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  1. Concomitant elevations of MMP-9, NGAL, proMMP-9/NGAL and neutrophil elastase in serum of smokers with chronic obstructive pulmonary disease.

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    Bchir, Sarra; Nasr, Hela Ben; Bouchet, Sandrine; Benzarti, Mohamed; Garrouch, Abdelhamid; Tabka, Zouhair; Susin, Santos; Chahed, Karim; Bauvois, Brigitte

    2017-07-01

    A growing body of evidence points towards smoking-related phenotypic differences in chronic obstructive pulmonary disease (COPD). As COPD is associated with systemic inflammation, we determined whether smoking status is related to serum levels of matrix metalloproteinase-9 (pro- and active MMP-9), neutrophil gelatinase-associated lipocalin (NGAL) and the proMMP-9/NGAL complex in patients with COPD. Serum samples were collected in 100 stable-phase COPD patients (82 smokers, 18 never-smokers) and 28 healthy adults (21 smokers, 7 never-smokers). Serum levels of studied factors were measured in ELISA. Our data provide the first evidence of simultaneously elevated serum levels of MMP-9, NGAL and proMMP-9/NGAL in COPD smokers. While the triad discriminated between smokers and non-smokers in the COPD group, MMP-9 and proMMP-9/NGAL (but not NGAL) discriminated between smokers with and without COPD. Adjustment for age and smoking pack-years did not alter the findings. Serum MMP-9, NGAL and proMMP-9/NGAL levels were not correlated with the GOLD stage or FEV1 decline. Furthermore, serum levels of neutrophil elastase (NE) and MMP-3 (but not of IL-6 and MMP-12) were also higher in COPD smokers than in healthy smokers before and after adjustment for age and pack-years. Among COPD smokers, levels of MMP-9, NGAL and proMMP-9/NGAL were positively correlated with NE (P < 0.0001) but not with the remaining factors. Gelatin zymography detected proMMP-9 in serum samples of healthy and COPD smoking groups. Our results suggest that associated serum levels of proMMP-9, NGAL, proMMP-9/NGAL and NE may reflect the state of systemic inflammation in COPD related to cigarette smoking. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  2. Bevacizumab exacerbates sinusoidal obstruction syndrome (SOS) in the animal model and increases MMP 9 production.

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    Jafari, Azin; Matthaei, Hanno; Wehner, Sven; Tonguc, Tolga; Kalff, Jörg C; Manekeller, Steffen

    2018-04-24

    Thanks to modern multimodal treatment the ouctome of patients with colorectal cancer has experienced significant improvements. As a downside, agent specific side effects have been observed such as sinusoidal obstruction syndrome (SOS) after oxaliplatin chemotherapy (OX). Bevazicumab targeting VEGF is nowadays comprehensively used in combination protocols with OX but its impact on hepatotoxicity is thus far elusive and focus of the present study. After MCT administration 67% of animals developed SOS. GOT serum concentration significantly increased in animals developing SOS ( p SOS. In contrast, animals receiving VEGF developed SOS merely in 40% while increasing the VEGF dose led to a further decrease in SOS development to 25%. MMP 9 concentration in animals developing SOS was significantly higher compared to controls ( p SOS paralleled by MMP 9 production. Therefore, OX-Bevacizumab combination therapies should be administered with caution, especially if liver parenchyma damage is apparent. Male Sprague-Dawley rats were gavaged Monocrotaline (MCT) to induce SOS. Recombinant VEGF or an Anti-VEGF antibody was administered to MCT-treated rats and the hepatotoxic effect monitored in defined time intervals. MMP 9 expression in the liver was measured by ELISA.

  3. Elevated ratio of MMP2/MMP9 activity is associated with poor response to chemotherapy in osteosarcoma

    International Nuclear Information System (INIS)

    Kunz, Pierre; Sähr, Heiner; Lehner, Burkhard; Fischer, Christian; Seebach, Elisabeth; Fellenberg, Jörg

    2016-01-01

    Matrix metalloproteinases (MMPs) are crucially involved in the regulation of multiple stages of cancer progression. Elevated MMP levels have been associated with the development of metastases and poor prognosis in several types of cancer. However, the role of MMPs in osteosarcoma and their prognostic value is still unclear. Available data are conflicting, most likely due to different technical approaches. We hypothesized that in contrast to total mRNA or protein levels frequently analyzed in previous studies the enzymatic activities of MMPs and their inhibitors the tissue inhibitors of matrix metalloproteinases (TIMPs) are closer related to their biological functions. We therefore aimed to evaluate the reliability of different zymography techniques for the quantification of MMP and TIMP activities in osteosarcoma biopsies in order to investigate their distribution, possible regulation and prognostic value. All analyses were done using cryo-conserved osteosarcoma pretreatment biopsies (n = 18). Gene and protein expression of MMPs and TIMPs were analyzed by RT-qPCR and western blot analysis, respectively. Overall MMP activity was analyzed by in situ zymography, individual MMP activities were analyzed by gelatin zymography. Reverse zymography was used to detect and quantify TIMP activities. Strong overall MMP activities could be detected in osteosarcoma pretreatment biopsies with MMP2 and MMP9 as predominant active MMPs. In contrast to total RNA or protein expression MMP2 and MMP9 activities showed significant quantitative differences between good and poor responders. While MMP9 activity was high in the good responder group and significantly decreased in the poor responder group, MMP2 activity showed a reverse distribution. Likewise, significant differences were detected concerning the activity of TIMPs resulting in a negative correlation of TIMP1 activity with MMP2 activity (p = 0.044) and negative correlations of TIMP2 and TIMP3 with MMP9 activity (p = 0.007 and p

  4. Matrix metalloproteinase (MMP) 9 transcription in mouse brain induced by fear learning.

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    Ganguly, Krishnendu; Rejmak, Emilia; Mikosz, Marta; Nikolaev, Evgeni; Knapska, Ewelina; Kaczmarek, Leszek

    2013-07-19

    Memory formation requires learning-based molecular and structural changes in neurons, whereas matrix metalloproteinase (MMP) 9 is involved in the synaptic plasticity by cleaving extracellular matrix proteins and, thus, is associated with learning processes in the mammalian brain. Because the mechanisms of MMP-9 transcription in the brain are poorly understood, this study aimed to elucidate regulation of MMP-9 gene expression in the mouse brain after fear learning. We show here that contextual fear conditioning markedly increases MMP-9 transcription, followed by enhanced enzymatic levels in the three major brain structures implicated in fear learning, i.e. the amygdala, hippocampus, and prefrontal cortex. To reveal the role of AP-1 transcription factor in MMP-9 gene expression, we have used reporter gene constructs with specifically mutated AP-1 gene promoter sites. The constructs were introduced into the medial prefrontal cortex of neonatal mouse pups by electroporation, and the regulation of MMP-9 transcription was studied after contextual fear conditioning in the adult animals. Specifically, -42/-50- and -478/-486-bp AP-1 binding motifs of the mouse MMP-9 promoter sequence have been found to play a major role in MMP-9 gene activation. Furthermore, increases in MMP-9 gene promoter binding by the AP-1 transcription factor proteins c-Fos and c-Jun have been demonstrated in all three brain structures under investigation. Hence, our results suggest that AP-1 acts as a positive regulator of MMP-9 transcription in the brain following fear learning.

  5. domain of matrix metalloproteinase-9 (MMP-9)

    Indian Academy of Sciences (India)

    2015-12-03

    Dec 3, 2015 ... Center for Food Products (Shanghai), Shanghai 200233, People's Republic of China ... gate the natural selection hypothesis of MMP-9, the orthologous sequences from ... fast evolving rate compared to the others analyzed.

  6. Altered Expression Levels of MMP1, MMP9, MMP12, TIMP1, and IL-1β as a Risk Factor for the Elevated IOP and Optic Nerve Head Damage in the Primary Open-Angle Glaucoma Patients

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    Lukasz Markiewicz

    2015-01-01

    Full Text Available The aim of presented work was to analyze the impact of particular polymorphic changes in the promoter regions of the -1607 1G/2G MMP1, -1562 C/T MMP9, -82 A/G MMP12, -511 C/T IL-1β, and 372 T/C TIMP1 genes on their expression level in POAG patients. Blood and aqueous humor samples acquired from 50 patients with POAG and 50 control subjects were used for QPCR and protein levels analysis by ELISA. In vivo promoter activity assays were carried on HTM cells using dual luciferase assay. All studied subjects underwent ophthalmic examination, including BCVA, intraocular pressure, slit-lamp examination, gonioscopy, HRT, and OCT scans. Patients with POAG are characterized by an increased mRNA expression of MMP1, MMP9, MMP12, and IL-1β genes as compared to the control group (P<0.001. Aqueous humor acquired from patients with POAG displayed increased protein expression of MMP1, MMP9, MMP12, and IL-1β compared to the control group (P<0.001. Allele -1607 1G of MMP1 gene possesses only 42,91% of the -1607 2G allele transcriptional activity and allele -1562 C of MMP9 gene possesses only 21,86% of the -1562 T allele. Increased expression levels of metalloproteinases can be considered as a risk factor for the development of POAG.

  7. Clinical significance of RECK and MMP-9 expression in ... - AJOL

    African Journals Online (AJOL)

    DR. NJ TONUKARI

    2012-04-17

    Apr 17, 2012 ... RECK [mouse anti-human monoclonal (MMP-9) or rabbit anti- human polyclonal ..... Li R, Deng Y (2010). Expression of RECK, RAGE and MMP-9 in ... Matrix metalloproteinase-2 and -9 involvement in canine tumors. Vet.

  8. Homocysteine enhances MMP-9 production in murine macrophages via ERK and Akt signaling pathways

    International Nuclear Information System (INIS)

    Lee, Seung Jin; Lee, Yi Sle; Seo, Kyo Won; Bae, Jin Ung; Kim, Gyu Hee; Park, So Youn; Kim, Chi Dae

    2012-01-01

    Homocysteine (Hcy) at elevated levels is an independent risk factor of cardiovascular diseases, including atherosclerosis. In the present study, we investigated the effect of Hcy on the production of matrix metalloproteinases (MMP) in murine macrophages. Among the MMP known to regulate the activities of collagenase and gelatinase, Hcy exclusively increased the gelatinolytic activity of MMP-9 in J774A.1 cells as well as in mouse peritoneal macrophages. Furthermore, this activity was found to be correlated with Western blot findings in J774A.1 cells, which showed that MMP-9 expression was concentration- and time-dependently increased by Hcy. Inhibition of the ERK and Akt pathways led to a significant decrease in Hcy-induced MMP-9 expression, and combined treatment with inhibitors of the ERK and Akt pathways showed an additive effects. Activity assays for ERK and Akt showed that Hcy increased the phosphorylation of both, but these phosphorylation were not affected by inhibitors of the Akt and ERK pathways. In line with these findings, the molecular inhibition of ERK and Akt using siRNA did not affect the Hcy-induced phosphorylation of Akt and ERK, respectively. Taken together, these findings suggest that Hcy enhances MMP-9 production in murine macrophages by separately activating the ERK and Akt signaling pathways. -- Highlights: ► Homocysteine (Hcy) induced MMP-9 production in murine macrophages. ► Hcy induced MMP-9 production through ERK and Akt signaling pathways. ► ERK and Akt signaling pathways were activated by Hcy in murine macrophages. ► ERK and Akt pathways were additively act on Hcy-induced MMP-9 production. ► Hcy enhances MMP-9 production in macrophages via activation of ERK and Akt signaling pathways in an independent manner.

  9. Homocysteine enhances MMP-9 production in murine macrophages via ERK and Akt signaling pathways

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    Lee, Seung Jin; Lee, Yi Sle; Seo, Kyo Won; Bae, Jin Ung; Kim, Gyu Hee; Park, So Youn; Kim, Chi Dae, E-mail: chidkim@pusan.ac.kr

    2012-04-01

    Homocysteine (Hcy) at elevated levels is an independent risk factor of cardiovascular diseases, including atherosclerosis. In the present study, we investigated the effect of Hcy on the production of matrix metalloproteinases (MMP) in murine macrophages. Among the MMP known to regulate the activities of collagenase and gelatinase, Hcy exclusively increased the gelatinolytic activity of MMP-9 in J774A.1 cells as well as in mouse peritoneal macrophages. Furthermore, this activity was found to be correlated with Western blot findings in J774A.1 cells, which showed that MMP-9 expression was concentration- and time-dependently increased by Hcy. Inhibition of the ERK and Akt pathways led to a significant decrease in Hcy-induced MMP-9 expression, and combined treatment with inhibitors of the ERK and Akt pathways showed an additive effects. Activity assays for ERK and Akt showed that Hcy increased the phosphorylation of both, but these phosphorylation were not affected by inhibitors of the Akt and ERK pathways. In line with these findings, the molecular inhibition of ERK and Akt using siRNA did not affect the Hcy-induced phosphorylation of Akt and ERK, respectively. Taken together, these findings suggest that Hcy enhances MMP-9 production in murine macrophages by separately activating the ERK and Akt signaling pathways. -- Highlights: ► Homocysteine (Hcy) induced MMP-9 production in murine macrophages. ► Hcy induced MMP-9 production through ERK and Akt signaling pathways. ► ERK and Akt signaling pathways were activated by Hcy in murine macrophages. ► ERK and Akt pathways were additively act on Hcy-induced MMP-9 production. ► Hcy enhances MMP-9 production in macrophages via activation of ERK and Akt signaling pathways in an independent manner.

  10. Investigation of MMP-2 and MMP-9 activities in canine sera with dilated cardiomyopathy.

    Science.gov (United States)

    Chegeni, S; Khaki, Z; Shirani, D; Vajhi, A; Taheri, M; Tamrchi, Y; Rostami, A

    2015-01-01

    Dilated cardiomyopathy (DCM) is accompanied by myocytes and connective tissue changes. Matrix metalloproteinases (MMPs) play important roles in cardiac remodeling. It seems that the gelatinases (MMP-2 and MMP-9) are effective enzymes in cardiomyopathy. Dilated cardiomyopathy was confirmed in 22 dogs (patient group) including 11 female and 11 male by clinical examination, auscultation, thoracic radiography and echocardiography. 17 healthy dogs (control group) with similar weight and breed to patients were also selected from referred cases to Small Animal Hospital of the Veterinary Faculty of Tehran University and the same diagnostic procedures were performed on them. After that, serum MMP-2 and MMP-9 of control and patient groups were measured by semi-quantitative zymography. Semiquantitative analysis of zymograms from canine serums with DCM showed that total MMP-9 in patients is more than control group, while there was no significant difference in total MMP-2 between the two groups. Pro-MMP-2 was not detected in patient group but its active form was present in both groups, of course MMP-2 activity in patients was significantly more than control. Active form of MMP-9 was detected only in patients. Although pro-MMP-9 was present in both groups, its level in control group was significantly higher than patients. The heart enlargement was observed in the left, right or both parts. Statistically significant differences in active form of MMP-2 and MMP-9 levels were observed between different groups of heart enlargement (right, left and both parts) compared to control but this difference was not significant considering chambers affected and VHS (vertebral heart score) groups. In conclusion, although there are some changes in serum MMP-2 and MMP-9 levels in canine DCM, it seems that increase of MMP-9 is more prominent than MMP-2 and neither of them were affected by heart enlargement or VHS grade.

  11. Gelatinase B/MMP-9 in Tumour Pathogenesis and Progression

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    Farina, Antonietta Rosella; Mackay, Andrew Reay, E-mail: andrewreay.mackay@univaq.it [Department of Applied Clinical and Biotechnological Sciences, University of L’Aquila, Via Vetoio, Coppito 2, L’Aquila 67100 (Italy)

    2014-01-27

    Since its original identification as a leukocyte gelatinase/type V collagenase and tumour type IV collagenase, gelatinase B/matrix metalloproteinase (MMP)-9 is now recognised as playing a central role in many aspects of tumour progression. In this review, we relate current concepts concerning the many ways in which gelatinase B/MMP-9 influences tumour biology. Following a brief outline of the gelatinase B/MMP-9 gene and protein, we analyse the role(s) of gelatinase B/MMP-9 in different phases of the tumorigenic process, and compare the importance of gelatinase B/MMP-9 source in the carcinogenic process. What becomes apparent is the importance of inflammatory cell-derived gelatinase B/MMP-9 in tumour promotion, early progression and triggering of the “angiogenic switch”, the integral relationship between inflammatory, stromal and tumour components with respect to gelatinase B/MMP-9 production and activation, and the fundamental role for gelatinase B/MMP-9 in the formation and maintenance of tumour stem cell and metastatic niches. It is also apparent that gelatinase B/MMP-9 plays important tumour suppressing functions, producing endogenous angiogenesis inhibitors, promoting inflammatory anti-tumour activity, and inducing apoptosis. The fundamental roles of gelatinase B/MMP-9 in cancer biology underpins the need for specific therapeutic inhibitors of gelatinase B/MMP-9 function, the use of which must take into account and substitute for tumour-suppressing gelatinase B/MMP-9 activity and also limit inhibition of physiological gelatinase B/MMP-9 function.

  12. Serum Levels of IL-1β, IL-6, TGF-β, and MMP-9 in Patients Undergoing Carotid Artery Stenting and Regulation of MMP-9 in a New In Vitro Model of THP-1 Cells Activated by Stenting

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    Rongrong Zhang

    2015-01-01

    Full Text Available Inflammation plays an important role in the pathophysiological process after carotid artery stenting (CAS. Monocyte is a significant source of inflammatory cytokines in vascular remodeling. Telmisartan could reduce inflammation. In our study, we first found that, after CAS, the serum IL-1β, IL-6, TGF-β, and MMP-9 levels were significantly increased, but only MMP-9 level was elevated no less than 3 months. Second, we established a new in vitro model, where THP-1 monocytes were treated with the supernatants of human umbilical vein endothelial cells (HUVECs that were scratched by pipette tips, which mimics monocytes activated by mechanical injury of stenting. The treatment enhanced THP-1 cell adhesion, migration and invasion ability, and the phosphorylation of ERK1/2 and Elk-1 and MMP-9 expression were significantly increased. THP-1 cells pretreated with PD98095 (ERK1/2 inhibitor attenuated the phosphorylation of ERK1/2 and Elk-1 and upregulation of MMP-9, while pretreatment with telmisartan merely decreased the phosphorylation of Elk-1 and MMP-9 expression. These results suggested that IL-1β, IL-6, TGF-β, and MMP-9 participate in the pathophysiological process after CAS. Our new in vitro model mimics monocytes activated by stenting. MMP-9 expression could be regulated through ERK1/2/Elk-1 pathway, and the protective effects of telmisartan after stenting are partly attributed to its MMP-9 inhibition effects via suppression of Elk-1.

  13. The MMP-9 -1562 C/T polymorphism in the presence of metabolic syndrome increases the risk of clinical events in patients with coronary artery disease.

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    Trine B Opstad

    Full Text Available Elevated levels of matrix metalloproteinase (MMP-9 have been associated with the metabolic syndrome (MetS and cardiovascular events. The MMP-9 -1562 C/T polymorphism has furthermore been shown as a risk factor for coronary artery disease (CAD. The non-favourable cardiometabolic state in MetS may increase the risk. We aimed to investigate the influence of MMP-9 -1562 C/T polymorphism in subjects with CAD and MetS.Patients (n = 1000 with verified CAD stratified in Mets +/- (n = 244/756, were analyzed for the MMP-9 -1562 C/T polymorphism and related to clinical events after 2 years follow-up. Serum levels of total MMP-9 and tissue inhibitor of matrix metalloproteinases (TIMP-1 were analyzed in all, whereas MMP-9 activity, extracellular matrix metalloproteinase inducer (EMMPRIN, and expression of the two genes were analyzed in a subset of 240 randomly selected patients.Totally, 106 clinical endpoints were recorded. In MetS; the T-allele associated with 5.5 fold increase in event rate (p<0.0001, increased with number of MetS components, a 117% increase in total MMP-9 levels (TT homozygous, p = 0.05, significantly higher total- and endogenous active MMP-9 and TIMP-1 levels (p<0.01 all, and EMMPRIN was inversely correlated with pro- and endogenous active MMP-9 (p<0.05, both. In non-MetS; the T-allele was not associated with new events, nor higher MMP-9 levels. EMMPRIN was significantly correlated with total MMP-9 and TIMP-1 (p<0.01, both and the two genes were inter-correlated (p<0.001.In CAD patients with MetS, the MMP-9 T-allele increased the risk of clinical events, probably mediated through elevated MMP-9 levels and altered MMP-9 regulation.

  14. Correlation of circulating MMP-9 with white blood cell count in humans: effect of smoking.

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    Soren Snitker

    Full Text Available Matrix metalloproteinase-9 (MMP-9 is an emerging biomarker for several disease conditions, where white blood cell (WBC count is also elevated. In this study, we examined the relationship between MMP-9 and WBC levels in apparently healthy smoking and non-smoking human subjects.We conducted a cross-sectional study to assess the relationship of serum MMP-9 with WBC in 383 men and 356 women. Next, we divided the male population (women do not smoke in this population into three groups: never (n = 243, current (n = 76 and former (n = 64 smokers and compared the group differences in MMP-9 and WBC levels and their correlations within each group.Circulating MMP-9 and WBC count are significantly correlated in men (R(2 = 0.13, p<0.001 and women (R(2 = 0.19, p<0.001. After stratification by smoking status, MMP-9 level was significantly higher in current smokers (mean ± SE; 663.3±43.4 ng/ml, compared to never (529.7±20.6 and former smokers (568±39.3. WBC count was changed in a similar pattern. Meanwhile, the relationship became stronger in current smokers with increased correlation coefficient of r = 0.45 or R(2 = 0.21 (p<0.001 and steeper slope of ß = 1.16±0.30 (p<0.001 in current smokers, compared to r = 0.26 or R(2 = 0.07 (p<0.001 and ß = 0.34±0.10 (p<0.001 in never smokers.WBC count accounts for 13% and 19% of MMP-9 variance in men and women, respectively. In non-smoking men, WBC count accounts for 7% of MMP-9 variance, but in smoking subjects, it accounts for up to 21% of MMP-9 variance. Thus, we have discovered a previously unrecognized correlation between the circulating MMP-9 and WBC levels in humans.

  15. Polimorfisme Gen MMP-9, Ekspresi MMP-9, dan Indeks Apoptosis Sel Serviks pada Kehamilan 21–36 Minggu

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    Udin Sabarudin

    2011-12-01

    Full Text Available Over expression and premature activation of matrix metalloproteinase (MMP can lead to degradation of amnion chorionic membrane which clinically called premature rupture of membrane (PROM. Increasing MMP activity caused by matrix metalloproteinase-9 (MMP-9 gene polymorphism (C-1562T will be followed by apoptosis. This study was aimed to find the differences between MMP-9 expression and cervical apoptotic index (AI and also MMP-9 (C-1562T polymorphism on 21–36 weeks of pregnancy with or without PROM. This was case control study and conducted in Dr. Hasan Sadikin Hospital and Bandung Networking Hospitals (May−November 2009. There were no significant correlation between MMP-9 expression and cervical AI in every variable on both groups. Three cases of PROM were found in mothers below 20 years of age. Women with 28−34 weeks of pregnancy had a greater risk for PROM than 21−28 weeks. Pregnant women with body mass index (BMI 19−26, had risk to have PROM. Only one sample that showed a MMP-9 (C-1562T polymorphism in the premature labor with PROM group. It can be concluded that there are no significant correlation between MMP-9 expression and cervical cells AI on both groups as well as MMP-9 (C-1562T polymorphism which can alter MMP-9 expression.

  16. Polymorphisms of the MMP-9 gene and abdominal aortic aneurysm

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    Smallwood, Linda; Allcock, Richard; van Bockxmeer, Frank; Warrington, Nicole; Palmer, Lyle J; Iacopetta, Barry; Golledge, Jonathan; Norman, Paul E

    2008-01-01

    Background Increased matrix metalloproteinase-9 (MMP-9) activity has been implicated in the formation of abdominal aortic aneurysms (AAAs). The aim of the present study was to explore the association between potentially functional variants of the MMP-9 gene and AAA. Method The −1562C>T and −1811A>T variants of the MMP-9 gene were genotyped in 678 men with AAAs (>30mm in diameter) and 659 controls (aortic diameter 19−22mm) recruited from a population-based trial of screening for AAAs. The levels of MMP-9 were measured in a random subset of 300 cases and 84 controls. The association between genetic variants (including haplotypes) and AAA was assessed using multivariate logistic regression. Results There was no association between the MMP-9 −1562C>T (OR 0.70 95%CI 0.27, 1.82) or −1811A>T (OR 0.71, 95%CI 0.28, 1.85) genotypes, or the most common haplotype (OR 0.81 95%CI 0.62, 1.05), and AAA. The serum MMP-9 concentration (ng/mL) was higher in cases than controls and in minor allele carriers in cases and controls although the differences were not statistically significant. Conclusion The results suggest that a genetic tendency to have higher levels of circulating MMP-9 is not associated with AAAs. PMID:18763261

  17. Suppression of MMP-9 by doxycycline in brain arteriovenous malformations

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    Li Jenny F

    2005-01-01

    Full Text Available Abstract Background The primary aim of this study is to demonstrate the feasibility of utilizing doxycycline to suppress matrix metalloproteinase-9 (MMP-9 in brain arteriovenous malformations (AVMs. Methods Ex-vivo treatment of AVM tissues: Intact AVM tissues were treated with doxycycline for 48 hours. Active and total MMP-9 in the medium were measured. Pilot trial: AVM patients received either doxycycline (100 mg or placebo twice a day for one week prior to AVM resection. Active and total MMP-9 in BVM tissues were measured. Results Ex-vivo treatment of AVM tissues: Doxycycline at 10 and 100 μg/ml significantly decreased MMP-9 levels in AVM tissues ex-vivo (total: control vs 10 vs 100 μg/ml = 100 ± 6 vs 60 ± 16 vs 61 ± 9%; active: 100 ± 8 vs 48 ± 16 vs 59 ± 10%. Pilot trial: 10 patients received doxycycline, and 4 patients received placebo. There was a trend for both MMP-9 levels to be lower in the doxycycline group than in the placebo group (total: 2.18 ± 1.94 vs 3.26 ± 3.58, P = .50; active: 0.48 ± 0.48 vs 0.95 ± 1.01 ng/100 μg protein, P = .25. Conclusions A clinically relevant concentration of doxycycline decreased MMP-9 in ex-vivo AVM tissues. Furthermore, there was a trend that oral doxycycline for as short as one week resulted in a decrease in MMP-9 in AVM tissues. Further studies are warranted to justify a clinical trial to test effects of doxycycline on MMP-9 expression in AVM tissues.

  18. Activation of MMP-9 activity by acrolein in saliva from patients with primary Sjögren's syndrome and its mechanism.

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    Uemura, Takeshi; Suzuki, Takehiro; Saiki, Ryotaro; Dohmae, Naoshi; Ito, Satoshi; Takahashi, Hoyu; Toida, Toshihiko; Kashiwagi, Keiko; Igarashi, Kazuei

    2017-07-01

    We have recently reported that the altered recognition patterns of immunoglobulins due to acrolein conjugation are at least partially responsible for autoimmune diseases in patients with primary Sjögren's syndrome (pSS). In the current study, it was found that the specific activity (activity/ng protein) of metalloproteinase-9 (MMP-9) in saliva was elevated about 2.4-fold in pSS patients. Accordingly, it was examined whether MMP-9 is activated by acrolein. It was found that the MMP-9 with 92kDa molecular weight was activated by acrolein. Under the conditions studied, Cys99, located in the propeptide, was conjugated with acrolein together with Cys230, 244, 302, 314, 329, 347, 361, 373, 388 and 516, which are located in fibronectin repeats and glycosyl domains, but not on the active site of MMP-9. In addition, 82 and 68kDa constructs of MMP-9s, lacking the NH 2 -terminal domain that contains Cys99, were not activated by acrolein. The results suggest that acrolein conjugation at Cys99 caused the active site of MMP-9 to be exposed. Activation of MMP-9 by acrolein was inhibited by cysteine, and slightly by lysine, because these amino acids inhibited acrolein conjugation with MMP-9. Conversely, MMP-9 activity in the presence of 50μM acrolein was enhanced by 100μM histidine. This was due to the inhibition of acrolein conjugation with His405 and 411 located at the Zn 2+ binding site of MMP-9. These results suggest that activation of 92kDa MMP-9 by acrolein is involved in tissue damage in pSS patients and is regulated by cysteine and histidine, and slightly by lysine. Activated 82 and 68kDa MMP-9s were not detected in saliva of pSS patients by Western blotting. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Mmp-9 responsive PEG cleavable nanovesicles for efficient delivery of chemotherapeutics to pancreatic cancer.

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    Kulkarni, Prajakta S; Haldar, Manas K; Nahire, Rahul R; Katti, Preeya; Ambre, Avinash H; Muhonen, Wallace W; Shabb, John B; Padi, Sathish K R; Singh, Raushan K; Borowicz, Pawel P; Shrivastava, D K; Katti, Kalpana S; Reindl, Katie; Guo, Bin; Mallik, Sanku

    2014-07-07

    Significant differences in biochemical parameters between normal and tumor tissues offer an opportunity to chemically design drug carriers which respond to these changes and deliver the drugs at the desired site. For example, overexpression of the matrix metalloproteinase-9 (MMP-9) enzyme in the extracellular matrix of tumor tissues can act as a trigger to chemically modulate the drug delivery from the carriers. In this study, we have synthesized an MMP-9-cleavable, collagen mimetic lipopeptide which forms nanosized vesicles with the POPC, POPE-SS-PEG, and cholesteryl-hemisuccinate lipids. The lipopeptide retains the triple-helical conformation when incorporated into these nanovesicles. The PEG groups shield the substrate lipopeptides from hydrolysis by MMP-9. However, in the presence of elevated glutathione levels, the PEG groups are reductively removed, exposing the lipopeptides to MMP-9. The resultant peptide-bond cleavage disturbs the vesicles' lipid bilayer, leading to the release of encapsulated contents. These PEGylated nanovesicles are capable of encapsulating the anticancer drug gemcitabine with 50% efficiency. They were stable in physiological conditions and in human serum. Effective drug release was demonstrated using the pancreatic ductal carcinoma cells (PANC-1 and MIAPaCa-2) in two-dimensional and three-dimensional "tumor-like" spheroid cultures. A reduction in tumor growth was observed after intravenous administration of the gemcitabine-encapsulated nanovesicles in the xenograft model of athymic, female nude mice.

  20. Measurement of MMP-9 and -12 degraded elastin (ELM) provides unique information on lung tissue degradation

    Science.gov (United States)

    2012-01-01

    Background Elastin is an essential component of selected connective tissues that provides a unique physiological elasticity. Elastin may be considered a signature protein of lungs where matrix metalloprotease (MMP) -9-and -12, may be considered the signature proteases of the macrophages, which in part are responsible for tissue damage during disease progression. Thus, we hypothesized that a MMP-9/-12 generated fragment of elastin may be a relevant biochemical maker for lung diseases. Methods Elastin fragments were identified by mass-spectrometry and one sequence, generated by MMP-9 and -12 (ELN-441), was selected for monoclonal antibody generation and used in the development of an ELISA. Soluble and insoluble elastin from lung was cleaved in vitro and the time-dependent release of fragments was assessed in the ELN-441 assay. The release of ELN-441 in human serum from patients with chronic obstructive pulmonary disease (COPD) (n = 10) and idiopathic pulmonary fibrosis (IPF) (n = 29) were compared to healthy matched controls (n = 11). Results The sequence ELN-441 was exclusively generated by MMP-9 and -12 and was time-dependently released from soluble lung elastin. ELN-441 levels were 287% higher in patients diagnosed with COPD (p elastin. This fragment was elevated in serum from patients with the lung diseases IPF and COPD, however these data needs to be validated in larger clinical settings. PMID:22818364

  1. Neutrophil Gelatinase-Associated Lipocalin (NGAL), Pro-Matrix Metalloproteinase-9 (pro-MMP-9) and Their Complex Pro-MMP-9/NGAL in Leukaemias

    Energy Technology Data Exchange (ETDEWEB)

    Bouchet, Sandrine; Bauvois, Brigitte, E-mail: brigitte.bauvois@crc.jussieu.fr [INSERM U1138, Université Pierre et Marie Curie, Université Paris-Descartes, Centre de Recherche des Cordeliers, Paris 75006 (France)

    2014-04-04

    Matrix metalloproteinase (MMP)-9 and neutrophil gelatinase-associated lipocalin (NGAL) have gained attention as cancer biomarkers. The inactive zymogen form of MMP-9 (pro-MMP-9) also exists as a disulphide-linked heterodimer bound to NGAL in humans. Leukaemias represent a heterogeneous group of neoplasms, which vary in their clinical behavior and pathophysiology. In this review, we summarize the current literature on the expression profiles of pro-MMP-9 and NGAL as prognostic factors in leukaemias. We also report the expression of the pro-MMP-9/NGAL complex in these diseases. We discuss the roles of (pro)-MMP-9 (active and latent forms) and NGAL in tumour development, and evaluate the mechanisms by which pro-MMP-9/NGAL may influence the actions of (pro)-MMP-9 and NGAL in cancer. Emerging knowledge about the coexpression and the biology of (pro)-MMP-9, NGAL and their complex in cancer including leukaemia may improve treatment outcomes.

  2. Urinary MMP-9/NGAL complex in children with acute cystitis.

    Science.gov (United States)

    Hatipoglu, Sami; Sevketoglu, Esra; Gedikbasi, Asuman; Yilmaz, Alev; Kiyak, Aysel; Mulazimoglu, Mehmet; Aydogan, Gonul; Ozpacaci, Tevfik

    2011-08-01

    The matrix metalloproteinase-9 (MMP-9) and neutrophil gelatinase associated lipocalin (NGAL) are shown to increase in an inflammatory situation. Based on our previous reports that NGAL can be detected in the urine of children with urinary tract infection (UTI), we also asked whether MMP-9/NGAL complex could be detected in the urine of children with UTI. This multicenter, prospective study was conducted between October 2009 and October 2010. Seventy-one patients with symptomatic culture proven UTI, 37 asymptomatic children with contaminated urine and 37 healthy children were recruited. Mean uMMP-9/NGAL/Cr levels were significantly higher in the UTI group than in the control group (p UTI. Using a cut-off value, sensitivity and specificity were 98.6 and 97.3%, respectively. The mean levels of uMMP-9/NGAL/cr in the UTI group were also significantly higher than those in the contamination group (p UTI group were significantly higher before treatment than after treatment (p UTI in children. Identification of NGAL-MMP-9/cr levels in the urine of suspected UTI patients may also be useful to differentiate between contamination and infection and for monitoring of treatment response in children.

  3. Mercury exposure induces cytoskeleton disruption and loss of renal function through epigenetic modulation of MMP9 expression.

    Science.gov (United States)

    Khan, Hafizurrahman; Singh, Radha Dutt; Tiwari, Ratnakar; Gangopadhyay, Siddhartha; Roy, Somendu Kumar; Singh, Dhirendra; Srivastava, Vikas

    2017-07-01

    Mercury is one of the major heavy metal pollutants occurring in elemental, inorganic and organic forms. Due to ban on most inorganic mercury containing products, human exposure to mercury generally occurs as methylmercury (MeHg) by consumption of contaminated fish and other sea food. Animal and epidemiological studies indicate that MeHg affects neural and renal function. Our study is focused on nephrotoxic potential of MeHg. In this study, we have shown for the first time how MeHg could epigenetically modulate matrix metalloproteinase 9(MMP9) to promote nephrotoxicity using an animal model of sub chronic MeHg exposure. MeHg caused renal toxicity as was seen by increased levels of serum creatinine and expression of early nephrotoxicity markers (KIM-1, Clusterin, IP-10, and TIMP). MeHg exposure also correlated strongly with induction of MMP9 mRNA and protein in a dose dependent manner. Further, while induction of MMP9 promoted cytoskeleton disruption and loss of cell-cell adhesion (loss of F-actin, Vimentin and Fibronectin), inhibition of MMP9 was found to reduce these disruptions. Mechanistic studies by ChIP analysis showed that MeHg modulated MMP9 by promoting demethylation of its regulatory region to increase its expression. Bisulfite sequencing identified critical CpGs in the first exon of MMP9 which were demethylated following MeHg exposure. ChIP studies also showed loss of methyl binding protein, MeCP2 and transcription factor PEA3 at the demethylated site confirming decreased CpG methylation. Our studies thus show how MeHg could epigenetically modulate MMP9 to promote cytoskeleton disruption leading to loss of renal function. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. DNA Methylation of MMP9 Is Associated with High Levels of MMP-9 Messenger RNA in Periapical Inflammatory Lesions.

    Science.gov (United States)

    Campos, Kelma; Gomes, Carolina Cavalieri; Farias, Lucyana Conceição; Silva, Renato Menezes; Letra, Ariadne; Gomez, Ricardo Santiago

    2016-01-01

    Matrix metalloproteinases (MMPs) are the major class of enzymes responsible for degradation of extracellular matrix components and participate in the pathogenesis of periapical inflammatory lesions. MMP expression may be regulated by DNA methylation. The purpose of the present investigation was to analyze the expression of MMP2 and MMP9 in periapical granulomas and radicular cysts and to test the hypothesis that, in these lesions, their transcription may be modulated by DNA methylation. Methylation-specific polymerase chain reaction was used to evaluate the DNA methylation pattern of the MMP2 gene in 13 fresh periapical granuloma samples and 10 fresh radicular cyst samples. Restriction enzyme digestion was used to assess methylation of the MMP9 gene in 12 fresh periapical granuloma samples and 10 fresh radicular cyst samples. MMP2 and MMP9 messenger RNA transcript levels were measured by quantitative real-time polymerase chain reaction. All periapical lesions and healthy mucosa samples showed partial methylation of the MMP2 gene; however, periapical granulomas showed higher MMP2 mRNA expression levels than healthy mucosa (P = .014). A higher unmethylated profile of the MMP9 gene was found in periapical granulomas and radicular cysts compared with healthy mucosa. In addition, higher MMP9 mRNA expression was observed in the periapical lesions compared with healthy tissues. The present study suggests that the unmethylated status of the MMP9 gene in periapical lesions may explain the observed up-regulation of messenger RNA transcription in these lesions. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  5. Repeated cadmium nebulizations induce pulmonary MMP-2 and MMP-9 production and enphysema in rats

    International Nuclear Information System (INIS)

    Kirschvink, Nathalie; Vincke, Gregoire; Fievez, Laurence; Onclinx, Cecile; Wirth, Delphine; Belleflamme, Michele; Louis, Renaud; Cataldo, Didier; Peck, Michael J.; Gustin, Pascal

    2005-01-01

    This study describes induction of pulmonary inflammation, production of matrix metalloprotease of type 2 (MMP-2) and type 9 (MMP-9), and emphysema in cadmium (Cd)-exposed rats. Sprague-Dawley rats were randomly distributed into two groups: one placebo-exposed group undergoing saline (NaCl 0.9%) inhalation (n = 30) and one Cd-exposed group undergoing cadmium (CdCl 2 0.1%) inhalation (n = 30). The animals of the placebo- and Cd-exposed groups were divided in five subgroups (n = 6). Subgroups underwent either a single exposure of 1 h or repeated exposures three times weekly for 1 h during 3 weeks (3W), 5 weeks (5W), 5 weeks followed by 2 weeks without exposure (5W + 2) or 5 weeks followed by 4 weeks without exposure (5W + 4). Each animal underwent determination of enhanced pause (Penh) as index of airflow limitation prior to the first exposure as well as before sacrifice. The animals were sacrificed the day after their last exposure. The left lung was fixed for histomorphometric analysis (determination of median interwall distance (MIWD)), whilst bronchoalveolar lavage fluid (BALF) was collected from the right lung. BALF was analyzed cytologically, and MMP-2 and MMP-9 levels were determined by gelatine zymography. Twelve rats previously instilled with pancreatic elastase were used as positive emphysema controls and underwent the same investigations. Cd-exposure induced a significant increase of BALF macrophages, neutrophils and MMP-9 up to 5W + 4, whereas MMP-2 gelatinolytic activity returned to baseline levels within 5W. MIWD was significantly increased in all repeatedly Cd-exposed groups and elastase-treated rats. Penh was increased in Cd-exposed rats after a single exposure and after 3W. MMP gelatinolytic activity was significantly correlated with macrophages, neutrophils and Penh. In repeatedly exposed rats, MIWD was positively and significantly correlated with MMP gelatinolytic activity, suggesting that increased MMP-2 and MMP-9 production favours the development

  6. Zymographic patterns of MMP-2 and MMP-9 in the CSF and cerebellum of dogs with subacute distemper leukoencephalitis.

    Science.gov (United States)

    Machado, Gisele F; Melo, Guilherme D; Souza, Milena S; Machado, Andressa A; Migliolo, Daniela S; Moraes, Olívia C; Nunes, Cáris M; Ribeiro, Erica S

    2013-07-15

    Distemper leukoencephalitis is a disease caused by the canine distemper virus (CDV) infection. It is a demyelinating disease affecting mainly the white matter of the cerebellum and areas adjacent to the fourth ventricle; the enzymes of the matrix metalloproteinases (MMPs) group, especially MMP-2 and MMP-9 have a key role in the myelin basic protein fragmentation and in demyelination, as well as in leukocyte traffic into the nervous milieu. To evaluate the involvement of MMPs during subacute distemper leukoencephalitis, we measured the levels of MMP-2 and MMP-9 by zymography in the cerebrospinal fluid (CSF) and in the cerebellum of 14 dogs naturally infected with CDV and 10 uninfected dogs. The infected dogs presented high levels of pro-MMP-2 in the CSF and elevated levels of pro-MMP-2 and pro-MMP-9 in the cerebellar tissue. Active MMP-2 was detected in the CSF of some infected dogs. As active MMP-2 and MMP-9 are required for cellular migration across the blood-brain barrier and any interference between MMPs and their inhibitors may result in an amplification of demyelination, this study gives additional support to the involvement of MMPs during subacute distemper leukoencephalitis and suggests that MMP-2 and MMP-9 may take part in the brain inflammatory changes of this disease. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. MMP9 polymorphisms and breast cancer risk: a report from the Shanghai Breast Cancer Genetics Study.

    Science.gov (United States)

    Beeghly-Fadiel, Alicia; Lu, Wei; Shu, Xiao-Ou; Long, Jirong; Cai, Qiuyin; Xiang, Yongbin; Gao, Yu-Tang; Zheng, Wei

    2011-04-01

    In addition to tumor invasion and angiogenesis, matrix metalloproteinase (MMP)9 also contributes to carcinogenesis and tumor growth. Genetic variation that may influence MMP9 expression was evaluated among participants of the Shanghai Breast Cancer Genetics Study (SBCGS) for associations with breast cancer susceptibility. In stage 1, 11 MMP9 single nucleotide polymorphisms (SNPs) were genotyped by the Affymetrix Targeted Genotyping System and/or the Affymetrix Genome-Wide Human SNP Array 6.0 among 4,227 SBCGS participants. One SNP was further genotyped using the Sequenom iPLEX MassARRAY platform among an additional 6,270 SBCGS participants. Associations with breast cancer risk were evaluated by odds ratios (OR) and 95% confidence intervals (CI) from logistic regression models that included adjustment for age, education, and genotyping stage when appropriate. In Stage 1, rare allele homozygotes for a promoter SNP (rs3918241) or a non-synonymous SNP (rs2274756, R668Q) tended to occur more frequently among breast cancer cases (P value = 0.116 and 0.056, respectively). Given their high linkage disequilibrium (D' = 1.0, r (2) = 0.97), one (rs3918241) was selected for additional analysis. An association with breast cancer risk was not supported by additional Stage 2 genotyping. In combined analysis, no elevated risk of breast cancer among homozygotes was found (OR: 1.2, 95% CI: 0.8-1.8). Common genetic variation in MMP9 was not found to be significantly associated with breast cancer susceptibility among participants of the Shanghai Breast Cancer Genetics Study.

  8. Irradiation-induced angiogenesis is associated with an MMP-9-miR-494-syndecan-1 regulatory loop in medulloblastoma cells.

    Science.gov (United States)

    Asuthkar, S; Velpula, K K; Nalla, A K; Gogineni, V R; Gondi, C S; Rao, J S

    2014-04-10

    Matrix metalloproteinase-9 (MMP-9) represents one of the most prominent proteins associated with tumorigenesis and is a modulator of the tumor microenvironment during angiogenesis. Recently, syndecan-1 (SDC1), a transmembrane heparan sulfate-bearing proteoglycan, was also speculated to have a critical role in contributing to angiogenesis when associated with MMP-9. However, the mechanism behind their synergistic regulation is not fully understood. In the current study, we report for the first time that ionizing radiation (IR)-induced MMP-9 enhances SDC1 shedding, corroborating to tube-inducing ability of medulloblastoma (MB) cells. Furthermore, we observed that the tumor angiogenesis is associated with higher MMP-9-SDC1 interactions on both the cell surface and extracellular medium. Our results also revealed the existence of a novel regulatory mechanism where MMP-9 drives the suppression of miR-494, resulting in enhanced SDC1 shedding and angiogenesis. From the in situ hybridization analysis, we found that MMP-9-specific shRNA (shMMP-9) treatment of mouse intracranial tumors resulted in elevated expression of miR-494. This negative correlation between MMP-9 and miR-494 levels was observed to be dependent on the methylation status of a miR-494 promoter-associated CpG island region (-186 to -20), which was confirmed by bisulfite-sequencing and methylation-specific PCR (MSP) analysis. Further, validation of MMP-9 and SDC1 3'-untranslated region (3'-UTR) targets with luciferase reporter assay provided a more favorable result for miR-494-mediated regulation of SDC1 but not of MMP-9, suggesting that the 3'-UTR of SDC1 mRNA is a direct target of miR-494. Overall, our results indicate that angiogenesis induced by radiotherapy is associated with an MMP-9-miR-494-SDC1 regulatory loop and that MMP-9-SDC1 activity creates a negative feedback loop by regulating the expression of miR-494.

  9. Neutrophil Gelatinase-Associated Lipocalin (NGAL, Pro-Matrix Metalloproteinase-9 (pro-MMP-9 and Their Complex Pro-MMP-9/NGAL in Leukaemias

    Directory of Open Access Journals (Sweden)

    Sandrine Bouchet

    2014-04-01

    Full Text Available Matrix metalloproteinase (MMP-9 and neutrophil gelatinase-associated lipocalin (NGAL have gained attention as cancer biomarkers. The inactive zymogen form of MMP-9 (pro-MMP-9 also exists as a disulphide-linked heterodimer bound to NGAL in humans. Leukaemias represent a heterogeneous group of neoplasms, which vary in their clinical behavior and pathophysiology. In this review, we summarize the current literature on the expression profiles of pro-MMP-9 and NGAL as prognostic factors in leukaemias. We also report the expression of the pro-MMP-9/NGAL complex in these diseases. We discuss the roles of (pro-MMP-9 (active and latent forms and NGAL in tumour development, and evaluate the mechanisms by which pro-MMP-9/NGAL may influence the actions of (pro-MMP-9 and NGAL in cancer. Emerging knowledge about the coexpression and the biology of (pro-MMP-9, NGAL and their complex in cancer including leukaemia may improve treatment outcomes.

  10. Circulating levels of matrix metalloproteinase-9 (MMP-9, neutrophil gelatinase-associated lipocalin (NGAL and their complex MMP-9/NGAL in breast cancer disease

    Directory of Open Access Journals (Sweden)

    Nonni Afroditi

    2009-11-01

    Full Text Available Abstract Background Recent evidence suggests that neutrophil gelatinase-associated lipocalin (NGAL expression is induced in many types of human cancer, while detection of its complex with matrix metalloproteinase-9 (MMP-9 is correlated with cancer disease status. We aim to evaluate the serum expression of MMP-9, NGAL and their complex (MMP-9/NGAL during the diagnostic work-up of women with breast abnormalities and investigate their correlation with disease severity. Methods The study included 113 women with non-palpable breast lesions undergoing vacuum-assisted breast biopsy for histological diagnosis, and 30 healthy women, which served as controls. Expression levels of MMP-9, NGAL and their complex MMP-9/NGAL were determined in peripheral blood samples with immunoenzymatic assays. Results Women with invasive ductal carcinoma exhibited significantly increased levels of MMP-9, NGAL and MMP-9/NGAL compared to healthy controls (MMP-9: p Conclusion These findings suggest that the serum measurement of MMP-9 and NGAL may be useful in non-invasively monitoring breast cancer progression, while supporting their potential role as early biomarkers of breast disease status.

  11. Cadmium exposure inhibits MMP2 and MMP9 activities in the prostate and testis

    International Nuclear Information System (INIS)

    Lacorte, Livia M.; Rinaldi, Jaqueline C.; Justulin, Luis A.; Delella, Flávia K.; Moroz, Andrei; Felisbino, Sérgio L.

    2015-01-01

    Matrix metalloproteinases (MMPs) are zinc (Zn 2+ ) and calcium (Ca 2+ ) dependant endopeptidases, capable of degradation of numerous components of the extracellular matrix. Cadmium (Cd 2+ ) is a well known environmental contaminant which could impair the activity of MMPs. In this sense, this study was conducted to evaluate if Cd 2+ intake inhibits these endopeptidases activities at the rat prostate and testicles and if it directly inhibits the activity of MMP2 and MMP9 at gelatinolytic assays when present in the incubation buffer. To investigate this hypothesis, Wistar rats (5 weeks old), were given tap water (untreated, n = 9), or 15 ppm CdCl 2 diluted in drinking water, during 10 weeks (n = 9) and 20 weeks (n = 9). The animals were euthanized and their ventral prostate, dorsal prostate, and testicles were removed. These tissue samples were processed for protein extraction and subjected to gelatin zymography evaluation. Additionally, we performed an experiment of gelatin zymography in which 5 μM or 2 mM cadmium chloride (CdCl 2 ) was directly dissolved at the incubation buffer, using the prostatic tissue samples from untreated animals that exhibited the highest MMP2 and MMP9 activities in the previous experiment. We have found that CdCl 2 intake in the drinking water led to the inhibition of 35% and 30% of MMP2 and MMP9 (p < 0.05) at the ventral prostate and testis, respectively, in Cd 2+ treated animals when compared to controls. Moreover, the activities of the referred enzymes were 80% and 100% inhibited by 5 μM and 2 mM of CdCl 2 , respectively, even in the presence of 10 mM of CaCl 2 within the incubation buffer solution. These important findings demonstrate that environmental cadmium contamination may deregulate the natural balance in the extracellular matrix turnover, through MMPs downregulation, which could contribute to the toxic effects observed in prostatic and testicular tissue after its exposure. - Highlights: • Wistar rats were given

  12. Cadmium exposure inhibits MMP2 and MMP9 activities in the prostate and testis

    Energy Technology Data Exchange (ETDEWEB)

    Lacorte, Livia M.; Rinaldi, Jaqueline C.; Justulin, Luis A.; Delella, Flávia K. [Univ Estadual Paulista – UNESP, Institute of Biosciences, Department of Morphology, Extracellular Matrix Laboratory, Botucatu, SP (Brazil); Moroz, Andrei [Univ Estadual Paulista – UNESP, School of Pharmaceutical Sciences, Department of Bioprocess and Biotechnology, Cell Culture Laboratory, Araraquara, SP (Brazil); Felisbino, Sérgio L., E-mail: felisbin@ibb.unesp.br [Univ Estadual Paulista – UNESP, Institute of Biosciences, Department of Morphology, Extracellular Matrix Laboratory, Botucatu, SP (Brazil)

    2015-02-20

    Matrix metalloproteinases (MMPs) are zinc (Zn{sup 2+}) and calcium (Ca{sup 2+}) dependant endopeptidases, capable of degradation of numerous components of the extracellular matrix. Cadmium (Cd{sup 2+}) is a well known environmental contaminant which could impair the activity of MMPs. In this sense, this study was conducted to evaluate if Cd{sup 2+} intake inhibits these endopeptidases activities at the rat prostate and testicles and if it directly inhibits the activity of MMP2 and MMP9 at gelatinolytic assays when present in the incubation buffer. To investigate this hypothesis, Wistar rats (5 weeks old), were given tap water (untreated, n = 9), or 15 ppm CdCl{sub 2} diluted in drinking water, during 10 weeks (n = 9) and 20 weeks (n = 9). The animals were euthanized and their ventral prostate, dorsal prostate, and testicles were removed. These tissue samples were processed for protein extraction and subjected to gelatin zymography evaluation. Additionally, we performed an experiment of gelatin zymography in which 5 μM or 2 mM cadmium chloride (CdCl{sub 2}) was directly dissolved at the incubation buffer, using the prostatic tissue samples from untreated animals that exhibited the highest MMP2 and MMP9 activities in the previous experiment. We have found that CdCl{sub 2} intake in the drinking water led to the inhibition of 35% and 30% of MMP2 and MMP9 (p < 0.05) at the ventral prostate and testis, respectively, in Cd{sup 2+} treated animals when compared to controls. Moreover, the activities of the referred enzymes were 80% and 100% inhibited by 5 μM and 2 mM of CdCl{sub 2}, respectively, even in the presence of 10 mM of CaCl{sub 2} within the incubation buffer solution. These important findings demonstrate that environmental cadmium contamination may deregulate the natural balance in the extracellular matrix turnover, through MMPs downregulation, which could contribute to the toxic effects observed in prostatic and testicular tissue after its

  13. UCAO (UNILATERAL CEREBRAL ARTERY OCCLUSSION METHOD INCREASES THE LEVEL OF MMP- 9 BRAIN TISSUE IN RATS MODEL OF ISCHEMIC STROKE

    Directory of Open Access Journals (Sweden)

    M. Rasjad Indra

    2016-07-01

    Full Text Available Background. For the last 5 years, 15.4% of total population died because of stroke, which 42.9% of those are caused by ischemic stroke. UCAO (Unilateral Cerebral Artery Occlusion is a stroke induction method by ligating mice’s carotid artery for 45 minutes. Thus, giving a hypoxic condition similar to stroke attack in human. This method is less complicated and far more efficient. MMP-9 is a stroke marker which is assayed by ELISA from the blood of test animal. Objective. This research was conducted to prove UCAO (Unilateral Cerebral Artery Occlusion method is capable to raise MMP-9 concentration in mice’s blood. Methods. This research was an experimental laboratory research with post-test only controlled group design. 8 male rats (8-10 weeks were divided into 2 groups, control and treatment which would be inducted into stroke by UCAO method. A day after the treatment group had been induced to stroke, both group were tested to measure the MMP-9 blood concentration through ELISA. Results. In this research, UCAO method had increased MMP-9 blood concentration in treatment group, compared to the control group. It is proved by the statistic tests, Mann-Whitney and Kruskal-Wallis, which showed a significant increase in treatment group (p < 0.05. Conclusion. Based on this result, it can be concluded that UCAO method is accepted as a method to create an ischemic stroke mice model.

  14. Concomitant lack of MMP9 and uPA disturbs physiological tissue remodeling

    DEFF Research Database (Denmark)

    Lund, Ida K; Nielsen, Boye S; Almholt, Kasper

    2011-01-01

    Urokinase-type plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP9, gelatinase B) have separately been recognized to play important roles in various tissue remodeling processes. In this study, we demonstrate that deficiency for MMP9 in combination with ablation of either uPA- or tiss......PAR, when MMP9 is absent. Notably, compensatory upregulation of uPA activity was seen in wounds from MMP9-deficient mice. Taken together, these studies reveal essential functional dependency between MMP9 and uPA during gestation and tissue repair.......Urokinase-type plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP9, gelatinase B) have separately been recognized to play important roles in various tissue remodeling processes. In this study, we demonstrate that deficiency for MMP9 in combination with ablation of either uPA- or tissue...

  15. Apoptosis induced by knockdown of uPAR and MMP-9 is mediated by inactivation of EGFR/STAT3 signaling in medulloblastoma.

    Directory of Open Access Journals (Sweden)

    Ramaprasada Rao Kotipatruni

    Full Text Available Medulloblastoma is a highly invasive cancer of central nervous system diagnosed mainly in children. Matrix metalloproteinase-9 (MMP-9 and urokinase plasminogen activator receptor (uPAR are over expressed in several cancers and well established for their roles in tumor progression. The present study is aimed to determine the consequences of targeting these molecules on medulloblastoma progression.Radiation is one of the foremost methods applied for treating cancer and considerable evidence showed that radiation elevated uPAR and MMP-9 expression in medulloblastoma cell. Therefore efforts are made to target these molecules in non-irradiated and irradiated medulloblastoma cells. Our results showed that siRNA-mediated knockdown of uPAR and MMP-9, either alone or in combination with radiation modulated a series of events leading to apoptosis. Down regulation of uPAR and MMP-9 inhibited the expression of anti-apoptotic molecules like Bcl-2, Bcl-xL, survivin, XIAP and cIAPI; activated BID cleavage, enhanced the expression of Bak and translocated cyctochrome C to cytosol. Capsase-3 and -9 activities were also increased in uPAR- and MMP-9-downregulated cells. The apoptosis induced by targeting MMP-9 and uPAR was initiated by inhibiting epidermal growth factor receptor (EGFR mediated activation of STAT3 and NF-κB related signaling molecules. Silencing uPAR and MMP-9 inhibited DNA binding activity of STAT3 and also reduced the recruitment of STAT3 protein at the promoter region of Bcl-2 and survivin genes. Our results suggest that inhibiting uPAR and MMP-9 reduced the expression of anti-apoptotic molecules by inactivating the transcriptional activity of STAT3. In addition, treating pre-established medulloblastoma with siRNAs against uPAR and MMP-9 both alone or in combination with radiation suppressed uPAR, MMP-9, EGFR, STAT3 expression and induced Bak activation leading to apoptosis.Taken together, our results illustrated that RNAi mediated targeting of

  16. Apparent suppression of MMP-9 activity by GD1a as determined by gelatin zymography.

    Science.gov (United States)

    Hu, Dan; Tan, Xuan; Sato, Toshinori; Yamagata, Sadako; Yamagata, Tatsuya

    2006-10-13

    Gelatin zymography is widely used to detect and evaluate matrix metalloproteinase-9 (MMP-9) activity. MMP-9 transcription was previously shown to be negatively regulated by ganglioside GD1a [D. Hu, Z. Man, T. Xuan, P. Wang, T. Takaku, S. Hyuga, X.S. Yao, T. Sato, S. Yamagata, T. Yamagata, Ganglioside GD1a regulation of matrix metalloproteinase-9 (MMP-9) expression in mouse FBJ cell Lines: GD1a suppression of MMP-9 expression stimulated by PI3K-Akt and p38 though not by the Erk signaling pathway, 2006, submitted for publication.]. Zymography of MMP-9 of FBJ-M5 cells preincubated with GD1a indicated a greater decrease in activity than expected from mRNA suppression. Incubation of conditioned medium containing MMP-9 with GD1a caused MMP-9 activity to decrease. Examination was thus made to confirm that MMP-9 activity is actually suppressed and/or MMP-9 protein undergoes degradation by GD1a. GD1a was found to have no effect on MMP-9 activity and Western blots indicated GD1a not to diminish MMP-9 during electrophoresis under reducing conditions. GD1a appeared to mediate the binding of a portion of MMP-9 with certain molecules, with consequently greater molecular mass on the gel, to cause decrease in the activity of MMP-9 at the site where it would normally appear. Caution should be used in doing gelatin zymography since molecules other than GD1a may similarly work, causing decrease in MMP-9 activity in zymography.

  17. Significance of the expression of matrix metalloproteinase-9 (MMP-9) in brain tissue of rat models of experimental intracerebral haemorrhage (ICH)

    International Nuclear Information System (INIS)

    Wu Jiami; Liu Shengda

    2005-01-01

    Objective: To study the relationship between the brain tissue expression of MMP-9 and brain water content in rat models of experimental ICH. Methods: Rat models of ICH were prepared with intracerebral (caudate nuclei) injection of autologous noncoagulated blood (50 μl). Animals were sacrificed at 6h, 12h, 24h, 48h, 72h, 120h, lw, 2w and the MMP-9 expressions at the periphery of intracerebral hematoma were examined with immunohisto chemistry. The brain water content was also determined at the same time. Control models were prepared with intracerebral sham injection of normal saline. Results: (1) In the ICH models, the number of MMP-9 positive capillaries at the periphery of hematoma began to rise at 6h (vs that of sham group, P < 0.01 ) with peak at 48h, then gradually dropped. At lwk, the number was still significantly higher than that in the sham group (P <0.01 ). However, there were no expression at 2wk. (2) The brain water content in the ICH group was significantly increased at 12h (vs sham group, P < 0.05) with peak at 72h. At lwk, the brain water content was still significantly higher in the ICH group (P <0.01 ) but at 2wk, the brain water content was about the same in both groups. (3) Animals injected with different amounts of blood (30 μl, 50 μl, 100 μl) showed increased expression of MMP-9 along with the increase of dose (P<0.01). (4) The MMP-9 expression was positively correlated with the brain water content (r=0.8291, P<0.05). Conclusion: In the rat models, MMP-9 expression was activated after ICH. The increase paralleled that of the amount of haemorrhage and brain water content. It was postulated that MMP-9 enhanced development of brain edema through degrading of the blood brain barrier component substances. (authors)

  18. THE ROLE OF MATRIX METALLOPROTEINASE MMP-9, ITS INHIBITOR TIMP-1 AND INTERLEUKINE-1β IN PATHOGENESIS OF TRAUMATIC BRAIN INJURY

    Directory of Open Access Journals (Sweden)

    S. V. Ziablitsev

    2016-09-01

      Resume Traumatic brain injury (TBI is accompanied by high rates of morbidity and mortality in both developed and undeveloped countries that makes it one of the most actual medical and social problems. In recent years matrix metalloproteinases are in increasing interest while studying TBI pathogenesis because of their ability to increase permeability of the blood-brain barrier and to cause nervous tissue matrix reorganization. The goal of given study was to investigate the role of matrix metalloproteinase MMP-9, its inhibitor TIMP-1 and interleukin IL-1β in pathogenesis of TBI. Methods: The study was performed on 98 mature white rats. Moderate severity TBI was modeled with one blow on the cranial vault by means of free-fall­ing plummet. Control group included 30 rats. Cytokines (IL-1b, IL-6, IL-8, TNF-a, MMP-9 and TIMP-1 levels were investi­gated in animals blood by means of ELISA on 1st, 3rd, 7th, 14th and 21st days after trauma. Results and discussion: MMP-9 levels increased by only 38,2% on the 1st day, but on the 3rd day there was its marked increase to 538%. It is known that metalloproteinases are released from the cells under the influence of various factors, including cytokines. On the 1st day after trauma it was IL-1β which increased by 705% showing the highest rise among other cytokines and exceeding increase in MMP-9 levels. This might indicate regulatory role of IL-1β.  A marked increase in MMP-9 levels in turn lead to TIMP-1 activation. Significant increase in TIMP-1 levels was determined on the 3rd day after trauma. On the 7th day there was a critical period with the highest levels of IL-1β (2147,2%, MMP-9 (720,3% and TIMR-1 (339,3%. Then all research indicators were decreasing with the most pronounced decrease in IL-1β and MMP-9. Conclusion: MMP-9 levels began to increase on the 1st day after trauma due to influence mainly IL-1β. An abrupt increase in MMP-9 in its turn caused an increase in TIMR-1 levels. Conclusion: Identified changes in

  19. Evaluation of inflammatory markers interleukin-6 (IL-6) and matrix metalloproteinase-9 (MMP-9) in asthma.

    Science.gov (United States)

    Naik, Srilata Puru; P A, Mahesh; B S, Jayaraj; Madhunapantula, SubbaRao V; Jahromi, Sarah Raeiszadeh; Yadav, Manish Kumar

    2017-08-01

    Even though IL-6 and MMP-9 are associated with airway inflammation in asthma, there is paucity of data in Indian population. To determine the levels of IL-6 and MMP-9 in the serum of patients suffering from asthma, and correlate with (a) disease severity, as per GINA guidelines; (b) clinical phenotypes; and (c) response to treatment. The levels of IL-6 and MMP-9 were compared between moderate persistent asthma (n = 25), severe persistent asthma (n = 25) and normal controls (n = 30). IL-6 and MMP-9 were measured by ELISA (R&D Systems Inc., USA and Canada) and compared between controls and asthmatics and between groups of different asthma severity, clinical variables, spirometry, and allergen sensitization. Spirometry was repeated after 2 months of ICS+LABA to assess response to treatment in relation to baseline IL-6 and MMP-9 levels. We observed a significant difference in both IL-6 and MMP-9 levels among asthmatics versus controls (p asthma (p asthma duration, total IgE, AEC, number of allergens sensitized and degree of sensitization. No significant correlation (p > 0.5) was observed with IL-6 and MMP-9 levels and FEV 1 improvement after 2 months of ICS+LABA. Higher levels of IL-6 and MMP-9 were observed in asthmatics as compared to controls and in severe persistent asthma as compared to moderate persistent asthma, higher levels of MMP-9 was associated with lower lung functions.

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

    Directory of Open Access Journals (Sweden)

    Khanh P Nguyen

    Full Text Available 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.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.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.

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

    Science.gov (United States)

    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

  2. MMP9 is protective against lethal inflammatory mass lesions in the mouse colon

    DEFF Research Database (Denmark)

    Hald, Andreas; Rønø, Birgitte; Melander, Maria C

    2011-01-01

    of individual members of the MMP family in animal models have been shown to have little effect. It has been speculated that this results from a functional overlap between individual MMPs and (as-yet-unclassified) functional overlaps between MMPs and other protease systems. We here present genetic data showing......, enlarged mesenteric lymph nodes, decreased thymus size and altered populations of circulating immune cells. A time-course study provided evidence that the massive lymphoid hyperplasia and reactive changes were secondary to discrete fibrinous lesions also observed in mice only deficient for plasminogen (Plg......), the zymogen for plasmin. These data demonstrate a non-appreciated vital protective role for MMP9 in the absence of Plg....

  3. MMP9 expression in oesophageal adenocarcinoma is upregulated with visceral obesity and is associated with poor tumour differentiation.

    LENUS (Irish Health Repository)

    Allott, Emma H

    2011-11-28

    Overweight and obesity is linked to increased incidence and mortality of many cancer types. Of all cancers, oesophageal adenocarcinoma (OAC) displays one of the strongest epidemiological links with obesity, accounting for up to 40% of cases, but molecular pathways driving this association remain largely unknown. This study aimed to elucidate mechanisms underpinning the association of obesity and cancer, and to determine if visceral obesity is associated with aggressive tumour biology in OAC. Following co-culture with visceral adipose tissue explants, expression of genes involved in tumour cell invasion and metastasis (matrix metalloproteinase (MMP)2 and MMP9) were upregulated between 10-fold (MMP2) and 5000-fold (MMP9), and expression of tumour suppressor p53 was downregulated 2-fold in OAC cell lines. Western blotting confirmed these results at the protein level, while zymographic analysis detected increased activity of MMPs in OAC cell lines following co-culture with adipose tissue explants. When OAC cell lines were cultured with adipose tissue conditioned media (ACM) from visceral adipose tissue, increased proliferative, migratory and invasive capacity of tumour cells was observed. In OAC patient tumour biopsies, elevated gene expression of MMP9 was associated with visceral obesity, measured by visceral fat area, while increased gene expression of MMP9 and decreased gene expression of tumour suppressor p53 was associated with poor tumour differentiation. These novel data highlight an important role for visceral obesity in upregulation of pro-tumour pathways contributing to aggressive tumour biology, and may ultimately lead to development of stratified treatment for viscerally obese OAC patients. © 2011 Wiley Periodicals, Inc.

  4. Increased CD147 and MMP-9 expression in the normal rat brain after gamma irradiation

    International Nuclear Information System (INIS)

    Li Hong; Wei Ming; Li Shenghui; Zhou Ziwei; Xu Desheng

    2013-01-01

    Radiation-induced vascular injury is a major complication of Gamma knife surgery (GKS). Previous studies have shown that CD147 and MMP-9 are closely associated with vascular remodeling and pathological angiogenesis. Thus, we analysed changes in CD147 and MMP-9 expression in the cerebral cortex to investigate the correlation between CD147 and MMP-9 in the rat following GKS. Adult male Wistar rats were subjected to GKS at a maximum dose of 75 Gy and then euthanized 1 to 12 weeks later. Using immunohistochemistry and western blot analysis, we found that CD147 and MMP-9 expression were markedly upregulated in the target area 8-12 weeks after GKS when compared with the control group. Immunofluorescent double staining demonstrated that CD147 signals colocalized with CD31, GFAP and MMP-9-positive cells. Importantly, CD147 levels correlated with increased MMP-9 expression in irradiated brain tissue. For the first time, these data demonstrate a potential relationship between CD147 and MMP-9 following GKS. In addition, our study also suggests that CD147 and MMP-9 may play a role in vascular injury after GKS. (author)

  5. Quantitative Evaluation of MMP-9 and TIMP-1 Promoter Methylation in Chronic Periodontitis.

    Science.gov (United States)

    Li, Xiting; Lu, Jiaxuan; Teng, Wei; Zhao, Chuanjiang; Ye, Xiaolei

    2018-03-01

    In this study, we investigated the promoter DNA methylation (DNAm) status of the MMP-9 and TIMP-1 genes in patients with chronic periodontitis to evaluate disease progression. Using pyrosequencing technology, DNAm levels of MMP-9 and TIMP-1 CpG islands were measured in 88 chronic periodontitis patients and 15 healthy controls. We found a positive correlation between methylation levels of MMP-9 CpG islands and the severity of chronic periodontitis. Methylated CpG islands were also closely associated with the duration of chronic periodontitis. Moreover, female patients exhibited lower methylation levels of MMP-9 but higher methylation levels of TIMP-1 compared with male patients, and the methylation levels of TIMP-1 gradually decreased with age. The findings of gender disparity in the DNAm of MMP-9 and TIMP-1 genes provide novel insights into chronic periodontitis.

  6. MMP-9 directed shRNAs as relevant inhibitors of matrix metalloproteinase 9 activity and signaling

    Directory of Open Access Journals (Sweden)

    Ewa Nowak

    2013-08-01

    Full Text Available Introduction: The main function of matrix metalloproteinases is the degradation of extracellular matrix components, which is related to changes in the proliferation of cells, their differentiation, motility, and death. MMPs play an important role in physiological processes such as embryogenesis, angiogenesis and tissue remodeling. The increase of MMPs activity is also observed in pathological conditions including tumorigenesis where MMP-2 (gelatinase A and MMP-9 (gelatinase B show the ability to degrade the basement membrane of vessels and they are involved in metastasis. The aim of our study was to verify the changes of MMP-9 enzymatic activity and the mobility of cells after inhibition of MMP-9 gene expression.Material and Methods: The oligonucleotide shRNA insert had been designed to silence MMP-9 gene expression and was cloned into the pSUPER.neo expression vector. The construct was introduced into the HeLa (CCL-2 cervical cancer cells by lipotransfection. Simultaneously in control cells MMP-9 were inhibited by doxycycline. Changes in activity of MMP-9 were analyzed by gelatin zymography and wound-healing assay.Results/Conclusions: Gelatin zymography allowed us to confirm that activity of MMP-9 in cells transfected by shRNA-MMP-9 and treated by doxycycline were similar and significantly lower in comparison with control cells. Phenotypic tests of migration in vitro confirm statistically significant (P<0.05 changes in cell migration – control cells healed 3 to 5 times faster in comparison with transfected or doxycycline treated cells. Our studies show the significant role of MMP-9 in mobility and invasiveness of tumor cells, thus indicating a potential target point of interest for gene therapy.

