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Sample records for acrolein activates matrix

  1. Acrolein, an α,β-unsaturated carbonyl, inhibits both growth and PSII activity in the cyanobacterium Synechocystis sp. PCC 6803.

    Shimakawa, Ginga; Iwamoto, Tatsuya; Mabuchi, Tomohito; Saito, Ryota; Yamamoto, Hiroshi; Amako, Katsumi; Sugimoto, Toshio; Makino, Amane; Miyake, Chikahiro

    2013-01-01

    In this study, we sought to determine whether and how an α,β-unsaturated carbonyl, acrolein, can inhibit the growth of the cyanobacterium Synechocystis sp. PCC6803 (S. 6803). Treatment of S. 6803 with 200 µM acrolein for 3 d significantly and irreversibly inhibited its growth. To elucidate the inhibitory mechanism, we examined the effects of acrolein on photosynthesis. In contrast to dark conditions, the addition of acrolein to S. 6803 under conditions of illumination lowered the CO₂-dependent O₂ evolution rate (photosynthetic activity). Furthermore, treatment with acrolein lowered the activity reducing dimethyl benzoquinone in photosystem II (PSII). Acrolein also suppressed the reduction rate for the oxidized form of the reaction center chlorophyll of photosystem I (PSI), P700. These results indicate that acrolein inhibited PSII activity in thylakoid membranes. The addition of 200 µM acrolein to the illuminated S. 6803 cells gradually increased the steady-state level (Fs) of Chl fluorescence and decreased the quantum yield of PSII. These results suggested that acrolein damaged the acceptor side of PSII. On the other hand, acrolein did not inhibit respiration. From the above results, we gained insight into the metabolism of acrolein and its physiological effects in S. 6803.

  2. Acrolein contributes strongly to antimicrobial and heterocyclic amine transformation activities of reuterin

    Engels, Christina; Schwab, Clarissa; Zhang, Jianbo; Stevens, Marc J. A.; Bieri, Corinne; Ebert, Marc-Olivier; McNeill, Kristopher; Sturla, Shana J.; Lacroix, Christophe

    2016-01-01

    Glycerol/diol dehydratases catalyze the conversion of glycerol to 3-hydroxypropionaldehyde (3-HPA), the basis of a multi-component system called reuterin. Reuterin has antimicrobial properties and undergoes chemical conjugation with dietary heterocyclic amines (HCAs). In aqueous solution reuterin is in dynamic equilibrium with the toxicant acrolein. It was the aim of this study to investigate the extent of acrolein formation at various physiological conditions and to determine its role in biological and chemical activities. The application of a combined novel analytical approach including IC-PAD, LC-MS and NMR together with specific acrolein scavengers suggested for the first time that acrolein, and not 3-HPA, is the active compound responsible for HCA conjugation and antimicrobial activity attributed to reuterin. As formation of the HCA conjugate was observed in vivo, our results imply that acrolein is formed in the human gut with implications on detoxification of HCAs. We propose to re-define the term reuterin to include acrolein. PMID:27819285

  3. Acrolein activates cell survival and apoptotic death responses involving the endoplasmic reticulum in A549 lung cells.

    Tanel, André; Pallepati, Pragathi; Bettaieb, Ahmed; Morin, Patrick; Averill-Bates, Diana A

    2014-05-01

    Acrolein, a highly reactive α,β-unsaturated aldehyde, is a product of endogenous lipid peroxidation. It is a ubiquitous environmental pollutant that is generated mainly by smoke, overheated cooking oil and vehicle exhaust. Acrolein damages cellular proteins, which could lead to accumulation of aberrantly-folded proteins in the endoplasmic reticulum (ER). This study determines the mechanisms involved in acrolein-induced apoptosis mediated by the ER and possible links with the ER stress response in human A549 lung cells. The exposure of cells to acrolein (15-50μM) for shorter times of 15 to 30min activated several ER stress markers. These included the ER chaperone protein BiP and the three ER sensors: (i) the survival/rescue molecules protein kinase RNA (PKR)-like ER kinase (PERK) and eukaryotic initiation factor 2 alpha (eIF2α) were phosphorylated; (ii) cleavage of activating transcription factor 6 (ATF6) occurred, and (iii) inositol-requiring protein-1 alpha (IRE1α) was phosphorylated. Acrolein (25-50μM) caused apoptotic cell death mediated by the ER after 2h, which was characterised by the induction of CHOP and activation of ER proteases calpain and caspase-4. Calpain and caspase-7 were the initiating factors for caspase-4 activation in acrolein-induced apoptosis. These results increase our knowledge about cellular responses to acrolein in lung cells, which have implications for human health.

  4. Acrolein-induced activation of mitogen-activated protein kinase signaling is mediated by alkylation of thioredoxin reductase and thioredoxin 1

    Matthew J. Randall

    2013-01-01

    Full Text Available Cigarette smoking remains a major health concern worldwide, and many of the adverse effects of cigarette smoke (CS can be attributed to its abundant electrophilic aldehydes, such as acrolein (2-propenal. Previous studies indicate that acrolein readily reacts with thioredoxin reductase 1 (TrxR1, a critical enzyme involved in regulation of thioredoxin (Trx-mediated redox signaling, by alkylation at its selenocysteine (Sec residue. Because alkylation of Sec within TrxR1 has significant implications for its enzymatic function, we explored the potential importance of TrxR1 alkylation in acrolein-induced activation or injury of bronchial epithelial cells. Exposure of human bronchial epithelial HBE1 cells to acrolein (1–30 μM resulted in dose-dependent loss of TrxR thioredoxin reductase activity, which coincided with its alkylation, as determined by biotin hydrazide labeling, and was independent of initial GSH status. To test the involvement of TrxR1 in acrolein responses in HBE1 cells, we suppressed TrxR1 using siRNA silencing or augmented TrxR1 by cell supplementation with sodium selenite. Acrolein exposure of HBE1 cells induced dose-dependent activation of the MAP kinases, extracellular regulated kinase (ERK, c-Jun N-terminal kinase (JNK, and p38, and activation of JNK was markedly enhanced after selenite-mediated induction of TrxR1, and was associated with increased alkylation of TrxR1. Conversely, siRNA silencing of TrxR1 significantly suppressed the ability of acrolein to activate JNK, and also appeared to attenuate acrolein-dependent activation of ERK and p38. Alteration of initial TrxR1 levels by siRNA or selenite supplementation also affected initial Trx1 redox status and acrolein-mediated alkylation of Trx1, but did not significantly affect acrolein-mediated activation of HO-1 or cytotoxicity. Collectively, our findings indicate that alkylation of TrxR1 and/or Trx1 may contribute directly to acrolein-mediated activation of MAP kinases

  5. Acrolein-induced activation of mitogen-activated protein kinase signaling is mediated by alkylation of thioredoxin reductase and thioredoxin 1.

    Randall, Matthew J; Spiess, Page C; Hristova, Milena; Hondal, Robert J; van der Vliet, Albert

    2013-01-01

    Cigarette smoking remains a major health concern worldwide, and many of the adverse effects of cigarette smoke (CS) can be attributed to its abundant electrophilic aldehydes, such as acrolein (2-propenal). Previous studies indicate that acrolein readily reacts with thioredoxin reductase 1 (TrxR1), a critical enzyme involved in regulation of thioredoxin (Trx)-mediated redox signaling, by alkylation at its selenocysteine (Sec) residue. Because alkylation of Sec within TrxR1 has significant implications for its enzymatic function, we explored the potential importance of TrxR1 alkylation in acrolein-induced activation or injury of bronchial epithelial cells. Exposure of human bronchial epithelial HBE1 cells to acrolein (1-30 μM) resulted in dose-dependent loss of TrxR thioredoxin reductase activity, which coincided with its alkylation, as determined by biotin hydrazide labeling, and was independent of initial GSH status. To test the involvement of TrxR1 in acrolein responses in HBE1 cells, we suppressed TrxR1 using siRNA silencing or augmented TrxR1 by cell supplementation with sodium selenite. Acrolein exposure of HBE1 cells induced dose-dependent activation of the MAP kinases, extracellular regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38, and activation of JNK was markedly enhanced after selenite-mediated induction of TrxR1, and was associated with increased alkylation of TrxR1. Conversely, siRNA silencing of TrxR1 significantly suppressed the ability of acrolein to activate JNK, and also appeared to attenuate acrolein-dependent activation of ERK and p38. Alteration of initial TrxR1 levels by siRNA or selenite supplementation also affected initial Trx1 redox status and acrolein-mediated alkylation of Trx1, but did not significantly affect acrolein-mediated activation of HO-1 or cytotoxicity. Collectively, our findings indicate that alkylation of TrxR1 and/or Trx1 may contribute directly to acrolein-mediated activation of MAP kinases such as JNK, and

  6. Ovicidal activity of acrolein vapors to Indian meal moth eggs of various ages.

    Pourmirza, Ali Asghr

    2007-09-01

    The effect of acrolein vapors against carefully aged eggs of Indian meal moth at 27 +/- 1 and 17 +/- 1 degrees C at different dosage levels of acrolein over various exposure times was determined. Considerable variation in the susceptibility of different age groups of eggs was apparent in the fiducial limits of the LD50 values. At both temperatures and 24 h exposure period, eggs aged 1-2 day-old were more tolerant to acrolein than other age groups. In all bioassays, eggs exposed to higher dosages of acrolein developed at smaller rate. This was significant for the eggs, which were exposed to the highest dosage for 24 h. Increasing the temperature from 17 +/- 1 to 27 +/- 1 degrees C greatly increased the efficacy of acrolein. Overall, at 27 +/- 1 degrees C eggs of P. interpunctella were killed by less than one-fourth of the dosage required for control at 17 +/- 1 degrees C. Acrolein achieved 50% mortality with a dosage of 3.80 mg L(-1) in 1-2 day-old eggs at 27 +/- 1 degrees C. At this temperature hatching was retarded and greatly reduced when eggs aged 1-2 day-old were exposed to 32 mg L(-1) of acrolein for the 24 h exposure period. There was no evidence of a hatch delay longer than the time spent under vapors for eggs exposed at 17 +/- 1 or 27 +/- 1 degrees C, indicating that some development must have occurred under fumigation.

  7. Induction of phase 2 enzymes by serum oxidized polyamines through activation of Nrf2: effect of the polyamine metabolite acrolein.

