose: Sustainability initiatives typically operate for a limited time period, but it is often unclear whether they have lasting effects. The purpose of this paper is to examine a laboratory fume hood campaign, in order to identify factors that might contribute or detract from long-term change persistence. Design/methodology/approach: The…

  9. The Academic Library Impact on Student Persistence

    ERIC Educational Resources Information Center

    Emmons, Mark; Wilkinson, Frances C.

    2011-01-01

    What impact does the academic library have on student persistence? This study explores the relationship between traditional library input and output measures of staff, collections, use, and services with fall-to-fall retention and six-year graduation rates at Association of Research Libraries member libraries. When controlling for race/ethnicity…

  10. The Contribution of Student Satisfaction to Persistence

    ERIC Educational Resources Information Center

    Schreiner, Laurie A.; Nelson, Denise D.

    2013-01-01

    This study of nearly 30,000 undergraduates at 61 four-year public and private institutions examines the influence of satisfaction on students' persistence in college. Data were collected using the Student Satisfaction Inventory (Schreiner & Juillerat, 1994) and were analyzed by class level. The hierarchical multiple regression analyses…

  11. Biofilm Matrix and Its Regulation in Pseudomonas aeruginosa

    PubMed Central

    Wei, Qing; Ma, Luyan Z.

    2013-01-01

    Biofilms are communities of microorganisms embedded in extracellular polymeric substances (EPS) matrix. Bacteria in biofilms demonstrate distinct features from their free-living planktonic counterparts, such as different physiology and high resistance to immune system and antibiotics that render biofilm a source of chronic and persistent infections. A deeper understanding of biofilms will ultimately provide insights into the development of alternative treatment for biofilm infections. The opportunistic pathogen Pseudomonas aeruginosa, a model bacterium for biofilm research, is notorious for its ability to cause chronic infections by its high level of drug resistance involving the formation of biofilms. In this review, we summarize recent advances in biofilm formation, focusing on the biofilm matrix and its regulation in P. aeruginosa, aiming to provide resources for the understanding and control of bacterial biofilms. PMID:24145749

  12. Persistence of undergraduate women in STEM fields

    NASA Astrophysics Data System (ADS)

    Pedone, Maggie Helene

    The underrepresentation of women in science, technology, engineering, and mathematics (STEM) is a complex problem that continues to persist at the postsecondary level, particularly in computer science and engineering fields. This dissertation explored the pre-college and college level factors that influenced undergraduate women's persistence in STEM. This study also examined and compared the characteristics of undergraduate women who entered STEM fields and non-STEM fields in 2003-2004. The nationally representative Beginning Postsecondary Students Longitudinal Study (BPS:04/09) data set was used for analysis. BPS:04/09 study respondents were surveyed three times (NPSAS:04, BPS:04/06, BPS:04/09) over a six-year period, which enabled me to explore factors related to long-term persistence. Astin's Input-Environment-Output (I-E-O) model was used as the framework to examine student inputs and college environmental factors that predict female student persistence (output) in STEM. Chi-square tests revealed significant differences between undergraduate women who entered STEM and non-STEM fields in 2003-2004. Differences in student demographics, prior academic achievement, high school course-taking patterns, and student involvement in college such as participation in study groups and school clubs were found. Notably, inferential statistics showed that a significantly higher proportion of female minority students entered STEM fields than non-STEM fields. These findings challenge the myth that underrepresented female minorities are less inclined to enter STEM fields. Logistic regression analyses revealed thirteen significant predictors of persistence for undergraduate women in STEM. Findings showed that undergraduate women who were younger, more academically prepared, and academically and socially involved in college (e.g., lived on campus, interacted with faculty, participated in study groups, fine arts activities, and school sports) were more likely to persist in STEM

  13. Fish population persistence in hydrologically variable landscapes.

    PubMed

    Bond, Nick R; Balcombe, Stephen R; Crook, David A; Marshall, Jonathan C; Menke, Norbert; Lobegeiger, Jaye S

    2015-06-01

    Forecasting population persistence in environments subjected to periodic disturbances represents a general challenge for ecologists. In arid and semiarid regions, climate change and human water use pose significant threats to the future persistence of aquatic biota whose populations typically depend on permanent refuge waterholes for their viability. As such, habitats are increasingly being lost as a result of decreasing runoff and increasing water extraction. We constructed a spatially explicit population model for golden perch Macquaria ambigua (Richardson), a native freshwater fish in the Murray-Darling Basin in eastern Australia. We then used the model to examine the effects of increased aridity, increased drought frequency, and localized human water extraction on population viability. Consistent with current observations, the model predicted golden perch population persistence under the current climate and levels of water use. Modeled increases in local water extraction greatly increased the risk of population decline, while scenarios of increasing aridity and drought frequency were associated with only minor increases in this risk. We conclude that natural variability in abundances and high turnover rates (extinction/recolonization) of local populations dictate the importance of spatial connectivity and periodic cycles of population growth. Our study also demonstrates an effective way to examine population persistence in intermittent and ephemeral river systems by integrating spatial and temporal dynamics of waterhole persistence with demographic processes (survival, recruitment, and dispersal) within a stochastic modeling framework. The approach can be used to help understand the impacts of natural and anthropogenic drivers, including water resource development, on the viability of biota inhabiting highly dynamic environments. PMID:26465032

  14. Rotenone persistence model for montane streams

    USGS Publications Warehouse

    Brown, Peter J.; Zale, Alexander V.

    2012-01-01

    The efficient and effective use of rotenone is hindered by its unknown persistence in streams. Environmental conditions degrade rotenone, but current label instructions suggest fortifying the chemical along a stream based on linear distance or travel time rather than environmental conditions. Our objective was to develop models that use measurements of environmental conditions to predict rotenone persistence in streams. Detailed measurements of ultraviolet radiation, water temperature, dissolved oxygen, total dissolved solids (TDS), conductivity, pH, oxidation–reduction potential (ORP), substrate composition, amount of organic matter, channel slope, and travel time were made along stream segments located between rotenone treatment stations and cages containing bioassay fish in six streams. The amount of fine organic matter, biofilm, sand, gravel, cobble, rubble, small boulders, slope, pH, TDS, ORP, light reaching the stream, energy dissipated, discharge, and cumulative travel time were each significantly correlated with fish death. By using logistic regression, measurements of environmental conditions were paired with the responses of bioassay fish to develop a model that predicted the persistence of rotenone toxicity in streams. This model was validated with data from two additional stream treatment reaches. Rotenone persistence was predicted by a model that used travel time, rubble, and ORP. When this model predicts a probability of less than 0.95, those who apply rotenone can expect incomplete eradication and should plan on fortifying rotenone concentrations. The significance of travel time has been previously identified and is currently used to predict rotenone persistence. However, rubble substrate, which may be associated with the degradation of rotenone by adsorption and volatilization in turbulent environments, was not previously considered.