  7. Heterogeneity of serum gelatinases MMP-2 and MMP-9 isoforms and charge variants

    Science.gov (United States)

    Rossano, Rocco; Larocca, Marilena; Riviello, Lea; Coniglio, Maria Gabriella; Vandooren, Jennifer; Liuzzi, Grazia Maria; Opdenakker, Ghislain; Riccio, Paolo

    2014-01-01

    The matrix metalloproteinases (MMPs) gelatinase A (MMP-2) and gelatinase B (MMP-9) are mediators of brain injury in multiple sclerosis (MS) and valuable biomarkers of disease activity. We applied bidimensional zymography (2-DZ) as an extension of classic monodimensional zymography (1-DZ) to analyse the complete pattern of isoforms and post-translational modifications of both MMP-9 and MMP-2 present in the sera of MS patients. The enzymes were separated on the basis of their isoelectric points (pI) and apparent molecular weights (Mw) and identified both by comparison with standard enzyme preparations and by Western blot analysis. Two MMP-2 isoforms, and at least three different isoforms and two different states of organization of MMP-9 (the multimeric MMP-9 and the N-GAL-MMP-9 complex) were observed. In addition, 2-DZ revealed for the first time that all MMP-9 and MMP-2 isoforms actually exist in the form of charge variants: four or five variants in the N-GAL complex, more charge variants in the case of MMP-9; and five to seven charge variants for MMP-2. Charge variants were also observed in recombinant enzymes and, after concentration, also in sera from healthy individuals. Sialylation (MMP-9) and phosphorylation (MMP-2) contributed to molecular heterogeneity. The detection of charge variants of MMP-9 and MMP-2 in MS serum samples illustrates the power of 2-DZ and demonstrates that in previous studies MMP mixtures, rather than single molecules, were analysed. These observations open perspectives for better diagnosis and prognosis of many diseases and need to be critically interpreted when applying other methods for MS and other diseases. PMID:24616914

  8. MMP-9 immunohistochemical expression is correlated with histologic grade in feline diffuse iris melanoma

    Directory of Open Access Journals (Sweden)

    Laura Nordio

    2018-06-01

    Full Text Available Feline diffuse iris melanoma (FDIM is the most common primary intraocular neoplasm in cats. It is usually a malignant tumor, even if slowly progressive, thus representing an unique spontaneous model of the aggressive, although rare, human iris melanoma. In cats, the extent of the tumor within the eye, expressed as histological grade, is considered a good predictor of survival. In the context of the neoplastic cells-tumor microenvironment interaction, Matrix Metalloproteinase-9 (MMP-9 is an endopeptidase able to digest the extracellular matrix with involvement in tumor invasion . MMP-9 expression has been positively correlated with metastasizing behavior in human posterior uveal melanoma. The present study investigates the expression of MMP-9 in a caseload of formalin-fixed paraffin-embedded FDIMs in relation to the histological grade  and mitotic index (MI (threshold=7/10 hpf. Sixty-one samples of FDIM evaluated on light microscopy (Fig. 1 were selected (grade I n=22, grade II n=20, grade III n=19. Immunohistochemical staining with standard ABC method was performed using a mouse anti-MMP-9 antibody. Results were semi-quantitatively scored and compared by Mann-Whitney U test. MMP-9 was expressed in 59,1% grade I FDIM, 90,0% grade II and 80,0% grade III. Tumors with MMP-9 expression in more than 50% of neoplastic cells were 13,6% in grade I cases, 40,0% in grade II and 36,8% in grade III. MMP-9 was expressed in 71,4% of FDIM with MI≤7 and 92,3% of FDIM with MI>7. MMP-9 expression differed significantly between grade I and the other two grades, and between groups with low and high MI. In conclusion, intense expression of MMP-9 seems to correlate with the histological aggressiveness of FDIM.

  9. Diagnostic Value of MMP-2 and MMP-9 in Synovial Fluid for Identifying Osteoarthritis in the Distal Interphalangeal Joint in Horses

    Directory of Open Access Journals (Sweden)

    P. Zrimšek

    2007-01-01

    Full Text Available Our aim was to examine the diagnostic potential of matrix metalloproteinases MMP-2 and MMP-9 for identifying osteoarthritis in the horse. Horses were divided into two groups - a positive group consisting of 28 horses with cartilage damage in the distal interphalangeal joint and a negative group of 17 control horses. Clinical examination of the horses included evaluation of lameness, flexion test, diagnostic nerve blocks, X-ray and arthroscopy. MMP-2 and MMP-9 were detected in synovial fluid using gelatin zymography. Monomers of MMP-2 and MMP-9 appeared not to be specific for osteoarthritis since they also occurred in control samples. In contrast, detection of active forms of MMPs was found to be more effective than radiological examination in identifying horses with osteoarthritis, on the grounds of higher sensitivity. Active forms of MMP-2 and MMP-9 were observed with 88.24% and 82.35% specificity respectively, indicating the high accuracy in correctly identifying horses without osteoarthritis. Thus, as an addition to clinical examination, detection of MMPs could improve the diagnosis of osteoarthritis. Detection of active forms of MMP-2 and MMP-9 was evaluated as an additional diagnostic tool in diagnosing osteoarthritis, especially in the case of a negative X-ray result. The proportions of animals with confirmed osteoarthritis, which tested positive, were found to be 81.82% and 76.92%, respectively. The results of this study confirm that active forms of MMP occur in synovial fluid of osteoarthritic joints more frequently than in synovial fluid from normal joints of the horse. Detection of active forms of MMP-2 and MMP-9 is shown to have an important diagnostic potential.

  10. IL-15 up-regulates the MMP-9 expression levels and induces inflammatory infiltration of macrophages in polymyositis through regulating the NF-kB pathway.

    Science.gov (United States)

    Yan, Wang; Fan, Weinv; Chen, Caijing; Wu, Yunqin; Fan, Zhenyi; Chen, Jiaqi; Chen, Zhaoying; Chen, Huimin

    2016-10-10

    This study was aimed to research the effects of IL-15 on inducing inflammatory infiltration of macrophages in polymyositis (PM) through the NF-kB pathway, and whether IL-15 was able to further regulate MMP-9 expression levels. Prepared PM cells, collected from the patients suffering from PM, were administered to SD rats. Also, a group of healthy SD rats was undergoing the same treatment as the control group. The test animals were treated with either anti-IL-15, IL-15, MMP-9 siRNA or ERK1/2 inhibitor. The blood toxicological parameters creatine kinase (CK) and CD163 were tested by using ELISA and immunohistochemistry assay. In addition, NF-kB expression in macrophages was measured by immunocytochemical assay. To measure the degree of cell infiltration the Transwell assay was performed. Lastly, western blot and zymography were carried out to compare MMP-9 and ERK expression levels between the two groups, both in vivo and in vitro. The results showed that S-CK, IL-15 and IL-15Rα levels increased rapidly after the conventional treatment was introduced to the PM infected SD rats. The PM model establishment and IL-15 treatment significantly increased the expressions of IL-15Rα, MMP-9, p-ERK and p-IKBα. However, the same effect can be suppressed by using anti-IL-15, MMP-9 siRNA or ERK1/2 inhibitor (P kB in the macrophages. IL-15 is able to significantly regulate the inflammatory infiltration of macrophages in PM patients through affecting the NF-kB pathway and MMP-9 expression levels. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Increased MMP-9 and TIMP-1 in mouse neonatal brain and plasma and in human neonatal plasma after hypoxia-ischemia: a potential marker of neonatal encephalopathy.

    Science.gov (United States)

    Bednarek, Nathalie; Svedin, Pernilla; Garnotel, Roselyne; Favrais, Géraldine; Loron, Gauthier; Schwendiman, Leslie; Hagberg, Henrik; Morville, Patrice; Mallard, Carina; Gressens, Pierre

    2012-01-01

    To implement neuroprotective strategies in newborns, sensitive and specific biomarkers are needed for identifying those who are at risk for brain damage. We evaluated the effectiveness of matrix metalloproteinases (MMPs) and their naturally occurring tissue inhibitors of metalloproteinases (TIMPs) in predicting neonatal encephalopathy (NE) damage in newborns. Plasma MMP-9 and TIMP-1 levels were upregulated as early as 1 h after the HI insult but not did not show such elevations after other types of injury (ibotenate-induced excitotoxicity, hypoxia, lipopolysaccharide-induced inflammation), and brain levels reflected this increase soon thereafter. We confirmed these results by carrying out plasma MMP-9 and TIMP-1 measurements in human newborns with NE. In these infants, protein levels of MMP-9 and TIMP-1 were found to be elevated during a short window up to 6 h after birth. This feature is particularly useful in identifying newborns in need of neuroprotection. A second peak observed 72 h after birth is possibly related to the second phase of energy failure after a HI insult. Our data, although preliminary, support the use of MMP-9 and TIMP-1 as early biomarkers for the presence and extent of perinatal brain injury in human term newborns. We first used a mouse model of neonatal HI injury to explore mechanistic aspects such as the time course of these markers after the hypoxia-ischemia event, and the correlation between the levels of these candidate markers in brain and plasma.

  12. Contributions of ocular surface components to matrix-metalloproteinases (MMP)-2 and MMP-9 in feline tears following corneal epithelial wounding.

    Science.gov (United States)

    Petznick, Andrea; Madigan, Michele C; Garrett, Qian; Sweeney, Deborah F; Evans, Margaret D M

    2013-01-01

    This study investigated ocular surface components that contribute to matrix-metalloproteinase (MMP)-2 and MMP-9 found in tears following corneal epithelial wounding. Laboratory short-haired cats underwent corneal epithelial debridement in one randomly chosen eye (n = 18). Eye-flush tears were collected at baseline and during various healing stages. Procedural control eyes (identical experimental protocol as wounded eyes except for wounding, n = 5) served as controls for tear analysis. MMP activity was analyzed in tears using gelatin zymography. MMP staining patterns were evaluated in ocular tissues using immunohistochemistry and used to determine MMP expression sites responsible for tear-derived MMPs. The proMMP-2 and proMMP-9 activity in tears was highest in wounded and procedural control eyes during epithelial migration (8 to 36 hours post-wounding). Wounded eyes showed significantly higher proMMP-9 in tears only during and after epithelial restratification (day 3 to 4 and day 7 to 28 post-wounding, respectively) as compared to procedural controls (pTears from wounded and procedural control eyes showed no statistical differences for pro-MMP-2 and MMP-9 (p>0.05). Immunohistochemistry showed increased MMP-2 and MMP-9 expression in the cornea during epithelial migration and wound closure. The conjunctival epithelium exhibited highest levels of both MMPs during wound closure, while MMP-9 expression was reduced in conjunctival goblet cells during corneal epithelial migration followed by complete absence of the cells during wound closure. The immunostaining for both MMPs was elevated in the lacrimal gland during corneal healing, with little/no change in the meibomian glands. Conjunctival-associated lymphoid tissue (CALT) showed weak MMP-2 and intense MMP-9 staining. Following wounding, migrating corneal epithelium contributed little to the observed MMP levels in tears. The major sources assessed in the present study for tear-derived MMP-2 and MMP-9 following

  13. Cationic star-shaped polymer as an siRNA carrier for reducing MMP-9 expression in skin fibroblast cells and promoting wound healing in diabetic rats

    Directory of Open Access Journals (Sweden)

    Li N

    2014-07-01

    Full Text Available Na Li,1,* Heng-Cong Luo,1,* Chuan Yang,1 Jun-Jie Deng,2 Meng Ren,1 Xiao-Ying Xie,1 Diao-Zhu Lin,1 Li Yan,1 Li-Ming Zhang2 1Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2DSAPM Lab and PCFM Lab, Institute of Polymer Science, Department of Polymer and Materials Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: Excessive expression of matrix metalloproteinase-9 (MMP-9 is deleterious to the cutaneous wound-healing process in the context of diabetes. The aim of the present study was to explore whether a cationic star-shaped polymer consisting of ß-cyclodextrin (ß-CD core and poly(amidoamine dendron arms (ß-CD-[D3]7 could be used as the gene carrier of small interfering RNA (siRNA to reduce MMP-9 expression for enhanced diabetic wound healing. Methods: The cytotoxicity of ß-CD-(D37 was investigated by 3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay (MMT method in the rat CRL1213 skin fibroblast cell line. The transfection efficiency of ß-CD-(D37/MMP-9-small interfering RNA (siRNA complexes was determined by confocal microscopy and flow cytometry. Quantitative real time (RT polymerase chain reaction was performed to measure the gene expression of MMP-9 after the transfection by ß-CD-(D37/MMP-9-siRNA complexes. The ß-CD-(D37/MMP-9-siRNA complexes were injected on the wounds of streptozocin-induced diabetic rats. Wound closure was measured on days 4 and 7 post-wounding. Results: ß-CD-(D37 exhibited low cytotoxicity in fibroblast cells, and easily formed the complexes with MMP-9-siRNA. The ß-CD-(D37/MMP-9-siRNA complexes were readily taken up by fibroblast cells, resulting in the downregulation of MMP-9 gene expression (P<0.01. Animal experiments revealed that the treatment by ß-CD-(D37/MMP-9-siRNA complexes enhanced wound

  14. High MMP-9 and TNF-α expression increase in preterm premature rupture of membranes

    Directory of Open Access Journals (Sweden)

    Sri Sulistyowati

    2016-05-01

    Expression of MMP-9 and TNF-α was higher in the amniotic membrane of preterm delivery subjects with PROM than in preterm delivery subjects without PROM and can thus be used as predictor to avoid PPROM.

  15. Association of MMP-2 and MMP-9 expression with recurrences in primary spontaneous pneumothorax.

    Science.gov (United States)

    Huang, Ying-Fong; Chiu, Wen-Chin; Chou, Shah-Hwa; Su, Yu-Han; Chen, Yu-Wen; Chai, Chee-Yin; Huang, Chih-Jen; Huang, Ming-Yii; Yuan, Shyng-Shiou F; Lee, Yi-Chen

    2017-01-01

    Primary spontaneous pneumothorax (PSP) is a common benign problem. However, PSP recurrence is still a troublesome complication for most patients. This study intended to determine the role of matrix metalloproteinase-2 (MMP-2) and MMP-9 in type II pneumocytes of patients with PSP and its relation with recurrence. Ninety-one patients who had undergone needlescopic video-assisted thoracoscopic surgery wedge resection of lung with identifiable blebs for PSP were included in this study. Immunohistochemical (IHC) staining was used to measure the expression of MMP-2 and MMP-9 in lung tissues of PSP patients. The results were further correlated with clinicopathological parameters and recurrence rates using chi-square or Fisher's exact test. The value of MMP-2 and MMP-9 for overall recurrence was analyzed by univariate and multivariable Cox regression model. IHC data revealed that MMP-2 and MMP-9 staining was predominantly observed in type II pneumocytes of patients with PSP. We found that MMP-2 and MMP-9 expression in PSP, especially male PSP patients, was significantly correlated with recurrence. In the univariate and multivariate analyses, MMP-2 and MMP-9 were statistically significant risk factors for overall recurrence in PSP patients. Therefore, high expression levels of MMP-2 and MMP-9 in type II pneumocytes show a positive correlation with PSP recurrence risk. Further studies are needed to validate whether reduction of MMP-2 and MMP-9 expression may be a promising way for decreasing the risk of PSP recurrence in the future. Copyright © 2016. Published by Elsevier Taiwan.

  16. Overexpression of TIMP-1 under the MMP-9 promoter interferes with wound healing in transgenic mice

    OpenAIRE

    Salonurmi, T.; Parikka, M.; Kontusaari, S.; Pirila, E.; Munaut, Carine; Salo, T.; Tryggvason, K.

    2004-01-01

    We have generated transgenic mice harboring the murine matrix metalloproteinase 9 (MMP-9) promoter cloned in front of human TIMP-1 cDNA. The transgenic mice were viable and fertile and exhibited normal growth and general development. During wound healing the mice were shown to express human TIMP-1 in keratinocytes that normally express MMP-9. However, the healing of skin wounds was significantly retarded with slow migration of keratinocytes over the wound in transgenic mice. In situ zymograph...

  17. Measurement of MMP-9 and -12 degraded elastin (ELM) provides unique information on lung tissue degradation

    DEFF Research Database (Denmark)

    Skjøt-Arkil, Helene; Clausen, Rikke E; Nguyen, Quoc Hai Trieu

    2012-01-01

    Elastin is an essential component of selected connective tissues that provides a unique physiological elasticity. Elastin may be considered a signature protein of lungs where matrix metalloprotease (MMP) -9-and -12, may be considered the signature proteases of the macrophages, which in part...... are responsible for tissue damage during disease progression. Thus, we hypothesized that a MMP-9/-12 generated fragment of elastin may be a relevant biochemical maker for lung diseases....

  18. The Biological Behaviors of Rat Dermal Fibroblasts Can Be Inhibited by High Levels of MMP9

    Directory of Open Access Journals (Sweden)

    Sheng-Neng Xue

    2012-01-01

    Full Text Available Aims. To explore the effects of the high expression of MMP9 on biological behaviors of fibroblasts. Methods. High glucose and hyperhomocysteine were used to induce MMP9 expression in skin fibroblasts. Cell proliferation was detected by flow cytometry and cell viability by CCK-8. ELISA assay was used to detect collagen (hydroxyproline secretion. Scratch test was employed to evaluate horizontal migration of cells and transwell method to evaluate vertical migration of cells. Results. The mRNA and protein expressions of MMP9 and its protease activity were significantly higher in cells treated with high glucose and hyperhomocysteine than those in control group. At the same time, the S-phase cell ratio, proliferation index, cell viability, collagen (hydroxyproline secretion, horizontal migration rate, and the number of vertical migration cells decreased in high-glucose and hyperhomocysteine-treated group. Tissue inhibitor of metalloproteinase 1 (TIMP1, which inhibits the activity of MMP9, recovered the above biological behaviors. Conclusions. High expression of MMP9 in skin fibroblasts could be induced by cultureing in high glucose and hyperhomocysteine medium, which inhibited cell biological behaviors. Inhibitions could be reversed by TIMP1. The findings suggested that MMP9 deters the healing of diabetic foot ulcers by inhibiting the biological behaviors of fibroblasts.

  19. Immunohistochemical expression of TGF-β1 and MMP-9 in periapical lesions.

    Science.gov (United States)

    Álvares, Pâmella Recco; Arruda, José Alcides Almeida de; Silva, Leorik Pereira da; Nascimento, George João Ferreira do; Silveira, Maria Fonseca da; Sobral, Ana Paula Veras

    2017-07-03

    The objective of this study was to evaluate the expression of matrix metalloproteinase 9 (MMP-9) and transforming growth factor beta (TGF-β1) in periapical lesion samples correlated with the intensity of the inflammatory infiltrate and thickness of the epithelial lining. Forty-five cases of periapical lesions (23 periapical granulomas and 22 radicular cysts) were subjected to morphological and immunohistochemical analyses using anti-MMP-9 and anti-TGF-β1 antibodies. The data were analyzed using the following tests: non-parametric Mann-Whitney, chi-square, Fisher's exact test and Spearman's correlation test (Pperiapical granulomas presented infiltrate grade III, in contrast with 32% of radicular cysts (Pcysts revealed the presence of atrophic epithelium in 86% of the cysts. The immunostaining of MMP-9 was score 2 in 67% of the granulomas and 77% of the cysts. Both lesions were predominantly score 1 for TGF-β1. Significant differences were confirmed between the expression scores of TGF-β1 and MMP-9 in periapical granulomas (p = 0.004) and in radicular cysts (p periapical granulomas and radicular cysts. This immunoregulatory cytokine seems more representative in asymptomatic lesions. The extracellular matrix remodeling process dependent on MMP-9 seems to be similar for both periapical granulomas and radicular cysts. TGF-β1 and MMP-9 may play an important role in the maintenance of periapical lesions.

  20. Proteomic analysis identifies MMP-9, DJ-1 and A1BG as overexpressed proteins in pancreatic juice from pancreatic ductal adenocarcinoma patients

    International Nuclear Information System (INIS)

    Tian, Mei; Cui, Ya-Zhou; Song, Guan-Hua; Zong, Mei-Juan; Zhou, Xiao-Yan; Chen, Yu; Han, Jin-Xiang

    2008-01-01

    There is an urgent need to discover more sensitive and specific biomarkers to improve early diagnosis and screen high-risk patients for pancreatic ductal adenocarcinoma (PDAC). Pancreatic juice is an ideal specimen for PDAC biomarkers discovery, because it is an exceptionally rich source of proteins released from pancreatic cancer cells. To identify novel potential biomarkers for PDAC from pancreatic juice, we carried out difference gel electrophoresis (DIGE) and tandem mass spectrometry (MS/MS) to compare the pancreatic juice profiling from 9 PDAC patients and 9 cancer-free controls. Of the identified differently expressed proteins, three up-regulated proteins in pancreatic cancer juice, matrix metalloproteinase-9 (MMP-9), oncogene DJ1 (DJ-1) and alpha-1B-glycoprotein precursor (A1BG), were selected for validation by Western blot and immunohistochemistry. Serum MMP-9 levels were also detected by enzyme linked immunosorbent assay (ELISA). Fourteen proteins were up-regulated and ten proteins were down-regulated in cancerous pancreatic juice compared with cancer-free controls. Increased MMP-9, DJ-1 and A1BG expression in cancerous pancreatic juice were confirmed by Western blot. Immunohistochemical study showed MMP-9, DJ-1 and A1BG positively expressed in 82.4%, 72.5% and 86.3% of pancreatic cancer tissues, significantly higher than that in normal pancreas tissues. Up-regulation of DJ-1 was associated with better differentiation (p < 0.05). Serum MMP-9 levels were significantly higher in PDAC (255.14 ng/ml) than those in chronic pancreatitis (210.22 ng/ml, p = 0.009) and healthy control (203.77 ng/ml, p = 0.027). The present proteome analysis revealed MMP-9, DJ-1 and A1BG proteins as elevated in pancreatic juice from PDAC, which suggest their further utility in PDAC diagnosis and screening. This is the first time A1BG was identified as a potential biomarker in pancreatic cancer associated samples. The measurement of serum MMP-9 might be clinically useful for PDAC

  1. Pharmacogenetic Inhibition of eIF4E-Dependent Mmp9 mRNA Translation Reverses Fragile X Syndrome-like Phenotypes

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    Christos G. Gkogkas

    2014-12-01

    Full Text Available Summary: Fragile X syndrome (FXS is the leading genetic cause of autism. Mutations in Fmr1 (fragile X mental retardation 1 gene engender exaggerated translation resulting in dendritic spine dysmorphogenesis, synaptic plasticity alterations, and behavioral deficits in mice, which are reminiscent of FXS phenotypes. Using postmortem brains from FXS patients and Fmr1 knockout mice (Fmr1−/y, we show that phosphorylation of the mRNA 5′ cap binding protein, eukaryotic initiation factor 4E (eIF4E, is elevated concomitant with increased expression of matrix metalloproteinase 9 (MMP-9 protein. Genetic or pharmacological reduction of eIF4E phosphorylation rescued core behavioral deficits, synaptic plasticity alterations, and dendritic spine morphology defects via reducing exaggerated translation of Mmp9 mRNA in Fmr1−/y mice, whereas MMP-9 overexpression produced several FXS-like phenotypes. These results uncover a mechanism of regulation of synaptic function by translational control of Mmp-9 in FXS, which opens the possibility of new treatment avenues for the diverse neurological and psychiatric aspects of FXS. : Fragile X syndrome (FXS is caused by dysregulation of translation in the brain. Gkogkas et al. show that phosphorylation of eukaryotic translation initiation factor 4E (eIF4E is increased in FXS postmortem brains and Fmr1−/y mice. Downregulation of eIF4E phosphorylation in Fmr1−/y mice rescues defects in dendritic spine morphology, synaptic plasticity, and social interaction via normalization of MMP-9 expression.

  2. Doxycycline attenuates acrolein-induced mucin production, in part by inhibiting MMP-9.

    Science.gov (United States)

    Ren, Shuang; Guo, Ling-Li; Yang, Jie; Liu, Dai-Shun; Wang, Tao; Chen, Lei; Chen, Ya-Juan; Xu, Dan; Feng, Yu-Lin; Wen, Fu-Qiang

    2011-01-10

    Matrix metalloproteinases (MMPs), especially MMP-9, have been found to increase the expression of epidermal growth factor (EGF) receptor, a possible regulator of acrolein-induced mucin expression in the airway epithelium. The aim of this study was to investigate whether doxycycline, a tetracycline antibiotic that inhibits MMPs, attenuates mucus production and synthesis of mucin MUC5AC in acrolein-exposed rats. Sprague-Dawley rats were exposed to acrolein aerosol [3.0parts/million (ppm), 6h/day, 12days] and they received 20mg/kg doxycycline daily by gavage, beginning two days before exposure to acrolein until the end of the experiment. The production of mucin glycoproteins and expression of the MMP-9 and MUC5AC genes were measured in rat trachea. The increase in levels of MMP-9 mRNA and protein in airway epithelium after acrolein exposure was accompanied by an increase in MUC5AC mRNA expression. Doxycycline significantly prevented these increases in acrolein-induced expression of MMP-9 and MUC5AC and attenuated mucus production in tracheal epithelium. These results indicate that doxycycline attenuated acrolein-induced mucin synthesis, in part by inhibiting expression of MMP-9. Thus doxycycline may have a prophylactic effect in the treatment of smoking-induced mucus hypersecretion. Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.

  3. The significance of MMP-9 examination in serum from embryo of gastric cancer model

    International Nuclear Information System (INIS)

    Liu Zhan; Zhao Xuejian; Wang Lu; Li Yulin; Zhang Lihong; Zhang Hong

    2003-01-01

    Objective: To investigate the changes matrix metalloproteinase-9 (MMP-9) content from sera of chick embryos during the progression of transformed models of gastric cancer cells on chorioallantoic membrane (CAM). Methods: Morphometric investigation method was used to study the tumor generation on CAM; Enzyme-linked immunosorbent assay (ELISA) method was used to test MMP-9 concentrations in chick embryos'sera transferred by cancer cells at different points of time; the relationship between MMP-9 and cancer biological characteristics was analyzed. Results: In the group of 1 x 10 6 ·ml -1 gastric cancer cells, a single clot which could be seen by naked eyes appeared at 72 hours after inoculation. With the time going on, the volumes of the clot became larger and larger, and the neovessels on CAM accumulated to the clot. In the group of 1 x 10 6 ·ml -1 gastric cancer cells, the MMP-9 content in sera extremely increased at 72 hours after inoculation and increased continuously till the maxim at 7 days after inoculation. Conclusion: The whole progression of cancer development is accompanied with the increase of MMP-9 concentration. This model is feasible to study the characteristics of gastric cancer

  4. p38 MAPK and MMP-9 cooperatively regulate mucus overproduction in mice exposed to acrolein fog.

    Science.gov (United States)

    Liu, Dai-Shun; Wang, Tao; Han, Su-Xia; Dong, Jia-Jia; Liao, Zeng-Lin; He, Guang-Ming; Chen, Lei; Chen, Ya-Juan; Xu, Dan; Hou, Yan; Li, Yan-Ping; Wen, Fu-Qiang

    2009-09-01

    To evaluate the role of p38 mitogen-activated protein kinase (MAPK) on mice airway inflammation, mucus production and the possible cross-talk between p38 MAPK and matrix metalloproteinase-9 (MMP-9) in mucin protein synthesis. Mice were exposed to 4.0 ppm of acrolein for 21 days with daily intraperitoneal injection of SB203580, a specific inhibitor of p38 MAPK. In control mice, sterile saline was administered instead. On days 7 and 21, mice were sacrificed to examine airway inflammation and mucus production by BALF cell counts, cytokine ELISA, and H&E and AB-PAS staining. The mRNA and protein levels of Muc5ac, p38 MAPK and MMP-9 in the lung were determined by RT-PCR, immunohistochemistry and Western blotting analysis. MMP-9 activity was measured by gelatin zymography. Both the numbers of inflammatory cells and mucus-secreting goblet cells were significantly increased in the airways of mice exposed to acrolein as compared to the control mice. Acrolein-increased phosphorylation of p38 MAPK was significantly reduced by SB203580. The airway inflammation and goblet cell hyperplasia after acrolein challenge were also attenuated by SB203580 administration. Moreover, SB203580 treatment decreased the acrolein-induced increase of Muc5ac and MMP-9 expression and MMP-9 activity in airway epithelium. The results indicate an important role of p38 MAPK in acrolein-induced airway inflammation and mucus hypersecretion in mice. The cooperation of p38 and MMP-9 may contribute to the mucin overproduction after inflammatory challenge.

  5. The Role of FAK in the Secretion of MMP9 after CD147 Stimulation in Macrophages.

    Science.gov (United States)

    Yu, Chen; Lixia, Yang; Ruiwei, Guo; Yankun, Shi; Jinshan, Ye

    2018-03-30

    To investigate whether focal adhesion kinase (FAK) can participate in the secretion of matrix metalloproteinase 9 (MMP9) after CD147 stimulation in THP-1 induced macrophages; thus, to explore the potential treatment perspectives for acute coronary syndrome (ACS).Phorbol-12-myristate-13-acetate (PMA) was used to induce THP-1 cells to differentiate into macrophages. To confirm the peak mRNA and protein expression of FAK and MMP9 after the stimulation of CD147, the macrophages were divided into 5 groups (0, 3, 6, 9, and 12 hours), with 0 hours group as control group. To investigate the role of FAK in the secretion of MMP9, with stimulation of CD147 for 9 hours, FAK inhibitor 14 was used to inhibit FAK Y397 phosphorylation. The mRNA and protein expressions were quantified by qRT-PCR and western blotting, respectively. (1) Relative mRNA expression of FAK and MMP9 were both significantly up-regulated (all P CD147, FAK peaked at 9 hours (3.908 ± 0.106 versus 1, P CD147 stimulation (all P CD147 up-regulates FAK, pFAK, and MMP9 mRNA and protein expressions in a dose-dependent manner. (4) FAK inhibitor 14 significantly reduced the relative protein expression level of pFAK (0.077 ± 0.012 versus 1, P CD147 stimulation.The results demonstrated that FAK Y397 phosphorylation was involved in the secretion of MMP9 after CD147 stimulation in macrophages and may play a role in the regulation of ACS.

  6. Immunohistochemical expression of TGF-β1 and MMP-9 in periapical lesions

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    Pâmella Recco ÁLVARES

    2017-07-01

    Full Text Available Abstract The objective of this study was to evaluate the expression of matrix metalloproteinase 9 (MMP-9 and transforming growth factor beta (TGF-β1 in periapical lesion samples correlated with the intensity of the inflammatory infiltrate and thickness of the epithelial lining. Forty-five cases of periapical lesions (23 periapical granulomas and 22 radicular cysts were subjected to morphological and immunohistochemical analyses using anti-MMP-9 and anti-TGF-β1 antibodies. The data were analyzed using the following tests: non-parametric Mann-Whitney, chi-square, Fisher’s exact test and Spearman’s correlation test (P<0.05. Analysis of inflammatory infiltrate revealed that 78% of periapical granulomas presented infiltrate grade III, in contrast with 32% of radicular cysts (P<0.001. Morphological evaluation of the epithelial thickness in radicular cysts revealed the presence of atrophic epithelium in 86% of the cysts. The immunostaining of MMP-9 was score 2 in 67% of the granulomas and 77% of the cysts. Both lesions were predominantly score 1 for TGF-β1. Significant differences were confirmed between the expression scores of TGF-β1 and MMP-9 in periapical granulomas (p = 0.004 and in radicular cysts (p < 0.001. Expression of TGF-β1 was different for periapical granulomas and radicular cysts. This immunoregulatory cytokine seems more representative in asymptomatic lesions. The extracellular matrix remodeling process dependent on MMP-9 seems to be similar for both periapical granulomas and radicular cysts. TGF-β1 and MMP-9 may play an important role in the maintenance of periapical lesions.

  7. Eradication of Helicobacter pylori infection favourably affects altered gastric mucosal MMP-9 levels

    NARCIS (Netherlands)

    Kubben, F.J.G.M.; Sier, C.F.M.; Schram, M.; Witte, T.A.M.C.; Veenendaal, R.A.; Duijn, W. van; Verheijen, J.H.; Hanemaaijer, R.; Lamers, C.B.H.W.; Verspaget, H.W.

    2007-01-01

    Background: Helicobacter pylori gastritis is recognized as an important pathogenetic factor in peptic ulcer disease and gastric carcinogenesis, and is accompanied by strongly enhanced gastric mucosal matrix metalloproteinase-9 (MMP-9) levels. Aim: This study was performed to investigate whether H.

  8. Correlation of MMP-9, GA, HbA1c, and adipokines levels with DR

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    Cheng Qian

    2017-12-01

    Full Text Available AIM: To investigate the correlation of matrix metalloproteinase -9(MMP-9, glycated albumin(GA, glycosylated hemoglobin(HbA1cand adipokines(including visfatin, resistin and leptinwith diabetic retinopathy(DR. METHODS: From March 2015 to March 2017, 74 patients with DR were treated in our hospital, including 40 patients(80 eyeswith non proliferative diabetic retinopathy(NPDRand 34 patients(68 eyeswith proliferative diabetic retinopathy(PDR, and diabetes mellitus 40 patients(80 eyeswith non DR(NDRand 40 healthy volunteers(80 eyeswere selected as controls, the levels of MMP-9, GA, HbA1c, visfatin, resistin and leptin in each group were detected. RESULTS: PDR group visfatin was 4.41±0.82ng/mL, was significantly lower than the NPDR group, NDR group and control group(PPPPrs=0.523, 0.461 and 0.414, Prs=-0.433, Prs=0.401 and 0.460, PCONCLUSION: MMP-9, GA, HbA1c, and adipokines may play a role in the development and progression of DR, in which MMP-9 is associated with adipokines, both are not significantly related to the levels of GA and HbA1c.

  9. Resveratrol protects primary cortical neuron cultures from transient oxygen-glucose deprivation by inhibiting MMP-9.

    Science.gov (United States)

    Gao, Dakuan; Huang, Tao; Jiang, Xiaofan; Hu, Shijie; Zhang, Lei; Fei, Zhou

    2014-06-01

    It was recently shown that resveratrol exerts neuroprotective effects against cerebral ischemia in mice. The aim of the present study was to further confirm these effects in in vitro primary cortical neuron cultures with transient oxygen-glucose deprivation (OGD), and to investigate whether these effects are due to the inhibition of matrix metalloproteinase-9 (MMP-9) and of cell apoptosis. Neuronal primary cultures of cerebral cortex were prepared from BALB/c mice embryos (13-15 days). Cells from 14- to 16-day cultures were subjected to OGD for 3 h, followed by 21 h of reoxygenation to simulate transient ischemia. Different doses of resveratrol were added into the culture medium during the simulation of transient ischemia. The effect of the extracellular signal-regulated kinase (ERK) inhibitor U0126 was studied by adding U0126 (5 µg/µl, 4 µl) into the culture medium during transient ischemia; as a control, we used treatment of cells with 50 µM of resveratrol. Cell viability was investigated using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) reduction assay. Cell apoptosis was assessed by flow cytometry. The effects of resveratrol on the expression of MMP-9 were analyzed by western blotting and reverse transcription-polymerase chain reaction (RT-PCR), while the levels of ERK, phosphorylated (p)-ERK, cleaved caspase-3, Bax and Bcl-2 were measured by western blotting. The results of the MTT assay showed that cell viability is significantly reduced by transient OGD. OGD induced cell apoptosis, the expression of Bax and the activation of caspase-3 and ERK, inhibited the expression of Bcl-2 and increased the expression of MMP-9, while these effects were reversed by treatment with resveratrol. The therapeutic efficacy of resveratrol was shown to be dose-dependent, with the most suitable dose range determined at 50-100 µM. Treatment with U0126 inhibited MMP-9 and Bax expression and caspase-3 activation, while it further promoted the

  10. Mycobacterium tuberculosis Upregulates TNF-α Expression via TLR2/ERK Signaling and Induces MMP-1 and MMP-9 Production in Human Pleural Mesothelial Cells.

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    Wei-Lin Chen

    Full Text Available Tumor necrosis factor (TNF-α and matrix metalloproteinases (MMPs are elevated in pleural fluids of tuberculous pleuritis (TBP where pleural mesothelial cells (PMCs conduct the first-line defense against Mycobacterium tuberculosis (MTB. However, the clinical implication of TNF-α and MMPs in TBP and the response of PMCs to MTB infection remain unclear.We measured pleural fluid levels of TNF-α and MMPs in patients with TBP (n = 18 or heart failure (n = 18 as controls. Radiological scores for initial effusion amount and residual pleural fibrosis at 6-month follow-up were assessed. In vitro human PMC experiments were performed to assess the effect of heat-killed M. tuberculosis H37Ra (MTBRa on the expression of TNF-α and MMPs.As compared with controls, the effusion levels of TNF-α, MMP-1 and MMP-9 were significantly higher and correlated positively with initial effusion amount in patients with TBP, while TNF-α and MMP-1, but not MMP-9, were positively associated with residual pleural fibrosis of TBP. Moreover, effusion levels of TNF-α had positive correlation with those of MMP-1 and MMP-9 in TBP. In cultured PMCs, MTBRa enhanced TLR2 and TLR4 expression, activated ERK signaling, and upregulated TNF-α mRNA and protein expression. Furthermore, knockdown of TLR2, but not TLR4, significantly inhibited ERK phosphorylation and TNF-α expression. Additionally, both MTBRa and TNF-α markedly induced MMP-1 and MMP-9 synthesis in human PMCs, and TNF-α neutralization substantially reduced the production of MMP-1, but not MMP-9, in response to MTBRa stimulation.MTBRa activates TLR2/ERK signalings to induce TNF-α and elicit MMP-1 and MMP-9 in human PMCs, which are associated with effusion volume and pleural fibrosis and may contribute to pathogenesis of TBP. Further investigation of manipulation of TNF-α and MMP expression in pleural mesothelium may provide new insights into the mechanisms and rational treatment strategies for TBP.

  11. Deriving a cardiac ageing signature to reveal MMP-9-dependent inflammatory signalling in senescence.

    Science.gov (United States)

    Ma, Yonggang; Chiao, Ying Ann; Clark, Ryan; Flynn, Elizabeth R; Yabluchanskiy, Andriy; Ghasemi, Omid; Zouein, Fouad; Lindsey, Merry L; Jin, Yu-Fang

    2015-06-01

    Cardiac ageing involves the progressive development of cardiac fibrosis and diastolic dysfunction coordinated by MMP-9. Here, we report a cardiac ageing signature that encompasses macrophage pro-inflammatory signalling in the left ventricle (LV) and distinguishes biological from chronological ageing. Young (6-9 months), middle-aged (12-15 months), old (18-24 months), and senescent (26-34 months) mice of both C57BL/6J wild type (WT) and MMP-9 null were evaluated. Using an identified inflammatory pattern, we were able to define individual mice based on their biological, rather than chronological, age. Bcl6, Ccl24, and Il4 were the strongest inflammatory markers of the cardiac ageing signature. The decline in early-to-late LV filling ratio was most strongly predicted by Bcl6, Il1r1, Ccl24, Crp, and Cxcl13 patterns, whereas LV wall thickness was most predicted by Abcf1, Tollip, Scye1, and Mif patterns. With age, there was a linear increase in cardiac M1 macrophages and a decrease in cardiac M2 macrophages in WT mice; of which, both were prevented by MMP-9 deletion. In vitro, MMP-9 directly activated young macrophage polarization to an M1/M2 mid-transition state. Our results define the cardiac ageing inflammatory signature and assign MMP-9 roles in mediating the inflammaging profile by indirectly and directly modifying macrophage polarization. Our results explain early mechanisms that stimulate ageing-induced cardiac fibrosis and diastolic dysfunction. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  12. Epigalloccatechin-3-gallate Inhibits Ocular Neovascularization and Vascular Permeability in Human Retinal Pigment Epithelial and Human Retinal Microvascular Endothelial Cells via Suppression of MMP-9 and VEGF Activation

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    Hak Sung Lee

    2014-08-01

    Full Text Available Epigalloccatechin-3-gallate (EGCG is the main polyphenol component of green tea (leaves of Camellia sinensis. EGCG is known for its antioxidant, anti-inflammatory, antiviral, and anti-carcinogenic properties. Here, we identify EGCG as a new inhibitor of ocular angiogenesis and its vascular permeability. Matrix metalloproteinases (MMPs and vascular endothelial growth factor (VEGF play a key role in the processes of extracellular matrix (ECM remodeling and microvascular permeability during angiogenesis. We investigated the inhibitory effects of EGCG on ocular neovascularization and vascular permeability using the retina oriented cells and animal models induced by VEGF and alkaline burn. EGCG treatment significantly decreased mRNA and protein expression levels of MMP-9 in the presence of 12-O-tetradecanoylphorbol-13-acetate (TPA and tumor necrosis factor alpha (TNF-α in human retinal pigment epithelial cells (HRPECs. EGCG also effectively protected ARPE-19 cells from cell death and attenuated mRNA expressions of key angiogenic factors (MMP-9, VEGF, VEGF Receptor-2 by inhibiting generation of reactive oxygen species (ROS. EGCG significantly inhibited proliferation, vascular permeability, and tube formation in VEGF-induced human retinal microvascular endothelial cells (HRMECs. Furthermore, EGCG significantly reduced vascular leakage and permeability by blood-retinal barrier breakdown in VEGF-induced animal models. In addition, EGCG effectively limited upregulation of MMP-9 and platelet endothelial cell adhesion molecule (PECAM/CD31 on corneal neovascularization (CNV induced by alkaline burn. Our data suggest that MMP-9 and VEGF are key therapeutic targets of EGCG for treatment and prevention of ocular angiogenic diseases such as age-related macular degeneration, diabetic retinopathy, and corneal neovascularization.

  13. Transcriptional Inhibition of Matrix Metal loproteinase 9 (MMP-9 Activity by a c-fos/Estrogen Receptor Fusion Protein is Mediated by the Proximal AP-1 Site of the MMP-9 Promoter and Correlates with Reduced Tumor Cell Invasion

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    David L. Crowe

    1999-10-01

    Full Text Available Tumor cell invasion of basement membranes is one of the hallmarks of malignant transformation. Tumor cells secrete proteolytic enzymes known as matrix metalloproteinases (MMPs which degrade extracellular matrix molecules. Increased expression of MMP-9 has been associated with acquisition of invasive phenotype in many tumors. However, multiple mechanisms for regulation of MMP-9 gene expression by tumor cell lines have been proposed. A number of transcription factor binding sites have been characterized in the upstream regulatory region of the MMP-9 gene, including those for AP-1. To determine how a specific AP-1 family member, c-fos, regulates MMP-9 promoter activity through these sites, we used an expression vector containing the c-fos coding region fused to the estrogen receptor (ER ligand binding domain. This construct is activated upon binding estradiol. Stable expression of this construct in ER negative squamous cell carcinoma (SCC lines produced an estradiol dependent decrease in the number of cells that migrated through a reconstituted basement membrane. This decreased invasiveness was accompanied by estradiol dependent downregulation of MMP-9 activity as determined by gelatin zymography. Estradiol also produced transcriptional downregulation of an MMP-9 promoter construct in cells transiently transfected with the c-fosER expression vector. This downregulation was mediated by the AP-1 site at —79 by in the MMP-9 promoter. We concluded that the proximal AP-1 site mediated the transcriptional downregulation of the MMP-9 promoter by a conditionally activated c-fos fusion protein.

  14. MMP-9 Serum Levels in Schizophrenic Patients during Treatment Augmentation with Sarcosine (Results of the PULSAR Study

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    Dominik Strzelecki

    2016-07-01

    Full Text Available Aim: Find changes in matrix metallopeptidase-9 (MMP-9 levels during augmentation of antipsychotic treatment with sarcosine and a relationship between schizophrenia symptoms severity and initial level of MMP-9. Method: Fifty-eight patients with diagnosis of schizophrenia with predominant negative symptoms participated in a six-month prospective RCT (randomized controlled trial. The patients received two grams of sarcosine (n = 28 or placebo (n = 30 daily. At the beginning, after six weeks and after six months MMP-9 levels were measured. Severity of symptomatology was assessed with the Positive and Negative Syndrome Scale (PANSS and Calgary Depression Scale for Schizophrenia (CDSS. Results: MMP-9 serum levels were stable after six weeks and six months in both groups. We noted improvement in negative symptoms, general psychopathology and total PANSS score in sarcosine group compared to placebo; however, there was no correlations between serum MMP-9 concentrations and PANSS scores in all assessments. Initial serum MMP-9 concentrations cannot be used as an improvement predictor acquired during sarcosine augmentation. Conclusions: Our results indicate that either MMP-9 is not involved in the N-methyl-d-aspartate (NMDA-dependent mechanism of sarcosine action in terms of clinical parameters or sarcosine induced changes in peripheral MMP-9 concentrations cannot be detected in blood assessments.

  15. MMP-9 Serum Levels in Schizophrenic Patients during Treatment Augmentation with Sarcosine (Results of the PULSAR Study).

    Science.gov (United States)

    Strzelecki, Dominik; Kałużyńska, Olga; Szyburska, Justyna; Wysokiński, Adam

    2016-07-09

    Find changes in matrix metallopeptidase-9 (MMP-9) levels during augmentation of antipsychotic treatment with sarcosine and a relationship between schizophrenia symptoms severity and initial level of MMP-9. Fifty-eight patients with diagnosis of schizophrenia with predominant negative symptoms participated in a six-month prospective RCT (randomized controlled trial). The patients received two grams of sarcosine (n = 28) or placebo (n = 30) daily. At the beginning, after six weeks and after six months MMP-9 levels were measured. Severity of symptomatology was assessed with the Positive and Negative Syndrome Scale (PANSS) and Calgary Depression Scale for Schizophrenia (CDSS). MMP-9 serum levels were stable after six weeks and six months in both groups. We noted improvement in negative symptoms, general psychopathology and total PANSS score in sarcosine group compared to placebo; however, there was no correlations between serum MMP-9 concentrations and PANSS scores in all assessments. Initial serum MMP-9 concentrations cannot be used as an improvement predictor acquired during sarcosine augmentation. Our results indicate that either MMP-9 is not involved in the N-methyl-d-aspartate (NMDA)-dependent mechanism of sarcosine action in terms of clinical parameters or sarcosine induced changes in peripheral MMP-9 concentrations cannot be detected in blood assessments.

  16. Increased expressions of MMP-2 and MMP-9 in lung following 12 Gy local irradiation

    International Nuclear Information System (INIS)

    Yang Kunyu; Liu Li; Zhang Tao; Wu Gang; Hu Yu; Ruebe, C.; Ruebe, C.

    2006-01-01

    Objective: To measure expressions of metalloproteinases and tissue inhibitors of metalloproteinases in the lung following thoracic irradiation of 12 Gy, and explore its possible role in the development of radiation-induced lung damage. Methods: C57BL/6J mice at age of 8 weeks were thoracically irradiated with 12 Gy X-rays (10 MV, 2.4 Gy/min, single exposure), and the control mice were sham-irradiated. The mice were sacrificed at 4 or 8 weeks after thoracic irradiation by decapitation. Lung tissues samples were collected. Expressions of MMP-2, MMP-9, MMP-3, MMP-13, TIMP-1, TIMP-2, and TIMP-3 in lung samples were measured. Results: There was no significant difference in expressions of MMP-3, MMP-13, TIMP-1 TIMP-2, and TIMP-3 in the lung between the two groups at 4 and 8 weeks after thoracic irradiation (or sham-irradiation). However, the expressions of MMP-2 were enhanced by 1.7 and 1.9 folds, and MMP-9 by 2.7 and 2.6 folds at 4 and 8 weeks after thoracic irradiation, respectively. Conclusion: Enhanced expressions of MMP-2 and MMP-9 in the lung were involved in the development of acute lung injury after thoracic irradiation, leading to a disruption of the structure and fibrosis. (authors)

  17. Matrix metalloproteinase 9 (MMP-9) mediated release of MMP-9 resistant stromal cell-derived factor 1α (SDF-1α) from surface modified polymer films.

    Science.gov (United States)

    Steinhagen, Max; Hoffmeister, Peter-Georg; Nordsieck, Karoline; Hötzel, Rudi; Baumann, Lars; Hacker, Michael C; Schulz-Siegmund, Michaela; Beck-Sickinger, Annette G

    2014-04-23

    Preparation of smart materials by coatings of established surfaces with biomolecules will lead to the next generation of functionalized biomaterials. Rejection of implants is still a major problem in medical applications but masking the implant material with protein coatings is a promising approach. These layers not only disguise the material but also equip it with a certain biological function. The anti-inflammatory chemokine stromal cell-derived factor 1α (SDF-1α) is well suited to take over this function, because it efficiently attracts stem cells and promotes their differentiation and proliferation. At least the initial stem cell homing requires the formation of a concentration gradient. Thus, a reliable and robust release mechanism of SDF-1α from the material is essential. Several proteases, most notably matrix metalloproteinases, are upregulated during inflammation, which, in principle, can be exploited for a tightly controlled release of SDF-1α. Herein, we present the covalent immobilization of M-[S4V]-SDF-1α on novel biodegradable polymer films, which consist of heterobifunctional poly(ethylene glycol) and oligolactide-based functionalized macromers. A peptidic linker with a trimeric matrix metalloproteinase 9 (MMP-9) cleavage site (MCS) was used as connection and the linkage between the three components was achieved by combination of expressed protein ligation and Cu(I) catalyzed azide/alkyne cycloaddition. The MCS was used for MMP-9 mediated release of M-[S4V]-SDF-1α from the biomaterial and the released SDF-1α derivative was biologically active and induced strong cell migration, which demonstrates the great potential of this system.

  18. Role of MMP-3 and MMP-9 and their haplotypes in risk of bladder cancer in North Indian cohort.

    Science.gov (United States)

    Srivastava, Priyanka; Mandhani, Anil; Kapoor, Rakesh; Mittal, Rama D

    2010-11-01

    Matrix metalloproteinases (MMPs) play critical roles in cancer development and progression. Nonsynonymous single nucleotide polymorphisms (SNPs) in functional domain of MMP-3 and MMP-9 contribute appreciably to cancer predisposition and aggression. To test this proposition we examined whether six SNPs of the MMP-3 and MMP-9 genes are associated with risk of bladder cancer (BC) in a North Indian population. Six SNPs of MMP-3 and MMP-9 were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in a case-control study including 200 BC patients and 200 age/gender/ethnicity-matched controls. Increased risk for BC susceptibility was observed in MMP-3 (1171) 5A/5A [P = 0.022; odds ratio (OR), 3.46; 95% confidence interval (CI), 1.20-9.98], MMP-9 (Q279R) QQ (P = 0.048; OR, 1.92; 95%CI, 1.01-3.66), MMP-9 (P574R) PR (P BCG)-treated non-muscle-invasive BC (NMIBC) patients (log-rank P = 0.025). Our data suggested that MMP-3-1171 5A/5A and MMP-9 (Q279R) QQ, MMP-9 (P574R) PR, PR + RR, and R allele are associated with high risk of BC.

  19. Clinical significance of determination of serum MMP9 and P III P levels in patients with pulmonary interstitial fibrosis

    International Nuclear Information System (INIS)

    Jia Cuiying

    2008-01-01

    Objective: To assess the clinical value of determination of serum matrix metallo-proteinase-9 (MMP 9 ) and type III pro-collagen peptide (PIIIP) levels in patients with pulmonary interstitial fibrosis. Methods: Serum MMP 9 (with ELISA) and PIIIP(with RIA) levels were determined in 46 patients with pulmonary interstitial fibrosis and 30 controls. Results: Serum MMP 9 and PIIIP levels in patients with pulmonary interstitial fibrosis were significantly higher than those in controls (P 9 and PIIIP might be used as clinical diagnostic markers for pulmonary interstitial fibrosis. (authors)

  20. Plasma levels of the MMP-9:TIMP-1 complex as prognostic biomarker in breast cancer: a retrospective study

    International Nuclear Information System (INIS)

    Thorsen, Stine B; Møller, Susanne; Brünner, Nils; Schrohl, Anne-Sofie; Stenvang, Jan; Christensen, Sarah LT; Würtz, Sidse Ø; Lundberg, Martin; Nielsen, Birgitte S; Vinther, Lena; Knowles, Mick; Gee, Nick; Fredriksson, Simon

    2013-01-01

    Worldwide more than one million women are annually diagnosed with breast cancer. A considerable fraction of these women receive systemic adjuvant therapy; however, some are cured by primary surgery and radiotherapy alone. Prognostic biomarkers guide stratification of patients into different risk groups and hence improve management of breast cancer patients. Plasma levels of Matrix Metalloproteinase-9 (MMP-9) and its natural inhibitor Tissue inhibitor of metalloproteinase-1 (TIMP-1) have previously been associated with poor patient outcome and resistance to certain forms of chemotherapy. To pursue additional prognostic information from MMP-9 and TIMP-1, the level of the MMP-9 and TIMP-1 complex (MMP-9:TIMP-1) was investigated in plasma from breast cancer patients. Detection of protein:protein complexes in plasma was performed using a commercially available ELISA kit and, for the first time, the highly sensitive in-solution proximity ligation assay (PLA). We screened plasma from 465 patients with primary breast cancer for prognostic value of the MMP-9:TIMP-1 complex. Both assays were validated and applied for quantification of MMP-9:TIMP-1 concentration. In this retrospective study, we analyzed the association between the concentration of the MMP-9:TIMP-1 complex and clinicopathological data and disease free survival (DFS) in univariate and multivariate survival analyses. Following successful validation both assays were applied for MMP-9:TIMP-1 measurements. Of the clinicopathological parameters, only menopausal status demonstrated significant association with the MMP-9:TIMP-1 complex; P = 0.03 and P = 0.028 for the ELISA and PLA measurements, respectively. We found no correlation between the MMP-9:TIMP-1 protein complex and DFS neither in univariate nor in multivariate survival analyses. Despite earlier reports linking MMP-9 and TIMP-1 with prognosis in breast cancer patients, we here demonstrate that plasma levels of the MMP-9:TIMP-1 protein complex hold no

  1. Comparison of circulating MMP-9, TIMP-1 and CA19-9 in the detection of pancreatic cancer

    DEFF Research Database (Denmark)

    Jørgensen, Maiken Thyregod; Brunner, Nils; Schaffalitzky de Muckadell, Ove B.

    2010-01-01

    , TIMP-1 and CA19-9 in detecting pancreatic ductal adenocarcinoma were 58.82%, 47.1% and 86%, respectively, with specificities of 34.6%, 69.2% and 73%. The AUCs of MMP-9, TIMP-1 and CA19-9 were 0.50, 0.64 and 0.84, respectively. Combining the three markers did not significantly improve detection......Background/Aim: The performance of the circulating tumor markers carbohydrate antigen 19-9 (CA19-9), matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) were evaluated separately and in combination for their potential value in detecting pancreatic ductal...... adenocarcinoma. PATIENTS AND METHODS: The patients had symptoms of pancreatic cancer. The discriminative strength of MMP-9 and TIMP-1 were compared to that of CA19-9 using receiver operating characteristics curves, area under the curves (AUC), specificity and sensitivity. RESULTS: The sensitivities of MMP-9...

  2. Matrix Metalloproteinase-9 (MMP-9 polymorphisms in patients with cutaneous malignant melanoma

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    Busam Klaus

    2007-03-01

    Full Text Available Abstract Background Cutaneous Malignant Melanoma causes over 75% of skin cancer-related deaths, and it is clear that many factors may contribute to the outcome. Matrix Metalloproteinases (MMPs play an important role in the degradation and remodeling of the extracellular matrix and basement membrane that, in turn, modulate cell division, migration and angiogenesis. Some polymorphisms are known to influence gene expression, protein activity, stability, and interactions, and they were shown to be associated with certain tumor phenotypes and cancer risk. Methods We tested seven polymorphisms within the MMP-9 gene in 1002 patients with melanoma in order to evaluate germline genetic variants and their association with progression and known risk factors of melanoma. The polymorphisms were selected based on previously published reports and their known or potential functional relevance using in-silico methods. Germline DNA was then genotyped using pyrosequencing, melting temperature profiles, heteroduplex analysis, and fragment size analysis. Results We found that reference alleles were present in higher frequency in patients who tend to sunburn, have family history of melanoma, higher melanoma stage, intransit metastasis and desmoplastic melanomas among others. However, after adjustment for age, sex, phenotypic index, moles, and freckles only Q279R, P574R and R668Q had significant associations with intransit metastasis, propensity to tan/sunburn and primary melanoma site. Conclusion This study does not provide strong evidence for further investigation into the role of the MMP-9 SNPs in melanoma progression.

  3. Vaginal Lactoferrin Modulates PGE2, MMP-9, MMP-2, and TIMP-1 Amniotic Fluid Concentrations

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    Alessandro Trentini

    2016-01-01

    Full Text Available Inflammation plays an important role in pregnancy, and cytokine and matrix metalloproteases (MMPs imbalance has been associated with premature rupture of membranes and increased risk of preterm delivery. Previous studies have demonstrated that lactoferrin (LF, an iron-binding protein with anti-inflammatory properties, is able to decrease amniotic fluid (AF levels of IL-6. Therefore, we aimed to evaluate the effect of vaginal LF administration on amniotic fluid PGE2 level and MMP-TIMP system in women undergoing genetic amniocentesis. One hundred and eleven women were randomly divided into controls (n=57 or treated with LF 4 hours before amniocentesis (n=54. Amniotic fluid PGE2, active MMP-9 and MMP-2, and TIMP-1 and TIMP-2 concentrations were determined by commercially available assays and the values were normalized by AF creatinine concentration. PGE2, active MMP-9, and its inhibitor TIMP-1 were lower in LF-treated group than in controls (p<0.01, p<0.005, and p<0.001, resp.. Conversely, active MMP-2 (p<0.0001 and MMP-2/TIMP-2 molar ratio (p<0.001 were increased, whilst TIMP-2 was unchanged. Our data suggest that LF administration is able to modulate the inflammatory response following amniocentesis, which may counteract cytokine and prostanoid imbalance that leads to abortion. This trial is registered with Clinical Trial number NCT02695563.

  4. Porphyromonas gingivalis decreases osteoblast proliferation through IL-6-RANKL/OPG and MMP-9/TIMPs pathways

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    Le Xuan

    2009-01-01

    Full Text Available Background: Porphyromonas gingivalis, an important periodontal pathogen, is closely associated with inflammatory alveolar bone resorption. This bacterium exerts its pathogenic effect indirectly through multiple virulence factors, such as lipopolysaccharides, fimbriae, and proteases. Another possible pathogenic path may be through a direct interaction with the host′s soft and hard tissues (e.g., alveolar bone, which could lead to periodontitis. Aims and Objectives: The aim of the present study was to investigate the direct effect of live and heat-inactivated P gingivalis on bone resorption, using an in vitro osteoblast culture model. Results: Optical microscopy and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide MTT assay revealed that live P gingivalis induced osteoblast detachment and reduced their proliferation. This effect was specific to live bacteria and was dependent on their concentration. Live P gingivalis increased IL-6 mRNA expression and protein production and downregulated RANKL and OPG mRNA expression. The effect of live P gingivalis on bone resorption was strengthened by an increase in MMP-9 expression and its activity. This increase was accompanied by an increase in TIMP-1 and TIMP-2 mRNA expression and protein production by osteoblasts infected with live P gingivalis. Conclusion: Overall, the results suggest that direct contact of P gingivalis with osteoblasts induces bone resorption through an inflammatory pathway that involves IL-6, RANKL/OPG, and MMP-9/TIMPs.

  5. Differential inhibition of activity, activation and gene expression of MMP-9 in THP-1 cells by azithromycin and minocycline versus bortezomib: A comparative study.

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    Jennifer Vandooren

    Full Text Available Gelatinase B or matrix metalloproteinase-9 (MMP-9 (EC 3.4.24.35 is increased in inflammatory processes and cancer, and is associated with disease progression. In part, this is due to MMP-9-mediated degradation of extracellular matrix, facilitating influx of leukocytes into inflamed tissues and invasion or metastasis of cancer cells. MMP-9 is produced as proMMP-9 and its propeptide is subsequently removed by other proteases to generate proteolytically active MMP-9. The significance of MMP-9 in pathologies triggered the development of specific inhibitors of this protease. However, clinical trials with synthetic inhibitors of MMPs in the fight against cancer were disappointing. Reports on active compounds which inhibit MMP-9 should be carefully examined in this regard. In a considerable set of recent publications, two antibiotics (minocycline and azythromycin and the proteasome inhibitor bortezomib, used in cancers, were reported to inhibit MMP-9 at different stages of its expression, activation or activity. The current study was undertaken to compare and to verify the impact of these compounds on MMP-9. With exception of minocycline at high concentrations (>100 μM, the compounds did not affect processing of proMMP-9 into MMP-9, nor did they affect direct MMP-9 gelatinolytic activity. In contrast, azithromycin specifically reduced MMP-9 mRNA and protein levels without affecting NF-κB in endotoxin-challenged monocytic THP-1 cells. Bortezomib, although being highly toxic, had no MMP-9-specific effects but significantly upregulated cyclooxygenase-2 (COX-2 activity and PGE2 levels. Overall, our study clarified that azithromycin decreased the levels of MMP-9 by reduction of gene and protein expression while minocycline inhibits proteolytic activity at high concentrations.

  6. Bmi-1 promotes the aggressiveness of glioma via activating the NF-kappaB/MMP-9 signaling pathway

    International Nuclear Information System (INIS)

    Jiang, Lili; Wu, Jueheng; Yang, Yi; Liu, Liping; Song, Libing; Li, Jun; Li, Mengfeng

    2012-01-01

    The prognosis of human glioma is poor, and the highly invasive nature of the disease represents a major impediment to current therapeutic modalities. The oncoprotein B-cell-specific Moloney murine leukemia virus integration site 1 protein (Bmi-1) has been linked to the development and progression of glioma; however, the biological role of Bmi-1 in the invasion of glioma remains unclear. A172 and LN229 glioma cells were engineered to overexpress Bmi-1 via stable transfection or to be silenced for Bmi-1 expression using RNA interfering method. Migration and invasiveness of the engineered cells were assessed using wound healing assay, Transwell migration assay, Transwell matrix penetration assay and 3-D spheroid invasion assay. MMP-9 expression and activity were measured using real-time PCR, ELISA and the gelatin zymography methods. Expression of NF-kappaB target genes was quantified using real-time PCR. NF-kappaB transcriptional activity was assessed using an NF-kappaB luciferase reporter system. Expression of Bmi-1 and MMP-9 in clinical specimens was analyzed using immunohistochemical assay. Ectopic overexpression of Bmi-1 dramatically increased, whereas knockdown of endogenous Bmi-1 reduced, the invasiveness and migration of glioma cells. NF-kappaB transcriptional activity and MMP-9 expression and activity were significantly increased in Bmi-1-overexpressing but reduced in Bmi-1-silenced cells. The reporter luciferase activity driven by MMP-9 promoter in Bmi-1-overexpressing cells was dependent on the presence of a functional NF-kappaB binding site, and blockade of NF-kappaB signaling inhibited the upregulation of MMP-9 in Bmi-1 overexpressing cells. Furthermore, expression of Bmi-1 correlated with NF-kappaB nuclear translocation as well as MMP-9 expression in clinical glioma samples. Bmi-1 may play an important role in the development of aggressive phenotype of glioma via activating the NF-kappaB/MMP-9 pathway and therefore might represent a novel therapeutic

  7. Correlation Between Th1, Th2 Cells and Levels of Serum MMP-2, MMP-9 in Children with Asthma

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    Xuan WANG

    2015-12-01

    Full Text Available Abstract Objective: To explore the correlation between Th1 and Th2 cells and the levels of serum matrix metalloproteinase-2 (MMP-2 and MMP-9 in children with asthma. Methods: A total of 89 children with asthma were divided into acute group (n=48 and chronic group (n=41 according to the course of disease, and 40 healthy children at the same term were collected as control group. The ratios of Th1 and Th2 cells as well as levels of MMP-2 and MMP-9 were compared in three groups, and the correlation between Th1 and Th2 cells and levels of MMP-2, MMP-9 was analyzed in acute group and chronic group. Results: When compared with control group, the ratios of Th1 and Th2 cells went down in both acute group and chronic group (P<0.01, while the levels of serum MMP-2 and MMP-9 up (P<0.01. The levels of serum MMP-2 and MMP-9 in acute group were dramatically higher than those in chronic group, and there was statistical significance (P<0.01. Pearson correlation analysis revealed that there was no significant correlation between Th1 and Th2 cells and MMP-2 level (r=0.148, P=0.314, r=0.299, P=0.058; r=0.183, P=0.214, r=0.289, P=0.067, whereas both Th1 and Th2 cells were negatively correlated with MMP-9 level in acute group and chronic group (r=-0.489, P=0.000, r=-0.324, P=0.039; r=-0.352, P=0.014, r=-0.357, P=0.022. Conclusion: Aberrant secretion of Th cells can not only damage the immune function of children with asthma, but also decrease the level of serum MMP-9, consequently affecting the collagen degradation and airway remodeling.

  8. Concentration of MMP-9, TNF-a and IL-6 in patients with tumors and tumor-like bone lesions

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    Puchinyan D.M.

    2017-09-01

    Full Text Available Aim: to determine the concentration of MMP-9, TNF-a and IL-6 in blood serum of patients with benign and malignant bone tumors and feasibility of cytokine data use for differential diagnostics of the neoplastic process nature. Material and Methods. Levels of matrix metalloproteinase-9 (MMP-9, tumor necrosis factor-a (TNF-a and interleukin-6 (IL-6 in blood serum were determined by the immunoenzyme method in 64 patients with bone tissue neoplasms (fibrous dysplasia, osteocystoma, giant-cell tumor, osteosarcoma, chondrosarcoma, bone metastases, multiple myeloma. Re-sults. MMP-9 level was heightened in patients suffered from chondrosarcoma and multiple myeloma. TNF-a and IL-6 expression was increased in cases with bone metastases. MMP-9, TNF-a and IL-6 levels were higher in cases with malignant bone neoplasms than in cases with benign bone tumors. Conclusion. MMP-9, TNF-a and IL-6 participate in the neoplastic process pathogenesis directly. Nevertheless it is too early to speak about the diagnostic value of the cytokines in cases with tumorous bone affection.

  9. Matrix metalloproteinases (MMP-2 and MMP-9) activity in corneal ulcer and ocular surface disorders determined by gelatin zymography.

    Science.gov (United States)

    Singh, Arti; Maurya, O P S; Jagannadhan, M V; Patel, Ashok

    2012-01-01

    The purpose of this paper is to determine the active form of matrix metalloproteinases (MMP-2 and MMP-9) in corneal ulcer and ocular surface disorder patients. A total of 35 patients of corneal ulcer, 20 patients of ocular surface disorders and 10 control subjects were included in this study and estimation of active form of MMP-2 and MMP-9 was done by gelatin zymography. Tear samples were collected by capillary tube method. Both pro- and active forms of MMP-9 were detected in 24 out of 35 patients with corneal ulcer and 15 out of 20 patients with ocular surface disorders. None of the patients were showing MMP-2 activity. Neither MMP-2 nor MMP-9 was detected in the control group. Active forms of MMP-9 are present in tears of severe ulcerative and ocular surface disorder patients. Thus, proteinase inhibitors have been recommended for the treatment of corneal ulcer and ocular surface disorders to reduced the progression of stromal ulcer and to minimize corneal scarring.

  10. Osteopontin and MMP9: Associations with VEGF Expression/Secretion and Angiogenesis in PC3 Prostate Cancer Cells

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    Gupta, Aditi; Zhou, Cindy Q.; Chellaiah, Meenakshi A., E-mail: mchellaiah@umaryland.edu [Department of Oncology and Diagnostic Sciences, Dental School, University of Maryland, Baltimore, MD 21201 (United States)

    2013-05-27

    Osteopontin and MMP9 are implicated in angiogenesis and cancer progression. The objective of this study is to gain insight into the molecular mechanisms underlying angiogenesis, and to elucidate the role of osteopontin in this process. We report here that osteopontin/αvβ3 signaling pathway which involves ERK1/2 phosphorylation regulates the expression of VEGF. An inhibitor to MEK or curcumin significantly suppressed the phosphorylation of ERK1/2 and expression of VEGF. MMP9 knockdown reduces the secretion but not the expression of VEGF. Moreover, MMP9 knockdown increases the release of angiostatin, a key protein that suppresses angiogenesis. Conditioned media from PC3 cells treated with curcumin or MEK inhibitor inhibited tube formation in vitro in human microvascular endothelial cells. Similar inhibitory effect on tube formation was found with conditioned media collected from PC3 cells expressing mutant-osteopontin at integrin-binding site and knockdown of osteopontin or MMP9. We conclude that MMP9 activation is associated with angiogenesis via regulation of secretion of VEGF and angiostatin in PC3 cells. Curcumin is thus a potential drug for cancer treatment because it demonstrated anti-angiogenic and anti-invasive properties.

  11. MMP2 and MMP9 participate in S1P-induced invasion of follicular ML-1 thyroid cancer cells.

    Science.gov (United States)

    Kalhori, Veronica; Törnquist, Kid

    2015-03-15

    The bioactive lipid sphingosine-1-phosphate (S1P) has emerged as a potent inducer of cancer cell migration and invasion. Previously, we have shown that S1P induces invasion of ML-1 follicular thyroid cancer cells via S1P receptors 1 and 3 (S1P1,3). Matrix metalloproteinases (MMPs) are zinc-dependent proteolytic enzymes used by cells for degradation of the extracellular matrix during invasion and migration. In the present study, we examined the role of MMP2 and MMP9 for S1P-induced invasion of ML-1 cells, and found that S1P regulates the secretion and activity of MMP2 and MMP9 via S1P1,3. Both pharmacological inhibitors and siRNA knockdown of MMP2 and MMP9 could attenuate S1P-induced invasion. Additionally, we show that calpains and Rac1 mediate S1P-induced secretion of MMP2 and MMP9. In conclusion, MMP2 and MMP9 participate in S1P-evoked follicular ML-1 thyroid cancer cell invasion. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Salivary matrix metalloproteinase (MMP-8) levels and gelatinase (MMP-9) activities in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Collin, H L; Sorsa, T; Meurman, J H; Niskanen, L; Salo, T; Rönkä, H; Konttinen, Y T; Koivisto, A M; Uusitupa, M

    2000-10-01

    We studied the salivary levels and activities of the matrix metalloproteinases (MMP) -8 and -9 in 45 type 2 diabetic patients and 77 control subjects. The patients' mean glycosylated haemoglobin (HbA1c) was 8.7%, indicating an unsatisfactory metabolic control of the disease. The MMP levels were further related to the clinical and microbiological periodontal findings as well as to salivary flow rate and other factors. The salivary flow rate, albumin and amylase concentrations were similar in type 2 diabetic patients to those in the control group. The mean gingival and periodontal pocket indexes were higher in the diabetes group. The number of potential periodontopathogenic bacteria was lower, however, in the diabetic than in the control group. Zymography and immunoblotting revealed that the major MMPs in the type 2 diabetic patients' saliva were MMP-8 and MMP-9. Salivary MMP levels and activities in type 2 diabetic patients were in general similar to those in the control group. However, the correlation coefficients using multiple regression analysis revealed that gingival bleeding, pocket depths and HbA1c were associated with increased MMP-8 levels which, in turn, were negatively predicted by elevated plasma lipid peroxide levels in the diabetic group. Our data on salivary MMP-8 and -9 do not support the concept of generalized neutrophil dysfunction in unbalanced diabetes. Moreover, plasma lipid peroxidation levels reflecting the increased oxidative burden, which is generated mainly by triggered neutrophils, do not indicate neutrophil dysfunction due to diabetes, but may rather be related to the increased tissue damage in an uncontrolled disease. However. advanced periodontitis in type 2 diabetes seems to be related to elevated salivary MMP-8 levels which might be useful in monitoring periodontal disease in diabetes.

  13. Regulation of MMP2 and MMP9 metalloproteinases by FSH and growth factors in bovine granulosa cells

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    Valerio M. Portela

    2009-01-01

    Full Text Available Matrix metalloproteinases (MMP are key enzymes involved in tissue remodeling. Within the ovary, they are believed to play a major role in ovulation, and have been linked to follicle atresia. To gain insight into the regulation of MMPs, we measured the effect of hormones and growth factors on MMP2 and MMP9 mRNA levels in non-luteinizing granulosa cells in serum-free culture. FSH and IGF1 both stimulated estradiol secretion and inhibited MMP2 and MMP9 mRNA abundance. In contrast, EGF and FGF2 both inhibited estradiol secretion but had no effect on MMP expression. At physiological doses, none of these hormones altered the proportion of dead cells. Although we cannot link MMP expression with apoptosis, the specific down regulation by the gonadotropic hormones FSH and IGF1 in vitro suggests that excess MMP2 and MMP9 expression is neither required nor desired for follicle development.