    Kwak, Mi-Kyoung; Kensler, Thomas W; Casero, Robert A

    2003-06-06

    The naturally occurring polycationic polyamines including putrescine, spermidine, and spermine play an important role in cell growth, differentiation, and gene expression. However, circulating polyamines are potential substrates for several oxidizing enzymes including copper-containing serum amine oxidase. These enzymes are capable of oxidizing serum polyamines to several toxic metabolites including aldehydes and H(2)O(2). In this study, we investigated the effects of polyamines as inducers of phase 2 enzymes and other genes that promote cell survival in a cell culture system in the presence of bovine serum. Spermidine and spermine (50 microM) increased NAD(P)H quinone oxidoreductase (NQO1) activity up to 3-fold in murine keratinocyte PE cells. Transcript levels for glutathione S-transferase (GST) A1, GST M1, NQO1, gamma-glutamylcysteine ligase regulatory subunit, and UDP-glucuronyltransferase 1A6 were significantly increased by spermidine and this effect was mediated through the antioxidant response element (ARE). The ARE from the mouse GST A1 promoter was activated about 9-fold by spermine and 5-fold by spermidine treatment, but could be inhibited by the amine oxidase inhibitor, aminoguanidine, suggesting that acrolein or hydrogen peroxide generated from polyamines by serum amine oxidase may be mediators for phase 2 enzyme induction. Elevations of ARE-luciferase expression and NQO1 enzyme activity by spermidine were not affected by catalase, while both were completely repressed by aldehyde dehydrogenase treatment. Direct addition of acrolein to PE cells induced multiple phase 2 genes and elevated nuclear levels of Nrf2, a transcription factor that binds to the ARE. Expression of mutant Nrf2 repressed the activation of the ARE-luciferase reporter by polyamines and acrolein. These results indicate that spermidine and spermine increase the expression of phase 2 genes in cells grown in culture through activation of the Nrf2-ARE pathway by generating the sulfhydryl

  8. Inactivation of GAPDH as one mechanism of acrolein toxicity.

    Nakamura, Mizuho; Tomitori, Hideyuki; Suzuki, Takehiro; Sakamoto, Akihiko; Terui, Yusuke; Saiki, Ryotaro; Dohmae, Naoshi; Igarashi, Kazuei; Kashiwagi, Keiko

    2013-01-25

    We have recently reported that acrolein is more toxic than reactive oxygen species. Thus, the mechanism of cell toxicity by acrolein was studied using mouse mammary carcinoma FM3A cells. Acrolein-conjugated proteins were separated by gel electrophoresis with subsequent determination of their amino acid sequence, and it was found that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was one of the major acrolein-conjugated proteins in cells. Acrolein interacted with cysteine-150 at the active site of GAPDH, and also with cysteine-282. When cells were treated with 8 μM acrolein, the activity of acrolein-conjugated GAPDH was greatly reduced, and the ATP content in cells was thus significantly reduced. In addition, it was shown that acrolein-conjugated GAPDH translocated to the nucleus, and the level of acetylated GAPDH and the number of TUNEL positive cells was increased, indicating that cell death is enhanced by acrolein-conjugated GAPDH. Inhibition of cell growth by acrolein was partially reversed when the cDNA encoding GAPDH was transformed into cells. These results indicate that inactivation of GAPDH is one mechanism that underlies cell toxicity caused by acrolein.

  9. A Potential Role for Acrolein in Neutrophil-Mediated Chronic Inflammation.

    Noerager, Brett D; Xu, Xin; Davis, Virginia A; Jones, Caleb W; Okafor, Svetlana; Whitehead, Alicia; Blalock, J Edwin; Jackson, Patricia L

    2015-12-01

    Neutrophils (PMNs) are key mediators of inflammatory processes throughout the body. In this study, we investigated the role of acrolein, a highly reactive aldehyde that is ubiquitously present in the environment and produced endogenously at sites of inflammation, in mediating PMN-mediated degradation of collagen facilitating proline-glycine-proline (PGP) production. We treated peripheral blood neutrophils with acrolein and analyzed cell supernatants and lysates for matrix metalloproteinase-9 (MMP-9) and prolyl endopeptidase (PE), assessed their ability to break down collagen and release PGP, and assayed for the presence of leukotriene A4 hydrolase (LTA4H) and its ability to degrade PGP. Acrolein treatment induced elevated production and functionality of collagen-degrading enzymes and generation of PGP fragments. Meanwhile, LTA4H levels and triaminopeptidase activity declined with increasing concentrations of acrolein thereby sparing PGP from enzymatic destruction. These findings suggest that acrolein exacerbates the acute inflammatory response mediated by neutrophils and sets the stage for chronic pulmonary and systemic inflammation.

  10. Synthesis of Reactive Polymers for Acrolein Capture Using AGET ATRP.

    Beringer, Laura T; Li, Shaohua; Gilmore, Gary; Lister, John; Averick, Saadyah

    2015-10-05

    Acrolein is a toxic metabolite of the anticancer agent cyclophosphamide (CP). Current strategies to mitigate acrolein toxicity are insufficient, and in this brief article, we report the synthesis of well-defined low molecular weight block copolymers using activators generated by electron transfer atom transfer radical polymerization (AGET ATRP) capable of reacting with the cytotoxic small molecule acrolein. Acrolein reactivity was introduced into the block copolymers via incorporation of either (a) aminooxy or (b) sulfhydryl groups. The cytoprotective effect of the polymers was compared to sodium 2-sulfanylethanesulfonate (mesna) the current gold standard for protection from CP urotoxicity, and we found that the polymers bearing sulfhydryl moieties demonstrated superior cytoprotective activity.

  11. Environmental risk limits for acrolein

    Bodar CWM; SEC

    2008-01-01

    Dit rapport geeft milieurisicogrenzen voor acroleine in (grond)water, bodem en lucht. Milieurisicogrenzen zijn de technisch-wetenschappelijke advieswaarden voor de uiteindelijke milieukwaliteitsnormen in Nederland. De milieurisicogrenzen voor acroleine zijn gebaseerd op de uitkomsten van de EU ris

  12. Acrolein cytotoxicity in hepatocytes involves endoplasmic reticulum stress, mitochondrial dysfunction and oxidative stress.

    Mohammad, Mohammad K; Avila, Diana; Zhang, Jingwen; Barve, Shirish; Arteel, Gavin; McClain, Craig; Joshi-Barve, Swati

    2012-11-15

    Acrolein is a common environmental, food and water pollutant and a major component of cigarette smoke. Also, it is produced endogenously via lipid peroxidation and cellular metabolism of certain amino acids and drugs. Acrolein is cytotoxic to many cell types including hepatocytes; however the mechanisms are not fully understood. We examined the molecular mechanisms underlying acrolein hepatotoxicity in primary human hepatocytes and hepatoma cells. Acrolein, at pathophysiological concentrations, caused a dose-dependent loss of viability of hepatocytes. The death was apoptotic at moderate and necrotic at high concentrations of acrolein. Acrolein exposure rapidly and dramatically decreased intracellular glutathione and overall antioxidant capacity, and activated the stress-signaling MAP-kinases JNK, p42/44 and p38. Our data demonstrate for the first time in human hepatocytes, that acrolein triggered endoplasmic reticulum (ER) stress and activated eIF2α, ATF-3 and -4, and Gadd153/CHOP, resulting in cell death. Notably, the protective/adaptive component of ER stress was not activated, and acrolein failed to up-regulate the protective ER-chaperones, GRP78 and GRP94. Additionally, exposure to acrolein disrupted mitochondrial integrity/function, and led to the release of pro-apoptotic proteins and ATP depletion. Acrolein-induced cell death was attenuated by N-acetyl cysteine, phenyl-butyric acid, and caspase and JNK inhibitors. Our data demonstrate that exposure to acrolein induces a variety of stress responses in hepatocytes, including GSH depletion, oxidative stress, mitochondrial dysfunction and ER stress (without ER-protective responses) which together contribute to acrolein toxicity. Our study defines basic mechanisms underlying liver injury caused by reactive aldehyde pollutants such as acrolein.

  13. The tobacco smoke component acrolein induces glucocorticoid resistant gene expression via inhibition of histone deacetylase.

    Randall, Matthew J; Haenen, Guido R M M; Bouwman, Freek G; van der Vliet, Albert; Bast, Aalt

    2016-01-05

    Chronic obstructive pulmonary disease (COPD) is the leading cause of cigarette smoke-related death worldwide. Acrolein, a crucial reactive electrophile found in cigarette smoke mimics many of the toxic effects of cigarette smoke-exposure in the lung. In macrophages, cigarette smoke is known to hinder histone deacetylases (HDACs), glucocorticoid-regulated enzymes that play an important role in the pathogenesis of glucocorticoid resistant inflammation, a common feature of COPD. Thus, we hypothesize that acrolein plays a role in COPD-associated glucocorticoid resistance. To examine the role of acrolein on glucocorticoid resistance, U937 monocytes, differentiated with PMA to macrophage-like cells were treated with acrolein for 0.5h followed by stimulation with hydrocortisone for 8h, or treated simultaneously with LPS and hydrocortisone for 8h without acrolein. GSH and nuclear HDAC activity were measured, or gene expression was analyzed by qPCR. Acrolein-mediated TNFα gene expression was not suppressed by hydrocortisone whereas LPS-induced TNFα expression was suppressed. Acrolein also significantly inhibited nuclear HDAC activity in macrophage-like cells. Incubation of recombinant HDAC2 with acrolein led to the formation of an HDAC2-acrolein adduct identified by mass spectrometry. Therefore, these results suggest that acrolein-induced inflammatory gene expression is resistant to suppression by the endogenous glucocorticoid, hydrocortisone.

  14. Acrolein cytotoxicity in hepatocytes involves endoplasmic reticulum stress, mitochondrial dysfunction and oxidative stress

    Mohammad, Mohammad K. [Department of Medicine, University of Louisville (United States); Alcohol Research Center, University of Louisville (United States); Avila, Diana [Department of Medicine, University of Louisville (United States); Department of Pharmacology and Toxicology, University of Louisville (United States); Alcohol Research Center, University of Louisville (United States); Zhang, Jingwen [Department of Medicine, University of Louisville (United States); Alcohol Research Center, University of Louisville (United States); Barve, Shirish [Department of Medicine, University of Louisville (United States); Department of Pharmacology and Toxicology, University of Louisville (United States); Alcohol Research Center, University of Louisville (United States); Arteel, Gavin [Department of Pharmacology and Toxicology, University of Louisville (United States); Alcohol Research Center, University of Louisville (United States); McClain, Craig [Department of Medicine, University of Louisville (United States); Department of Pharmacology and Toxicology, University of Louisville (United States); Alcohol Research Center, University of Louisville (United States); Robley Rex VAMC, Louisville, KY (United States); Joshi-Barve, Swati, E-mail: s0josh01@louisville.edu [Department of Medicine, University of Louisville (United States); Department of Pharmacology and Toxicology, University of Louisville (United States); Alcohol Research Center, University of Louisville (United States)

    2012-11-15

    Acrolein is a common environmental, food and water pollutant and a major component of cigarette smoke. Also, it is produced endogenously via lipid peroxidation and cellular metabolism of certain amino acids and drugs. Acrolein is cytotoxic to many cell types including hepatocytes; however the mechanisms are not fully understood. We examined the molecular mechanisms underlying acrolein hepatotoxicity in primary human hepatocytes and hepatoma cells. Acrolein, at pathophysiological concentrations, caused a dose-dependent loss of viability of hepatocytes. The death was apoptotic at moderate and necrotic at high concentrations of acrolein. Acrolein exposure rapidly and dramatically decreased intracellular glutathione and overall antioxidant capacity, and activated the stress-signaling MAP-kinases JNK, p42/44 and p38. Our data demonstrate for the first time in human hepatocytes, that acrolein triggered endoplasmic reticulum (ER) stress and activated eIF2α, ATF-3 and -4, and Gadd153/CHOP, resulting in cell death. Notably, the protective/adaptive component of ER stress was not activated, and acrolein failed to up-regulate the protective ER-chaperones, GRP78 and GRP94. Additionally, exposure to acrolein disrupted mitochondrial integrity/function, and led to the release of pro-apoptotic proteins and ATP depletion. Acrolein-induced cell death was attenuated by N-acetyl cysteine, phenyl-butyric acid, and caspase and JNK inhibitors. Our data demonstrate that exposure to acrolein induces a variety of stress responses in hepatocytes, including GSH depletion, oxidative stress, mitochondrial dysfunction and ER stress (without ER-protective responses) which together contribute to acrolein toxicity. Our study defines basic mechanisms underlying liver injury caused by reactive aldehyde pollutants such as acrolein. -- Highlights: ► Human primary hepatocytes and cultured cell lines are used. ► Multiple cell death signaling pathways are activated by acrolein. ► Novel finding of