  15. Kaposi’s Sarcoma Herpesvirus Genome Persistence

    PubMed Central

    Juillard, Franceline; Tan, Min; Li, Shijun; Kaye, Kenneth M.

    2016-01-01

    Kaposi’s sarcoma-associated herpesvirus (KSHV) has an etiologic role in Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease. These diseases are most common in immunocompromised individuals, especially those with AIDS. Similar to all herpesviruses, KSHV infection is lifelong. KSHV infection in tumor cells is primarily latent, with only a small subset of cells undergoing lytic infection. During latency, the KSHV genome persists as a multiple copy, extrachromosomal episome in the nucleus. In order to persist in proliferating tumor cells, the viral genome replicates once per cell cycle and then segregates to daughter cell nuclei. KSHV only expresses several genes during latent infection. Prominent among these genes, is the latency-associated nuclear antigen (LANA). LANA is responsible for KSHV genome persistence and also exerts transcriptional regulatory effects. LANA mediates KSHV DNA replication and in addition, is responsible for segregation of replicated genomes to daughter nuclei. LANA serves as a molecular tether, bridging the viral genome to mitotic chromosomes to ensure that KSHV DNA reaches progeny nuclei. N-terminal LANA attaches to mitotic chromosomes by binding histones H2A/H2B at the surface of the nucleosome. C-terminal LANA binds specific KSHV DNA sequence and also has a role in chromosome attachment. In addition to the essential roles of N- and C-terminal LANA in genome persistence, internal LANA sequence is also critical for efficient episome maintenance. LANA’s role as an essential mediator of virus persistence makes it an attractive target for inhibition in order to prevent or treat KSHV infection and disease. PMID:27570517

  16. Persistence drives gene clustering in bacterial genomes

    PubMed Central

    Fang, Gang; Rocha, Eduardo PC; Danchin, Antoine

    2008-01-01

    Background Gene clustering plays an important role in the organization of the bacterial chromosome and several mechanisms have been proposed to explain its extent. However, the controversies raised about the validity of each of these mechanisms remind us that the cause of this gene organization remains an open question. Models proposed to explain clustering did not take into account the function of the gene products nor the likely presence or absence of a given gene in a genome. However, genomes harbor two very different categories of genes: those genes present in a majority of organisms – persistent genes – and those present in very few organisms – rare genes. Results We show that two classes of genes are significantly clustered in bacterial genomes: the highly persistent and the rare genes. The clustering of rare genes is readily explained by the selfish operon theory. Yet, genes persistently present in bacterial genomes are also clustered and we try to understand why. We propose a model accounting specifically for such clustering, and show that indispensability in a genome with frequent gene deletion and insertion leads to the transient clustering of these genes. The model describes how clusters are created via the gene flux that continuously introduces new genes while deleting others. We then test if known selective processes, such as co-transcription, physical interaction or functional neighborhood, account for the stabilization of these clusters. Conclusion We show that the strong selective pressure acting on the function of persistent genes, in a permanent state of flux of genes in bacterial genomes, maintaining their size fairly constant, that drives persistent genes clustering. A further selective stabilization process might contribute to maintaining the clustering. PMID:18179692

  17. Long persistent luminescence in the ultraviolet in Pb(2+)-doped Sr2MgGe2O7 persistent phosphor.

    PubMed

    Liang, Yanjie; Liu, Feng; Chen, Yafei; Sun, Kangning; Pan, Zhengwei

    2016-01-28

    We extend the persistent luminescence into the ultraviolet spectral region by developing a new ultraviolet persistent phosphor Sr2MgGe2O7:Pb(2+). The Sr2MgGe2O7:Pb(2+) phosphor exhibits strong persistent luminescence peaking at 370 nm and a long persistence time of >12 h after excitation. The phosphor also exhibits a photo-stimulated persistent luminescence capability. PMID:26691008

  18. The matrix of inspiration

    NASA Astrophysics Data System (ADS)

    Oehlmann, Dietmar; Ohlmann, Odile M.; Danzebrink, Hans U.

    2005-04-01

    perform this exchange, as a matrix, understood as source, of new ideas.

  19. Matrix cracking in brittle-matrix composites with tailored interfaces

    SciTech Connect

    Danchaivijit, S.; Chao, L.Y.; Shetty, D.K.

    1995-10-01

    Matrix cracking from controlled through cracks with bridging filaments was studied in a model unidirectional composite of SiC filaments in an epoxy-bonded alumina matrix. An unbonded, frictional interface was produced by moderating the curing shrinkage of the epoxy with the alumina filler and coating the filaments with a releasing agent. Uniaxial tension test specimens (2.5 x 25 x 125 mm) with filament-bridged through cracks were fabricated by a novel two-step casting technique involving casting, precracking and joining of cracked and uncracked sections. Distinct matrix-cracking stresses, corresponding to the extension of the filament-bridged cracks, were measured in uniaxial tension tests using a high-sensitivity extensometer. The crack-length dependence of the matrix-cracking stress was found to be in good agreement with the prediction of a fracture-mechanics analysis that employed a new crack-closure force-crack-opening displacement relation in the calculation of the stress intensity for fiber-bridged cracks. The prediction was based on independent experimental measurements of the matrix fracture toughness (K{sub cm}), the interfacial sliding friction stress ({tau}) and the residual stress in the matrix ({sigma}{sub m}{sup I}). The matrix-cracking stress for crack lengths (2a) greater than 3 mm was independent of the crack length and agreed with the prediction of the steady-state theory of Budiansky, Hutchinson and Evans. Tests on specimens without the deliberately introduced cracks indicated a matrix-cracking stress significantly higher than the steady-state stress.

  20. Type VI Collagen Regulates Dermal Matrix Assembly and Fibroblast Motility.

    PubMed

    Theocharidis, Georgios; Drymoussi, Zoe; Kao, Alexander P; Barber, Asa H; Lee, David A; Braun, Kristin M; Connelly, John T

    2016-01-01

    Type VI collagen is a nonfibrillar collagen expressed in many connective tissues and implicated in extracellular matrix (ECM) organization. We hypothesized that type VI collagen regulates matrix assembly and cell function within the dermis of the skin. In the present study we examined the expression pattern of type VI collagen in normal and wounded skin and investigated its specific function in new matrix deposition by human dermal fibroblasts. Type VI collagen was expressed throughout the dermis of intact human skin, at the expanding margins of human keloid samples, and in the granulation tissue of newly deposited ECM in a mouse model of wound healing. Generation of cell-derived matrices (CDMs) by human dermal fibroblasts with stable knockdown of COL6A1 revealed that type VI collagen-deficient matrices were significantly thinner and contained more aligned, thicker, and widely spaced fibers than CDMs produced by normal fibroblasts. In addition, there was significantly less total collagen and sulfated proteoglycans present in the type VI collagen-depleted matrices. Normal fibroblasts cultured on de-cellularized CDMs lacking type VI collagen displayed increased cell spreading, migration speed, and persistence. Taken together, these findings indicate that type VI collagen is a key regulator of dermal matrix assembly, composition, and fibroblast behavior and may play an important role in wound healing and tissue regeneration. PMID:26763426