  14. A prospective study to assess the value of MMP-9 in improving the appropriateness of urgent referrals for colorectal cancer

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    Hobbs Richard FD

    2006-10-01

    Full Text Available Abstract Background Bowel cancer is common and is a major cause of death. Most people with bowel symptoms who meet the criteria for urgent referral to secondary care will not be found to have bowel cancer, and some people who are found to have cancer will have been referred routinely rather than urgently. If general practitioners could better identify people who were likely to have bowel cancer or conditions that may lead to bowel cancer, the pressure on hospital clinics may be reduced, enabling these patients to be seen more quickly. Increased levels of an enzyme called matrix metalloproteinase 9 (MMP-9 have been found to be associated with such conditions, and this can be measured from a blood sample. This study aims to find out whether measuring MMP-9 levels could improve the appropriateness of urgent referrals for patients with bowel symptoms. Methods People aged 18 years or older referred to a colorectal clinic will be asked to complete a questionnaire about symptoms, recent injuries or chronic illnesses (these can increase the level of matrix metalloproteinases and family history of bowel cancer. A blood sample will be taken from people who consent to take part to assess MMP-9 levels, and the results of examination at the clinic and/or investigations arising from the clinic visit will be collected from hospital records. The accuracy of MMP-9 will be assessed by comparing the MMP-9 level with the resulting diagnosis. The combination of factors (e.g. symptoms and MMP-9 level that best predict a diagnosis of malignancy (invasive disease or polyps will be determined. Discussion Although guidelines are in place to facilitate referrals to colorectal clinics, symptoms alone do not adequately distinguish people with malignancy from people with benign conditions. This study will establish whether MMP-9 could assist this process. If this were the case, measurement of MMP-9 levels could be used by general practitioners to assist in the identification

  15. Evaluation of the accuracy of serum MMP-9 as a test for colorectal cancer in a primary care population

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    Colbourne Lynne

    2006-10-01

    Full Text Available Abstract Background Bowel cancer is common and is a major cause of death. Meta-analysis of randomised controlled trials estimates that screening for colorectal cancer using faecal occult blood (FOB test reduces mortality from colorectal cancer by 16%. However, FOB testing has a low positive predictive value, with associated unnecessary cost, risk and anxiety from subsequent investigation, and is unacceptable to a proportion of the target population. Increased levels of an enzyme called matrix metalloproteinase 9 (MMP-9 have been found to be associated with colorectal cancer, and this can be measured from a blood sample. Serum MMP-9 is potentially an accurate, low risk and cost-effective population screening tool. This study aims to evaluate the accuracy of serum MMP-9 as a test for colorectal cancer in a primary care population. Methods/Design People aged 50 to 69 years, who registered in participating general practices in the West Midlands Region, will be asked to complete a questionnaire that asks about symptoms. Respondents who describe any colorectal symptoms (except only abdominal bloating and/or anal symptoms and are prepared to provide a blood sample for MMP9 estimation and undergo a colonoscopy (current gold standard investigation will be recruited at GP based clinics by a research nurse. Those unfit for colonoscopy will be excluded. Colonoscopies will be undertaken in dedicated research clinics. The accuracy of MMP-9 will be assessed by comparing the MMP-9 level with the colonoscopy findings, and the combination of factors (e.g. symptoms and MMP-9 level that best predict a diagnosis of malignancy (invasive disease or polyps will be determined. Discussion Colorectal cancer is a major cause of morbidity and mortality. Most colorectal cancers arise from adenomas and there is a period for early detection by screening, but available tests have risks, are unacceptable to many, have high false positive rates or are expensive. This study will

  16. Pre-Treatment of Platinum Resistant Ovarian Cancer Cells with an MMP-9/MMP-2 Inhibitor Prior to Cisplatin Enhances Cytotoxicity as Determined by High Content Screening

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    John J. O'Leary

    2013-01-01

    Full Text Available Platinum resistance is a major cause of treatment failure in ovarian cancer. We previously identified matrix metalloproteinase 9 (MMP-9 as a potential therapeutic target of chemoresistant disease. A2780cis (cisplatin-resistant and A2780 (cisplatin-sensitive ovarian carcinoma cell lines were used. The cytotoxic effect of MMP-9/MMP-2 inhibitor, (2R-2-[(4-Biphenylsulfonyl amino]-3 phenylpropionic acid (C21H19NO4S alone or in combination with cisplatin was determined using high content screening. Protein expression was examined using immunohistochemistry and ELISA. Co-incubation of cisplatin and an MMP-9/MMP-2 inhibitor, (2R-2-[(4-Biphenylsulfonyl amino]-3 phenylpropionic acid (C21H19NO4S resulted in significantly greater cytotoxicity as compared to either treatment alone in a cisplatin resistant MMP-9 overexpressing cell line; A2780cis. In addition, pre-incubating with MMP-9i prior to cisplatin further enhances the cytotoxic effect. No significant difference was observed in MMP-9 protein in tissue but a trend towards increased MMP-9 was observed in recurrent serum. We propose that MMP-9/MMP-2i may be utilized in the treatment of recurrent/chemoresistant ovarian cancers that overexpress MMP-9 mRNA but its role in vivo remains to be evaluated.

  17. Tumour-associated neutrophils and loss of epithelial PTEN can promote corticosteroid-insensitive MMP-9 expression in the chronically inflamed lung microenvironment.

    Science.gov (United States)

    Vannitamby, Amanda; Seow, Huei Jiunn; Anderson, Gary; Vlahos, Ross; Thompson, Michelle; Steinfort, Daniel; Irving, Louis B; Bozinovski, Steven

    2017-12-01

    Matrix metalloproteinase-9 (MMP-9) is increased in a number of pathological lung conditions, where the proteinase contributes to deleterious remodelling of the airways. While both lung cancer and COPD are associated with increased MMP-9 expression, the cellular and molecular drivers of MMP-9 remain unresolved. In this study, MMP-9 transcript measured within the tumour region from patients with non-small-cell lung cancer (NSCLC) and coexisting COPD was found to be uniformly increased relative to adjacent tumour-free tissue. MMP-9 gene expression and immunohistochemistry identified tumour-associated neutrophils, but not macrophages, as a predominant source of this proteinase. In addition, PTEN gene expression was significantly reduced in tumour and there was evidence of epithelial MMP-9 expression. To explore whether PTEN can regulate epithelial MMP-9 expression, a small interfering (si)RNA knockdown strategy was used in Beas-2B bronchial epithelial cells. PTEN knockdown by siRNA selectively increased MMP-9 expression in response to lipopolysaccharide in a corticosteroid-insensitive manner. In summary, tumour-associated neutrophils represent an important source of MMP-9 in NSCLC, and loss of epithelial PTEN may further augment steroid-insensitive expression. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  18. 4-Hydroxynonenal enhances MMP-9 production in murine macrophages via 5-lipoxygenase-mediated activation of ERK and p38 MAPK

    International Nuclear Information System (INIS)

    Lee, Seung J.; Kim, Chae E.; Yun, Mi R.; Seo, Kyo W.; Park, Hye M.; Yun, Jung W.; Shin, Hwa K.; Bae, Sun S.; Kim, Chi D.

    2010-01-01

    Exaggerated levels of 4-hydroxynonenal (HNE) and 5-lipoxygenase (5-LO) co-exist in macrophages in atherosclerotic lesions, and activated macrophages produce MMP-9 that degrades atherosclerotic plaque constituents. This study investigated the effects of HNE on MMP-9 production, and the potential role for 5-LO derivatives in MMP-9 production in murine macrophages. Stimulation of J774A.1 cells with HNE led to activation of 5-LO, as measured by leukotriene B 4 (LTB 4 ) production. This was associated with an increased production of MMP-9, which was blunted by inhibition of 5-LO with MK886, a 5-LO inhibitor or with 5-LO siRNA. A cysteinyl-LT 1 (cysLT 1 ) receptor antagonist, REV-5901 as well as a BLT 1 receptor antagonist, U-75302, also attenuated MMP-9 production induced by HNE. Furthermore, LTB 4 and cysLT (LTC 4 and LTD 4 ) enhanced MMP-9 production in macrophages, suggesting a pivotal role for 5-LO in HNE-mediated production of MMP-9. Among the MAPK pathways, LTB 4 and cysLT enhanced phosphorylation of ERK and p38 MAPK, but not JNK. Linked to these results, a p38 MAPK inhibitor as well as an ERK inhibitor blunted MMP-9 production induced by LT. Collectively, these data suggest that 5-LO-derived LT mediates HNE-induced MMP-9 production via activation of ERK and p38 MAPK pathways, consequently leading to plaque instability in atherosclerosis.

  19. Clinical significance of determination of changes of serum ferritin, MMP-2 and MMP-9 levels and after transfusion of red blood cells in patients with chronic nephritis

    International Nuclear Information System (INIS)

    Yuan Haitao; Li Xinhua; He Haoming

    2010-01-01

    Objective: To explore the changes of serum Ferritin, MMP-2 and MMP-9 contents after transfusion of red blood cells in patients with chronic nephritis. Methods: Serum Ferritin (with RIA) and serum MMP-2, MMP-9 (with ELISA) levels were measured in 32 patients with chronic nephritis both before and after a course of transfusion of red blood cells and 35 controls. Results: Before transfusion, the serum Ferritin, MMP-9 levels in the patients were significantly lower than those in controls (P 0.05). Conclusion: Determination of serum Ferritin, MMP-2 and MMP-9 levels is clinically useful for management of patients with chronic nephritis. (authors)

  20. Regulation of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of MMP, and progesterone secretion in luteinized granulosa cells from normally ovulating women with polycystic ovary disease.

    Science.gov (United States)

    Ben-Shlomo, Izhar; Goldman, Shlomit; Shalev, Eliezer

    2003-03-01

    To investigate the regulation of MMP-9, TIMP-1, and progesterone via three signal transduction pathways in luteinized granulosa cells from normal ovulatory and PCOD women. In vitro study. Laboratory for Research in Reproductive Sciences, Department of Obstetrics and Gynecology, Ha'Emek Hospital, Afula, Israel. Ten normal ovulatory and 10 women with polycystic ovary disease (PCOD) treated in an assisted reproduction program. Cultured cells were exposed to phorbol 12-myristate 13-acetate (TPA), acting via protein kinase C (PKC), to epidermal growth factor (EGF), acting via protein tyrosine kinase (PTK), and to forskolin, acting via protein kinase A (PKA). Secretion of MMP-9, TIMP-1, and progesterone. Phorbol 12-myristate 13-acetate elicited an increase in MMP-9 and TIMP-1 secretion in both groups and apparently did not affect progesterone secretion. Epidermal growth factor did not change significantly neither MMP-9 nor TIMP-1 secretion but dose dependently decreased MMP-9-TIMP-1 ratio and increased progesterone secretion in the PCOD group. Forskolin inhibited MMP-9 activity and increased TIMP-1 and progesterone secretion in both groups. Progesterone production was inversely related to the ratio of MMP-9-TIMP-1 regardless of cell origin. In this preliminary study, similar and divergent patterns have emerged in the regulation of MMP-9 and TIMP-1 in human luteinized granulosa cells. Repressing MMP-9-TIMP-1 ratio may have an important modulatory effect on progesterone secretion.

  1. Matrix Metalloproteinase-3 (MMP-3) Is an Endogenous Activator of the MMP-9 Secreted by Placental Leukocytes: Implication in Human Labor.

    Science.gov (United States)

    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

    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. 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. 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. In this work we confirm that placental leukocytes from human term

  2. Genetic variations of MMP9 gene and intracerebral hemorrhage susceptibility: a case-control study in Chinese Han population.

    Science.gov (United States)

    Yang, Jie; Wu, Bo; Lin, Sen; Zhou, Junshan; Li, Yingbin; Dong, Wei; Arima, Hisatomi; Zhang, Chanfei; Liu, Yukai; Liu, Ming

    2014-06-15

    To investigate the association between genetic variations of matrix metalloproteinase 9 (MMP9) gene and intracerebral hemorrhage (ICH) susceptibility in Chinese Han population. The clinical data and peripheral blood samples from the patients with ICH and hypertension, and controlled subjects with hypertension only, were collected. MassARRAY Analyzer was used to genotype the tagger single nucleotide polymorphism (SNP) of MMP9 gene. Haploview4.2 and Unphased3.1.7 were employed to construct haplotypes and to analyze the association between genetic variations (alleles, genotypes and haplotypes) of MMP9 gene and ICH susceptibility. 181 patients with ICH and hypertension, and 197 patients with hypertension only, were recruited between Sep 2009 and Oct 2010. Patients in the ICH group were younger (61.80 ± 13.27 vs. 72.44 ± 12.71 years, ppopulation. Our logistical regression analysis showed that there were no significant associations between genetic variations of the MPP9 gene and ICH susceptibility (all p>0.05). The genetic variations of MMP9 gene were not significantly associated with ICH susceptibility in the Chinese Han population. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Clinical evidence for a protective role of lipocalin-2 against MMP-9 autodegradation and the impact for gastric cancer

    NARCIS (Netherlands)

    Kubben, F.J.G.M.; Sier, C.F.M.; Hawinkels, L.J.A.C.; Tschesche, H.; Duijn, W. van; Zuidwijk, K.; Reijden, J.J. van der; Hanemaaijer, R.; Griffioen, G.; Lamers, C.B.H.W.; Verspaget, H.W.

    2007-01-01

    Recently, complexes of matrix metalloproteinase matrix metalloproteinase-9 (MMP-9) with lipocalin-2 (neutrophil gelatinase-associated lipocalin) were found in the urine obtained from breast cancer patients, while these were completely absent in that obtained from healthy controls. In vitro data

  4. An ex vivo study on immunohistochemical localization of MMP-7 and MMP-9 in temporomandibular joint discs with internal derangement

    Directory of Open Access Journals (Sweden)

    C. Loreto

    2013-04-01

    Full Text Available Internal derangement (ID is among the most common disorders of the temporomandibular joint (TMJ. Previous research by our group highlighted a correlation between apoptosis and TMJ ID. Metalloproteinases (MMP-7 and -9 have been shown to play an important role in extracellular matrix ECM homeostasis and, through it, in joint disc remodelling. The immunohistochemical expression of MMP-7 and -9 was investigated in discs from patients with TMJ ID and from healthy donors and compared with the degree of histological tissue degeneration. The collagen fibre arrangement in pathological discs exhibited varying degrees of disruption. New vessels were consistently detected; endothelial cells from these vessels were immunolabelled with both MMP-7 and MMP-9. More or less intense MMP-7 and MMP-9 immunolabelling was detected in the cytoplasm of disc cells from all patients. MMP-7 and MMP-9 immunostaining was significantly different between pathological and normal discs and correlated with the extent of histopathological degeneration. MMP-7 and MMP-9 upregulation in discs from patients with TMJ ID demonstrates their involvement in disc damage in this disorder. A greater understanding of these processes could help identify ways to curb MMP overproduction without affecting their tissue remodelling action. The design of specific inhibitors for these MMPs would not only help to gain insights into the biological roles of MMPs, but would also aid in developing therapeutic interventions for diseases associated with abnormal ECM degradation.

  5. Interleukin-6 triggers human cerebral endothelial cells proliferation and migration: The role for KDR and MMP-9

    International Nuclear Information System (INIS)

    Yao, Jianhua S.; Zhai Wenwu; Young, William L.; Yang Guoyuan

    2006-01-01

    Interleukin-6 (IL-6) is involved in angiogenesis. However, the underlying mechanisms are unknown. Using human cerebral endothelial cell (HCEC), we report for First time that IL-6 triggers HCEC proliferation and migration in a dose-dependent manner, specifically associated with enhancement of VEGF expression, up-regulated and phosphorylated VEGF receptor-2 (KDR), and stimulated MMP-9 secretion. We investigated the signal pathway of IL-6/IL-6R responsible for KDR's regulation. Pharmacological inhibitor of PI3K failed to inhibit IL-6-mediated VEGF overexpression, while blocking ERK1/2 with PD98059 could abolish IL-6-induced KDR overexpression. Further, neutralizing endogenous VEGF attenuated KDR expression and phosphorylation, suggesting that IL-6-induced KDR activation is independent of VEGF stimulation. MMP-9 inhibitor GM6001 significantly decreases HCEC proliferation and migration (p < 0.05), indicating the crucial function of MMP-9 in promoting angiogenic changes in HCECs. We conclude that IL-6 triggers VEGF-induced angiogenic activity through increasing VEGF release, up-regulates KDR expression and phosphorylation through activating ERK1/2 signaling, and stimulates MMP-9 overexpression

  6. Assessment of gelatinases (MMP-2 and MMP-9) by gelatin zymography.

    Science.gov (United States)

    Toth, Marta; Sohail, Anjum; Fridman, Rafael

    2012-01-01

    Gelatin zymography is a simple yet powerful method to detect proteolytic enzymes capable of degrading gelatin from various biological sources. It is particularly useful for the assessment of two key members of the matrix metalloproteinase family, MMP-2 (gelatinase A) and MMP-9 (gelatinase B), due to their potent gelatin-degrading activity. This polyacrylamide gel electrophoresis-based method can provide a reliable assessment of the type of gelatinase, relative amount, and activation status (latent, compared with active enzyme forms) in cultured cells, tissues, and biological fluids. The method can be used to investigate factors that regulate gelatinase expression and modulate zymogen activation in experimental systems. The system provides information on the pattern of gelatinase expression and activation in human cancer tissues and how this relates to cancer progression. Interpretation of the data obtained in gelatin zymography requires a thorough understanding of the principles and pitfalls of the technique; this is particularly important when evaluating enzyme levels and the presence of active gelatinase species. If properly used, gelatin zymography is an excellent tool for the study of gelatinases in biological systems.

  7. Bmi-1 promotes the aggressiveness of glioma via activating the NF-kappaB/MMP-9 signaling pathway

    Directory of Open Access Journals (Sweden)

    Jiang Lili

    2012-09-01

    Full Text Available Abstract Background The prognosis of human glioma is poor, and the highly invasive nature of the disease represents a major impediment to current therapeutic modalities. The oncoprotein B-cell-specific Moloney murine leukemia virus integration site 1 protein (Bmi-1 has been linked to the development and progression of glioma; however, the biological role of Bmi-1 in the invasion of glioma remains unclear. Methods A172 and LN229 glioma cells were engineered to overexpress Bmi-1 via stable transfection or to be silenced for Bmi-1 expression using RNA interfering method. Migration and invasiveness of the engineered cells were assessed using wound healing assay, Transwell migration assay, Transwell matrix penetration assay and 3-D spheroid invasion assay. MMP-9 expression and activity were measured using real-time PCR, ELISA and the gelatin zymography methods. Expression of NF-kappaB target genes was quantified using real-time PCR. NF-kappaB transcriptional activity was assessed using an NF-kappaB luciferase reporter system. Expression of Bmi-1 and MMP-9 in clinical specimens was analyzed using immunohistochemical assay. Results Ectopic overexpression of Bmi-1 dramatically increased, whereas knockdown of endogenous Bmi-1 reduced, the invasiveness and migration of glioma cells. NF-kappaB transcriptional activity and MMP-9 expression and activity were significantly increased in Bmi-1-overexpressing but reduced in Bmi-1-silenced cells. The reporter luciferase activity driven by MMP-9 promoter in Bmi-1-overexpressing cells was dependent on the presence of a functional NF-kappaB binding site, and blockade of NF-kappaB signaling inhibited the upregulation of MMP-9 in Bmi-1 overexpressing cells. Furthermore, expression of Bmi-1 correlated with NF-kappaB nuclear translocation as well as MMP-9 expression in clinical glioma samples. Conclusions Bmi-1 may play an important role in the development of aggressive phenotype of glioma via activating the NF-kappaB/MMP

  8. 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) produces edema due to BBB disruption induced by MMP-9 activation in rat hippocampus.

    Science.gov (United States)

    Pérez-Hernández, Mercedes; Fernández-Valle, María Encarnación; Rubio-Araiz, Ana; Vidal, Rebeca; Gutiérrez-López, María Dolores; O'Shea, Esther; Colado, María Isabel

    2017-05-15

    The recreational drug of abuse, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) disrupts blood-brain barrier (BBB) integrity in rats through an early P2X 7 receptor-mediated event which induces MMP-9 activity. Increased BBB permeability often causes plasma proteins and water to access cerebral tissue leading to vasogenic edema formation. The current study was performed to examine the effect of a single neurotoxic dose of MDMA (12.5 mg/kg, i.p.) on in vivo edema development associated with changes in the expression of the perivascular astrocytic water channel, AQP4, as well as in the expression of the tight-junction (TJ) protein, claudin-5 and Evans Blue dye extravasation in the hippocampus of adult male Dark Agouti rats. We also evaluated the ability of the MMP-9 inhibitor, SB-3CT (25 mg/kg, i.p.), to prevent these changes in order to validate the involvement of MMP-9 activation in MDMA-induced BBB disruption. The results show that MDMA produces edema of short duration temporally associated with changes in AQP4 expression and a reduction in claudin-5 expression, changes which are prevented by SB-3CT. In addition, MDMA induces a short-term increase in both tPA activity and expression, a serine-protease which is involved in BBB disruption and upregulation of MMP-9 expression. In conclusion, this study provides evidence enough to conclude that MDMA induces edema of short duration due to BBB disruption mediated by MMP-9 activation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Curcumin inhibits EMMPRIN and MMP-9 expression through AMPK-MAPK and PKC signaling in PMA induced macrophages.

    Science.gov (United States)

    Cao, Jiatian; Han, Zhihua; Tian, Lei; Chen, Kan; Fan, Yuqi; Ye, Bozhi; Huang, Weijian; Wang, Changqian; Huang, Zhouqing

    2014-09-21

    In coronary arteries, plaque disruption, the major acute clinical manifestations of atherosclerosis, leads to a subsequent cardiac event, such as acute myocardial infarction (AMI) and unstable angina pectoris (UA). Numerous reports have shown that high expression of MMP-9 (matrix metalloproteinase-9), MMP-13 (matrix metalloproteinase-13) and EMMPRIN (extracellular matrix metalloproteinase induce) in monocyte/macrophage results in the plaque progression and destabilization. Curcumin exerts well-known anti-inflammatory and antioxidant effects and probably has a protective role in the atherosclerosis. The purpose of our study was to investigate the molecular mechanisms by which curcumin affects MMP-9, MMP13 and EMMPRIN in PMA (phorbol 12-myristate 13-acetate) induced macrophages. Human monocytic cells (THP-1 cells) were pretreated with curcumin or compound C for 1 h, and then induced by PMA for 48 h. Total RNA and proteins were collected for real-time PCR and Western blot analysis, respectively. In the present study, the exposure to curcumin resulted in attenuated JNK, p38, and ERK activation and decreased expression of MMP-9, MMP-13 and EMMPRIN in PMA induced macrophages. Moreover, we demonstrated that AMPK (AMP-activated protein kinase) and PKC (Protein Kinase C) was activated by PMA during monocyte/macrophage differentiation. Furthermore, curcumin reversed PMA stimulated PKC activation and suppressed the chronic activation of AMPK, which in turn reduced the expression of MMP-9, MMP-13 and EMMPRIN. Therefore, it is suggested that curcumin by inhibiting AMPK-MAPK (mitogen activated protein kinase) and PKC pathway may led to down-regulated EMMPRIN, MMP-9 and MMP-13 expression in PMA-induced THP-1 cells.

  10. Modulation of MMP-2 and MMP-9 in Churg-Strauss syndrome respiratory mucosa: potential monitoring parameters.

    Science.gov (United States)

    Leone, A; Uzzo, M L; Gerbino, A; Tortorici, S; Tralongo, P; Cappello, F; Incandela, S; Spatola, G F; Jurjus, A R

    2014-01-01

    Churg-Strauss (CSS) syndrome is rare and of unknown etiology. It is associated with vasculitis, blood eosinophilia and granulomatosis, and affects multiple organs and systems at various stages of the disease. Specific diagnostic and monitoring tests are not yet available. This study aims to assess the changes in MMP-2 and MMP-9 along with the histopathological alterations in two cases of CSS, as possible potential diagnostic and monitoring criteria. Two adult male patients were diagnosed with CSS in the otorhinolaryngology clinic in the University of Palermo, based on multiple clinical and histopathologic criteria. Biopsies of respiratory mucosa were taken after the consent of the patients, processed for routine histopathology and immunohistochemistry as well as quantitative polymerase chain reaction (qPCR). Similar biopsies were also taken from a non- CSS patient. The Assessment of MMP-2 and MMP-9 was performed using both immunohistochemistry and qPCR techniques. Histopathological alterations in the respiratory mucosa were consistent with vasculitis and granulomatous tissue formation, in addition to inflammatory cell infiltration with abundance of eosinophils. Immunohistochemistry assay performed on the samples derived from the two CSS patients showed a relative and remarkable increase of both MMP-2 and MMP-9 compared to controls. Such an increase was consistent with the qPCR results which depicted a significant increase between 20 and 30% for both MMP-2 and MMP-9, respectively. Since the secretion of MMPs is an essential step in angiogenesis, could these enzymatic factors be used as parameters to diagnose or monitor the evolution of CSS? The small number of samples analyzed in this study does not allow us to suggest a general statement correlating the increase in expression of MMP-2 and MMP-9 to the appearance or evolution of vasculitis; it is only speculative.

  11. TNF-α promotes human retinal pigment epithelial (RPE) cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression through activation of Akt/mTORC1 signaling

    International Nuclear Information System (INIS)

    Wang, Cheng-hu; Cao, Guo-Fan; Jiang, Qin; Yao, Jin

    2012-01-01

    Highlights: ► TNF-α induces MMP-9 expression and secretion to promote RPE cell migration. ► MAPK activation is not critical for TNF-α-induced MMP-9 expression. ► Akt and mTORC1 signaling mediate TNF-α-induced MMP-9 expression. ► SIN1 knockdown showed no significant effect on MMP-9 expression by TNF-α. -- Abstract: Tumor necrosis factor-alpha (TNF-α) promotes in vitro retinal pigment epithelial (RPE) cell migration to initiate proliferative vitreoretinopathy (PVR). Here we report that TNF-α promotes human RPE cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression. Inhibition of MMP-9 by its inhibitor or its neutralizing antibody inhibited TNF-α-induced in vitro RPE cell migration. Reversely, exogenously-added active MMP-9 promoted RPE cell migration. Suppression Akt/mTOR complex 1(mTORC1) activation by LY 294002 and rapamycin inhibited TNF-α-mediated MMP-9 expression. To introduce a constitutively active Akt (CA-Akt) in cultured RPE cells increased MMP-9 expression, and to block mTORC1 activation by rapamycin inhibited its effect. RNA interference (RNAi)-mediated silencing of SIN1, a key component of mTOR complex 2 (mTORC2), had no effect on MMP-9 expression or secretion. In conclusion, this study suggest that TNF-α promotes RPE cell migration by inducing MMP-9 expression through activation of Akt/ mTORC1, but not mTORC2 signaling.

  12. TNF-{alpha} promotes human retinal pigment epithelial (RPE) cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression through activation of Akt/mTORC1 signaling

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Cheng-hu; Cao, Guo-Fan [The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029 (China); Jiang, Qin, E-mail: Jqin710@vip.sina.com [The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029 (China); Yao, Jin, E-mail: dryaojin@yahoo.com [The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029 (China)

    2012-08-17

    Highlights: Black-Right-Pointing-Pointer TNF-{alpha} induces MMP-9 expression and secretion to promote RPE cell migration. Black-Right-Pointing-Pointer MAPK activation is not critical for TNF-{alpha}-induced MMP-9 expression. Black-Right-Pointing-Pointer Akt and mTORC1 signaling mediate TNF-{alpha}-induced MMP-9 expression. Black-Right-Pointing-Pointer SIN1 knockdown showed no significant effect on MMP-9 expression by TNF-{alpha}. -- Abstract: Tumor necrosis factor-alpha (TNF-{alpha}) promotes in vitro retinal pigment epithelial (RPE) cell migration to initiate proliferative vitreoretinopathy (PVR). Here we report that TNF-{alpha} promotes human RPE cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression. Inhibition of MMP-9 by its inhibitor or its neutralizing antibody inhibited TNF-{alpha}-induced in vitro RPE cell migration. Reversely, exogenously-added active MMP-9 promoted RPE cell migration. Suppression Akt/mTOR complex 1(mTORC1) activation by LY 294002 and rapamycin inhibited TNF-{alpha}-mediated MMP-9 expression. To introduce a constitutively active Akt (CA-Akt) in cultured RPE cells increased MMP-9 expression, and to block mTORC1 activation by rapamycin inhibited its effect. RNA interference (RNAi)-mediated silencing of SIN1, a key component of mTOR complex 2 (mTORC2), had no effect on MMP-9 expression or secretion. In conclusion, this study suggest that TNF-{alpha} promotes RPE cell migration by inducing MMP-9 expression through activation of Akt/ mTORC1, but not mTORC2 signaling.

  13. pVHL co-ordinately regulates CXCR4/CXCL12 and MMP2/MMP9 expression in human clear-cell renal cell carcinoma

    DEFF Research Database (Denmark)

    Struckmann, K; Mertz, Kd; Steu, S

    2008-01-01

    Loss of pVHL function, characteristic for clear-cell renal cell carcinoma (ccRCC), causes increased expression of CXCR4 chemokine receptor, which triggers expression of metastasis-associated MMP2/MMP9 in different human cancers. The impact of pVHL on MMP2/MMP9 expression and their relationship to...

  14. Chrysin inhibits tumor promoter-induced MMP-9 expression by blocking AP-1 via suppression of ERK and JNK pathways in gastric cancer cells.

    Directory of Open Access Journals (Sweden)

    Yong Xia

    Full Text Available Cell invasion is a crucial mechanism of cancer metastasis and malignancy. Matrix metalloproteinase-9 (MMP-9 is an important proteolytic enzyme involved in the cancer cell invasion process. High expression levels of MMP-9 in gastric cancer positively correlate with tumor aggressiveness and have a significant negative correlation with patients' survival times. Recently, mechanisms suppressing MMP-9 by phytochemicals have become increasingly investigated. Chrysin, a naturally occurring chemical in plants, has been reported to suppress tumor metastasis. However, the effects of chrysin on MMP-9 expression in gastric cancer have not been well studied. In the present study, we tested the effects of chrysin on MMP-9 expression in gastric cancer cells, and determined its underlying mechanism. We examined the effects of chrysin on MMP-9 expression and activity via RT-PCR, zymography, promoter study, and western blotting in human gastric cancer AGS cells. Chrysin inhibited phorbol-12-myristate 13-acetate (PMA-induced MMP-9 expression in a dose-dependent manner. Using AP-1 decoy oligodeoxynucleotides, we confirmed that AP-1 was the crucial transcriptional factor for MMP-9 expression. Chrysin blocked AP-1 via suppression of the phosphorylation of c-Jun and c-Fos through blocking the JNK1/2 and ERK1/2 pathways. Furthermore, AGS cells pretreated with PMA showed markedly enhanced invasiveness, which was partially abrogated by chrysin and MMP-9 antibody. Our results suggest that chrysin may exert at least part of its anticancer effect by controlling MMP-9 expression through suppression of AP-1 activity via a block of the JNK1/2 and ERK1/2 signaling pathways in gastric cancer AGS cells.

  15. Resveratrol Targeting of Carcinogen-Induced Brain Endothelial Cell Inflammation Biomarkers MMP-9 and COX-2 is Sirt1-Independent

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    Borhane Annabi

    2012-01-01

    Full Text Available The occurrence of a functional relationship between the release of metalloproteinases (MMPs and the expression of cyclooxygenase (COX-2, two inducible pro-inflammatory biomarkers with important pro-angiogenic effects, has recently been inferred. While brain endothelial cells play an essential role as structural and functional components of the blood-brain barrier (BBB, increased BBB breakdown is thought to be linked to neuroinflammation. Chemopreventive mechanisms targeting both MMPs and COX-2 however remain poorly investigated. In this study, we evaluated the pharmacological targeting of Sirt1 by the diet-derived and antiinflammatory polyphenol resveratrol. Total RNA, cell lysates, and conditioned culture media from human brain microvascular endothelial cells (HBMEC were analyzed using qRT-PCR, immunoblotting, and zymography respectively. Tissue scan microarray analysis of grade I–IV brain tumours cDNA revealed increased gene expression of Sirt-1 from grade I–III but surprisingly not in grade IV brain tumours. HBMEC were treated with a combination of resveratrol and phorbol 12-myristate 13-acetate (PMA, a carcinogen known to increase MMP-9 and COX-2 through NF-κB. We found that resveratrol efficiently reversed the PMA-induced MMP-9 secretion and COX-2 expression. Gene silencing of Sirt1, a critical modulator of angiogenesis and putative target of resveratrol, did not lead to significant reversal of MMP-9 and COX-2 inhibition. Decreased resveratrol inhibitory potential of carcinogen-induced IκB phosphorylation in siSirt1-transfected HBMEC was however observed. Our results suggest that resveratrol may prevent BBB disruption during neuroinflammation by inhibiting MMP-9 and COX-2 and act as a pharmacological NF-κB signal transduction inhibitor independent of Sirt1.

  16. Discovery of a highly selective chemical inhibitor of matrix metalloproteinase-9 (MMP-9) that allosterically inhibits zymogen activation.

    Science.gov (United States)

    Scannevin, Robert H; Alexander, Richard; Haarlander, Tara Mezzasalma; Burke, Sharon L; Singer, Monica; Huo, Cuifen; Zhang, Yue-Mei; Maguire, Diane; Spurlino, John; Deckman, Ingrid; Carroll, Karen I; Lewandowski, Frank; Devine, Eric; Dzordzorme, Keli; Tounge, Brett; Milligan, Cindy; Bayoumy, Shariff; Williams, Robyn; Schalk-Hihi, Celine; Leonard, Kristi; Jackson, Paul; Todd, Matthew; Kuo, Lawrence C; Rhodes, Kenneth J

    2017-10-27

    Aberrant activation of matrix metalloproteinases (MMPs) is a common feature of pathological cascades observed in diverse disorders, such as cancer, fibrosis, immune dysregulation, and neurodegenerative diseases. MMP-9, in particular, is highly dynamically regulated in several pathological processes. Development of MMP inhibitors has therefore been an attractive strategy for therapeutic intervention. However, a long history of failed clinical trials has demonstrated that broad-spectrum MMP inhibitors have limited clinical utility, which has spurred the development of inhibitors selective for individual MMPs. Attaining selectivity has been technically challenging because of sequence and structural conservation across the various MMPs. Here, through a biochemical and structural screening paradigm, we have identified JNJ0966, a highly selective compound that inhibited activation of MMP-9 zymogen and subsequent generation of catalytically active enzyme. JNJ0966 had no effect on MMP-1, MMP-2, MMP-3, MMP-9, or MMP-14 catalytic activity and did not inhibit activation of the highly related MMP-2 zymogen. The molecular basis for this activity was characterized as an interaction of JNJ0966 with a structural pocket in proximity to the MMP-9 zymogen cleavage site near Arg-106, which is distinct from the catalytic domain. JNJ0966 was efficacious in reducing disease severity in a mouse experimental autoimmune encephalomyelitis model, demonstrating the viability of this therapeutic approach. This discovery reveals an unprecedented pharmacological approach to MMP inhibition, providing an opportunity to improve selectivity of future clinical drug candidates. Targeting zymogen activation in this manner may also allow for pharmaceutical exploration of other enzymes previously viewed as intractable drug targets. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Morphological changes of cerebral vessels and expression patterns of MMP-2 and MMP-9 on cerebrovascular wall of alcoholic rats.

    Science.gov (United States)

    Qi, Qian; Liu, Xia; Zhang, Guozhong; He, Wenjing; Ma, Rufei; Cong, Bin; Li, Yingmin

    2014-01-01

    Alcohol abuse increases the incidence of cerebral accidents, which correlates with cerebrovascular structural changes. The present study was designed to observe the cerebrovascular remodeling of drinking rats with light microscopy and transmission electron microscopy (TEM). Short-term alcohol administration induced apparent amplification of perivascular spaces around small vessels in brain tissue, while long-term administration caused pathological changes of basilar arteries (BAs), including endothelial exfoliation, inner elastic lamina (IEL) fragmentation and thickening of tunica media and adventitia. In addition, the relationship between cerebrovascular remodeling and MMP-2 and MMP-9 synthesized by endothelial cells and vascular smooth muscle cells was explored by immunohistochemistry. The two protein expression in cerebral vessels changed dynamically, peaking at 1-2 weeks after treatment, and decreasing as treatment continued. These results suggest that MMP-2 and MMP-9 may play a significant role in blood-brain barrier disruption after alcohol abuse. But the chronic changes of cerebral arteries resulted from drinking are not coincident with time course of MMP-2 and MMP-9 expression in situ.

  18. Possible Association between Serum Matrix Metalloproteinase-9 (MMP-9) Levels and Relapse in Depressed Patients following Electroconvulsive Therapy (ECT).

    Science.gov (United States)

    Shibasaki, Chiyo; Itagaki, Kei; Abe, Hiromi; Kajitani, Naoto; Okada-Tsuchioka, Mami; Takebayashi, Minoru

    2018-03-01

    Matrix metalloproteinases are involved in neuroinflammatory processes, which could underlie depression. Serum levels of MMP-9 and MMP-2 in depressed patients are significantly altered following electroconvulsive therapy, but an association between altered matrix metalloproteinases after successful ECT and possible relapse has yet to be investigated. Serum was obtained twice, before and immediately after a course of electroconvulsive therapy, from 38 depressed patients. Serum was also collected, once, from two groups of age- and gender-matched healthy controls, 40 volunteers in each group. Possible associations between levels of matrix metalloproteinases and relapse during a 1-year follow-up period were analyzed. Excluding patients who did not respond to electroconvulsive therapy and patients lost to follow-up, data from 28 patients were evaluated. Eighteen of the patients (64.3%) relapsed within 1 year. In the group that did not relapse, serum levels of MMP-9 were significantly decreased after a course of electroconvulsive therapy, but not in the group that relapsed. No association between MMP-2 and relapse was observed. The degree of change in serum MMP-9 change could be associated with relapse following electroconvulsive therapy in depressed patients. © The Author 2017. Published by Oxford University Press on behalf of CINP.

  19. Association of MMP-9 Haplotypes and TIMP-1 Polymorphism with Spontaneous Deep Intracerebral Hemorrhage in the Taiwan Population.

    Directory of Open Access Journals (Sweden)

    Wei-Min Ho

    Full Text Available Spontaneous deep intracerebral hemorrhage (SDICH is a devastating stroke subtype. The causes of SDICH are heterogeneous. Matrix metalloproteinase-9 (MMP-9, Gelantinase B has been shown to relate to stroke and the development of aneurysm and may increase risks of intracerebral hemorrhage. MMP activities are modulated by their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMPs. We analyzed the genetic variants of MMP-9 and TIMP-1 and SDICH susceptibility.Associations were tested by logistic regression or general linear models with adjusting for multiple covariables. Multiplicative terms between genes were applied to detect the interaction effects on SDICH. Permutation testing of 1,000 replicates was performed for empirical estimates.In the group of ≥65 years old (y/o, we found associations of SDICH with rs3787268 (Odds ratio [OR] = 0.48, 95% confidence interval [CI] 0.27 to 0.86, P = 0.01 and haplotype1 (Hap1 (OR = 0.48, 95% CI 0.26 to 0.86, P = 0.014. For TIMP1 gene, rs4898 was associated with SDICH in the elder male group (OR = 0.35, 95% CI 0.15 to 0.81, P = 0.015. In contrast, in the younger male group, there were associations of SDICH with rs2250889 (OR = 0.48, 95% CI 0.27 to 0.84, P = 0.01 and Hap3 (OR = 0.61, 95% CI 0.38 to 0.97, P = 0.04. We found significant genetic interaction between TIMP-1 and MMP-9 in SDICH susceptibility among younger male subjects (P = 0.004. In subjects carrying rs4898 minor allele, carriers with Hap3 had lower SDICH risk than non-carriers (OR = 0.19, 95% CI 0.07 to 0.51, P = 0.001. In addition, this study showed that when young males were exposed to alcohol, Hap3 was a protective factor of SDICH (OR = 0.06, 95% CI 0.01 to 0.27, P = 0.0002. In contrast, when they were exposed to smoke, Hap2 carriers had increased risk of SDICH (OR = 2.45, 95% CI 1.05 to 5.73, P = 0.04.This study showed modest to moderate effects of MMP-9 and TIMP-1 polymorphisms on SDICH risks with significant age differences

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

    Science.gov (United States)

    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. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  1. Inhibition of EMMPRIN and MMP-9 Expression by Epigallocatechin-3-Gallate through 67-kDa Laminin Receptor in PMA-Induced Macrophages.

    Science.gov (United States)

    Wang, Qi-Ming; Wang, Hao; Li, Ya-Fei; Xie, Zhi-Yong; Ma, Yao; Yan, Jian-Jun; Gao, Yi Fan Wei; Wang, Ze-Mu; Wang, Lian-Sheng

    2016-01-01

    It is well documented that overexpression of EMMPRIN (extracellular matrix metalloproteinase inducer) and MMPs (matrix metalloproteinases) by monocytes/macrophages plays an important role in atherosclerotic plaque rupture. Green tea polyphenol epigallocatechin-3-gallate (EGCG) has a variety of pharmacological properties and exerts cardiovascular protective effects. Recently, the 67-kD laminin receptor (67LR) has been identified as a cell surface receptor of EGCG. The aim of the present study was to evaluate the effects of EGCG on the expression of EMMPRIN and MMP-9 in PMA-induced macrophages, and the potential mechanisms underlying its effects. Human monocytic THP-1 cells were induced to differentiate into macrophages with phorbol 12-myristate 13-acetate (PMA). Protein expression and MMP-9 activity were assayed by Western blot and Gelatin zymography, respectively. Real-time PCR was used to examine EMMPRIN and MMP-9 mRNA expression. We showed that EGCG (10-50µmol/L) significantly inhibited the expression of EMMPRIN and MMP-9 and activation of extracellular signal-regulated kinase 1/2 (ERK1/2), p38 and c-Jun N-terminal kinase (JNK) in PMA-induced macrophages. Downregulation of EMMPRIN by gene silencing hindered PMA-induced MMP-9 secretion and expression, indicating an important role of EMMPRIN in the inhibition of MMP-9 by EGCG. Moreover, 67LR was involved in EGCG-mediated suppression of EMMPRIN and MMP-9 expression. Anti-67LR antibody treatment led to abrogation of the inhibitory action of EGCG on the expression of EMMPRIN and MMP-9 and activation of ERK1/2, p38, and JNK. Our results indicate that EGCG restrains EMMPRIN and MMP-9 expression via 67LR in PMA-induced macrophages, which also suggests that EGCG may be a possible therapeutic agent for stabilizing atherosclerotic plaque. © 2016 The Author(s) Published by S. Karger AG, Basel.

  2. Inhibition of EMMPRIN and MMP-9 Expression by Epigallocatechin-3-Gallate through 67-kDa Laminin Receptor in PMA-Induced Macrophages

    Directory of Open Access Journals (Sweden)

    Qi-Ming Wang

    2016-11-01

    Full Text Available Background/Aims: It is well documented that overexpression of EMMPRIN (extracellular matrix metalloproteinase inducer and MMPs (matrix metalloproteinases by monocytes/macrophages plays an important role in atherosclerotic plaque rupture. Green tea polyphenol epigallocatechin-3-gallate (EGCG has a variety of pharmacological properties and exerts cardiovascular protective effects. Recently, the 67-kD laminin receptor (67LR has been identified as a cell surface receptor of EGCG. The aim of the present study was to evaluate the effects of EGCG on the expression of EMMPRIN and MMP-9 in PMA-induced macrophages, and the potential mechanisms underlying its effects. Methods: Human monocytic THP-1 cells were induced to differentiate into macrophages with phorbol 12-myristate 13-acetate (PMA. Protein expression and MMP-9 activity were assayed by Western blot and Gelatin zymography, respectively. Real-time PCR was used to examine EMMPRIN and MMP-9 mRNA expression. Results: We showed that EGCG (10-50µmol/L significantly inhibited the expression of EMMPRIN and MMP-9 and activation of extracellular signal-regulated kinase 1/2 (ERK1/2, p38 and c-Jun N-terminal kinase (JNK in PMA-induced macrophages. Downregulation of EMMPRIN by gene silencing hindered PMA-induced MMP-9 secretion and expression, indicating an important role of EMMPRIN in the inhibition of MMP-9 by EGCG. Moreover, 67LR was involved in EGCG-mediated suppression of EMMPRIN and MMP-9 expression. Anti-67LR antibody treatment led to abrogation of the inhibitory action of EGCG on the expression of EMMPRIN and MMP-9 and activation of ERK1/2, p38, and JNK. Conclusion: Our results indicate that EGCG restrains EMMPRIN and MMP-9 expression via 67LR in PMA-induced macrophages, which also suggests that EGCG may be a possible therapeutic agent for stabilizing atherosclerotic plaque.

  3. Extracellular matrix proteins matrix metallopeptidase 9 (MMP9) and soluble intercellular adhesion molecule 1 (sICAM-1) and correlations with clinical staging in euthymic bipolar disorder.

    Science.gov (United States)

    Reininghaus, Eva Z; Lackner, Nina; Birner, Armin; Bengesser, Susanne; Fellendorf, Frederike T; Platzer, Martina; Rieger, Alexandra; Queissner, Robert; Kainzbauer, Nora; Reininghaus, Bernd; McIntyre, Roger S; Mangge, Harald; Zelzer, Sieglinde; Fuchs, Dietmar; Dejonge, Silvia; Müller, Norbert

    2016-03-01

    Matrix metallopeptidase 9 (MMP9) and soluble intercellular adhesion molecule 1 (sICAM-1) are both involved in the restructuring of connective tissues. Evidence also implicates MMP9 and sICAM in cardiovascular and neoplastic diseases, where blood levels may be a marker of disease severity or prognosis. In individuals with bipolar disorder (BD), higher risk for cardiovascular illness has been extensively reported. The aim of this investigation was to measure and compare peripheral levels of serum MMP9 and sICAM in adults with euthymic BD and healthy controls (HC). Furthermore, we focussed on correlations with illness severity and metabolic parameters. MMP9 levels among the BD sample (n = 112) were significantly higher than among the HC (n = 80) (MMP9: F = 9.885, p = 0.002, η(2)  = 0.058) after controlling for confounding factors. Patients with BD in a later, progressive stage of disease showed significantly higher MMP9 as well as sICAM-1 levels compared to patients with BD in an earlier stage of disease (MMP9: F = 5.8, p = 0.018, η(2)  = 0.054; sICAM-1: F = 5.6, p = 0.020, η(2)  = 0.052). Correlation analyses of cognitive measures revealed a negative association between performance on the d2 Test of Attention and MMP9 (r = -0.287, p = 0.018) in the BD sample. Despite the sample being euthymic (i.e., according to conventional criteria) at the time of analysis, we found significant correlations between MMP9 as well as sICAM-1 and subthreshold depressive/hypomanic symptoms. A collection of disparate findings herein point to a role of MMP9 and cICAM-1 in the patho-progressive process of BD: the increased levels of serum MMP9 and sICAM-1, the correlation between higher levels of these parameters, progressive stage, and cognitive dysfunction in BD, and the positive correlation with subthreshold symptoms. As sICAM-1 and MMP9 are reliable biomarkers of inflammatory and early atherosclerotic disease, these markers may provide indications of the

  4. The in vitro and in vivo effects of microRNA-133a on intervertebral disc destruction by targeting MMP9 in spinal tuberculosis.

    Science.gov (United States)

    Wang, Xin-Wen; Liu, Ji-Jun; Wu, Qi-Ning; Wu, Shu-Fang; Hao, Ding-Jun

    2017-11-01

    We aim to investigate the role of microRNA-133a (miR-133a) in intervertebral disc destruction by targeting MMP9 in spinal tuberculosis (TB). Rabbit models with spinal TB were established and assigned to the blank, miR-133a mimic, miR-133a inhibitor and negative control (NC) groups. Primary notochordal cells were extracted and separately transfected with miR-133a mimics, miR-133a inhibitor, miR-nonsense sequence control (NC), si-NC and si-MMP9. QRT-PCR and Western blot assay were used to detect the expression of MMP-9, Collagen I, Collagen II and Collagen-X. Gelatin Zymography was performed to detect MMP9 activity. Immunohistochemistry was used to detect the expression of Collagen I, Collagen II and Collagen-X proteins. Osteoclast morphology and the number of osteoclast cells were observed after Tartrate resistant acid phosphatase staining. MMP9, Collagen-X and Collagen I expression and MMP9 activity were higher while the expression of Collagen II was lower in the miR-133a mimic group than the miR-NC group. MMP9, Collagen-X Collagen I and MMP9 activities were lower and Collagen II expression was higher in the miR-133a inhibitor group than the miR-NC group. Compared with the si-NC group, the si-MMP9 group showed increased Collagen II expression but decreased expression of MMP9, Collagen-X and Collagen I and MMP9 activity. A reduced amount of osteoclast cells exhibited in the miR-133a mimic group while an increased number was seen in the miR-133a inhibitor group compared to the blank group. MiR-133a could inhibit Collagen degradation by down-regulating MMP-9 expression to attenuate the destructive effects of spinal TB on intervertebral disc. Copyright © 2017. Published by Elsevier Inc.

  5. Clinical significance of determination the changes of serum CGRP, MMP-9 and TIMP-1 levels both before and after treatment in pediatric patients with bronchial asthma

    International Nuclear Information System (INIS)

    Chen Guijin

    2011-01-01

    Objective: To explore the changes of serum CGRP, MMP-9 and TIMP-1 levels after treatment in pediatric patients with bronchial asthma. Methods: Serum CGRP(with RIA), MMP-9, TIMP-1 (with ELISA) levels were measured in 32 patients with bronchial asthma both before and after treatment as well as in 35 controls. Results: Before treatment, the serum CGRP levels was significantly lower in patients than those in controls (P 0.05). Conclusion: Abnormal lower CGRP and high MMP-9, TIMP-1 levels might play an important role in the pathogenesis and development of bronchial asthma in children. (authors)

  6. Interação toxicogenética de polimorfismos da metaloproteinase-9 (MMP-9) da matriz extracelular e exposição ao mercúrio : efeitos sobre a atividade plasmática da MMP-9

    OpenAIRE

    Anna Laura Bechara Jacob Ferreira

    2010-01-01

    Resumo: A exposição ao mercúrio (Hg) causa efeitos deletérios à saúde, incluindo doenças cardiovasculares. Embora os mecanismos não estejam precisamente definidos, metaloproteinases (MMPs) -2 e -9 podem estar envolvidas. Expressão e atividades aumentadas destas MMPs são demonstradas em diversas condições patológicas, e estudos demonstraram que os níveis circulantes de MMPs poderiam ser usados como marcadores de risco cardiovascular. O gene que codifica a MMP-9 apresenta polimorfismos que afet...

  7. Down-Regulation of Neuropathy Target Esterase in Preeclampsia Placenta Inhibits Human Trophoblast Cell Invasion via Modulating MMP-9 Levels

    Directory of Open Access Journals (Sweden)

    Ting Zhong

    2018-02-01

    Full Text Available Background/Aims: Neuropathy target esterase (NTE, also known as neurotoxic esterase is proven to deacylate phosphatidylcholine (PC to glycerophosphocholine as a phospholipase B. Recently; studies showed that artificial phosphatidylserine/PC microvesicles can induce preeclampsia (PE-like changes in pregnant mice. However, it is unclear whether NTE plays a key role in the pathology of PE, a pregnancy-related disease, which was characterized by deficient trophoblast invasion and reduced trophoblast-mediated remodeling of spiral arteries. The aim of this study was to investigate the expression pattern of NTE in the placenta from women with PE and normal pregnancy, and the molecular mechanism of NTE involved in the development of PE. Methods: NTE expression levels in placentas from 20 pregnant women with PE and 20 healthy pregnant women were detected using quantitative PCR and immunohistochemistry staining. The effect of NTE on trophoblast migration and invasion and the underlying mechanisms were examined in HTR-8/SVneo cell lines by transfection method. Results: NTE mRNA and protein expression levels were significantly decreased in preeclamptic placentas than normal control. Over-expression of NTE in HTR-8/SVneo cells significantly promoted trophoblast cells migration and invasion and was associated with increased MMP-9 levels. Conversely, shRNA-mediated down-regulation of NTE markedly inhibited the cell migration and invasion. In addition, silencing NTE reduced the MMP-9 activity and phosphorylated Erk1/2 and AKT levels. Conclusions: Our results suggest that the decreased NTE may contribute to the development of PE through impairing trophoblast invasion by down-regulating MMP-9 via the Erk1/2 and AKT signaling pathway.

  8. Purification and characterization of recombinant full-length and protease domain of murine MMP-9 expressed in Drosophila S2 cells

    DEFF Research Database (Denmark)

    Rasch, Morten G; Lund, Ida K; Illemann, Martin

    2010-01-01

    MMP-9. Constructs encoding zymogens of full-length murine MMP-9 and a version lacking the O-glycosylated linker region and hemopexin domains were therefore generated and expressed in stably transfected Drosophila S2 insect cells. After 7 days of induction the expression levels of the full......-length and truncated versions were 5 mg/l and 2 mg/l, respectively. The products were >95% pure after gelatin Sepharose chromatography and possessed proteolytic activity when analyzed by gelatin zymography. Using the purified full-length murine MMP-9 we raised polyclonal antibodies by immunizations of rabbits......Matrix metalloproteinase-9 (MMP-9) is a 92-kDa soluble pro-enzyme implicated in pathological events including cancer invasion. It is therefore an attractive target for therapeutic intervention studies in mouse models. Development of inhibitors requires sufficient amounts of correctly folded murine...

  9. Rac1/β-Catenin Signalling Pathway Contributes to Trophoblast Cell Invasion by Targeting Snail and MMP9

    Directory of Open Access Journals (Sweden)

    Minghua Fan

    2016-03-01

    Full Text Available Background/Aims: Preeclampsia is an idiopathic and serious complication during gestation in which placental trophoblast cells differentiate into several functional subtypes, including highly invasive extravillous trophoblasts (EVTs. Although the cause and pathogenesis of preeclampsia have remained unclear, numerous studies have suggested that the inadequacy of EVT invasion leads to imperfect uterine spiral artery remodelling, which plays a crucial role in the development of preeclampsia. Rac1, or Ras-related C3 botulinum toxin substrate 1, was found to be a key regulator of the migration, invasion uand apoptosis of various tumour cells. Because EVTs share similar invasive and migratory biological behaviours with malignant cells, this study aimed to determine whether the Rac1 signalling pathway affects trophoblast invasion and is thus involved in the pathogenesis of preeclampsia. Methods: We measured the activity of Rac1 and its downstream targets, β-catenin, Snail and MMP9 in placental tissues from patients experiencing a normal pregnancy and those with preeclampsia. Furthermore, we treated HTR-8/SVneo cells with a shRNA Rac1 vector and the β-catenin inhibitor IWP-2 and explored Rac1 signalling pathway activation as well as the effects of Snail and β-catenin on trophoblast invasion. Results: In placental samples from patients experiencing a normal pregnancy and those with preeclampsia, active Rac1 levels and MMP9 protein and mRNA levels were significantly decreased in term pregnancy samples compared to early pregnancy samples. Lower levels were found in preeclampsia samples than in normal term pregnancy samples, and these levels significantly declined in severe preeclampsia samples compared with mild preeclampsia samples. Further analyses demonstrated that both Rac1 shRNA and the β-catenin inhibitor significantly suppressed MMP9 and Snail activation in trophoblasts, thus impairing trophoblast invasion. Notably, silencing Rac1 down

  10. Tumor necrosis factor-α induces MMP-9 expression via p42/p44 MAPK, JNK, and nuclear factor-κB in A549 cells

    International Nuclear Information System (INIS)

    Lin, C.-C.; Tseng, Hsiao-Wei; Hsieh, Hsi-Lung; Lee, Chiang-Wen; Wu, C.-Y.; Cheng, C.-Y.; Yang, C.-M.

    2008-01-01

    Matrix metalloproteinases (MMPs), in particular MMP-9, have been shown to be induced by cytokines including tumor necrosis factor-α (TNF-α) and contributes to airway inflammation. However, the mechanisms underlying MMP-9 expression induced by TNF-α in human A549 cells remain unclear. Here, we showed that TNF-α induced production of MMP-9 protein and mRNA is determined by zymographic, Western blotting, RT-PCR and ELISA assay, which were attenuated by inhibitors of MEK1/2 (U0126), JNK (SP600125), and NF-κB (helenalin), and transfection with dominant negative mutants of ERK2 (ΔERK) and JNK (ΔJNK), and siRNAs for MEK1, p42 and JNK2. TNF-α-stimulated phosphorylation of p42/p44 MAPK and JNK were attenuated by pretreatment with the inhibitors U0126 and SP600125 or transfection with dominant negative mutants of ΔERK and ΔJNK. Furthermore, the involvement of NF-κB in TNF-α-induced MMP-9 production was consistent with that TNF-α-stimulated degradation of IκB-α and translocation of NF-κB into the nucleus which were blocked by helenalin, but not by U0126 and SP600125, revealed by immunofluorescence staining. The regulation of MMP-9 gene transcription by MAPKs and NF-κB was further confirmed by gene luciferase activity assay. MMP-9 promoter activity was enhanced by TNF-α in A549 cells transfected with wild-type MMP-9-Luc, which was inhibited by helenalin, U0126, or SP600125. In contrast, TNF-α-stimulated MMP-9 luciferase activity was totally lost in cells transfected with mutant-NF-κB MMP-9-luc. Moreover, pretreatment with actinomycin D and cycloheximide attenuated TNF-α-induced MMP-9 expression. These results suggest that in A549 cells, phosphorylation of p42/p44 MAPK, JNK, and transactivation of NF-κB are essential for TNF-α-induced MMP-9 gene expression

  11. The hemopexin and O-glycosylated domains tune gelatinase B/MMP-9 bioavailability via inhibition and binding to cargo receptors

    DEFF Research Database (Denmark)

    Van den Steen, Philippe E; Van Aelst, Ilse; Hvidberg, Vibeke

    2006-01-01

    Gelatinase B/matrix metalloproteinase-9 (MMP-9), a key regulator and effector of immunity, contains a C-terminal hemopexin domain preceded by a unique linker sequence of approximately 64 amino acid residues. This linker sequence is demonstrated to be an extensively O-glycosylated (OG) domain with...... domains down-regulate the bioavailability of active MMP-9 and the interactions with the cargo receptors are proposed to be the original function of hemopexin domains in MMPs....

  12. Bee venom suppresses PMA-mediated MMP-9 gene activation via JNK/p38 and NF-kappaB-dependent mechanisms.

    Science.gov (United States)

    Cho, Hyun-Ji; Jeong, Yun-Jeong; Park, Kwan-Kyu; Park, Yoon-Yub; Chung, Il-Kyung; Lee, Kwang-Gill; Yeo, Joo-Hong; Han, Sang-Mi; Bae, Young-Seuk; Chang, Young-Chae

    2010-02-17

    Bee venom has been used for the treatment of inflammatory diseases such as rheumatoid arthritis and for the relief of pain in traditional oriental medicine. The purpose of this study is to elucidate the effects of bee venom on MMP-9 expression and determine possible mechanisms by which bee venom relieves or prevents the expression of MMP-9 during invasion and metastasis of breast cancer cells. We examined the expression and activity of MMP-9 and possible signaling pathway affected in PMA-induced MCF-7 cells. Bee venom was obtained from the National Institute of Agricultural Science and Technology of Korea. Matrigel invasion assay, wound-healing assay, zymography assay, western blot assay, electrophoretic mobility shift assay and luciferase gene assay were used for assessment. Bee venom inhibited cell invasion and migration, and also suppressed MMP-9 activity and expression, processes related to tumor invasion and metastasis, in PMA-induced MCF-7 cells. Bee venom specifically suppressed the phosphorylation of p38/JNK and at the same time, suppressed the protein expression, DNA binding and promoter activity of NF-kappaB. The levels of phosphorylated ERK1/2 and c-Jun did not change. We also investigated MMP-9 inhibition by melittin, apamin and PLA(2), representative single component of bee venom. We confirmed that PMA-induced MMP-9 activity was significantly decreased by melittin, but not by apamin and phospholipase A(2). These data demonstrated that the expression of MMP-9 was abolished by melittin, the main component of bee venom. Bee venom inhibits PMA-induced MMP-9 expression and activity by inhibition of NF-kappaB via p38 MAPK and JNK signaling pathways in MCF-7 cells. These results indicate that bee venom can be a potential anti-metastatic and anti-invasive agent. This useful effect may lead to future clinical research on the anti-cancer properties of bee venom. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  13. Fisetin inhibits epidermal growth factor-induced migration of ARPE-19 cells by suppression of AKT activation and Sp1-dependent MMP-9 expression.

    Science.gov (United States)

    Lin, Hung-Yu; Chen, Yong-Syuan; Wang, Kai; Chien, Hsiang-Wen; Hsieh, Yi-Hsien; Yang, Shun-Fa

    2017-01-01

    Proliferative vitreoretinopathy (PVR) can result in abnormal migration of RPE cells. Fisetin is a naturally occurring compound that has been reported to have antitumor effects, but its effects on epidermal growth factor (EGF)-induced cell migration and the underlying mechanisms remain unclear. Effects of fisetin on EGF-induced cell viability and migration were examined with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and in vitro migration assays. Reverse transcription-PCR (RT-PCR) and immunoblotting were performed to evaluate matrix metallopeptidase-9 (MMP-9) expression and activation of specificity protein-1 (Sp1) and protein kinase B (AKT) in ARPE-19 cells treated with EGF and with or without fisetin. Luciferase and chromatin immunoprecipitation (ChIP) assays were performed to examine Sp1 transcription activity and MMP-9 binding activity. Fisetin did not affect ARPE-19 cell viability and significantly inhibited the EGF-induced migration capacity of ARPE-19 cells. Furthermore, fisetin exerted an antimigratory effect and suppressed MMP-9 mRNA and protein expression. Treatment with EGF induced phosphorylation of AKT and expression of MMP-9 and Sp1. Fisetin combined with LY294002 (an inhibitor of AKT) prevented the EGF-induced migration involved in downregulation of Sp1 and MMP-9 expression. Luciferase and ChIP assays suggested that fisetin remarkably decreased the EGF-induced transcription activity of MMP-9 and Sp1 and inhibited EGF-mediated Sp1 from directly binding to the MMP-9 promoter in ARPE-19 cells. Fisetin inhibited EGF-induced cell migration via modulation of AKT/Sp1-dependent MMP-9 transcriptional activity. Therefore, fisetin may be a potential agent in the treatment of migratory PVR diseases.

  14. Fisetin inhibits epidermal growth factor–induced migration of ARPE-19 cells by suppression of AKT activation and Sp1-dependent MMP-9 expression

    Science.gov (United States)

    Lin, Hung-Yu; Chen, Yong-Syuan; Wang, Kai; Chien, Hsiang-Wen

    2017-01-01

    Purpose Proliferative vitreoretinopathy (PVR) can result in abnormal migration of RPE cells. Fisetin is a naturally occurring compound that has been reported to have antitumor effects, but its effects on epidermal growth factor (EGF)–induced cell migration and the underlying mechanisms remain unclear. Methods Effects of fisetin on EGF-induced cell viability and migration were examined with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and in vitro migration assays. Reverse transcription–PCR (RT–PCR) and immunoblotting were performed to evaluate matrix metallopeptidase-9 (MMP-9) expression and activation of specificity protein-1 (Sp1) and protein kinase B (AKT) in ARPE-19 cells treated with EGF and with or without fisetin. Luciferase and chromatin immunoprecipitation (ChIP) assays were performed to examine Sp1 transcription activity and MMP-9 binding activity. Results Fisetin did not affect ARPE-19 cell viability and significantly inhibited the EGF-induced migration capacity of ARPE-19 cells. Furthermore, fisetin exerted an antimigratory effect and suppressed MMP-9 mRNA and protein expression. Treatment with EGF induced phosphorylation of AKT and expression of MMP-9 and Sp1. Fisetin combined with LY294002 (an inhibitor of AKT) prevented the EGF-induced migration involved in downregulation of Sp1 and MMP-9 expression. Luciferase and ChIP assays suggested that fisetin remarkably decreased the EGF-induced transcription activity of MMP-9 and Sp1 and inhibited EGF-mediated Sp1 from directly binding to the MMP-9 promoter in ARPE-19 cells. Conclusions Fisetin inhibited EGF-induced cell migration via modulation of AKT/Sp1–dependent MMP-9 transcriptional activity. Therefore, fisetin may be a potential agent in the treatment of migratory PVR diseases. PMID:29296070

  15. The ERK1/2 Inhibitor U0126 Attenuates Diabetes-Induced Upregulation of MMP-9 and Biomarkers of Inflammation in the Retina

    Directory of Open Access Journals (Sweden)

    Ghulam Mohammad

    2013-01-01

    Full Text Available This study was conducted to determine the expression of matrix metalloproteinase-9 (MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1 in a time-dependent manner and the effect of extracellular-signal-regulated kinases-1/2 (ERK1/2 inhibition on the expressions of MMP-9, TIMP-1, and inflammatory biomarkers in the retinas of diabetic rats. The expression of MMP-9 was quantified by zymography, and the mRNA level of MMP-9 and TIMP-1 was quantified by RT-PCR. The expression of inducible nitric oxide synthase (iNOS, interleukin-6 (IL-6, and tumor necrosis factor-alpha (TNF-α was examined by Western blot analysis. MMP-9 expression was significantly higher in diabetic rat retinas compared to controls at all time points.TIMP-1 expression was nonsignificantly upregulated at 1week of diabetes and was significantly downregulated at 4 and 12 weeks of diabetes. Intravitreal administration of the ERK1/2 inhibitor U0126 prior to induction of diabetes decreased ERK1/2 activation, attenuated diabetes-induced upregulation of MMP-9, iNOS, IL-6, and TNF-α and upregulated TIMP-1 expression. In MMP-9 knockout mice, diabetes had no effect on retinal iNOS expression and its level remained unchanged. These data provide evidence that ERK1/2 signaling pathway is involved in MMP-9, iNOS, IL-6, and TNF-α induction in diabetic retinas and suggest that ERK1/2 can be a novel therapeutic target in diabetic retinopathy.

  16. BRD4 Phosphorylation Regulates HPV E2-Mediated Viral Transcription, Origin Replication, and Cellular MMP-9 Expression

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    Shwu-Yuan Wu

    2016-08-01

    Full Text Available Post-translational modification can modulate protein conformation and alter binding partner recruitment within gene regulatory regions. Here, we report that bromodomain-containing protein 4 (BRD4, a transcription co-factor and chromatin regulator, uses a phosphorylation-induced switch mechanism to recruit E2 protein encoded by cancer-associated human papillomavirus (HPV to viral early gene and cellular matrix metalloproteinase-9 (MMP-9 promoters. Enhanced MMP-9 expression, induced upon keratinocyte differentiation, occurs via BRD4-dependent recruitment of active AP-1 and NF-κB to their target sequences. This is triggered by replacement of AP-1 family members JunB and JunD by c-Jun and by re-localization of NF-κB from the cytoplasm to the nucleus. In addition, BRD4 phosphorylation is critical for E2- and origin-dependent HPV DNA replication. A class of phospho-BRD4-targeting compounds, distinct from the BET bromodomain inhibitors, effectively blocks BRD4 phosphorylation-specific functions in transcription and factor recruitment.

  17. EL IGF-II ESTIMULA LA ACTIVIDAD DE MMP-9 Y MMP-2 EN UN MODELO DE TROFOBLASTO HUMANO

    Directory of Open Access Journals (Sweden)

    Myriam Sánchez-Gómez

    2011-01-01

    Full Text Available La invasión del útero por el trofoblasto extravelloso de placenta de primer trimestre depende de la secreción de metaloproteasas de matriz (MMPs las cuales degradan la matriz extracelular; dentro de las cuales las gelatinasas MMP-9 y MMP-2 juegan un papel muy importante. El objetivo de este trabajo fue determinar el efecto de los ligandos del sistema de factores de crecimiento similares a la insulina (IGF en la actividad de gelatinasas en una línea celular establecida de trofoblasto extravelloso invasivo, HTR8/SVneo. Mediante ensayos de zimografía se encontró que el tratamiento con IGF-II 10 nM estimula la actividad de proMMP-9 y proMMP-2 únicamente a las 24 horas. Dosis mayores de IGF-II mostraron un efecto inhibitorio en la actividad proteasa. Adicionalmente, el IGF-II 10 nM estimuló la actividad de otras dos gelatinasas no identificadas de peso molecular 52 kDa tras tratamiento por 24 horas. Ni la insulina ni el IGF-I en concentraciones 10 nM mostraron un efecto estimulador en la actividad de las gelatinasas. Estos resultados muestran el papel potencial del sistema IGF en la regulación de la invasión celular y ayudan a comprender el desarrollo del crecimiento maligno.

  18. Loss of PDEF, a prostate-derived Ets factor is associated with aggressive phenotype of prostate cancer: Regulation of MMP 9 by PDEF

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    Meacham Randall B

    2010-06-01

    Full Text Available Abstract Background Prostate-derived Ets factor (PDEF is expressed in tissues of high epithelial content including prostate, although its precise function has not been fully established. Conventional therapies produce a high rate of cure for patients with localized prostate cancer, but there is, at present, no effective treatment for intervention in metastatic prostate cancer. These facts underline the need to develop new approaches for early diagnosis of aggressive prostate cancer patients, and mechanism based anti-metastasis therapies that will improve the outlook for hormone-refractory prostate cancer. In this study we evaluated role of prostate-derived Ets factor (PDEF in prostate cancer. Results We observed decreased PDEF expression in prostate cancer cell lines correlated with increased aggressive phenotype, and complete loss of PDEF protein in metastatic prostate cancer cell lines. Loss of PDEF expression was confirmed in high Gleason Grade prostate cancer samples by immuno-histochemical methods. Reintroduction of PDEF profoundly affected cell behavior leading to less invasive phenotypes in three dimensional cultures. In addition, PDEF expressing cells had altered cell morphology, decreased FAK phosphorylation and decreased colony formation, cell migration, and cellular invasiveness. In contrast PDEF knockdown resulted in increased migration and invasion as well as clonogenic activity. Our results also demonstrated that PDEF downregulated MMP9 promoter activity, suppressed MMP9 mRNA expression, and resulted in loss of MMP9 activity in prostate cancer cells. These results suggested that loss of PDEF might be associated with increased MMP9 expression and activity in aggressive prostate cancer. To confirm results we investigated MMP9 expression in clinical samples of prostate cancer. Results of these studies show increased MMP9 expression correlated with advanced Gleason grade. Taken together our results demonstrate decreased PDEF expression

  19. Matrix metalloproteinase (MMP-9 in cancer-associated fibroblasts (CAFs is suppressed by omega-3 polyunsaturated fatty acids in vitro and in vivo.

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    Ayumi Taguchi

    Full Text Available Cancer associated fibroblasts (CAFs are responsible for tumor growth, angiogenesis, invasion, and metastasis. Matrix metalloproteinase (MMP-9 secreted from cancer stroma populated by CAFs is a prerequisite for cancer angiogenesis and metastasis. Omega-3 polyunsaturated fatty acids (omega-3 PUFA have been reported to have anti-tumor effects on diverse types of malignancies. Fat-1 mice, which can convert omega-6 to omega-3 PUFA independent of diet, are useful to investigate the functions of endogenous omega-3 PUFA. To examine the effect of omega-3 PUFA on tumorigenesis, TC-1 cells, a murine epithelial cell line immortalized by human papillomavirus (HPV oncogenes, were injected subcutaneously into fat-1 or wild type mice. Tumor growth and angiogenesis of the TC-1 tumor were significantly suppressed in fat-1 compared to wild type mice. cDNA microarray of the tumors derived from fat-1 and wild type mice revealed that MMP-9 is downregulated in fat-1 mice. Immunohistochemical study demonstrated immunoreactivity for MMP-9 in the tumor stromal fibroblasts was diffusely positive in wild type whereas focal in fat-1 mice. MMP-9 was expressed in primary cultured fibroblasts isolated from fat-1 and wild type mice but was not expressed in TC-1 cells. Co-culture of fibroblasts with TC-1 cells enhanced the expression and the proteinase activity of MMP-9, although the protease activity of MMP-9 in fat-1-derived fibroblasts was lower than that in wild type fibroblasts. Our data suggests that omega-3 PUFAs suppress MMP-9 induction and tumor angiogenesis. These findings may provide insight into mechanisms by which omega-3 PUFAs exert anti-tumor effects by modulating tumor microenvironment.