  15. Acrolein stimulates eicosanoid release from bovine airway epithelial cells

    Doupnik, C.A.; Leikauf, G.D. (Univ. of Cincinnati College of Medicine, OH (USA))

    1990-10-01

    Injury to the airway mucosa after exposure to environmental irritants is associated with pulmonary inflammation and bronchial hyperresponsiveness. To better understand the relationships between mediator release and airway epithelial cell injury during irritant exposures, we studied the effects of acrolein, a low-molecular-weight aldehyde found in cigarette smoke, on arachidonic acid metabolism in cultured bovine tracheal epithelial cells. Confluent airway epithelial cell monolayers, prelabeled with (3H)arachidonic acid, released significant levels of 3H activity when exposed (20 min) to 100 microM acrolein. (3H)arachidonic acid products were resolved using reverse-phase high-performance liquid chromatography. Under control conditions the released 3H activity coeluted predominantly with the cyclooxygenase product, prostaglandin (PG) E2. After exposure to acrolein, significant peaks in 3H activity coeluted with the lipoxygenase products 12-hydroxyeicosatetraenoic acid (HETE) and 15-HETE, as well as with PGE2, PGF2 alpha, and 6-keto-PGF1 alpha. Dose-response relationships for acrolein-induced release of immunoreactive PGF2 alpha and PGE2 from unlabeled epithelial monolayers demonstrated 30 microM acrolein as the threshold dose, with 100 microM acrolein inducing nearly a fivefold increase in both PGF2 alpha and PGE2. Cellular viability after exposure to 100 microM acrolein, determined by released lactate dehydrogenase activity, was not affected until exposure periods were greater than or equal to 2 h. These results implicate the airway epithelial cell as a possible source of eicosanoids after exposure to acrolein.

  16. The effects of acetaldehyde and acrolein on muscle catabolism in C2 myotubes.

    Rom, Oren; Kaisari, Sharon; Aizenbud, Dror; Reznick, Abraham Z

    2013-12-01

    The toxic aldehydes acetaldehyde and acrolein were previously suggested to damage skeletal muscle. Several conditions in which exposure to acetaldehyde and acrolein is increased were associated with muscle wasting and dysfunction. These include alcoholic myopathy, renal failure, oxidative stress, and inflammation. A main exogenous source of both acetaldehyde and acrolein is cigarette smoking, which was previously associated with increased muscle catabolism. Recently, we have shown that exposure of skeletal myotubes to cigarette smoke stimulated muscle catabolism via increased oxidative stress, activation of p38 MAPK, and upregulation of muscle-specific E3 ubiquitin ligases. In this study, we aimed to investigate the effects of acetaldehyde and acrolein on catabolism of skeletal muscle. Skeletal myotubes differentiated from the C2 myoblast cell line were exposed to acetaldehyde or acrolein and their effects on signaling pathways related to muscle catabolism were studied. Exposure of myotubes to acetaldehyde did not promote muscle catabolism. However, exposure to acrolein caused increased generation of free radicals, activation of p38 MAPK, upregulation of the muscle-specific E3 ligases atrogin-1 and MuRF1, degradation of myosin heavy chain, and atrophy of myotubes. Inhibition of p38 MAPK by SB203580 abolished acrolein-induced muscle catabolism. Our findings demonstrate that acrolein but not acetaldehyde activates a signaling cascade resulting in muscle catabolism in skeletal myotubes. Although within the limitations of an in vitro study, these findings indicate that acrolein may promote muscle wasting in conditions of increased exposure to this aldehyde.

  17. Acrolein induced both pulmonary inflammation and the death of lung epithelial cells.

    Sun, Yang; Ito, Sachiko; Nishio, Naomi; Tanaka, Yuriko; Chen, Nana; Isobe, Ken-Ichi

    2014-09-02

    Acrolein, a compound found in cigarette smoke, is a major risk factor for respiratory diseases. Previous research determined that both acrolein and cigarette smoke produced reactive oxygen species (ROS). As many types of pulmonary injuries are associated with inflammation, this study sought to ascertain the extent to which exposure to acrolein advanced inflammatory state in the lungs. Our results showed that intranasal exposure of mice to acrolein increased CD11c(+)F4/80(high) macrophages in the lungs and increased ROS formation via induction of NF-κB signaling. Treatment with acrolein activated macrophages and led to their increased production of ROS and expression of several key pro-inflammatory cytokines. In in vitro studies, acrolein treatment of bone marrow-derived GM-CSF-dependent immature macrophages (GM-IMs), activated the cells and led to their increased production of ROS and expression of several key pro-inflammatory cytokines. Acrolein treatment of macrophages induced apoptosis of lung epithelial cells. Inclusion of an inhibitor of ROS formation markedly decreased acrolein-mediated macrophage activation and reduced the extent of epithelial cell death. These results indicate that acrolein can cause lung damage, in great part by mediating the increased release of pro-inflammatory cytokines/factors by macrophages.

  18. Aldose reductase regulates acrolein-induced cytotoxicity in human small airway epithelial cells.

    Yadav, Umesh C S; Ramana, K V; Srivastava, Satish K

    2013-12-01

    Aldose reductase (AR), a glucose-metabolizing enzyme, reduces lipid aldehydes and their glutathione conjugates with more than 1000-fold efficiency (Km aldehydes 5-30 µM) relative to glucose. Acrolein, a major endogenous lipid peroxidation product as well as a component of environmental pollutants and cigarette smoke, is known to be involved in various pathologies including atherosclerosis, airway inflammation, COPD, and age-related disorders, but the mechanism of acrolein-induced cytotoxicity is not clearly understood. We have investigated the role of AR in acrolein-induced cytotoxicity in primary human small airway epithelial cells (SAECs). Exposure of SAECs to varying concentrations of acrolein caused cell death in a concentration- and time-dependent manner. AR inhibition by fidarestat prevented the low-dose (5-10 µM) but not the high-dose (>10 µM) acrolein-induced SAEC death. AR inhibition protected SAECs from low-dose (5 µM) acrolein-induced cellular reactive oxygen species (ROS). Inhibition of acrolein-induced apoptosis by fidarestat was confirmed by decreased condensation of nuclear chromatin, DNA fragmentation, comet tail moment, and annexin V fluorescence. Further, fidarestat inhibited acrolein-induced translocation of the proapoptotic proteins Bax and Bad from the cytosol to the mitochondria and that of Bcl2 and BclXL from the mitochondria to the cytosol. Acrolein-induced cytochrome c release from mitochondria was also prevented by AR inhibition. The mitogen-activated protein kinases (MAPKs), such as extracellular signal-regulated kinases 1 and 2, stress-activated protein kinase/c-Jun NH2-terminal kinase, and p38MAPK, and c-Jun were transiently activated in airway epithelial cells by acrolein in a concentration- and time-dependent fashion, which was significantly prevented by AR inhibition. These results suggest that AR inhibitors could prevent acrolein-induced cytotoxicity in the lung epithelial cells.

  19. Acrolein induces Alzheimer's disease-like pathologies in vitro and in vivo.

    Huang, Ying-Juan; Jin, Ming-Hua; Pi, Rong-Biao; Zhang, Jun-Jie; Ouyang, Ying; Chao, Xiao-Juan; Chen, Mei-Hui; Liu, Pei-Qing; Yu, Jian-Chen; Ramassamy, Charles; Dou, Juan; Chen, Xiao-Hong; Jiang, Yi-Ming; Qin, Jian

    2013-03-13

    The pathologic mechanisms of Alzheimer's disease (AD) have not been fully uncovered. Acrolein, a ubiquitous dietary pollutant and by-product of oxidative stress, can induce cytotoxicity in neurons, which might play an important role in the etiology of AD. Here, we examined the effects of Acrolein on the AD pathologies in vitro and in vivo. We found Acrolein induced HT22 cells death in concentration- and time-dependent manners. Interestingly, Acrolein increased proteins' levels of amyloid precursor protein (APP), β-secretase (BACE-1) and the amyloid β-peptide transporter receptor for advanced glycation end products, and decreased A-disintegrin and metalloprotease (ADAM) 10 levels. In vivo, chronic oral exposure to Acrolein (2.5 mg/kg/day by intragastric gavage for 8 weeks) induced mild cognitive declination and pyknosis/atrophy of hippocampal neurons. The activity of superoxide dismutase was down-regulated while the level of malondialdehyde was up-regulated in rat brain. Moreover, Acrolein resulted in activation of astrocytes, up-regulation of BACE-1 in cortex and down-regulation of ADAM-10 in hippocampus and cortex. Taken together, our findings suggest that exposure to Acrolein induces AD-like pathology in vitro and in vivo. Scavenging Acrolein might be beneficial for the therapy of AD.

  20. Protective effect of crocin on acrolein-induced tau phosphorylation in the rat brain.

    Rashedinia, Marzieh; Lari, Parisa; Abnous, Khalil; Hosseinzadeh, Hossein

    2015-01-01

    Acrolein, as a by-product of lipid peroxidation, is implicated in brain aging and in the pathogenesis of oxidative stressmediated neurodegenerative disorders such as Alzheimer's disease (AD). Widespread human exposure to the toxic environmental pollutant that is acrolein renders it necessary to evaluate the effects of exogenous acrolein on the brain. This study investigated the toxic effects of oral administration of 3 mg/kg/day acrolein on the rat cerebral cortex. Moreover, the neuroprotective effects of crocin, the main constituent of saffron, against acrolein toxicity were evaluated. We showed that acrolein decreased concentration of glutathione (GSH) and increased levels of malondialdehyde (MDA), Amyloid-beta (Abeta) and phospho-tau in the brain. Simultaneously, acrolein activated Mitogen-Activated Protein Kinases (MAPKs) signalling pathways. Co-administration of crocin significantly attenuated MDA, Abeta and p-tau levels by modulating MAPKs signalling pathways. Our data demonstrated that environmental exposure to acrolein triggers some molecular events which contribute to brain aging and neurodisorders. Additionally, crocin as an antioxidant is a promising candidate for treatment of neurodegenerative disorders, such as brain aging and AD.

  1. IRIS Toxicological Review of Acrolein (2003 Final)

    EPA announced the release of the final report, Toxicological Review of Acrolein: in support of the Integrated Risk Information System (IRIS). The updated Summary for Acrolein and accompanying toxicological review have been added to the IRIS Database.