  1. Genotype imputation via matrix completion.

    PubMed

    Chi, Eric C; Zhou, Hua; Chen, Gary K; Del Vecchyo, Diego Ortega; Lange, Kenneth

    2013-03-01

    Most current genotype imputation methods are model-based and computationally intensive, taking days to impute one chromosome pair on 1000 people. We describe an efficient genotype imputation method based on matrix completion. Our matrix completion method is implemented in MATLAB and tested on real data from HapMap 3, simulated pedigree data, and simulated low-coverage sequencing data derived from the 1000 Genomes Project. Compared with leading imputation programs, the matrix completion algorithm embodied in our program MENDEL-IMPUTE achieves comparable imputation accuracy while reducing run times significantly. Implementation in a lower-level language such as Fortran or C is apt to further improve computational efficiency. PMID:23233546

  2. High Temperature Polymer Matrix Composites

    NASA Technical Reports Server (NTRS)

    1985-01-01

    These are the proceedings of the High Temperature Polymer Matrix Composites Conference held at the NASA Lewis Research Center on March 16 to 18, 1983. The purpose of the conference is to provide scientists and engineers working in the field of high temperature polymer matrix composites an opportunity to review, exchange, and assess the latest developments in this rapidly expanding area of materials technology. Technical papers are presented in the following areas: (1) matrix development; (2) adhesive development; (3) characterization; (4) environmental effects; and (5) applications.

  3. Canonical density matrix perturbation theory.

    PubMed

    Niklasson, Anders M N; Cawkwell, M J; Rubensson, Emanuel H; Rudberg, Elias

    2015-12-01

    Density matrix perturbation theory [Niklasson and Challacombe, Phys. Rev. Lett. 92, 193001 (2004)] is generalized to canonical (NVT) free-energy ensembles in tight-binding, Hartree-Fock, or Kohn-Sham density-functional theory. The canonical density matrix perturbation theory can be used to calculate temperature-dependent response properties from the coupled perturbed self-consistent field equations as in density-functional perturbation theory. The method is well suited to take advantage of sparse matrix algebra to achieve linear scaling complexity in the computational cost as a function of system size for sufficiently large nonmetallic materials and metals at high temperatures. PMID:26764847

  4. Mechanotransduction and extracellular matrix homeostasis

    PubMed Central

    Humphrey, Jay D.; Dufresne, Eric R.; Schwartz, Martin A.

    2015-01-01

    Preface Soft connective tissues at steady state are yet dynamic; resident cells continually read environmental cues and respond to promote homeostasis, including maintenance of the mechanical properties of the extracellular matrix that are fundamental to cellular and tissue health. The mechanosensing process involves assessment of the mechanics of the matrix by the cells through integrins and the actomyosin cytoskeleton, and is followed by a mechano-regulation process that includes the deposition, rearrangement, or removal of matrix to maintain overall form and function. Progress toward understanding the molecular, cellular, and tissue scale effects that promote mechanical homeostasis has helped identify key questions for future research. PMID:25355505

  5. Matrix Elements for Hylleraas CI

    NASA Astrophysics Data System (ADS)

    Harris, Frank E.

    The limitation to at most a single interelectron distance in individual configurations of a Hylleraas-type multiconfiguration wave function restricts significantly the types of integrals occurring in matrix elements for energy calculations, but even then if the formulation is not handled efficiently the angular parts of these integrals escalate to create expressions of great complexity. This presentation reviews ways in which the angular-momentum calculus can be employed to systematize and simplify the matrix element formulas, particularly those for the kinetic-energy matrix elements.

  6. Statistic versus stochastic characterization of persistent droughts

    NASA Astrophysics Data System (ADS)

    Gonzalez-Perez, J.; Valdes, J. B.

    2005-12-01

    Droughts are one of more devastating natural disasters. A drought event is always related with deficiency in precipitation over a time period. As longer are the drought periods, larger are the damages associated with, following a potential relationship. Additionally, the extension covered by an event also increases its impact, because it makes difficult to compensate the deficit from neighbourhood water resources. Therefore, the characterization of a drought by its persistent deficit, and the area over which it extends are main points to be carried on. The Standardized Precipitation Index (SPI) provides a statistical characterization of the deficits. Its computation, for different aggregation time scales, allows a persistence evaluation. Another more recent statistic that may be applied in drought characterization is the extreme persistent probability function (e.p.f.), which characterizes the persistence of extreme realizations in a random sequence. This work presents an analysis of the differences in performance of the SPI and the e.p.f. in the statistical characterization of a drought event. The inclusion of the persistency directly in the statistic gives to the e.p.f. an advantage over the SPI. Furthermore, the relationship between the e.p.f. and its mean frequency of recurrence is known. Thus, the e.p.f. may be applied to provide either statistic or stochastic characterization of a drought event. Both criteria were compared, showing that the stochastic characterization produces a better drought indicator. The stochastic characterization using the e.p.f. as a criterion yields the new Drought Frequency Index (DFI). The index is applicable to any random water related variable to identify drought events. Its main advantages over the SPI are the direct inclusion of persistence, and its larger robustness to the time scale. To incorporate the spatial extension in the characterization of a drought event, the new DFI may also be evaluated to characterize the drought

  7. Matrix product operators, matrix product states, and ab initio density matrix renormalization group algorithms

    NASA Astrophysics Data System (ADS)

    Chan, Garnet Kin-Lic; Keselman, Anna; Nakatani, Naoki; Li, Zhendong; White, Steven R.

    2016-07-01

    Current descriptions of the ab initio density matrix renormalization group (DMRG) algorithm use two superficially different languages: an older language of the renormalization group and renormalized operators, and a more recent language of matrix product states and matrix product operators. The same algorithm can appear dramatically different when written in the two different vocabularies. In this work, we carefully describe the translation between the two languages in several contexts. First, we describe how to efficiently implement the ab initio DMRG sweep using a matrix product operator based code, and the equivalence to the original renormalized operator implementation. Next we describe how to implement the general matrix product operator/matrix product state algebra within a pure renormalized operator-based DMRG code. Finally, we discuss two improvements of the ab initio DMRG sweep algorithm motivated by matrix product operator language: Hamiltonian compression, and a sum over operators representation that allows for perfect computational parallelism. The connections and correspondences described here serve to link the future developments with the past and are important in the efficient implementation of continuing advances in ab initio DMRG and related algorithms.