  20. Complexity in differentiating the expression of truncated or matured forms of MMP-2 and MMP-9 through zymography in rat brain tissues after acute ischaemic stroke.

    Science.gov (United States)

    Alam, Mustafa; Shuaib, Ashfaq

    2013-05-30

    Matrix metalloproteinases (MMPs) play an important role in the pathogenesis of ischaemic stroke. In particular, the mature forms of MMPs 2 and 9 have similar sizes and share gelatine as a common substrate. Both MMPs are upregulated in ischaemic stroke and play detrimental roles during stroke pathogenesis. Throughout this study, we demonstrated that pro-MMP-2 and pro-MMP-9 from ischaemic rat brain tissue homogenate is detected either through immunoblotting or zymography because of the remarkable size difference between these enzymes (72 versus 95 kDa, respectively). However, the mature MMP-2 and MMP-9 cannot be discriminated through zymography because of the almost identical sizes of these forms (66 and 67 kDa, respectively). The use of gelatine zymography on ischaemic rat brain tissue homogenate revealed a 65-kDa MMP band, corresponding to the heterogeneous band of mature MMP-2 and/or MMP-9. Furthermore, we also detected mature MMPs of 65 kDa generated from both recombinant human MMP-2 and MMP-9. Using a pull down assay in rat brain tissue homogenate with gelatine-agarose beads, we showed increased activities for both the pro and mature forms of MMP-2 and MMP-9. However, we could not determine the origin of the respective mature MMPs from the heterogeneous band. Thus, in this study, we demonstrated that the identification and quantification of mature MMP-2 and MMP-9 could not be achieved using zymography alone. Therefore, the development of a reliable technique to identify and measure the respective MMPs is needed to test new stroke therapies targeting MMP-2 and MMP-9. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Transcription Factor SOX5 Promotes the Migration and Invasion of Fibroblast-Like Synoviocytes in Part by Regulating MMP-9 Expression in Collagen-Induced Arthritis

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    Yumeng Shi

    2018-04-01

    Full Text Available ObjectivesFibroblast-like synoviocytes (FLS exhibit a unique aggressive phenotype in rheumatoid arthritis (RA. Increased FLS migration and subsequent invasion of the extracellular matrix are essential to joint destruction in RA. Our previous research reported that transcription factor SOX5 was highly expressed in RA-FLS. Here, the effects of SOX5 in RA-FLS migration and invasion will be investigated.MethodsThe migration and invasion of RA-FLS were evaluated using a transwell chamber assay. The expression of several potential SOX5-targeted genes, including matrix metalloproteinases (MMP-1, 2, 3 and 9, chemokines (CCL4, CCL2, CCR5 and CCR2, and pro-inflammatory cytokines (TNF-α and IL-6, were examined in RA-FLS using SOX5 gain- and loss-of-function study. The molecular mechanisms of SOX5-mediated MMP-9 expressions were assayed by luciferase reporter gene and chromatin immunoprecipitation (ChIP studies. The in vivo effect of SOX5 on FLS migration and invasion was examined using collagen-induced arthritis (CIA in DBA/1J mice.ResultsKnockdown SOX5 decreased lamellipodium formation, migration, and invasion of RA-FLS. The expression of MMP-9 was the only gene tested to be concomitantly affected by silencing or overexpressing SOX5. ChIP assay revealed that SOX5 was bound to the MMP-9 promoter in RA-FLS. The overexpression of SOX5 markedly enhanced the MMP-9 promoter activity, and specific deletion of a putative SOX5-binding site in MMP-9 promoter diminished this promoter-driven transcription in FLS. Locally knocked down SOX5 inhibited MMP-9 expression in the joint tissue and reduced pannus migration and invasion into the cartilage in CIA mice.ConclusionSOX5 plays a novel role in mediating migration and invasion of FLS in part by regulating MMP-9 expression in RA.

  2. Transcription Factor SOX5 Promotes the Migration and Invasion of Fibroblast-Like Synoviocytes in Part by Regulating MMP-9 Expression in Collagen-Induced Arthritis.

    Science.gov (United States)

    Shi, Yumeng; Wu, Qin; Xuan, Wenhua; Feng, Xiaoke; Wang, Fang; Tsao, Betty P; Zhang, Miaojia; Tan, Wenfeng

    2018-01-01

    Fibroblast-like synoviocytes (FLS) exhibit a unique aggressive phenotype in rheumatoid arthritis (RA). Increased FLS migration and subsequent invasion of the extracellular matrix are essential to joint destruction in RA. Our previous research reported that transcription factor SOX5 was highly expressed in RA-FLS. Here, the effects of SOX5 in RA-FLS migration and invasion will be investigated. The migration and invasion of RA-FLS were evaluated using a transwell chamber assay. The expression of several potential SOX5-targeted genes, including matrix metalloproteinases (MMP-1, 2, 3 and 9), chemokines (CCL4, CCL2, CCR5 and CCR2), and pro-inflammatory cytokines (TNF-α and IL-6), were examined in RA-FLS using SOX5 gain- and loss-of-function study. The molecular mechanisms of SOX5-mediated MMP-9 expressions were assayed by luciferase reporter gene and chromatin immunoprecipitation (ChIP) studies. The in vivo effect of SOX5 on FLS migration and invasion was examined using collagen-induced arthritis (CIA) in DBA/1J mice. Knockdown SOX5 decreased lamellipodium formation, migration, and invasion of RA-FLS. The expression of MMP-9 was the only gene tested to be concomitantly affected by silencing or overexpressing SOX5. ChIP assay revealed that SOX5 was bound to the MMP-9 promoter in RA-FLS. The overexpression of SOX5 markedly enhanced the MMP-9 promoter activity, and specific deletion of a putative SOX5-binding site in MMP-9 promoter diminished this promoter-driven transcription in FLS. Locally knocked down SOX5 inhibited MMP-9 expression in the joint tissue and reduced pannus migration and invasion into the cartilage in CIA mice. SOX5 plays a novel role in mediating migration and invasion of FLS in part by regulating MMP-9 expression in RA.

  3. Fraxinus rhynchophylla ethanol extract attenuates carbon tetrachloride-induced liver fibrosis in rats via down-regulating the expressions of uPA, MMP-2, MMP-9 and TIMP-1.

    Science.gov (United States)

    Peng, Wen-Huang; Tien, Yun-Chen; Huang, Chih-Yang; Huang, Tai-Hung; Liao, Jung-Chun; Kuo, Chao-Lin; Lin, Ying-Chih

    2010-02-17

    To investigate the effect of Fraxinus rhynchophylla ethanol extract (FR(EtOH)) on liver fibrosis induced by carbon tetrachloride (CCl(4)) in rats. Rat hepatic fibrosis was induced by oral administration of CCl(4). Sixty SD rats were divided randomly into 6 groups: control, CCl(4) group, silymarin group and three FR(EtOH)-treated groups. Except for the rats in control group, all rats were administered orally with CCl(4) (20%, 0.2 mL/100g body weight) twice a week for 8 weeks. Rats in FR(EtOH) groups were treated daily with FR(EtOH) (0.1, 0.5 and 1.0 g/kg, p.o.) throughout the whole experimental period. Liver function parameters (such as activities of serum GOT and GPT levels), activities of liver anti-oxidant enzymes (such as catalase, SOD, GPx) and expressions of uPA, tPA, MMP-2, MMP-9 and TIMP-1, -2, -3, -4 in the liver fibrosis pathway were detected. The results showed that FR(EtOH) (0.1, 0.5 and 1.0 g/kg BW) significantly reduced the elevated activities of sGOT and sGPT caused by CCl(4). FR(EtOH) (0.1 and 0.5 g/kg BW) and significantly increased the activities of GSH-Px. The histopathological study showed that FR(EtOH) (0.1 and 0.5 g/kg BW) reduced the incidence of liver lesions, including hepatic cells cloudy swelling, lymphocytes infiltration, cytoplasm vacuolization hepatic necrosis and fibrous connective tissue proliferated induced by CCl(4) in rats. In our study it was showed that CCl(4)-treated group significantly increased the protein levels of uPA, MMP-2, MMP-9 and TIMP-1. FR(EtOH) (0.1 and 0.5 g/kg BW) could inhibit the protein levels of uPA, MMP-2, MMP-9 and TIMP-1. Finally, the amount of esculetin in the FR(EtOH) was 33.54 mg/g extract. Oral administration of FR(EtOH) significantly reduces CCl(4)-induced hepatic fibrosis in rats, probably by exerting a protective effect against hepatocellular fibrosis by its free radical scavenging ability. FR(EtOH) down-regulated the expressions of uPA, MMP-2 and MMP-9 in CCl(4)-induced liver fibrosis in rats

  4. Effects of an oral MMP-9 and -12 inhibitor, AZD1236, on biomarkers in moderate/severe COPD

    DEFF Research Database (Denmark)

    Dahl, Ronald; Titlestad, Ingrid Louise; Lindqvist, Ari

    2012-01-01

    Abstract Background There is a pressing need for new forms of treatment for COPD. Based on the known pathophysiology of COPD, inhibition of matrix metalloproteinases is a theoretically promising approach. This Phase IIa study evaluated the effects of AZD1236, a selective MMP-9 and MMP-12 inhibitor......, on the biomarkers of inflammation and emphysematous lung tissue degradation in patients with moderate-to-severe COPD. Methods This was a multinational, randomized, double-blind, placebo-controlled signal-searching study conducted in men and women aged ≥40 years with stable moderate-to-severe COPD. After a 2–6-week......-term signal-searching study, although possible evidence of an impact on desmosine may suggest the potential value of selective inhibitors of MMPs in the treatment of COPD in longer term trials....

  5. Salvia miltiorrhiza extract inhibits TPA-induced MMP-9 expression and invasion through the MAPK/AP-1 signaling pathway in human breast cancer MCF-7 cells.

    Science.gov (United States)

    Kim, Jeong-Mi; Noh, Eun-Mi; Song, Hyun-Kyung; Lee, Minok; Lee, Soo Ho; Park, Sueng Hyuk; Ahn, Chan-Keun; Lee, Guem-San; Byun, Eui-Baek; Jang, Beom-Su; Kwon, Kang-Beom; Lee, Young-Rae

    2017-09-01

    Cancer cell invasion is crucial for metastasis. A major factor in the capacity of cancer cell invasion is the activation of matrix metalloproteinase-9 (MMP-9), which degrades the extracellular matrix. Salvia miltiorrhiza has been used as a promotion for blood circulation to remove blood stasis. Numerous previous studies have demonstrated that S. miltiorrhiza extracts (SME) decrease lipid levels and inhibit inflammation. However, the mechanism behind the effect of SME on breast cancer invasion has not been identified. The inhibitory effects of SME on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MMP-9 expression were assessed using western blotting, reverse transcription-quantitative polymerase chain reaction and zymography assays. MMP-9 upstream signal proteins, including mitogen-activated protein kinases and activator protein 1 (AP-1) were also investigated. Cell invasion was assessed using a matrigel invasion assay. The present study demonstrated the inhibitory effects of the SME ethanol solution on MMP-9 expression and cell invasion in TPA-treated MCF-7 breast cancer cells. SME suppressed TPA-induced MMP-9 expression and MCF-7 cell invasion by blocking the transcriptional activation of AP-1. SME may possess therapeutic potential for inhibiting breast cancer cell invasiveness.

  6. Quercetin inhibits the invasion of murine melanoma B16-BL6 cells by decreasing pro-MMP-9 via the PKC pathway.

    Science.gov (United States)

    Zhang, Xian-Ming; Huang, Shao-Peng; Xu, Qiang

    2004-01-01

    On the basis of the inhibitory effect of quercetin on the invasion of melanoma B16-BL6 cells previously reported by us, the mechanisms of quercetin-mediated inhibition of invasion were further investigated in the present study. The ability of B16-BL6 cells to invade and migrate was evaluated in terms of the numbers of cells penetrating a reconstituted basement membrane in the Transwell coculture system. The relative levels and activities of matrix metalloproteinase-9 (MMP-9) and MMP-2 were determined by gelatin zymography and quantified using LabWorks 4.0 software. The quercetin-mediated inhibition of invasion was partially blocked by phorbol-12,13-dibutyrate (PDB), a PKC (protein kinase C) activator, and by doxorubicin, a PKC inhibitor. Only the proforms of MMP-9 (92 kDa) and MMP-2 (72 kDa) were detected by gelatin zymography. Quercetin dose-dependently decreased the gelatinolytic activity of pro-MMP-9. Doxorubicin also markedly reversed the quercetin-induced decrease. Quercetin showed a dose-dependent antagonism of increases in gelatinolytic activity of pro-MMP-9 induced by PDB and free fatty acid (another PKC activator). Together with the report that quercetin directly reduces PKC activity, the results reported here suggest that quercetin may inhibit the invasion of B16-BL6 cells by decreasing pro-MMP-9 via the PKC pathway.

  7. Estrogen induced metastatic modulators MMP-2 and MMP-9 are targets of 3,3'-diindolylmethane in thyroid cancer.

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    Shilpi Rajoria

    2011-01-01

    Full Text Available Thyroid cancer is the most common endocrine related cancer with increasing incidences during the past five years. Current treatments for thyroid cancer, such as surgery or radioactive iodine therapy, often require patients to be on lifelong thyroid hormone replacement therapy and given the significant recurrence rates of thyroid cancer, new preventive modalities are needed. The present study investigates the property of a natural dietary compound found in cruciferous vegetables, 3,3'-diindolylmethane (DIM, to target the metastatic phenotype of thyroid cancer cells through a functional estrogen receptor.Thyroid cancer cell lines were treated with estrogen and/or DIM and subjected to in vitro adhesion, migration and invasion assays to investigate the anti-metastatic and anti-estrogenic effects of DIM. We observed that DIM inhibits estrogen mediated increase in thyroid cell migration, adhesion and invasion, which is also supported by ER-α downregulation (siRNA studies. Western blot and zymography analyses provided direct evidence for this DIM mediated inhibition of E(2 enhanced metastasis associated events by virtue of targeting essential proteolytic enzymes, namely MMP-2 and MMP-9.Our data reports for the first time that DIM displays anti-estrogenic like activity by inhibiting estradiol enhanced thyroid cancer cell proliferation and in vitro metastasis associated events, namely adhesion, migration and invasion. Most significantly, MMP-2 and MMP-9, which are known to promote and enhance metastasis, were determined to be targets of DIM. This anti-estrogen like property of DIM may lead to the development of a novel preventive and/or therapeutic dietary supplement for thyroid cancer patients by targeting progression of the disease.

  8. β2-Adrenoceptor is involved in connective tissue remodeling in regenerating muscles by decreasing the activity of MMP-9.

    Science.gov (United States)

    Silva, Meiricris T; Nascimento, Tábata L; Pereira, Marcelo G; Siqueira, Adriane S; Brum, Patrícia C; Jaeger, Ruy G; Miyabara, Elen H

    2016-07-01

    We investigated the role of β2-adrenoceptors in the connective tissue remodeling of regenerating muscles from β2-adrenoceptor knockout (β2KO) mice. Tibialis anterior muscles from β2KO mice were cryolesioned and analyzed after 3, 10, and 21 days. Regenerating muscles from β2KO mice showed a significant increase in the area density of the connective tissue and in the amount of collagen at 10 days compared with wild-type (WT) mice. A greater increase occurred in the expression levels of collagen I, III, and IV in regenerating muscles from β2KO mice evaluated at 10 days compared with WT mice; this increase continued at 21 days, except for collagen III. Matrix metalloproteinase (MMP-2) activity increased to a similar extent in regenerating muscles from both β2KO and WT mice at 3 and 10 days. This was also the case for MMP-9 activity in regenerating muscles from both β2KO and WT mice at 3 days; however, at 10 days post-cryolesion, this activity returned to baseline levels only in WT mice. MMP-3 activity was unaltered in regenerating muscles at 10 days. mRNA levels of tumor necrosis factor-α increased in regenerating muscles from WT and β2KO mice at 3 days and, at 10 days post-cryolesion, returned to baseline only in WT mice. mRNA levels of interleukin-6 increased in muscles from WT mice at 3 days post-cryolesion and returned to baseline at 10 days post-cryolesion but were unchanged in β2KO mice. Our results suggest that the β2-adrenoceptor contributes to collagen remodeling during muscle regeneration by decreasing MMP-9 activity.

  9. Deafferentation-Induced Redistribution of MMP-2, but Not of MMP-9, Depends on the Emergence of GAP-43 Positive Axons in the Adult Rat Cochlear Nucleus

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    Michaela Fredrich

    2011-01-01

    Full Text Available The matrix metalloproteinases MMP-9 and MMP-2, major modulators of the extracellular matrix (ECM, were changed in amount and distribution in the rat anteroventral cochlear nucleus (AVCN following its sensory deafferentation by cochlear ablation. To determine what causal relationships exist between the redistribution of MMP-9 and MMP-2 and deafferentation-induced reinnervation, kainic acid was stereotaxically injected into the ventral nucleus of the trapezoid body (VNTB prior to cochlear ablation, killing cells that deliver the growth associated protein 43 (GAP-43 into AVCN. Deafferentation-induced changes in the pattern of MMP-9 staining remained unaffected by VNTB lesions. By contrast, changes in the distribution of MMP-2 normally evoked by sensory deafferentation were reversed if GAP-43 positive axons were prevented to grow in AVCN. In conclusion, GAP-43-containing axons emerging in AVCN after cochlear ablation seem to be causal for the maintenance of MMP-2-mediated ECM remodeling.

  10. Possible Mechanisms of Di(2-ethylhexyl Phthalate-Induced MMP-2 and MMP-9 Expression in A7r5 Rat Vascular Smooth Muscle Cells

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    Mei-Fen Shih

    2015-12-01

    Full Text Available Proliferation and migration of vascular smooth muscle cells (VSMC are important in the development and/or progression of many cardiovascular diseases, including atherosclerosis. Evidence shows that matrix metalloproteinase (MMP-2 and MMP-9 are related to the pathogenesis of atherosclerosis. The expressions of MMP-2 and MMP-9 in atherosclerosis are regulated via various pathways, such as p38 mitogen activated protein kinase (MAPK, extracellular signal regulated kinase 1 and 2 (ERK1/2, Akt, and nuclear factor kappa (NF-κB. Di(2-ethylhexyl phthalate (DEHP has been shown to induce atherosclerosis by increasing tumor necrosis factor (TNF-α, interleukin (IL-6, and intercellular adhesion molecule (ICAM productions. However, whether DEHP poses any effects on MMP-2 or MMP-9 expression in VSMC has not yet been answered. In our studies, rat aorta VSMC was treated with DEHP (between 2 and 17.5 ppm and p38 MAPK, ERK1/2, Akt, NF-κB, and MMP-2 and MMP-9 proteins and activities were measured. Results showed that the presence of DEHP can induce higher MMP-2 and MMP-9 expression than the controls. Similar results on MMP-regulating proteins, i.e., p38 MAPK, ERK1/2, Akt, and NF-κB, were also observed. In summary, our current results have showed that DEHP can be a potent inducer of atherosclerosis by increasing MMP-2 and MMP-9 expression at least through the regulations of p38 MAPK, ERK1/2, Akt, and NF-κB.

  11. Use of matrix metalloproteinase-9 (MMP-9 and its tissue inhibitor (TIMP-1 in the pathomorphological diagnosis of carotid pathology: literature review and own observations

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    Yu. I. Kuzyk

    2016-04-01

    Full Text Available Matrix metalloproteinases (MMPs are the degradative enzymes of the extracellular matrix. Currently, the role of MMP-2 and MMP-9 in the progression of atherosclerosis (AS is proved. The question of possible involvement of MMP-9 into elastin degradation in fibromuscular dysplasia (FMD and pathological tortuosity (PT remains open and insufficiently explored. The aim of the study – analysis of the current literature on the role of degradative enzymes in the development of carotid pathology and study of the expression of type I, III, IV collagens, MMP-9 and TIPM-1 in the wall of the carotid arteries in FMD, PT and AS. Materials and methods included literature review and own research. Immunohistochemical study of type I, III and IV collagens, TIMP-1 and MMP-9 was carried out on surgical material of patients with main carotid diseases: three observations with AS, two – with FMD, two – with PT. The level of expression was assessed by semiquantitative method. Results. Own observations showed that in FMD types I and III collagen content in the media and in the adventitia remains unchanged. MMP-9 expression level reached the highest level of intensity in atherosclerotic plaques, particularly in macrophages, constituting the main part of the atheromatous mass. Moderate intensity of expression is noted in FMD and PT. In PT expression prevailed in the lower third of the media on the border with adventitia, including the adventitia, in FMD – mainly in the media. The level of TIMP-1 is weakly positive in PT and FMD, negative in AS. Conclusions. These results demonstrate the possibility of using MMP-9 and TIMP-1 as a morphological marker determining pathological processes in carotid pathology. Data of immunohistochemical study of type I, II, IV collagens indicate moderate expression of collagen type I in FMD and PT, severe expression of collagen III in FMD, moderate in PT. Type IV collagen is highly expressed in atherosclerotic plaques. For AS high

  12. Multiplex N-terminome analysis of MMP-2 and MMP-9 substrate degradomes by iTRAQ-TAILS quantitative proteomics.

    Science.gov (United States)

    Prudova, Anna; auf dem Keller, Ulrich; Butler, Georgina S; Overall, Christopher M

    2010-05-01

    Proteolysis is a major protein posttranslational modification that, by altering protein structure, affects protein function and, by truncating the protein sequence, alters peptide signatures of proteins analyzed by proteomics. To identify such modified and shortened protease-generated neo-N-termini on a proteome-wide basis, we developed a whole protein isobaric tag for relative and absolute quantitation (iTRAQ) labeling method that simultaneously labels and blocks all primary amines including protein N- termini and lysine side chains. Blocking lysines limits trypsin cleavage to arginine, which effectively elongates the proteolytically truncated peptides for improved MS/MS analysis and peptide identification. Incorporating iTRAQ whole protein labeling with terminal amine isotopic labeling of substrates (iTRAQ-TAILS) to enrich the N-terminome by negative selection of the blocked mature original N-termini and neo-N-termini has many advantages. It enables simultaneous characterization of the natural N-termini of proteins, their N-terminal modifications, and proteolysis product and cleavage site identification. Furthermore, iTRAQ-TAILS also enables multiplex N-terminomics analysis of up to eight samples and allows for quantification in MS2 mode, thus preventing an increase in spectral complexity and extending proteome coverage by signal amplification of low abundance proteins. We compared the substrate degradomes of two closely related matrix metalloproteinases, MMP-2 (gelatinase A) and MMP-9 (gelatinase B), in fibroblast secreted proteins. Among 3,152 unique N-terminal peptides identified corresponding to 1,054 proteins, we detected 201 cleavage products for MMP-2 and unexpectedly only 19 for the homologous MMP-9 under identical conditions. Novel substrates identified and biochemically validated include insulin-like growth factor binding protein-4, complement C1r component A, galectin-1, dickkopf-related protein-3, and thrombospondin-2. Hence, N-terminomics analyses

  13. Purification and characterization of recombinant full-length and protease domain of murine MMP-9 expressed in Drosophila S2 cells

    DEFF Research Database (Denmark)

    Rasch, Morten G; Lund, Ida K.; Illemann, Martin

    2010-01-01

    -length and truncated versions were 5 mg/l and 2 mg/l, respectively. The products were >95% pure after gelatin Sepharose chromatography and possessed proteolytic activity when analyzed by gelatin zymography. Using the purified full-length murine MMP-9 we raised polyclonal antibodies by immunizations of rabbits...

  14. Fine-structural distribution of MMP-2 and MMP-9 activities in the rat skeletal muscle upon training: a study by high-resolution in situ zymography.

    Science.gov (United States)

    Yeghiazaryan, Marine; Żybura-Broda, Katarzyna; Cabaj, Anna; Włodarczyk, Jakub; Sławińska, Urszula; Rylski, Marcin; Wilczyński, Grzegorz M

    2012-07-01

    Matrix metalloproteinases (MMPs) are key regulators of extracellular matrix remodeling, but have also important intracellular targets. The purpose of this study was to examine the activity and subcellular localization of the gelatinases MMP-2 and MMP-9 in skeletal muscle of control and physically trained rats. In control hind limb muscle, the activity of the gelatinases was barely detectable. In contrast, after 5 days of intense exercise, in Soleus (Sol), but not Extensor digitorum longus (EDL) muscle, significant upregulation of gelatinolytic activity in myofibers was observed mainly in the nuclei, as assessed by high resolution in situ zymography. The nuclei of quiescent satellite cells did not contain the activity. Within the myonuclei, the gelatinolytic activity colocalized with an activated RNA Polymerase II. Also in Sol, but not in EDL, there were few foci of mononuclear cells with strongly positive cytoplasm, associated with apparent necrotic myofibers. These cells were identified as activated satellite cells/myoblasts. No extracellular gelatinase activity was observed. Gel zymography combined with subcellular fractionation revealed training-related upregulation of active MMP-2 in the nuclear fraction, and increase of active MMP-9 in the cytoplasmic fraction of Sol. Using RT-PCR, selective increase in MMP-9 mRNA was observed. We conclude that training activates nuclear MMP-2, and increases expression and activity of cytoplasmic MMP-9 in Sol, but not in EDL. Our results suggest that the gelatinases are involved in muscle adaptation to training, and that MMP-2 may play a novel role in myonuclear functions.

  15. Tissue levels of matrix metalloproteinases MMP-2 and MMP-9 are related to the overall survival of patients with gastric carcinoma

    NARCIS (Netherlands)

    Sier, C.F.M.; Kubben, F.J.G.M.; Ganesh, S.; Heerding, M.M.; Griffioen, G.; Hanemaaijer, R.; Krieken, J.H.J.M. van; Lamers, C.B.H.W.; Verspaget, H.W.

    1996-01-01

    Proteinases are involved in tumour invasion and metastasis. Several matrix metalloproteinases (MMPs) have been shown to be increased in various human carcinomas. We assessed the levels of MMP-2 (gelatinase A) and MMP-9 (gelatinase B) in 50 gastric carcinomas and corresponding mucosa using

  16. Delayed wound healing in aged skin rat models after thermal injury is associated with an increased MMP-9, K6 and CD44 expression.

    Science.gov (United States)

    Simonetti, Oriana; Oriana, Simonetti; Lucarini, Guendalina; Guendalina, Lucarini; Cirioni, Oscar; Oscar, Cirioni; Zizzi, Antonio; Antonio, Zizzi; Orlando, Fiorenza; Fiorenza, Orlando; Provinciali, Mauro; Mauro, Provinciali; Di Primio, Roberto; Roberto, Di Primio; Giacometti, Andrea; Andrea, Giacometti; Offidani, Annamaria; Annamaria, Offidani

    2013-06-01

    Age-related differences in wound healing have been documented but little is known about the wound healing mechanism after burns. Our aim was to compare histological features and immunohistochemical expression of matrix metalloproteinase-9 (MMP-9), collagen IV, K6 and CD44 in the burn wound healing process in aged and young rats. Following burns the appearance of the wound bed in aged rats had progressed but slowly, resulting in a delayed healing process compared to the young rats. At 21 days after injury, epithelial K6, MMP-9 and CD44 expression was significantly increased in aged rats with respect to young rats; moreover, in the aged rat group we observed a not fully reconstituted basement membrane. K6, MMP-9 and CD44 expression was significantly increased in wounded skin compared to unwounded skin both in young and aged rats. We hypothesise that delayed burn skin wound healing process in the aged rats may represent an age dependent response to injury where K6, MMP-9 and CD44 play a key role. It is therefore possible to suggest that these factors contribute to the delayed wound healing in aged skin and that modulation could lead to a better and faster recovery of skin damage in elderly. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.

  17. Expressions of Matrix Metalloproteinases (MMP-2, MMP-7, and MMP-9) and Their Inhibitors (TIMP-1, TIMP-2) in Inflammatory Bowel Diseases.

    Science.gov (United States)

    Jakubowska, Katarzyna; Pryczynicz, Anna; Iwanowicz, Piotr; Niewiński, Andrzej; Maciorkowska, Elżbieta; Hapanowicz, Jerzy; Jagodzińska, Dorota; Kemona, Andrzej; Guzińska-Ustymowicz, Katarzyna

    2016-01-01

    Crohn's disease (CD) and ulcerative colitis (UC) belong to a group of inflammatory bowel diseases (IBD). The aim of our study was to evaluate the expression of MMP-2, MMP-7, MMP-9, TIMP-1, and TIMP-2 in ulcerative colitis and Crohn's disease. The study group comprised 34 patients with UC and 10 patients with CD. Evaluation of MMP-2, MMP-7, MMP-9, TIMP-1, and TIMP-2 expression in tissue samples was performed using immunohistochemistry. The overexpression of MMP-9 and TIMP-1 was dominant in both the glandular epithelium and inflammatory infiltration in UC patients. In contrast, in CD subjects the positive expression of MMP-2 and TIMP-1 was in glandular tubes while mainly MMP-7 and TIMP-2 expression was in inflammatory infiltration. Metalloproteinases' expression was associated with the presence of erosions, architectural tissue changes, and inflammatory infiltration in the lamina propria of UC patients. The expression of metalloproteinase inhibitors correlated with the presence of eosinophils and neutrophils in UC and granulomas in CD patients. Our studies indicate that the overexpression of metalloproteinases and weaker expression of their inhibitors may determine the development of IBD. It appears that MMP-2, MMP-7, and MMP-9 may be a potential therapeutic target and the use of their inhibitors may significantly reduce UC progression.

  18. Expressions of Matrix Metalloproteinases (MMP-2, MMP-7, and MMP-9 and Their Inhibitors (TIMP-1, TIMP-2 in Inflammatory Bowel Diseases

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    Katarzyna Jakubowska

    2016-01-01

    Full Text Available Crohn’s disease (CD and ulcerative colitis (UC belong to a group of inflammatory bowel diseases (IBD. The aim of our study was to evaluate the expression of MMP-2, MMP-7, MMP-9, TIMP-1, and TIMP-2 in ulcerative colitis and Crohn’s disease. The study group comprised 34 patients with UC and 10 patients with CD. Evaluation of MMP-2, MMP-7, MMP-9, TIMP-1, and TIMP-2 expression in tissue samples was performed using immunohistochemistry. The overexpression of MMP-9 and TIMP-1 was dominant in both the glandular epithelium and inflammatory infiltration in UC patients. In contrast, in CD subjects the positive expression of MMP-2 and TIMP-1 was in glandular tubes while mainly MMP-7 and TIMP-2 expression was in inflammatory infiltration. Metalloproteinases’ expression was associated with the presence of erosions, architectural tissue changes, and inflammatory infiltration in the lamina propria of UC patients. The expression of metalloproteinase inhibitors correlated with the presence of eosinophils and neutrophils in UC and granulomas in CD patients. Our studies indicate that the overexpression of metalloproteinases and weaker expression of their inhibitors may determine the development of IBD. It appears that MMP-2, MMP-7, and MMP-9 may be a potential therapeutic target and the use of their inhibitors may significantly reduce UC progression.

  19. Immunohistochemical analysis of MMP-9, MMP-2 and TIMP-1, TIMP-2 expression in the central nervous system following infection with viral and bacterial meningitis.

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    Lech Chyczewski

    2009-01-01

    Full Text Available Matrix metalloproteinases (MMPs are capable of degrading components of the basal lamina of cerebral vessels, thereby disrupting the blood-brain barrier and inducing leukocyte recruitment. This study provides comprehensive information regarding the cell specificity of matrix metalloproteinases (MMP-2, MMP-9 and their binding tissue inhibitors (TIMP-1, TIMP-2 in the central nervous system during viral and bacterial meningitis. Specifically, we evaluated the immunoreactivity of MMPs and TIMPs in various cell types in brain parenchyma and meninges obtained from autopsy tissues. We found that a higher proportion of endothelial cells were positive for MMP-9 during meningitis when compared to controls. In addition, the immunoreactivity of MMP-9 decreased and the immunoreactivity of TIMP-1 increased in astrocytes upon infection. Furthermore, the results of this study revealed that mononuclear cells were highly immunoreactive for TIMP-1, TIMP-2 and MMP-9 during viral meningitis and that the expression of TIMPs in polymorphonuclear cells was even higher during bacterial meningitis. Taken together the results of this study indicated that the central nervous system resident cells and inflammatory infiltrates contribute to MMPs activity and that the expression patterns vary between cell types and in response to viral and bacterial meningitis.

  20. Nitro-oxidative stress, VEGF and MMP-9 in patients with cirrhotic and non-cirrhotic portal hypertension.

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    Muti, Leon Adrian; Pârvu, Alina Elena; Crăciun, Alexandra M; Miron, Nicolae; Acalovschi, Monica

    2015-01-01

    Nitro-oxidative stress may have pathophysiological consequences. The study aimed to assess the nitro-oxidative stress, the vascular growth factor, and metalloproteinase-9 levels in patients with noncirrohic and cirrhotic portal hypertension. Patients with noncirrhotic portal hypertension (n=50) and cirrhotic portal hypertension (n=50) from the 3rd Medical Clinic in Cluj-Napoca Romania were prospectively enrolled between October 2004 and October 2006. A control group of healthy volunteers (n=50) was also evaluated. Nitro-oxidative stress was assessed by measuring serum concentration of nitrites and nitrate, 3-nitrotyrosine, total oxidative status, total antioxidant reactivity, and oxidative stress index. Serum vascular growth factor and matrix metalloproteinase-9 were also determined. Serum nitrites and nitrate levels significantly increased in both noncirrhotic (pportal hypertension (p=0.057). 3-nitrotyrosine also increased in noncirrhotic (p=0.001) and cirrhotic portal hypertension patients (p=0.014). Total oxidative status showed a significant increase in noncirrhotic (pportal hypertension (pportal hypertension (pportal hypertension a significant systemic nitro-oxidative stress was found, correlated with an increase of VEGF. MMP-9 decreased in noncirrhotic portal hypertension.

  1. Extracellular vesicles secreted from cancer cell lines stimulate secretion of MMP-9, IL-6, TGF-β1 and EMMPRIN.

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    Jasmina S Redzic

    Full Text Available Extracellular vesicles (EVs are key contributors to cancer where they play an integral role in cell-cell communication and transfer pro-oncogenic molecules to recipient cells thereby conferring a cancerous phenotype. Here, we purified EVs using straightforward biochemical approaches from multiple cancer cell lines and subsequently characterized these EVs via multiple biochemical and biophysical methods. In addition, we used fluorescence microscopy to directly show internalization of EVs into the recipient cells within a few minutes upon addition of EVs to recipient cells. We confirmed that the transmembrane protein EMMPRIN, postulated to be a marker of EVs, was indeed secreted from all cell lines studied here. We evaluated the response to EV stimulation in several different types of recipient cells lines and measured the ability of these purified EVs to induce secretion of several factors highly upregulated in human cancers. Our data indicate that purified EVs preferentially stimulate secretion of several proteins implicated in driving cancer in monocytic cells but only harbor limited activity in epithelial cells. Specifically, we show that EVs are potent stimulators of MMP-9, IL-6, TGF-β1 and induce the secretion of extracellular EMMPRIN, which all play a role in driving immune evasion, invasion and inflammation in the tumor microenvironment. Thus, by using a comprehensive approach that includes biochemical, biological, and spectroscopic methods, we have begun to elucidate the stimulatory roles.

  2. Tumor Necrosis Factor-Like Weak Inducer of Apoptosis Promotes Hepatic Stellate Cells Migration via Canonical NF-κB/MMP9 Pathway.

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    Mingcui Xu

    Full Text Available In the liver, the signal and function of tumor necrosis factor-like weak inducer of apoptosis (TWEAK have mainly been assessed in association with liver regeneration. However, the effects of TWEAK on liver fibrosis have not been fully elucidated. To investigate the effects of TWEAK on human hepatic stellate cells (HSCs and to explore the relevant potential mechanisms, human HSCs line-LX-2 were cultured with TWEAK. Cell migration was detected by transwell assay; cell viability was evaluated by Cell Counting Kit-8; the expression of MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP11, MMP12, MMP13 gene was identified by quantitative real-time polymerase chain reaction and western blotting; the activity of matrix metalloproteinases (MMPs was tested by enzyme-linked immuno sorbent assay; small interfering RNA transfection was applied for depletion of MMP9 and p65. The result of transwell assay revealed that TWEAK promoted LX-2 migration. Subsequently, our data testified that the expression and activity of MMP9 was induced by TWEAK in LX-2 cells, which enhanced the migration. Furthermore, our findings showed that TWEAK upregulated the phosphorylation of IκBα and p65 protein to increase MMP9 expression in LX-2 cells. Meanwhile, the alpha-smooth muscle actin, vimentin and desmin expression were upregulated following TWEAK treatment. The results in the present study revealed that TWEAK promotes HSCs migration via canonical NF-κB/MMP9 pathway, which possibly provides a molecular basis targeting TWEAK for the therapy of liver fibrosis.

  3. Ang-(1-7) exerts protective role in blood-brain barrier damage by the balance of TIMP-1/MMP-9.

    Science.gov (United States)

    Wu, Jitao; Zhao, Duo; Wu, Shuang; Wang, Dan

    2015-02-05

    Cerebrovascular disease (CVD) ranks as the top three health risks, specially cerebral ischemia characterized with the damage of blood-brain barrier (BBB). The angiotensin Ang-(1-7) was proven to have a protective effect on cerebrovascular diseases. However, its role on blood-brain barrier and the underlying molecular mechanism remains unclear. In this study, Ang-(1-7) significantly relieved damage of ischemia reperfusion injury on blood-brain barrier in cerebral ischemia reperfusion injury (IRI) rats. Furthermore, its treatment attenuated BBB permeability and brain edema. Similarly, Ang-(1-7) also decreased the barrier permeability of brain endothelial cell line RBE4. Further analysis showed that Ang-(1-7) could effectively restore tight junction protein (claudin-5 and zonula occludens ZO-1) expression levels both in IRI-rats and hypoxia-induced RBE4 cells. Furthermore, Ang-(1-7) stimulation down-regulated hypoxia-induced matrix metalloproteinase-9 (MMP-9) levels, whose silencing with (matrix metalloproteinase-9 hemopexin domain) MMP9-PEX inhibitor significantly increased the expression of claudin-5 and ZO-1. Further mechanism analysis demonstrated that Ang-(1-7) might junction protein levels by tissue inhibitor of metalloproteinase 1 (TIMP1)-MMP9 pathway, because Ang-(1-7) enhanced TIMP1 expression, whose silencing obviously attenuated the inhibitor effect of Ang-(1-7) on MMP-9 levels and decreased Ang-(1-7)-triggered increase in claudin-5 and ZO-1. Together, this study demonstrated a protective role of Ang-(1-7) in IRI-induced blood-brain barrier damage by TIMP1-MMP9-regulated tight junction protein expression. Accordingly, Ang-(1-7) may become a promising therapeutic agent against IRI and its complications. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. MMP-9, uPA and uPAR proteins expression and its prognostic significance in esophageal squamous cell carcinoma treated by radiotherapy

    International Nuclear Information System (INIS)

    Zhu Shuchai; Wang Yafei; Su Jingwei; Wang Yuxiang; Shen Wenbin; Li Juan

    2008-01-01

    Objective: To explore the the prognostic significance of MMP-9, uPA and uPAR protein expression and its relationship with clinical-pathologic factors in esophageal squamous cell carcinoma treated by radiotherapy. Methods: MMP-9, uPA and uPAR protein expression was measured in 59 esophageal carcinomas and 41 peri-carcinoma tissues with immunohistochemistry. The relationship between the protein expression and the clinical-pathological parameters was analyzed, and the prognostic factors in esophageal squamous cell carcinoma treated by radiotherapy alone was evaluated. Results: The rates of positive expression of MMP-9, uPA and uPAR were 85%, 76% and 78% in esophageal carcinoma and 39%, 49% and 44% in peri-carcinoma tissues (χ 2 =22.54, 8.04 and 12.18; P=0.000,0.005 and 0.000). The rates of positive expression of MMP-9 was 79% and 100% when the depth of tumor invasion was ≤2 cm and >2 cm(P= 0.048), respectively. The expression of uPA was significantly correlated with the status of fat interspace between the esophageal lesion and the vertebra in CT scanning image. When the fat interspace existed and disappeared, the rates of strong positive expression was 44% and 70%, respectively (χ 2 =4.21, P=0.040). The positive expression rate of uPA was significantly correlated with distant metastasis, which was 100% in patients with distant metastasis and 68.89% in those without distant metastasis(χ 2 =4.12, P=0.042). The positive expression rate of MMP-9, uPA and uPAR did not affect the prognosis and the short-term result of esophageal carcinoma treated by radiotherapy alone. Conclusions: The protein expression of MMP-9, uPA and uPAR may correlate with local infiltration and distant metastasis in esophageal squamous cell carcinoma. Protein expression may not influence the prognosis of esophageal carcinoma treated by radio therapy, though long time followed-up is still needed. (authors)

  5. Involvement of CD147 in overexpression of MMP-2 and MMP-9 and enhancement of invasive potential of PMA-differentiated THP-1

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    Tang Hao

    2005-05-01

    Full Text Available Abstract Background During infection and inflammation, circulating blood monocytes migrate from the intravascular compartments to the extravascular compartments, where they mature into tissue macrophages. The maturation process prepares the cells to actively participate in the inflammatory and immune responses, and many factors have been reported to be involved in the process. We found in our study that CD147 played a very important role in this process. Results By using PMA-differentiated human monocyte cells line THP-1, we found that CD147 mediated matrix metalloproteinases (MMPs expression of the leukemic THP-1 cells and thus enhanced the invasiveness of THP-1 cells. After 24 hours of PMA-induced monocyte differentiation, the mean fluorescence intensity of CD147 in differentiated THP-1 cells (289.61 ± 31.63 was higher than that of the undifferentiated THP-1 cells (205.1 ± 19.25. There was a significant increase of the levels of proMMP-2, proMMP-9 and their activated forms in the differentiated THP-1 cells. Invasion assays using reconstituted basement membrane showed a good correlation between the invasiveness of THP-1 cells and the production of MMP-2 and MMP-9. The difference in the MMPs expression and the invasive ability was significantly blocked by HAb18G/CD147 antagonistic peptide AP-9. The inhibitory rate of the secretion of proMMP-9 in the undifferentiated THP-1 cells was 45.07%. The inhibitory rate of the secretion of proMMP-9, the activated MMP-9 and proMMP-2 in the differentiated THP-1 cells was 52.90%, 53.79% and 47.80%, respectively. The inhibitory rate of invasive potential in the undifferentiated cells and the differentiated THP-1 cells was 41.82 % and 25.15%, respectively. Conclusion The results suggest that the expression of CD147 is upregulated during the differentiation of monocyte THP-1 cells to macrophage cells, and CD147 induces the secretion and activation of MMP-2 and MMP-9 and enhances the invasive ability of THP-1

  6. MMP8, MMP9 AND TIMP1 LEVELS IN GCF AND GINGIVAL TISSUE OF PATIENTS WITH GINGIVAL OVERGROWTH DURING ORTHODONTIC TREATMENT

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    Petra Surlin

    2012-03-01

    Full Text Available Aim. Periodontal remodellng produced during dental orthodontic treatment represents a series of biologicallyactive substances, part of them playing some role in the initiation and propagation of inflammatory processes. The present study aims at demonstrating the MMP8, MMP9 and TIMP1 levels intervening in tissular periodontal remodeling produced during orthodontic treatments, accompanied by gingival overgrowth, as a reaction of the marginal periodontium to mechanical stress. Materials and Method. Selected for the study were 21 patients – 13 females and 8 males – with ages between 13 and 32 years (17.6±1.3 years affected with dento-maxillary anomalies, who received orthodontic treatment with fixed apparatus. Sampling from the gingival fluid was performed 6 times, namely: 1 hour prior to the application of the orthodontic apparatus, 4 hours after its application, again after 8 and 24 hours and then 1 and, respectively, 2 weeks later. If gingival hypertrophy was installed (HTG, the hypertrophic gingiva was removed, and an immuno-histo-chemical examination was made. The patient was weekly monitorized in the first 6 weeks – during the initial orthodontic treatment, then monthly, samples being taken over from the gingival sulcus on each visit made in the first 6 weeks. Results. MMP-9 immuno-marking was positive both at corione level and in the deep structures of the covering epithelium. The positive cells at MMP-9 evidenced different intensities at the level of each structure forming the gingival mucous membrane. In four of the cases under analysis, disorganization of the normal layering/stratification of the epithelium was evidenced, along with the presence of numerous red cells in the chorione of the mucous membrane. In such cases, immuno-marking to MMP8 showed a normal intensity, even if few positive cells, dispersed among the extravasated red cells could be observed. Immunologically, MMP8 and MMP9 obey the same pattern, registering maximum

  7. Baicalein inhibits pulmonary carcinogenesis-associated inflammation and interferes with COX-2, MMP-2 and MMP-9 expressions in-vivo

    Energy Technology Data Exchange (ETDEWEB)

    Chandrashekar, Naveenkumar; Selvamani, Asokkumar; Subramanian, Raghunandhakumar; Pandi, Anandakumar; Thiruvengadam, Devaki, E-mail: devakit@yahoo.co.uk

    2012-05-15

    -α, IL-1β, i-NOS and NF-κBp65 at protein levels. ► BE modulates the expressions of MMP-2, MMP-9 and COX-2 at protein and mRNA levels. ► BE decreases LPO levels and enhances antioxidant status.

  8. Changes of MMP-9 and IL-1β in serum and cerebrospinal-fluid in children with central nervous system infection

    Institute of Scientific and Technical Information of China (English)

    Shu-Qin Jiao

    2016-01-01

    Objective:To provide a new basis for the detection of the central nervous system infection cases, we explored and compared the role of cerebrospinal-fluid (CSF), matrix metalloproteinases 9 (MMP-9) and interleukin 1 (the level of IL -1β) in the central nervous system (CNS).Methods:Sixty cases of children acute central nervous system infection were selected, including 30 cases of viral encephalitis children (VE) and 30 cases of purulent meningitis children (PM). Forty cases of non-central nervous system infection children were control group. The serum albumin (SA1b) of each group was detected by full-automatic analysis instrument, and the CSF albumin (CA1b) was detected by immunoephelometry and the albumin index (AQ) was accounted. ELISE was used to detect the levels of MMP-9 and IL-1β in serum and cerebrospinal-fluid.Results:The level of MMP-9 in the serum of groups of VE, PM and control were (267.84 ± 91.88) μg/L, (488.98 ± 159.07) μg/L and (133.04 ± 31.68) μg/L, while in the CSF were (37.18 ± 17.78) μg/L, (117.9 ± 42.87) μg/L and (10.36 ± 5.43) μg/L; The level of IL-1β in serum of groups of PM, VE and control were (19.69 ± 11.12) ng/L, (24.37 ± 4.13) ng/L and (15.01 ± 3.89) ng/L, while in the CSF were (66.94 ± 10.65) ng/L, (106.27 ± 12.79) ng/L and (49.98 ± 12.59) ng/L; The level of CAlb were (0.53 ± 0.15) g/L, (1.05 ± 0.27) g/L and (0.17 ± 0.07) g/L and AQ were (13.75 ± 3.44), (26.99 ± 7.28) and (4.63 ± 2.04). The PM, VE were respectively compared with the control, the levels of IL-1β and MMP-9 in serum and CSF all increased, with statistically significant difference.The VE, compared to the PM, the level of IL-1β in serum and CSF all decreased, with statistically significant difference; The level of MMP-9 in serum and CSF all decreased, with statistically significant difference. The level of CA1b and AQ in the VE and PM all increased, with a statistically significant difference. The level of MMP-9 and IL-1β in serum and CSF of the

  9. Andrographolide suppresses proliferation of human colon cancer SW620 cells through the TLR4/NF-κB/MMP-9 signaling pathway.

    Science.gov (United States)

    Zhang, Rui; Zhao, Jian; Xu, Jian; Jiao, De-Xin; Wang, Jian; Gong, Zhi-Qiang; Jia, Jian-Hui

    2017-10-01

    Modern pharmacological research has revealed that andrographolide has various functions, including anti-bacterial, anti-inflammatory and anti-viral effects, immunoregulation, treating cardiovascular and cerebrovascular diseases, and prevention and treatment of alcoholic liver injury. The present study investigated whether andrographolide suppresses the proliferation of human colon cancer cell through the Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB/matrix metalloproteinase-9 (MMP-9) signaling pathway. The MTT assay and lactate dehydrogenase assay were used to evaluate the anticancer effects of andrographolide on cell proliferation and cytotoxicity in human colon cancer SW620 cells. Flow cytometry was used to analyze the anticancer effects of andrographolide on apoptosis by Annexin V-fluorescein isothiocyanate/propidium iodide kit. The effects of andrographolide on the activity of caspase-3/9 were measured using ELISA. Western blot analysis was also used to analyze the protein expression of TLR4, myeloid differentiation primary response gene 88 (MyD88), NF-κB-p65 and MMP-9. In the present study, it was found that andrographolide suppressed the cell proliferation, augmented cytotoxicity, evoked cell apoptosis and activated caspase-3/9 activities in human colon cancer SW620 cells. The results revealed that the anti-proliferation effects of andrographolide on the SW620 cells was associated with the inhibition of TLR4, MyD88, NF-κB-p65 and MMP-9 signaling activation. The results suggest that andrographolide is a promising drug for treatment of human colon cancer via suppression of the TLR4/NF-κB/MMP-9 signaling pathway.

  10. Serum Matrix Metalloproteinase-2, -7 and -9 (MMP-2, MMP-7, MMP-9 levels as Prognostic Markers in Patients with Colorectal Cancer

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    Elena Kostova

    2012-12-01

    Full Text Available Introduction: Matrix metalloproteinases are produced by tumour cells, hence, they may be associated with tumour progression including invasion, migration, angiogenesis and metastasis. Finding prognostic markers to better identify patients with higher risk for poor survival would be valuable in order to customize pre- and postoperative treatment as well as to enable closer follow-up of these patients. Aim of our study was to examineMMP-2, MMP-7 and MMP-9 serum levels and correlated them with pathological data such as stage of the colorectal cancer (CRC and outcome.Methods: The investigation included 82 patients with operable CRC without distant metastases, who had underwent blood tests in order to determine the MMP-2, MMP-7 and MMP-9 serum levels in the following time periods: preoperatively, 3, 6, 9 and 12 months postoperatively.Results: The values of the investigated MMPs decrease postoperatively and start to increase 6 month later in patients of all stages of the disease, reaching the highest value 12 month postoperatively with statistically important differences of MMP-2, MMP-7 and MMP-7 serum levels in terms of disease staging and defined points of time. Analysis of the results showed that the MMP-2 serum levels obtained 3 and 12 months postoperatively,than MMP-7 serum levels 12 months postoperatively and the MMP-9 serum levels in all analyzed points in time were in significant association with the CRC patients’outcome.Conclusion: The MMP-2, MMP-7 and especially MMP-9 serum values could be important indicators for diagnosis of the patients with CRC and for monitoring of disease progression.

  11. Hibiscus sabdariffa Leaf Extract Inhibits Human Prostate Cancer Cell Invasion via Down-Regulation of Akt/NF-κB/MMP-9 Pathway

    Science.gov (United States)

    Chiu, Chun-Tang; Chen, Jing-Hsien; Chou, Fen-Pi; Lin, Hui-Hsuan

    2015-01-01

    Hibiscus sabdariffa leaf has been previously shown to possess hypoglycemic, hypolipidemic, and antioxidant effects, and induce tumor cell apoptosis. However, the molecular mechanisms involved in the anticancer activity of H. sabdariffa leaf extract (HLE) are poorly understood. The object of the study was to examine the anti-invasive potential of HLE. First, HLE was demonstrated to be rich in polyphenols. The results of wound-healing assay and in vitro transwell assay revealed that HLE dose-dependently inhibited the migration and invasion of human prostate cancer LNCaP (lymph node carcinoma of the prostate) cells under non-cytotoxic concentrations. Our results further showed that HLE exerted an inhibitory effect on the activity and expressions of matrix metalloproteinase-9 (MMP-9). The HLE-inhibited MMP-9 expression appeared to be a consequence of nuclear factor-kappaB (NF-κB) inactivation because its DNA-binding activity was suppressed by HLE. Molecular data showed all these influences of HLE might be mediated via inhibition of protein kinase B (PKB, also known as Akt)/NF-κB/MMP-9 cascade pathway, as demonstrated by the transfection of Akt1 overexpression vector. Finally, the inhibitory effect of HLE was proven by its inhibition on the growth of LNCaP cells and the expressions of metastasis-related molecular proteins in vivo. These findings suggested that the inhibition of MMP-9 expression by HLE may act through the suppression of the Akt/NF-κB signaling pathway, which in turn led to the reduced invasiveness of the cancer cells. PMID:26115086

  12. Hibiscus sabdariffa Leaf Extract Inhibits Human Prostate Cancer Cell Invasion via Down-Regulation of Akt/NF-kB/MMP-9 Pathway.

    Science.gov (United States)

    Chiu, Chun-Tang; Chen, Jing-Hsien; Chou, Fen-Pi; Lin, Hui-Hsuan

    2015-06-24

    Hibiscus sabdariffa leaf has been previously shown to possess hypoglycemic, hypolipidemic, and antioxidant effects, and induce tumor cell apoptosis. However, the molecular mechanisms involved in the anticancer activity of H. sabdariffa leaf extract (HLE) are poorly understood. The object of the study was to examine the anti-invasive potential of HLE. First, HLE was demonstrated to be rich in polyphenols. The results of wound-healing assay and in vitro transwell assay revealed that HLE dose-dependently inhibited the migration and invasion of human prostate cancer LNCaP (lymph node carcinoma of the prostate) cells under non-cytotoxic concentrations. Our results further showed that HLE exerted an inhibitory effect on the activity and expressions of matrix metalloproteinase-9 (MMP-9). The HLE-inhibited MMP-9 expression appeared to be a consequence of nuclear factor-kappaB (NF-κB) inactivation because its DNA-binding activity was suppressed by HLE. Molecular data showed all these influences of HLE might be mediated via inhibition of protein kinase B (PKB, also known as Akt)/NF-kB/MMP-9 cascade pathway, as demonstrated by the transfection of Akt1 overexpression vector. Finally, the inhibitory effect of HLE was proven by its inhibition on the growth of LNCaP cells and the expressions of metastasis-related molecular proteins in vivo. These findings suggested that the inhibition of MMP-9 expression by HLE may act through the suppression of the Akt/NF-kB signaling pathway, which in turn led to the reduced invasiveness of the cancer cells.

  13. Increase in IL-6, TNF-a, and MMP-9, but not sICAM-1, concentrations depends on exercise duration

    DEFF Research Database (Denmark)

    Reihmane, Dace; Jurka, Antra; Tretjakovs, Peteris

    2013-01-01

    ), tumour necrosis factor-α (TNF-α), soluble form of intercellular adhesion molecule-1 (sICAM-1), and matrix metalloproteinase-9 (MMP-9) was studied in 22 half-marathon (HM) and 18 marathon (M) male amateur runners who completed their exercise task in 1.8 ± 0.2 (mean ± standard deviation) and 3.6 ± 0.4 h...

  14. Effect of PCI on inflammatory factors, cTnI, MMP-9 and NT-pro BNP in patients with unstable angina pectoris

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    Ke-Tong Liu

    2016-05-01

    Full Text Available Objective: To investigate the effect of PCI on inflammatory factors, cTnI, MMP-9and NTpro BNP in patients with unstable angina pectoris. Methods: A total of 80 unstable angina pectoris patients were divided into observation group (40 cases and control group (40 cases. The observation group was given the therapy of PCI, and the control group was given coronary angiography. To observe the of inflammatory factors, cTnI, MMP-9 and NT-pro BNP were tested and compared before and after operation. Results: At 24 h after operation, CRP and IL-18 levels were increased significantly after treatment inoperation groups, there was no difference on inflammatory factors in control group, and had significant difference on inflammatory factors in two groups; At 24 h after operation, cTnI, MMP-9 and NT-pro BNP levels were increased significantly after treatment inoperation groups, there was no difference on inflammatory factors in control group, and had significant difference on inflammatory factors in two groups. Conclusion: PCI therapy can induce inflammation and myocardial injury in patients with unstable angina pectoris.

  15. Glycine tomentella Hayata inhibits IL-1β and IL-6 production, inhibits MMP-9 activity, and enhances RAW264.7 macrophage clearance of apoptotic cells

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    Sun Yu-Shu

    2010-11-01

    Full Text Available Abstract Background To assess the effects of Glycine tomentella Hayata (GTH, a traditional herbal medicine for treatment of rheumatic diseases on the expression of the proinflammatory cytokines and on the clearance of apoptotic cells by macrophages. Methods RAW264.7 cells were cultured with lipopolysaccharide (LPS in the presence or absence of ethanol extract of GTH. The expression of proinflammatory cytokines IL-1β, IL-6, and TNF-α, and inducible nitric oxide synthase (iNOS and transglutaminase 2 (TG2 were assayed by reverse transcriptase-polymerase chain reaction (RT-PCR and enzyme-linked immunosorbent assay (ELISA. Matrix metalloproteinase (MMP-2 and MMP-9 were assayed by gelatin zymography. For detecting uptake of apoptotic cells, RAW264.7 cells were cultured with carboxyfluorescein diacetate (CFDA-stained apoptotic cells and assayed by flow cytometry. Results The major components of GTH analyzed by high-performance liquid chromatography (HPLC chromatogram were daidzein (42.5%, epicatechin (28.8%, and naringin (9.4%. GTH treatment inhibited the expression of proinflammatory cytokines IL-1β, IL-6 and MMP-9 but did not affect the expression of TNF-α and iNOS. GTH significantly enhanced the expression of TG2 and the clearance of apoptotic cells by RAW264.7 macrophages. Conclusions GTH inhibits proinflammatory cytokine secretion and MMP-9 activity, enhances apoptotic cell uptake and up-regulates TG2 expression. Our data show that GTH might have beneficial effects on rheumatic diseases.

  16. Baicalin Attenuates Hypoxia-Induced Pulmonary Arterial Hypertension to Improve Hypoxic Cor Pulmonale by Reducing the Activity of the p38 MAPK Signaling Pathway and MMP-9

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    Shuangquan Yan

    2016-01-01

    Full Text Available Baicalin has a protective effect on hypoxia-induced pulmonary hypertension in rats, but the mechanism of this effect remains unclear. Thus, investigating the potential mechanism of this effect was the aim of the present study. Model rats that display hypoxic pulmonary hypertension and cor pulmonale under control conditions were successfully generated. We measured a series of indicators to observe the levels of pulmonary arterial hypertension, pulmonary arteriole remodeling, and right ventricular remodeling. We assessed the activation of p38 mitogen-activated protein kinase (MAPK in the pulmonary arteriole walls and pulmonary tissue homogenates using immunohistochemistry and western blot analyses, respectively. The matrix metalloproteinase- (MMP- 9 protein and mRNA levels in the pulmonary arteriole walls were measured using immunohistochemistry and in situ hybridization. Our results demonstrated that baicalin not only reduced p38 MAPK activation in both the pulmonary arteriole walls and tissue homogenates but also downregulated the protein and mRNA expression levels of MMP-9 in the pulmonary arteriole walls. This downregulation was accompanied by the attenuation of pulmonary hypertension, arteriole remodeling, and right ventricular remodeling. These results suggest that baicalin may attenuate pulmonary hypertension and cor pulmonale, which are induced by chronic hypoxia, by downregulating the p38 MAPK/MMP-9 pathway.

  17. Expression of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinases 1 (TIMP-1) by colorectal cancer cells and adjacent stroma cells - associations with histopathology and patients outcome

    DEFF Research Database (Denmark)

    Jensen, Søren Astrup; Vainer, Ben; Bartels, Annette

    2010-01-01

    AIM: To elucidate cellular features accountable for colorectal cancers' (CRC) capability to invade normal tissue and to metastasize, we investigated the level of the collagenase matrix metalloproteinase 9 (MMP-9) and its physiological inhibitor tissue inhibitor of metalloproteinases 1 (TIMP-1) in...... cells is associated with poor prognosis independent of its function as inhibitor of MMP-9. MMP-9 and TIMP-1 are important mediators of the host-cancer cell interaction in the tumour microenvironment with significant influence on the histopathology and on prognosis of CRC....

  18. Protective effect of naringenin in experimental ischemic stroke: down-regulated NOD2, RIP2, NF-κB, MMP-9 and up-regulated claudin-5 expression.

    Science.gov (United States)

    Bai, Xue; Zhang, Xiangjian; Chen, Linyu; Zhang, Jian; Zhang, Lan; Zhao, Xumeng; Zhao, Ting; Zhao, Yuan

    2014-08-01

    Inflammatory damage plays a pivotal, mainly detrimental role in cerebral ischemic pathogenesis and may represent a promising target for treatment. Naringenin (NG) has gained growing appreciation for its beneficial biological effects through its anti-inflammatory property. Whether this protective effect applies to cerebral ischemic injury, we therefore investigate the potential neuroprotective role of NG and the underlying mechanisms. Focal cerebral ischemia in male Sprague-Dawley rats was induced by permanent middle cerebral artery occlusion (pMCAO) and NG was pre-administered intragastrically once daily for four consecutive days before surgery. Neurological deficit, brain water content and infarct volume were measured at 24 h after stroke. Immunohistochemistry, Western blot and RT-qPCR were used to explore the anti-inflammatory potential of NG in the regulation of NOD2, RIP2 and NF-κB in ischemic cerebral cortex. Additionally, the activities of MMP-9 and claudin-5 were analyzed to detect NG's influence on blood-brain barrier. Compared with pMCAO and Vehicle groups, NG noticeably improved neurological deficit, decreased infarct volume and edema at 24 h after ischemic insult. Consistent with these results, our data also indicated that NG significantly downregulated the expression of NOD2, RIP2, NF-κB and MMP-9, and upregulated the expression of claudin-5 (P < 0.05). The results provided a neuroprotective profile of NG in cerebral ischemia, this effect was likely exerted by down-regulated NOD2, RIP2, NF-κB, MMP-9 and up-regulated claudin-5 expression.

  19. MicroRNA-206 regulates the secretion of inflammatory cytokines and MMP9 expression by targeting TIMP3 in Mycobacterium tuberculosis-infected THP-1 human macrophages.

    Science.gov (United States)

    Fu, Xiangdong; Zeng, Lihong; Liu, Zhi; Ke, Xue; Lei, Lin; Li, Guobao

    2016-08-19

    Tuberculosis (TB) is a serious disease that is characterized by Mycobacterium tuberculosis (M.tb)-triggered immune system impairment and lung tissue damage shows limited treatment options. MicroRNAs (miRNAs) are regulators of gene expression that play critical roles in many human diseases, and can be up- or downregulated by M.tb infection in macrophage. Recently, tissue inhibitor of matrix metalloproteinase (TIMP) 3 has been found to play roles in regulating macrophage inflammation. Here, we found that TIMP3 expression was regulated by miR-206 in M.tb-infected THP-1 human macrophages. In THP-1 cells infected with M.tb, the miR-206 level was significantly upregulated and the expression of TIMP3 was markedly decreased when the secretion of inflammatory cytokines was increased. Inhibition of miR-206 markedly suppressed inflammatory cytokine secretion and upregulated the expression of TIMP3. In contrast, the upregulation of miR-206 promoted the matrix metalloproteinase (MMP) 9 levels and inhibited TIMP3 levels. Using a dual-luciferase reporter assay, a direct interaction between miR-206 and the 3'-untranslated region (UTR) of TIMP3 was confirmed. SiTIMP3, the small interfering RNA (siRNA) specific for TIMP3, significantly attenuated the suppressive effects of miR-206-inhibitor on inflammatory cytokine secretion and MMP9 expression. Our data suggest that miR-206 may function as an inflammatory regulator and drive the expression of MMP9 in M.tb-infected THP-1 cells by targeting TIMP3, indicating that miR-206 is a potential therapeutic target for patients with TB. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Flavonoids targeting of IκB phosphorylation abrogates carcinogen-induced MMP-9 and COX-2 expression in human brain endothelial cells

    Directory of Open Access Journals (Sweden)

    Tahanian E

    2011-05-01

    Full Text Available Elizabeth Tahanian¹, Luis Arguello Sanchez¹, Tze Chieh Shiao², René Roy², Borhane Annabi¹¹Centre de Recherche BioMED, ²Centre de Recherche PharmaQAM, Département de chimie, Université du Québec à Montréal, QC, CanadaAbstract: Brain endothelial cells play an essential role as structural and functional components of the blood–brain barrier (BBB. Increased BBB breakdown and brain injury are associated with neuroinflammation and are thought to trigger mechanisms involving matrix metalloproteinase upregulation. Emerging evidence also indicates that cyclooxygenase (COX inhibition limits BBB disruption, but the mechanisms linking metalloproteinase to COX remain unknown. In this study, we sought to investigate the nuclear factor-kappa B (NF-κB signaling pathway, a common pathway in both the regulation of matrix metalloproteinase-9 (MMP-9 and COX-2 expression, and the inhibitory properties of several chemopreventive flavonoids. Human brain microvascular endothelial cells were treated with a combination of phorbol 12-myristate 13-acetate (PMA, a carcinogen documented to increase MMP-9 and COX-2 through NF-κB, and several naturally occurring flavonoids. Among the molecules tested, we found that fisetin, apigenin, and luteolin specifically and dose-dependently antagonized PMA-induced COX-2 and MMP-9 gene and protein expressions as assessed by qRT-PCR, immunoblotting, and zymography respectively. We further demonstrate that flavonoids impact on IκK-mediated phosphorylation activity as demonstrated by the inhibition of PMA-induced IκB phosphorylation levels. Our results suggest that BBB disruption during neuroinflammation could be pharmacologically reduced by a specific class of flavonoids acting as NF-κB signal transduction inhibitors.Keywords: blood–brain barrier, flavonoids, neuroinflammation, NF-κB signal transduction inhibitors

  1. Metastatic function of BMP-2 in gastric cancer cells: The role of PI3K/AKT, MAPK, the NF-{kappa}B pathway, and MMP-9 expression

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Myoung Hee [Graduate School of Medicine, Korea University College of Medicine, Korea University, Seoul 136-705 (Korea, Republic of); Oh, Sang Cheul [Division of Oncology/Hematology, Department of Internal Medicine, Korea University College of Medicine, Korea University, Seoul 136-705 (Korea, Republic of); Lee, Hyun Joo [Department of Pathology, Korea University College of Medicine, Korea University, Seoul 136-705 (Korea, Republic of); Kang, Han Na; Kim, Jung Lim [Graduate School of Medicine, Korea University College of Medicine, Korea University, Seoul 136-705 (Korea, Republic of); Kim, Jun Suk [Division of Oncology/Hematology, Department of Internal Medicine, Korea University College of Medicine, Korea University, Seoul 136-705 (Korea, Republic of); Yoo, Young A., E-mail: ydanbi@korea.ac.kr [Brain Korea 21 Program for Biomedical Science, Korea University College of Medicine, Korea University, Seoul 136-705 (Korea, Republic of)

    2011-07-15

    Bone morphogenetic proteins (BMPs) have been implicated in tumorigenesis and metastatic progression in various types of cancer cells, but the role and cellular mechanism in the invasive phenotype of gastric cancer cells is not known. Herein, we determined the roles of phosphoinositide 3-kinase (PI3K)/AKT, extracellular signal-regulated protein kinase (ERK), nuclear factor (NF)-{kappa}B, and matrix metalloproteinase (MMP) expression in BMP-2-mediated metastatic function in gastric cancer. We found that stimulation of BMP-2 in gastric cancer cells enhanced the phosphorylation of AKT and ERK. Accompanying activation of AKT and ERK kinase, BMP-2 also enhanced phosphorylation/degradation of I{kappa}B{alpha} and the nuclear translocation/activation of NF-{kappa}B. Interestingly, blockade of PI3K/AKT and ERK signaling using LY294002 and PD98059, respectively, significantly inhibited BMP-2-induced motility and invasiveness in association with the activation of NF-{kappa}B. Furthermore, BMP-2-induced MMP-9 expression and enzymatic activity was also significantly blocked by treatment with PI3K/AKT, ERK, or NF-{kappa}B inhibitors. Immunohistochemistry staining of 178 gastric tumor biopsies indicated that expression of BMP-2 and MMP-9 had a significant positive correlation with lymph node metastasis and a poor prognosis. These results indicate that the BMP-2 signaling pathway enhances tumor metastasis in gastric cancer by sequential activation of the PI3K/AKT or MAPK pathway followed by the induction of NF-{kappa}B and MMP-9 activity, indicating that BMP-2 has the potential to be a therapeutic molecular target to decrease metastasis.

  2. Anti-inflammatory activities of inotilone from Phellinus linteus through the inhibition of MMP-9, NF-κB, and MAPK activation in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Guan-Jhong Huang

    Full Text Available Inotilone was isolated from Phellinus linteus. The anti-inflammatory effects of inotilone were studied by using lipopolysaccharide (LPS-stimulated mouse macrophage RAW264.7 cells and λ-carrageenan (Carr-induced hind mouse paw edema model. Inotilone was tested for its ability to reduce nitric oxide (NO production, and the inducible nitric oxide synthase (iNOS expression. Inotilone was tested in the inhibitor of mitogen-activated protein kinase (MAPK [extracellular signal-regulated protein kinase (ERK, c-Jun NH(2-terminal kinase (JNK, p38], and nuclear factor-κB (NF-κB, matrix-metalloproteinase (MMP-9 protein expressions in LPS-stimulated RAW264.7 cells. When RAW264.7 macrophages were treated with inotilone together with LPS, a significant concentration-dependent inhibition of NO production was detected. Western blotting revealed that inotilone blocked the protein expression of iNOS, NF-κB, and MMP-9 in LPS-stimulated RAW264.7 macrophages, significantly. Inotilone also inhibited LPS-induced ERK, JNK, and p38 phosphorylation. In in vivo tests, inotilone decreased the paw edema at the 4(th and the 5(th h after Carr administration, and it increased the activities of catalase (CAT, superoxide dismutase (SOD, and glutathione peroxidase (GPx. We also demonstrated that inotilone significantly attenuated the malondialdehyde (MDA level in the edema paw at the 5(th h after Carr injection. Inotilone decreased the NO and tumor necrosis factor (TNF-α levels on serum at the 5(th h after Carr injection. Western blotting revealed that inotilone decreased Carr-induced iNOS, cyclooxygenase-2 (COX-2, NF-κB, and MMP-9 expressions at the 5(th h in the edema paw. An intraperitoneal (i.p. injection treatment with inotilone diminished neutrophil infiltration into sites of inflammation, as did indomethacin (Indo. The anti-inflammatory activities of inotilone might be related to decrease the levels of MDA, iNOS, COX-2, NF-κB, and MMP-9 and increase the activities

  3. Chronic cerebral hypoperfusion-induced impairment of Aβ clearance requires HB-EGF-dependent sequential activation of HIF1α and MMP9.