  2. Acrolein and Human Disease: Untangling the Knotty Exposure Scenarios Accompanying Several Diverse Disorders.

    Burcham, Philip C

    2017-01-17

    Acrolein is a highly toxic electrophile that participates in many diseases, yet efforts to delineate its precise mechanistic contributions to specific conditions are complicated by its wide distribution within human environments. This Perspective develops the proposal that due to its mixed status as environmental pollutant, metabolic byproduct, and endotoxicant which forms via ubiquitous pathophysiological processes, many diseases likely involve acrolein released from multiple sources. Although the category boundaries are indistinct, at least four identifiable exposure scenarios are identifiable. First, in some syndromes, such as those accompanying chronic or acute intoxication with smoke, whatever role acrolein plays in disease pathogenesis mainly traces to exogenous sources such as the combustion of tobacco or other organic matter. A second exposure category involves xenobiotics that undergo metabolism within the body to release acrolein. Still other health conditions, however, involve acrolein that forms via several endogenous pathways, some of which are activated upon intoxication with xenobiotics (i.e., Exposure Category 3), while still others accompany direct physical trauma to body tissues (Exposure Category 4). Further complicating efforts to clarify the role of endogenous acrolein in human disease is the likelihood that many such syndromes are complex phenomena that resemble "chemical mixture exposures" by involving multiple toxic substances simultaneously. This Perspective contends that while recent decades have witnessed much progress in describing the deleterious effects of acrolein at the cellular and molecular levels, more work is needed to define the contributions of different acrolein sources to "real-world" health conditions in human subjects.

  3. Metabolic shift in lung alveolar cell mitochondria following acrolein exposure.

    Agarwal, Amit R; Yin, Fei; Cadenas, Enrique

    2013-11-15

    Acrolein, an α,β unsaturated electrophile, is an environmental pollutant released in ambient air from diesel exhausts and cooking oils. This study examines the role of acrolein in altering mitochondrial function and metabolism in lung-specific cells. RLE-6TN, H441, and primary alveolar type II (pAT2) cells were exposed to acrolein for 4 h, and its effect on mitochondrial oxygen consumption rates was studied by XF Extracellular Flux analysis. Low-dose acrolein exposure decreased mitochondrial respiration in a dose-dependent manner because of alteration in the metabolism of glucose in all the three cell types. Acrolein inhibited glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity, leading to decreased substrate availability for mitochondrial respiration in RLE-6TN, H441, and pAT2 cells; the reduced GAPDH activity was compensated in pAT2 cells by an increase in the activity of glucose-6-phosphate dehydrogenase, the regulatory control of the pentose phosphate pathway. The decrease in pyruvate from glucose metabolism resulted in utilization of alternative sources to support mitochondrial energy production: palmitate-BSA complex increased mitochondrial respiration in RLE-6TN and pAT2 cells. The presence of palmitate in alveolar cells for surfactant biosynthesis may prove to be the alternative fuel source for mitochondrial respiration. Accordingly, a decrease in phosphatidylcholine levels and an increase in phospholipase A2 activity were found in the alveolar cells after acrolein exposure. These findings have implications for understanding the decrease in surfactant levels frequently observed in pathophysiological situations with altered lung function following exposure to environmental toxicants.

  4. Acrolein relaxes mouse isolated tracheal smooth muscle via a TRPA1-dependent mechanism.

    Cheah, Esther Y; Burcham, Philip C; Mann, Tracy S; Henry, Peter J

    2014-05-01

    Airway sensory C-fibres express TRPA1 channels which have recently been identified as a key chemosensory receptor for acrolein, a toxic and highly prevalent component of smoke. TRPA1 likely plays an intermediary role in eliciting a range of effects induced by acrolein including cough and neurogenic inflammation. Currently, it is not known whether acrolein-induced activation of TRPA1 produces other airway effects including relaxation of mouse airway smooth muscle. The aims of this study were to examine the effects of acrolein on airway smooth muscle tone in mouse isolated trachea, and to characterise the cellular and molecular mechanisms underpinning the effects of acrolein. Isometric tension recording studies were conducted on mouse isolated tracheal segments to characterise acrolein-induced relaxation responses. Release of the relaxant PGE₂ was measured by EIA to examine its role in the response. Use of selective antagonists/inhibitors permitted pharmacological characterisation of the molecular and cellular mechanisms underlying this relaxation response. Acrolein induced dose-dependent relaxation responses in mouse isolated tracheal segments. Importantly, these relaxation responses were significantly inhibited by the TRPA1 antagonists AP-18 and HC-030031, an NK₁ receptor antagonist RP-67580, and the EP₂ receptor antagonist PF-04418948, whilst completely abolished by the non-selective COX inhibitor indomethacin. Acrolein also caused rapid PGE₂ release which was suppressed by HC-030031. In summary, acrolein induced a novel bronchodilator response in mouse airways. Pharmacologic studies indicate that acrolein-induced relaxation likely involves interplay between TRPA1-expressing airway sensory C-fibres, NK₁ receptor-expressing epithelial cells, and EP₂-receptor expressing airway smooth muscle cells.

  5. Acrolein involvement in sensory and behavioral hypersensitivity following spinal cord injury in the rat.

    Due, Michael R; Park, Jonghyuck; Zheng, Lingxing; Walls, Michael; Allette, Yohance M; White, Fletcher A; Shi, Riyi

    2014-03-01

    Growing evidence suggests that oxidative stress, as associated with spinal cord injury (SCI), may play a critical role in both neuroinflammation and neuropathic pain conditions. The production of the endogenous aldehyde acrolein, following lipid peroxidation during the inflammatory response, may contribute to peripheral sensitization and hyperreflexia following SCI via the TRPA1-dependent mechanism. Here, we report that there are enhanced levels of acrolein and increased neuronal sensitivity to the aldehyde for at least 14 days after SCI. Concurrent with injury-induced increases in acrolein concentration is an increased expression of TRPA1 in the lumbar (L3-L6) sensory ganglia. As proof of the potential pronociceptive role for acrolein, intrathecal injections of acrolein revealed enhanced sensitivity to both tactile and thermal stimuli for up to 10 days, supporting the compound's pro-nociceptive functionality. Treatment of SCI animals with the acrolein scavenger hydralazine produced moderate improvement in tactile responses as well as robust changes in thermal sensitivity for up to 49 days. Taken together, these data suggest that acrolein directly modulates SCI-associated pain behavior, making it a novel therapeutic target for preclinical and clinical SCI as an analgesic. Following spinal cord injury (SCI), acrolein involvement in neuropathic pain is likely through direct activation and elevated levels of pro-nociceptive channel TRPA1. While acrolein elevation correlates with neuropathic pain, suppression of this aldehyde by hydralazine leads to an analgesic effect. Acrolein may serve as a novel therapeutic target for preclinical and clinical SCI to relieve both acute and chronic post-SCI neuropathic pain.

  6. The Uremic Toxin Acrolein Promotes Suicidal Erythrocyte Death

    Mohamed Siyabeldin E. Ahmed

    2013-05-01

    Full Text Available Background: Anemia is a major complication of end stage renal disease. The anemia is mainly the result of impaired formation of erythrocytes due to lack of erythropoietin and iron deficiency. Compelling evidence, however, points to the contribution of accelerated erythrocyte death, which decreases the life span of circulating erythrocytes. Erythrocytes may enter suicidal death or eryptosis, which is characterized by cell shrinkage and by cell membrane scrambling with phosphatidylserine-exposure at the erythrocyte surface. Triggers of eryptosis include increase of cytosolic Ca2+-activity ([Ca2+]i. Erythrocytes could be sensitized to cytosolic Ca2+ by ceramide. In end stage renal disease, eryptosis may possibly be stimulated by uremic toxins. The present study explored, whether the uremic toxin acrolein could trigger eryptosis. Methods: Cell volume was estimated from forward scatter, phosphatidylserine-exposure from annexin-V-binding, hemolysis from hemoglobin release, [Ca2+]i from Fluo3-fluorescence, and ceramide from fluorescent antibodies. Results: A 48 h exposure to acrolein (30 - 50 µM did not significantly modify [Ca2+]i but significantly decreased forward scatter and increased annexin-V-binding. Acrolein further triggered slight, but significant hemolysis and increased ceramide formation in erythrocytes. Acrolein (50 µM induced annexin-V-binding was significantly blunted in the nominal absence of extracellular Ca2+. Acrolein augmented the annexin-V-binding following treatment with Ca2+ ionophore ionomycin (1 µM. Conclusion: Acrolein stimulates suicidal erythrocyte death or eryptosis, an effect at least in part due to stimulation of ceramide formation with subsequent sensitisation of the erythrocytes to cytosolic Ca2+.

  7. Kinetics and Mechanism of Protein Tyrosine Phosphatase 1B (PTP1B) Inactivation by Acrolein

    Seiner, Derrick R.; LaButti, Jason N.; Gates, Kent S.

    2010-01-01

    Human cells are exposed to the electrophilic α,β-unsaturated aldehyde acrolein from a variety of sources. Reaction of acrolein with functionally critical protein thiol residues can yield important biological consequences. Protein tyrosine phosphatases (PTPs) are an important class of cysteine-dependent enzymes whose reactivity with acrolein previously has not been well characterized. These enzymes catalyze the dephosphorylation of phosphotyrosine residues on proteins via a phosphocysteine intermediate. PTPs work in tandem with protein tyrosine kinases to regulate a number of critically important mammalian signal transduction pathways. We find that acrolein is a potent time-dependent inactivator of the enzyme PTP1B (kinact = 0.02 ± 0.005 s−1, KI = 2.3 ± 0.6 × 10−4 M). Enzyme activity does not return upon gel filtration of the inactivated enzyme and addition of the competitive phosphatase inhibitor vanadate slows inactivation of PTP1B by acrolein. Together these observations suggest that acrolein covalently modifies the active site of PTP1B. Mass spectrometric analysis reveals that acrolein modifies the catalytic cysteine residue at the active site of the enzyme. Aliphatic aldehydes such as glyoxal, acetaldehyde, and propanal are relatively weak inactivators of PTP1B under the conditions employed here. Similarly, unsaturated aldehydes such as crotonaldehyde and 3-methyl-2-butenal bearing substitution at the alkene terminus are poor inactivators of the enzyme. Overall, the data suggest that enzyme inactivation occurs via conjugate addition of the catalytic cysteine residue to the carbon-carbon double bond of acrolein. The results indicate that inactivation of PTPs should be considered as a possible contributor to the diverse biological activities of acrolein and structurally-related α,β-unsaturated aldehydes. PMID:17655273

  8. Kinetics and mechanism of protein tyrosine phosphatase 1B inactivation by acrolein.

    Seiner, Derrick R; LaButti, Jason N; Gates, Kent S

    2007-09-01

    Human cells are exposed to the electrophilic alpha,beta-unsaturated aldehyde acrolein from a variety of sources. The reaction of acrolein with functionally critical protein thiol residues can yield important biological consequences. Protein tyrosine phosphatases (PTPs) are an important class of cysteine-dependent enzymes whose reactivity with acrolein previously has not been well-characterized. These enzymes catalyze the dephosphorylation of phosphotyrosine residues on proteins via a phosphocysteine intermediate. PTPs work in tandem with protein tyrosine kinases to regulate a number of critically important mammalian signal transduction pathways. We find that acrolein is a potent time-dependent inactivator of the enzyme PTP1B ( k inact = 0.02 +/- 0.005 s (-1) and K I = 2.3 +/- 0.6 x 10 (-4) M). The enzyme activity does not return upon gel filtration of the inactivated enzyme, and addition of the competitive phosphatase inhibitor vanadate slows inactivation of PTP1B by acrolein. Together, these observations suggest that acrolein covalently modifies the active site of PTP1B. Mass spectrometric analysis reveals that acrolein modifies the catalytic cysteine residue at the active site of the enzyme. Aliphatic aldehydes such as glyoxal, acetaldehyde, and propanal are relatively weak inactivators of PTP1B under the conditions employed here. Similarly, unsaturated aldehydes such as crotonaldehyde and 3-methyl-2-butenal bearing substitution at the alkene terminus are poor inactivators of the enzyme. Overall, the data suggest that enzyme inactivation occurs via conjugate addition of the catalytic cysteine residue to the carbon-carbon double bond of acrolein. The results indicate that inactivation of PTPs should be considered as a possible contributor to the diverse biological activities of acrolein and structurally related alpha,beta-unsaturated aldehydes.