  8. Matrix product operators, matrix product states, and ab initio density matrix renormalization group algorithms.

    PubMed

    Chan, Garnet Kin-Lic; Keselman, Anna; Nakatani, Naoki; Li, Zhendong; White, Steven R

    2016-07-01

    Current descriptions of the ab initio density matrix renormalization group (DMRG) algorithm use two superficially different languages: an older language of the renormalization group and renormalized operators, and a more recent language of matrix product states and matrix product operators. The same algorithm can appear dramatically different when written in the two different vocabularies. In this work, we carefully describe the translation between the two languages in several contexts. First, we describe how to efficiently implement the ab initio DMRG sweep using a matrix product operator based code, and the equivalence to the original renormalized operator implementation. Next we describe how to implement the general matrix product operator/matrix product state algebra within a pure renormalized operator-based DMRG code. Finally, we discuss two improvements of the ab initio DMRG sweep algorithm motivated by matrix product operator language: Hamiltonian compression, and a sum over operators representation that allows for perfect computational parallelism. The connections and correspondences described here serve to link the future developments with the past and are important in the efficient implementation of continuing advances in ab initio DMRG and related algorithms. PMID:27394094

  9. Stochastic determination of matrix determinants.

    PubMed

    Dorn, Sebastian; Ensslin, Torsten A

    2015-07-01

    Matrix determinants play an important role in data analysis, in particular when Gaussian processes are involved. Due to currently exploding data volumes, linear operations-matrices-acting on the data are often not accessible directly but are only represented indirectly in form of a computer routine. Such a routine implements the transformation a data vector undergoes under matrix multiplication. While efficient probing routines to estimate a matrix's diagonal or trace, based solely on such computationally affordable matrix-vector multiplications, are well known and frequently used in signal inference, there is no stochastic estimate for its determinant. We introduce a probing method for the logarithm of a determinant of a linear operator. Our method rests upon a reformulation of the log-determinant by an integral representation and the transformation of the involved terms into stochastic expressions. This stochastic determinant determination enables large-size applications in Bayesian inference, in particular evidence calculations, model comparison, and posterior determination. PMID:26274302

  10. Stochastic determination of matrix determinants

    NASA Astrophysics Data System (ADS)

    Dorn, Sebastian; Enßlin, Torsten A.

    2015-07-01

    Matrix determinants play an important role in data analysis, in particular when Gaussian processes are involved. Due to currently exploding data volumes, linear operations—matrices—acting on the data are often not accessible directly but are only represented indirectly in form of a computer routine. Such a routine implements the transformation a data vector undergoes under matrix multiplication. While efficient probing routines to estimate a matrix's diagonal or trace, based solely on such computationally affordable matrix-vector multiplications, are well known and frequently used in signal inference, there is no stochastic estimate for its determinant. We introduce a probing method for the logarithm of a determinant of a linear operator. Our method rests upon a reformulation of the log-determinant by an integral representation and the transformation of the involved terms into stochastic expressions. This stochastic determinant determination enables large-size applications in Bayesian inference, in particular evidence calculations, model comparison, and posterior determination.

  11. Performance Appraisal for Matrix Management.

    ERIC Educational Resources Information Center

    Edwards, M. R.; Sproull, J. Ruth

    1985-01-01

    A matrix management system designed for use by a highly technical nuclear weapons research and development facility to improve productivity and flexibility by the use of multiple authority, responsibility, and accountability relationships is described. (MSE)

  12. Extracellular matrix and wound healing.

    PubMed

    Maquart, F X; Monboisse, J C

    2014-04-01

    Extracellular matrix has been known for a long time as an architectural support for the tissues. Many recent data, however, have shown that extracellular matrix macromolecules (collagens, elastin, glycosaminoglycans, proteoglycans and connective tissue glycoproteins) are able to regulate many important cell functions, such as proliferation, migration, protein synthesis or degradation, apoptosis, etc., making them able to play an important role in the wound repair process. Not only the intact macromolecules but some of their specific domains, that we called "Matrikines", are also able to regulate many cell activities. In this article, we will summarize main findings showing the effects of extracellular matrix macromolecules and matrikines on connective tissue and epithelial cells, particularly in skin, and their potential implication in the wound healing process. These examples show that extracellular matrix macromolecules or some of their specific domains may play a major role in wound healing. Better knowledge of these interactions may suggest new therapeutic targets in wound healing defects. PMID:24650524

  13. Persistence of interest in science, technology, engineering and mathematics: An analysis of persisting and non-persisting students

    NASA Astrophysics Data System (ADS)

    White, Jeffry L.

    While there has been an increase in enrollment, interest in science, technology, engineering, and mathematics (STEM) has been declining on college campuses since 1967. Higher enrollment does not transfer to an increase in the number of minorities in the STEM fields. The majority-minority enrollment ratio is nearly 2:1 but the gap widens to 4:1 when it comes to graduation. In fact, underrepresented minorities (URM) earned only 12% of the STEM degrees awarded in 1998. When the higher attrition and lower graduation rates of URM are scrutinized, upwards of 60% changed majors or dropped out of STEM. Further investigation reveals the most frequently cited reasons for departure were loss of initial interest, developed a greater interest in another field, or were turned off by the STEM disciplines. A primarily exploratory study was conducted into the conditions necessary for academic interest in the STEM fields to persist. A model based on student engagement (Astin, 1977) and interest operations (Prenzel, 1988a) theories was used with a random sample of URM at universities participating in the Ohio Science and Engineering Alliance. Survey research was employed to investigate interest development and the effect of student retention programs and activities on such interest. The latter part of the study could not be fully examined when 95% reported not utilizing retention services. For the section on interest, an online survey using a 5-point Likert scale was validated using principal components analysis. A binominal logistic regression was used to predict membership in one of two possible groups: persisters and students at-risk for not persisting. The major conclusions are: (1) While 3 variables (feelings, learning and difficulty) were statistically significant only one, feelings was substantively significant. (2) Persistence increased 80.9% for each 1-unit increase in feelings and 9.9% for learning. (3) Persistence decreased 19.8% for each one-unit increase in difficulty

  14. Molybdenum disilicide alloy matrix composite

    DOEpatents

    Petrovic, John J.; Honnell, Richard E.; Gibbs, W. Scott

    1991-01-01

    Compositions of matter consisting of matrix materials having silicon carbide dispersed throughout them and methods of making the compositions. A matrix material is an alloy of an intermetallic compound, molybdenum disilicide, and at least one secondary component which is a refractory silicide. The silicon carbide dispersant may be in the form of VLS whiskers, VS whiskers, or submicron powder or a mixture of these forms.

  15. Molybdenum disilicide alloy matrix composite

    DOEpatents

    Petrovic, J.J.; Honnell, R.E.; Gibbs, W.S.

    1991-12-03

    Compositions of matter consisting of matrix materials having silicon carbide dispersed throughout them and methods of making the compositions are disclosed. A matrix material is an alloy of an intermetallic compound, molybdenum disilicide, and at least one secondary component which is a refractory silicide. The silicon carbide dispersant may be in the form of VLS whiskers, VS whiskers, or submicron powder or a mixture of these forms. 3 figures.