    Science.gov (United States)

    Ashok, Anushruti; Rai, Nagendra Kumar; Raza, Waseem; Pandey, Rukmani; Bandyopadhyay, Sanghamitra

    2016-11-01

    Chronic cerebral hypoperfusion (CCH) manifests Alzheimer's Disease (AD) neuropathology, marked by increased amyloid beta (Aβ). Besides, hypoxia stimulates Heparin-binding EGF-like growth factor (HB-EGF) mRNA expression in the hippocampus. However, involvement of HB-EGF in CCH-induced Aβ pathology remains unidentified. Here, using Bilateral Common Carotid Artery Occlusion mouse model, we explored the mechanism of HB-EGF regulated Aβ induction in CCH. We found that HB-EGF inhibition suppressed, while exogenous-HB-EGF triggered hippocampal Aβ, proving HB-EGF-dependent Aβ increase. We also detected that HB-EGF affected the expression of primary Aβ transporters, receptor for advanced glycation end-products (RAGE) and lipoprotein receptor-related protein-1 (LRP-1), indicating impaired Aβ clearance across the blood-brain barrier (BBB). An HB-EGF-dependent loss in BBB integrity supported impaired Aβ clearance. The effect of HB-EGF on Amyloid Precursor Protein pathway was relatively insignificant, suggesting a lesser effect on Aβ generation. Delving into BBB disruption mechanism demonstrated HB-EGF-mediated stimulation of Matrix metalloprotease-9 (MMP9), which affected BBB via HB-EGF-ectodomain shedding and epidermal growth factor receptor activation. Examining the intersection of HB-EGF-regulated pathway and hypoxia revealed HB-EGF-dependent increase in transcription factor, Hypoxia-inducible factor-1alpha (HIF1α). Further, via binding to hypoxia-responsive elements in MMP9 gene, HIF1α stimulated MMP9 expression, and therefore appeared as a prominent intermediary in HB-EGF-induced BBB damage. Overall, our study reveals the essential role of HB-EGF in triggering CCH-mediated Aβ accumulation. The proposed mechanism involves an HB-EGF-dependent HIF1α increase, generating MMP9 that stimulates soluble-HB-EGF/EGFR-induced BBB disintegration. Consequently, CCH-mediated hippocampal RAGE and LRP-1 deregulation together with BBB damage impair Aβ transport and clearance

  4. Gallic acid-capped gold nanoparticles inhibit EGF-induced MMP-9 expression through suppression of p300 stabilization and NFκB/c-Jun activation in breast cancer MDA-MB-231 cells

    International Nuclear Information System (INIS)

    Chen, Ying-Jung; Lee, Yuan-Chin; Huang, Chia-Hui; Chang, Long-Sen

    2016-01-01

    Triple-negative breast cancers (TNBCs) are highly invasive and have a higher rate of distant metastasis. Matrix metalloproteinase-9 (MMP-9) plays a crucial role in EGF/EGFR-mediated malignant progression and metastasis of TNBCs. Various studies have revealed that treatment with gallic acid down-regulates MMP-9 expression in cancer cells, and that conjugation of phytochemical compounds with gold nanoparticles (AuNPs) increases the anti-tumor activity of the phytochemical compounds. Thus, the effect of gallic acid-capped AuNPs (GA-AuNPs) on MMP-9 expression in EGF-treated TNBC MDA-MB-231 cells was analyzed in the present study. The so-called green synthesis of AuNPs by means of gallic acid was performed at pH 10, and the resulting GA-AuNPs had spherical shape with an average diameter of approximately 50 nm. GA-AuNPs notably suppressed migration and invasion of EGF-treated cells, and inhibited EGF-induced MMP-9 up-regulation. GA-AuNPs abrogated EGF-induced Akt/p65 and ERK/c-Jun phosphorylation, leading to down-regulation of MMP-9 mRNA and protein expression in EGF-treated cells. Meanwhile, EGF-induced p300 stabilization was found to be involved in MMP-9 expression, whereas GA-AuNPs inhibited the EGF-promoted stability of the p300 protein. Although GA-AuNPs and gallic acid suppressed EGF-induced MMP-9 up-regulation via the same signaling pathway, the effective concentration of gallic acid was approximately 100-fold higher than that of GA-AuNPs for inhibition of MMP-9 expression in EGF-treated cells to a similar extent. Collectively, our data indicate that, in comparison with gallic acid, GA-AuNPs have a superior ability to inhibit EGF/EGFR-mediated MMP-9 expression in TNBC MDA-MB-231 cells. Our findings also point to a way to improve the anti-tumor activity of gallic acid. - Highlights: • Gallic acid-capped gold nanoparticles inhibit EGF-induced MMP-9 expression. • EGF-induced MMP-9 expression via p300 stabilization and NFκB/c-Jun activation. • Gallic acid

  5. Gallic acid-capped gold nanoparticles inhibit EGF-induced MMP-9 expression through suppression of p300 stabilization and NFκB/c-Jun activation in breast cancer MDA-MB-231 cells

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Ying-Jung; Lee, Yuan-Chin; Huang, Chia-Hui [Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan (China); Chang, Long-Sen, E-mail: lschang@mail.nsysu.edu.tw [Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan (China); Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China)

    2016-11-01

    Triple-negative breast cancers (TNBCs) are highly invasive and have a higher rate of distant metastasis. Matrix metalloproteinase-9 (MMP-9) plays a crucial role in EGF/EGFR-mediated malignant progression and metastasis of TNBCs. Various studies have revealed that treatment with gallic acid down-regulates MMP-9 expression in cancer cells, and that conjugation of phytochemical compounds with gold nanoparticles (AuNPs) increases the anti-tumor activity of the phytochemical compounds. Thus, the effect of gallic acid-capped AuNPs (GA-AuNPs) on MMP-9 expression in EGF-treated TNBC MDA-MB-231 cells was analyzed in the present study. The so-called green synthesis of AuNPs by means of gallic acid was performed at pH 10, and the resulting GA-AuNPs had spherical shape with an average diameter of approximately 50 nm. GA-AuNPs notably suppressed migration and invasion of EGF-treated cells, and inhibited EGF-induced MMP-9 up-regulation. GA-AuNPs abrogated EGF-induced Akt/p65 and ERK/c-Jun phosphorylation, leading to down-regulation of MMP-9 mRNA and protein expression in EGF-treated cells. Meanwhile, EGF-induced p300 stabilization was found to be involved in MMP-9 expression, whereas GA-AuNPs inhibited the EGF-promoted stability of the p300 protein. Although GA-AuNPs and gallic acid suppressed EGF-induced MMP-9 up-regulation via the same signaling pathway, the effective concentration of gallic acid was approximately 100-fold higher than that of GA-AuNPs for inhibition of MMP-9 expression in EGF-treated cells to a similar extent. Collectively, our data indicate that, in comparison with gallic acid, GA-AuNPs have a superior ability to inhibit EGF/EGFR-mediated MMP-9 expression in TNBC MDA-MB-231 cells. Our findings also point to a way to improve the anti-tumor activity of gallic acid. - Highlights: • Gallic acid-capped gold nanoparticles inhibit EGF-induced MMP-9 expression. • EGF-induced MMP-9 expression via p300 stabilization and NFκB/c-Jun activation. • Gallic acid

  6. Development and validation of an enzyme-linked immunosorbent assay for the quantification of a specific MMP-9 mediated degradation fragment of type III collagen--A novel biomarker of atherosclerotic plaque remodeling

    DEFF Research Database (Denmark)

    Barascuk, Natasha; Vassiliadis, Efstathios; Larsen, Lise

    2011-01-01

    Degradation of collagen in the arterial wall by matrix metalloproteinases is the hallmark of atherosclerosis. We have developed an ELISA for the quantification of type III collagen degradation mediated by MMP-9 in urine.......Degradation of collagen in the arterial wall by matrix metalloproteinases is the hallmark of atherosclerosis. We have developed an ELISA for the quantification of type III collagen degradation mediated by MMP-9 in urine....

  7. Paeoniflorin Suppressed High Glucose-Induced Retinal Microglia MMP-9 Expression and Inflammatory Response via Inhibition of TLR4/NF-κB Pathway Through Upregulation of SOCS3 in Diabetic Retinopathy.

    Science.gov (United States)

    Zhu, Su-Hua; Liu, Bing-Qian; Hao, Mao-Juan; Fan, Yi-Xin; Qian, Cheng; Teng, Peng; Zhou, Xiao-Wei; Hu, Liang; Liu, Wen-Tao; Yuan, Zhi-Lan; Li, Qing-Ping

    2017-10-01

    Diabetic retinopathy (DR) is a serious-threatening complication of diabetes and urgently needed to be treated. Evidence has accumulated indicating that microglia inflammation within the retina plays a critical role in DR. Microglial matrix metalloproteinase 9 (MMP-9) has an important role in the destruction of the integrity of the blood-retinal barrier (BRB) associated with the development of DR. MMP-9 was also considered important for regulating inflammatory responses. Paeoniflorin, a monoterpene glucoside, has a potent immunomodulatory effect on microglia. We hypothesized that paeoniflorin could significantly suppress microglial MMP-9 activation induced by high glucose and further relieve DR. BV2 cells were used to investigate the effects and mechanism of paeoniflorin. The activation of MMP-9 was measured by gelatin zymography. Cell signaling was measured by western blot assay and immunofluorescence assay. High glucose increased the activation of MMP-9 in BV2 cells, which was abolished by HMGB1, TLR4, p38 MAPK, and NF-κB inhibition. Phosphorylation of p38 MAPK induced by high glucose was decreased by TLR4 inhibition in BV2 cells. Paeoniflorin induced suppressor of cytokine signaling 3 (SOCS3) expression and reduced MMP-9 activation in BV2 cells. The effect of paeoniflorin on SOCS3 was abolished by the TLR4 inhibitor. In streptozotocin (STZ)-induced diabetes mice, paeoniflorin induced SOCS3 expression and reduced MMP-9 activation. Paeoniflorin suppressed STZ-induced IBA-1 and IL-1β expression and decreased STZ-induced high blood glucose level. In conclusion, paeoniflorin suppressed high glucose-induced retinal microglia MMP-9 expression and inflammatory response via inhibition of the TLR4/NF-κB pathway through upregulation of SOCS3 in diabetic retinopathy.

  8. 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.

    Science.gov (United States)

    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.

  9. Detection of the matrix metalloproteinases MMP-2 and MMP-9 and tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2 in llama (Lama glama) oviduct.

    Science.gov (United States)

    Zampini, R; Argañaraz, M E; Miceli, D C; Apichela, S A

    2014-06-01

    Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are involved in several reproductive events like oocyte-spermatozoa interaction and semen liquefaction. In order to study their role in the llama oviductal reproductive process, MMP activity in oviductal fluid (OF) was assayed. Considering that llama genome sequences are partially known, a strategy to procure cDNA sequences of MMP-2, MMP-9, TIMP-1 and TIMP-2 was designed. Afterwards, their expression patterns in the different llama oviductal segments were assayed. Gelatine zymograms detected 62 and 94 kDa protease activities that matched MMP-2 and pro-MMP-9, respectively. Expression pattern analysis showed that MMP and TIMP mRNAs were present in ampulla, isthmus, utero-tubal junction (UTJ) and papilla. Altogether, these findings support the argument that MMPs/TIMPs are produced in the oviduct and secreted into the oviductal lumen. Our results encourage further studies to elucidate the role of these proteins in reproductive oviductal events. © 2014 Blackwell Verlag GmbH.

  10. Fish oil improves motor function, limits blood-brain barrier disruption, and reduces Mmp9 gene expression in a rat model of juvenile traumatic brain injury.

    Science.gov (United States)

    Russell, K L; Berman, N E J; Gregg, P R A; Levant, B

    2014-01-01

    The effects of an oral fish oil treatment regimen on sensorimotor, blood-brain barrier, and biochemical outcomes of traumatic brain injury (TBI) were investigated in a juvenile rat model. Seventeen-day old Long-Evans rats were given a 15mL/kg fish oil (2.01g/kg EPA, 1.34g/kg DHA) or soybean oil dose via oral gavage 30min prior to being subjected to a controlled cortical impact injury or sham surgery, followed by daily doses for seven days. Fish oil treatment resulted in less severe hindlimb deficits after TBI as assessed with the beam walk test, decreased cerebral IgG infiltration, and decreased TBI-induced expression of the Mmp9 gene one day after injury. These results indicate that fish oil improved functional outcome after TBI resulting, at least in part from decreased disruption of the blood-brain barrier through a mechanism that includes attenuation of TBI-induced expression of Mmp9. © 2013 Elsevier Ltd. All rights reserved.

  11. Azilsartan increases levels of IL-10, down-regulates MMP-2, MMP-9, RANKL/RANK, Cathepsin K and up-regulates OPG in an experimental periodontitis model.

    Directory of Open Access Journals (Sweden)

    Aurigena Antunes de Araújo

    Full Text Available AIMS: The aim of this study was to evaluate the effects of azilsartan (AZT on bone loss, inflammation, and the expression of matrix metallo proteinases (MMPs, receptor activator of nuclear factor κB ligand (RANKL, receptor activator of nuclear factor κB (RANK, osteoprotegerin (OPG, cyclooxygenase-2 (COX-2, and cathepsin K in periodontal tissue in a rat model of ligature-induced periodontitis. MATERIALS AND METHODS: Male Wistar albino rats were randomly divided into 5 groups of 10 rats each: (1 nonligated, water; (2 ligated, water; (3 ligated, 1 mg/kg AZT; (4 ligated, 5 mg/kg AZT; and (5 ligated, 10 mg/kg AZT. All groups were treated with saline or AZT for 10 days. Periodontal tissues were analyzed by histopathology and immunohistochemical detection of MMP-2, MMP-9, COX-2, RANKL, RANK, OPG, and cathepsin K. Levels of IL-1β, IL-10, TNF-α, myeloperoxidase (MPO, and glutathione (GSH were determined by ELISA. RESULTS: Treatment with 5 mg/kg AZT resulted in reduced MPO (p<0.05 and IL-1β (p<0.05, increased levels of IL-10 (p<0.05, and reduced expression of MMP-2, MMP-9, COX-2, RANK, RANKL, cathepsin K, and increased expression of OPG. CONCLUSIONS: These findings reveal that AZT increases anti-inflammatory cytokines and GSH and decreases bone loss in ligature-induced periodontitis in rats.

  12. Modification of the association between antipsychotic treatment response and childhood adversity by MMP9 gene variants in a first-episode schizophrenia cohort.

    Science.gov (United States)

    McGregor, Nathaniel; Thompson, Nicole; O'Connell, Kevin Sean; Emsley, Robin; van der Merwe, Lize; Warnich, Louise

    2018-04-01

    Antipsychotics remain the most effective, and wide used option for ameliorating the symptoms of schizophrenia. However, inter-individual differences in treatment outcome are vast and suggest a role for genetic and environmental factors in affording favourable outcomes. A notable epigenetic relationship which has gained considerable traction in recent literature is the way in which the severity of childhood trauma can modify associations seen between genetic variation and antipsychotic treatment response. A potential mechanism of action which may facilitate this relationship is synaptic plasticity. This study investigated the role of variants in matrix metallopeptidase 9 (MMP9), a gene involved in synaptic plasticity, with treatment outcome considering the severity of childhood trauma as an interacting variable. The cohort comprised South African first episode schizophrenia patients treated with a single injectable antipsychotic, flupenthixol decanoate, monitored over 12 months. Relationships between novel and previously described variants, and haplotypes, with antipsychotic treatment response were found to be modified when considering childhood trauma as an interacting variable. This study provides the first evidence for the involvement of polymorphisms within MMP9 and the severity of childhood trauma in antipsychotic treatment response, and warrants further investigation into the role gene-environment interactions may play in the betterment of antipsychotic treatment strategies. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Rapid Exercise-Induced Mobilization of Dendritic Cells Is Potentially Mediated by a Flt3L- and MMP-9-Dependent Process in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Nathalie Deckx

    2015-01-01

    Full Text Available In healthy individuals, one exercise bout induces a substantial increase in the number of circulating leukocytes, while their function is transiently suppressed. The effect of one exercise bout in multiple sclerosis (MS is less studied. Since recent evidence suggests a role of dendritic cells (DC in the pathogenesis of MS, we investigated the effect of one combined endurance/resistance exercise bout on the number and function of DC in MS patients and healthy controls. Our results show a rapid increase in the number of DC in response to physical exercise in both MS patients and controls. Further investigation revealed that in particular DC expressing the migratory molecules CCR5 and CD62L were increased upon acute physical activity. This may be mediated by Flt3L- and MMP-9-dependent mobilization of DC, as demonstrated by increased circulating levels of Flt3L and MMP-9 following one exercise bout. Circulating DC display reduced TLR responsiveness after acute exercise, as evidenced by a less pronounced upregulation of activation markers, HLA-DR and CD86, on plasmacytoid DC and conventional DC, respectively. Our results indicate mobilization of DC, which may be less prone to drive inflammatory processes, following exercise. This may present a negative feedback mechanism for exercise-induced tissue damage and inflammation.

  14. The impact of carboplatin and toceranib phosphate on serum vascular endothelial growth factor (VEGF) and metalloproteinase-9 (MMP-9) levels and survival in canine osteosarcoma.

    Science.gov (United States)

    Gieger, Tracy L; Nettifee-Osborne, Julie; Hallman, Briana; Johannes, Chad; Clarke, Dawn; Nolan, Michael W; Williams, Laurel E

    2017-07-01

    In this pilot study, 10 dogs with osteosarcoma (OSA) were treated with amputation and subsequent carboplatin chemotherapy (300 mg/m 2 IV q3wk × 4 doses) followed by toceranib phosphate (2.75 mg/kg PO q48h starting at day 14 post carboplatin). Monthly clinical monitoring and serum measurements of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) were acquired. No dogs were removed from the study due to toxicity. Levels of VEGF and MMP-9 did not change over time. Seven dogs died related to local recurrence and/or pulmonary or bone metastasis and the remainder died of other causes. Median OSA-free survival was 238 d with 34% 1-year progression-free survival. Median overall survival was 253 d with 30% alive at 1.5 y and 10% alive at 2 y. Although this regimen was well-tolerated, survival times did not exceed previously published data from dogs treated with amputation plus chemotherapy alone.

  15. Expressão da MMP-9 e do VEGF no câncer de mama: correlação com outros indicadores de prognóstico Expression of MMP-9 and VEGF in breast cancer: correlation with other prognostic indicators

    Directory of Open Access Journals (Sweden)

    Flavio Cabreira Jobim

    2008-06-01

    Full Text Available OBJETIVO: analisar a expressão da metaloproteinase da matriz 9 (MMP-9 e do fator de crescimento vascular endotelial (VEGF em um grupo de pacientes com câncer primário de mama, e correlacioná-los entre si e com outros indicadores de prognóstico. MÉTODOS: estudo transversal que analisou a expressão da MMP-9 e do VEGF em 88 casos consecutivos de tumores primários de mama. As amostras foram obtidas de pacientes portadoras de câncer primário de mama, submetidas a tratamento cirúrgico no Hospital de Clínicas de Porto Alegre da Universidade Federal do Rio Grande do Sul, no período de janeiro de 2000 a dezembro de 2004. A técnica de imuno-histoquímica, usando o complexo avidina-biotina-peroxidase, foi aplicada para avaliar a imunoreação dos antígenos nos tumores. A expressão qualitativa das proteínas foi avaliada por meio da observação da intensidade da coloração acastanhada dos anticorpos no citoplasma das células malignas, considerando positiva quando pelo menos uma célula tumoral apresentava coloração nítida e inequívoca para cada um destes marcadores. Para a determinação do escore qualitativo (0=ausente, 1=fraca, 2=média e 3=forte, foi considerada a intensidade da coloração citoplasmática mais forte na lâmina, independente do número de células coradas. A expressão quantitativa foi determinada pela percentagem média de células coradas, observadas em pelo menos dez campos microscópicos. A quantificação final da expressão da MMP-9 e do VEGF foi feita por meio da aplicação do algoritmo HSCORE=Σ[(I+1]xPC, no qual I e PC representam a intensidade da coloração e a percentagem das células coradas, respectivamente. RESULTADOS: a MMP-9 e o VEGF apresentaram alto percentual de positividade nos tumores estudados. A expressão final mostrou escore mediano de 180 e 190, respectivamente. Quando se comparou a expressão da MMP-9 e do VEGF com as variáveis "idade", "diâmetro tumoral", "tipo histológico", "grau

  16. Proteins in Soy Might Have a Higher Role in Cancer Prevention than Previously Expected: Soybean Protein Fractions Are More Effective MMP-9 Inhibitors Than Non-Protein Fractions, Even in Cooked Seeds

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    Ana Lima

    2017-02-01

    Full Text Available The search for anticancer MMP-9 inhibitors (MMPIs in food products has become a major goal for research. MMPIs in soy have been related only to saponins and isoflavones, but recently, low specific protein fractions in soybeans were shown to reduce MMP-9 activity as well. The present work aimed at comparing the MMPI potential of protein fractions (P and non-protein fractions (NP isolated from soybean seeds, before and after soaking and cooking, mimicking dietary exposures. Reverse and substrate zymography, as well as a fluoregenic DQ gelatin assay were used to evaluate MMP-9 activities. Colon cancer cell migration and proliferation was also tested in HT29 cells. Regarding MMP-9 inhibition, proteins in soy presented IC50 values 100 times lower than non-protein extracts, and remained active after cooking, suggesting that proteins may be more effective MMP-9 inhibitors than non-protein compounds. Using the determined IC50 concentrations, NP fractions were able to induce higher inhibitions of HT29 cell migration and proliferation, but not through MMP-9 inhibition, whilst protein fractions were shown to specifically inhibit MMP-9 activity. Overall, our results show that protein fractions in soybeans might have a higher role in soy-related cancer prevention as MMPIs than previously expected. Being nontoxic and active at lower concentrations, the discovery of these heat-resistant specific MMPI proteins in soy can be of significant importance for cancer preventive diets, particularly considering the increasing use of soy proteins in food products and the controversy around isoflavones amongst consumers.

  17. The potential protective effect of Physalis peruviana L. against carbon tetrachloride-induced hepatotoxicity in rats is mediated by suppression of oxidative stress and downregulation of MMP-9 expression.

    Science.gov (United States)

    Al-Olayan, Ebtisam M; El-Khadragy, Manal F; Aref, Ahmed M; Othman, Mohamed S; Kassab, Rami B; Abdel Moneim, Ahmed E

    2014-01-01

    The active constituent profile in Cape gooseberry (Physalis peruviana L.) juice was determined by GC-MS. Quercetin and kaempferol were active components in the juice. In this study we have evaluated its potential protective effect on hepatic injury and fibrosis induced by carbon tetrachloride (CCl4). Twenty-eight rats divided into 4 groups: Group I served as control group, and Group II received weekly i.p. injection of 2 mL CCl4/kg bwt for 12 weeks. Group III were supplemented with Physalis juice via the drinking water. The animals of Group IV received Physalis juice as Group III and also were intraperitoneally injected weekly with 2 mL CCl4/kg bwt for 12 weeks. Hepatoprotective effect was evaluated by improvement in liver enzymes serum levels, reduction in collagen areas, downregulation in expression of the fibrotic marker MMP-9, reduction in the peroxidative marker malonaldehyde and the inflammatory marker nitric oxide, and restoration of the activity of antioxidant enzymatic and nonenzymatic systems, namely, glutathione content, superoxide dismutase, catalase, glutathione-S-transferase, glutathione peroxidase, and glutathione reductase activities. The results show that the potential hepatoprotective effects of Physalis peruviana may be due to physalis acts by promotion of processes that restore hepatolobular architecture and through the inhibition of oxidative stress pathway.

  18. Loss of MURC/Cavin-4 induces JNK and MMP-9 activity enhancement in vascular smooth muscle cells and exacerbates abdominal aortic aneurysm.

    Science.gov (United States)

    Miyagawa, Kotaro; Ogata, Takehiro; Ueyama, Tomomi; Kasahara, Takeru; Nakanishi, Naohiko; Naito, Daisuke; Taniguchi, Takuya; Hamaoka, Tetsuro; Maruyama, Naoki; Nishi, Masahiro; Kimura, Taizo; Yamada, Hiroyuki; Aoki, Hiroki; Matoba, Satoaki

    2017-06-03

    Abdominal aortic aneurysm (AAA) is relatively common in elderly patients with atherosclerosis. MURC (muscle-restricted coiled-coil protein)/Cavin-4 modulating the caveolae function of muscle cells is expressed in cardiomyocytes, skeletal muscle cells and smooth muscle cells. Here, we show a novel functional role of MURC/Cavin-4 in vascular smooth muscle cells (VSMCs) and AAA development. Both wild-type (WT) and MURC/Cavin-4 knockout (MURC -/- ) mice subjected to periaortic application of CaCl 2 developed AAAs. Six weeks after CaCl 2 treatment, internal and external aortic diameters were significantly increased in MURC -/- AAAs compared with WT AAAs, which were accompanied by advanced fibrosis in the tunica media of MURC -/- AAAs. The activity of JNK and matrix metalloproteinase (MMP) -2 and -9 were increased in MURC -/- AAAs compared with WT AAAs at 5 days after CaCl 2 treatment. At 6 weeks after CaCl 2 treatment, MURC -/- AAAs exhibited attenuated JNK activity compared with WT AAAs. There was no difference in the activity of MMP-2 or -9 between saline and CaCl 2 treatments. In MURC/Cavin-4-knockdown VSMCs, TNFα-induced activity of JNK and MMP-9 was enhanced compared with control VSMCs. Furthermore, WT, MURC -/- , apolipoprotein E -/- (ApoE -/- ), and MURC/Cavin-4 and ApoE double-knockout (MURC -/- ApoE -/- ) mice were subjected to angiotensin II (Ang II) infusion. In both ApoE -/- and MURC -/- ApoE -/- mice infused for 4 weeks with Ang II, AAAs were promoted. The internal aortic diameter was significantly increased in Ang II-infused MURC -/- ApoE -/- mice compared with Ang II-infused ApoE -/- mice. In MURC/Cavin-4-knockdown VSMCs, Ang II-induced activity of JNK and MMP-9 was enhanced compared with control VSMCs. Our results suggest that MURC/Cavin-4 in VSMCs modulates AAA progression at the early stage via the activation of JNK and MMP-9. MURC/Cavin-4 is a potential therapeutic target against AAA progression. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Effect of glutamine-enriched nutritional support on intestinal mucosal barrier function, MMP-2, MMP-9 and immune function in patients with advanced gastric cancer during perioperative chemotherapy.

    Science.gov (United States)

    Wang, Juan; Li, Yanfen; Qi, Yuanling

    2017-09-01

    We studied the effects of glutamine-enriched nutritional support on intestinal mucosal barrier, matrix metalloproteinase (MMP)-2, MMP-9 and immune function during perioperative chemotherapy in patients with advanced gastric cancer. The study was conducted on 94 patients with advanced gastric cancer admitted from April 2015 to March 2016. They were randomly divided into observation and control groups, n=47. Control group was given basic nutritional support whereas glutamine-enriched nutritional support was given to patients in observation group. High-performance liquid chromatography was used to measure lactulose and mannitol ratio in urine (L/M) and ELISA was used to measure D-lactate levels before chemotherapy and in the 1st, 2nd and 3rd cycle of chemotherapy. Immunoglobulin level was detected by immune turbidimetry assay, T lymphocyte subsets were determined by flow cytometry after 3 cycles of chemotherapy, MMP-2 and MMP-9 of patients were compared between the two groups. The serious adverse reactions incidence (grade and IV) of patients were observed. To evaluate the life quality of patients, QLQ-C30 was used after 6 months. The levels of L/M and D-lactate in both groups after the first cycle of chemotherapy were significantly higher than that before chemotherapy; they began to decline after the second or third cycle, but were still significantly higher than the levels before chemotherapy (pgroups after 1st, 2nd, 3rd cycle after chemotherapy, L/M and D-lactate levels of patients in the observation group were significantly lower than in the control group (pgroup was significantly lower than control group (pgroup were significantly higher than control group (pnutritional support can effectively protect the intestinal mucosal barrier function in patients with advanced gastric cancer in their perioperative chemotherapy, improve the level of MMP-2 and MMP-9 in patients with advanced gastric cancer, enhance their immune function, reduce the incidence of adverse

  20. Gallic acid-capped gold nanoparticles inhibit EGF-induced MMP-9 expression through suppression of p300 stabilization and NFκB/c-Jun activation in breast cancer MDA-MB-231 cells.

    Science.gov (United States)

    Chen, Ying-Jung; Lee, Yuan-Chin; Huang, Chia-Hui; Chang, Long-Sen

    2016-11-01

    Triple-negative breast cancers (TNBCs) are highly invasive and have a higher rate of distant metastasis. Matrix metalloproteinase-9 (MMP-9) plays a crucial role in EGF/EGFR-mediated malignant progression and metastasis of TNBCs. Various studies have revealed that treatment with gallic acid down-regulates MMP-9 expression in cancer cells, and that conjugation of phytochemical compounds with gold nanoparticles (AuNPs) increases the anti-tumor activity of the phytochemical compounds. Thus, the effect of gallic acid-capped AuNPs (GA-AuNPs) on MMP-9 expression in EGF-treated TNBC MDA-MB-231 cells was analyzed in the present study. The so-called green synthesis of AuNPs by means of gallic acid was performed at pH10, and the resulting GA-AuNPs had spherical shape with an average diameter of approximately 50nm. GA-AuNPs notably suppressed migration and invasion of EGF-treated cells, and inhibited EGF-induced MMP-9 up-regulation. GA-AuNPs abrogated EGF-induced Akt/p65 and ERK/c-Jun phosphorylation, leading to down-regulation of MMP-9 mRNA and protein expression in EGF-treated cells. Meanwhile, EGF-induced p300 stabilization was found to be involved in MMP-9 expression, whereas GA-AuNPs inhibited the EGF-promoted stability of the p300 protein. Although GA-AuNPs and gallic acid suppressed EGF-induced MMP-9 up-regulation via the same signaling pathway, the effective concentration of gallic acid was approximately 100-fold higher than that of GA-AuNPs for inhibition of MMP-9 expression in EGF-treated cells to a similar extent. Collectively, our data indicate that, in comparison with gallic acid, GA-AuNPs have a superior ability to inhibit EGF/EGFR-mediated MMP-9 expression in TNBC MDA-MB-231 cells. Our findings also point to a way to improve the anti-tumor activity of gallic acid. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. RNA interference targeting carbohydrate sulfotransferase 3 diminishes macrophage accumulation, inhibits MMP-9 expression and promotes lung recovery in murine pulmonary emphysema.

    Science.gov (United States)

    Kai, Yoshiro; Tomoda, Koichi; Yoneyama, Hiroyuki; Yoshikawa, Masanori; Kimura, Hiroshi

    2015-12-09

    Chondroitin sulfate proteoglycans are an important mediators in inflammation and leukocyte trafficking. However, their roles in pulmonary emphysema have not been explored. In a murine model of elastase-induced pulmonary emphysema, we found increased carbohydrate sulfotransferase 3 (CHST3), a specific enzyme that synthesizes chondroitin 6-sulfate proteoglycan (C6SPG). To elucidate the role of C6SPG, we investigated the effect of small interfering RNA (siRNA) targeting CHST3 that inhibits C6SPG-synthesis on the pathogenesis of pulmonary emphysema. Mice were intraperitoneally injected with CHST3 siRNA or negative control siRNA on day0 and 7 after intratracheal instillation of elastase. Histology, respiratory function, glycosaminoglycans (GAGs) content, bronchoalveolar lavage (BAL), elastin staining and gene expressions of tumor necrosis factor (TNF)-α and matrix metalloproteinase (MMP)-9 mRNA were evaluated on day7 and/or day21. CHST3 mRNA increased at day 7 and decreased thereafter in lung. CHST3 siRNA successfully inhibited the expression of CHST3 mRNA throughout the study and this was associated with significant reduction of GAGs and C6SPG. Airway destruction and respiratory function were improved by the treatment with CHST3 siRNA. CHST3 siRNA reduced the number of macrophages both in BAL and lung parenchyma and also suppressed the increased expressions of TNF-α and MMP-9 mRNA. Futhermore, CHST3 siRNA improved the reduction of the elastin in the alveolar walls. CHST3 siRNA diminishes accumulation of excessive macrophages and the mediators, leading to accelerate the functional recovery from airway damage by repair of the elastin network associated with pulmonary emphysema.

  2. Serum-Induced Differentiation of Glioblastoma Neurospheres Leads to Enhanced Migration/Invasion Capacity That Is Associated with Increased MMP9.

    Directory of Open Access Journals (Sweden)

    Justin V Joseph

    Full Text Available Glioblastoma (GBM is a highly infiltrative brain tumor in which cells with properties of stem cells, called glioblastoma stem cells (GSCs, have been identified. In general, the dominant view is that GSCs are responsible for the initiation, progression, invasion and recurrence of this tumor. In this study, we addressed the question whether the differentiation status of GBM cells is associated with their invasive capacity. For this, several primary GBM cell lines were used, cultured either as neurospheres known to enrich for GSCs or in medium supplemented with 10% FCS that promotes differentiation. The differentiation state of the cells was confirmed by determining the expression of stem cell and differentiation markers. The migration/invasion potential of these cells was tested using in vitro assays and intracranial mouse models. Interestingly, we found that serum-induced differentiation enhanced the invasive potential of GBM cells, which was associated with enhanced MMP9 expression. Chemical inhibition of MMP9 significantly reduced the invasive potential of differentiated cells in vitro. Furthermore, the serum-differentiated cells could revert back to an undifferentiated/stem cell state that were able to form neurospheres, although with a reduced efficiency as compared to non-differentiated counterparts. We propose a model in which activation of the differentiation program in GBM cells enhances their infiltrative potential and that depending on microenvironmental cues a significant portion of these cells are able to revert back to an undifferentiated state with enhanced tumorigenic potential. Thus, effective therapy should target both GSCs and differentiated offspring and targeting of differentiation-associated pathways may offer therapeutic opportunities to reduce invasive growth of GBM.

  3. Platelet-derived growth factor-D modulates extracellular matrix homeostasis and remodeling through TIMP-1 induction and attenuation of MMP-2 and MMP-9 gelatinase activities

    International Nuclear Information System (INIS)

    Borkham-Kamphorst, Erawan; Alexi, Pascal; Tihaa, Lidia; Haas, Ute; Weiskirchen, Ralf

    2015-01-01

    Platelet-derived growth factor-D (PDGF-D) is a more recent recognized growth factor involved in the regulation of several cellular processes, including cell proliferation, transformation, invasion, and angiogenesis by binding to and activating its cognate receptor PDGFR-β. After bile duct ligation or in the carbon tetrachloride-induced hepatic fibrosis model , PDGF-D showed upregulation comparable to PDGF-B. Moreover, adenoviral PDGF-D gene transfer induced hepatic stellate cell proliferation and liver fibrosis. We here investigated the molecular mechanism of PDGF-D involvement in liver fibrogenesis. Therefore, the GRX mouse cell line was stimulated with PDGF-D and evaluated for fibrotic markers and PDGF-D signaling pathways in comparison to the other PDGF isoforms. We found that PDGF-D failed to enhance Col I and α-smooth muscle actin (α-SMA) production but has capacity to upregulate expression of the tissue inhibitor of metalloprotease 1 (TIMP-1) resulting in attenuation of MMP-2 and MMP-9 gelatinase activity as indicated by gelatinase zymography. This phenomenon was restored through application of a PDGF-D neutralizing antibody. Unexpectedly, PDGF-D incubation decreased both PDGFR-α and -β in mRNA and protein levels, and PDGF-D phosphorylated typrosines specific for PDGFR-α and -β. We conclude that PDGF-D intensifies fibrogenesis by interfering with the fibrolytic activity of the TIMP-1/MMP system and that PDGF-D signaling is mediated through both PDGF-α and -β receptors. - Highlights: • PDGF-D signals through PDGF receptor type α and β. • PDGF-D modulates extracellular matrix homeostasis and remodeling. • Like PDGF-B, PDGF-D triggers phosphorylation of PLC-γ, Akt/PKB, JNK, ERK1/2, and p38. • PDGF-D induces TIMP-1 expression through ERK and p38 MAPK. • PDGF-D attenuates MMP-2 and MMP-9 gelatinase activities

  4. A novel cell line derived from pleomorphic adenoma expresses MMP2, MMP9, TIMP1, TIMP2, and shows numeric chromosomal anomalies.

    Directory of Open Access Journals (Sweden)

    Aline Semblano Carreira Falcão

    Full Text Available Pleomorphic adenoma is the most common salivary gland neoplasm, and it can be locally invasive, despite its slow growth. This study aimed to establish a novel cell line (AP-1 derived from a human pleomorphic adenoma sample to better understand local invasiveness of this tumor. AP-1 cell line was characterized by cell growth analysis, expression of epithelial and myoepithelial markers by immunofluorescence, electron microscopy, 3D cell culture assays, cytogenetic features and transcriptomic study. Expression of matrix metalloproteinases (MMPs and their tissue inhibitors (TIMPs was also analyzed by immunofluorescence and zymography. Furthermore, epithelial and myoepithelial markers, MMPs and TIMPs were studied in the tumor that originated the cell line. AP-1 cells showed neoplastic epithelial and myoepithelial markers, such as cytokeratins, vimentin, S100 protein and smooth-muscle actin. These molecules were also found in vivo, in the tumor that originated the cell line. MMPs and TIMPs were observed in vivo and in AP-1 cells. Growth curve showed that AP-1 exhibited a doubling time of 3.342 days. AP-1 cells grown inside Matrigel recapitulated tumor architecture. Different numerical and structural chromosomal anomalies were visualized in cytogenetic analysis. Transcriptomic analysis addressed expression of 7 target genes (VIM, TIMP2, MMP2, MMP9, TIMP1, ACTA2 e PLAG1. Results were compared to transcriptomic profile of non-neoplastic salivary gland cells (HSG. Only MMP9 was not expressed in both libraries, and VIM was expressed solely in AP-1 library. The major difference regarding gene expression level between AP-1 and HSG samples occurred for MMP2. This gene was 184 times more expressed in AP-1 cells. Our findings suggest that AP-1 cell line could be a useful model for further studies on pleomorphic adenoma biology.

  5. Effects of dihydropyrano coumarins from Ferulago macrocarpa on VEGF, MMP9, MMP2 and study of binding modes using computational methods

    Directory of Open Access Journals (Sweden)

    2017-11-01

    Full Text Available Background and objectives: Ferulago macrocarpa of Apiaceae (Umbelliferae is native to the highlands of the west of Iran which contains dihydrocoumarins from phenolic class. Studies have shown that phenolic compounds at physiological concentrations could inhibit two groups of gelatinase matrix metalloproteinases (MMP2, MMP9. Due to the high diversity of coumarins in the plant, the possibility of the compounds to inhibit plant enzymes seem to be mentioned. Methods: Acetone extract of the plant was prepared and then winterized. Afterwards, dihydropyranocoumarins were purified using normal phase column chromatography and preparative HPLC, and their structures were verified. After culturing the cells, at confluence step, supernatants were collected at 24 and 48 h soup and non-proliferation medium containing 2% albumin. The pure substances were applied on cell lines U87MG and WEHI for evaluation of VEGF, MMP-2 and 9 activities. In the computational processing, the structures were docked in the active site of metalloproteinases 9, and significant interactions were determined. Subsequently, ligand-protein complexes were subjected to molecular dynamics simulation in water, and thermodynamic properties were calculated. (MMP9 code= 1L6J, MMP2 code= 1CK7. Results: Regarding cytotoxicity results, IC50 of prantschimgin and grandivitin in WEHI cell line were 521.63, 232. 66, and in U87MG cell line were 575.58, 322.0 lpg/mL, respectively. Conclusion: Two coumarins, prantschimgin and grandivitin with the potential inhibitory effects on the activity of MMP 2,9 and anti-angiogenesis were purified from F. macrocarpa fruits. The application can be expected to have therapeutic efficacy in cancer cell lines U87MG and WEHI.

  6. Comparison of immunoexpression of VEGF, TGF-β and MMP-9 in ameloblastoma and adenomatoid odontogenic tumor = Comparação da imunoexpressão de VEGF, TGF-β e MMP-9 em ameloblastoma e tumor odontogênico adenomatóide

    Directory of Open Access Journals (Sweden)

    Ferreira, Stefânia Jeronimo

    2015-01-01

    Full Text Available Objetivo: Estudos sobre tumores odontogênicos têm identificado várias disfunções moleculares envolvidas no seu desenvolvimento, e alguns mecanismos como a angiogênese e modulação da matriz são objetos úteis para investigar as diferenças no comportamento biológico destes tumores. Alguns marcadores importantes para identificar a agressividade do tumor por imunoistoquímica são as proteínas VEGF, TGF-ß e MMP-9. Este estudo teve como objetivo comparar a expressão imunoistoquímica de VEGF, TGF-ß e MMP-9 entre ameloblastoma e tumor odontogênico adenomatoide (TOA. Métodos: Imunoexpressão de VEGF, TGF-ß e MMP-9 foi estudada em 15 ameloblastomas sólidos e 15 TOA. Uma análise semiquantitativa das células imunomarcadas foi realizada e a análise estatística foi feita usando o teste não paramétrico de Mann-Whitney e o teste de correlação de Spearman, com nível de significância de 0,05 (P0. 05. Conclusão: Os resultados sugerem o envolvimento da angiogênese na progressão tumoral de ameloblastomas e o efeito indutor de células estromais em TOA, portanto, justificando o seu potencial de crescimento mais baixo

  7. Once-weekly 22microg subcutaneous IFN-beta-1a in secondary progressive MS: a 3-year follow-up study on brain MRI measurements and serum MMP-9 levels

    DEFF Research Database (Denmark)

    Wu, X; Kuusisto, H; Dastidar, P

    2007-01-01

    : There was no obvious effect on the number of contrast medium-enhancing lesions, the volume of T1 or T2 lesions or level of serum MMP-9, nor was any effect detected on the relapse rate and the Expanded Disability Status Scale (EDSS). Brain atrophy progression was not affected by the treatment. CONCLUSION: The lack......OBJECTIVE: To study the effect of weekly injected subcutaneous interferon (IFN)-beta-1a 22 microg on the extent of brain lesions on magnetic resonance imaging (MRI) and the level of serum matrix metalloproteinase (MMP)-9 in patients with secondary progressive multiple sclerosis (SPMS). SUBJECTS...... of effect on MRI, clinical outcomes or the levels of MMP-9 indicates that subcutaneous administration of low-dose low-frequency IFN-beta-1a is insufficient in controlling either the inflammatory constitutes or the neurodegenerative changes of advanced SPMS. Udgivelsesdato: 2007-Jul...

  8. Platelet-derived growth factor-D modulates extracellular matrix homeostasis and remodeling through TIMP-1 induction and attenuation of MMP-2 and MMP-9 gelatinase activities

    Energy Technology Data Exchange (ETDEWEB)

    Borkham-Kamphorst, Erawan, E-mail: ekamphorst@ukaachen.de; Alexi, Pascal; Tihaa, Lidia; Haas, Ute; Weiskirchen, Ralf, E-mail: rweiskirchen@ukaachen.de

    2015-02-13

    Platelet-derived growth factor-D (PDGF-D) is a more recent recognized growth factor involved in the regulation of several cellular processes, including cell proliferation, transformation, invasion, and angiogenesis by binding to and activating its cognate receptor PDGFR-β. After bile duct ligation or in the carbon tetrachloride-induced hepatic fibrosis model{sub ,} PDGF-D showed upregulation comparable to PDGF-B. Moreover, adenoviral PDGF-D gene transfer induced hepatic stellate cell proliferation and liver fibrosis. We here investigated the molecular mechanism of PDGF-D involvement in liver fibrogenesis. Therefore, the GRX mouse cell line was stimulated with PDGF-D and evaluated for fibrotic markers and PDGF-D signaling pathways in comparison to the other PDGF isoforms. We found that PDGF-D failed to enhance Col I and α-smooth muscle actin (α-SMA) production but has capacity to upregulate expression of the tissue inhibitor of metalloprotease 1 (TIMP-1) resulting in attenuation of MMP-2 and MMP-9 gelatinase activity as indicated by gelatinase zymography. This phenomenon was restored through application of a PDGF-D neutralizing antibody. Unexpectedly, PDGF-D incubation decreased both PDGFR-α and -β in mRNA and protein levels, and PDGF-D phosphorylated typrosines specific for PDGFR-α and -β. We conclude that PDGF-D intensifies fibrogenesis by interfering with the fibrolytic activity of the TIMP-1/MMP system and that PDGF-D signaling is mediated through both PDGF-α and -β receptors. - Highlights: • PDGF-D signals through PDGF receptor type α and β. • PDGF-D modulates extracellular matrix homeostasis and remodeling. • Like PDGF-B, PDGF-D triggers phosphorylation of PLC-γ, Akt/PKB, JNK, ERK1/2, and p38. • PDGF-D induces TIMP-1 expression through ERK and p38 MAPK. • PDGF-D attenuates MMP-2 and MMP-9 gelatinase activities.

  9. Matrix stiffness-upregulated LOXL2 promotes fibronectin production, MMP9 and CXCL12 expression and BMDCs recruitment to assist pre-metastatic niche formation.

    Science.gov (United States)

    Wu, Sifan; Zheng, Qiongdan; Xing, Xiaoxia; Dong, Yinying; Wang, Yaohui; You, Yang; Chen, Rongxin; Hu, Chao; Chen, Jie; Gao, Dongmei; Zhao, Yan; Wang, Zhiming; Xue, Tongchun; Ren, Zhenggang; Cui, Jiefeng

    2018-05-04

    Higher matrix stiffness affects biological behavior of tumor cells, regulates tumor-associated gene/miRNA expression and stemness characteristic, and contributes to tumor invasion and metastasis. However, the linkage between higher matrix stiffness and pre-metastatic niche in hepatocellular carcinoma (HCC) is still largely unknown. We comparatively analyzed the expressions of LOX family members in HCC cells grown on different stiffness substrates, and speculated that the secreted LOXL2 may mediate the linkage between higher matrix stiffness and pre-metastatic niche. Subsequently, we investigated the underlying molecular mechanism by which matrix stiffness induced LOXL2 expression in HCC cells, and explored the effects of LOXL2 on pre-metastatic niche formation, such as BMCs recruitment, fibronectin production, MMPs and CXCL12 expression, cell adhesion, etc. RESULTS: Higher matrix stiffness significantly upregulated LOXL2 expression in HCC cells, and activated JNK/c-JUN signaling pathway. Knockdown of integrin β1 and α5 suppressed LOXL2 expression and reversed the activation of above signaling pathway. Additionally, JNK inhibitor attenuated the expressions of p-JNK, p-c-JUN, c-JUN and LOXL2, and shRNA-c-JUN also decreased LOXL2 expression. CM-LV-LOXL2-OE and rhLOXL2 upregulated MMP9 expression and fibronectin production obviously in lung fibroblasts. Moreover, activation of Akt pathway contributed to LOXL2-induced fibronectin upregulation. LOXL2 in CM as chemoattractant increased motility and invasion of BMCs, implicating a significant role of LOXL2 in BMCs recruitment. Except that, CM-LV-LOXL2-OE as chemoattractant also increased the number of migrated HCC cells, and improved chemokine CXCL12 expression in lung fibroblasts. The number of HCC cells adhered to surface of lung fibroblasts treated with CM-LV-LOXL2-OE was remarkably higher than that of the control cells. These results indicated that the secreted LOXL2 facilitated the motility of HCC cells and

  10. Infection of human monocyte-derived dendritic cells by ANDES Hantavirus enhances pro-inflammatory state, the secretion of active MMP-9 and indirectly enhances endothelial permeability

    Directory of Open Access Journals (Sweden)

    Lopez-Lastra Marcelo

    2011-05-01

    Full Text Available Abstract Background Andes virus (ANDV, a rodent-borne Hantavirus, is the major etiological agent of Hantavirus cardiopulmonary syndrome (HCPS in South America, which is mainly characterized by a vascular leakage with high rate of fatal outcomes for infected patients. Currently, neither specific therapy nor vaccines are available against this pathogen. ANDV infects both dendritic and epithelial cells, but in despite that the severity of the disease directly correlates with the viral RNA load, considerable evidence suggests that immune mechanisms rather than direct viral cytopathology are responsible for plasma leakage in HCPS. Here, we assessed the possible effect of soluble factors, induced in viral-activated DCs, on endothelial permeability. Activated immune cells, including DC, secrete gelatinolytic matrix metalloproteases (gMMP-2 and -9 that modulate the vascular permeability for their trafficking. Methods A clinical ANDES isolate was used to infect DC derived from primary PBMC. Maturation and pro-inflammatory phenotypes of ANDES-infected DC were assessed by studying the expression of receptors, cytokines and active gMMP-9, as well as some of their functional status. The ANDES-infected DC supernatants were assessed for their capacity to enhance a monolayer endothelial permeability using primary human vascular endothelial cells (HUVEC. Results Here, we show that in vitro primary DCs infected by a clinical isolate of ANDV shed virus RNA and proteins, suggesting a competent viral replication in these cells. Moreover, this infection induces an enhanced expression of soluble pro-inflammatory factors, including TNF-α and the active gMMP-9, as well as a decreased expression of anti-inflammatory cytokines, such as IL-10 and TGF-β. These viral activated cells are less sensitive to apoptosis. Moreover, supernatants from ANDV-infected DCs were able to indirectly enhance the permeability of a monolayer of primary HUVEC. Conclusions Primary human DCs

  11. Expression of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinases 1 (TIMP-1) by colorectal cancer cells and adjacent stroma cells--associations with histopathology and patients outcome

    DEFF Research Database (Denmark)

    Jensen, Søren Astrup; Vainer, Ben; Bartels, Annette

    2010-01-01

    To elucidate cellular features accountable for colorectal cancers' (CRC) capability to invade normal tissue and to metastasize, we investigated the level of the collagenase matrix metalloproteinase 9 (MMP-9) and its physiological inhibitor tissue inhibitor of metalloproteinases 1 (TIMP-1) in canc...

  12. MMP-9/ANC score as a predictive biomarker for efficacy of bevacizumab plus platinum doublet chemotherapy in patients with advanced or recurrent non-squamous non-small cell lung cancer.

    Science.gov (United States)

    Hiura, Kazuya; Shiraishi, Akiko; Suzuki, Chinami; Takamura, Kei; Yamamoto, Makoto; Komori, Hitoshi; Watanabe, Yasuhiro; Iwaki-Egawa, Sachiko

    2015-01-01

    Bevacizumab is a recombinant humanized monoclonal antibody against vascular endothelial growth factor (VEGF), which is a key regulator of tumor angiogenesis. To evaluate biomarkers to predict the benefit of paclitaxel and carboplatin plus bevacizumab (PCB) therapy in patients with advanced or recurrent non-squamous non-small cell lung cancer. Among 21 patients treated with PCB, 10 were included in the good responder group and 11 in the non-responder group. Serum VEGF, MMP-2 and MMP-9 were measured using ELISA. There were no significant differences in these markers levels between groups. However, the good responder group showed a significantly higher pre-treatment MMP-9/ absolute neutrophil count (ANC) score than the non-responder group before the treatment (p= 0.014), and there was a positive correlation between the score and the tumor reduction rate (r= 0.57, p= 0.016). Furthermore, by dividing patients into a high scoring group (MMP-9/ANC ≥ median, n= 11) and a low scoring group (MMP-9/ANC ANC score before PCB treatment may be a suitable biomarker to assess the anti-tumor effects of PCB therapy.

  13. Increased expression of metalloproteinase-2 and -9 (MMP-2, MMP-9), tissue inhibitor of metalloproteinase-1 and -2 (TIMP-1, TIMP-2), and EMMPRIN (CD147) in multiple myeloma.

    Science.gov (United States)

    Urbaniak-Kujda, Donata; Kapelko-Slowik, Katarzyna; Prajs, Iwona; Dybko, Jarosław; Wolowiec, Dariusz; Biernat, Monika; Slowik, Miroslaw; Kuliczkowski, Kazimierz

    2016-01-01

    Activity of metalloproteinases (MMP) is controlled both by specific tissue inhibitors (TIMP) and activators (extracellular matrix metalloproteinase inducer, EMMPRIN). There are few data available concerning concentration the bone marrow of MMP-2, MMP-9, TIMP-1, and TIMP-2, or EMMPRIM expression by bone marrow mesenchymal stromal cells (BMSCs) in patients with multiple myeloma (MM). We studied 40 newly diagnosed, untreated patients: 18 males and 22 females with de novo MM and 11 healthy controls. Bone marrow was collected prior to therapy. BMSCs were derived by culturing bone marrow cells on MesenCult. Protein concentrations were determined in bone marrow plasma and culture supernatants by ELISA. EMMPRIN expression by BMSCs was assessed by flow cytometry. The median concentrations of MMP-9, TIMP-1, and TIMP-2 in both marrow plasma and culture supernatants were significantly higher in MM patients than controls. EMMPRIN expression and ratios MMP-9/TIMP-1 and MMP-2/TIMP-2 were higher in MM patients, our results demonstrate that in MM patients MMP-2 and MMP-9 are secreted in higher amounts and are not balanced by inhibitors.

  14. IL-6, IL-8, MMP-2, MMP-9 are overexpressed in Fanconi anemia cells through a NF-κB/TNF-α dependent mechanism.

    Science.gov (United States)

    Epanchintsev, Alexey; Shyamsunder, Pavithra; Verma, Rama S; Lyakhovich, Alex

    2015-12-01

    Fanconi anemia (FA) is a rare autosomal recessive genetic disorder associated with a bone-marrow failure, genome instability, hypersensitivity to DNA crosslinking agents and a predisposition to cancer. Mutations have been documented in 16 FA genes that participate in the FA-BRCA DNA repair pathway, a fundamental pathway in the development of the disease and the presentation of its symptoms. FA cells have been characterized by an overproduction of cytokines, MAPKs, and Interleukins. Through this study we have identified the overexpression of additional secretory factors such as IL-6, IL-8, MMP-2, and MMP-9 in FA cells and in cells depleted of FANCA or FANCC and proved that their expression is under the control of NF-κB/TNF-α signaling pathways. We also demonstrated that these overexpressed secretory factors were effective in promoting the proliferation, migration, and invasion of surrounding tumor cells a fundamental event in the process of epithelial mesenchymal transition (EMT) and that they also modulated the expression of EMT markers such as E-cadherin and SNAIL. Overall our data suggest that the upregulation of EMT promoting factors in FA may contribute to predisposing FA patients to cancer, thereby providing new insights into possible therapeutic interventions. © 2014 Wiley Periodicals, Inc.

  15. Elevated mazes as animal models of anxiety: effects of serotonergic agents

    Directory of Open Access Journals (Sweden)

    Simone H. Pinheiro

    2007-03-01

    Full Text Available This article reviews reported results about the effects of drugs that act upon the serotonergic neurotransmission measured in three elevated mazes that are animal models of anxiety. A bibliographic search has been performed in MEDLINE using different combinations of the key words X-maze, plus-maze, T-maze, serotonin and 5-HT, present in the title and/or the abstract, with no time limit. From the obtained abstracts, several publications were excluded on the basis of the following criteria: review articles that did not report original results, species other than the rat, intracerebral drug administration alone, genetically manipulated rats, and animals having any kind of experimental pathology. The reported results indicate that the effect of drugs on the inhibitory avoidance task performed in the elevated T-maze and on the spatio temporal indexes of anxiety measured in the X and plus mazes correlate with their effect in patients diagnosed with generalized anxiety disorder. In contrast, the drug effects on the one-way escape task in the elevated T-maze predict the drug response of panic disorder patients. Overall, the drug effects assessed with the avoidance task in the T-maze are more consistent than those measured through the anxiety indexes of the X and plus mazes. Therefore, the elevated T-maze is a promising animal model of generalized anxiety and panic disorder.No presente artigo, revisamos resultados publicados relatando efeitos de drogas que atuam na neurotransmissão serotonérgica medidos em três labirintos elevados, que são modelos animais de ansiedade. Realizamos uma busca bibliográfica no MEDLINE, usando diferentes combinações das palavras-chave: X-maze, plus-maze, T-maze, serotonin e 5-HT, presentes no título ou no resumo, sem limite de tempo. Dos resumos obtidos, vários foram excluídos com base nos seguintes critérios: artigos de revisão que não continham resultados originais, espécies diferentes do rato, apenas inje

  16. Anti-RhoC siRNAs inhibit the proliferation and invasiveness of breast cancer cells via modulating the KAI1, MMP9, and CXCR4 expression

    Directory of Open Access Journals (Sweden)

    Xu X

    2017-03-01

    Full Text Available Xu-Dong Xu,1 Han-Bin Shen,1 Li Zhu,2 Jian-Qin Lu,2 Lin Zhang,3 Zhi-Yong Luo,3 Ya-Qun Wu3 1Department of Thyroid and Breast Surgery, The Fifth Hospital of Wuhan, Hanyang District, 2Department of Oncology, 3Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China Abstract: Overexpression of RhoC in breast cancer cells indicates poor prognosis. In the present study, we aim to investigate the possible antitumor effects of anti-RhoC small-interfering RNA (siRNA in inflammatory breast cancer cells. In this study, a specific anti-RhoC siRNA was used to inhibit RhoC synthesis. Transfection of anti-RhoC siRNA into two IBC cells SUM149 and SUM190 induced extensive degradation of target mRNA and led to significant decrease in the synthesis of protein. Anti-RhoC siRNA inhibited cell proliferation and invasion, increased cell apoptosis, and induced cell cycle arrest in vitro. Moreover, the transfection of siRNA increased the expression of KAI1 and decreased the expression of MMP9 and CXCR4 in both mRNA and protein levels. Furthermore, transplantation tumor experiments in BALB/c-nu mice showed that intratumoral injection of anti-RhoC siRNA inhibited tumor growth and increased survival rate. Our results suggested that RhoC gene silencing with specific anti-RhoC siRNA would be a potential therapeutic method for metastatic breast cancer. Keywords: gene silencing, proliferation, apoptosis, cell cycle arrest

  17. BubR1 Acts as a Promoter in Cellular Motility of Human Oral Squamous Cancer Cells through Regulating MMP-2 and MMP-9

    Directory of Open Access Journals (Sweden)

    Chou-Kit Chou

    2015-07-01

    Full Text Available BubR1 is a critical component of spindle assembly checkpoint, ensuring proper chromatin segregation during mitosis. Recent studies showed that BubR1 was overexpressed in many cancer cells, including oral squamous cell carcinomas (OSCC. However, the effect of BubR1 on metastasis of OSCC remains unclear. This study aimed to unravel the role of BubR1 in the progression of OSCC and confirm the expression of BubR1 in a panel of malignant OSCC cell lines with different invasive abilities. The results of quantitative real-time PCR showed that the mRNA level of BubR1 was markedly increased in four OSCC cell lines, Ca9-22, HSC3, SCC9 and Cal-27 cells, compared to two normal cells, normal human oral keratinocytes (HOK and human gingival fibroblasts (HGF. Moreover, the expression of BubR1 in these four OSCC cell lines was positively correlated with their motility. Immunofluorescence revealed that BubR1 was mostly localized in the cytosol of human gingival carcinoma Ca9-22 cells. BubR1 knockdown significantly decreased cellular invasion but slightly affect cellular proliferation on both Ca9-22 and Cal-27 cells. Consistently, the activities of metastasis-associated metalloproteinases MMP-2 and MMP-9 were attenuated in BubR1 knockdown Ca9-22 cells, suggesting the role of BubR1 in promotion of OSCC migration. Our present study defines an alternative pathway in promoting metastasis of OSCC cells, and the expression of BubR1 could be a prognostic index in OSCC patients.

  18. [Zymography--method for quantitation of activity on gelatinase A (pro-MMP-2, 72 kDa) and gelatinase B (pro-MMP-9, 92 kDa) in serum of patients with breast cancer].

    Science.gov (United States)

    Sliwowska, Izabela; Kopczyński, Zygmunt

    2007-01-01

    Zymography is an electrophoretic method for measuring proteolytic activity. The method is based on polyacrylamide gels impregnated with a protein substrate (gelatin, casein), which is degraded by the proteases. It is already widely used for research on extracellular matrix degrading enzymes, in particular the matrix metalloproteinases (MMPs). The aim of this study was to evaluate the zymography used to estimate gelatinase A (pro-MMP-2, 72 kDa) and gelatinase B (pro-MMP-9, 92 kDa) in serum of women with breast cancer. The study was conducted on the serum of 90 female with breast cancer aged 32-85 years (average 57.2 year) and in a group of 30 women with benign breast diseases aged 34-87 years (average 55.4 year). The results showed significantly higher activity ofgelatinase A and gelatinase B in the group of women with breast cancer that in the control group. The activity of gelatinase A was over 0.48 AU/ml in 50 women (55.6%) and gelatinase B in 46 women in this group (51.1%). Further analysis showed a strong correlation between activity of gelatinase A and B and advance stage of breast cancer, lymph node status, and tumour burden. An elevated activity of gelatinases in patients with breast cancer confirms the role of these enzymes in the development of such tumours. There was no significant difference in the gelatinases activity between the serum samples from patients with breast cancer and those from women with benign breast diseases. The diagnostic sensitivity of this procedure used to estimate gelatinase A and gelatinase B activity carried out 56% and 51%, and the diagnostic specificity 75% and 77%, respectively. Zymography is a simple, sensitive, and functional assay for analysing proteolytic activity of gelatinase A and gelatinase B. The diagnostic accuracy of gelatinases evaluation is limited by the lack of sensitivity and specificity in early stage of the disease and in differentiation of breast cancer from benign diseases. Measuring their activity in serum

  19. Effect of non-surgical periodontal therapy on C-reactive protein, oxidative stress, and matrix metalloproteinase (MMP)-9 and MMP-2 levels in patients with type 2 diabetes: a randomized controlled study.

    Science.gov (United States)

    Koromantzos, Panagiotis A; Makrilakis, Konstantinos; Dereka, Xanthippi; Offenbacher, Steven; Katsilambros, Nicholas; Vrotsos, Ioannis A; Madianos, Phoebus N

    2012-01-01

    It is well accepted that glycemic control in patients with diabetes mellitus (DM) is affected by systemic inflammation and oxidative stress. The effect of periodontal therapy on these systemic factors may be related to improvement on glycemic status. The aim of the present study is to assess over a period of 6 months the effect of non-surgical periodontal therapy on serum levels of high-sensitivity C-reactive protein (hsCRP), d-8-iso prostaglandin F2a (d-8-iso) as a marker of oxidative stress, and matrix metalloproteinase (MMP)-2 and MMP-9 on patients with type 2 DM. Sixty participants with type 2 DM and moderate to severe periodontal disease were randomized into intervention (IG) and control (CG) groups. IG received scaling and root planing, whereas CG received supragingival cleaning at baseline and scaling and root planing at 6 months. Participants of both groups were evaluated at baseline and 1, 3, and 6 months. Periodontal data recorded at each visit included probing depth, clinical attachment loss, bleeding on probing, and gingival index. Blood was collected at each visit for the assay of serum glycated hemoglobin A1c (A1c), hsCRP, d-8-iso, MMP-2, and MMP-9. Although there was a trend to a reduction in hsCRP, d-8-iso and MMP-9 it did not reach statistical significance. MMP-2 levels remained unchanged after periodontal treatment. Effective non-surgical periodontal treatment of participants with type 2 DM and moderate to severe periodontal disease improved significantly A1c levels but did not result in a statistically significant improvement in hsCRP, d-8-iso, MMP-2, and MMP-9 levels.

  20. The co-existence of the IL-18+183 A/G and MMP-9 -1562 C/T polymorphisms is associated with clinical events in coronary artery disease patients.

    Directory of Open Access Journals (Sweden)

    Trine B Opstad

    Full Text Available Interleukin (IL-18 has been associated with severity of atherosclerosis and discussed to predict cardiovascular (CV events. We have previously shown that the IL-18+183 G-allele significantly reduces IL-18 levels. This study was aimed to investigate the prognostic significance of the IL-18+183 A/G polymorphism (rs5744292, single and in coexistence with the matrix metalloproteinase (MMP-9 -1562 C/T (rs3918242 polymorphism, in patients with stable coronary artery disease (CAD. Serum levels of IL-18, MMP-9 and tissue inhibitor of matrix metalloproteinase (TIMP-1 were additionally assessed.1001 patients with angiographically verified CAD were genotyped and the biomarkers were measured accordingly. After two years follow-up, 10.6% experienced new clinical events; acute myocardial infarction (AMI, stroke, unstable angina pectoris and death.The IL-18+183 G-allele associated with 35% risk reduction in composite endpoints after adjusting for potential covariates (p = 0.044. The IL-18+183 AA/MMP-9 -1562 CT/TT combined genotypes associated with a significant increase in risk of composite endpoints (OR = 1.87; 95% CI = 1.13-3.11, p = 0.015, adjusted. Patients with clinical events presented with significantly higher IL-18 levels as compared to patients without (p = 0.011, adjusted. The upper tertile of IL-18 levels associated with an increase in risk of AMI as compared to lower tertiles (OR = 2.36; 95% CI = 1.20-4.64, p = 0.013, adjusted.The IL-18+183 A/G polymorphism, single and in combination with MMP-9 genotypes, may influence the risk of clinical events in stable CAD patients.

  1. Matrix metalloproteinase-9 (MMP9) is involved in the TNF-α-induced fusion of human M13SV1-Cre breast epithelial cells and human MDA-MB-435-pFDR1 cancer cells.

    Science.gov (United States)

    Weiler, Julian; Mohr, Marieke; Zänker, Kurt S; Dittmar, Thomas

    2018-04-10

    In addition to physiological events such as fertilisation, placentation, osteoclastogenesis, or tissue regeneration/wound healing, cell fusion is involved in pathophysiological conditions such as cancer. Cell fusion, which applies to both the proteins and conditions that induce the merging of two or more cells, is not a fully understood process. Inflammation/pro-inflammatory cytokines might be a positive trigger for cell fusion. Using a Cre-LoxP-based cell fusion assay we demonstrated that the fusion between human M13SV1-Cre breast epithelial cells and human MDA-MB-435-pFDR1 cancer cells was induced by the pro-inflammatory cytokine tumour necrosis factor-α (TNF-α). The gene expression profile of the cells in the presence of TNF-α and under normoxic and hypoxic conditions was analysed by cDNA microarray analysis. cDNA microarray data were verified by qPCR, PCR, Western blot and zymography. Quantification of cell fusion events was determined by flow cytometry. Proteins of interest were either blocked or knocked-down using a specific inhibitor, siRNA or a blocking antibody. The data showed an up-regulation of various genes, including claudin-1 (CLDN1), ICAM1, CCL2 and MMP9 in M13SV1-Cre and/or MDA-MB-435-pFDR1 cells. Inhibition of these proteins using a blocking ICAM1 antibody, CLDN1 siRNA or an MMP9 inhibitor showed that only the blockage of MMP9 was correlated with a decreased fusion rate of the cells. Likewise, the tetracycline-based antibiotic minocycline, which exhibits anti-inflammatory properties, was also effective in both inhibiting the TNF-α-induced MMP9 expression in M13SV1-Cre cells and blocking the TNF-α-induced fusion frequency of human M13SV1-Cre breast epithelial cells and human MDA-MB-435-pFDR1 cancer cells. The matrix metalloproteinase-9 (MMP9) is most likely involved in the TNF-α-mediated fusion of human M13SV1-Cre breast epithelial cells and human MDA-MB-435-pFDR1 cancer cells. Likewise, our data indicate that the tetracycline

  2. Associations of rs3918242 and rs2285053 MMP-9 and MMP-2 polymorphisms with the risk, severity, and short- and long-term complications of degenerative mitral valve diseases: a 4.8-year prospective cohort study.