  9. Curcumin analog 1, 5-bis (2-trifluoromethylphenyl)-1, 4-pentadien-3-one exhibits enhanced ability on Nrf2 activation and protection against acrolein-induced ARPE-19 cell toxicity

    Li, Yuan [Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, FIST, Xi' an Jiaotong University, Xi' an (China); Zou, Xuan [Center for Translational Medicine, FIST, Xi' an Jiaotong University, Xi' an (China); Cao, Ke; Xu, Jie; Yue, Tingting [Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, FIST, Xi' an Jiaotong University, Xi' an (China); Dai, Fang; Zhou, Bo [State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou (China); Lu, Wuyuan [Center for Translational Medicine, FIST, Xi' an Jiaotong University, Xi' an (China); Feng, Zhihui, E-mail: zhfeng@mail.xjtu.edu.cn [Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, FIST, Xi' an Jiaotong University, Xi' an (China); Liu, Jiankang, E-mail: j.liu@mail.xjtu.edu.cn [Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, FIST, Xi' an Jiaotong University, Xi' an (China)

    2013-11-01

    Curcumin, a phytochemical agent in the spice turmeric, has received increasing attention for its anticancer, anti-inflammatory and antioxidant properties. However, application of curcumin has been limited due to its insolubility in water and poor bioavailability both clinically and experimentally. In addition, the protective effects and mechanisms of curcumin in eye diseases have been poorly studied. In the present study, we synthesized a curcumin analog, 1, 5-bis (2-trifluoromethylphenyl)-1, 4-pentadien-3-one (C3), which displayed improved protective effect against acrolein-induced toxicity in a human retinal pigment epithelial cell line (ARPE-19). At 5 μM, curcumin completely protected against acrolein-induced cell oxidative damage and preserved GSH levels and mitochondrial function. Surprisingly, C3 displayed a complete protective effect at 0.5 μM, which was much more efficient than curcumin. Both 0.5 μM C3 and 5 μM curcumin induced Nrf2 nuclear translocation and Nrf2 target genes transcription similarly. Experiments using Nrf2 siRNA showed that the protective effects of curcumin and C3 were eliminated by Nrf2 knockdown. Additionally, both curcumin and C3 activated the PI3/Akt pathway, however, Nrf2 activation was independent of this pathway, and therefore, we hypothesized that both curcumin and C3 activated phase II enzymes via directly disrupting the Nrf2/Keap1 complex and promoting Nrf2's nuclear translocation. Since acrolein challenge of ARPE-19 cells has been used as a model of smoking and age-related macular degeneration (AMD), we concluded that the curcumin analog, C3, may be a more promising drug candidate for its potential application for the prevention and treatment of eye diseases, such as AMD. - Highlights: • We examine toxicity effects of cigarette smoking component acrolein in retina cells. • We report a more efficient curcumin analog (C3) protecting cellular function. • Mitochondrial function and phase II enzyme activation are the

  10. Acrolein decreases endothelial cell migration and insulin sensitivity through induction of let-7a.

    O'Toole, Timothy E; Abplanalp, Wesley; Li, Xiaohong; Cooper, Nigel; Conklin, Daniel J; Haberzettl, Petra; Bhatnagar, Aruni

    2014-08-01

    Acrolein is a major reactive component of vehicle exhaust, and cigarette and wood smoke. It is also present in several food substances and is generated endogenously during inflammation and lipid peroxidation. Although previous studies have shown that dietary or inhalation exposure to acrolein results in endothelial activation, platelet activation, and accelerated atherogenesis, the basis for these effects is unknown. Moreover, the effects of acrolein on microRNA (miRNA) have not been studied. Using AGILENT miRNA microarray high-throughput technology, we found that treatment of cultured human umbilical vein endothelial cells with acrolein led to a significant (>1.5-fold) upregulation of 12, and downregulation of 15, miRNAs. Among the miRNAs upregulated were members of the let-7 family and this upregulation was associated with decreased expression of their protein targets, β3 integrin, Cdc34, and K-Ras. Exposure to acrolein attenuated β3 integrin-dependent migration and reduced Akt phosphorylation in response to insulin. These effects of acrolein on endothelial cell migration and insulin signaling were reversed by expression of a let-7a inhibitor. Also, inhalation exposure of mice to acrolein (1 ppm x 6 h/day x 4 days) upregulated let-7a and led to a decrease in insulin-stimulated Akt phosphorylation in the aorta. These results suggest that acrolein exposure has broad effects on endothelial miRNA repertoire and that attenuation of endothelial cell migration and insulin signaling by acrolein is mediated in part by the upregulation of let-7a. This mechanism may be a significant feature of vascular injury caused by inflammation, oxidized lipids, and exposure to environmental pollutants.

  11. Modification and inactivation of Cu,Zn-superoxide dismutase by the lipid peroxidation product, acrolein

    Jung Hoon Kang

    2013-11-01

    Full Text Available Acrolein is the most reactive aldehydic product of lipidperoxidation and is found to be elevated in the brain whenoxidative stress is high. The effects of acrolein on the structureand function of human Cu,Zn-superoxide dismutase (SOD wereexamined. When Cu,Zn-SOD was incubated with acrolein, thecovalent crosslinking of the protein was increased, and the loss ofenzymatic activity was increased in a dose-dependent manner.Reactive oxygen species (ROS scavengers and copper chelatorsinhibited the acrolein-mediated Cu,Zn-SOD modification and theformation of carbonyl compound. The present study shows thatROS may play a critical role in acrolein-induced Cu,Zn-SODmodification and inactivation. When Cu,Zn-SOD that has beenexposed to acrolein was subsequently analyzed by amino acidanalysis, serine, histidine, arginine, threonine and lysine residueswere particularly sensitive. It is suggested that the modificationand inactivation of Cu,Zn-SOD by acrolein could be produced bymore oxidative cell environments. [BMB Reports 2013; 46(11:555-560

  12. Modification and inactivation of Cu,Zn-superoxide dismutase by the lipid peroxidation product, acrolein.

    Kang, Jung Hoon

    2013-11-01

    Acrolein is the most reactive aldehydic product of lipid peroxidation and is found to be elevated in the brain when oxidative stress is high. The effects of acrolein on the structure and function of human Cu,Zn-superoxide dismutase (SOD) were examined. When Cu,Zn-SOD was incubated with acrolein, the covalent crosslinking of the protein was increased, and the loss of enzymatic activity was increased in a dose-dependent manner. Reactive oxygen species (ROS) scavengers and copper chelators inhibited the acrolein-mediated Cu,Zn-SOD modification and the formation of carbonyl compound. The present study shows that ROS may play a critical role in acrolein-induced Cu,Zn-SOD modification and inactivation. When Cu,Zn-SOD that has been exposed to acrolein was subsequently analyzed by amino acid analysis, serine, histidine, arginine, threonine and lysine residues were particularly sensitive. It is suggested that the modification and inactivation of Cu,Zn-SOD by acrolein could be produced by more oxidative cell environments.

  13. POTENTIATION OF PULMONARY REFLEX RESPONSE TO CAPSAICIN 24 HOURS FOLLOWING WHOLE-BODY ACROLEIN EXPOSURE IS MEDIATED BY TRPV1

    Pulmonary C-fibers are stimulated by irritant air pollutants producing apnea, bronchospasm, and decrease in HR. C-fiber chemoreflex activation is mediated by TRPV1 and release of substance P. While acrolein has been shown to stimulate C-fibers, the persistence of acrolein effect...

  14. Glucose-stimulated acrolein production from unsaturated fatty acids.

    Medina-Navarro, R; Duran-Reyes, G; Diaz-Flores, M; Hicks, J J; Kumate, J

    2004-02-01

    Glucose auto-oxidation may be a significant source of reactive oxygen species (ROS), and also be important in the lipid peroxidation process, accompanied by the release of toxic reactive products. We wanted to demonstrate that acrolein can be formed directly and actively from free fatty acids in a hyperglycemic environment. A suspension of linoleic and arachidonic acids (2.5 mM) was exposed to different glucose concentrations (5, 10 and 15 mmol/L) in vitro. The samples were extracted with organic solvents, partitioned, followed at 255-267 nm, and analysed using capillary electrophoresis and mass spectroscopy. The total release of aldehydes significantly (P < 0.01) increased from 1.0 to 5.1, 8.3 and 13.1 micromol/L after 6 hours of incubation, proportional to glucose concentrations. It was possible to verify a correlate hydroperoxide formation as well. Among the lipid peroxidation products, acrolein (5% of total) and its condensing product, 4-hydroxy-hexenal, were identified. From the results presented here, it was possible to demonstrate the production of acrolein, probably as a fatty acid product, due to free radicals generated from the glucose auto-oxidation process. The results led us to propose that acrolein, which is one of the most toxic aldehydes, is produced during hyperglycemic states, and may lead to tissue injury, as one of the initial problems to be linked to high levels of glucose in vivo.

  15. Update of the exploratory report Acrolein

    Slooff W; Bont PFH; Janus JA; Pronk MEJ; Ros JPM; ECO; PPCbv; ACT; LAE

    1994-01-01

    The report is an update of the exploratory report acrolein (Slooff et al., 1991) that served as a basis for the discussion during the exploratory meeting on acrolein in March 1992. The meeting supported the conclusion that priority should be given to the compartment air and to the risks to humans.