  16. Universal Keplerian state transition matrix

    NASA Technical Reports Server (NTRS)

    Shepperd, S. W.

    1985-01-01

    A completely general method for computing the Keplerian state transition matrix in terms of Goodyear's universal variables is presented. This includes a new scheme for solving Kepler's problem which is a necessary first step to computing the transition matrix. The Kepler problem is solved in terms of a new independent variable requiring the evaluation of only one transcendental function. Furthermore, this transcendental function may be conveniently evaluated by means of a Gaussian continued fraction.

  17. Molybdenum disilicide alloy matrix composite

    DOEpatents

    Petrovic, John J.; Honnell, Richard E.; Gibbs, W. Scott

    1990-01-01

    Compositions of matter consisting of matrix matrials having silicon carbide dispersed throughout them and methods of making the compositions. A matrix material is an alloy of an intermetallic compound, molybdenum disilicide, and at least one secondary component which is a refractory silicide. The silicon carbide dispersant may be in the form of VLS whiskers, VS whiskers, or submicron powder or a mixture of these forms.

  18. Form development sample test matrix

    SciTech Connect

    Ebbinghaus, B B

    1999-10-15

    This document summarizes the status of sample fabrication and analysis in the Form Development Sample Test Matrix. Since its publication in the ''Baseline Formulation'' report (UCRL-ID- 133089, PIP-99-O 12) and in the ''Complete Single-Phase Sample Fabrications that Support the Licensing Application and Complete Process and Compositional Extreme Sample Fabrications that Support the Licensing Application'' report (PIP-99-078), the Sample Test Matrix has been updated and expanded. This version is current though September 30, 1999.

  19. Biofilm formation by enteric pathogens and its role in plant colonization and persistence.

    PubMed

    Yaron, Sima; Römling, Ute

    2014-11-01

    The significant increase in foodborne outbreaks caused by contaminated fresh produce, such as alfalfa sprouts, lettuce, melons, tomatoes and spinach, during the last 30 years stimulated investigation of the mechanisms of persistence of human pathogens on plants. Emerging evidence suggests that Salmonella enterica and Escherichia coli, which cause the vast majority of fresh produce outbreaks, are able to adhere to and to form biofilms on plants leading to persistence and resistance to disinfection treatments, which subsequently can cause human infections and major outbreaks. In this review, we present the current knowledge about host, bacterial and environmental factors that affect the attachment to plant tissue and the process of biofilm formation by S. enterica and E. coli, and discuss how biofilm formation assists in persistence of pathogens on the plants. Mechanisms used by S. enterica and E. coli to adhere and persist on abiotic surfaces and mammalian cells are partially similar and also used by plant pathogens and symbionts. For example, amyloid curli fimbriae, part of the extracellular matrix of biofilms, frequently contribute to adherence and are upregulated upon adherence and colonization of plant material. Also the major exopolysaccharide of the biofilm matrix, cellulose, is an adherence factor not only of S. enterica and E. coli, but also of plant symbionts and pathogens. Plants, on the other hand, respond to colonization by enteric pathogens with a variety of defence mechanisms, some of which can effectively inhibit biofilm formation. Consequently, plant compounds might be investigated for promising novel antibiofilm strategies. PMID:25351039

  20. SCORPION II persistent surveillance system update

    NASA Astrophysics Data System (ADS)

    Coster, Michael; Hunt, Cassandra

    2011-06-01

    This paper highlights the most recently added features and benefits available in the latest generation of Northrop Grumman SCORPION II persistent surveillance and target recognition systems. By leveraging smaller, lighter, and more power efficient SCORPION II sensor and universal gateway components, with foliage penetrating ad-hoc network communications, persistent field programmable systems that are easier to conceal can be optimized for both image capture and data exfiltration. In addition to the SCORPION II suite of sensor components, a growing list of over sixty different sensor and camera types from a variety of manufacturers have been integrated with the SCORPION Gateway family. In addition to updating several different COP systems, SCORPION and SCORPION II data can be directly processed using a common sensor status graphical user interface (GUI) that allows for viewing and analysis of images and sensor data from hundreds of SCORPION system gateways on single or multiple displays.

  1. Emotional persistence in online chatting communities

    NASA Astrophysics Data System (ADS)

    Garas, Antonios; Garcia, David; Skowron, Marcin; Schweitzer, Frank

    2012-05-01

    How do users behave in online chatrooms, where they instantaneously read and write posts? We analyzed about 2.5 million posts covering various topics in Internet relay channels, and found that user activity patterns follow known power-law and stretched exponential distributions, indicating that online chat activity is not different from other forms of communication. Analysing the emotional expressions (positive, negative, neutral) of users, we revealed a remarkable persistence both for individual users and channels. I.e. despite their anonymity, users tend to follow social norms in repeated interactions in online chats, which results in a specific emotional ``tone'' of the channels. We provide an agent-based model of emotional interaction, which recovers qualitatively both the activity patterns in chatrooms and the emotional persistence of users and channels. While our assumptions about agent's emotional expressions are rooted in psychology, the model allows to test different hypothesis regarding their emotional impact in online communication.

  2. UAV Cooperation Architectures for Persistent Sensing

    SciTech Connect

    Roberts, R S; Kent, C A; Jones, E D

    2003-03-20

    With the number of small, inexpensive Unmanned Air Vehicles (UAVs) increasing, it is feasible to build multi-UAV sensing networks. In particular, by using UAVs in conjunction with unattended ground sensors, a degree of persistent sensing can be achieved. With proper UAV cooperation algorithms, sensing is maintained even though exceptional events, e.g., the loss of a UAV, have occurred. In this paper a cooperation technique that allows multiple UAVs to perform coordinated, persistent sensing with unattended ground sensors over a wide area is described. The technique automatically adapts the UAV paths so that on the average, the amount of time that any sensor has to wait for a UAV revisit is minimized. We also describe the Simulation, Tactical Operations and Mission Planning (STOMP) software architecture. This architecture is designed to help simulate and operate distributed sensor networks where multiple UAVs are used to collect data.

  3. Mitochondrial DNA replacement versus nuclear DNA persistence

    NASA Astrophysics Data System (ADS)

    Serva, Maurizio

    2006-10-01

    In this paper we consider two populations whose generations are not overlapping and whose size is large. The number of males and females in both populations is constant. Any generation is replaced by a new one and any individual has two parents concerning nuclear DNA and a single one (the mother) concerning mtDNA. Moreover, at any generation some individuals migrate from the first population to the second. In a finite random time T, the mtDNA of the second population is completely replaced by the mtDNA of the first. In the same time, the nuclear DNA is not completely replaced and a fraction F of the ancient nuclear DNA persists. We compute both T and F. Since this study shows that complete replacement of mtDNA in a population is compatible with the persistence of a large fraction of nuclear DNA, it may have some relevance for the 'out of Africa'/multiregional debate in palaeoanthropology.