    Science.gov (United States)

    Balistreri, Carmela Rita; Allegra, Alberto; Crapanzano, Floriana; Pisano, Calogera; Triolo, Oreste Fabio; Argano, Vincenzo; Candore, Giuseppina; Lio, Domenico; Ruvolo, Giovanni

    2016-01-01

    Degenerative forms of mitral valve diseases (MVDs) are very complex pathologies. Thus, it is difficult to make generalizations about the disease pathways or genetic risk factors contributing to these diseases. However, a key role of metalloproteinases (MMPs) in their pathophysiology is emerging. Thus, we performed for the first time a perspective study to assess eventual associations of some functional single nucleotide polymorphisms (SNPs) in MMP-2 and MMP-9 genes with the MVD risk, symptom severity, and short- and long-term (4.8 years) complications. For this purpose, 90 patients and two control groups were genotyped for rs3918242, rs243865, and rs2285053 MMP-2 and MMP-9 gene SNPs, and systemic levels of pro-atrial natriuretic peptide (pro-ANP) and two enzymes were quantified and correlated to genotypes of MMP-2 and MMP-9 SNPs studied. In addition, associations between these SNPs and symptom severity and short- and long-term (4.8 years) complications were evaluated. Interestingly, rs3918242 MMP-9 and rs2285053 MMP-2 SNPs were significantly represented in cases than two control groups and were associated with a higher MVD risk, as demonstrated using dominant/recessive models. Cases stratified for NYHA symptoms and particularly those NYHA III+IV with rs3918242 CT+TT MMP-9 and rs2285053CT+TT genotypes also showed higher severity related to significant higher systemic levels of MMP enzymes and pro-ANP at enrolment and 4.8 follow-up times. In addition, cases with these genotypes and particularly those NYHA III+IV had a very significant percentage of complications, particularly at the 4.8 follow-up. Surprisingly, 20% of patient controls developed MVD at 4.8-year follow-up and were carriers of these genotypes. Thus, the associations observed seem to suggest that the two SNPs might represent useful biomarkers and targets for preventing and monitoring MVDs and developing personalized treatments, consenting a more appropriate management and outcome. Copyright © 2016

  3. Relationship of {sup 99m}Tc-HYNIC annexin V uptake to microvessel density, FasL and MMP-9 expression, and the number of tumour-infiltrating lymphocytes in head and neck carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Vermeersch, Hubert; Loose, David [Department of Head and Neck Surgery, University Hospital Ghent (Belgium); Mervillie, Kris; Cuvelier, Claude [Department of Pathology, University Hospital Ghent (Belgium); Lahorte, Christophe; Slegers, Guido [Department of Radiopharmacy, Ghent University (Belgium); Dierck, Rudi Andre; Van de Wiele, Christophe [Division of Nuclear Medicine, University Hospital Ghent, De Pintelaan 185B, 9000, Ghent (Belgium); Steinmetz, Neil [Theseus Imaging Corporation, Cambridge, Massachusetts (United States)

    2004-07-01

    This study reports on the relationship between quantitative {sup 99m}Tc-HYNIC radiolabelled annexin V tumour uptake measurements, Fas ligand (FasL) expression, matrix metalloproteinase-9 (MMP-9) expression, microvessel density (MVD) and the number of tumour-infiltrating lymphocytes in squamous cell carcinoma of the head and neck (SCCHN) patients. Twenty-eight patients (24 men and 4 women; mean age 59 years, range 43-83 years) suffering from a primary (n, number of patients=22) or locally recurrent (n=6) SCCHN were studied. All patients underwent a spiral CT scan, allowing estimation of lesion size in three dimensions, and {sup 99m}Tc-HYNIC annexin V scintigraphy within 1 week of each other. Biopsies or resection of the suspected primary tumour or local recurrence for histopathological analysis were performed on all patients within a period of 10 days following {sup 99m}Tc-HYNIC annexin V scintigraphy. The percentage uptake of the injected dose of {sup 99m}Tc-HYNIC annexin V in visible tumour lesions on scintigrams divided by the tumour volume, derived from CT, was related to MVD and to histological score (HSCORE) values for MMP-9 and FasL expression as well as to the number of tumour-infiltrating lymphocytes (CD45 staining). Median percentage absolute tumour uptake of the injected dose/cm{sup 3} tumour volume derived from tomographic images was 0.0001% (SD 0.0001%) at 5-6 h p.i. (range: 0.000007-0.0003%). Mean HSCORE for MMP-9 tumour staining was 2.1 (SD 0.84). Mean HSCORE for FasL tumour staining was 2.49 (SD 0.92). At the sites of tumour containing the highest number of vessels, the mean MVD was 20 vessels/field at the hot spot (range 1-73). The median number of tumour-infiltrating lymphocytes was 500 (range 100-5,000). The percentage absolute tumour uptake of the injected dose/cm{sup 3} tumour volume derived from tomographic images correlated linearly with FasL HSCORES(r=0.47, P=0.02). No correlation was found between the percentage absolute tumour uptake of the

  4. Relationship of 99mTc-HYNIC annexin V uptake to microvessel density, FasL and MMP-9 expression, and the number of tumour-infiltrating lymphocytes in head and neck carcinoma

    International Nuclear Information System (INIS)

    Vermeersch, Hubert; Loose, David; Mervillie, Kris; Cuvelier, Claude; Lahorte, Christophe; Slegers, Guido; Dierck, Rudi Andre; Van de Wiele, Christophe; Steinmetz, Neil

    2004-01-01

    This study reports on the relationship between quantitative 99m Tc-HYNIC radiolabelled annexin V tumour uptake measurements, Fas ligand (FasL) expression, matrix metalloproteinase-9 (MMP-9) expression, microvessel density (MVD) and the number of tumour-infiltrating lymphocytes in squamous cell carcinoma of the head and neck (SCCHN) patients. Twenty-eight patients (24 men and 4 women; mean age 59 years, range 43-83 years) suffering from a primary (n, number of patients=22) or locally recurrent (n=6) SCCHN were studied. All patients underwent a spiral CT scan, allowing estimation of lesion size in three dimensions, and 99m Tc-HYNIC annexin V scintigraphy within 1 week of each other. Biopsies or resection of the suspected primary tumour or local recurrence for histopathological analysis were performed on all patients within a period of 10 days following 99m Tc-HYNIC annexin V scintigraphy. The percentage uptake of the injected dose of 99m Tc-HYNIC annexin V in visible tumour lesions on scintigrams divided by the tumour volume, derived from CT, was related to MVD and to histological score (HSCORE) values for MMP-9 and FasL expression as well as to the number of tumour-infiltrating lymphocytes (CD45 staining). Median percentage absolute tumour uptake of the injected dose/cm 3 tumour volume derived from tomographic images was 0.0001% (SD 0.0001%) at 5-6 h p.i. (range: 0.000007-0.0003%). Mean HSCORE for MMP-9 tumour staining was 2.1 (SD 0.84). Mean HSCORE for FasL tumour staining was 2.49 (SD 0.92). At the sites of tumour containing the highest number of vessels, the mean MVD was 20 vessels/field at the hot spot (range 1-73). The median number of tumour-infiltrating lymphocytes was 500 (range 100-5,000). The percentage absolute tumour uptake of the injected dose/cm 3 tumour volume derived from tomographic images correlated linearly with FasL HSCORES(r=0.47, P=0.02). No correlation was found between the percentage absolute tumour uptake of the injected dose/cm 3 tumour

  5. Patients with hepatic breast cancer metastases demonstrate highly specific profiles of matrix metalloproteinases MMP-2 and MMP-9 after SIRT treatment as compared to other primary and secondary liver tumours

    International Nuclear Information System (INIS)

    Golubnitschaja, Olga; Yeghiazaryan, Kristina; Stricker, Helena; Trog, Daniela; Schild, Hans H.; Berliner, Leonard

    2016-01-01

    Patients with primary and metastatic liver malignancies represent a highly heterogeneous patient pool characterised by some of the shortest life expectancies amongst oncology patients. Investigation and better understanding of liver malignancies is an emerging field which requires high-quality multidisciplinary research and collaboration. A study of 158 patients with primary hepatic carcinomas and secondary liver metastases, altogether 15 cancer types of different origin, who underwent selective internal radiation therapy (SIRT) with Yttrium 90 or transarterial chemoembolisation, was undertaken in an effort to detect distinguishing features with respect to activity profiles of both blood matrix metalloproteinase (MMP-2 and MMP-9). Noteworthy, stratification of all hepatic cancer groups with respect to MMP-2 and MMP-9 activities revealed characteristic patterns specifically in patients with hepatic breast cancer metastases who had undergone SIRT. In contrast to all other groups, these patients demonstrated well-consolidated profiles of both MMPs, reflecting a common feature, namely an immediate and durable increase of their activity after the SIRT treatment. Although the total number of patients in the breast cancer group is relatively small (15 patients), since increased activities of MMP-2 and MMP-9 are well known prognostic factors for poor outcomes of oncologic patients, the significance and clear group-specificity (from 15 ones investigated here) of this previously unanticipated finding requires particular attention and further investigations. Particularly important is to determine, whether this increase of the metalloproteinase activity was provoked by SIRT, as well as whether special selection criteria are required for patients with breast cancer metastases to the liver who are being considered for SIRT. It is recommended that a more focused, multidisciplinary and large-scaled investigations of the possible adverse effects of SIRT in patients with advanced

  6. Ethanolic extracts of babandotan leaves (Ageratum conyzoides L.) prevents inflammation and proteoglycan degradation by inhibiting TNF-α andMMP-9 on osteoarthritis rats induced by monosodium iodoacetate

    Institute of Scientific and Technical Information of China (English)

    Anton Bahtiar; Mutiara Nurazizah; Tirza Roselina; Anita Paulina Tambunan; Ade Arsianti

    2017-01-01

    Objective: To analyze the effects of Ageratum conyzoides L. on the monosodium iodoacetate induced osteoarthritis rats. Methods: Thin layer chromatography was performed to analyze the constituents of the babandotan extract leaves. White male Sprague-Dawley rats used in this study were divided into 6 groups: normal control and negative control groups, both given 0.5% carboxymethyl cellulose; the positive control group that was given glucosamine and chondroitin suspension (486 mg/200 g B.W.); the 3 dose variation extract groups including dose 1, 2, and 3 that were given 40, 80, and 160 mg/200 g B.W. respectively on day 29 until 50. All the groups were induced with 0.05 mL monosodium iodoacetate (20 mg/mL) on day 1, except normal control induced by saline. Measurement of edema volume of rat knees was performed on day 0, 8, 15, 22, 29, 43, and 50. Hematology data was measured at day 1, 29 and 50. Serum was collected at day 50 to evaluate TNF-α and MMP-9 by ELISA. Cartilagehistopathology was evaluated by staining with H&E and Safranin-o-fast green staining on day 50. Results: The babandotan leaves extract dose 2 (80 mg/200 g B.W.) and dose 3 (160 mg/200 g B.W.) could decrease the edema volume, increase the area and thickness of articular cartilage, and increase proteoglycan level. Particularly, dose 3 (160 mg/200 g B.W.) of extract babandotan leaves were able to significantly decrease the number of leukocytes, lymphocytes and udem volume, and decrease TNF alpha and MMP-9 levels. Conclusions: Babandotan leaves extract can recover inflammation and cartilages degradation by inhibiting TNF-α ininflammation processes and MMP-9 in the collagenase reaction in the cartilages.

  7. Recombinant human brain natriuretic peptide attenuates trauma-/haemorrhagic shock-induced acute lung injury through inhibiting oxidative stress and the NF-κB-dependent inflammatory/MMP-9 pathway.

    Science.gov (United States)

    Song, Zhi; Zhao, Xiu; Liu, Martin; Jin, Hongxu; Wang, Ling; Hou, Mingxiao; Gao, Yan

    2015-12-01

    Acute lung injury (ALI) is one of the most serious complications in traumatic patients and is an important part of multiple organ dysfunction syndrome (MODS). Recombinant human brain natriuretic peptide (rhBNP) is a peptide with a wide range of biological activity. In this study, we investigated local changes in oxidative stress and the NF-κB-dependent matrix metalloproteinase-9 (MMP-9) pathway in rats with trauma/haemorrhagic shock (TH/S)-induced ALI and evaluated the effects of pretreatment with rhBNP. Forty-eight rats were randomly divided into four groups: sham operation group, model group, low-dosage rhBNP group and high-dosage rhBNP group (n = 12 for each group). Oxidative stress and MPO activity were measured by ELISA kits. MMP-9 activity was detected by zymography analysis. NF-κB activity was determined using Western blot assay. With rhBNP pretreatment, TH/S-induced protein leakage, increased MPO activity, lipid peroxidation and metalloproteinase (MMP)-9 activity were inhibited. Activation of antioxidative enzymes was reversed. The phosphorylation of NF-κB and the degradation of its inhibitor IκB were suppressed. The results suggested that the protection mechanism of rhBNP is possibly mediated through upregulation of anti-oxidative enzymes and inhibition of NF-κB activation. More studies are needed to further evaluate whether rhBNP is a suitable candidate as an effective inhaling drug to reduce the incidence of TH/S-induced ALI. © 2016 The Authors. International Journal of Experimental Pathology © 2016 International Journal of Experimental Pathology.

  8. Th, U, Ra and rare earth element distributions in farm animal tissues from an elevated natural radiation background environment

    International Nuclear Information System (INIS)

    Linsalata, Paul; Morse, Robert; Ford, Helen; Eisenbud, Merril; Franca, E.P.; de Castro, M.B.; Lobao, Nazyo; Sachett, Ivanor; Carlos, Marcia

    1991-01-01

    A field study was conducted in an area of elevated natural background radioactivity (the Pocos de Caldas plateau, Brazil) to assess tissue concentrations and the comparative bioavailability of isotopic Th (IV), U (IV, VI), Ra (II) and light rare earth elements (REE), i.e. La (III) and Ce (III, IV) in adult steers, pigs and chickens. The assessment of comparative bioavailability was aided by normalizing tissue concentrations to local soil concentrations, i.e. by calculating soil-to-tissue concentration ratios (CRs). Mean CRs (for muscle/soil) in these animals were very similar for U, La and Th which, as a group, decreased among the farm animals sampled as (all x 10 -4 ): chicken (1) ≥ steer (0.7) ≥ pig (0.4). For 226 Ra, CRs in muscle decreased in the same order among animals although mean values were 3-5 times greater than those quoted. Much greater values and greater differences among the elements are noted for bone/soil CRs, which for all animals decreased as: Ra >> U > La=Th, indicating the order of elemental bioavailability (assuming bone to be the major retention compartment). Isotopic ratios in farm animal tissue are shown to resemble closely those in soils over which the animals forage, with few exceptions, indicating the importance of the soil component in the transfer of these elements to tissues. (author)

  9. Immunohistochemical detection of metalloproteinase-9 (MMP-9, anti-oxidant like 1 protein (AOP-1 and synaptosomal-associated protein (SNAP-25 in the cerebella of dogs naturally infected with spontaneous canine distemper

    Directory of Open Access Journals (Sweden)

    Tereza C. Cardoso

    2011-04-01

    Full Text Available In most viral infections of the central nervous system (CNS, the integrity of brain extracelluar matrix (ECM, oxidative stress and dysfunction in neuronal transmission may contribute to the observed pathology. The purpose of this study was to investigate the role of these factors in demyelinating canine distemper virus (CDV infections. Regardless of ECM integrity, the expression of metalloproteinase-9 (MMP-9 was visualized in microglial-like cells, whereas the expression of anti-oxidant like-1 (AOP-1 and synaptosomal associated protein (SNAP-25 was frequently detected in Purkinje cells (r2 = 0.989; p < 0.05, regardless of whether the lesions were classified as acute or chronic. Increased numbers of immunolabeled microglia-like cells and reactive gliosis were observed in advanced cases of demyelinating CDV, suggesting that the expression of AOP-1 and SNAP-25 is correlated with the ultimate death of affected cells. Our findings bring a new perspective to understanding the role of the AOP-1, MMP-9 and SNAP-25 proteins in mediating chronic leukoencephalitis caused by CDV. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 1, pp. 41–48

  10. In vitro progesterone modulation on bacterial endotoxin-induced production of IL-1β, TNFα, IL-6, IL-8, IL-10, MIP-1α, and MMP-9 in pre-labor human term placenta.

    Science.gov (United States)

    Garcia-Ruíz, G; Flores-Espinosa, P; Preciado-Martínez, E; Bermejo-Martínez, L; Espejel-Nuñez, A; Estrada-Gutierrez, G; Maida-Claros, R; Flores-Pliego, A; Zaga-Clavellina, Veronica

    2015-10-07

    During human pregnancy, infection/inflammation represents an important factor that increases the risk of developing preterm labor. The purpose of this study was to determine if pre-treatment with progesterone has an immunomodulatory effect on human placenta production of endotoxin-induced inflammation and degradation of extracellular matrix markers. Placentas were obtained under sterile conditions from pregnancies delivered at term before the onset of labor by cesarean section. Explants from central cotyledons of 10 human placentas were pre-treated with different concentrations of progesterone (0.01, 01, 1.0 μM) and then stimulated with 1000 ng/mL of LPS of Escherichia coli. Cytokines TNFα, IL-1β, IL-6, IL-8, MIP-1α, IL-10 concentrations in the culture medium were then measured by specific ELISA. Secretion profile of MMP-9 was evaluated by ELISA and zymogram. Statistical differences were determined by one-way ANOVA followed by the appropriate ad hoc test; P progesterone significantly blunted (73, 56, 56, 75, 25, 48 %) the secretion of TNF-α, IL-1β, IL-6, IL-8, MIP-1α, IL-10, respectively. The MMP-9 induced by LPS treatment was inhibited only with the highest concentration of progesterone. Mifepristone (RU486) blocked the immunosuppressive effect of progesterone. The present results support the concept that progesterone could be part of the compensatory mechanism that limits the inflammation-induced cytotoxic effects associated with an infection process during gestation.

  11. Ultrasensitive multi-analyte electrochemical immunoassay based on GNR-modified heated screen-printed carbon electrodes and PS@PDA-metal labels for rapid detection of MMP-9 and IL-6.

    Science.gov (United States)

    Shi, Jian-Jun; He, Ting-Ting; Jiang, Fang; Abdel-Halim, E S; Zhu, Jun-Jie

    2014-05-15

    An ultrasensitive electrochemical immunoassay was developed for rapid detection of interleukin-6 (IL-6) and matrix metallopeptidase-9 (MMP-9); the method utilized PS@PDA-metal nanocomposites based on graphene nanoribbon (GNR)-modified heated screen-printed carbon electrode (HSPCE). Because of the good hydrophilicity and low toxicity, GNRs were used to immobilize antibodies (Ab) and amplify the electrochemical signal. PS@PDA-metal was used to label antibodies and generate a strong electrochemical signal in acetic buffer. A sandwich strategy was adopted to achieve simultaneous detection of MMP-9 and IL-6 based on HSPCE without cross-talk between adjacent electrodes in the range of 10(-5) to 10(3) ng mL(-1) with detection limits of 5 fg mL(-1) and 0.1 pg mL(-1) (S/N=3), respectively. The proposed method showed wide detection range, low detection limit, acceptable stability and good reproducibility. Satisfactory results were also obtained in the practical samples, thus showing this is a promising technique for simultaneous clinical detection of biocomponent proteins. © 2013 Elsevier B.V. All rights reserved.

  12. MMP9 but Not EGFR, MET, ERCC1, P16, and P-53 Is Associated with Response to Concomitant Radiotherapy, Cetuximab, and Weekly Cisplatin in Patients with Locally Advanced Head and Neck Cancer

    Directory of Open Access Journals (Sweden)

    George Fountzilas

    2009-01-01

    Full Text Available Concomitant administration of radiotherapy with cisplatin or radiotherapy with cetuximab appear to be the treatment of choice for patients with locally advanced head and neck cancer. In the present retrospective analysis, we investigated the predictive role of several biomarkers in an unselected cohort of patients treated with concomitant radiotherapy, weekly cisplatin, and cetuximab (CCRT. We identified 37 patients treated with this approach, of which 13 (35% achieved a complete response and 10 (27% achieved a partial response. Severe side effects were mainly leucopenia, dysphagia, rash, and anemia. Tumor EGFR, MET, ERCC1, and p-53 protein and/or gene expression were not associated with treatment response. In contrast, high MMP9 mRNA expression was found to be significantly associated with objective response. In conclusion, CCRT is feasible and active. MMP9 was the only biomarker tested that appears to be of predictive value in cetuximab treated patients. However, this is a hypothesis generating study and the results should not be viewed as definitive evidence until they are validated in a larger cohort.

  13. Unexpected competitiveness of Methanosaeta populations at elevated acetate concentrations in methanogenic treatment of animal wastewater.

    Science.gov (United States)

    Chen, Si; Cheng, Huicai; Liu, Jiang; Hazen, Terry C; Huang, Vicki; He, Qiang

    2017-02-01

    Acetoclastic methanogenesis is a key metabolic process in anaerobic digestion, a technology with broad applications in biogas production and waste treatment. Acetoclastic methanogenesis is known to be performed by two archaeal genera, Methanosaeta and Methanosarcina. The conventional model posits that Methanosaeta populations are more competitive at low acetate levels (competitiveness of Methanosaeta at elevated acetate was further supported by the enrichment of Methanosaeta with high concentrations of acetate (20 mM). The dominance of Methanosaeta in the methanogen community could be reproduced in anaerobic digesters with the direct addition of acetate to above 20 mM, again supporting the competitiveness of Methanosaeta over Methanosarcina at elevated acetate levels. This study for the first time systematically demonstrated that the dominance of Methanosaeta populations in anaerobic digestion could be linked to the competitiveness of Methanosaeta at elevated acetate concentrations. Given the importance of acetoclastic methanogenesis in biological methane production, findings from this study could have major implications for developing strategies for more effective control of methanogenic treatment processes.

  14. Higher expression of vascular endothelial growth factor (VEGF and its receptor VEGFR-2 (Flk-1 and metalloproteinase-9 (MMP-9 in a rat model of peritoneal endometriosis is similar to cancer diseases

    Directory of Open Access Journals (Sweden)

    Nasciutti Luiz E

    2010-01-01

    Full Text Available Abstract Background Endometriosis is a common disease characterized by the presence of a functional endometrium outside the uterine cavity, causing pelvic pain, dysmenorrheal, and infertility. This disease has been associated to development of different types of malignancies; therefore new blood vessels are essential for the survival of the endometrial implant. Our previous observations on humans showed that angiogenesis is predominantly found in rectosigmoid endometriosis, a deeply infiltrating disease. In this study, we have established the experimental model of rat peritoneal endometriosis to evaluate the process of angiogenesis and to compare with eutopic endometrium. Methods We have investigated the morphological characteristics of these lesions and the vascular density, VEGF and its receptor Flk-1 and MMP-9 expression, and activated macrophage distribution, using immunohistochemistry and RT-PCR. Results As expected, the auto-transplantation of endometrium pieces into the peritoneal cavity is a well-established method for endometriosis induction in rats. The lesions were cystic and vascularized, and demonstrated histological hallmarks of human pathology, such as endometrial glands and stroma. The vascular density and the presence of VEGF and Flk-1 and MMP-9 were significantly higher in endometriotic lesions than in eutopic endometrium, and confirmed the angiogenic potential of these lesions. We also observed an increase in the number of activated macrophages (ED-1 positive cells in the endometriotic lesions, showing a positive correlation with VEGF. Conclusion The present endometriosis model would be useful for investigation of the mechanisms of angiogenesis process involved in the peritoneal attachment of endometrial cells, as well as of the effects of therapeutic drugs, particularly with antiangiogenic activity.

  15. Hericium erinaceus Inhibits TNF-α-Induced Angiogenesis and ROS Generation through Suppression of MMP-9/NF-κB Signaling and Activation of Nrf2-Mediated Antioxidant Genes in Human EA.hy926 Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Hebron C. Chang

    2016-01-01

    Full Text Available Hericium erinaceus (HE is an edible mushroom that has been shown to exhibit anticancer and anti-inflammatory activities. We investigated the antiangiogenic and antioxidant potentials of ethanol extracts of HE in human endothelial (EA.hy926 cells upon tumor necrosis factor-α- (TNF-α- stimulation (10 ng/mL. The underlying molecular mechanisms behind the pharmacological efficacies were elucidated. We found that noncytotoxic concentrations of HE (50–200 μg/mL significantly inhibited TNF-α-induced migration/invasion and capillary-like tube formation of endothelial cells. HE treatment suppressed TNF-α-induced activity and/or overexpression of matrix metalloproteinase-9 (MMP-9 and intercellular adhesion molecule-1 (ICAM-1. Furthermore, HE downregulated TNF-α-induced nuclear translocation and transcriptional activation of nuclear factor-κB (NF-κB followed by suppression of I-κB (inhibitor-κB degradation. Data from fluorescence microscopy illustrated that increased intracellular ROS production upon TNF-α-stimulation was remarkably inhibited by HE pretreatment in a dose-dependent manner. Notably, HE triggered antioxidant gene expressions of heme oxygenase-1 (HO-1, γ-glutamylcysteine synthetase (γ-GCLC, and glutathione levels, which may contribute to inhibition of ROS. Increased antioxidant status was associated with upregulated nuclear translocation and transcriptional activation of NF-E2 related factor-2 (Nrf2 in HE treated cells. Our findings conclude that antiangiogenic and anti-inflammatory activities of H. erinaceus may contribute to its anticancer property through modulation of MMP-9/NF-κB and Nrf2-antioxidant signaling pathways.

  16. Hericium erinaceus Inhibits TNF-α-Induced Angiogenesis and ROS Generation through Suppression of MMP-9/NF-κB Signaling and Activation of Nrf2-Mediated Antioxidant Genes in Human EA.hy926 Endothelial Cells.

    Science.gov (United States)

    Chang, Hebron C; Yang, Hsin-Ling; Pan, Jih-Hao; Korivi, Mallikarjuna; Pan, Jian-You; Hsieh, Meng-Chang; Chao, Pei-Min; Huang, Pei-Jane; Tsai, Ching-Tsan; Hseu, You-Cheng

    2016-01-01

    Hericium erinaceus (HE) is an edible mushroom that has been shown to exhibit anticancer and anti-inflammatory activities. We investigated the antiangiogenic and antioxidant potentials of ethanol extracts of HE in human endothelial (EA.hy926) cells upon tumor necrosis factor-α- (TNF-α-) stimulation (10 ng/mL). The underlying molecular mechanisms behind the pharmacological efficacies were elucidated. We found that noncytotoxic concentrations of HE (50-200 μg/mL) significantly inhibited TNF-α-induced migration/invasion and capillary-like tube formation of endothelial cells. HE treatment suppressed TNF-α-induced activity and/or overexpression of matrix metalloproteinase-9 (MMP-9) and intercellular adhesion molecule-1 (ICAM-1). Furthermore, HE downregulated TNF-α-induced nuclear translocation and transcriptional activation of nuclear factor-κB (NF-κB) followed by suppression of I-κB (inhibitor-κB) degradation. Data from fluorescence microscopy illustrated that increased intracellular ROS production upon TNF-α-stimulation was remarkably inhibited by HE pretreatment in a dose-dependent manner. Notably, HE triggered antioxidant gene expressions of heme oxygenase-1 (HO-1), γ-glutamylcysteine synthetase (γ-GCLC), and glutathione levels, which may contribute to inhibition of ROS. Increased antioxidant status was associated with upregulated nuclear translocation and transcriptional activation of NF-E2 related factor-2 (Nrf2) in HE treated cells. Our findings conclude that antiangiogenic and anti-inflammatory activities of H. erinaceus may contribute to its anticancer property through modulation of MMP-9/NF-κB and Nrf2-antioxidant signaling pathways.

  17. Animals

    International Nuclear Information System (INIS)

    Skuterud, L.; Strand, P.; Howard, B.J.

    1997-01-01

    The radionuclides of most concern with respect to contamination of animals after a nuclear accident are radioiodine, radiocaesium and radiostrontium (ICRP 30, 1979). Of the other significant anthropogenic radionuclides likely to be released in most accidents, only small proportions of that ingested will be absorbed in an animals gut, and the main animal products, milk and meat, will not normally be contaminated to a significant extent. Animal products will mostly be contaminated as a result of ingestion of contaminated feed and possibly, but to a much lesser extent, from inhalation (for radioiodine only). Direct external contamination of animals is of little or no consequence in human food production. Radioiodine and radiostrontium are important with respect to contamination of milk; radiocaesium contaminates both milk and meat. The physical and chemical form of a radionuclide can influence its absorption in the animal gut. For example, following the Chernobyl accident radiocaesium incorporated into vegetation by root uptake was more readily absorbed than that associated with the original deposit. The transfer of radiocaesium and radiostrontium to animals will be presented both as transfer coefficients and aggregated transfer coefficients. For most animal meat products, only radiocaesium is important as other radionuclides do not significantly contaminate muscle. Farm animal products are the most important foodstuff determining radiocaesium intake by the average consumer in the Nordic countries. The major potential source of radioiodine and radiostrontium to humans is milk and milk products. Of the different species, the smaller animals have the highest transfer of radiocaesium from fodder to meat and milk. (EG)

  18. Animator

    Science.gov (United States)

    Tech Directions, 2008

    2008-01-01

    Art and animation work is the most significant part of electronic game development, but is also found in television commercials, computer programs, the Internet, comic books, and in just about every visual media imaginable. It is the part of the project that makes an abstract design idea concrete and visible. Animators create the motion of life in…

  19. Animals

    Energy Technology Data Exchange (ETDEWEB)

    Skuterud, L.; Strand, P. [Norwegian Radiation Protection Authority (Norway); Howard, B.J. [Inst. of Terrestrial Ecology (United Kingdom)

    1997-10-01

    The radionuclides of most concern with respect to contamination of animals after a nuclear accident are radioiodine, radiocaesium and radiostrontium (ICRP 30, 1979). Of the other significant anthropogenic radionuclides likely to be released in most accidents, only small proportions of that ingested will be absorbed in an animals gut, and the main animal products, milk and meat, will not normally be contaminated to a significant extent. Animal products will mostly be contaminated as a result of ingestion of contaminated feed and possibly, but to a much lesser extent, from inhalation (for radioiodine only). Direct external contamination of animals is of little or no consequence in human food production. Radioiodine and radiostrontium are important with respect to contamination of milk; radiocaesium contaminates both milk and meat. The physical and chemical form of a radionuclide can influence its absorption in the animal gut. For example, following the Chernobyl accident radiocaesium incorporated into vegetation by root uptake was more readily absorbed than that associated with the original deposit. The transfer of radiocaesium and radiostrontium to animals will be presented both as transfer coefficients and aggregated transfer coefficients. For most animal meat products, only radiocaesium is important as other radionuclides do not significantly contaminate muscle. Farm animal products are the most important foodstuff determining radiocaesium intake by the average consumer in the Nordic countries. The major potential source of radioiodine and radiostrontium to humans is milk and milk products. Of the different species, the smaller animals have the highest transfer of radiocaesium from fodder to meat and milk. (EG). 68 refs.

  20. MMP1, MMP9, and COX2 Expressions in Promonocytes Are Induced by Breast Cancer Cells and Correlate with Collagen Degradation, Transformation-Like Morphological Changes in MCF-10A Acini, and Tumor Aggressiveness

    Directory of Open Access Journals (Sweden)

    G. K. Chimal-Ramírez

    2013-01-01

    Full Text Available Tumor-associated immune cells often lack immune effector activities, and instead they present protumoral functions. To understand how tumors promote this immunological switch, invasive and noninvasive breast cancer cell (BRC lines were cocultured with a promonocytic cell line in a Matrigel-based 3D system. We hypothesized that if communication exists between tumor and immune cells, coculturing would result in augmented expression of genes associated with tumor malignancy. Upregulation of proteases MMP1 and MMP9 and inflammatory COX2 genes was found likely in response to soluble factors. Interestingly, changes were more apparent in promonocytes and correlated with the aggressiveness of the BRC line. Increased gene expression was confirmed by collagen degradation assays and immunocytochemistry of prostaglandin 2, a product of COX2 activity. Untransformed MCF-10A cells were then used as a sensor of soluble factors with transformation-like capabilities, finding that acini formed in the presence of supernatants of the highly aggressive BRC/promonocyte cocultures often exhibited total loss of the normal architecture. These data support that tumor cells can modify immune cell gene expression and tumor aggressiveness may importantly reside in this capacity. Modeling interactions in the tumor stroma will allow the identification of genes useful as cancer prognostic markers and therapy targets.

  1. Development towards compact nitrocellulose interferometric biochips for dry eye diagnosis based on MMP9, S100A6 and CST4 biomarkers using a Point-of-Care device

    Science.gov (United States)

    Santamaría, Beatriz; Laguna, María. Fe; López-Romero, David; López-Hernandez, A.; Sanza, F. J.; Lavín, A.; Casquel, R.; Maigler, M.; Holgado, M.

    2018-02-01

    A novel compact optical biochip based on a thin layer-sensing BICELL surface of nitrocellulose is used for in-situ labelfree detection of dry eye disease (DED). In this work the development of a compact biosensor that allows obtaining quantitative diagnosis with a limited volume of sample is reported. The designed sensors can be analyzed with an optical integrated Point-of-Care read-out system based on the "Increase Relative Optical Power" principle which enhances the performance and Limit of Detection. Several proteins involved with dry eye dysfunction have been validated as biomarkers. Presented biochip analyzes three of those biomarkers: MMP9, S100A6 and CST4. BICELLs based on nitrocellulose permit to immobilize antibodies for each biomarker recognition. The optical response obtained from the biosensor through the readout platform is capable to recognize specifically the desired proteins in the concentrations range for control eye (CE) and dry eye syndrome (DES). Preliminary results obtained will allow the development of a dry eye detection device useful in the area of ophthalmology and applicable to other possible diseases related to the eye dysfunction.

  2. A smart pH-responsive nano-carrier as a drug delivery system for the targeted delivery of ursolic acid: suppresses cancer growth and metastasis by modulating P53/MMP-9/PTEN/CD44 mediated multiple signaling pathways.

    Science.gov (United States)

    Jiang, Kai; Chi, Ting; Li, Tao; Zheng, Guirong; Fan, Lulu; Liu, Yajun; Chen, Xiufen; Chen, Sijia; Jia, Lee; Shao, Jingwei

    2017-07-13

    Ursolic acid (UA) has been recently used as a promising anti-tumor and cancer metastatic chemo-preventive agent due to its low toxicity and liver-protecting property. However, the low bioavailability and nonspecific tumor targeting restrict its further clinical application. To address the problem, a silica-based mesoporous nanosphere (MSN) controlled-release drug delivery system (denoted UA@M-CS-FA) was designed and successfully synthesized, and was functionalized with folic acid (FA) and pH-sensitive chitosan (CS) for the targeted delivery of UA to folate receptor (FR) positive tumor cells. UA@M-CS-FA were spherical with mean diameter below 150 nm, and showed about -20 mV potential. Meanwhile, UA@M-CS-FA exhibited a pH-sensitive release manner and high cellular uptake in FR over-expressing HeLa cancer cells. Also, in vitro cellular assays suggested that UA@M-CS-FA inhibited cancer cell growth, invasion and migration. Mechanistically, UA@M-CS-FA induced cancer cell apoptosis and inhibited migration via cell cycle arrest in the G0/G1 stage, regulating the PARP/Bcl-2/MMP-9/CD44/PTEN/P53. Importantly, in vivo experiments further confirmed that UA@M-CS-FA significantly suppressed the tumor progression and lung metastasis in tumor-bearing nude mice. Immunohistochemical analysis revealed that UA@M-CS-FA treatment regulated CD44, a biomarker of cancer metastasis. Overall, our data demonstrated that a CS and FA modified MSN controlled-release drug delivery system could help broaden the usage of UA and reflect the great application potential of the UA as an anticancer or cancer metastatic chemopreventive agent.

  3. Evaluation of point-of-care test for elevated tear matrix metalloproteinase 9 in post-LASIK dry eyes.

    Science.gov (United States)

    Chan, Tommy C Y; Ye, Cong; Chan, Kwok Ping; Chu, Kai On; Jhanji, Vishal

    2016-09-01

    To evaluate the performance of a point-of-care test for detection of matrix metalloproteinase 9 (MMP-9) levels in post-laser-assisted in situ keratomileusis (LASIK) dry eyes. A comparative study between patients with mild to moderate post-LASIK dry eyes and age-matched normal subjects was conducted. Ocular surface disease index (OSDI), tear break-up time (TBUT), and tear film MMP-9 and total protein levels were compared between the two groups. A point-of-care test device (RPS InflammaDry, Sarasota, Florida, USA) was utilised to confirm elevated MMP-9 levels in tear film. Fourteen post-LASIK dry eyes and 34 normal eyes were included. There was no significant difference in age and gender between both groups (p>0.175). The OSDI was significantly higher (25.5±7.7 vs 7.4±2.5; pdry eye compared with normal subjects. The tear film MMP-9 levels were 52.7±32.5 ng/mL in dry eyes and 4.1±2.1 ng/mL in normal eyes (p40 ng/mL in 7/14 (50.0%) post-LASIK dry eyes. The InflammaDry was positive in 8/14 (57.1%) post-LASIK eyes. All positive cases had tear film MMP-9 levels ≥38.03 ng/mL. Agreement between InflammaDry and MMP-9 was excellent with Cohen κ value of 0.857 in post-LASIK dry eyes. Only half of post-LASIK dry eyes were found to have significant inflammation associated with elevated MMP-9. The OSDI is useful to non-specifically identify patients with symptomatic dry eye while the InflammaDry determined which patients with dry eye were associated with significant inflammation that may guide therapeutic management decisions. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  4. IL-8、 MMP-9、 INF-γ的检测对结核性脑膜炎及病毒性脑膜炎发病的意义%Detection of interleukin-8, matrix metalloproteinase-9 and interferon gamma levels in the cerebrospinal fluid of patients with tuberculous meningitis and viral meningitis

    Institute of Scientific and Technical Information of China (English)

    朱飞; 张家堂; 邢小微; 贺路星; 赵威; 郎森阳; 于生元

    2012-01-01

    目的 探讨脑脊液中白细胞介素-8(IL-8)、基质金属蛋白酶-9(MMP-9)、干扰素-γ(INF-γ)含量的检测对结核性脑膜炎及病毒性脑膜炎的临床诊断价值. 方法 选取解放军总医院、解放军第三0九医院自2010年8月至2011年11月住院的患者,其中结核性脑膜炎组20例,病毒性脑膜炎组15例,非感染性神经系统疾病组20例.用ELISA法检测3组患者脑脊液IL-8、MMP-9、INF-γ含量,并进行比较分析. 结果 结核性脑膜炎组患者脑脊液中IL-8、MMP-9、INF-γ的含量高于病毒性脑膜炎组和非感染性神经系统疾病组差异有统计学意义(P<0.05).病毒性脑膜炎组患者脑脊液中IL-8、MMP-9含量高于非感染性神经系统组(P<0.05).病毒性脑膜炎组患者脑脊液中INF-γ含量与非感染性神经系统疾病组比较差异无统计学意义(P>0.05). 结论 脑脊液中IL-8、MMP-9、INF-γ含量的检测对结核性脑膜炎具有一定的辅助诊断意义.IL-8、MMP-9在病毒性脑膜炎的发病和进展中亦起到一定作用.临床上若在患者脑脊液中检测到高水平的INF-γ,较之IL-8、MMP-9对于结核性脑膜炎更具诊断价值.%Objective To investigate the diagnostic values of interleukin-8 (IL-8), matrix metalloproteinase-9 (MMP-9) and interferon gamma (INF-γ) levels in patients with tuberculous meningitis and viral meningitis by detecting the contents of these biomarkers in the cerebrospinal fluid (CSF). Methods Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of IL-8,MMP-9 and INF-γ in the CSF of patients with tuberculous meningitis (n=20),viral meningitis (n=15) and noninfectious neurologic diseases (n=20) who admitted to our hospital from August 2010 to November 2011. Results The IL-8,MMP-9 and INF-γlevels in the samples from the tuberculous meningitis patients were significantly higher than those from either viral meningitis or noninfectious neurologic diseases (P<0.05).The contents of IL-8

  5. Animal evolution and atmospheric pO2: is there a link between gradual animal adaptation to terrain elevation due to Ural orogeny and survival of subsequent hypoxic periods?

    Science.gov (United States)

    Kurbel, Sven

    2014-10-22

    Considering evolution of terrestrial animals as something happening only on flat continental plains seems wrong. Many mountains have arisen and disappeared over the geologic time scale, so in all periods some areas of high altitude existed, with reduced oxygen pressure (pO2) and increased aridity. During orogeny, animal species of the raising terrain can slowly adapt to reduced oxygen levels.This review proposes that animal evolution was often driven by atmospheric oxygen availability. Transitions of insect ancestors and amphibians out of water are here interpreted as events forced by the lack of oxygen in shallow and warm water during Devonian. Hyperoxia during early Carboniferous allowed giant insects to be predators of lowlands, forcing small amphibians to move to higher terrains, unsuitable to large insects due to reduced pO2. In arid mountainous habitats, ascended animals evolved in early reptiles with more efficient lungs and improved circulation. Animals with alveolar lungs became the mammalian ancestors, while those with respiratory duct lungs developed in archosaurs. In this interpretation, limb precursors of wings and pneumatised bones might have been adaptations for moving on steep slopes.Ural mountains have risen to an estimated height of 3000 m between 318 and 251 Mya. The earliest archosaurs have been found on the European Ural side, estimated 275 Myr old. It is proposed that Ural orogeny slowly elevated several highland habitats within the modern Ural region to heights above 2500 m. Since this process took near 60 Myr, animals in these habitats fully to adapted to hypoxia.The protracted P-Tr hypoxic extinction event killed many aquatic and terrestrial animals. Devastated lowland areas were repopulated by mammaliaformes that came down from mountainous areas. Archosaurs were better adapted to very low pO2, so they were forced to descend to the sea level later when the lack of oxygen became severe. During the Triassic period, when the relative content

  6. The relationship between anxiety and depression in animal models: a study using the forced swimming test and elevated plus-maze

    Directory of Open Access Journals (Sweden)

    R. Andreatini

    1999-09-01

    Full Text Available The present study evaluated the correlation between the behavior of mice in the forced swimming test (FST and in the elevated plus-maze (PM. The effect of the order of the experiments, i.e., the influence of the first test (FST or PM on mouse behavior in the second test (PM or FST, respectively was compared to handled animals (HAND. The execution of FST one week before the plus-maze (FST-PM, N = 10, in comparison to mice that were only handled (HAND-PM, N = 10 in week 1, decreased % open entries (HAND-PM: 33.6 ± 2.9; FST-PM: 20.0 ± 3.9; mean ± SEM; P0.10. A prior test in the plus-maze (PM-FST did not change % immobility time in the FST when compared to the HAND-FST group (HAND-FST: 57.7 ± 3.9; PM-FST: 65.7 ± 3.2; mean ± SEM; P>0.10. Since these data suggest that there is an order effect, the correlation was evaluated separately with each test sequence: FST-PM (N = 20 and PM-FST (N = 18. There was no significant correlation between % immobility time in the FST and plus-maze indexes (% time and entries in open arms in any test sequence (r: -0.07 to 0.18. These data suggest that mouse behavior in the elevated plus-maze is not related to behavior in the forced swimming test and that a forced swimming test before the plus-maze has an anxiogenic effect even after a one-week interval.

  7. Elevating your elevator talk

    Science.gov (United States)

    An important and often overlooked item that every early career researcher needs to do is compose an elevator talk. The elevator talk, named because the talk should not last longer than an average elevator ride (30 to 60 seconds), is an effective method to present your research and yourself in a clea...

  8. Evolution of shear stress, protein expression, and vessel area in an animal model of arterial dilatation in hemodialysis grafts

    Science.gov (United States)

    Misra, Sanjay; Fu, Alex A.; Misra, Khamal D.; Glockner, James F.; Mukhopadyay, Debabrata

    2010-01-01

    Purpose To evaluate the wall shear stress, protein expression of matrix metalloproteinases-2 (MMP-2), -9 (MMP-9), and the inhibitors (tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), and -2 (TIMP-2)), and vessel area over time in a porcine model for hemodialysis polytetrafluoroethylene (PTFE) grafts. Materials and methods In 21 pigs, subtotal renal infarction was performed and 28 days later, a PTFE graft was placed to connect the carotid artery to the ipsilateral jugular vein. Phase contrast MR was used to measure blood flow and vessel area at 1, 3, 7, and 14 days after graft placement. Wall shear stress was estimated from Poiseuille’s law. Animals were sacrificed at day 3 (N=7), day 7 (N=7), and day 14 (N=7) and expression of MMP-2, MMP-9, TIMP-1, and TIMP-2 were determined at the grafted and control arteries. Results The mean wall shear stress of the grafted artery was higher than the control artery at all time points (P<0.05). It peaked by day 3 and decreased by days 7–14 as the vessel area nearly doubled. By days 7–14, there was a significant increase in active MMP-2 followed by a significant increase in pro and active MMP-9 by day 14 (P<0.05, grafted artery versus control). TIMP-1 expression peaked by day 7 and then decreased while TIMP-2 expression was decreased at days 7–14. Conclusions The wall shear stress of the grafted artery peaks by day 3 with increased MMP-2 activity by days 7–14 followed by pro and active MMP-9 by day 14 and the vessel area nearly doubled. PMID:20123196

  9. Local Matrix Metalloproteinase 9 Level Determines Early Clinical Presentation of ST-Segment-Elevation Myocardial Infarction.

    Science.gov (United States)

    Nishiguchi, Tsuyoshi; Tanaka, Atsushi; Taruya, Akira; Emori, Hiroki; Ozaki, Yuichi; Orii, Makoto; Shiono, Yasutsugu; Shimamura, Kunihiro; Kameyama, Takeyoshi; Yamano, Takashi; Yamaguchi, Tomoyuki; Matsuo, Yoshiki; Ino, Yasushi; Kubo, Takashi; Hozumi, Takeshi; Hayashi, Yasushi; Akasaka, Takashi

    2016-12-01

    Early clinical presentation of ST-segment-elevation myocardial infarction (STEMI) and non-ST-segment-elevation myocardial infarction affects patient management. Although local inflammatory activities are involved in the onset of MI, little is known about their impact on early clinical presentation. This study aimed to investigate whether local inflammatory activities affect early clinical presentation. This study comprised 94 and 17 patients with MI (STEMI, 69; non-STEMI, 25) and stable angina pectoris, respectively. We simultaneously investigated the culprit lesion morphologies using optical coherence tomography and inflammatory activities assessed by shedding matrix metalloproteinase 9 (MMP-9) and myeloperoxidase into the coronary circulation before and after stenting. Prevalence of plaque rupture, thin-cap fibroatheroma, and lipid arc or macrophage count was higher in patients with STEMI and non-STEMI than in those with stable angina pectoris. Red thrombus was frequently observed in STEMI compared with others. Local MMP-9 levels were significantly higher than systemic levels (systemic, 42.0 [27.9-73.2] ng/mL versus prestent local, 69.1 [32.2-152.3] ng/mL versus poststent local, 68.0 [35.6-133.3] ng/mL; Pclinical presentation in patients with MI. Local inflammatory activity for atherosclerosis needs increased attention. © 2016 American Heart Association, Inc.

  10. Amniotic fluid MMP-9 and neurotrophins in autism spectrum disorders

    DEFF Research Database (Denmark)

    Abdallah, Morsi; Pearce, Brad D; Larsen, Nanna

    2012-01-01

    Evidence suggests that some developmental disorders, such as autism spectrum disorders (ASDs), are caused by errors in brain plasticity. Given the important role of matrix metalloproteinases (MMPs) and neurotrophins (NTs) in neuroplasticity, amniotic fluid samples for 331 ASD cases and 698...

  11. Matrix Metalloproteinases Contribute to Neuronal Dysfunction in Animal Models of Drug Dependence, Alzheimer's Disease, and Epilepsy

    Directory of Open Access Journals (Sweden)

    Hiroyuki Mizoguchi

    2011-01-01

    Full Text Available Matrix metalloproteinases (MMPs and tissue inhibitors of metalloproteinases (TIMPs remodel the pericellular environment by regulating the cleavage of extracellular matrix proteins, cell surface components, neurotransmitter receptors, and growth factors that mediate cell adhesion, synaptogenesis, synaptic plasticity, and long-term potentiation. Interestingly, increased MMP activity and dysregulation of the balance between MMPs and TIMPs have also been implicated in various pathologic conditions. In this paper, we discuss various animal models that suggest that the activation of the gelatinases MMP-2 and MMP-9 is involved in pathogenesis of drug dependence, Alzheimer's disease, and epilepsy.

  12. Elevated phosphatase of regenerating liver 3 (PRL-3) promotes cytoskeleton reorganization, cell migration and invasion in endometrial stromal cells from endometrioma.

    Science.gov (United States)

    Zhan, Hong; Ma, Junyan; Ruan, Fei; Bedaiwy, Mohamed A; Peng, Bo; Wu, Ruijin; Lin, Jun

    2016-04-01

    Is phosphatase of regenerating liver-3 (PRL-3) associated with increased motility of endometriotic cells from endometrioma? Elevated PRL-3 promotes cytoskeleton reorganization, cell migration and invasion of endometrial stromal cells (ESCs) from endometrioma. Overexpression of PRL-3 is associated with cancer cell migration, invasion and metastatic phenotype. Primary human ESCs were isolated from eutopic endometrium of women without endometriosis (EuCo, n = 10), with histologically proven endometrioma (EuEM, n = 19) and from the cyst wall of ovarian endometriosis (OvEM, n = 26). The expression of PRL-3 in ESCs derived from EuCo, EuEM and OvEM at different phases of menstrual cycle were compared. The protein and mRNA levels of PRL-3 were examined by western blot and RT-qPCR, respectively. ESCs from OvEM were transfected with/without short hairpin RNA (shRNA) or small interfering RNA (siRNA). Additionally, a plasmid-mediated delivery system was used to achieve PRL-3 overexpression in ESCs from EuEM. The cellular distribution of F-actin and α-tubulin were examined by immunocytochemistry. Cell motility was evaluated by a transwell migration/invasion assay. The protein and mRNA levels of PRL-3 are significantly elevated in ESCs from OvEM compared with EuCo and EuEM. The expression of PRL-3 was not altered between proliferative phase and secretory phase in ESCs from all groups. Knockdown of PRL-3 significantly modified the distribution of F-actin and α-tubulin cytoskeleton, inhibited cell migration and invasion. Endogenous inhibition of PRL-3 attenuated the expression of Ras homolog gene family members A and C (RhoA, RhoC), Rho-associated coiled-coil-containing protein kinase 1 (ROCK1) and matrix metalloproteinase (MMP) 9, but not MMP2 in ESCs from OvEM. Additionally, overexpression of PRL-3 in ESCs from EuEM up-regulates cell migration and invasion, and increases the expression of RhoA, RhoC, ROCK1 and MMP9. Lack of in vivo animal studies is the major limitation of our

  13. Inflammation and oxidative stress are elevated in the brain, blood, and adrenal glands during the progression of post-traumatic stress disorder in a predator exposure animal model.

    Science.gov (United States)

    Wilson, C Brad; McLaughlin, Leslie D; Nair, Anand; Ebenezer, Philip J; Dange, Rahul; Francis, Joseph

    2013-01-01

    This study sought to analyze specific pathophysiological mechanisms involved in the progression of post-traumatic stress disorder (PTSD) by utilizing an animal model. To examine PTSD pathophysiology, we measured damaging reactive oxygen species and inflammatory cytokines to determine if oxidative stress and inflammation in the brain, adrenal glands, and systemic circulation were upregulated in response to constant stress. Pre-clinical PTSD was induced in naïve, male Sprague-Dawley rats via a predator exposure/psychosocial stress regimen. PTSD group rats were secured in Plexiglas cylinders and placed in a cage with a cat for one hour on days 1 and 11 of a 31-day stress regimen. In addition, PTSD group rats were subjected to psychosocial stress whereby their cage cohort was changed daily. This model has been shown to cause heightened anxiety, exaggerated startle response, impaired cognition, and increased cardiovascular reactivity, all of which are common symptoms seen in humans with PTSD. At the conclusion of the predator exposure/psychosocial stress regimen, the rats were euthanized and their brains were dissected to remove the hippocampus, amygdala, and pre-frontal cortex (PFC), the three areas commonly associated with PTSD development. The adrenal glands and whole blood were also collected to assess systemic oxidative stress. Analysis of the whole blood, adrenal glands, and brain regions revealed oxidative stress increased during PTSD progression. In addition, examination of pro-inflammatory cytokine (PIC) mRNA and protein demonstrated neurological inflammatory molecules were significantly upregulated in the PTSD group vs. controls. These results indicate oxidative stress and inflammation in the brain, adrenal glands, and systemic circulation may play a critical role in the development and further exacerbation of PTSD. Thus, PTSD may not be solely a neurological pathology but may progress as a systemic condition involving multiple organ systems.

  14. Behavioral assessments of BTBR T+Itpr3tf/J mice by tests of object attention and elevated open platform: Implications for an animal model of psychiatric comorbidity in autism.

    Science.gov (United States)

    Chao, Owen Y; Yunger, Richelle; Yang, Yi-Mei

    2018-07-16

    Autism spectrum disorders (ASD) are diagnosed based on the behavioral criteria of impaired social interaction, defective communication and repetitive behaviors. Psychiatric comorbidities, such as anxiety and intellectual disability, are commonly present in ASD. The BTBR T+ Itpr3tf/J (BTBR) mice display a range of autistic phenotypes, yet whether this mouse model is appropriate to study psychiatric comorbidity in ASD remains unclear. We addressed this issue by subjecting the BTBR animals to three-chambered apparatus, open field, object attention test and elevated open platform. Compared to C57BL/6J control mice, the BTBR mice displayed hyperactivity in most of the tests. In the three-chamber assessment, they exhibited deficits in sociability. In the open field, more grooming and thigmotaxis and less rearing behaviors were observed. They also showed impaired object-based attention. On the elevated open platform, the BTBR animals stayed more to the edges than in the center of the platform. To further examine the properties of this test, naïve C57BL/6J mice were randomly administrated with saline or an anxiogenic substance, caffeine. The caffeine group demonstrated a similar behavioral pattern as the BTBR mice. When the saline group was re-exposed to the same platform, the time they stayed in the center substantially increased, likely due to reduced anxiety by habituation. These results indicate that the BTBR were more anxious than control mice on the open platform. Taken together, the BTBR strain exhibit emotional and cognitive impairments in addition to autistic behaviors, suggesting that they can be a valid model for ASD with psychiatric comorbidity. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Long Noncoding RNA Taurine-Upregulated Gene1 (TUG1) Promotes Tumor Growth and Metastasis Through TUG1/Mir-129-5p/Astrocyte-Elevated Gene-1 (AEG-1) Axis in Malignant Melanoma.

    Science.gov (United States)

    Long, Jianwen; Menggen, Qiqige; Wuren, Qimige; Shi, Quan; Pi, Xianming

    2018-03-15

    BACKGROUND Malignant melanoma is a class of malignant tumors derived from melanocytes. lncRNAs have been considered as pro-/anti-tumor factors in progression of cancers. The function of lncRNA TUG1 on growth of melanoma was investigated in this study. MATERIAL AND METHODS The TUG1 and miR-129-5p expression were examined via qRT-PCR. The protein expression was investigated by Western blotting assay. Luciferase reporter assay was used to assess if lncRNA TUG1 can bind to miR-129-5p and if miR-129-5p can target AEG1 mRNA. CCK-8 and apoptosis assay were used to detect cell growth and apoptosis. The metastasis of melanoma cells was detected by wound-healing and Transwell assays. The effects of TUG1 on growth of melanoma in vivo and cell chemoresistance were investigated via xenograft animal experiment and CCK-8 assay. RESULTS The expression of TUG1 and AEG1 was elevated and the miR-129-5p level was decreased in melanoma specimens and cell lines. Downregulation of either TUG1 or AEG1 suppressed cell growth and metastasis. miR-129-5p can bind directly to AEG1 and TUG1 can directly sponge miR-129-5p. Inhibition of TUG1 expression suppressed the expression of Bcl-2, MMP-9, and cyclin D1, and raised the level of cleaved caspase3 by modulating AEG1 level in melanoma cells. Inhibition of TUG1 reduced the growth of tumors in vivo and improved the chemosensitivity of A375 cells to cisplatin and 5-FU. CONCLUSIONS Reduction of TUG1 level suppressed cell growth and metastasis by regulating AEG1 expression mediated by targeting miR-129-5p. Suppression of lnc TUG1 may be a promising therapeutic strategy in the treatment of malignant melanoma.

  16. Data Elevator

    Energy Technology Data Exchange (ETDEWEB)

    2017-04-29

    Data Elevator: Efficient Asynchronous Data Movement in Hierarchical Storage Systems Multi-layer storage subsystems, including SSD-based burst buffers and disk-based parallel file systems (PFS), are becoming part of HPC systems. However, software for this storage hierarchy is still in its infancy. Applications may have to explicitly move data among the storage layers. We propose Data Elevator for transparently and efficiently moving data between a burst buffer and a PFS. Users specify the final destination for their data, typically on PFS, Data Elevator intercepts the I/O calls, stages data on burst buffer, and then asynchronously transfers the data to their final destination in the background. This system allows extensive optimizations, such as overlapping read and write operations, choosing I/O modes, and aligning buffer boundaries. In tests with large-scale scientific applications, Data Elevator is as much as 4.2X faster than Cray DataWarp, the start-of-art software for burst buffer, and 4X faster than directly writing to PFS. The Data Elevator library uses HDF5's Virtual Object Layer (VOL) for intercepting parallel I/O calls that write data to PFS. The intercepted calls are redirected to the Data Elevator, which provides a handle to write the file in a faster and intermediate burst buffer system. Once the application finishes writing the data to the burst buffer, the Data Elevator job uses HDF5 to move the data to final destination in an asynchronous manner. Hence, using the Data Elevator library is currently useful for applications that call HDF5 for writing data files. Also, the Data Elevator depends on the HDF5 VOL functionality.

  17. An elevator

    Energy Technology Data Exchange (ETDEWEB)

    Loginovskiy, V.I.; Medinger, N.V.; Rasskazov, V.A.; Solonitsyn, V.A.

    1983-01-01

    An elevator is proposed which includes a body, spring loaded cams and a shut-off ring. To increase the reliability of the elevator by eliminating the possibility of spontaneous shifting of the shut-off ring, the latter is equipped with handles hinged to it and is made with evolvent grooves. The cams are equipped with rollers installed in the evolvent grooves of the shut off ring, where the body is made with grooves for the handles.

  18. Monocular Elevation Deficiency - Double Elevator Palsy

    Science.gov (United States)

    ... Español Condiciones Chinese Conditions Monocular Elevation Deficiency/ Double Elevator Palsy En Español Read in Chinese What is monocular elevation deficiency (Double Elevator Palsy)? Monocular Elevation Deficiency, also known by the ...

  19. The use of acute phase proteins for monitoring animal health and welfare in the pig production chain: the validation of an immunochromatographic method for the detection of elevated levels of pig-MAP.

    Science.gov (United States)

    Piñeiro, Matilde; Morales, Joaquín; Vizcaíno, Elena; Murillo, José Alberto; Klauke, Thorsten; Petersen, Brigitte; Piñeiro, Carlos

    2013-11-01

    The serum concentration of acute phase proteins (APPs) increases in the presence of disease or stress, which makes APPs notable parameters for the global assessment of animal health and welfare. A rapid, immunochromatographic test (ICT) for the detection of elevated levels of pig Major Acute-phase Protein (pig-MAP), one of the main APPs in pigs, was evaluated in more than 1400 pig serum samples obtained from commercial farms. The ICT showed a good performance with a relative sensitivity (Sn) and specificity (Sp) of 94 and 97%, respectively, for a threshold of 1.5mg/mL (comparison with ELISA). Differences in the pig-MAP levels and the number of positive samples with the ICT were observed within the season of sampling, farms, and age groups at one farm, according to the presence of disease or lesions. The ICT was also evaluated in blood samples obtained at slaughter in association with the carcase inspection. The results from this study indicate that the ICT may be used for the evaluation of groups of pigs, after analysing one sub-sample of these pigs, and might be a useful tool in routine health and welfare monitoring programmes aimed to improve the quality of pig production. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Elevator wheel

    Energy Technology Data Exchange (ETDEWEB)

    Zhornik, V.I.; Cherkov, Ye.M.; Simonov, A.A.

    1982-01-01

    An elevator wheel is suggested for unloading a sunken product from a bath of a heavy-average separator including discs of a bucket with inner walls, and covering sheets hinged to the buckets. In order to improve the degree of dehydration of the removed product, the inner wall of each bucket is made of sheets installed in steps with gaps of one in relation to the other.

  1. An elevator

    Energy Technology Data Exchange (ETDEWEB)

    Gusev, A.S.; Peshkov, L.P.; Rozin, M.M.; Shestov, A.G.

    1983-01-01

    An elevator is proposed which includes a body, a flap, a lock with a catch and a spring-loaded shut-off clamp in the form of upper and lower horizontal levers which are connected by a handle and an axle and one end of which is made in the form of an eccentric cam. The size of the eccentricity of the cam of the levers is increased toward the handle of the clamp in order to increase the operational reliability and to extend the service life.

  2. An elevator

    Energy Technology Data Exchange (ETDEWEB)

    Rastorguyev, M.A.; Maloyarovslavtesv, D.A.; Prokopov, O.I.; Tukayev, Sh.V.; Zanilov, I.F.

    1983-01-01

    An elevator is proposed which includes a body with a turning collar locking device and a rod with longitudinal grooves, which are flexibly linked with jaws positioned in grooves in the body. To increase safety through ensuring automatic locking of the jaws in the closed position, the locking device is made in the form of head on wedges, spring loaded relative to the collar and made with cams and positioned with the capability of interacting with the grooves of the rod and through the cams with the collar.

  3. Bucket elevator

    OpenAIRE

    Chromek, Jiří

    2013-01-01

    Cílem této bakalářské práce je návrh svislého korečkového elevátoru, který má sloužit k dopravě obilovin s dopravní výškou 19 m a dopravovaným množstvím 100 t/hod. Práce se skládá z popisu korečkového elevátoru a jeho hlavních částí, zmiňující se v úvodní rešerši. Tato práce je zaměřena na funkční a kapacitní výpočet, určení pohonu a napínacího zařízení. Další výpočet je kontrolní, skládající se z pevnostní kontroly hnacího hřídele, výpočtu pera, životnosti ložisek a výpočtu napínacího zaříze...

  4. Animal research

    DEFF Research Database (Denmark)

    Olsson, I.A.S.; Sandøe, Peter

    2012-01-01

    This article presents the ethical issues in animal research using a combined approach of ethical theory and analysis of scientific findings with bearing on the ethical analysis. The article opens with a general discussion of the moral acceptability of animal use in research. The use of animals...... in research is analyzed from the viewpoint of three distinct ethical approaches: contractarianism, utilitarianism, and animal rights view. On a contractarian view, research on animals is only an ethical issue to the extent that other humans as parties to the social contract care about how research animals...... are faring. From the utilitarian perspective, the use of sentient animals in research that may harm them is an ethical issue, but harm done to animals can be balanced by benefit generated for humans and other animals. The animal rights view, when thoroughgoing, is abolitionist as regards the use of animals...

  5. Artemisia argyi attenuates airway inflammation in ovalbumin-induced asthmatic animals.

    Science.gov (United States)

    Shin, Na-Rae; Ryu, Hyung-Won; Ko, Je-Won; Park, Sung-Hyeuk; Yuk, Heung-Joo; Kim, Ha-Jung; Kim, Jong-Choon; Jeong, Seong-Hun; Shin, In-Sik

    2017-09-14

    Artemisia argyi is a traditional herbal medicine in Korea and commonly called as mugwort. It is traditionally used as food source and tea to control abdominal pain, dysmenorrhea, uterine hemorrhage, and inflammation. We investigated the effects of A. argyi (TOTAL) and dehydromatricarin A (DA), its active component on ovalbumin (OVA)-induced allergic asthma. The animals were sensitized on day 0 and 14 by intraperitoneal injection of OVA with aluminum hydroxide. On day 21, 22 and 23 after the initial sensitization, the animals received an airway challenge with OVA for 1h using an ultrasonic nebulizer. TOTAL (50 and 100mg/kg) or DA (10 and 20mg/kg) were administered to mice by oral gavage once daily from day 18-23. Airway hyperresponsiveness (AHR) was measured 24h after final OVA challenge. TOTAL and DA treated animals reduced inflammatory cell counts, cytokines and AHR in asthmatic animals, which was accompanied with inflammatory cell accumulation and mucus hypersecretion. Furthermore, TOTAL and DA significantly declined Erk phosphorylation and the expression of MMP-9 in asthmatic animals. In conclusion, we indicate that Total and DA suppress allergic inflammatory responses caused by OVA challenge. It was considered that A. argyi has a potential for treating allergic asthma. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  6. National Elevation Dataset (NED)

    Data.gov (United States)

    Kansas Data Access and Support Center — The U.S. Geological Survey has developed a National Elevation Database (NED). The NED is a seamless mosaic of best-available elevation data. The 7.5-minute elevation...

  7. Elevated Liver Enzymes

    Science.gov (United States)

    Symptoms Elevated liver enzymes By Mayo Clinic Staff Elevated liver enzymes may indicate inflammation or damage to cells in the liver. Inflamed or ... than normal amounts of certain chemicals, including liver enzymes, into the bloodstream, which can result in elevated ...

  8. Animal Bites

    Science.gov (United States)

    Wild animals usually avoid people. They might attack, however, if they feel threatened, are sick, or are protecting their ... or territory. Attacks by pets are more common. Animal bites rarely are life-threatening, but if they ...

  9. Animal experimentation

    OpenAIRE

    Laz, Alak; Cholakova, Tanya Stefanova; Vrablova, Sofia; Arshad, Naverawaheed

    2016-01-01

    Animal experimentation is a crucial part of medical science. One of the ways to define it is any scientific experiment conducted for research purposes that cause any kind of pain or suffering to animals. Over the years, the new discovered drugs or treatments are first applied on animals to test their positive outcomes to be later used by humans. There is a debate about violating ethical considerations by exploiting animals for human benefits. However, different ethical theories have been made...

  10. Animal models

    DEFF Research Database (Denmark)

    Gøtze, Jens Peter; Krentz, Andrew

    2014-01-01

    In this issue of Cardiovascular Endocrinology, we are proud to present a broad and dedicated spectrum of reviews on animal models in cardiovascular disease. The reviews cover most aspects of animal models in science from basic differences and similarities between small animals and the human...

  11. Animal Deliberation

    NARCIS (Netherlands)

    Driessen, C.P.G.

    2014-01-01

    While much has been written on environmental politics on the one hand, and animal ethics and welfare on the other, animal politics, as the interface of the two, is underexamined. There are key political implications in the increase of animal protection laws, the rights of nature, and political

  12. Liposomal Tumor Targeting in Drug Delivery Utilizing MMP-2- and MMP-9-Binding Ligands

    Directory of Open Access Journals (Sweden)

    Oula Penate Medina

    2011-01-01

    Full Text Available Nanotechnology offers an alternative to conventional treatment options by enabling different drug delivery and controlled-release delivery strategies. Liposomes being especially biodegradable and in most cases essentially nontoxic offer a versatile platform for several different delivery approaches that can potentially enhance the delivery and targeting of therapies to tumors. Liposomes penetrate tumors spontaneously as a result of fenestrated blood vessels within tumors, leading to known enhanced permeability and subsequent drug retention effects. In addition, liposomes can be used to carry radioactive moieties, such as radiotracers, which can be bound at multiple locations within liposomes, making them attractive carriers for molecular imaging applications. Phage display is a technique that can deliver various high-affinity and selectivity peptides to different targets. In this study, gelatinase-binding peptides, found by phage display, were attached to liposomes by covalent peptide-PEG-PE anchor creating a targeted drug delivery vehicle. Gelatinases as extracellular targets for tumor targeting offer a viable alternative for tumor targeting. Our findings show that targeted drug delivery is more efficient than non-targeted drug delivery.

  13. Angiogenesis in vestibular schwannomas: expression of extracellular matrix factors MMP-2, MMP-9, and TIMP-1

    DEFF Research Database (Denmark)

    Møller, Martin Nue; Werther, Kim; Nalla, Amarnadh

    2010-01-01

    Vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) are potent mediators of tumor angiogenesis. It has been demonstrated that vestibular schwannoma VEGF expression correlates with tumor growth pattern, whereas knowledge on the expression of MMPs is lacking. This study...

  14. Elevation of Matrix Metalloproteinases in Different Areas of Ascending Aortic Aneurysms in Patients with Bicuspid and Tricuspid Aortic Valves

    Directory of Open Access Journals (Sweden)

    Salah A. Mohamed

    2012-01-01

    Full Text Available Our aim is to investigate the elevation of matrix proteins in tissues obtained from distal, above the sinotubular junction (proximal, concave, and convex sites of aneurysms in the ascending aorta using a simultaneous multiplex protein detection system. Tissues were collected from 41 patients with ascending aortic aneurysms. A total of 31 patients had a bicuspid aortic valve (BAV, whereas 10 had a tricuspid aortic valve (TAV. Concave and convex aortic site samples were collected from all patients, whereas proximal and distal convexity samples were obtained from 19 patients with BAV and 7 patients with TAV. Simultaneous detection of matrix metalloproteinases (MMPs and their inhibitors (TIMPs was performed at each of the four aortic sites. MMP-2 levels were higher in the concave aortic sites than in the convex aortic sites. In contrast, MMP-8 levels were higher in the convex sites than in the concave sites, as were MMP-9 levels. In both BAV and TAV patients, TIMP-3 levels were higher in the concave sites than in the convex sites. However, TIMP-2 and TIMP-4 levels were significantly elevated in the sinotubular proximal aorta of BAV patients. Simultaneous detection of MMPs and TIMPs revealed different levels at different aortic sites in the same patient.

  15. Efeito da Gymnema sylvestre na elevação da lipidemia após administração de gordura de origem animal em ratos wistar - DOI: 10.4025/actascibiolsci.v26i3.1602 The influence of Gymnema sylvestre on the elevation of blood levels of lipids after administration of animal fat in male wistar rats - DOI: 10.4025/actascibiolsci.v26i3.1602

    Directory of Open Access Journals (Sweden)

    Márcia Regina Batista

    2004-04-01

    Full Text Available Neste trabalho investigamos a influência da Gymnema sylvestre (Gs na elevação da lipidemia após administração de gordura de origem animal em ratos machos Wistar (230g - 250g. Os animais, em jejum por 22 horas, foram divididos em 5 grupos que receberam via intragástrica às 8h os seguintes tratamentos: 1 2mL de gordura suína Batavo®/kg de peso corpóreo (GSB; 2 GSB + 500mg/kg de peso corpóreo de Gs (Gs 500mg; 3 GSB + 1g/kg de peso corpóreo de Gs (Gs 1g; 4 Gs 500mg; 5 Gs 1g. Os animais foram sacrificados 30min após a administração destas substâncias. Não observamos diferenças significativas na concentração sérica de lipídeos totais, triglicerídeos e colesterol total nos ratos que receberam GSB na ausência ou presença de Gs 500mg ou Gs 1g. Portanto, nossos resultados sugerem que a Gs não afeta a absorção intestinal de lipídeosThe aim of the present experiment was to investigate the influence of Gymnema sylvestre (Gs on the elevation of blood levels of lipids after administration of animal fat in male Wistar rats (230–250g. The animals, which were fasted for 22h, were separated in five groups that received (8:00 a.m intragastric administration of: 1 2ml of pork fat Batavo® /kg of body weight (PFB; 2 PFB+500mg/kg of Gs body weight (Gs 500mg; 3 PFB + 1g/kg of Gs body weight (Gs 1 g; 4 Gs 500mg; 5 Gs 1g. The animals were sacrificed 30min after the administration of these substances. No significant differences were verified in the serum concentration of total lipids, triglycerides and cholesterol in the animals, which received PBF in the presence or absence of Gs 500mg or Gs 1g. Therefore, the results showed that Gs could not affect the intestinal absorption of lipids

  16. Animated Asphalt

    DEFF Research Database (Denmark)

    Paldam, Camilla Skovbjerg

    2015-01-01

    to be understood? How does animation differ in different media? And in particular by focusing on and questioning the gender positions inherent in Mitchell’s theory. Animation has an erotic component of seduction and desire, and what pictures want, becomes for Mitchell, what women want. There is of course no simple...

  17. Animal magic

    Science.gov (United States)

    Denny, Mark

    2017-11-01

    Writing a popular-science book about animal biophysics is hard work. Authors must read through hundreds of research papers as the subject is so multidisciplinary. On both counts of research and writing, Matin Durrani and Liz Kalaugher have done a good to excellent job with their book Furry Logic: the Physics of Animal Life

  18. Animal ethics

    DEFF Research Database (Denmark)

    Palmer, Clare; Sandøe, Peter

    2011-01-01

    This chapter describes and discusses different views concerning our duties towards animals. First, we explain why it is necessary to engage in thinking about animal ethics and why it is not enough to rely on feelings alone. Secondly, we present and discuss five different kinds of views about...

  19. ANIMAL code

    International Nuclear Information System (INIS)

    Lindemuth, I.R.

    1979-01-01

    This report describes ANIMAL, a two-dimensional Eulerian magnetohydrodynamic computer code. ANIMAL's physical model also appears. Formulated are temporal and spatial finite-difference equations in a manner that facilitates implementation of the algorithm. Outlined are the functions of the algorithm's FORTRAN subroutines and variables

  20. Animal Detectives

    Science.gov (United States)

    Mulvey, Bridget; Warnock, Carly

    2015-01-01

    During a two-week inquiry-based 5E learning cycle unit, children made observations and inferences to guide their explorations of animal traits and habitats (Bybee 2014). The children became "animal detectives" by studying a live-feed webcam and digital images of wolves in their natural habitat, reading books and online sources about…

  1. Animation & Neurocinematics*

    DEFF Research Database (Denmark)

    Carpe Pérez, Inmaculada Concepción

    2015-01-01

    , indeed, can be considered a social/ emotional learning media, which goes beyond the limitations of live action movies. This is due to the diversity of techniques, and its visual plasticity that constructs the impossible. Animators are not real actors but more like the midwife who brings the anima...... into aliveness, which requires knowing how emotions work. Ed Hooks as an expert in training animators and actors, always remarks: “emotions tend to lead to action”. In this paper we want to argue that by producing animated films, as we watch them, cause a stronger effect, not only in our brains, but also in our...... bodies. By using animation as a learning tool we can explore the world of emotions and question beliefs, feelings and actions in order to express our voices and enhance our communication, and well-being, both, internally and with others. Animation can be the visual expression of the emotions in movement...

  2. Iowa Bedrock Surface Elevation

    Data.gov (United States)

    Iowa State University GIS Support and Research Facility — This Digital Elevation Model (DEM) of the bedrock surface elevation in Iowa was compiled using all available data, principally information from GEOSAM, supplemented...

  3. Animal experimentation.

    Science.gov (United States)

    Kolar, Roman

    2006-01-01

    Millions of animals are used every year in often times extremely painful and distressing scientific procedures. Legislation of animal experimentation in modern societies is based on the supposition that this is ethically acceptable when certain more or less defined formal (e.g. logistical, technical) demands and ethical principles are met. The main parameters in this context correspond to the "3Rs" concept as defined by Russel and Burch in 1959, i.e. that all efforts to replace, reduce and refine experiments must be undertaken. The licensing of animal experiments normally requires an ethical evaluation process, often times undertaken by ethics committees. The serious problems in putting this idea into practice include inter alia unclear conditions and standards for ethical decisions, insufficient management of experiments undertaken for specific (e.g. regulatory) purposes, and conflicts of interest of ethics committees' members. There is an ongoing societal debate about ethical issues of animal use in science. Existing EU legislation on animal experimentation for cosmetics testing is an example of both the public will for setting clear limits to animal experiments and the need to further critically examine other fields and aspects of animal experimentation.

  4. Animal Transports

    Directory of Open Access Journals (Sweden)

    Diana Ludrovcová

    2016-08-01

    Full Text Available Purpose and Originality: The research is aimed to the animal transports issue, from two points of view – first is the animal cruelty and second is the policy and economic consideration. The goal is to acquaint the readers with the transports risks and its cruelty and evaluation of the economic, political aspects for he involved countries. The study is oriented on more points of view, what is rare in works with a similar theme. Method: This paper examines many issues and examinations from different authors and subsequently summarized the findings with authors own knowledge to one expanded unit. Results: Results proves, that livestock transports have negative impact on animal´s health, environment. Number of transported animals is rising every year. Society: Research familiarize the society with the animal transports, cruelty against animals during them, and influence of transports on some countries, their economy, policy. People get better informed and can form their own opinion on this topic. They may start acting, undertaking some steps to improve the present situation, what could help a lot to animals and environment. Limitations / further research: Future research could show progress and improvement of transports, quality of food supply and economics.

  5. Animal tumors

    International Nuclear Information System (INIS)

    Gillette, E.L.