  16. Lithium prevents acrolein-induced neurotoxicity in HT22 mouse hippocampal cells.

    Huang, Yingjuan; Qin, Jian; Chen, Meihui; Chao, Xiaojuan; Chen, Ziwei; Ramassamy, Charles; Pi, Rongbiao; Jin, Minghua

    2014-04-01

    Acrolein is a highly electrophilic alpha, beta-unsaturated aldehyde to which humans are exposed in many situations and has been implicated in neurodegenerative diseases, such as Alzheimer's disease. Lithium is demonstrated to have neuroprotective and neurotrophic effects in brain ischemia, trauma, neurodegenerative disorders, and psychiatric disorders. Previously we have found that acrolein induced neuronal death in HT22 mouse hippocampal cells. In this study, the effects of lithium on the acrolein-induced neurotoxicity in HT22 cells as well as its mechanism(s) were investigated. We found that lithium protected HT22 cells against acrolein-induced damage by the attenuation of reactive oxygen species and the enhancement of the glutathione level. Lithium also attenuated the mitochondrial dysfunction caused by acrolein. Furthermore, lithium significantly increased the level of phospho-glycogen synthase kinase-3 beta (GSK-3β), the non-activated GSK-3β. Taken together, our findings suggest that lithium is a protective agent for acrolein-related neurotoxicity.

  17. Quantum chemical study of the acrolein (CH2CHCHO) + OH + O2 reactions.

    Asatryan, Rubik; da Silva, Gabriel; Bozzelli, Joseph W

    2010-08-19

    Acrolein, a beta-unsaturated (acrylic) aldehyde, is one of the simplest multifunctional molecules, containing both alkene and aldehyde groups. Acrolein is an atmospheric pollutant formed in the photochemical oxidation of the anthropogenic VOC 1,3-butadiene, and serves as a model compound for methacrolein (MACR) and methyl vinyl ketone (MVK), the major oxidation products of the biogenic VOC isoprene. In addition, acrolein is involved in combustion and biological oxidation processes. This study presents a comprehensive theoretical analysis of the acrolein + OH + O(2) addition reactions, which is a key photochemical oxidation sequence, using the G3SX and CBS-QB3 theoretical methods. Both ab initio protocols provide relatively similar results, although the CBS-QB3 method systematically under-predicts literature heats of formation using atomization enthalpies, and also provides lower transition state barrier heights. Several new low-energy pathways for unimolecular reaction of the acrolein-OH-O(2) radicals are identified, with energy at around or below that of the acrolein-OH isomers + O(2). In each case these novel reactions have the potential to reform the hydroxyl radical (OH) and form coproducts that include glyoxal, glycolaldehyde (HOCH(2)CHO), formaldehyde (HCHO), CO, and substituted epoxides. Analogous reaction schemes are developed for the photochemical oxidation of MACR and MVK, producing a number of observed oxidation products. The reaction MACR + OH + O(2) --> hydroxyacetone + OH + CO is expected to be of particular importance. This study also proposes that O(2) addition to chemically activated acrolein-OH adducts can provide prompt regeneration of OH in the atmospheric oxidation of acrolein, via a double activation mechanism. This mechanism can also be extended to isoprene, MVK, and MACR. The importance of the novel chemistry revealed here in the atmospheric oxidation of acrolein and other structurally related OVOCs and VOCs requires further investigation

  18. Korean Red Ginseng water extract inhibits COX-2 expression by suppressing p38 in acrolein-treated human endothelial cells

    Seung Eun Lee

    2014-01-01

    Full Text Available Cigarette smoke is considered a major risk factor for vascular diseases. There are many toxic compounds in cigarette smoke, including acrolein and other α,β-unsaturated aldehydes, which are regarded as mediators of inflammation and vascular dysfunction. Furthermore, recent studies have revealed that acrolein, an α,β-unsaturated aldehyde in cigarette smoke, induces inflammatory mediator expression, which is known to be related to vascular diseases. In this study, we investigated whether Korean Red Ginseng (KRG water extract suppressed acrolein-induced cyclooxygenase (COX-2 expression in human umbilical vein endothelial cells (HUVECs. Acrolein-induced COX-2 expression was accompanied by increased levels of phosphorylated p38 in HUVECs and KRG inhibited COX-2 expression in HUVECs. These results suggest that KRG suppresses acrolein-induced COX-2 expression via inhibition of the p38 mitogen-activated protein kinase signaling pathway. In addition, KRG exhibited an inhibitory effect on acrolein-induced apoptosis, as demonstrated by annexin V–propidium iodide staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay. Consistent with these results, KRG may exert a vasculoprotective effect through inhibition of COX-2 expression in acrolein-stimulated human endothelial cells.

  19. Decrease in acrolein toxicity based on the decline of polyamine oxidases.

    Uemura, Takeshi; Nakamura, Mizuho; Sakamoto, Akihiko; Suzuki, Takehiro; Dohmae, Naoshi; Terui, Yusuke; Tomitori, Hideyuki; Casero, Robert A; Kashiwagi, Keiko; Igarashi, Kazuei

    2016-10-01

    We have shown recently that acrolein is strongly involved in cell damage during brain infarction and chronic renal failure. To study the mechanism of acrolein detoxification, we tried to isolate Neuro2a cells with reduced sensitivity to acrolein toxicity (Neuro2a-ATD cells). In one cell line, Neuro2a-ATD1, the level of glutathione (GSH) was increased. We recently isolated a second cell line, Neuro2a-ATD2, and found that acrolein-producing enzymes [polyamine oxidases (PAO); i.e. acetylpolyamine oxidase (AcPAO), and spermine oxidase (SMO)] are reduced in this cell line due to changes at the level of transcription. In the Neuro2a-ATD2 cells, the IC50 of acrolein increased from 4.2 to 6.8μM, and the levels of FosB and C/EBPβ - transcription factors involved in the transcription of AcPAO and SMO genes - were reduced. Transfection of siRNAs for FosB and C/EBPβ reduced the levels of AcPAO and SMO, respectively. In addition, the synthesis of FosB and AcPAO was also decreased by siRNA for C/EBPβ, because C/EBPβ is one of the transcription factors for the FosB gene. It was also found that transfection of siRNA for C/EBPβ decreased SMO promoter activity in Neuro2a cells but not in ATD2 cells confirming that a decrease in C/EBPβ is involved in the reduced SMO activity in Neuro2a-ATD2 cells. Furthermore, transfection of the cDNA for AcPAO or SMO into Neuro2a cells increased the toxicity of acrolein. These results suggest that acrolein is mainly produced from polyamines by PAO.

  20. Acrolein contributes to TRPA1 up-regulation in peripheral and central sensory hypersensitivity following spinal cord injury.

    Park, Jonghyuck; Zheng, Lingxing; Acosta, Glen; Vega-Alvarez, Sasha; Chen, Zhe; Muratori, Breanne; Cao, Peng; Shi, Riyi

    2015-12-01

    Acrolein, an endogenous aldehyde, has been shown to be involved in sensory hypersensitivity after rat spinal cord injury (SCI), for which the pathogenesis is unclear. Acrolein can directly activate a pro-algesic transient receptor protein ankyrin 1 (TRPA1) channel that exists in sensory neurons. Both acrolein and TRPA1 mRNA are elevated post SCI, which contributes to the activation of TRPA1 by acrolein and consequently, neuropathic pain. In the current study, we further showed that, post-SCI elevation of TRPA1 mRNA exists not only in dorsal root ganglias but also in both peripheral (paw skin) and central endings of primary afferent nerves (dorsal horn of spinal cord). This is the first indication that pain signaling can be over-amplified in the peripheral skin by elevated expressions of TRPA1 following SCI, in addition over-amplification previously seen in the spinal cord and dorsal root ganglia. Furthermore, we show that acrolein alone, in the absence of physical trauma, could lead to the elevation of TRPA1 mRNA at various locations when injected to the spinal cord. In addition, post-SCI elevation of TRPA1 mRNA could be mitigated using acrolein scavengers. Both of these attributes support the critical role of acrolein in elevating TRPA1 expression through gene regulation. Taken together, these data indicate that acrolein is likely a critical causal factor in heightening pain sensation post-SCI, through both the direct binding of TRPA1 receptor, and also by boosting the expression of TRPA1. Finally, our data also further support the notion that acrolein scavenging may be an effective therapeutic approach to alleviate neuropathic pain after SCI. We propose that the trauma-mediated elevation of acrolein causes neuropathic pain through at least two mechanisms: acrolein stimulates the production of transient receptor protein ankyrin 1 (TRPA1) in both central and peripheral locations, and it activates TRPA1 channels directly. Therefore, acrolein appears to be a critical

  1. Pyrolysis of D-Glucose to Acrolein

    Chong Shen; Igor Ying Zhang; Gang Fu; Xin Xu

    2011-01-01

    Despite of its great importance, the detailed molecular mechanism for carbohydrate pyrolysis remains poorly understood. We perform a density functional study with a newly developed XYG3 functional on the processes for D-glucose pyrolysis to acrolein. The most feasible reaction pathway starts from an isomerization from D-glucose to D-fructose, which then undergoes a cyclic Grob fragmentation, followed by a concerted electrocyclic dehydration to yield acrolein. This mechanism can account for the known experimental results.

  2. Pyrolysis of D-Glucose to Acrolein

    Shen, Chong; Zhang, Igor Ying; Fu, Gang; Xu, Xin

    2011-06-01

    Despite of its great importance, the detailed molecular mechanism for carbohydrate pyrolysis remains poorly understood. We perform a density functional study with a newly developed XYG3 functional on the processes for D-glucose pyrolysis to acrolein. The most feasible reaction pathway starts from an isomerization from D-glucose to D-fructose, which then undergoes a cyclic Grob fragmentation, followed by a concerted electrocyclic dehydration to yield acrolein. This mechanism can account for the known experimental results.

  3. Differences in lysine adduction by acrolein and methyl vinyl ketone: implications for cytotoxicity in cultured hepatocytes.

    Kaminskas, Lisa M; Pyke, Simon M; Burcham, Philip C

    2005-11-01

    Acrolein is a highly toxic environmental pollutant that readily alkylates the epsilon-amino group of lysine residues in proteins. In model systems, such chemistry involves sequential addition of two acrolein molecules to a given nitrogen, forming bis-Michael-adducted species that undergo aldol condensation and dehydration to form Nepsilon-(3-formyl-3,4-dehydropiperidino)lysine. Whether this ability to form cyclic adducts participates in the toxicity of acrolein is unknown. To address this issue, we compared the chemistry of protein adduction by acrolein to that of its close structural analogue methyl vinyl ketone, expecting that the alpha-methyl group would hinder the intramolecular cyclization of any bis-adducted species formed by methyl vinyl ketone. Both acrolein and methyl vinyl ketone displayed comparable protein carbonylating activity during in vitro studies with the model protein bovine serum albumin, confirming the alpha,beta,-unsaturated bond of both compounds is an efficient Michael acceptor for protein nucleophiles. However, differences in adduction chemistry became apparent during the use of electrospray ionization-MS to monitor reaction products in a lysine-containing peptide after modification by each compound. For example, although a Schiff base adduct was detected following reaction of the peptide with acrolein, an analogous species was not formed by methyl vinyl ketone. Furthermore, while ions corresponding to mono- and bis-Michael adducts were detected at the N-terminus and lysine residues following peptide modification by both carbonyls, only acrolein modification generated ions attributable to cyclic adducts. Despite these differences in adduction chemistry, in mouse hepatocytes, the two compounds exhibited very comparable abilities to induce rapid, concentration-dependent cell death as well as protein carbonylation. These findings suggest that the acute toxicity of short-chain alpha,beta-unsaturated carbonyl compounds involves their ability to

  4. Acrolein, an α,β-unsaturated aldehyde, irreversibly inhibits the acetylation of aromatic amine xenobiotics by human arylamine N-acetyltransferase 1.