  4. The persistence of American Indian health disparities.

    PubMed

    Jones, David S

    2006-12-01

    Disparities in health status between American Indians and other groups in the United States have persisted throughout the 500 years since Europeans arrived in the Americas. Colonists, traders, missionaries, soldiers, physicians, and government officials have struggled to explain these disparities, invoking a wide range of possible causes. American Indians joined these debates, often suggesting different explanations. Europeans and Americans also struggled to respond to the disparities, sometimes working to relieve them, sometimes taking advantage of the ill health of American Indians. Economic and political interests have always affected both explanations of health disparities and responses to them, influencing which explanations were emphasized and which interventions were pursued. Tensions also appear in ongoing debates about the contributions of genetic and socioeconomic forces to the pervasive health disparities. Understanding how these economic and political forces have operated historically can explain both the persistence of the health disparities and the controversies that surround them. PMID:17077399

  5. Persistent Hypoglycemia in Patient with Hodgkin's Disease

    PubMed Central

    Lim, Harold Cinco; Munshi, Lubna Bashir; Sharon, David

    2015-01-01

    Hypoglycemia is a rare complication of Hodgkin's disease. Several explanations have been postulated but the exact pathophysiology is not well understood. We are presenting a case of newly diagnosed Stage IV Hodgkin's disease that developed persistent and recurrent hypoglycemia despite giving glucagon, repeated 50% dextrose, and D5 and D10 continuous infusion. Hypoglycemia workup showed the C-peptide level to be low. Patient was suspected of having hypoglycemia related to lymphoma and was given a trial of prednisone which resolved the hypoglycemic episodes and made the patient euglycemic for the rest of his hospital stay. The presence of a substance that mimicked the effects of insulin was highly suspected. Several case reports strengthen the hypothesis of an insulin-like growth factor or antibodies secreted by the cancer cells causing hypoglycemia in Hodgkin's disease but none of them have been confirmed. Further investigation is warranted to more clearly define the pathophysiology of persistent hypoglycemia in patients with Hodgkin's disease. PMID:26839722

  6. The Persistence of American Indian Health Disparities

    PubMed Central

    Jones, David S.

    2006-01-01

    Disparities in health status between American Indians and other groups in the United States have persisted throughout the 500 years since Europeans arrived in the Americas. Colonists, traders, missionaries, soldiers, physicians, and government officials have struggled to explain these disparities, invoking a wide range of possible causes. American Indians joined these debates, often suggesting different explanations. Europeans and Americans also struggled to respond to the disparities, sometimes working to relieve them, sometimes taking advantage of the ill health of American Indians. Economic and political interests have always affected both explanations of health disparities and responses to them, influencing which explanations were emphasized and which interventions were pursued. Tensions also appear in ongoing debates about the contributions of genetic and socioeconomic forces to the pervasive health disparities. Understanding how these economic and political forces have operated historically can explain both the persistence of the health disparities and the controversies that surround them. PMID:17077399

  7. The persistence length of adsorbed dendronized polymers

    NASA Astrophysics Data System (ADS)

    Grebikova, Lucie; Kozhuharov, Svilen; Maroni, Plinio; Mikhaylov, Andrey; Dietler, Giovanni; Schlüter, A. Dieter; Ullner, Magnus; Borkovec, Michal

    2016-07-01

    The persistence length of cationic dendronized polymers adsorbed onto oppositely charged substrates was studied by atomic force microscopy (AFM) and quantitative image analysis. One can find that a decrease in the ionic strength leads to an increase of the persistence length, but the nature of the substrate and of the generation of the side dendrons influence the persistence length substantially. The strongest effects as the ionic strength is being changed are observed for the fourth generation polymer adsorbed on mica, which is a hydrophilic and highly charged substrate. However, the observed dependence on the ionic strength is much weaker than the one predicted by the Odijk, Skolnik, and Fixman (OSF) theory for semi-flexible chains. Low-generation polymers show a variation with the ionic strength that resembles the one observed for simple and flexible polyelectrolytes in solution. For high-generation polymers, this dependence is weaker. Similar dependencies are found for silica and gold substrates. The observed behavior is probably caused by different extents of screening of the charged groups, which is modified by the polymer generation, and to a lesser extent, the nature of the substrate. For highly ordered pyrolytic graphite (HOPG), which is a hydrophobic and weakly charged substrate, the electrostatic contribution to the persistence length is much smaller. In the latter case, we suspect that specific interactions between the polymer and the substrate also play an important role.The persistence length of cationic dendronized polymers adsorbed onto oppositely charged substrates was studied by atomic force microscopy (AFM) and quantitative image analysis. One can find that a decrease in the ionic strength leads to an increase of the persistence length, but the nature of the substrate and of the generation of the side dendrons influence the persistence length substantially. The strongest effects as the ionic strength is being changed are observed for the fourth

  8. Persistence diagrams of cortical surface data.

    PubMed

    Chung, Moo K; Bubenik, Peter; Kim, Peter T

    2009-01-01

    We present a novel framework for characterizing signals in images using techniques from computational algebraic topology. This technique is general enough for dealing with noisy multivariate data including geometric noise. The main tool is persistent homology which can be encoded in persistence diagrams. These diagrams visually show how the number of connected components of the sublevel sets of the signal changes. The use of local critical values of a function differs from the usual statistical parametric mapping framework, which mainly uses the mean signal in quantifying imaging data. Our proposed method uses all the local critical values in characterizing the signal and by doing so offers a completely new data reduction and analysis framework for quantifying the signal. As an illustration, we apply this method to a 1D simulated signal and 2D cortical thickness data. In case of the latter, extra homological structures are evident in an control group over the autistic group. PMID:19694279

  9. Persisting weakness after withdrawal of a statin.

    PubMed

    Mygland, Åse; Ljøstad, Unn; Krossnes, Bård Kronen

    2014-01-01

    An 81-year-old woman treated with simvastatin for several years followed by atorvastatin for about 1 year presented with fatigue, weakness and unsteady gait. The finding of elevated creatine kinase (CK) and symmetric muscle weakness around shoulders and hips led to suspicion of a toxic statin-associated myopathy. Atorvastatin was withdrawn, but her weakness persisted. Owing to persisting weakness, an autoimmune myopathy (myositis) was suspected, but initially disregarded since a muscle biopsy showed necrotic muscle fibres without inflammatory cell infiltrates and myositis-specific autoantibodies were absent. After 18 months with slowly progressive weakness and increasing CK values, awareness of new knowledge about autoimmunity as a cause of necrotic myopathy, led to a successful treatment trial with intravenous immunoglobulines, followed by steroids and metothrexate. Antibodies to the target enzyme of statins (HMGCR (3-hydroksy-3-methylglutaryl-coenzyme A reductase)) were detected in her serum, and she was diagnosed with autoimmune necrotic myositis probably triggered by atorvastatin. PMID:24713712

  10. Persistent Identifiers for Dutch cultural heritage institutions

    NASA Astrophysics Data System (ADS)