    1983-01-01

    There are few trained veterinary radiation oncologists and the expense of facilities has limited the extent to which this modality is used. In recent years, a few cobalt teletherapy units and megavoltage x-ray units have been employed in larger veterinary institutions. In addition, some radiation oncologists of human medical institutions are interested and willing to cooperate with veterinarians in the treatment of animal tumors. Carefully designed studies of the response of animal tumors to new modalities serve two valuable purposes. First, these studies may lead to improved tumor control in companion animals. Second, these studies may have important implications to the improvement of therapy of human tumors. Much remains to be learned of animal tumor biology so that appropriate model systems can be described for such studies. Many of the latter studies can be sponsored by agencies interested in the improvement of cancer management

  6. Mentalizing animals

    DEFF Research Database (Denmark)

    Kasperbauer, Tyler Joshua

    2017-01-01

    Ethicists have tended to treat the psychology of attributing mental states to animals as an entirely separate issue from the moral importance of animals’ mental states. In this paper I bring these two issues together. I argue for two theses, one descriptive and one normative. The descriptive thesis...... holds that ordinary human agents use what are generally called phenomenal mental states (e.g., pain and other emotions) to assign moral considerability to animals. I examine recent empirical research on the attribution of phenomenal states and agential states (e.g., memory and intelligence) to argue...... that phenomenal mental states are the primary factor, psychologically, for judging an animal to be morally considerable. I further argue that, given the role of phenomenal states in assigning moral considerability, certain theories in animal ethics will meet significant psychological resistance. The normative...

  7. Animated Symbols

    DEFF Research Database (Denmark)

    Frolunde, Lisbeth

    Afhandlingen omfatter et case studie der belyser hvordan unge lærer ved at designe, eller producere, multimedie tekster, her med fokus på animationsfilm. Empiri består af film, fotos, storyboards skabt af 21 elever på et dansk gymnasium, samt videooptagelser og interviews. De semiotiske 'design...

  8. Animated Reconstruction of Forensic Animation

    OpenAIRE

    Hala, Albert; Unver, Ertu

    1998-01-01

    An animated accident display in court can be significant evidentiary tool. Computer graphics animation reconstructions which can be shown in court are cost effective, save valuable time and illustrate complex and technical issues, are realistic and can prove or disprove arguments or theories with reference to the perplexing newtonian physics involved in many accidents: this technology may well revolutionise accident reconstruction, thus enabling prosecution and defence to be more effective in...

  9. Animal toxicology

    Energy Technology Data Exchange (ETDEWEB)

    Amdur, M.

    1996-12-31

    The chapter evaluates results of toxicological studies on experimental animals to investigate health effects of air pollutants and examines the animal data have predicted the response to human subject. Data are presented on the comparative toxicity of sulfur dioxide and sulfuric acid. The animal data obtained by measurement of airway resistance in guinea pigs and of bronchial clearance of particles in donkeys predicted clearly that sulfuric acid was more irritant than sulfur dioxide. Data obtained on human subjects confirmed this prediction. These acute studies also correctly predicted the comparative toxicity of the two compounds in two year studies of monkeys. Such chronic studies are not possible in human subjects but it is a reasonable to assume that sulfuric acid would be more toxic than sulfur dioxide. Current findings in epidemiological studies certainly support this assumption.

  10. Animal evolution

    DEFF Research Database (Denmark)

    Nielsen, Claus

    This book provides a comprehensive analysis of evolution in the animal kingdom. It reviews the classical, morphological information from structure and embryology, as well as the new data gained from studies using immune stainings of nerves and muscles and blastomere markings, which makes it possi......This book provides a comprehensive analysis of evolution in the animal kingdom. It reviews the classical, morphological information from structure and embryology, as well as the new data gained from studies using immune stainings of nerves and muscles and blastomere markings, which makes...

  11. De stille elever

    DEFF Research Database (Denmark)

    Winther-Lindqvist, Ditte Alexandra

    2012-01-01

    Det er blevet en afgørende samværskompetence i uddannelsessystemet at stå aktivt frem og deltage verbalt i skoleklassens liv både fagligt og socialt. Men ikke alle elever deltager lige villigt verbalt i plenum. Artiklen handler om de stille elever og konsekvenserne af stillehed i skolen. Det...... foreslås at skolesystemet sanktionerer ældre elever hårdere for stillehed end yngre elever og det forklares med at skolelivet også er en kultivering henimod elevhed som social identitet og denne er der forventning om at eleverne mestrer i udskolingen....

  12. Animal Science.

    Science.gov (United States)

    VanCleave, Janice

    2001-01-01

    Presents a set of hands-on, outdoor science experiments designed to teach elementary school students about animal adaptation. The experiments focus on: how color camouflage affects an insect population; how spiderlings find a home; and how chameleons camouflage themselves by changing color. (SM)

  13. Animal radiographs

    International Nuclear Information System (INIS)

    Anon.

    1993-01-01

    This chapter presents historical x rays of a wide variety of animals taken within 5 years of the discovery of x radiation. Such photos were used as tests or as illustrations for radiographic publications. Numerous historical photographs are included. 10 refs

  14. Animal impacts

    Science.gov (United States)

    Norbert V. DeByle

    1985-01-01

    The aspen ecosystem is rich in number and species of animals, especially in comparison to associated coniferous forest types. This natural species diversity and richness has been both increased and influenced by the introduction of domestic livestock. The high value of the aspen type as a forage resource for livestock and as forage and cover for wildlife makes the...

  15. Animated symbols

    DEFF Research Database (Denmark)

    Frølunde, Lisbeth

    2008-01-01

    an analytic working model called Animated Symbols concerning critical reflection in a dialogic learning process. The model shows dialogue as interactions that involve two types of transformation: inner ‘learning processes' and outer signs and symbols. The classroom-based research study is part of a Ph...

  16. Biotecnologia animal

    Directory of Open Access Journals (Sweden)

    Luiz Lehmann Coutinho

    2010-01-01

    Full Text Available A biotecnologia animal tem fornecido novas ferramentas para os programas de melhoramento e, dessa forma, contribuído para melhorar a eficiência da produção dos produtos de origem animal. No entanto, os avanços têm sido mais lentos do que antecipados, especialmente em razão da dificuldade na identificação dos genes responsáveis pelas características fenotípicas de interesse zootécnico. Três estratégias principais têm sido utilizadas para identificar esses genes - mapeamento de QTL, genes candidatos e sequenciamento de DNA e mRNA - e cada uma tem suas vantagens e limitações. O mapeamento de QTL permite determinar as regiões genômicas que contêm genes, mas o intervalo de confiança do QTL pode ser grande e conter muitos genes. A estratégia de genes candidatos é limitada por causa do conhecimento ainda restrito das funções de todos os genes. Os sequenciamentos de genomas e de sequências expressas podem auxiliar na identificação da posição de genes e de vias metabólicas associadas à característica de interesse. A integração dessas estratégias por meio do desenvolvimento de programas de bioinformática permitirá a identificação de novos genes de interesse zootécnico. Assim, os programas de melhoramento genético se beneficiarão pela inclusão da informação obtida diretamente do DNA na avaliação do mérito genético dos plantéis disponíveis.Animal biotechnology is providing new tools for animal breeding and genetics and thus contributing to advances in production efficiency and quality of animal products. However, the progress is slower than anticipated, mainly because of the difficulty involved in identifying genes that control phenotypic characteristics of importance to the animal industry. Three main strategies: QTL mapping, candidate genes and DNA and mRNA sequencing have been used to identify genes of economic interest to animal breeding and each has advantages and disadvantages. QTL mapping allows

  17. Undervisning af tosprogede elever

    DEFF Research Database (Denmark)

    Horst, Christian

    2003-01-01

    Artiklen fremdrager hovedresultaterne fra Virginia P. Collier's og Wayne P. Thomas's længdeundersøgelser af tosprogede elever i USA, som formentlig er de mest omfattende undersøgelser af undervisningen af tosprogede elever overhovedet. Resultaterne diskuteres i relation til udviklingen af en...

  18. Effects of elevated CO

    NARCIS (Netherlands)

    Xue, Sha; Yang, Xiaomei; Liu, Guobin; Gai, Lingtong; Zhang, Changsheng; Ritsema, Coen J.; Geissen, Violette

    2017-01-01

    Elevated CO2 and drought are key consequences of climate change and affect soil processes and plant growth. This study investigated the effects of elevated CO2 and drought on the microbial biomass and enzymatic activities in the rhizospheres of Bothriochloa ischaemum and

  19. Animal facilities

    International Nuclear Information System (INIS)

    Fritz, T.E.; Angerman, J.M.; Keenan, W.G.; Linsley, J.G.; Poole, C.M.; Sallese, A.; Simkins, R.C.; Tolle, D.

    1981-01-01

    The animal facilities in the Division are described. They consist of kennels, animal rooms, service areas, and technical areas (examining rooms, operating rooms, pathology labs, x-ray rooms, and 60 Co exposure facilities). The computer support facility is also described. The advent of the Conversational Monitor System at Argonne has launched a new effort to set up conversational computing and graphics software for users. The existing LS-11 data acquisition systems have been further enhanced and expanded. The divisional radiation facilities include a number of gamma, neutron, and x-ray radiation sources with accompanying areas for related equipment. There are five 60 Co irradiation facilities; a research reactor, Janus, is a source for fission-spectrum neutrons; two other neutron sources in the Chicago area are also available to the staff for cell biology studies. The electron microscope facilities are also described

  20. Animal Locomotion

    CERN Document Server

    Taylor, Graham K; Tropea, Cameron

    2010-01-01

    This book provides a wide-ranging snapshot of the state-of-the-art in experimental research on the physics of swimming and flying animals. The resulting picture reflects not only upon the questions that are of interest in current pure and applied research, but also upon the experimental techniques that are available to answer them. Doubtless, many new questions will present themselves as the scope and performance of our experimental toolbox develops over the coming years.

  1. Elevator and hydraulics; Elevator to yuatsu

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, I. [Hitachi, Ltd., Tokyo (Japan)

    1994-07-15

    A hydraulic type elevator is installed in relatively lower buildings as compared with a rope type elevator, but the ratio in the number of installation of the former elevator is increasing. This paper explains from its construction and features to especially various control systems for the riding comfort and safety. A direct push-up system with hydraulic jacks arranged beneath a car, and an indirect push-up system that has hydraulic jacks arranged on flank of a car and transmits the movement of a plunger via a rope are available. The latter system eliminates the need of large holes to embed hydraulic jacks. While the speed is controlled by controlling flow rates of high-pressure oil, the speed, position, acceleration and even time differential calculus of the acceleration must be controlled severely. The system uses two-step control for the through-speed and the landing speed. Different systems that have been realized may include compensation for temperatures in flow rate control valves, load pressures, and oil viscosity, from learning control to fuzzy control for psychological effects, or control of inverters in motors. 13 refs., 12 figs., 1 tab.

  2. Elevators or stairs?

    Science.gov (United States)

    Shah, Sachin; O’Byrne, Michael; Wilson, Merne; Wilson, Thomas

    2011-01-01

    Background: Staff in hospitals frequently travel between floors and choose between taking the stairs or elevator. We compared the time savings with these two options. Methods: Four people aged 26–67 years completed 14 trips ranging from one to six floors, both ascending and descending. We compared the amount of time per floor travelled by stairs and by two banks of elevators. Participants reported their fatigue levels using a modified Borg scale. We performed two-way analysis of variance to compare the log-transformed data, with participant and time of day as independent variables. Results: The mean time taken to travel between each floor was 13.1 (standard deviation [SD] 1.7) seconds by stairs and 37.5 (SD 19.0) and 35.6 (SD 23.1) seconds by the two elevators (F = 8.61, p elevator equaled about 15 minutes a day. Self-reported fatigue was less than 13 (out of 20) on the Borg scale for all participants, and they all stated that they were able to continue their duties without resting. The extra time associated with elevator use was because of waiting for its arrival. There was a difference in the amount of time taken to travel by elevator depending on the time of day and day of the week. Interpretation: Taking the stairs rather than the elevator saved about 15 minutes each workday. This 3% savings per workday could translate into improved productivity as well as increased fitness. PMID:22159365

  3. Animation of Antimicrobial Resistance

    Science.gov (United States)

    ... Animal & Veterinary Cosmetics Tobacco Products Animal & Veterinary Home Animal & Veterinary Safety & Health Antimicrobial Resistance Animation of Antimicrobial Resistance Share Tweet Linkedin Pin ...

  4. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... Animal & Veterinary Cosmetics Tobacco Products Animal & Veterinary Home Animal & Veterinary Safety & Health Antimicrobial Resistance Animation of Antimicrobial Resistance Share Tweet Linkedin Pin ...

  5. Surgery-induced hippocampal angiotensin II elevation causes blood-brain barrier disruption via MMP/TIMP in aged rats

    Directory of Open Access Journals (Sweden)

    Zhengqian eLi

    2016-04-01

    Full Text Available Reversible BBB disruption has been uniformly reported in several animal models of postoperative cognitive dysfunction (POCD. Nevertheless, the precise mechanism underlying this occurrence remains unclear. Using an aged rat model of POCD, we investigated the dynamic changes in expression of molecules involved in BBB disintegration, matrix metalloproteinase-2 (MMP-2 and -9 (MMP-9, as well as three of their endogenous tissue inhibitors (TIMP-1, -2, -3, and tried to establish the correlation between MMP/TIMP balance and surgery-induced hippocampal BBB disruption. We validated the increased hippocampal expression of angiotensin II (Ang II and Ang II receptor type 1 (AT1 after surgery. We also found MMP/TIMP imbalance as early as 6 h after surgery, together with increased BBB permeability and decreased expression of Occludin and zonula occludens-1 (ZO-1, as well as increased basal lamina protein laminin at 24 h postsurgery. The AT1 antagonist candesartan restored MMP/TIMP equilibrium and modulated expression of Occludin and laminin, but not ZO-1, thereby improving BBB permeability. These events were accompanied by suppression of the surgery-induced canonical nuclear factor-κB (NF-κB activation cascade. Nevertheless, AT1 antagonism did not affect nuclear receptor peroxisome proliferator-activated receptor-γ expression. Collectively, these findings suggest that surgery-induced Ang II release impairs BBB integrity by activating NF-κB signaling and disrupting downstream MMP/TIMP balance via AT1 receptor.

  6. Animated war

    DEFF Research Database (Denmark)

    Frølunde, Lisbeth

    2012-01-01

    in production: Gzim Rewind (Sweden, 2011) by Knutte Wester, and In-World War (USA, expected 2011) by DJ Bad Vegan. These films have themes of war and include film scenes that are ‘machinima’ (real-time animation made in 3D graphic environments) within live action film scenes. Machinima harnesses...... DIY multimedia storytellers explore new ways to tell and to ‘animate’ stories. The article contains four parts: introduction to machinima and the notions of resemiosis and authorial practice, presentation of DIY filmmaking as a practice that intertwines with new networked economics, analysis...

  7. Animal models.

    Science.gov (United States)

    Walker, Ellen A

    2010-01-01

    As clinical studies reveal that chemotherapeutic agents may impair several different cognitive domains in humans, the development of preclinical animal models is critical to assess the degree of chemotherapy-induced learning and memory deficits and to understand the underlying neural mechanisms. In this chapter, the effects of various cancer chemotherapeutic agents in rodents on sensory processing, conditioned taste aversion, conditioned emotional response, passive avoidance, spatial learning, cued memory, discrimination learning, delayed-matching-to-sample, novel-object recognition, electrophysiological recordings and autoshaping is reviewed. It appears at first glance that the effects of the cancer chemotherapy agents in these many different models are inconsistent. However, a literature is emerging that reveals subtle or unique changes in sensory processing, acquisition, consolidation and retrieval that are dose- and time-dependent. As more studies examine cancer chemotherapeutic agents alone and in combination during repeated treatment regimens, the animal models will become more predictive tools for the assessment of these impairments and the underlying neural mechanisms. The eventual goal is to collect enough data to enable physicians to make informed choices about therapeutic regimens for their patients and discover new avenues of alternative or complementary therapies that reduce or eliminate chemotherapy-induced cognitive deficits.

  8. Elevated temperature fracture mechanics

    International Nuclear Information System (INIS)

    Tomkins, B.

    1979-01-01

    The application of fracture mechanics concepts to cracks at elevated temperatures is examined. Particular consideration is given to the characterisation of crack tip stress-strain fields and parameters controlling crack extension under static and cyclic loads. (author)

  9. Indsatser for tosprogede elever

    DEFF Research Database (Denmark)

    Andersen, Dines; Jakobsen, Vibeke; Jensen, Vibeke Myrup

    Fagligt set klarer tosprogede elever sig dårligere i skolen og det videre uddannelsessystem end ’danske’ elever. Kommuner og folkeskoler har derfor sat en række tiltag i værk, som sigter mod at forbedre de tosprogede elevers skole- og uddannelsessituation. Rapporten kortlægger og analyserer...... af klasseundervisningen. Analysen viser, at de elever, der bliver taget ud af klassen for at få ekstra undervisning i dansk som andetsprog, klarer sig dårligere end elever, der modtager ekstraundervisningen i klassen eller uden for skoletid. Undersøgelsen er baseret på spørgeskemaundersøgelser blandt...... kommunale forvaltningschefer, skoleledere, lærere og forældre til børn i 2. klasse samt lærere til og elever i 9. klasse, SFI’s forløbsundersøgelse af årgang 1995 og registerdata. Undersøgelsen er via Ministeriet for Børn og Undervisning betalt med midler fra satspuljeaftalen 2009 om integration....

  10. Bioethical Problems: Animal Welfare, Animal Rights.

    Science.gov (United States)

    March, B. E.

    1984-01-01

    Discusses various bioethical issues and problems related to animal welfare and animal rights. Areas examined include: Aristotelian views; animal welfare legislation; Darwin and evolutionary theory; animal and human behavior; and vegetarianism. A 14-point universal declaration of the rights of animals is included. (JN)

  11. Animal welfare: an animal science approach.

    Science.gov (United States)

    Koknaroglu, H; Akunal, T

    2013-12-01

    Increasing world population and demand for animal-derived protein puts pressure on animal production to meet this demand. For this purpose animal breeding efforts were conducted to obtain the maximum yield that the genetic makeup of the animals permits. Under the influence of economics which is the driving force behind animal production, animal farming became more concentrated and controlled which resulted in rearing animals under confinement. Since more attention was given on economics and yield per animal, animal welfare and behavior were neglected. Animal welfare which can be defined as providing environmental conditions in which animals can display all their natural behaviors in nature started gaining importance in recent years. This does not necessarily mean that animals provided with good management practices would have better welfare conditions as some animals may be distressed even though they are in good environmental conditions. Consumers are willing to pay more for welfare-friendly products (e.g.: free range vs caged egg) and this will change the animal production practices in the future. Thus animal scientists will have to adapt themselves for the changing animal welfare rules and regulations that differ for farm animal species and countries. In this review paper, animal welfare is discussed from an animal science standpoint. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  12. National Elevation Dataset

    Science.gov (United States)

    ,

    2002-01-01

    The National Elevation Dataset (NED) is a new raster product assembled by the U.S. Geological Survey. NED is designed to provide National elevation data in a seamless form with a consistent datum, elevation unit, and projection. Data corrections were made in the NED assembly process to minimize artifacts, perform edge matching, and fill sliver areas of missing data. NED has a resolution of one arc-second (approximately 30 meters) for the conterminous United States, Hawaii, Puerto Rico and the island territories and a resolution of two arc-seconds for Alaska. NED data sources have a variety of elevation units, horizontal datums, and map projections. In the NED assembly process the elevation values are converted to decimal meters as a consistent unit of measure, NAD83 is consistently used as horizontal datum, and all the data are recast in a geographic projection. Older DEM's produced by methods that are now obsolete have been filtered during the NED assembly process to minimize artifacts that are commonly found in data produced by these methods. Artifact removal greatly improves the quality of the slope, shaded-relief, and synthetic drainage information that can be derived from the elevation data. Figure 2 illustrates the results of this artifact removal filtering. NED processing also includes steps to adjust values where adjacent DEM's do not match well, and to fill sliver areas of missing data between DEM's. These processing steps ensure that NED has no void areas and artificial discontinuities have been minimized. The artifact removal filtering process does not eliminate all of the artifacts. In areas where the only available DEM is produced by older methods, then "striping" may still occur.

  13. Interaktive tavler - interaktive elever

    DEFF Research Database (Denmark)

    Reusch, Charlotte F.; Otzen, Elsebeth

    Abstract, Poster-præsentation 13.-14. juni 2012, Pilotprojekt: Interaktive tavler – interaktive elever Lektor, cand. pæd., Elsebeth Otzen og Lektor, cand. mag., Charlotte Reusch, Institut for Skole og Læring, Læreruddannelsen, Professionshøjskolen Metropol, København Hvordan motiverer en interaktiv...... tavle lærere og elever? Hvad sker der mellem elev, stof og lærer, når læreren bliver i stand til at billedliggøre og dynamisere sine oplæg på tavlen? Bliver læreroplæg prioriteret? Bliver eleverne aktive, eller ender den interaktive tavle med blot at understøtte lærerens envejskommunikation til klassen......? Og hvad sker der mellem eleverne? Disse spørgsmål var igangsættende for arbejdet med pilotprojektet Interaktive tavler – interaktive elever, som blev afviklet i skoleåret 2010-2011. Projektet blev udført af en tværfaglig gruppe, bestående af lektorer i matematik, biologi og dansk i læreruddannelsen...

  14. Udeskole og elevers handlekompetence

    DEFF Research Database (Denmark)

    Breiting, Søren

    2011-01-01

    Elever elsker at komme væk fra undervisningen i skolen. Er det positivt eller negativt? Og hvad har betydning for, at eleverne får mest muligt ud af oplevelserne uden for skolen? Forskellige former for udeskole giver nogle oplagte muligheder, så eleverne udvikler sig som engagerede borgere i et...

  15. Interaktive tavler - interaktive elever

    DEFF Research Database (Denmark)

    Reusch, Charlotte; Otzen, Elsebeth

    Abstract, Poster-præsentation 13.-14. juni 2012, Pilotprojekt: Interaktive tavler ? interaktive elever Lektor, cand. pæd., Elsebeth Otzen og Lektor, cand. mag., Charlotte Reusch, Institut for Skole og Læring, Læreruddannelsen, Professionshøjskolen Metropol, København Hvordan motiverer en interaktiv...... tavle lærere og elever? Hvad sker der mellem elev, stof og lærer, når læreren bliver i stand til at billedliggøre og dynamisere sine oplæg på tavlen? Bliver læreroplæg prioriteret? Bliver eleverne aktive, eller ender den interaktive tavle med blot at understøtte lærerens envejskommunikation til klassen......? Og hvad sker der mellem eleverne? Disse spørgsmål var igangsættende for arbejdet med pilotprojektet Interaktive tavler ? interaktive elever, som blev afviklet i skoleåret 2010-2011. Projektet blev udført af en tværfaglig gruppe, bestående af lektorer i matematik, biologi og dansk i læreruddannelsen...

  16. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... video) Animation of Antimicrobial Resistance (text version) Arabic Translation of Animation of Antimicrobial Resistance Chinese Translation of Animation of Antimicrobial Resistance French Translation of ...

  17. The wild animal as a research animal

    NARCIS (Netherlands)

    Swart, JAA

    2004-01-01

    Most discussions on animal experimentation refer to domesticated animals and regulations are tailored to this class of animals. However, wild animals are also used for research, e. g., in biological field research that is often directed to fundamental ecological-evolutionary questions or to

  18. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... Emitting Products Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Animal & Veterinary Home Animal & Veterinary Safety & Health ... Emitting Products Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products

  19. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... Radiation-Emitting Products Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Animal & Veterinary Home Animal & Veterinary Safety & ... Radiation-Emitting Products Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products

  20. Learning Anime Studio

    CERN Document Server

    Troftgruben, Chad

    2014-01-01

    Anime Studio is your complete animation program to help you create 2D movies, cartoons, anime, and cut out animations. You can create your own animated shorts and use Anime Studio to produce cartoon animations for film, video, or streaming over the Web, which can be enjoyed on YouTube, Vimeo, and other popular sites. Anime Studio is great for hobbyists and professionals alike, combining tools for both illustration and animation. With Anime Studio's easy-to-use interface, you will be creating an animated masterpiece in no time. This practical, step-by-step guide will provide you with a structur

  1. Skuldertesten "Kombineret Elevation"

    DEFF Research Database (Denmark)

    Clausen, Mikkel Bek; Overkær, Brian

    2010-01-01

    Formål: At udarbejde en testprotokol for testen Kombineret Elevation (KE) og undersøge test-retest variationen ved test af elite svømmere, samt diskutere testens relevans og validitet. Materiale og Metode: 9 elite og 10 sub-elite svømmere, heraf var 11 mænd og 8 kvinder, gennemførte testen KE 2...

  2. Evaluation of Religious Animations in the IRIB

    Directory of Open Access Journals (Sweden)

    Nematoallah Moussa Pour

    2008-11-01

    Full Text Available Religious education has an elevated status and a great value in Iranian religious society. Using different methods and instruments to realize this goal has been always considered by those involved in education. At the present time, television is an effective means for communicating with social groups. One of those groups is children who can be exposed to messages by animations. The effectiveness of animation is a function of the manner in which it has been produced. Therefore, we can ask whether psychological principles have been observed in the production of religious animations for children. This article, written for evaluating religious animations used in the television, aims at identifying sixteen principles governing the production of animations for children. To do this, the authors referred to authentic sources in psychology and media studies after gathering data and composing them, managed to identify the principles governing the production of animation. The numbers of these principles have been applied to the production of animations, a checklist was prepared and the data were extracted from analyzing two religious animations, two domestic non-religious animations and two foreign non-religious animations. Non-religious animations were analyzed to make possible the suggested that the producers of religious animations pay special attention to do this point.

  3. SERUM CONCENTRATIONS OF MATRIX METALLOPROTEINASE-9, -13 AND TIMP-1 IN AN OVARIECTOMIZED WISTAR RAT MODEL OF OSTEOPOROSIS

    Directory of Open Access Journals (Sweden)

    Armine V. Grigoryan

    2017-12-01

    Full Text Available Introduction. Osteoporosis is a disease characterized by decreased bone density and destruction of the microarchitectonics of the bone structure. This leads to increased bone fragility and risk of fracture, particularly of the hip, spine, wrist and shoulder. Osteoporosis is known as „The Silent Epidemic of the Century“ because bone loss occurs without symptoms. An altered ovarian function is one of the most common causes of osteoporosis. Indicators for altered bone homeostasis are the changes in serum levels of matrix metalloproteinases (MMPs and their tissue inhibitors (TIMPs. Objective. The aim of current study was to determine the activity of alkaline phosphatase (ALP and serum concentrations of MMP-9, MMP-13 and TIMP-1 in the ovariectomized rats. Materials and Methods. An experiment was performed on 35 female Wistar rats at reproductive age – 2 months divided into 2 groups: group 1 (G1-20 animals were sham-operated (sham and group 2 (G2-15 were ovariectomized (ovx. Results. The concentrations of ALP, MMP-9, MMP-13 and TIMP-1 in G2 were significantly increased compared to G1 (p<0.05. Conclusion. Our study confirmed that the serum activity of ALP, which is a marker of bone formation, was elevated in rats with OVX-induced osteoporosis. Although the level of TIMP-1 is increased, the level of MMP 9 in G2 is also increased, that confirms the thesis that MMP-9 may be a marker for osteoclast activity.

  4. A spider elevator

    Energy Technology Data Exchange (ETDEWEB)

    Butylkin, A.V.; Butylkin, V.A.; Izosimov, A.M.

    1983-01-01

    A spider elevator is proposed which contains a body, a wedge clamp with wedges hinged to each other, a subassembly for holding the wedge clamp in the open and closed positions and a mechanism for changing the wedge clamp, which is made in the form of levers with ears for cleats and installed in the body with the capability of turning. To increase reliability in the operational mode through using the external force for clamping the pipe, the free ends of the levers are hinged with the body by a power cylinder.

  5. Elevator Control Strategies

    OpenAIRE

    Ceder, Frederick; Nordin, Alexandra

    2013-01-01

    The purpose of this essay is to investigate if it is eective to switch strategies for elevators during one day in an oce building. This essay describes some of the strategies in use today, followed by a comparison and analysis of two of the strategies described. We have also implemented optimizations to one of these strategies. From our test results we can conclude that our optimized strategy worked and produced better results on average waiting time and total traveling time than the two stra...

  6. [Animal experimentation, animal welfare and scientific research].

    Science.gov (United States)

    Tal, H

    2013-10-01

    Hundreds of thousands of laboratory animals are being used every year for scientific experiments held in Israel, mostly mice, rats, rabbits, guinea pigs, and a few sheep, cattle, pigs, cats, dogs, and even a few dozen monkeys. In addition to the animals sacrificed to promote scientific research, millions of animals slain every year for other purposes such as meat and fine leather fashion industries. While opening a front against all is an impossible and perhaps an unjustified task, the state of Israel enacted the Animal Welfare (Animal Experimentation) Law (1994). The law aims to regulate scientific animal experiments and to find the appropriate balance between the need to continue to perform animal experiments for the advancement of research and medicine, and at the same time to avoid unnecessary trials and minimize animal suffering. Among other issues the law deals with the phylogenetic scale according to which experimental animals should be selected, experiments for teaching and practicing, and experiments for the cosmetic industry. This article discusses bioethics considerations in animal experiments as well as the criticism on the scientific validity of such experiments. It further deals with the vitality of animal studies and the moral and legal obligation to prevent suffering from laboratory animals.

  7. Automatic pipe elevator

    Energy Technology Data Exchange (ETDEWEB)

    Haney, K.M.; Willis, C.A.

    1987-03-17

    This patent describes an elevator adapted for use with a power swivel for supporting a drilling or production tubular, the elevator comprising: at least two jaws, each jaw having a clamping surface; a connector member for supporting the jaws, the connector member comprising an upper end, a lower end, means for coupling the upper end to the power swivel, means for coupling the lower end to a tubular. The member also comprises means for defining a passageway extending from the upper end to the lower end through the connector member to allow drilling mud to be passed from the power swivel through the bore, into the tubular; and linkage means mounted between the connector member and the jaws for coupling the jaws to the connector member and for maintaining the clamping surfaces of the jaws in clamping engagement with the tubular when the connector member and the tubular are urged apart relative to one another. The linkage means is configured such that the force by which the clamping surfaces clamp the tubular increases as the force urging the connector member and the tubular apart increases.

  8. Elevation data for floodplain mapping

    National Research Council Canada - National Science Library

    Committee on Floodplain Mapping Technologies; National Research Council; Division on Earth and Life Studies; National Research Council

    2007-01-01

    .... Elevation Data for Floodplain Mapping shows that there is sufficient two-dimensional base map imagery to meet FEMA's flood map modernization goals, but that the three-dimensional base elevation data...

  9. An elevator wheel

    Energy Technology Data Exchange (ETDEWEB)

    Zhornik, V.I.; Cherkov, Ye.M.; Simonov, A.A.

    1982-01-01

    This invention deals with mineral enrichment and is primarily for unloading submerged products of enrichment during separation in heavy mediums. An elevator wheel is proposed for unloading the submerged product from the bath of a heavy to medium separator which includes ladle disks with internal walls and overlapping sheets hinged to the ends. In order to increase the degree of dehydration of the unloaded product, the internal wall of each ladle is made of sheets installed in stages with clearances relative to each other. The advantages of the proposed device include an improvement in the degree of dehydration of the submerged product in the ladles and a reduction in the carry away of the heavy medium with the enrichment products.

  10. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... Animal & Veterinary Safety & Health Antimicrobial Resistance Animation of Antimicrobial Resistance Share Tweet Linkedin Pin it More sharing options ... CVM) produced a nine-minute animation explaining how antimicrobial resistance both emerges and proliferates among bacteria. Over time, ...

  11. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... Animal & Veterinary Safety & Health Antimicrobial Resistance Animation of Antimicrobial Resistance Share Tweet Linkedin Pin it More sharing options ... of Animation of Antimicrobial Resistance More in Antimicrobial ... Antimicrobial Resistance Monitoring System About NARMS 2015 NARMS Integrated ...

  12. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... Animal & Veterinary Safety & Health Antimicrobial Resistance Animation of Antimicrobial Resistance Share Tweet Linkedin Pin it More sharing ... CVM) produced a nine-minute animation explaining how antimicrobial resistance both emerges and proliferates among bacteria. Over ...

  13. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... Home Food Drugs Medical Devices Radiation-Emitting Products Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Animal & ... back Food Drugs Medical Devices Radiation-Emitting Products Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products

  14. Animal Feeding Operations

    Science.gov (United States)

    ... type=”submit” value=”Submit” /> Healthy Water Home Animal Feeding Operations Recommend on Facebook Tweet Share Compartir ... of Concentrated Animal Feeding Operations (CAFOs) What are Animal Feeding Operations (AFOs)? According to the United States ...

  15. Macrophage-derived osteopontin is fragmented by MMP-9 to hinder angiogenesis in the post-myocardial infarction left ventricle

    DEFF Research Database (Denmark)

    Nielsen, Signe Holm; Flynn, E.R.; Lindsey, M.

    2017-01-01

    Extracellular matrix (ECM) turnover is a key event during remodeling of the left ventricle (LV) following myocardial infarction (MI). Turnover includes ECM degradation of existing ECM to remove necrotic myocytes and synthesis to produce new ECM to form the infarct scar. Matrix metalloproteinases...

  16. Expression and inhibition of matrix metalloproteinase (MMP)-8, MMP-9 and MMP-12 in early colonic anastomotic repair

    DEFF Research Database (Denmark)

    Krarup, Peter-Martin; Eld, Mikkel; Heinemeier, Katja

    2013-01-01

    of specific MMPs responsible for the weakening of anastomoses can be used to optimise MMP inhibition therapy. We aimed to quantify transcript and protein levels of multiple MMPs in colonic anastomoses and evaluate the effect of inhibiting the MMPs that displayed the highest expression levels on anastomotic...

  17. The possible role of matrix metalloproteinase (MMP)-2 and MMP-9 in cancer, e.g. acute leukemia

    NARCIS (Netherlands)

    Klein, G.; Vellenga, E.; Fraaije, M.W.; Kamps, W.A.; Bont, E.S.J.M. de

    2004-01-01

    In the past decades, a lot of effort has been put in identifying the role of matrix metalloproteinases (MMPs) in cancer. The main role of MMPs in angiogenesis, tumor growth and metastasis is degradation of extracellular matrix (ECM) and release and/or activation of growth factors through their

  18. Protective effect of Galectin-9 in murine model of lung emphysema: Involvement of neutrophil migration and MMP-9 production

    Science.gov (United States)

    Horio, Yuko; Ichiyasu, Hidenori; Kojima, Keisuke; Saita, Naoki; Migiyama, Yohei; Iriki, Toyohisa; Fujii, Kazuhiko; Niki, Toshiro; Hirashima, Mitsuomi; Kohrogi, Hirotsugu

    2017-01-01

    Purpose Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow obstruction and pulmonary emphysema. Persistent inflammation and remodeling of the lungs and airways result in reduced lung function and a lower quality of life. Galectin (Gal)-9 plays a crucial role as an immune modulator in various diseases. However, its role in the pathogenesis of pulmonary emphysema is unknown. This study investigates whether Gal-9 is involved in pulmonary inflammation and changes in emphysema in a porcine pancreatic elastase (PPE)-induced emphysema model. Materials and methods Gal-9 was administered to mice subcutaneously once daily from 1 day before PPE instillation to day 5. During the development of emphysema, lung tissue and bronchoalveolar lavage fluid (BALF) were collected. Histological and cytological findings, concentrations of chemokines and matrix metalloproteinases (MMPs) in the BALF, and the influence of Gal-9 treatment on neutrophils were analyzed. Results Gal-9 suppressed the pathological changes of PPE-induced emphysema. The mean linear intercept (Lm) of Gal-9-treated emphysema mice was significantly lower than that of PBS-treated emphysema mice (66.1 ± 3.3 μm vs. 118.8 ± 14.8 μm, respectively; p emphysema progressed significantly compared with that in wild–type (WT) mice (108.7 ± 6.58 μm vs. 77.19 ± 6.97 μm, respectively; p emphysema by inhibiting the infiltration of neutrophils and decreasing MMPs levels. Exogenous Gal-9 could be a potential therapeutic agent for COPD. PMID:28704475

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

    Directory of Open Access Journals (Sweden)

    Eline Bredal Furenes

    2014-01-01

    Full Text Available 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.

  20. Seeing the animal

    DEFF Research Database (Denmark)

    Harfeld, Jes Lynning; Cornou, Cecile; Kornum, Anna

    2016-01-01

    This article discusses the notion that the invisibility of the animalness of the animal constitutes a fundamental obstacle to change within current production systems. It is discussed whether housing animals in environments that resemble natural habitats could lead to a re-animalization...... of the animals, a higher appreciation of their moral significance, and thereby higher standards of animal welfare. The basic claim is that experiencing the animals in their evolutionary and environmental context would make it harder to objectify animals as mere bioreactors and production systems. It is argued...... that the historic objectification of animals within intensive animal production can only be reversed if animals are given the chance to express themselves as they are and not as we see them through the tunnel visions of economy and quantifiable welfare assessment parameters....

  1. Animal rights, animal minds, and human mindreading.

    Science.gov (United States)

    Mameli, M; Bortolotti, L

    2006-02-01

    Do non-human animals have rights? The answer to this question depends on whether animals have morally relevant mental properties. Mindreading is the human activity of ascribing mental states to other organisms. Current knowledge about the evolution and cognitive structure of mindreading indicates that human ascriptions of mental states to non-human animals are very inaccurate. The accuracy of human mindreading can be improved with the help of scientific studies of animal minds. However, the scientific studies do not by themselves solve the problem of how to map psychological similarities (and differences) between humans and animals onto a distinction between morally relevant and morally irrelevant mental properties. The current limitations of human mindreading-whether scientifically aided or not-have practical consequences for the rational justification of claims about which rights (if any) non-human animals should be accorded.

  2. Group control of elevators

    Energy Technology Data Exchange (ETDEWEB)

    Umeda, Yasukazu; Hikita, Shiro; Tuji, Sintaro (Mitsubishi Electric Corp., Tokyo (Japan))

    1988-09-05

    Items to be evaluated in the group control of elevators, and a typical control system are described. A new system in which the fuzzy rule base is employed is introduced together with the configuration. The items to be evaluated are waiting time, riding time, accuracy of forecasting, energy saving, and ease of usage. The everage waiting time of less than 20 seconds with less than 3% waiting rate of more than 60 seconds is accepted as a satisfactory service condition. There are many conflicting matters in group-controlling, and the study for the controlling must deal with the optimization of multi-purpose problems. The standards for group-control evaluation differ according to building structures and the tastes of users, and an important problem is where to give emphasis of the evaluation. The TRAFFIC PATTERN LEARNING METHOD has been applied in the system for careful control to accommodate the traffic. No specific function is provided for the evaluation, but the call allocation is made by fuzzy rule-base. The configuration of a new group-control system is introduced. 7 references, 7 figures, 1 table.

  3. Animal Production Research Advances

    African Journals Online (AJOL)

    Animal Production Research Advances is a peer-review journal established expressly to promote the production of all animal species utilized as food. The journal has an international scope and is intended for professionals in animal production and related sciences. We solicit contributions from animal production and ...

  4. Animal Bites: First Aid

    Science.gov (United States)

    First aid Animal bites: First aid Animal bites: First aid By Mayo Clinic Staff These guidelines can help you care for a minor animal bite, such ... 26, 2017 Original article: http://www.mayoclinic.org/first-aid/first-aid-animal-bites/basics/ART-20056591 . Mayo ...

  5. Ian Ingram: Next Animals

    DEFF Research Database (Denmark)

    2015-01-01

    Ian Ingram: Next Animals is an exhibition catalogue presenting research on the work by Ian Ingram in relation to his exhibition Next Animals at Nikolaj Kunsthal in 2015.......Ian Ingram: Next Animals is an exhibition catalogue presenting research on the work by Ian Ingram in relation to his exhibition Next Animals at Nikolaj Kunsthal in 2015....

  6. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... Español Search FDA Submit search Popular Content Home Food Drugs Medical Devices Radiation-Emitting Products Vaccines, ... Biologics Animal & Veterinary Cosmetics Tobacco Products Animal & Veterinary Home Animal & Veterinary Safety & Health Antimicrobial Resistance Animation of ...

  7. First Aid: Animal Bites

    Science.gov (United States)

    ... last rabies vaccination, if known any recent unusual behavior by the animal the animal's location, if known if the animal ... Scratches First Aid: Cuts First Aid: Skin Infections Cat Scratch ... Safe Around Animals Cuts, Scratches, and Abrasions Rabies Cuts, Scratches, and ...

  8. Physics for Animation Artists

    Science.gov (United States)

    Chai, David; Garcia, Alejandro L.

    2011-01-01

    Animation has become enormously popular in feature films, television, and video games. Art departments and film schools at universities as well as animation programs at high schools have expanded in recent years to meet the growing demands for animation artists. Professional animators identify the technological facet as the most rapidly advancing…

  9. Carotenoids in Marine Animals

    Science.gov (United States)

    Maoka, Takashi

    2011-01-01

    Marine animals contain various carotenoids that show structural diversity. These marine animals accumulate carotenoids from foods such as algae and other animals and modify them through metabolic reactions. Many of the carotenoids present in marine animals are metabolites of β-carotene, fucoxanthin, peridinin, diatoxanthin, alloxanthin, and astaxanthin, etc. Carotenoids found in these animals provide the food chain as well as metabolic pathways. In the present review, I will describe marine animal carotenoids from natural product chemistry, metabolism, food chain, and chemosystematic viewpoints, and also describe new structural carotenoids isolated from marine animals over the last decade. PMID:21566799

  10. Carotenoids in Marine Animals

    OpenAIRE

    Maoka, Takashi

    2011-01-01

    Marine animals contain various carotenoids that show structural diversity. These marine animals accumulate carotenoids from foods such as algae and other animals and modify them through metabolic reactions. Many of the carotenoids present in marine animals are metabolites of β-carotene, fucoxanthin, peridinin, diatoxanthin, alloxanthin, and astaxanthin, etc. Carotenoids found in these animals provide the food chain as well as metabolic pathways. In the present review, I will describe marine a...

  11. Ethics in Animal Experimentation

    Directory of Open Access Journals (Sweden)

    Yusuf Ergun

    2010-08-01

    Full Text Available Experimental animals are frequently used to obtain information for primarily scientific reasons. In the present review, ethics in animal experimentation is examined. At first, the history of animal experimentation and animal rights is outlined. Thereafter, the terms in relation with the topic are defined. Finally, prominent aspects of 3Rs constituting scientific and ethical basis in animal experimentation are underlined. [Archives Medical Review Journal 2010; 19(4.000: 220-235

  12. Animal experiments in radiotherapy. II. Large animals

    Energy Technology Data Exchange (ETDEWEB)

    Probert, J C; Hughes, D B

    1975-03-01

    A review has been made of factors of importance when using large animals for organ or partial body irradiation research. The problem has been considered from the viewpoint of the clinician. The rabbit, cat, dog, pig and monkey have been examined in detail for suitability as laboratory animals. Dosimetric and volume features have been reviewed.

  13. Matrix Metalloproteinase-9/Neutrophil Gelatinase-Associated Lipocalin Complex Activity in Human Glioma Samples Predicts Tumor Presence and Clinical Prognosis

    Directory of Open Access Journals (Sweden)

    Ming-Fa Liu

    2015-01-01

    Full Text Available Matrix metalloproteinase-9/neutrophil gelatinase-associated lipocalin (MMP-9/NGAL complex activity is elevated in brain tumors and may serve as a molecular marker for brain tumors. However, the relationship between MMP-9/NGAL activity in brain tumors and patient prognosis and treatment response remains unclear. Here, we compared the clinical characteristics of glioma patients with the MMP-9/NGAL activity measured in their respective tumor and urine samples. Using gelatin zymography assays, we found that MMP-9/NGAL activity was significantly increased in tumor tissues (TT and preoperative urine samples (Preop-1d urine. Activity was reduced by seven days after surgery (Postop-1w urine and elevated again in cases of tumor recurrence. The MMP-9/NGAL status correlated well with MRI-based tumor assessments. These findings suggest that MMP-9/NGAL activity could be a novel marker to detect gliomas and predict the clinical outcome of patients.

  14. Lærer-elev-relationer

    DEFF Research Database (Denmark)

    Laursen, Per Fibæk; Nielsen, Anne Maj

    2015-01-01

    I kapitlet belyser vi relationskompetence i forholdet mellem lærer og elever og hvordan læreren kan arbejde med forhold til elever og med sin opmærksomhed på relationsarbejdet. Afslutningsvis ser vi på hvordan lærere fortsat kan udvikle deres relationskompetence.......I kapitlet belyser vi relationskompetence i forholdet mellem lærer og elever og hvordan læreren kan arbejde med forhold til elever og med sin opmærksomhed på relationsarbejdet. Afslutningsvis ser vi på hvordan lærere fortsat kan udvikle deres relationskompetence....

  15. Tanzania Elevation and Surface Characteristics

    Data.gov (United States)

    US Agency for International Development — The dataset displays Elevation, Slope, Aspect, Topographic Position Index, Terrain Ruggedness, and Roughness based on Shuttle Radar Topography Mission (SRTM) (3...

  16. Matrix metalloproteinase-9 expression in the nuclear compartment of neurons and glial cells in aging and stroke.

    Science.gov (United States)

    Pirici, Daniel; Pirici, Ionica; Mogoanta, Laurentiu; Margaritescu, Otilia; Tudorica, Valerica; Margaritescu, Claudiu; Ion, Daniela A; Simionescu, Cristiana; Coconu, Marieta

    2012-10-01

    Matrix metalloproteinases (MMPs) are well-recognized denominators for extracellular matrix remodeling in the pathology of both ischemic and hemorrhagic strokes. Recent data on non-nervous system tissue showed intracellular and even intranuclear localizations for different MMPs, and together with this, a plethora of new functions have been proposed for these intracellular active enzymes, but are mostly related to apoptosis induction and malign transformation. In neurons and glial cells, on human tissue, animal models and cell cultures, different active MMPs have been also proven to be located in the intra-cytoplasmic or intra-nuclear compartments, with no clear-cut function. In the present study we show for the first time on human tissue the nuclear expression of MMP-9, mainly in neurons and to a lesser extent in astrocytes. We have studied ischemic and hemorrhagic stroke patients, as well as aged control patients. Age and ischemic suffering seemed to be the best predictors for an elevated MMP-9 nuclear expression, and there was no evidence of a clear-cut extracellular proteolytic activity for this compartment, as revealed by intact vascular basement membranes and assessment of vascular densities. More, the majority of the cells expressing MMP-9 in the nuclear compartment also co-expressed activated-caspase 3, indicating a possible link between nuclear MMP-9 localization and apoptosis in neuronal and glial cells following an ischemic or hemorrhagic event. These results, besides showing for the first time the nuclear localization of MMP-9 on a large series of human stroke and aged brain tissues, raise new questions regarding the unknown spectrum of the functions MMPs in human CNS pathology. © 2011 Japanese Society of Neuropathology.

  17. Elevation of the diaphragmatic cupola

    International Nuclear Information System (INIS)

    Semenov, V.M.; Talesnik, M.R.

    1988-01-01

    Altogether 45 patients with elevation of the diaphragmatic cupola were examined. A high frequency of erroneous initial interpretation of examination results was noted in inflammatory and tumorous lesions and congenital conditions. Routine and contrast methods (pneumoperitoneum, bronchography, pleurography and fistulography) were used. Disease-related methods of X-ray investigation were proposed. A variety of causes of diaphragm elevation was indicated

  18. Space Station tethered elevator system

    Science.gov (United States)

    Haddock, Michael H.; Anderson, Loren A.; Hosterman, K.; Decresie, E.; Miranda, P.; Hamilton, R.

    1989-01-01

    The optimized conceptual engineering design of a space station tethered elevator is presented. The tethered elevator is an unmanned, mobile structure which operates on a ten-kilometer tether spanning the distance between Space Station Freedom and a platform. Its capabilities include providing access to residual gravity levels, remote servicing, and transportation to any point along a tether. The report discusses the potential uses, parameters, and evolution of the spacecraft design. Emphasis is placed on the elevator's structural configuration and three major subsystem designs. First, the design of elevator robotics used to aid in elevator operations and tethered experimentation is presented. Second, the design of drive mechanisms used to propel the vehicle is discussed. Third, the design of an onboard self-sufficient power generation and transmission system is addressed.

  19. Changes in host-parasitoid food web structure with elevation.

    Science.gov (United States)

    Maunsell, Sarah C; Kitching, Roger L; Burwell, Chris J; Morris, Rebecca J

    2015-03-01

    temperatures and changes in vegetation communities that are likely to result from climate change may have a restructuring effect on host-parasitoid food webs. Our translocation experiment, however, indicated that leaf miners currently escaping parasitism at high elevations may not automatically experience higher parasitism under warmer conditions and future changes in food web structure may depend on the ability of parasitoids to adapt to novel hosts. © 2014 The Authors. Journal of Animal Ecology © 2014 British Ecological Society.

  20. TIMP-1 resistant matrix metalloproteinase-9 is the predominant serum active isoform associated with MRI activity in patients with multiple sclerosis.

    Science.gov (United States)

    Trentini, Alessandro; Manfrinato, Maria C; Castellazzi, Massimiliano; Tamborino, Carmine; Roversi, Gloria; Volta, Carlo A; Baldi, Eleonora; Tola, Maria R; Granieri, Enrico; Dallocchio, Franco; Bellini, Tiziana; Fainardi, Enrico

    2015-08-01

    The activity of matrix metalloproteinase-9 (MMP-9) depends on two isoforms, an 82 kDa active MMP-9 modulated by its specific tissue inhibitor (TIMP-1), and a 65 kDa TIMP-1 resistant active MMP-9. The relevance of these two enzymatic isoforms in multiple sclerosis (MS) is still unknown. To investigate the contribution of the TIMP-1 modulated and resistant active MMP-9 isoforms to MS pathogenesis. We measured the serum levels of the 82 kDa and TIMP-1 resistant active MMP-9 isoforms by activity assay systems in 86 relapsing-remitting MS (RRMS) patients, categorized according to clinical and magnetic resonance imaging (MRI) evidence of disease activity, and in 70 inflammatory (OIND) and 69 non-inflammatory (NIND) controls. Serum levels of TIMP-1 resistant MMP-9 were more elevated in MS patients than in OIND and NIND (p < 0.05, p < 0.02, respectively). Conversely, 82 kDa active MMP-9 was higher in NIND than in the OIND and MS patients (p < 0.01 and p < 0.00001, respectively). MRI-active patients had higher levels of TIMP-1 resistant MMP-9 and 82 kDa active MMP-9, than did those with MRI inactive MS (p < 0.01 and p < 0.05, respectively). Our findings suggested that the TIMP-1 resistant MMP-9 seem to be the predominantly active isoform contributing to MS disease activity. © The Author(s), 2015.

  1. RETHINKING THE ANIMATE, RE-ANIMATING THOUGHT

    Directory of Open Access Journals (Sweden)

    Tim Ingold

    2013-12-01

    Full Text Available Animism is often described as the imputation of life to inert objects. Such imputation is more typical of people in western societies who dream of finding life on other planets than of indigenous peoples to whom the label of animism has classically been applied. These peoples are united not in their beliefs but in a way of being that is alive and open to a world in continuous birth. In this animic ontology, beings do not propel themselves across a ready-made world but rather issue forth through a world-in-formation, along the lines of their relationships. To its inhabitants this weather-world, embracing both sky and earth, is a source of astonishment but not surprise. Re-animating the ‘western’ tradition of thought means recovering the sense of astonishment banished from offi cial science.

  2. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... FDA Submit search Popular Content Home Food Drugs Medical Devices Radiation-Emitting Products Vaccines, Blood & Biologics Animal & ... by Product Area Product Areas back Food Drugs Medical Devices Radiation-Emitting Products Vaccines, Blood & Biologics Animal & ...

  3. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... Veterinary Safety & Health Antimicrobial Resistance Animation of Antimicrobial Resistance Share Tweet Linkedin Pin it More sharing options ... produced a nine-minute animation explaining how antimicrobial resistance both emerges and proliferates among bacteria. Over time, ...

  4. Occupational Animal Allergy.

    Science.gov (United States)

    Stave, Gregg M

    2018-02-16

    This review explores animal allergen exposure in research laboratories and other work settings, focusing on causes and prevention. (1) Consistent with the hygiene hypothesis, there is new evidence that early childhood exposure to pets produces changes in the gut microbiome that likely lead to a lower risk of allergy. (2) Anaphylaxis from laboratory animal bites occurs more frequently than suggested by prior literature. (3) Animal allergens represent an occupational hazard in a wide variety of work settings ranging from fields that work with animals to public settings like schools and public transportation where allergens are brought into or are present in the workplace. Exposure to animal allergens can result in allergy, asthma, and anaphylaxis. Animal allergy has been most studied in the research laboratory setting, where exposure reduction can prevent the development of allergy. Similar prevention approaches need to be considered for other animal work environments and in all settings where animal allergens are present.

  5. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... produced material may be copied, reproduced, and distributed as long as FDA's Center for Veterinary Medicine is cited as the corporate author. Animation Animation of Antimicrobial Resistance ( ...

  6. Animal Science Project

    International Nuclear Information System (INIS)

    Anon.

    Researches carried out in the 'Animal Science Project' of the Agricultural Nuclear Energy Center, Piracicaba, Sao Paulo state, Brazil, are described. Such researches comprise : immunology and animal nutrition. Tracer techniques are employed in this study. (M.A.) [pt

  7. "Name" that Animal

    Science.gov (United States)

    Laird, Shirley

    2010-01-01

    In this article, the author describes a texture and pattern project. Students started by doing an outline contour drawing of an animal. With the outline drawn, the students then write one of their names to fit "inside" the animal.

  8. Morris Animal Foundation

    Science.gov (United States)

    ... Yours Today » Give the Gift of Health to Animals This Holiday Season. Until December 31, your gift ... bizarre molecules. Learn More » A Tireless Advocate for Animals and Science. “If it has a heartbeat, I ...

  9. PROTECTIVE COLORATION IN ANIMALS

    OpenAIRE

    Leena Lakhani

    2017-01-01

    Animals have range of defensive markings which helps to the risk of predator detection (camouflage), warn predators of the prey’s unpalatability (aposematism) or fool a predator into mimicry, masquerade. Animals also use colors in advertising, signalling services such as cleaning to animals of other species, to signal sexual status to other members of the same species. Some animals use color to divert attacks by startle (dalmatic behaviour), surprising a predator e.g. with eyespots or other f...

  10. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... Skip to common links HHS U.S. Department of Health and Human Services U.S. Food and Drug Administration ... Tobacco Products Animal & Veterinary Home Animal & Veterinary Safety & Health Antimicrobial Resistance Animation of Antimicrobial Resistance Share Tweet ...

  11. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... menu Skip to common links HHS U.S. Department of Health and Human Services U.S. Food and Drug Administration ... Tobacco Products Animal & Veterinary Home Animal & Veterinary Safety & Health Antimicrobial Resistance Animation of Antimicrobial Resistance Share Tweet Linkedin Pin it More ...

  12. Who likes circus animals?

    OpenAIRE

    Zanola, Roberto

    2008-01-01

    Using a sample based on 268 questionnaires submitted to people attending the Acquatico Bellucci circus, Italy, this paper analyzes the circusgoers's preferences for circus animals. Results show that higher preferences for circus animals are related to frequency of consumption. However, differently from what commonly expected, more educated and younger people seem to be less sensitive to the claims of animal welfare organizations.

  13. Animal violence demystified

    NARCIS (Netherlands)

    Natarajan, Deepa; Caramaschi, Doretta

    2010-01-01

    Violence has been observed in humans and animals alike, indicating its evolutionary/biological significance. However, violence in animals has often been confounded with functional forms of aggressive behavior. Currently, violence in animals is identified primarily as either a quantitative behavior

  14. Conservation implications of deforestation across an elevational gradient in the Eastern Arc Mountains, Tanzania

    DEFF Research Database (Denmark)

    Hall, Jaclyn; Burgess, Neil David; Lovett, Jon

    2009-01-01

    Deforestation is a major threat to the conservation of biodiversity, especially within global centers of endemism for plants and animals. Elevation, the major environmental gradient in mountain regions of the world, produces a rapid turnover of species, where some species may exist only in narrow...... elevations and target conservation and restoration efforts throughout these ecosystems' entire elevational ranges.......Deforestation is a major threat to the conservation of biodiversity, especially within global centers of endemism for plants and animals. Elevation, the major environmental gradient in mountain regions of the world, produces a rapid turnover of species, where some species may exist only in narrow...... elevational ranges. We use newly compiled datasets to assess the conservation impact of deforestation on threatened trees across an elevational gradient within the Eastern Arc Mountains of Tanzania. The Eastern Arc has suffered an estimated 80% total loss in historical forest area and has lost 25% of forest...

  15. Mutant matrix metalloproteinase-9 reduces postoperative peritoneal adhesions in rats.

    Science.gov (United States)

    Atta, Hussein; El-Rehany, Mahmoud; Roeb, Elke; Abdel-Ghany, Hend; Ramzy, Maggie; Gaber, Shereen

    2016-02-01

    Postoperative peritoneal adhesions continue to be a major source of morbidity and occasional mortality. Studies have shown that matrix metalloproteinase-9 (MMP-9) levels are decreased postoperatively which may limits matrix degradation and participate in the development of peritoneal adhesions. In this proof-of-principle study, we evaluated the effect of gene therapy with catalytically inactive mutant MMP-9 on postoperative peritoneal adhesions in rats. Adenovirus encoding mutant MMP-9 (Ad-mMMP-9) or saline was instilled in the peritoneal cavity after cecal and parietal peritoneal injury in rats. Expression of mutant MMP-9 transcript was verified by sequencing. Adenovirus E4 gene expression, adhesion scores, MMP-9, tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) and transforming growth factor-β1 (TGF-β1) expression were evaluated at sacrifice one week after treatment. Both mutant MMP-9 transcripts and adenovirus E4 gene were expressed in Ad-mMMP-9 treated adhesions. Adhesions severity decreased significantly (p = 0.036) in the Ad-mMMP-9-treated compared with saline-treated adhesions. Expression of MMP-9 mRNA and protein were elevated (p = 0.001 and p = 0.029, respectively) in the Ad-mMMP-9-treated adhesions compared with saline-treated adhesions. While tPA levels were increased (p = 0.02) in Ad-mMMP-9 treated adhesions compared with saline-treated adhesions, TGF-β1 and PAI-1 levels were decreased (p = 0.017 and p = 0.042, respectively). No difference in mortality were found between groups (p = 0.64). Mutant MMP-9 gene therapy effectively transduced peritoneal adhesions resulting in reduction of severity of primary peritoneal adhesions. Copyright © 2016 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

  16. Context-Aware Elevator Scheduling

    OpenAIRE

    Strang, Thomas; Bauer, Christian

    2007-01-01

    Research on context-aware systems is usually user-centric and thus focussed on the context of a specific user to serve his or her needs in an optimized way. In this paper, we want to apply core concepts developed in research on context-awareness in a system-centric way, namely to elevator systems. We show with three different examples that the performance of an elevator system can be significantly improved if the elevator control has access to contextual knowledge. The first example demons...

  17. Animal models of dementia

    DEFF Research Database (Denmark)

    Olsson, I. Anna S.; Sandøe, Peter

    2011-01-01

    This chapter aims to encourage scientists and others interested in the use of animal models of disease – specifically, in the study of dementia – to engage in ethical reflection. It opens with a general discussion of the moral acceptability of animal use in research. Three ethical approaches...... are here distinguished. These serve as points of orientation in the following discussion of four more specific ethical questions: Does animal species matter? How effective is disease modelling in delivering the benefits claimed for it? What can be done to minimize potential harm to animals in research? Who...... bears responsibility for the use of animals in disease models?...

  18. Animal welfare impact assessments

    DEFF Research Database (Denmark)

    Sandøe, Peter; Gamborg, Christian

    2017-01-01

    aimed at dealing with wild animals. McCulloch and Reiss argue that this could be remedied by means of a “mandatory application of formal and systematic Animal Welfare Impact Assessment (AWIA)”. Optimistically, they consider that an AWIA could help to resolve controversies involving wild animals. The aim...... is a welfare issue. Furthermore, we argue that AWIA is unlikely to prevent serious moral disagreements over how to weigh concerns about wild animals against priorities in human health, the health of domestic and farm animals, and biodiversity, but that it may nonetheless serve to limit harms imposed......Control of wild animals may give rise to controversy, as is seen in the case of badger control to manage TB in cattle in the UK. However, it is striking that concerns about the potential suffering of the affected animals themselves are often given little attention or completely ignored in policies...

  19. Pelvic Organ Support in Animals with Partial Loss of Fibulin-5 in the Vaginal Wall.

    Science.gov (United States)

    Chin, Kathleen; Wieslander, Cecilia; Shi, Haolin; Balgobin, Sunil; Montoya, T Ignacio; Yanagisawa, Hiromi; Word, R Ann

    2016-01-01

    Compromise of elastic fiber integrity in connective tissues of the pelvic floor is most likely acquired through aging, childbirth-associated injury, and genetic susceptibility. Mouse models of pelvic organ prolapse demonstrate systemic deficiencies in proteins that affect elastogenesis. Prolapse, however, does not occur until several months after birth and is thereby acquired with age or after parturition. To determine the impact of compromised levels of fibulin-5 (Fbln5) during adulthood on pelvic organ support after parturition and elastase-induced injury, tissue-specific conditional knockout (cKO) mice were generated in which doxycycline (dox) treatment results in deletion of Fbln5 in cells that utilize the smooth muscle α actin promoter-driven reverse tetracycline transactivator and tetracycline responsive element-Cre recombinase (i.e., Fbln5f/f/SMA++-rtTA/Cre+, cKO). Fbln5 was decreased significantly in the vagina of cKO mice compared with dox-treated wild type or controls (Fbln5f/f/SMA++-rtTA/Cre-/-). In controls, perineal body length (PBL) and bulge increased significantly after delivery but declined to baseline values within 6-8 weeks. Although overt prolapse did not occur in cKO animals, these transient increases in PBL postpartum were amplified and, unlike controls, parturition-induced increases in PBL (and bulge) did not recover to baseline but remained significantly increased for 12 wks. This lack of recovery from parturition was associated with increased MMP-9 and nondetectable levels of Fbln5 in the postpartum vagina. This predisposition to prolapse was accentuated by injection of elastase into the vaginal wall in which overt prolapse occurred in cKO animals, but rarely in controls. Taken together, our model system in which Fbln5 is conditionally knock-downed in stromal cells of the pelvic floor results in animals that undergo normal elastogenesis during development but lose Fbln5 as adults. The results indicate that vaginal fibulin-5 during

  20. Pelvic Organ Support in Animals with Partial Loss of Fibulin-5 in the Vaginal Wall.

    Directory of Open Access Journals (Sweden)

    Kathleen Chin

    Full Text Available Compromise of elastic fiber integrity in connective tissues of the pelvic floor is most likely acquired through aging, childbirth-associated injury, and genetic susceptibility. Mouse models of pelvic organ prolapse demonstrate systemic deficiencies in proteins that affect elastogenesis. Prolapse, however, does not occur until several months after birth and is thereby acquired with age or after parturition. To determine the impact of compromised levels of fibulin-5 (Fbln5 during adulthood on pelvic organ support after parturition and elastase-induced injury, tissue-specific conditional knockout (cKO mice were generated in which doxycycline (dox treatment results in deletion of Fbln5 in cells that utilize the smooth muscle α actin promoter-driven reverse tetracycline transactivator and tetracycline responsive element-Cre recombinase (i.e., Fbln5f/f/SMA++-rtTA/Cre+, cKO. Fbln5 was decreased significantly in the vagina of cKO mice compared with dox-treated wild type or controls (Fbln5f/f/SMA++-rtTA/Cre-/-. In controls, perineal body length (PBL and bulge increased significantly after delivery but declined to baseline values within 6-8 weeks. Although overt prolapse did not occur in cKO animals, these transient increases in PBL postpartum were amplified and, unlike controls, parturition-induced increases in PBL (and bulge did not recover to baseline but remained significantly increased for 12 wks. This lack of recovery from parturition was associated with increased MMP-9 and nondetectable levels of Fbln5 in the postpartum vagina. This predisposition to prolapse was accentuated by injection of elastase into the vaginal wall in which overt prolapse occurred in cKO animals, but rarely in controls. Taken together, our model system in which Fbln5 is conditionally knock-downed in stromal cells of the pelvic floor results in animals that undergo normal elastogenesis during development but lose Fbln5 as adults. The results indicate that vaginal fibulin-5

  1. Pelvic Organ Support in Animals with Partial Loss of Fibulin-5 in the Vaginal Wall

    Science.gov (United States)

    Shi, Haolin; Balgobin, Sunil; Montoya, T. Ignacio; Yanagisawa, Hiromi; Word, R. Ann

    2016-01-01

    Compromise of elastic fiber integrity in connective tissues of the pelvic floor is most likely acquired through aging, childbirth-associated injury, and genetic susceptibility. Mouse models of pelvic organ prolapse demonstrate systemic deficiencies in proteins that affect elastogenesis. Prolapse, however, does not occur until several months after birth and is thereby acquired with age or after parturition. To determine the impact of compromised levels of fibulin-5 (Fbln5) during adulthood on pelvic organ support after parturition and elastase-induced injury, tissue-specific conditional knockout (cKO) mice were generated in which doxycycline (dox) treatment results in deletion of Fbln5 in cells that utilize the smooth muscle α actin promoter-driven reverse tetracycline transactivator and tetracycline responsive element-Cre recombinase (i.e., Fbln5f/f/SMA++-rtTA/Cre+, cKO). Fbln5 was decreased significantly in the vagina of cKO mice compared with dox-treated wild type or controls (Fbln5f/f/SMA++-rtTA/Cre-/-). In controls, perineal body length (PBL) and bulge increased significantly after delivery but declined to baseline values within 6–8 weeks. Although overt prolapse did not occur in cKO animals, these transient increases in PBL postpartum were amplified and, unlike controls, parturition-induced increases in PBL (and bulge) did not recover to baseline but remained significantly increased for 12 wks. This lack of recovery from parturition was associated with increased MMP-9 and nondetectable levels of Fbln5 in the postpartum vagina. This predisposition to prolapse was accentuated by injection of elastase into the vaginal wall in which overt prolapse occurred in cKO animals, but rarely in controls. Taken together, our model system in which Fbln5 is conditionally knock-downed in stromal cells of the pelvic floor results in animals that undergo normal elastogenesis during development but lose Fbln5 as adults. The results indicate that vaginal fibulin-5 during

  2. FEMA DFIRM Base Flood Elevations

    Data.gov (United States)

    Minnesota Department of Natural Resources — The Base Flood Elevation (BFE) table is required for any digital data where BFE lines will be shown on the corresponding Flood Insurance Rate Map (FIRM). Normally,...

  3. Advanced energy saving hydraulic elevator

    Energy Technology Data Exchange (ETDEWEB)

    Garrido, A.; Sevilleja, J.; Servia, A.

    1993-08-24

    An hydraulic elevator is described comprising: a counterweighted elevator comprising a car, a counterweight, and a rope connecting the car and the counterweight; a ram having a first reaction surface for driving one of the car or the counterweight upwardly and a second reaction surface for driving one of the car or the counterweight downwardly; multiplier means for moving the car a distance greater than a stroke of the ram, the multiplier means connecting the ram to the counterweighted elevator, the multiplier means comprising: a first pulley; a second pulley; means for rigidly connecting the first and second pulley, the means having a length corresponding to a rise of the hydraulic elevator, the means attaching to the ram; and a pulley rope which: has a first end attaching to a first fixed point, extends about the first pulley, extends about the second pulley, and has a second end attaching to a second fixed point.

  4. Space Elevators Preliminary Architectural View

    Science.gov (United States)

    Pullum, L.; Swan, P. A.

    Space Systems Architecture has been expanded into a process by the US Department of Defense for their large scale systems of systems development programs. This paper uses the steps in the process to establishes a framework for Space Elevator systems to be developed and provides a methodology to manage complexity. This new approach to developing a family of systems is based upon three architectural views: Operational View OV), Systems View (SV), and Technical Standards View (TV). The top level view of the process establishes the stages for the development of the first Space Elevator and is called Architectural View - 1, Overview and Summary. This paper will show the guidelines and steps of the process while focusing upon components of the Space Elevator Preliminary Architecture View. This Preliminary Architecture View is presented as a draft starting point for the Space Elevator Project.

  5. Coastal Digital Elevation Models (DEMs)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Digital elevation models (DEMs) of U.S. and other coasts that typically integrate ocean bathymetry and land topography. The DEMs support NOAA's mission to understand...

  6. Base Flood Elevation (BFE) Lines

    Data.gov (United States)

    Department of Homeland Security — The Base Flood Elevation (BFE) table is required for any digital data where BFE lines will be shown on the corresponding Flood Insurance Rate Map (FIRM). Normally if...

  7. Elevated Fixed Platform Test Facility

    Data.gov (United States)

    Federal Laboratory Consortium — The Elevated Fixed Platform (EFP) is a helicopter recovery test facility located at Lakehurst, NJ. It consists of a 60 by 85 foot steel and concrete deck built atop...

  8. Energy efficient elevators and escalators

    Energy Technology Data Exchange (ETDEWEB)

    Patrao, Carlos; Fong, Joao; Almeida, Anibal de (Dep. Electrical Engineering, Univ. of Coimbra, Coimbra (Portugal)); Rivet, Luc

    2009-07-01

    Elevators and escalators are the crucial element that makes it practical to live and work several floors above ground - more than 4,3 million units are installed in Europe. Due to ageing of the European population the installation of elevators in single family houses is experiencing a significant growth, as well as equipping existing buildings. Elevators use about 4% of the electricity in tertiary sector buildings. High untapped saving potentials exist with respect to energy-efficient technologies, investment decisions and behavioural approaches, in these sectors. This paper presents preliminary results from the IEE project E4, whose overall objective is the improvement of the energy performance of elevators and escalators, in tertiary sector buildings and in multi family residential buildings. The project is characterizing people conveyors electricity consumption in the tertiary sector and in residential buildings in the EU. The installed park is characterised by a survey among elevators national associations in each country. An assessment of the barriers has been made in the first phase of the project and will be presented. Monitoring campaigns in elevators and escalators are being conducted in each country according to a common developed methodology. More than fifty elevators and escalators will be audited. This will allow the collection of load curves (start up, travel up and down, travel full and empty), including the characterization of standby consumption. Standby consumption of an elevator can represent up to 80% of the total energy consumed per year, and can be drastically reduced. This paper presents the preliminary results of the first ten audits performed in Portugal by Isr-UC.

  9. 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

    Science.gov (United States)

    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

  10. Correlation between matrix metalloproteinase-9 and endometriosis.

    Science.gov (United States)

    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.

  11. Animals as disgust elicitors

    DEFF Research Database (Denmark)

    Kasperbauer, Tyler Joshua

    2015-01-01

    This paper attempts to explain how and why nonhuman animals elicit disgust in human beings. I argue that animals elicit disgust in two ways. One is by triggering disease–protection mechanisms, and the other is by eliciting mortality salience, or thoughts of death. I discuss how these two types...... of disgust operate and defend their conceptual and theoretical coherence against common objections. I also outline an explanatory challenge for disgust researchers. Both types of disgust indicate that a wide variety of animals produce aversive and avoidant reactions in human beings. This seems somewhat odd......, given the prominence of animals in human lives. The challenge, then, is explaining how humans cope with the presence of animals. I propose, as a hypothesis for further exploration, that we cope with animals, and our disgust responses to them, by attributing mental states that mark them as inferior...

  12. Draught animals and welfare.

    Science.gov (United States)

    Ramaswamy, N S

    1994-03-01

    In fifty developing countries, which contain half of the total human population of the world, there is a heavy dependence on draught animals as an energy source. These animals are used for agriculture operations in 52% of cultivated areas of the world, as well as for hauling 25 million carts. This situation is likely to continue for at least another fifty years. The work performed annually by these draught animals would require 20 million tons of petroleum, valued at US$6 billion, if it were performed by motorized vehicles. The poor working conditions of these animals often adversely affect their productivity. The application of improved technology and better management (i.e. through better feed and health services, and improved design of agricultural implements and carts) could considerably improve the welfare of these animals. Improved systems would generate sufficient benefits for the economy to justify the required investment. High priority should therefore be given to draught animal power in the economic development agenda.