    Bui, Linh C; Manaa, Amine; Xu, Ximing; Duval, Romain; Busi, Florent; Dupret, Jean-Marie; Rodrigues-Lima, Fernando; Dairou, Julien

    2013-07-01

    Acrolein is an electrophilic α,β-unsaturated aldehyde of industrial, pharmaceutic, and toxicologic importance to which we are exposed in environmental, occupational, and therapeutic situations. Acrolein is known to exert different biologic effects through reactions with cellular macromolecules such as DNA, certain proteins, or glutathione. In many situations (such as in tobacco smoke or other fumes), exposure to acrolein occurs concomitantly with other compounds such as aromatic amine chemicals. Interestingly, it has been shown that acrolein could impact the cellular metabolism of aromatic xenobiotics through an indirect mechanism based on the transcriptional induction of phase II xenobiotic-metabolizing enzymes. Here we report a novel mechanism by which acrolein acts on the metabolism of aromatic foreign chemicals. We provide molecular, kinetic, and cellular evidence that acrolein can react directly and irreversibly with arylamine N-acetyltransferases, a major family of xenobiotic-metabolizing enzymes involved in the metabolization of aromatic amine chemicals. Formation of an acrolein adduct with a catalytic cysteine residue in the active site is responsible for the impairment of aromatic amine acetylation by the enzyme. This biochemical process may represent an additional mechanism by which acrolein impacts the metabolism and fate of aromatic amine drugs and pollutants.

  5. Chitosan nanoparticle-based neuronal membrane sealing and neuroprotection following acrolein-induced cell injury

    Shi Riyi

    2010-01-01

    Full Text Available Abstract Background The highly reactive aldehyde acrolein is a very potent endogenous toxin with a long half-life. Acrolein is produced within cells after insult, and is a central player in slow and progressive "secondary injury" cascades. Indeed, acrolein-biomolecule complexes formed by cross-linking with proteins and DNA are associated with a number of pathologies, especially central nervous system (CNS trauma and neurodegenerative diseases. Hydralazine is capable of inhibiting or reducing acrolein-induced damage. However, since hydralazine's principle activity is to reduce blood pressure as a common anti-hypertension drug, the possible problems encountered when applied to hypotensive trauma victims have led us to explore alternative approaches. This study aims to evaluate such an alternative - a chitosan nanoparticle-based therapeutic system. Results Hydralazine-loaded chitosan nanoparticles were prepared using different types of polyanions and characterized for particle size, morphology, zeta potential value, and the efficiency of hydralazine entrapment and release. Hydralazine-loaded chitosan nanoparticles ranged in size from 300 nm to 350 nm in diameter, and with a tunable, or adjustable, surface charge. Conclusions We evaluated the utility of chitosan nanoparticles with an in-vitro model of acrolein-mediated cell injury using PC -12 cells. The particles effectively, and statistically, reduced damage to membrane integrity, secondary oxidative stress, and lipid peroxidation. This study suggests that a chitosan nanoparticle-based therapy to interfere with "secondary" injury may be possible.

  6. Reductive detoxification of acrolein as a potential role for aldehyde reductase (AKR1A) in mammals.

    Kurahashi, Toshihiro; Kwon, Myoungsu; Homma, Takujiro; Saito, Yuka; Lee, Jaeyong; Takahashi, Motoko; Yamada, Ken-Ichi; Miyata, Satoshi; Fujii, Junichi

    2014-09-12

    Aldehyde reductase (AKR1A), a member of the aldo-keto reductase superfamily, suppresses diabetic complications via a reduction in metabolic intermediates; it also plays a role in ascorbic acid biosynthesis in mice. Because primates cannot synthesize ascorbic acid, a principle role of AKR1A appears to be the reductive detoxification of aldehydes. In this study, we isolated and immortalized mouse embryonic fibroblasts (MEFs) from wild-type (WT) and human Akr1a-transgenic (Tg) mice and used them to investigate the potential roles of AKR1A under culture conditions. Tg MEFs showed higher methylglyoxal- and acrolein-reducing activities than WT MEFs and also were more resistant to cytotoxicity. Enzymatic analyses of purified rat AKR1A showed that the efficiency of the acrolein reduction was about 20% that of glyceraldehyde. Ascorbic acid levels were quite low in the MEFs, and while the administration of ascorbic acid to the cells increased the intracellular levels of ascorbic acid, it had no affect on the resistance to acrolein. Endoplasmic reticulum stress and protein carbonylation induced by acrolein treatment were less evident in Tg MEFs than in WT MEFs. These data collectively indicate that one of the principle roles of AKR1A in primates is the reductive detoxification of aldehydes, notably acrolein, and protection from its detrimental effects.

  7. A model of hemorrhagic cystitis induced with acrolein in mice

    C.K.L.P. Batista

    2006-11-01

    Full Text Available Acrolein is a urinary metabolite of cyclophosphamide and ifosfamide, which has been reported to be the causative agent of hemorrhagic cystitis induced by these compounds. A direct cytotoxic effect of acrolein, however, has not yet been demonstrated. In the present study, the effects of intravesical injection of acrolein and mesna, the classical acrolein chemical inhibitor, were evaluated. Male Swiss mice weighing 25 to 35 g (N = 6 per group received saline or acrolein (25, 75, 225 µg intravesically 3, 6, 12, and 24 h before sacrifice for evaluation of bladder wet weight, macroscopic and histopathological changes by Gray's criteria, and 3 and 24 h for assessment of increase in vascular permeability. In other animals, mesna was administered intravesically (2 mg or systemically (80 mg/kg 1 h before acrolein. Intravesical administration of acrolein induced a dose- and time-dependent increase in vascular permeability and bladder wet weight (within 3 h: 2.2- and 21-fold increases in bladder wet weight and Evans blue dye exuded, respectively, at doses of 75 µg/bladder, as confirmed by Gray's criteria. Pretreatment with mesna (2-mercaptoethanesulfonic acid, which interacts with acrolein resulting in an inactive compound, inhibited all changes induced by acrolein. Our results are the first demonstration that intravesical administration of acrolein induces hemorrhagic cystitis. This model of acrolein-induced hemorrhagic cystitis in mice may be an important tool for the evaluation of the mechanism by which acrolein induces bladder lesion, as well as for investigation of new uroprotective drugs.

  8. Differential regulation of c-jun and CREB by acrolein and 4-hydroxynonenal.

    Pugazhenthi, Subbiah; Phansalkar, Ketaki; Audesirk, Gerald; West, Anne; Cabell, Leigh

    2006-01-01

    In Alzheimer's disease (AD), oxidative stress-induced lipid peroxidation leads to accumulation of unsaturated aldehydes including acrolein and 4-hydroxynonenal (4HNE) in brain. In this study, we examined the effects of these lipid peroxidation products on apoptotic pathways in cultured neurons. Acrolein and 4HNE increased the levels of active phosphorylated forms of c-jun and CREB, the transcription factors that promote apoptosis and cell survival, respectively. However, they decreased the activity of CREB-dependent BDNF promoter while they increased the activity of promoters responsive to c-jun. We hypothesized that this differential regulation could be due to competition between proapoptotic c-jun and cytoprotective CREB for CBP (CREB-binding protein), a coactivator shared by several transcription factors. In support of this hypothesis, we demonstrate that the decrease of BDNF promoter activity by acrolein and 4HNE could be restored (i) by cotransfection with CBP, (ii) by cotransfection with VP 16-CREB, a constitutively active form of CREB that does not depend on CBP for its activation, or (iii) by inhibiting JNK-mediated c-jun activation. Finally, adenoviral transduction of hippocampal neurons with VP 16-CREB resulted in significant reduction in caspase-3 activation by acrolein and 4HNE. These observations suggest that lipid peroxidation-induced differential regulation of CREB and c-jun might play a role in neurodegeneration in AD.

  9. Acrolein metabolites, diabetes and insulin resistance.

    Feroe, Aliya G; Attanasio, Roberta; Scinicariello, Franco

    2016-07-01

    Acrolein is a dietary and environmental pollutant that has been associated in vitro to dysregulate glucose transport. We investigated the association of urinary acrolein metabolites N-acetyl-S-(3-hydroxypropyl)-l-cysteine (3-HPMA) and N-acetyl-S-(carboxyethyl)-l-cysteine (CEMA) and their molar sum (∑acrolein) with diabetes using data from investigated 2027 adults who participated in the 2005-2006 National Health and Nutrition Examination Survey (NHANES). After excluding participants taking insulin or other diabetes medication we, further, investigated the association of the compounds with insulin resistance (n=850), as a categorical outcome expressed by the homeostatic model assessment (HOMA-IR>2.6). As secondary analyses, we investigated the association of the compounds with HOMA-IR, HOMA-β, fasting insulin and fasting plasma glucose. The analyses were performed using urinary creatinine as independent variable in the models, and, as sensitivity analyses, the compounds were used as creatinine corrected variables. Diabetes as well as insulin resistance (defined as HOMA-IR>2.6) were positively associated with the 3-HPMA, CEMA and ∑Acrolein with evidence of a dose-response relationship (pCEMA compared to the lowest quartile were significantly associated with higher HOMA-IR, HOMA-β and fasting insulin with a dose-response relationship. The highest 3rd quartile of 3-HPMA and ∑Acrolein were positively and significantly associated with HOMA-IR, HOMA-β and fasting insulin. These results suggest a need of further studies to fully understand the implications of acrolein with type 2 diabetes and insulin.

  10. Polyamine modification by acrolein exclusively produces 1,5-diazacyclooctanes: a previously unrecognized mechanism for acrolein-mediated oxidative stress.

    Tsutsui, Ayumi; Imamaki, Rie; Kitazume, Shinobu; Hanashima, Shinya; Yamaguchi, Yoshiki; Kaneda, Masato; Oishi, Shinya; Fujii, Nobutaka; Kurbangalieva, Almira; Taniguchi, Naoyuki; Tanaka, Katsunori

    2014-07-28

    Acrolein, a toxic unsaturated aldehyde generated as a result of oxidative stress, readily reacts with a variety of nucleophilic biomolecules. Polyamines, which produced acrolein in the presence of amine oxidase, were then found to react with acrolein to produce 1,5-diazacyclooctane, a previously unrecognized but significant downstream product of oxidative stress. Although diazacyclooctane formation effectively neutralized acrolein toxicity, the diazacyclooctane hydrogel produced through a sequential diazacyclooctane polymerization reaction was highly cytotoxic. This study suggests that diazacyclooctane formation is involved in the mechanism underlying acrolein-mediated oxidative stress.