    Ras, Marcel; Kruithof, Gijsbert

    2016-04-01

    Over the past years, more and more collections belonging to archives, libraries, media, museums, and knowledge institutes are being digitised and made available online. These are exciting times for ALM institutions. They are realising that, in the information society, their collections are goldmines. Unfortunately most heritage institutions in the Netherlands do not yet meet the basic preconditions for long-term availability of their collections. The digital objects often have no long lasting fixed reference yet. URL's and web addresses change. Some digital objects that were referenced in Europeana and other portals can no longer be found. References in scientific articles have a very short life span, which is damaging for scholarly research. In 2015, the Dutch Digital Heritage Network (NDE) has started a two-year work program to co-ordinate existing initiatives in order to improve the (long-term) accessibility of the Dutch digital heritage for a wide range of users, anytime, anyplace. The Digital Heritage Network is a partnership established on the initiative of the Ministry of Education, Culture and Science. The members of the NDE are large, national institutions that strive to professionally preserve and manage digital data, e.g. the National Library, The Netherlands Institute for Sound and Vision, the Netherlands Cultural Heritage Agency, the Royal Netherlands Academy of Arts and Sciences, the National Archive of the Netherlands and the DEN Foundation, and a growing number of associations and individuals both within and outside the heritage sector. By means of three work programmes the goals of the Network should be accomplished and improve the visibility, the usability and the sustainability of digital heritage. Each programme contains of a set of projects. Within the sustainability program a project on creating a model for persistent identifiers is taking place. The main goals of the project are (1) raise awareness among cultural heritage institutions on the

  11. Persistent Disparities in Adult Hematopoietic Cell Transplantation.

    PubMed

    Crockett, David G; Loberiza, Fausto R

    2015-09-01

    The use of large databases has provided advancements in the understanding of racial, ethnic, and socioeconomic disparities in the field of adult hematopoietic cell transplants (HCT). Disparities exist on individual, institutional, and systemic levels for both allogeneic and autologous HCT. We reviewed the most recent publications that utilized large databases to elucidate disparities in HCT and placed them into historical context of the other major studies in the field. Two emerging themes were identified. These themes are persistent inequalities in both allogeneic HCT and autologous HCT for myeloma and the importance of improving homogeneity of care in HCT. Minimization of inequalities can be achieved only with an understanding of the persistent barriers that exist in the field. PMID:26104908

  12. Persistent docetaxel-induced supravenous erythematous eruption*

    PubMed Central

    Fernandes, Karina de Almeida Pinto; Felix, Paulo Antônio Oldani

    2015-01-01

    Taxanes are drugs used to treat many types of cancer, including breast and lung cancer. The most common side effects of these drugs are neutropenia and mucositis. Signs of skin toxicity are observed in about 65% of cases and include alopecia, hypersensitivity reactions, persistent supravenous erythematous eruption, nail changes, scleroderma reactions and others. We report two cases of skin reaction to docetaxel and warn that it is not necessary to interrupt the treatment in these cases. PMID:26560218

  13. Management of persistent inflammatory large joint monoarthritis.

    PubMed

    Byng-Maddick, Rachel; Jeyalingam, Lukshmy; Keat, Andrew

    2012-12-01

    Persistent inflammatory monoarthritis is inflammation of one joint, with symptoms lasting beyond 3 months. Approximately 50 % of cases are self-limiting; others will transform into oligo- or polyarticular disease, but a significant minority remain as a persistent inflammatory monoarthritis, which are often resistant to standard therapies used for oligo- or polyarticular disease and constitute a difficult therapeutic problem. However, there are no clear guidelines for treatment of this category of patients or an evidence-based consensus view on best treatment. A literature search was done through PubMed using 'monoarthritis', 'chronic synovitis' and 'persistent inflammatory monoarthritis' as search terms. Reports were located using references to related articles; reports in humans and animals, published in English, were included. Persistent inflammatory monoarthritis has a variable disease course, generally with a better prognosis than polyarthritis. There is no clear evidence for the use of traditional DMARDS in monoarthritis, and treatment algorithms are extrapolated from oligo- or polyarticular disease. Intra-articular anti-tumour necrosis factor (TNF) has been used with similar efficacy to intra-articular corticosteroids, and as yet, there are no reported cases of systemic anti-TNF use in monoarthritis. Synovectomy may be of use, with lower risk of recurrent disease, in open synovectomy. There is paucity of evidence for best practice in the management of chronic monoarthritis. Questions remain concerning the indications for invasive procedures and the balance between toxicity of systemic therapies versus the intended benefits to prevent disability. There is a pressing need for further studies and randomised controlled trials to be performed in this subset of patients. PMID:23108886

  14. [Persistent idiopathic facial pain and atypical odontalgia].

    PubMed

    Gaul, Charly; Ettlin, Dominik; Pfau, Doreen B

    2013-01-01

    The terms 'persistent idiopathic facial pain' (PIFP) and 'atypical odontalgia' (AO) are currently used as exclusion diagnoses for chronic toothache and chronic facial pain. Knowledge about these pain conditions in medical and dental practices is of crucial importance for the prevention of iatrogenic tissue damage by not-indicated invasive interventions, such as endodontic treatment and tooth extraction. In the present paper, etiology and pathogenesis, differential diagnostic criteria, and diagnostic approaches will be explained and relevant therapeutic principles will be outlined. PMID:23916270

  15. Persistence of antigen in nonarthritic joints.

    PubMed Central

    Fox, A; Glynn, L E

    1975-01-01

    The presence of antigen, IgG and C3 was shown by radioautography and immunofluorescence in the collagenous tissues of the joints of animals injected intra-articularly with antigen after having been previously immunized with that antigen in Freund's incomplete adjuvant. Since these joints were shown to be virtually free of inflammatory reactions, we suggest that the persistence of immune complexes activating complement cannot fully explain the chronicity of experimental allergic arthritis. Images PMID:769709

  16. Persistent Mobility Disability After Neurotoxic Chemotherapy

    PubMed Central

    Fitzgerald, G. Kelley; Studenski, Stephanie A.

    2010-01-01

    Background and Purpose The impact of cancer and its treatments on balance and functional mobility in older adults remains unknown but is increasingly important, given the evolution of cancer treatments. Subacute and more persistent side effects such as chemotherapy-induced peripheral neuropathy are on the rise, and the effects on mobility and balance, as well as the prognosis for resolution of any functional deficits, must be established before interventions can be trialed. The purpose of this case report is to describe the severity and long-term persistence of mobility decline in an older adult who received neurotoxic chemotherapy. To our knowledge, this is the first case report to describe an older adult with chemotherapy-induced peripheral neuropathy using results of standardized balance and mobility tests and to focus on prognosis by repeating these measures more than 2 years after chemotherapy. Case Description An 81-year-old woman received a neurotoxic agent (paclitaxel) after curative mastectomy for breast cancer. Baseline testing prior to taxane therapy revealed a socially active woman with no reported functional deficits or neuropathic symptoms, 1.2-m/s gait speed, and performance at the ceiling on balance and gait portions of a standardized mobility measure. Outcomes After 3 cycles, paclitaxel therapy was stopped by the oncologist because of neurotoxicity. Declines as large as 50% were seen in performance-based measures at 12 weeks and persisted at 2.5 years, and the patient reported recurrent falls, cane use, and mobility-related disability. Discussion This case highlights the extent to which function can decline in an older individual receiving neurotoxic chemotherapy, the potential for these deficits to persist years after treatment is stopped, and the need for physical therapy intervention and further research in this population. PMID:20813818

  17. Persistent HIV-1 replication during antiretroviral therapy

    PubMed Central

    Martinez-Picado, Javier; Deeks, Steven G.