  13. Lightning safety of animals.

    Science.gov (United States)

    Gomes, Chandima

    2012-11-01

    This paper addresses a concurrent multidisciplinary problem: animal safety against lightning hazards. In regions where lightning is prevalent, either seasonally or throughout the year, a considerable number of wild, captive and tame animals are injured due to lightning generated effects. The paper discusses all possible injury mechanisms, focusing mainly on animals with commercial value. A large number of cases from several countries have been analyzed. Economically and practically viable engineering solutions are proposed to address the issues related to the lightning threats discussed.

  14. Our love for animals.

    Science.gov (United States)

    Scruton, Roger

    2013-12-01

    Love does not necessarily benefit its object, and cost-free love may damage both object and subject. Our love of animals mobilises several distinct human concerns and should not be considered always as a virtue or always as a benefit to the animals themselves. We need to place this love in its full psychological, cultural, and moral context in order to assess what form it ought to take if animals are to benefit from it.

  15. ANIMALS IN RESOCIALIZATION

    OpenAIRE

    Czerw, Monika

    2017-01-01

    The benefits of relations between humans and animals have encouraged both scientists and members of other communities to popularize the knowledge in the field of animal-assisted therapy. Currently, animal-assisted therapy has been used not only in therapy, but also in resocialization. The increasing popularity of this form of supporting maladjusted people who are isolated from society or people with disabilities encouraged both practitioners and researchers to organize knowledge, thus reducin...

  16. Elevated placental adenosine signaling contributes to the pathogenesis of preeclampsia.

    Science.gov (United States)

    Iriyama, Takayuki; Sun, Kaiqi; Parchim, Nicholas F; Li, Jessica; Zhao, Cheng; Song, Anren; Hart, Laura A; Blackwell, Sean C; Sibai, Baha M; Chan, Lee-Nien L; Chan, Teh-Sheng; Hicks, M John; Blackburn, Michael R; Kellems, Rodney E; Xia, Yang

    2015-02-24

    Preeclampsia is a prevalent hypertensive disorder of pregnancy and a leading cause of maternal and neonatal morbidity and mortality worldwide. This pathogenic condition is speculated to be caused by placental abnormalities that contribute to the maternal syndrome. However, the specific factors and signaling pathways that lead to impaired placentas and maternal disease development remain elusive. Using 2 independent animal models of preeclampsia (genetically engineered pregnant mice with elevated adenosine exclusively in placentas and a pathogenic autoantibody-induced preeclampsia mouse model), we demonstrated that chronically elevated placental adenosine was sufficient to induce hallmark features of preeclampsia, including hypertension, proteinuria, small fetuses, and impaired placental vasculature. Genetic and pharmacological approaches revealed that elevated placental adenosine coupled with excessive A₂B adenosine receptor (ADORA2B) signaling contributed to the development of these features of preeclampsia. Mechanistically, we provided both human and mouse evidence that elevated placental CD73 is a key enzyme causing increased placental adenosine, thereby contributing to preeclampsia. We determined that elevated placental adenosine signaling is a previously unrecognized pathogenic factor for preeclampsia. Moreover, our findings revealed the molecular basis underlying the elevation of placental adenosine and the detrimental role of excess placental adenosine in the pathophysiology of preeclampsia, and thereby, we highlight novel therapeutic targets. © 2014 American Heart Association, Inc.

  17. 3D Animation Essentials

    CERN Document Server

    Beane, Andy

    2012-01-01

    The essential fundamentals of 3D animation for aspiring 3D artists 3D is everywhere--video games, movie and television special effects, mobile devices, etc. Many aspiring artists and animators have grown up with 3D and computers, and naturally gravitate to this field as their area of interest. Bringing a blend of studio and classroom experience to offer you thorough coverage of the 3D animation industry, this must-have book shows you what it takes to create compelling and realistic 3D imagery. Serves as the first step to understanding the language of 3D and computer graphics (CG)Covers 3D anim

  18. Animal MRI Core

    Data.gov (United States)

    Federal Laboratory Consortium — The Animal Magnetic Resonance Imaging (MRI) Core develops and optimizes MRI methods for cardiovascular imaging of mice and rats. The Core provides imaging expertise,...

  19. Complex behavior of elevators in peak traffic

    Science.gov (United States)

    Nagatani, Takashi

    2003-08-01

    We study the dynamical behavior of elevators in the morning peak traffic. We present a stochastic model of the elevators to take into account the interactions between elevators through passengers. The dynamics of the elevators is expressed in terms of a coupled nonlinear map with noises. The number of passengers carried by an elevator and the time-headway between elevators exhibit the complex behavior with varying elevator trips. It is found that the behavior of elevators exhibits a deterministic chaos even if there are no noises. The chaotic motion depends on the loading parameter, the maximum capacity of an elevator, and the number of elevators. When the loading parameter is superior to the threshold, each elevator carries a full load of passengers throughout its trip. The dependence of the threshold (transition point) on the elevator capacity is clarified.

  20. Vessels for elevated temperature service

    International Nuclear Information System (INIS)

    O'Donnell, W.J.; Porowski, J.S.

    1983-01-01

    The subject is covered in chapters, entitled: introduction (background; elevated temperature concerns; design tools); design of pressure vessels for elevated temperature per ASME code; basic elevated temperature failure modes; allowable stresses and strains per ASME code (basic allowable stress limits; ASME code limits for bending; time-fraction summations; strain limits; buckling and instability; negligible creep and stress-rupture effects); combined membrane and bending stresses in creep regime; thermal stress cycles; bounding methods based on elastic core concept (bounds on accumulated strains; more accurate bounds; strain ranges; maximum stresses; strains at discontinuities); elastic follow-up; creep strain concentrations; time-dependent fatigue (combined creep rupture and fatigue damage; limits for inelastic design analyses; limits for elastic design analyses); flaw evaluation techniques; type 316 stainless steel; type 304 stainless steel; steel 2 1/4Cr1Mo; Inconel 718; Incolloy 800; Hastelloy X; detailed inelastic design analyses. (U.K.)

  1. Troponin elevation in subarachnoid hemorrhage

    Directory of Open Access Journals (Sweden)

    Ioannis N. Mavridis

    2015-03-01

    Full Text Available Troponin (tr elevation in aneurysmal subarachnoid hemorrhage (SAH patients is often difficult to be appropriately assessed by clinicians, causing even disagreements regarding its management between neurosurgeons and cardiologists. The purpose of this article was to review the literature regarding the clinical interpretation of tr elevation in SAH. We searched for articles in PubMed using the key words: “troponin elevation” and “subarachnoid hemorrhage”. All of them, as well as relative neurosurgical books, were used for this review. Some type of cardiovascular abnormality develops in most SAH patients. Neurogenic stunned myocardium is a frequent SAH complication, due to catecholamine surge which induces cardiac injury, as evidenced by increased serum tr levels, electrocardiographic (ECG changes and cardiac wall motion abnormalities. Tr elevation, usually modest, is an early and specific marker for cardiac involvement after SAH and its levels peak about two days after SAH. Cardiac tr elevation predictors include poor clinical grade, intraventricular hemorrhage, loss of consciousness at ictus, global cerebral edema, female sex, large body surface area, lower systolic blood pressure, higher heart rate and prolonged Q-Tc interval. Elevated tr levels are associated with disability and death (especially tr >1 μg/L, worse neurological grade, systolic and diastolic cardiac dysfunction, pulmonary congestion, longer intensive care unit stay and incidence of vasospasm. Tr elevation is a common finding in SAH patients and constitutes a rightful cause of worry about the patients' cardiac function and prognosis. It should be therefore early detected, carefully monitored and appropriately managed by clinicians.

  2. Endangered Animals. Second Grade.

    Science.gov (United States)

    Popp, Marcia

    This second grade teaching unit centers on endangered animal species around the world. Questions addressed are: What is an endangered species? Why do animals become extinct? How do I feel about the problem? and What can I do? Students study the definition of endangered species and investigate whether it is a natural process. They explore topics…

  3. Animals in the Classroom

    Science.gov (United States)

    Roy, Ken

    2011-01-01

    Use of animals in middle school science classrooms is a curriculum component worthy of consideration, providing proper investigation and planning are addressed. A responsible approach to this action, including safety, must be adopted for success. In this month's column, the author provides some suggestions on incorporating animals into the…

  4. Urban Animals and Us

    DEFF Research Database (Denmark)

    2013-01-01

    species. But instead of teaching animals like the parrot to mimic and understand people, the sound conducted by humans become translated into non-human message through the ‘BirdFlute’. 3) The experiment 'InterFed' explores power relationships through the device ‘PhotoTwin’ - that traps both animal...

  5. Plant or Animal?

    Science.gov (United States)

    Bowman, Frank; Matthews, Catherine E.

    1996-01-01

    Presents activities that use marine organisms with plant-like appearances to help students build classification skills and illustrate some of the less obvious differences between plants and animals. Compares mechanisms by which sessile plants and animals deal with common problems such as obtaining energy, defending themselves, successfully…

  6. Animal welfare and eggs

    DEFF Research Database (Denmark)

    Andersen, Laura Mørch

    and private good attributes of different types of eggs. We find that the estimated correlations are consistent with the levels of animal welfare, and that consumers perceiving a stronger connection between animal welfare and the organic label have higher willingness to pay for organic eggs, even when we...

  7. Cocombustion of animal meal

    International Nuclear Information System (INIS)

    Roggen, M.

    2001-01-01

    The electricity production companies are prepared to co-fire animal meal in their coal-fired power stations. Tests conducted at the Maasvlakte power station, Netherlands, demonstrate that adding animal meal to the coal has no negative influence on human beings, the environment, the plant or the fly ash quality

  8. Companion Animals. [Information Packet.

    Science.gov (United States)

    National Anti-Vivisection Society, Chicago, IL.

    This collection of articles reprinted from other National Anti-Vivisection Society (NAVS) publications was compiled to educate the public on issues of importance to NAVS concerning companion animals. Topics covered include spaying and neutering, animal safety, pet theft, and the use of cats and dogs in research. The article on spaying and…

  9. Animal damage to birch

    Science.gov (United States)

    James S. Jordan; Francis M. Rushmore

    1969-01-01

    A relatively few animal species are responsible for most of the reported damage to the birches. White-tailed deer, yellow-bellied sapsuckers, porcupines, moose, and hares are the major animals involved. We will review reports of damage, discuss the underlying causes, and describe possible methods of control. For example, heavy deer browsing that eliminates birch...

  10. Animal damage management handbook.

    Science.gov (United States)

    Hugh C. Black

    1994-01-01

    This handbook treats animal damage management (ADM) in the West in relation to forest, range, and recreation resources; predator management is not addressed. It provides a comprehensive reference of safe, effective, and practical methods for managing animal damage on National Forest System lands. Supporting information is included in references after each chapter and...

  11. The Classroom Animal: Snails.

    Science.gov (United States)

    Kramer, David S.

    1985-01-01

    Points out that snails are interesting and easily-managed classroom animals. One advantage of this animal is that it requires no special attention over weekends or holidays. Background information, anatomy, reproduction, and feeding are discussed, along with suggestions for housing aquatic and/or land snails. (DH)

  12. Political Communication with Animals

    NARCIS (Netherlands)

    Meijer, E.

    2013-01-01

    In this article I sketch the outlines of a theory of political human-animal conversations, based on ideas about language that I borrow from Ludwig Wittgenstein’s later work, in particular his notion of language-games. I present this theory as a supplement to the political theory of animal rights Sue

  13. Indian draught animals power

    Directory of Open Access Journals (Sweden)

    K. L. Phaniraja

    Full Text Available With the modernization of agriculture, the use of mechanical power in agriculture has increased but draught animal power (DAP continues to be used on Indian farms due to small holdings and hill agriculture. More than 55% of the total cultivated area is still being managed by using draught animals as against about 20% by tractors. India possessed the finest breeds of draught animals. Bullocks, buffaloes and camels are the major draught animals for field operations. Horses, mules, donkeys, yak and mithun are the pack animals for transport. The quality of work from the draught animals depends upon the power developed by them. The design of traditional implements is based on long experience and these have served the purpose of the farmers. However there is plenty of scope to improve the design based on animal-machine-environment interaction so as to have more output and increased efficiency without jeopardizing animal health. [Vet World 2009; 2(10.000: 404-407

  14. Historie i spillefilm - for elever

    DEFF Research Database (Denmark)

    Tønnesen, Lone Guldbrandt

    2016-01-01

    MOOC om historiebrug i spillefilm, hvor elever kan lære om, hvordan spillefilm bruger fortiden, og om hvordan vores opfattelse af historien både sætter sig spor i filmene og bliver påvirket af dem.......MOOC om historiebrug i spillefilm, hvor elever kan lære om, hvordan spillefilm bruger fortiden, og om hvordan vores opfattelse af historien både sætter sig spor i filmene og bliver påvirket af dem....

  15. Tether Elevator Crawler Systems (TECS)

    Science.gov (United States)

    Swenson, Frank R.

    1987-01-01

    One of the needs of the experimenters on the space station is access to steady and controlled-variation microgravity environments. A method of providing these environments is to place the experiment on a tether attached to the space station. This provides a high degree of isolation from structural oscillations and vibrations. Crawlers can move these experiments along the tethers to preferred locations, much like an elevator. This report describes the motion control laws developed for these crawlers and the testing of laboratory models of these tether elevator crawlers.

  16. Elevated environmental temperature and methamphetamine neurotoxicity

    International Nuclear Information System (INIS)

    Miller, Diane B.; O'Callaghan, James P.

    2003-01-01

    Amphetamines have been of considerable research interest for the last several decades. More recent work has renewed interest in the role of ambient temperature in both the toxicity and neurotoxicity of these drugs. We have determined that the striatal dopaminergic neurotoxicity observed in the mouse is linked in some fashion to both body and environmental temperature. Most studies of d-methamphetamine (d-METH) neurotoxicity are conducted at standard laboratory ambient temperatures (e.g., ∼21-22 deg. C) and utilizing a repeated dosage regimen (e.g., three to four injections spaced 2 h apart). A lowering of the ambient temperature provides neuro protection, while an elevation increases neurotoxicity. d-METH causes long-term depletions of triatal dopamine (DA) that are accompanied by other changes that are indicative of nerve terminal degeneration. These include argyrophilia, as detected by silver degeneration stains, and an elevation in glial fibrillary acidic protein (GFAP), a marker of reactive gliosis in response to injury, as well as a long-term decrease in tyrosine hydroxylase (TH) protein levels. here we show that increasing the ambient temperature during and for some time following dosing increases the neurotoxicity of d-METH. Mice (female 57BL6/J) given a single dosage of d-METH (20 mg/kg s.c.) and maintained at the usual laboratory ambient temperature show minimal striatal damage (an ∼15% depletion of DA and an ∼ 86% increase in GFAP). substantial striatal damage (e.g., an ∼70% depletion of DA and an ∼200% elevation in GFAP) was induced by this regimen if mice were maintained at 27 deg. C for 24 or 72 h following dosing. An increase in neurotoxicity was also apparent in mice kept at an elevated temperature for only 5 or 9 h, but keeping animals at 27 deg. C for 24 or 72 h was the most effective in increasing the neurotoxicity of d-METH. Our data show how a relatively minor change in ambient temperature can have a major impact on the degree of

  17. Becoming Sheep, Becoming Animal..

    DEFF Research Database (Denmark)

    Grum, Charlotte; Svabo, Connie

    reading of a particular historical subject and to explore the messy constituents of the very categories of women and animals. In general she is occupied with how to animate and perform the intra-active entanglement of subjectivity and materiality.The “Becoming Sheep” project produced a variety of visual......-acting and becoming with the heath habitat, the other by-passing human and non-human animals, the changing weather and their fluctuating biological needs. She wanted to explore the discursive and material effects of a site specific human-nonhuman animal intra-action, to challenge the gendered and anthropocentric...... practice.Continuing explorations of how to undo authorship, activate multiple subject positions and animate the very resources through which we practice and continuously become, for this conference artist Charlotte Grum has invited Connie Svabo, Associate Professor in Performance-Design at Roskilde...

  18. Sketching with animation

    DEFF Research Database (Denmark)

    Vistisen, Peter

    This book offers a contribution to the theory, method and techniques involved in the use of animation as a tool for temporal design sketching. Lifted from its traditional role as a genre of entertainment and art and reframed in the design domain, animation offers support during the early phases...... of exploring and assessing the potential of new and emerging digital technologies. This approach is relatively new and has been touched upon by few academic contributions in the past. Thus, the aim of the text is not to promote a claim that sketching with animation is an inherently new phenomenon. Instead......, the aim is to present a range of analytical arguments and experimental results that indicate the need for a systematic approach to realising the potential of animation within design sketching. This will establish the foundation for what we label animation-based sketching....

  19. Is animal experimentation fundamental?

    Science.gov (United States)

    d'Acampora, Armando José; Rossi, Lucas Félix; Ely, Jorge Bins; de Vasconcellos, Zulmar Acciolli

    2009-01-01

    The understanding about the utilization of experimental animals in scientific research and in teaching is many times a complex issue. Special attention needs to be paid to attain the understanding by the general public of the importance of animal experimentation in experimental research and in undergraduate medical teaching. Experimental teaching and research based on the availability of animals for experimentation is important and necessary for the personal and scientific development of the physician-to-be. The technological arsenal which intends to mimic experimentation animals and thus fully replace their use many times does not prove to be compatible with the reality of the living animal. The purpose of this paper is to discuss aspects concerning this topic, bringing up an issue which is complex and likely to arouse in-depth reflections.

  20. Animal ethics dilemma

    DEFF Research Database (Denmark)

    Dich, Trine; Hansen, Tina; Algers, Anne

    2006-01-01

    ) the blind hens; (2) ANDi the genetically modified monkey; (3) euthanasia of a healthy dog; (4) animal slaughter; and (5) rehabilitation of seals. Special consideration has been given to enhancing the pedagogic value of the program. Students can control their learning by selecting a variety of ways......'Animal Ethics Dilemma' is a freely available computer-supported learning tool (www.animalethicsdilemma.net or www.aedilemma.net) which has been developed primarily for veterinary undergraduates but is applicable also to students in other fields of animal science. The objectives of the computer...... program are to promote students' understanding of the ethics related to animal use, to illustrate ethical dilemmas that arise in animal use, to broaden students' moral imagination, and to enable students to differentiate between types of ethical argument. The program comprises five case studies: (1...

  1. Principles of animal extrapolation

    Energy Technology Data Exchange (ETDEWEB)

    Calabrese, E.J.

    1991-01-01

    Animal Extrapolation presents a comprehensive examination of the scientific issues involved in extrapolating results of animal experiments to human response. This text attempts to present a comprehensive synthesis and analysis of the host of biomedical and toxicological studies of interspecies extrapolation. Calabrese's work presents not only the conceptual basis of interspecies extrapolation, but also illustrates how these principles may be better used in selection of animal experimentation models and in the interpretation of animal experimental results. The book's theme centers around four types of extrapolation: (1) from average animal model to the average human; (2) from small animals to large ones; (3) from high-risk animal to the high risk human; and (4) from high doses of exposure to lower, more realistic, doses. Calabrese attacks the issues of interspecies extrapolation by dealing individually with the factors which contribute to interspecies variability: differences in absorption, intestinal flora, tissue distribution, metabolism, repair mechanisms, and excretion. From this foundation, Calabrese then discusses the heterogeneticity of these same factors in the human population in an attempt to evaluate the representativeness of various animal models in light of interindividual variations. In addition to discussing the question of suitable animal models for specific high-risk groups and specific toxicological endpoints, the author also examines extrapolation questions related to the use of short-term tests to predict long-term human carcinogenicity and birth defects. The book is comprehensive in scope and specific in detail; for those environmental health professions seeking to understand the toxicological models which underlay health risk assessments, Animal Extrapolation is a valuable information source.

  2. Elevated circulating PAI-1 levels are related to lung function decline, systemic inflammation, and small airway obstruction in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Wang H

    2016-09-01

    correlation analysis showed that circulating PAI-1 was inversely correlated with pulmonary function parameters including the ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC, FEV1/Pre (justified r=-0.308, P<0.001; justified r=-0.295, P=0.001, respectively and SAO indicators such as FEV3/FVC, MMEF25–75/Pre (justified r=-0.289, P=0.001; justified r=-0.273, P=0.002, respectively, but positively related to the inflammatory marker CRP (justified r=0.351, P<0.001, the small airway remolding biomarker TIMP-1, and MMP-9 (justified r=0.498, P<0.001; justified r=0.267, P=0.002, respectively. Besides, multivariable linear analysis showed that FEV1/FVC, CRP, and TIMP-1 were independent parameters associated with PAI-1. Conclusion: Our findings first illustrate that elevated serum PAI-1 levels are related to the lung function decline, systemic inflammation, and SAO in COPD, suggesting that PAI-1 may play critical roles in the pathogenesis of COPD. Keywords: plasminogen activator inhibitor-1 (PAI-1, chronic obstructive pulmonary disease (COPD, systemic inflammation, small airway obstruction (SAO

  3. Dannelsen af den ansvarlige elev

    DEFF Research Database (Denmark)

    Larsen, Jesper

    2010-01-01

    Denne artikel handler om den del af lærergerningen, der har at gøre med udarbejdelse af elevplaner. Der tages udgangspunkt i en foucaultsk forståelse, hvor beskrivelsen af den enkelte elev udtrykker et særligt normativt ideal om, hvilke former for elevhed der er de ønskværdige i den danske...

  4. Methylphenidatinduceret ST-elevations-myokardieinfarkt

    DEFF Research Database (Denmark)

    Ruwald, Martin Huth; Ruwald, Anne-Christine Huth; Tønder, Niels

    2012-01-01

    Adult attention deficit and hyperkinetic disorder (ADHD) is increasingly diagnosed and treated with methylphenidate. We present the case of an 20 year-old man, who was diagnosed with ADHD and suffered a ST elevation acute myocardial infarction due to coronary vasospasm related to an overdose...

  5. Elevated lactate during psychogenic hyperventilation

    NARCIS (Netherlands)

    ter Avest, E.; Patist, F. M.; ter Maaten, J. C.; Nijsten, M. W. N.

    Study objective Elevated arterial lactate levels are closely related to morbidity and mortality in various patient categories. In the present retrospective study, the relation between arterial lactate, partial pressure of carbon dioxide (Pco(2)) and pH was systematically investigated in patients who

  6. Computer facial animation

    CERN Document Server

    Parke, Frederic I

    2008-01-01

    This comprehensive work provides the fundamentals of computer facial animation and brings into sharper focus techniques that are becoming mainstream in the industry. Over the past decade, since the publication of the first edition, there have been significant developments by academic research groups and in the film and games industries leading to the development of morphable face models, performance driven animation, as well as increasingly detailed lip-synchronization and hair modeling techniques. These topics are described in the context of existing facial animation principles. The second ed

  7. Environmentally friendly animal litter

    Science.gov (United States)

    Chett, Boxley; McKelvie, Jessica

    2013-08-20

    A method of making an animal litter that includes geopolymerized ash, wherein, the animal litter is made from a quantity of a pozzolanic ash mixed with a sufficient quantity of water and an alkaline activator to initiate a geopolymerization reaction that forms geopolymerized ash. After the geopolymerized ash is formed, it is dried, broken into particulates, and sieved to a desired size. These geopolymerized ash particulates are used to make a non-clumping or clumping animal litter. Odor control may be accomplished with the addition of a urease inhibitor, pH buffer, an odor eliminating agent, and/or fragrance.

  8. Animal Telemetry Network (ATN)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — These data (updated daily) are from the Animal Telemetry Network (ATN) program. Begun as one of the field projects in the international Census of Marine Life, the...

  9. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... search Popular ... produced a nine-minute animation explaining how antimicrobial resistance both emerges and proliferates among bacteria. Over time, the use of antimicrobial drugs will ...

  10. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... bacteria. Over time, the use of antimicrobial drugs will result in the development of resistant strains of ... and other key audiences. We hope this animation will make the concept more understandable to non-scientists ...

  11. Animal-free toxicology

    DEFF Research Database (Denmark)

    Knudsen, Lisbeth E

    2013-01-01

    Human data on exposure and adverse effects are the most appropriate for human risk assessment, and modern toxicology focuses on human pathway analysis and the development of human biomarkers. Human biomonitoring and human placental transport studies provide necessary information for human risk...... assessment, in accordance with the legislation on chemical, medicine and food safety. Toxicology studies based on human mechanistic and exposure information can replace animal studies. These animal-free approaches can be further supplemented by new in silico methods and chemical structure......-activity relationships. The inclusion of replacement expertise in the international Three Rs centres, the ongoing exploration of alternatives to animal research, and the improvement of conditions for research animals, all imply the beginning of a paradigm shift in toxicology research toward the use of human data....

  12. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... Food and Drug Administration's (FDA's) Center for Veterinary Medicine (CVM) produced a nine-minute animation explaining how ... efforts are underway in both veterinary and human medicine to preserve the effectiveness of these drugs. One ...

  13. Animal health and production

    International Nuclear Information System (INIS)

    Kallfelz, F.A.; Lengemann, F.W.

    1984-01-01

    Some applications of the use of radioisotopes and radiation in animal health and production research are reviewed. These include various techniques associated with both the qualitative localization and quantitative measurements of isotopes in animals; comparator studies in which measurement of the radioactivity in one part of a system will allow computation of the mass or volume in another part; in vivo and in vitro applications of isotope dilution studies; and the use of isotopes in dynamic systems analyses. The use of stable isotopes in mass spectrometry, activation analysis and nuclear magnetic resonance in animal research is also briefly reviewed. Finally some of the successful uses of radiation produced by radioactive sources or various types of generators of electromagnetic radiations in animal production and health studies are described. (U.K.)

  14. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... About FDA Contact FDA Browse by Product Area Product Areas back Food Drugs Medical Devices Radiation-Emitting Products Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products

  15. Animal Product Safety Information

    Science.gov (United States)

    ... Home Animal & Veterinary Safety & Health Product Safety Information Product Safety Information Share Tweet Linkedin Pin it More ... to report adverse experiences with veterinary drugs. Additional Product Information Questions and Answers: Evanger’s Dog and Cat ...

  16. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... complex. This video was designed to make the concept of antimicrobial resistance more real and understandable to ... audiences. We hope this animation will make the concept more understandable to non-scientists by showing how ...

  17. Animal transportation networks

    Science.gov (United States)

    Perna, Andrea; Latty, Tanya

    2014-01-01

    Many group-living animals construct transportation networks of trails, galleries and burrows by modifying the environment to facilitate faster, safer or more efficient movement. Animal transportation networks can have direct influences on the fitness of individuals, whereas the shape and structure of transportation networks can influence community dynamics by facilitating contacts between different individuals and species. In this review, we discuss three key areas in the study of animal transportation networks: the topological properties of networks, network morphogenesis and growth, and the behaviour of network users. We present a brief primer on elements of network theory, and then discuss the different ways in which animal groups deal with the fundamental trade-off between the competing network properties of travel efficiency, robustness and infrastructure cost. We consider how the behaviour of network users can impact network efficiency, and call for studies that integrate both network topology and user behaviour. We finish with a prospectus for future research. PMID:25165598

  18. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... lawmakers, consumer representatives and other key audiences. We hope this animation will make the concept more understandable ... English FDA Accessibility Careers FDA Basics FOIA No FEAR Act Site Map Nondiscrimination Website Policies U.S. Food ...

  19. [Alternatives to animal testing].

    Science.gov (United States)

    Fabre, Isabelle

    2009-11-01

    The use of alternative methods to animal testing are an integral part of the 3Rs concept (refine, reduce, replace) defined by Russel & Burch in 1959. These approaches include in silico methods (databases and computer models), in vitro physicochemical analysis, biological methods using bacteria or isolated cells, reconstructed enzyme systems, and reconstructed tissues. Emerging "omic" methods used in integrated approaches further help to reduce animal use, while stem cells offer promising approaches to toxicologic and pathophysiologic studies, along with organotypic cultures and bio-artificial organs. Only a few alternative methods can so far be used in stand-alone tests as substitutes for animal testing. The best way to use these methods is to integrate them in tiered testing strategies (ITS), in which animals are only used as a last resort.

  20. Trade, Environment & Animal Welfare

    DEFF Research Database (Denmark)

    Morrison, Peter; Nielsen, Laura

    2013-01-01

    Regulation of animal welfare and the environment under the WTO GATT and GATS Agreements - including introduction of the innovative idea of limiting consumption abroad (mode 2) for e.g. bull fights.......Regulation of animal welfare and the environment under the WTO GATT and GATS Agreements - including introduction of the innovative idea of limiting consumption abroad (mode 2) for e.g. bull fights....

  1. Nanotechnology and animal health

    Directory of Open Access Journals (Sweden)

    Shiva Kumar

    Full Text Available Nanotechnology, although still in the early stages of its development, is beginning to equip scientists, engineers and biologists to work at the cellular and molecular levels for significant benefits in healthcare and animal medicine. It is reasonable to presume over the next couple of decades that nanobiotechnology industries and unique developments will be revolutionising animal health and medicine. [Veterinary World 2010; 3(12.000: 567-569

  2. Modelling Farm Animal Welfare

    Science.gov (United States)

    Collins, Lisa M.; Part, Chérie E.

    2013-01-01

    Simple Summary In this review paper we discuss the different modeling techniques that have been used in animal welfare research to date. We look at what questions they have been used to answer, the advantages and pitfalls of the methods, and how future research can best use these approaches to answer some of the most important upcoming questions in farm animal welfare. Abstract The use of models in the life sciences has greatly expanded in scope and advanced in technique in recent decades. However, the range, type and complexity of models used in farm animal welfare is comparatively poor, despite the great scope for use of modeling in this field of research. In this paper, we review the different modeling approaches used in farm animal welfare science to date, discussing the types of questions they have been used to answer, the merits and problems associated with the method, and possible future applications of each technique. We find that the most frequently published types of model used in farm animal welfare are conceptual and assessment models; two types of model that are frequently (though not exclusively) based on expert opinion. Simulation, optimization, scenario, and systems modeling approaches are rarer in animal welfare, despite being commonly used in other related fields. Finally, common issues such as a lack of quantitative data to parameterize models, and model selection and validation are discussed throughout the review, with possible solutions and alternative approaches suggested. PMID:26487411

  3. Animal and human influenzas.

    Science.gov (United States)

    Peiris, M; Yen, H-L

    2014-08-01

    Influenza type A viruses affect humans and other animals and cause significant morbidity, mortality and economic impact. Influenza A viruses are well adapted to cross species barriers and evade host immunity. Viruses that cause no clinical signs in wild aquatic birds may adapt in domestic poultry to become highly pathogenic avian influenza viruses which decimate poultry flocks. Viruses that cause asymptomatic infection in poultry (e.g. the recently emerged A/H7N9 virus) may cause severe zoonotic disease and pose a major pandemic threat. Pandemic influenza arises at unpredictable intervals from animal viruses and, in its global spread, outpaces current technologies for making vaccines against such novel viruses. Confronting the threat of influenza in humans and other animals is an excellent example of a task that requires a One Health approach. Changes in travel, trade in livestock and pets, changes in animal husbandry practices, wet markets and complex marketing chains all contribute to an increased risk of the emergence of novel influenza viruses with the ability to cross species barriers, leading to epizootics or pandemics. Coordinated surveillance at the animal- human interface for pandemic preparedness, risk assessment, risk reduction and prevention at source requires coordinated action among practitioners in human and animal health and the environmental sciences. Implementation of One Health in the field can be challenging because of divergent short-term objectives. Successful implementation requires effort, mutual trust, respect and understanding to ensure that long-term goals are achieved without adverse impacts on agricultural production and food security.

  4. Does size matter? Animal units and animal unit months

    Science.gov (United States)

    Lamar Smith; Joe Hicks; Scott Lusk; Mike Hemmovich; Shane Green; Sarah McCord; Mike Pellant; John Mitchell; Judith Dyess; Jim Sprinkle; Amanda Gearhart; Sherm Karl; Mike Hannemann; Ken Spaeth; Jason Karl; Matt Reeves; Dave Pyke; Jordan Spaak; Andrew Brischke; Del Despain; Matt Phillippi; Dave Weixelmann; Alan Bass; Jessie Page; Lori Metz; David Toledo; Emily Kachergis

    2017-01-01

    The concepts of animal units, animal unit months, and animal unit equivalents have long been used as standards for range management planning, estimating stocking rates, reporting actual use, assessing grazing fees, ranch appraisal, and other purposes. Increasing size of cattle on rangelands has led some to suggest that the definition of animal units and animal unit...

  5. AnimationsØen

    DEFF Research Database (Denmark)

    Frølunde, Lisbeth; Israel, Samuel Ben; Dam, Jannie

    2007-01-01

    Et digitalt undervisningsmateriale om at undervise i film. Omfatter lærervejledning og bibliografi. Der vises klips fra DRs arkiver om animationsfilm. Materialet beskriver empiriindsamling til Ph.d. projekt og viser film lavet af elever som deltog i forskningsprojektet. Materialet er publiceret p...

  6. Elevator deflections on the icing process

    Science.gov (United States)

    Britton, Randall K.

    1990-01-01

    The effect of elevator deflection of the horizontal stabilizer for certain icing parameters is investigated. Elevator deflection can severely change the lower and upper leading-edge impingement limits, and ice can accrete on the elevator itself. Also, elevator deflection had practically no effect on the maximum local collection efficiency. It is shown that for severe icing conditions (large water droplets), elevator deflections that increase the projected height of the airfoil can significantly increase the total collection efficiency of the airfoil.

  7. Keratoconus Progression in Patients With Allergy and Elevated Surface Matrix Metalloproteinase 9 Point-of-Care Test.

    Science.gov (United States)

    Mazzotta, Cosimo; Traversi, Claudio; Mellace, Pierfrancesco; Bagaglia, Simone A; Zuccarini, Silvio; Mencucci, Rita; Jacob, Soosan

    2017-10-04

    To assess keratoconus (KC) progression in patients with allergies who also tested positive to surface matrix metalloproteinase 9 (MMP-9) point-of-care test. Prospective comparative study including 100 stage I-II keratoconic patients, mean age 16.7±4.6 years. All patients underwent an anamnestic questionnaire for concomitant allergic diseases and were screened with the MMP-9 point-of-care test. Patients were divided into two groups: patients KC with allergies (KC AL) and patients KC without allergies (KC NAL). Severity of allergy was established by papillary subtarsal response grade and KC progression assessed by Scheimpflug corneal tomography, corrected distance visual acuity (CDVA) measurement in a 12-month follow-up. The KC AL group included 52 patients and the KC NAL group 48. In the KC AL group, 42/52 of patients (81%) were positive to MMP-9 point-of-care test versus two positive patients in the KC NAL group (4%). The KC AL group data showed a statistically significant decrease of average CDVA, from 0.155±0.11 to 0.301±0.2 logarithm of the minimum angle of resolution (Paverage. The KC NAL group revealed a slight KC progression without statistically significant changes. Pearson correlation test showed a high correlation between Kmax worsening and severity of PSR in the KC AL group. The study demonstrated a statistically significant progression of KC in patients with concomitant allergies, positive to MMP-9 point-of-care test versus negative. A high correlation between severity of allergy and KC progression was documented.

  8. Når elever producerer

    DEFF Research Database (Denmark)

    Bremholm, Jesper; Hansen, Rune; Slot, Marie Falkesgaard

    2017-01-01

    Dette kapitel præsenterer centrale resultater fra studiet Elevopgaver og elevproduktion i det 21. århundrede der blandt andet rummer den første større kvantitative undersøgelse af opgavedidaktik og elevers produktive arbejde i den danske grundskole. Studiet omfatter også en kvalitativ del, og i...... undersøgelsen præsenteres og diskuteres gennem en række konkrete eksempler fra de berørte fag. I forhold til elevers produktive arbejde peger undersøgelsens resultater både på potentialer og særlige barrierer i forbindelse med at udvikle en kompetenceorienteret undervisning. I kapitlet argumenteres desuden...

  9. Læring mellem elever

    DEFF Research Database (Denmark)

    Georgsen, Marianne; Davidsen, Jacob

    2010-01-01

    I denne rapport præsenteres resultater fra følgeforskningen til projektet Læring gennem Bevægelse, som er gennemført på Søndervangskolen i Hammel i perioden august 2009 - maj 2010. Projektet er gennemført i samspil mellem lærere, it-vejleder, elever og skolens ledelse. Projektets overordnede formål...

  10. Science on a space elevator

    Energy Technology Data Exchange (ETDEWEB)

    Laubscher, B. E. (Bryan E.); Jorgensen, A. M. (Anders M.)

    2004-01-01

    The Space Elevator (SE) represents a major paradigm shift in space access. If the SE's promise of low cost access can be realized, everything becomes economically more feasible to accomplish in space. In this paper we describe in-situ science stations mounted on a science-dedicated space elevator tether. The concept presented here involves a carbon nanotube ribbon that is constructed by an existing space elevator and then science sensors are stationed along the ribbon at differing altitudes. The finished ribbon can be moved across the earth to the position at which its scientific measurements are to be taken. The ability to station scientific, in-situ instrumentation at different altitudes for round-the-clock observations is a unique capability of the SE. The environments that the science packages sense range from the troposphere out beyond the magnetopause of the magnetosphere on the solar side of the earth. Therefore, the very end of the SE can sense the solar wind. The measurements at various points along its length include temperature, pressure, density, sampling, chemical analyses, wind speed, turbulence, free oxygen, electromagnetic radiation, cosmic rays, energetic particles and plasmas in the earth's magnetosphere and the solar wind. There exist some altitudes that are difficult to access with aircraft or balloons or rockets and so remain relatively unexplored. The space elevator solves these problems and opens these regions up to in-situ measurements. Without the need for propulsion, the SE provides a more benign and pristine environment for atmospheric measurements than available with powered aircraft. Moreover, replacing and upgrading instrumentation is expected to be very cost effective with the SE. Moving and stationing the science SE affords the opportunity to sense multiple regions of the atmosphere. The SE's geosynchronous, orbital motion through the magnetosphere, albeit nominally with Earth's magnetic field, will trace a plane

  11. Naturalness and Animal Welfare.

    Science.gov (United States)

    Yeates, James

    2018-04-05

    Naturalness is considered important for animals, and is one criterion for assessing how we care for them. However, it is a vague and ambiguous term, which needs definition and assessments suitable for scientific and ethical questions. This paper makes a start on that aim. This paper differentiates the term from other related concepts, such as species-typical behaviour and wellbeing. It identifies contingent ways in which naturalness might be used, as: (i) prompts for further welfare assessment; (ii) a plausible hypothesis for what safeguards wellbeing; (iii) a threshold for what is acceptable; (iv) constraints on what improvements are unacceptable; and (v) demarcating what is not morally wrong, because of a lack of human agency. It then suggests an approach to evaluating animals' behaviour that is quantitative, is based on reality, and which assesses naturalness by degrees. It proposes classing unaffected wild populations as natural by definition. Where animals might have been affected by humans, they should be compared to the closest population(s) of unaffected animals. This approach could allow us both to assess naturalness scientifically, and to make practical decisions about the behaviour of domestic animals.

  12. ANIMAL ENTEROTOXIGENIC ESCHERICHIA COLI

    Science.gov (United States)

    Dubreuil, J. Daniel; Isaacson, Richard E.; Schifferli, Dieter M.

    2016-01-01

    Enterotoxigenic Escherichia coli (ETEC) is the most common cause of E. coli diarrhea in farm animals. ETEC are characterized by the ability to produce two types of virulence factors; adhesins that promote binding to specific enterocyte receptors for intestinal colonization and enterotoxins responsible for fluid secretion. The best-characterized adhesins are expressed in the context of fimbriae, such as the F4 (also designated K88), F5 (K99), F6 (987P), F17 and F18 fimbriae. Once established in the animal small intestine, ETEC produces enterotoxin(s) that lead to diarrhea. The enterotoxins belong to two major classes; heat-labile toxin that consist of one active and five binding subunits (LT), and heat-stable toxins that are small polypeptides (STa, STb, and EAST1). This chapter describes the disease and pathogenesis of animal ETEC, the corresponding virulence genes and protein products of these bacteria, their regulation and targets in animal hosts, as well as mechanisms of action. Furthermore, vaccines, inhibitors, probiotics and the identification of potential new targets identified by genomics are presented in the context of animal ETEC. PMID:27735786

  13. Animal models of sarcoidosis.

    Science.gov (United States)

    Hu, Yijie; Yibrehu, Betel; Zabini, Diana; Kuebler, Wolfgang M

    2017-03-01

    Sarcoidosis is a debilitating, inflammatory, multiorgan, granulomatous disease of unknown cause, commonly affecting the lung. In contrast to other chronic lung diseases such as interstitial pulmonary fibrosis or pulmonary arterial hypertension, there is so far no widely accepted or implemented animal model for this disease. This has hampered our insights into the etiology of sarcoidosis, the mechanisms of its pathogenesis, the identification of new biomarkers and diagnostic tools and, last not least, the development and implementation of novel treatment strategies. Over past years, however, a number of new animal models have been described that may provide useful tools to fill these critical knowledge gaps. In this review, we therefore outline the present status quo for animal models of sarcoidosis, comparing their pros and cons with respect to their ability to mimic the etiological, clinical and histological hallmarks of human disease and discuss their applicability for future research. Overall, the recent surge in animal models has markedly expanded our options for translational research; however, given the relative early stage of most animal models for sarcoidosis, appropriate replication of etiological and histological features of clinical disease, reproducibility and usefulness in terms of identification of new therapeutic targets and biomarkers, and testing of new treatments should be prioritized when considering the refinement of existing or the development of new models.

  14. Animals and ICE

    DEFF Research Database (Denmark)

    van Hemmen, J Leo; Christensen-Dalsgaard, Jakob; Carr, Catherine E

    2016-01-01

    experimental and mathematical foundation, it is known that there is a low-frequency regime where the internal time difference (iTD) as perceived by the animal may well be 2-5 times higher than the external ITD, the interaural time difference, and that there is a frequency plateau over which the fraction i......TD/ITD is constant. There is also a high-frequency regime where the internal level (amplitude) difference iLD as perceived by the animal is much higher than the interaural level difference ILD measured externally between the two ears. The fundamental tympanic frequency segregates the two regimes. The present special...... issue devoted to "internally coupled ears" provides an overview of many aspects of ICE, be they acoustic, anatomical, auditory, mathematical, or neurobiological. A focus is on the hotly debated topic of what aspects of ICE animals actually exploit neuronally to localize a sound source....

  15. Theriocide: Naming Animal Killing

    Directory of Open Access Journals (Sweden)

    Piers Beirne

    2014-08-01

    Full Text Available In this essay I recommend ‘theriocide’ as the name for those diverse human actions that cause the deaths of animals. Like the killing of one human by another, theriocide may be socially acceptable or unacceptable, legal or illegal. It may be intentional or unintentional and may involve active maltreatment or passive neglect. Theriocide may occur one-on-one, in small groups or in large-scale social institutions. The numerous and sometimes intersecting sites of theriocide include intensive rearing regimes; hunting and fishing; trafficking; vivisection; militarism; pollution; and human-induced climate change. If the killing of animals by humans is as harmful to them as homicide is to humans, then the proper naming of such deaths offers a remedy, however small, to the extensive privileging of human lives over those of other animals. Inevitably, the essay leads to a shocking question: Is theriocide murder?

  16. Animal Poetry and Empathy

    Directory of Open Access Journals (Sweden)

    Tirza Brüggemann

    2017-04-01

    Full Text Available This article discusses how our ideas of empathy are influenced by the dichotomy of mind versus body, also known as Cartesian dualism. Within the aesthetic field, this dichotomy is seen when researchers define narrative empathy as imaginatively reconstructing the fictional character’s thoughts and feelings. Conversely, the empathy aroused by a non-narrative work of art is seen as an unconscious bodily mirroring of movements, postures or moods. Thinking dualistically does not only have consequences for what we consider human nature; it also affects our view on animals. To show the untenability of dualistic thinking, this article focuses on the animal poetry genre. Using the ideas of the French phenomenologist Maurice Merleau-Ponty, I analyze two animal poems: “Inventing a Horse” by Meghan O’Rourke and “Spermaceti” by Les Murray. The analysis of these two poems suggests that the presiding ideas about aesthetic empathy and empathy in general need re-evaluation.

  17. Animal violence demystified.

    Science.gov (United States)

    Natarajan, Deepa; Caramaschi, Doretta

    2010-01-01

    Violence has been observed in humans and animals alike, indicating its evolutionary/biological significance. However, violence in animals has often been confounded with functional forms of aggressive behavior. Currently, violence in animals is identified primarily as either a quantitative behavior (an escalated, pathological and abnormal form of aggression characterized primarily by short attack latencies, and prolonged and frequent harm-oriented conflict behaviors) or a qualitative one (characterized by attack bites aimed at vulnerable parts of the opponent's body and context independent attacks regardless of the environment or the sex and type of the opponent). Identification of an operational definition for violence thus not only helps in understanding its potential differences from adaptive forms of aggression but also in the selection of appropriate animal models for both. We address this issue theoretically by drawing parallels from research on aggression and appeasement in humans and other animals. We also provide empirical evidences for violence in mice selected for high aggression by comparing our findings with other currently available potentially violent rodent models. The following violence-specific features namely (1) Display of low levels of pre-escalatory/ritualistic behaviors. (2) Immediate and escalated offense durations with low withdrawal rates despite the opponent's submissive supine and crouching/defeat postures. (3) Context independent indiscriminate attacks aimed at familiar/unfamiliar females, anaesthetized males and opponents and in neutral environments. (4) Orientation of attack-bites toward vulnerable body parts of the opponent resulting in severe wounding. (5) Low prefrontal serotonin (5-HT) levels upon repeated aggression. (6) Low basal heart rates and hyporesponsive hypothalamus-pituitary-adrenocortical (HPA) axis were identified uniquely in the short attack latency (SAL) mice suggesting a qualitative difference between violence and

  18. Animal violence demystified

    Directory of Open Access Journals (Sweden)

    Deepa Natarajan

    2010-04-01

    Full Text Available Violence has been observed in humans and animals alike, indicating its evolutionary/ biological significance. However, violence in animals has often been confounded with functional forms of aggressive behavior. Currently, violence in animals is identified primarily as either a quantitative behavior (an escalated, pathological and abnormal form of aggression characterized primarily by short attack latencies, and prolonged and frequent harm-oriented conflict behaviors or a qualitative one (characterized by attack bites aimed at vulnerable parts of the opponent’s body and context independent attacks regardless of the environment or the sex and type of the opponent. Identification of an operational definition for violence thus not only helps in understanding its potential differences from adaptive forms of aggression but also in the selection of appropriate animal models for both. To begin with, we address this issue theoretically by drawing parallels from research on aggression and appeasement in humans and other animals. We also provide empirical evidences for violence in mice selected for high aggression by comparing our findings with other currently available potentially violent rodent models. The following violence-specific features namely 1. Display of low levels of pre-escalatory/ritualistic behaviors. 2. Immediate and escalated offense durations with low withdrawal rates despite the opponent’s submissive supine and crouching/defeat postures. 3. Context independent indiscriminate attacks aimed at familiar/unfamiliar females, anaesthetized males and opponents and in neutral environments. 4. Orientation of attack-bites toward vulnerable body parts of the opponent resulting in severe wounding 5. Low pre-frontal serotonin (5-HT levels upon repeated aggression. 6. Low basal heart rates and hyporesponsive hypothalamus-pituitary-adrenocortical (HPA axis were identified uniquely in the short attack latency (SAL mice suggesting a qualitative

  19. Animals exposed to radon

    International Nuclear Information System (INIS)

    Masse, R.; Morin, M.; Lafuma, J.; Morlier, J.P.; Chameaud, J.; Bredon, P.

    1992-01-01

    'There is sufficient evidence that 222 Rn is a carcinogen in animals': this statement was important for the classification of radon as carcinogenic to man, outside of uranium mine atmospheres, clearly identified by epidemiology as causing lung cancer. Since recent reviews of animal experiments have been given by NCRP and by IARC, this review will be mainly limited to the recent results which came from two laboratories in the last 20 years. Battelle Pacific Northwest Laboratories (PNL), USA, and COGEMA Laboratoire de Pathologie Professionnelle (LPP) France. (author)

  20. Antibiotics in Animal Products

    Science.gov (United States)

    Falcão, Amílcar C.

    The administration of antibiotics to animals to prevent or treat diseases led us to be concerned about the impact of these antibiotics on human health. In fact, animal products could be a potential vehicle to transfer drugs to humans. Using appropri ated mathematical and statistical models, one can predict the kinetic profile of drugs and their metabolites and, consequently, develop preventive procedures regarding drug transmission (i.e., determination of appropriate withdrawal periods). Nevertheless, in the present chapter the mathematical and statistical concepts for data interpretation are strictly given to allow understanding of some basic pharma-cokinetic principles and to illustrate the determination of withdrawal periods

  1. Animal models of tinnitus.

    Science.gov (United States)

    Brozoski, Thomas J; Bauer, Carol A

    2016-08-01

    Presented is a thematic review of animal tinnitus models from a functional perspective. Chronic tinnitus is a persistent subjective sound sensation, emergent typically after hearing loss. Although the sensation is experientially simple, it appears to have central a nervous system substrate of unexpected complexity that includes areas outside of those classically defined as auditory. Over the past 27 years animal models have significantly contributed to understanding tinnitus' complex neurophysiology. In that time, a diversity of models have been developed, each with its own strengths and limitations. None has clearly become a standard. Animal models trace their origin to the 1988 experiments of Jastreboff and colleagues. All subsequent models derive some of their features from those experiments. Common features include behavior-dependent psychophysical determination, acoustic conditions that contrast objective sound and silence, and inclusion of at least one normal-hearing control group. In the present review, animal models have been categorized as either interrogative or reflexive. Interrogative models use emitted behavior under voluntary control to indicate hearing. An example would be pressing a lever to obtain food in the presence of a particular sound. In this type of model animals are interrogated about their auditory sensations, analogous to asking a patient, "What do you hear?" These models require at least some training and motivation management, and reflect the perception of tinnitus. Reflexive models, in contrast, employ acoustic modulation of an auditory reflex, such as the acoustic startle response. An unexpected loud sound will elicit a reflexive motor response from many species, including humans. Although involuntary, acoustic startle can be modified by a lower-level preceding event, including a silent sound gap. Sound-gap modulation of acoustic startle appears to discriminate tinnitus in animals as well as humans, and requires no training or

  2. Marine animal stings or bites

    Science.gov (United States)

    Stings - marine animals; Bites - marine animals ... Things you can do to prevent a marine animal sting or bite include: Swim near a lifeguard. Observe posted signs that may warn of danger from jellyfish or other hazardous marine life. ...

  3. Animal Bites of the Hand

    Science.gov (United States)

    ... Therapist? Media Find a Hand Surgeon Home Anatomy Animal Bites Email to a friend * required fields From * ... key to prevent problems from a bite. CAUSES Animal Bites Millions of animal bites occur in the ...

  4. Animal rights and animal experimentation. Implications for physicians.

    Science.gov (United States)

    Gelpi, A. P.

    1991-01-01

    Practicing physicians are just becoming aware of the animal rights movement, which during the 1980s spawned numerous acts of violence against research facilities throughout the United States. The animal rightists are challenging physicians to show moral justification for the human exploitation of nature and the world of subhuman species. They have aroused public interest in animal welfare, sparked protective legislation for experimental animals, and indirectly encouraged the creation of committees to oversee the conduct of animal experimentation and the conditions of animal confinement. This controversy has necessitated a closer look at the questions of animal experimentation and animal rights against the backdrop of human experimentation and human rights. Physicians and specialists in animal care seek to alleviate suffering and anxiety, and, as moderates, they may be able to bring both sides of the animal rights controversy together in a spirit of mutual tolerance and in the common cause of promoting both human and animal welfare. PMID:1949772

  5. Mechanism for elevated temperature leaching

    International Nuclear Information System (INIS)

    Kenna, B.T.; Murphy, K.D.

    1979-01-01

    Long-term, elevated temperature leaching and subsequent electron microprobe analysis of simulated waste glass and ceramic materials have been completed. A cyclic leaching pattern was found in all systems over a 20-month period. It appears that the leaching of mobile ions by simple diffusional processes is modified by more complex chemical interactions. The release of immobile ions is primarily a function of their chemical interactions in the matrix which suggests that these ions may be complex species when released into solution. A mechanism is proposed which incorporates these ideas and the cyclic phenomenon observed

  6. PLC VVVF Elevator Control System

    OpenAIRE

    Tang, Yujian; Gui, Tianyu

    2016-01-01

    The aim of the thesis is to introduce the PLC VVVF elevator and its control system. The thesis can be divided into three parts. The first part is about the overview of the lift: the kinds of the lift and the structure of the lift, it shows the knowledge about the components and the operating systems of the lift. The second part is about the PLC control system, it’s about the operations of the lift from the introduction about the hardware and software of the PLC control system. And the thi...

  7. Amorphisation during elevated temperature implantation

    International Nuclear Information System (INIS)

    Carter, G.; Nobes, M.J.; Elliman, R.G.

    1994-01-01

    Transition state theory is employed to predict the rates of amorphous zone recrystallization by direct thermal and radiation mediated thermal annealing processes. These rates are functions of zone radius and are employed to describe the competition between amorphous zone generation and annealing during elevated temperature heavy ion implantation of, particularly, Si and the accumulation of amorphousness with increasing ion fluence. This analysis predicts a change from monotonic to sigmoidal to biexponential accumulation functions with increasing annealing rate or substrate temperature in agreement with experiments. A logarithmic dependence of ion flux density upon substrate temperature for the achievement of defined fractional amorphisation is predicted and is also in agreement with the experiment. (author)

  8. Laboratory Animal Sciences Program (LASP)

    Data.gov (United States)

    Federal Laboratory Consortium — The Laboratory Animal Sciences Program (LASP) is a comprehensive resource for scientists performing animal-based research to gain a better understanding of cancer,...

  9. Effect of methyl mercaptophos in different combinations with elevated atmospheric temperature and ultraviolet radiation

    International Nuclear Information System (INIS)

    Gabovich, R.D.; Murashko, V.A.

    1975-01-01

    Rats were exposed to methyl mercaptophos (I) vapor combined with various doses of uv irradiation at 22deg or 37deg. Changes in the levels of serum alkaline phosphatase, hepatic and serum cholinestrerase, adrenal ascorbic acid, and other parameters indicated that the animals' resistance to the effects of I was decreased by: a) low uv irradiation, b) elevated temperature, or c) combined elevated temperature and excessive uv irradiation

  10. Farm animal welfare

    DEFF Research Database (Denmark)

    Sandøe, Peter; Christiansen, Stine Billeschou; Appleby, M. C.

    2003-01-01

    An experimental survey was undertaken to explore the links between the characteristics of a moral issue, the degree of moral intensity/moral imperative associated with the issue (Jones, 1991), and people’s stated willingness to pay (wtp) for policy to address the issue. Two farm animal welfare...

  11. Killing animals for recreation?

    DEFF Research Database (Denmark)

    Gamborg, Christian; Jensen, Frank Søndergaard; Sandøe, Peter

    2018-01-01

    Hunters in the Western world today do not need to hunt to obtain food and other animal products. So why do they hunt? This paper examines the motives of hunters, the motives ascribed to hunters by members of the general public, and the role motives play for the moral acceptability of hunting among...

  12. Antibiotic resistance in animals.

    Science.gov (United States)

    Barton, Mary D; Pratt, Rachael; Hart, Wendy S

    2003-01-01

    There is currently no systematic surveillance or monitoring of antibiotic resistance in Australian animals. Registration of antibiotics for use in animals is tightly controlled and has been very conservative. Fluoroquinolones have not been registered for use in food producing animals and other products have been removed from the market because of human health concerns. In the late 1970s, the Animal Health Committee coordinated a survey of resistance in Salmonella and Escherichia coli isolates from cattle, pigs and poultry and in bovine Staphylococcus aureus. Some additional information is available from published case reports. In samples collected prior to the withdrawal of avoparcin from the market, no vancomycin resistant Enterococcus faecium or Enterococcus faecalis were detected in samples collected from pigs, whereas some vanA enterococci, including E. faecium and E. faecalis, were found in chickens. No vanB enterococci were detected in either species. Virginiamycin resistance was common in both pig and poultry isolates. Multiple resistance was common in E. coli and salmonellae isolates. No fluoroquinolone resistance was found in salmonellae, E. coli or Campylobacter. Beta-lactamase production is common in isolates from bovine mastitis, but no methicillin resistance has been detected. However, methicillin resistance has been reported in canine isolates of Staphylococcus intermedius and extended spectrum beta-lactamase producing E. coli has been found in dogs.

  13. Georeferencing Animal Specimen Datasets

    NARCIS (Netherlands)

    van Erp, M.G.J.; Hensel, R.; Ceolin, D.; van der Meij, M.

    2014-01-01

    For biodiversity research, the field of study that is concerned with the richness of species of our planet, it is of the utmost importance that the location of an animal specimen find is known with high precision. Due to specimens often having been collected over the course of many years, their

  14. ANIMAL MODELS IN SURGICAL

    African Journals Online (AJOL)

    ASSEMBLED BY

    experiment also requires a project license. Finally, ... driving, overloading, torture, terrifying or cause or process or permit any animal to be so treated, Cause or permit .... all in an attempt to eliminate or reduce to a minimum discomfort and pain ...

  15. Cytogenetics in animal production

    Directory of Open Access Journals (Sweden)

    L. Iannuzzi

    2010-04-01

    Full Text Available Cytogenetics applied to domestic animals is a useful biotechnology to be applied in the genetic improvement of livestock. Indeed, it can be used to select reproducers free chromosome abnormalities which are responsible for abnormal body conformation (aneuploidy, lower fertility (balanced chromosome abnormalities or sterility (sex chromosome abnormalities. Cytogenetics may also be applied to assess environmental pollution by studying animals living in hazardous areas and using them as biological indicators (sentinels. Chromosomes also represent optimal biological structures to study the evolution among related (bovids and unrelated (bovidshumans species, especially using comparative FISH-mapping which is one of the most powerful tools to establish the correct order of loci along chromosomes. These comparisons allow us to transfer useful information from richer genomes (human to those of domestic animals. Moreover, the use of specific molecular markers and the FISH-technique on both mitotic and extended (fiber-FISH chromosomes, has heralded a new era of cytogenetics, allowing swift extension of genetic physical maps, better anchoring of both linkage and RH-maps to specific chromosome regions, and use in a variety of applications (clinical cases, embryo and sperm analyses, evolution. In this study a brief review of these fields of the animal cytogenetics is presented.

  16. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... Skip to common links HHS U.S. Department of Health and Human Services U.S. Food and Drug Administration A to Z Index Follow FDA En Español Search FDA Submit search ... & Health Antimicrobial Resistance Animation of Antimicrobial Resistance Share Tweet ...

  17. Modelling Farm Animal Welfare

    Directory of Open Access Journals (Sweden)

    Chérie E. Part

    2013-05-01

    Full Text Available The use of models in the life sciences has greatly expanded in scope and advanced in technique in recent decades. However, the range, type and complexity of models used in farm animal welfare is comparatively poor, despite the great scope for use of modeling in this field of research. In this paper, we review the different modeling approaches used in farm animal welfare science to date, discussing the types of questions they have been used to answer, the merits and problems associated with the method, and possible future applications of each technique. We find that the most frequently published types of model used in farm animal welfare are conceptual and assessment models; two types of model that are frequently (though not exclusively based on expert opinion. Simulation, optimization, scenario, and systems modeling approaches are rarer in animal welfare, despite being commonly used in other related fields. Finally, common issues such as a lack of quantitative data to parameterize models, and model selection and validation are discussed throughout the review, with possible solutions and alternative approaches suggested.

  18. Animal culture: chimpanzee conformity?

    Science.gov (United States)

    van Schaik, Carel P

    2012-05-22

    Culture-like phenomena in wild animals have received much attention, but how good is the evidence and how similar are they to human culture? New data on chimpanzees suggest their culture may even have an element of conformity. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. An animated virtual drummer

    NARCIS (Netherlands)

    Kragtwijk, M.; Giagourta, V.; Nijholt, Antinus; Strintzis, M.G.; Zwiers, Jakob

    2001-01-01

    We describe a system for the automatic generation of a 3D animation of a drummer playing along with a given piece of music. The input, consisting of a sound wave, is analysed to determine which drums are struck at what moments. The Standard MIDI File format is used to store the recognised notes.

  20. Pathological anxiety in animals

    NARCIS (Netherlands)

    Ohl, F.; Arndt, S.S.; Staay, van der F.J.

    2008-01-01

    selective breeding programmes in domestic and laboratory animals generally focus on physiological and/or anatomical characteristics. However, selection may have an (unintended) impact on other characteristics and may lead to dysfunctional behaviour that can affect biological functioning and, as a

  1. Animal imaging using immersion

    Science.gov (United States)

    Kalogerakis, Konstantinos S.; Kotz, Kenneth T.; Rand, Kendra; Faris, Gregory W.

    2003-07-01

    We are using rodent animal models to study and compare contrast mechanisms for detection of breast cancer. These measurements are performed with the animals immersed in a matching scattering medium. The matching scattering medium or liquid tissue phantom comprises a mixture of Ropaque (hollow acrylic/styrene microspheres) and ink. We have previously applied matched imaging to imaging in humans. Surrounding the imaged region with a matched tissue phantom compensates for variations in tissue thickness and geometry, provides more uniform illumination, and allows better use of the dynamic range of the imaging system. If the match is good, the boundaries of the imaged region should almost vanish, enhancing the contrast from internal structure as compared to contrast from the boundaries and surface topography. For our measurements in animals, the immersion plays two additional roles. First, we can readily study tumors through tissue thickness similar to that of a human breast. Although the heterogeneity of the breast is lost, this is a practical method to study the detection of small tumors and monitor changes as they grow. Second, the immersion enhances our ability to quantify the contrast mechanisms for peripheral tumors on the animal because the boundary effects on photon migration are eliminated. We are currently developing two systems for these measurements. One is a continuous-wave (CW) system based on near-infrared LED illumination and a CCD (charge-coupled device) camera. The second system, a frequency domain system, can help quantify the changes observed with the CW system.

  2. Hope for Animals

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 20; Issue 8. Hope for Animals. Prasanna Venkhatesh V. Book Review Volume 20 Issue 8 August 2015 pp 753-754. Fulltext. Click here to view fulltext PDF. Permanent link: https://www.ias.ac.in/article/fulltext/reso/020/08/0753-0754. Author Affiliations.

  3. Cancer Statistics Animator

    Science.gov (United States)

    This tool allows users to animate cancer trends over time by cancer site and cause of death, race, and sex. Provides access to incidence, mortality, and survival. Select the type of statistic, variables, format, and then extract the statistics in a delimited format for further analyses.

  4. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... Pin it Email Print The Food and Drug Administration's (FDA's) Center for Veterinary Medicine (CVM) produced a nine-minute animation explaining how antimicrobial resistance both emerges and proliferates among bacteria. Over time, the use of antimicrobial drugs will result in ...

  5. Mapping farm animal genomes

    Czech Academy of Sciences Publication Activity Database

    Čepica, Stanislav

    1998-01-01

    Roč. 43, č. 9 (1998), s. 386 ISSN 0044-4847. [Genetics Day-International conference on animal genetics /18./. 08.09.1998-10.09.1998, České Budějovice] R&D Projects: GA ČR GA523/96/0597 Subject RIV: EB - Genetics ; Molecular Biology

  6. ANIMAL MODELS FOR IMMUNOTOXICITY

    Science.gov (United States)

    Greater susceptibility to infection is a hallmark of compromised immune function in humans and animals, and is often considered the benchmark against which the predictive value of immune function tests are compared. This focus of this paper is resistance to infection with the pa...

  7. Do Animals Have Memes?

    NARCIS (Netherlands)

    Reader, S.M.; Laland, K.N.

    1999-01-01

    Imitation has been put forward as a defining feature of memetic transmission. Since there is currently poor evidence for imitation in non-human animals, such definitions have been interpreted as restricting meme theory to the study of human behaviour patterns and birdsong. We believe this is a

  8. Diffusion rates for elevated releases

    International Nuclear Information System (INIS)

    Ramsdell, J.V.

    1983-11-01

    A search of the literature related to diffusion from elevated sources has determined that an adequate data base exists for use in developing parameterizations for estimating diffusion rates for material released from free standing stacks at nuclear power plants. A review of published data analyses indicates that a new parameterization of horizontal diffusion rates specifically for elevated releases is not likely to significantly change the magnitudes of horizontal diffusion coefficients on the average. However, the uncertainties associated with horizontal diffusion coefficient estimates under any given set of atmospheric conditions could be reduced by a new parameterization. Similarly, a new parameterization of vertical diffusion rates would be unlikely to significantly alter the magnitudes of diffusion coefficients for unstable atmospheric conditons. However, for neutral and stable atmospheric conditions, a new parameterization of vertical diffusion rates might increase vertical diffusion coefficients significantly. The increase would move ground-level time-integrated concentration maxima closer to the plant and would increase the maxima. 55 references, 2 figures, 4 tables

  9. Operation experience with elevated ammonia

    International Nuclear Information System (INIS)

    Vankova, Katerina; Kysela, Jan; Malac, Miroslav; Petrecky, Igor; Svarc, Vladimir

    2011-01-01

    The 10 VVER units in the Czech and Slovak Republics are all in very good water chemistry and radiation condition, yet questions have arisen regarding the optimization of cycle chemistry and improved operation in these units. To address these issues, a comprehensive experimental program for different water chemistries of the primary circuit was carried out at the Rez Nuclear Research Institute, Czech Republic, with the goal of judging the influence of various water chemistries on radiation build-up. Four types of water chemistries were compared: standard VVER water chemistry (in common use), direct hydrogen dosing without ammonia, standard VVER water chemistry with elevated ammonia levels, and zinc dosing to standard VVER water chemistry. The test results showed that the types of water chemistry other than the common one have benefits for the operation of the nuclear power plant (NPP) primary circuit. Operation experience with elevated ammonia at NPP Dukovany Units 3 and 4 is presented which validates the experimental results, demonstrating improved corrosion product volume activity. (orig.)

  10. Digitial Elevation Model (DEM) 100K

    Data.gov (United States)

    Kansas Data Access and Support Center — Digital Elevation Model (DEM) is the terminology adopted by the USG to describe terrain elevation data sets in a digital raster form. The standard DEM consists of a...

  11. Digtial Elevation Model (DEM) 250K

    Data.gov (United States)

    Kansas Data Access and Support Center — Digital Elevation Model (DEM) is the terminology adopted by the USGS to describe terrain elevation data sets in a digital raster form. The standard DEM consists of a...

  12. Digital Elevation Model (DEM) 24K

    Data.gov (United States)

    Kansas Data Access and Support Center — Digital Elevation Model (DEM) is the terminology adopted by the USGS to describe terrain elevation data sets in a digital raster form. The standard DEM consists of a...

  13. The role of some biochemical and hemotological factors in animal mortality

    International Nuclear Information System (INIS)

    Zapol'skaya, N.A.; Fedorova, A.V.; Yakovleva, N.G.

    1978-01-01

    Correlations were sought between mortality of animals and some biochemical indices. These included elevated levels of deoxycytidine in urine (an indicator of DNA metabolism), elevated levels of histamine, reduced cholinesterase activity in blood, and changes in peripheral blood morphology (reduced erythrocyte and lymphocyte counts). These indices were found to correlate directly with mortality. Regression equations were derived for all the indices studied

  14. Bucket elevator type continuous unloader; Basket elevator gata renzokushiki anroda

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-04-20

    This unloader was delivered to Wakayama branch of Sumikin Butsuryu in the site of Wakayama steel plant of Sumitomo Metal Industries Ltd. for landing sub-materials for ironworks. Main specifications: (1) Capacity: 400t/h for limestone, 280t/h for gypsum, (2) Kinds of ships: 5,000DWT maximum, (3) Boom swing radius: 20m. Features: (1) Simple light-weight unloader for not large ships for main materials but small coastal service ships which works with not swing motion but only traveling and normal-directional motion of the under structure of a bucket elevator unit, (2) Various useful functions such as ground conveyance, truck loading, back yard stacking and back yard shipment for handling of various sub-materials. (translated by NEDO)

  15. Fostering Kinship with Animals: Animal Portraiture in Humane Education

    Science.gov (United States)

    Kalof, Linda; Zammit-Lucia, Joe; Bell, Jessica; Granter, Gina

    2016-01-01

    Visual depictions of animals can alter human perceptions of, emotional responses to, and attitudes toward animals. Our study addressed the potential of a slideshow designed to activate emotional responses to animals to foster feelings of kinship with them. The personal meaning map measured changes in perceptions of animals. The participants were…

  16. Global warming leads to more uniform spring phenology across elevations.

    Science.gov (United States)

    Vitasse, Yann; Signarbieux, Constant; Fu, Yongshuo H

    2018-01-30

    One hundred years ago, Andrew D. Hopkins estimated the progressive delay in tree leaf-out with increasing latitude, longitude, and elevation, referred to as "Hopkins' bioclimatic law." What if global warming is altering this well-known law? Here, based on ∼20,000 observations of the leaf-out date of four common temperate tree species located in 128 sites at various elevations in the European Alps, we found that the elevation-induced phenological shift (EPS) has significantly declined from 34 d⋅1,000 m -1 conforming to Hopkins' bioclimatic law in 1960, to 22 d⋅1,000 m -1 in 2016, i.e., -35%. The stronger phenological advance at higher elevations, responsible for the reduction in EPS, is most likely to be connected to stronger warming during late spring as well as to warmer winter temperatures. Indeed, under similar spring temperatures, we found that the EPS was substantially reduced in years when the previous winter was warmer. Our results provide empirical evidence for a declining EPS over the last six decades. Future climate warming may further reduce the EPS with consequences for the structure and function of mountain forest ecosystems, in particular through changes in plant-animal interactions, but the actual impact of such ongoing change is today largely unknown.

  17. History of Elevators and Related Research

    Science.gov (United States)

    Abe, Shigeru; Watanabe, Eiki

    The history of traction drive elevators in Japan is described. The electrical technologies such as the microprocessor car control and the VVVF motor control made remarkable progress leading to higher reliability and energy savings. Then, the various machine-room-less elevators have been developed and the space saving technology, such as the shuttle and the double-deck elevators become important, too. The elevators used for evacuation in case of emergencies are also discussed.

  18. [Animal testing ethics and human testing. Thoughts on our conduct with and our relationship to animals].

    Science.gov (United States)

    Locker, Alfred

    2004-01-01

    After many years of experimental work with animals of diverse species, the author felt confronted with the question whether the great expenditure of sacrificed animal life would pay off when compared with the results gained. By self-critically considering his work, he gradually experienced a conversion from an unconcerned experimenter to a man feeling a deep sympathy with his fellow creatures. This motivated him to ponder the true nature of animals. Instead of applying ethics--though justified in its own realm--the author preferred to look at the problem using the General Systems Theory (GST), which can describe "the other side" of any system, the side into which any system may occasionally or necessarily transform. It occurred to him to assume that--provided we see a living organism as a system (as Ludwig von Bertalanffy, the founder of GST, did)--the "other side" of the animal would correspond to an innocent "genius" who suffers for man (thereby assuming a Christ-like position), whereas in its transitory life the true essence of the animal is hidden. Thus, by fancifully viewing the role of animals destined to suffer, a connection between GST and theology or religion arises. The consequence for us would be to pay honour to the test animal, irrespective of whether or not painful experiments could be avoided. The differentiation between a sacrifice (spiritually surrendering for a greater good) and a victim (involuntarily subjected to suffering) reveals that the experimental animal primarily belongs to the latter. But it can be elevated to the former when the full meaning of its suffering becomes obvious. The same holds true for "human testing", if, in contrast to the formidable atrocities, e.g. of concentration camps, the momentum of voluntariness is guaranteed, as pioneers of medical research frequently demonstrated by carrying out experiments on themselves.

  19. 21 CFR 890.3930 - Wheelchair elevator.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Wheelchair elevator. 890.3930 Section 890.3930 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... elevator. (a) Identification. A wheelchair elevator is a motorized lift device intended for medical...

  20. 46 CFR 183.540 - Elevators.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Elevators. 183.540 Section 183.540 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER VESSELS (UNDER 100 GROSS TONS) ELECTRICAL INSTALLATION Miscellaneous Systems and Requirements § 183.540 Elevators. Each elevator on a vessel must meet the requirements of ANSI A 17.1 ...