    2016-01-01

    Purpose of review The present review will highlight some of the recent findings regarding the capacity of HIV-1 to replicate during antiretroviral therapy (ART). Recent findings Although ART is highly effective at inhibiting HIV replication, it is not curative. Several mechanisms contribute to HIV persistence during ART, including HIV latency, immune dysfunction, and perhaps persistent low-level spread of the virus to uninfected cells (replication). The success in curing HIV will depend on efficiently targeting these three aspects. The degree to which HIV replicates during ART remains controversial. Most studies have failed to find any evidence of HIV evolution in blood, even with samples collected over many years, although a recent very intensive study of three individuals suggested that the virus population does shift, at least during the first few months of therapy. Stronger but still not definitive evidence for replication comes from a series of studies in which standard regimens were intensified with an integration inhibitor, resulting in changes in episomal DNA (blood) and cell-associated RNA (tissue). Limited drug penetration within tissues and the presence of immune sanctuaries have been argued as potential mechanisms allowing HIV to spread during ART. Mathematical models suggest that HIV replication and evolution is possible even without the selection of fully drug-resistant variants. As persistent HIV replication could have clinical consequences and might limit the efficacy of curative interventions, determining if HIV replicates during ART and why, should remain a key focus of the HIV research community. Summary Residual viral replication likely persists in lymphoid tissues, at least in a subset of individuals. Abnormal levels of immune activation might contribute to sustain virus replication. PMID:27078619

  18. Information persistence using XML database technology

    NASA Astrophysics Data System (ADS)

    Clark, Thomas A.; Lipa, Brian E. G.; Macera, Anthony R.; Staskevich, Gennady R.

    2005-05-01

    The Joint Battlespace Infosphere (JBI) Information Management (IM) services provide information exchange and persistence capabilities that support tailored, dynamic, and timely access to required information, enabling near real-time planning, control, and execution for DoD decision making. JBI IM services will be built on a substrate of network centric core enterprise services and when transitioned, will establish an interoperable information space that aggregates, integrates, fuses, and intelligently disseminates relevant information to support effective warfighter business processes. This virtual information space provides individual users with information tailored to their specific functional responsibilities and provides a highly tailored repository of, or access to, information that is designed to support a specific Community of Interest (COI), geographic area or mission. Critical to effective operation of JBI IM services is the implementation of repositories, where data, represented as information, is represented and persisted for quick and easy retrieval. This paper will address information representation, persistence and retrieval using existing database technologies to manage structured data in Extensible Markup Language (XML) format as well as unstructured data in an IM services-oriented environment. Three basic categories of database technologies will be compared and contrasted: Relational, XML-Enabled, and Native XML. These technologies have diverse properties such as maturity, performance, query language specifications, indexing, and retrieval methods. We will describe our application of these evolving technologies within the context of a JBI Reference Implementation (RI) by providing some hopefully insightful anecdotes and lessons learned along the way. This paper will also outline future directions, promising technologies and emerging COTS products that can offer more powerful information management representations, better persistence mechanisms and

  19. PERSISTENT PLACOID MACULOPATHY: A NEW CLINICAL ENTITY

    PubMed Central

    Golchet, Pamela R.; Jampol, Lee M.; Wilson, David; Yannuzzi, Lawrence A.; Ober, Michael; Stroh, Edward

    2006-01-01

    Purpose To describe a previously unreported clinical entity superficially resembling macular serpiginous choroiditis but with a distinct presentation and clinical course. Methods A retrospective review of the medical records of five patients, aged 50 to 68 years, exhibiting this entity seen at five different centers from 1999 to 2006. Results The lesions in the patients in this study are in some respects similar to those of acute macular serpiginous choroiditis. The patients had well-delineated whitish plaque-like lesions involving the macula and sparing the peripapillary areas of both eyes. In contrast to serpiginous choroiditis, visual acuity remained good despite early involvement of the fovea until complications related to choroidal neovascularization (CNV) or pigmentary mottling developed. The angiographic characteristics and the clinical course were also atypical. Fluorescein angiography revealed well-defined early hypofluorescent areas, which partially filled-in in the late phase. Indocyanine green angiography showed the hypofluorescence to be persistent. Unlike serpiginous choroiditis, the white macular lesions faded over a period of months to years, but the characteristic angiographic findings often persisted longer. CNV developed in nine of 10 eyes with subsequent conversion to disciform macular scars in seven of 10 eyes. Unlike serpiginous choroiditis, none of the eyes showed chorioretinal scar formation unless related to CNV. Conclusion Persistent placoid maculopathy has features resembling macular serpiginous choroiditis but differs in its clinical course and effect on visual acuity. It appears to be a new entity. The majority of eyes develop CNV, which results in loss of central vision. PMID:17471331

  20. Improving Underrepresented Minority Student Persistence in STEM

    PubMed Central

    Estrada, Mica; Burnett, Myra; Campbell, Andrew G.; Campbell, Patricia B.; Denetclaw, Wilfred F.; Gutiérrez, Carlos G.; Hurtado, Sylvia; John, Gilbert H.; Matsui, John; McGee, Richard; Okpodu, Camellia Moses; Robinson, T. Joan; Summers, Michael F.; Werner-Washburne, Maggie; Zavala, MariaElena

    2016-01-01

    Members of the Joint Working Group on Improving Underrepresented Minorities (URMs) Persistence in Science, Technology, Engineering, and Mathematics (STEM)—convened by the National Institute of General Medical Sciences and the Howard Hughes Medical Institute—review current data and propose deliberation about why the academic “pathways” leak more for URM than white or Asian STEM students. They suggest expanding to include a stronger focus on the institutional barriers that need to be removed and the types of interventions that “lift” students’ interests, commitment, and ability to persist in STEM fields. Using Kurt Lewin’s planned approach to change, the committee describes five recommendations to increase URM persistence in STEM at the undergraduate level. These recommendations capitalize on known successes, recognize the need for accountability, and are framed to facilitate greater progress in the future. The impact of these recommendations rests upon enacting the first recommendation: to track successes and failures at the institutional level and collect data that help explain the existing trends. PMID:27543633