  11. Threshold photoelectron spectroscopy of acetaldehyde and acrolein

    Yencha, Andrew J., E-mail: ayencha@albany.edu [Department of Chemistry, University at Albany, State University of New York, Albany, NY 12222 (United States); Siggel-King, Michele R.F. [Cockcroft Institute, Sci-Tech Daresbury, Warrrington WA4 4AD (United Kingdom); Department of Physics, University of Liverpool, Liverpool L69 3BX (United Kingdom); King, George C. [Department of Physics and Astronomy and Photon Science Institute, Manchester University, Manchester M13 9PL (United Kingdom); Malins, Andrew E.R. [Cockcroft Institute, Sci-Tech Daresbury, Warrrington WA4 4AD (United Kingdom); Eypper, Marie [School of Chemistry, University of Southampton, Southampton SO17 1BJ (United Kingdom)

    2013-04-15

    Highlights: •High-resolution threshold photoelectron spectrum of acetaldehyde. •High-resolution threshold photoelectron spectrum of acrolein. •High-resolution total photoion yield spectrum of acetaldehyde. •High-resolution total photoion yield spectrum of acrolein. •Determination of vertical ionization potentials in acetaldehyde and acrolein. -- Abstract: High-resolution (6 meV and 12 meV) threshold photoelectron (TPE) spectra of acetaldehyde and acrolein (2-propenal) have been recorded over the valence binding energy region 10–20 eV, employing synchrotron radiation and a penetrating-field electron spectrometer. These TPE spectra are presented here for the first time. All of the band structures observed in the TPE spectra replicate those found in their conventional HeI photoelectron (PE) spectra. However, the relative band intensities are found to be dramatically different in the two types of spectra that are attributed to the different dominant operative formation mechanisms. In addition, some band shapes and their vertical ionization potentials are found to differ in the two types of spectra that are associated with the autoionization of Rydberg states in the two molecules.

  12. Acrolein and embryogenesis: an experimental study

    Chhibber, G.; Cilani, S.H.

    1986-01-01

    The effects of acrolein were studied on the chick embryos of 48 and 72 hr of incubation. Acrolein was dissolved in physiological saline and injected into the air sacs of the eggs at doses ranging from 0.001 to 0.1 mg per egg. The controls received and equal amount of saline only (0.1 ml per egg). All the embryos including controls were examined at Day 13. In all, 600 eggs were utilized for this investigation. At 48 hr incubation, the percentage survival ranged from 80 to 0 as the dosage of acrolein was increased. Embryonic mortality following 72 hr incubation did not increase significantly at any dose level. Gross malformations such as short and twisted limbs, everted viscera, microphthalmia, short and twisted neck, and hemorrhage over the body were observed. The frequency and the types of gross abnormalities did not vary much in the 48- or 72-hr-treated groups. The incidence of malformation in the controls was low. The results of this study indicates that acrolein is embryotoxic at higher doses and moderately teratogenic to chick embryogenesis.

  13. Neutrophil activator of matrix metalloproteinase-2 (NAM).

    Rollo, Ellen E; Hymowitz, Michelle; Schmidt, Cathleen E; Montana, Steve; Foda, Hussein; Zucker, Stanley

    2006-01-01

    We have isolated a novel soluble factor(s), neutrophil activator of matrix metalloproteinases (NAM), secreted by unstimulated normal human peripheral blood neutrophils that causes the activation of cell secreted promatrix metalloproteinase-2 (proMMP-2). Partially purified preparations of NAM have been isolated from the conditioned media of neutrophils employing gelatin-Sepharose chromatography and differential membrane filter centrifugation. NAM activity, as assessed by exposing primary human umbilical vein endothelial cells (HUVEC) or HT1080 cells to NAM followed by gelatin zymography, was seen within one hour. Tissue inhibitor of metalloproteinase-2 (TIMP-2) and hydroxamic acid derived inhibitors of MMPs (CT1746 and BB94) abrogated the activation of proMMP-2 by NAM, while inhibitors of serine and cysteine proteases showed no effect. NAM also produced an increase in TIMP-2 binding to HUVEC and HT1080 cell surfaces that was inhibited by TIMP-2, CT1746, and BB94. Time-dependent increases in MT1-MMP protein and mRNA were seen following the addition of NAM to cells. These data support a role for NAM in cancer dissemination.

  14. Effects of cyclophosphamide and acrolein in organoid cultures of mouse limb bud cells grown in the presence of adult rat hepatocytes.

    Ghaida, J; Merker, H J

    1992-01-01

    The effects were evaluated of cyclophosphamide (CPA) and its metabolite, acrolein, on chondrogenesis in organoid cultures of mouse limb bud mesenchymal cells co-cultured with non-enzymatically isolated adult rat hepatocytes. The studies were conducted with or without the simultaneous addition of 2-mercaptoethanesulphonic acid sodium (mesna) or glutathione (GSH). Alcian blue binding assay and light and electron microscopic techniques were used. Increasing concentrations of the two compounds (bioactivated CPA, 18-180 mum; acrolein, 50-500 mum) led to a dose-dependent inhibition of chondrogenesis associated with cellular dedifferentiation and/or cytotoxicity. Addition of mesna (1 mm) or GSH (1 mm) partially protected the cultures against CPA and acrolein. However, the protective effect depended on the dose of CPA or acrolein used. A higher protection was observed with mesna than with GSH, and the effect was more pronounced with acrolein than with CPA. The morphological findings suggested that CPA and acrolein acted by different mechanisms. Bioactivated CPA primarily inhibited the differentiation process, whereas acrolein exhibited a high cytotoxic activity affecting particularly monolayer cells that normally grow on the periphery of the cultures. These findings suggest that acrolein possesses a specific mode of action directed towards this type of cell. This could be explained by the specific shape and/or behaviour of the cells (i.e. cytoskeletal arrangement, proliferation rate, migration activity, intercellular communication pattern, etc.). The results demonstrated that the cell system used was suitable for the performance of cytotoxicity and teratogenicity studies such as those conducted with CPA and acrolein.

  15. Protective effects of caffeic acid and caffeic acid phenethyl ester against acrolein-induced neurotoxicity in HT22 mouse hippocampal cells.

    Huang, Yingjuan; Jin, Minghua; Pi, Rongbiao; Zhang, Junjie; Chen, Meihui; Ouyang, Ying; Liu, Anmin; Chao, Xiaojuan; Liu, Peiqing; Liu, Jun; Ramassamy, Charles; Qin, Jian

    2013-02-22

    Acrolein-induced oxidative stress is hypothesized to involve in the etiology of Alzheimer's disease (AD). Caffeic acid (CA) and caffeic acid phenethyl ester (CAPE) have antioxidative and neuroprotective properties. The present study investigated the protective effects of CA/CAPE on acrolein-induced oxidative neuronal toxicity. HT22 mouse hippocampal cells were pretreated with CA/CAPE and then exposed to acrolein. Cell viability, intracellular reactive oxygen species (ROS), and glutathione (GSH) level were measured. MAPKs and Akt/GSK3β signaling proteins as well as α/β-secretase of amyloid protein precursor were assayed by Western blotting. Pretreatment with CA/CAPE significantly attenuated acrolein-induced neurotoxicity, ROS accumulation, and GSH depletion. Further study suggested that CA/CAPE showed protective effects against acrolein by modulating MAPKs and Akt/GSK3β signaling pathways. Moreover, CA/CAPE restored the changes of β-secretase (BACE-1) and/or activation of α-secretase (ADAM-10) induced by acrolein. These findings suggest that CA/CAPE may provide a promising approach for the treatment of acrolein-related neurodegenerative diseases, such as AD.

  16. Acrolein modification impairs key functional features of rat apolipoprotein E: identification of modified sites by mass spectrometry.

    Tran, Tuyen N; Kosaraju, Malathi G; Tamamizu-Kato, Shiori; Akintunde, Olayemi; Zheng, Ying; Bielicki, John K; Pinkerton, Kent; Uchida, Koji; Lee, Yuan Yu; Narayanaswami, Vasanthy

    2014-01-21

    Apolipoprotein E (apoE), an antiatherogenic apolipoprotein, plays a significant role in the metabolism of lipoproteins. It lowers plasma lipid levels by acting as a ligand for the low-density lipoprotein receptor (LDLr) family of proteins, in addition to playing a role in promoting macrophage cholesterol efflux in atherosclerotic lesions. The objective of this study is to examine the effect of acrolein modification on the structure and function of rat apoE and to determine the sites and nature of modification by mass spectrometry. Acrolein is a highly reactive aldehyde, which is generated endogenously as one of the products of lipid peroxidation and is present in the environment in pollutants such as tobacco smoke and heated oils. In initial studies, acrolein-modified apoE was identified by immunoprecipitation using an acrolein-lysine specific antibody in the plasma of 10-week old male rats that were exposed to filtered air (FA) or low doses of environmental tobacco smoke (ETS). While both groups displayed acrolein-modified apoE in the lipoprotein fraction, the ETS group had higher levels in the lipid-free fraction compared with the FA group. This observation provided the rationale to further investigate the effect of acrolein modification on rat apoE at a molecular level. Treatment of recombinant rat apoE with a 10-fold molar excess of acrolein resulted in (i) a significant decrease in lipid-binding and cholesterol efflux abilities, (ii) impairment in the LDLr- and heparin-binding capabilities, and (iii) significant alterations in the overall stability of the protein. The disruption in the functional abilities is attributed directly or indirectly to acrolein modification yielding an aldimine adduct at K149 and K155 (+38); a propanal adduct at K135 and K138 (+56); an N(ε)-(3-methylpyridinium)lysine (MP-lysine) at K64, K67, and K254 (+76), and an N(ε)-(3-formyl-3,4-dehydropiperidino)lysine (FDP-lysine) derivative at position K68 (+94), as determined by matrix

  17. Proteomic analysis of rat cerebral cortex following subchronic acrolein toxicity.

    Rashedinia, Marzieh; Lari, Parisa; Abnous, Khalil; Hosseinzadeh, Hossein

    2013-10-01

    Acrolein, a member of reactive α,β-unsaturated aldehydes, is a major environmental pollutant. Acrolein is also produced endogenously as a toxic by-product of lipid peroxidation. Because of high reactivity, acrolein may mediate oxidative damages to cells and tissues. It has been shown to be involved in a wide variety of pathological states including pulmonary, atherosclerosis and neurodegenerative diseases. In this study we employed proteomics approach to investigate the effects of subchronic oral exposures to 3mg/kg of acrolein on protein expression profile in the brain of rats. Moreover effects of acrolein on malondialdehyde (MDA) levels and reduced glutathione (GSH) content were investigated. Our results revealed that treatment with acrolein changed levels of several proteins in diverse physiological process including energy metabolism, cell communication and transport, response to stimulus and metabolic process. Interestingly, several differentially over-expressed proteins, including β-synuclein, enolase and calcineurin, are known to be associated with human neurodegenerative diseases. Changes in the levels of some proteins were confirmed by Western blot. Moreover, acrolein increases the level of MDA, as a lipid peroxidation biomarker and decreased GSH concentrations, as a non-enzyme antioxidant in the brain of acrolein treated rats. These findings suggested that acrolein induces the oxidative stress and lipid peroxidation in the brain, and so that may contribute to the pathophysiology of neurological disorders.

  18. Proteomic analysis of rat cerebral cortex following subchronic acrolein toxicity

    Rashedinia, Marzieh; Lari, Parisa [Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of); Abnous, Khalil, E-mail: Abnouskh@mums.ac.r [Pharmaceutical Research Center, Department of Medicinal Chemistry, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of); Hosseinzadeh, Hossein, E-mail: Hosseinzadehh@mums.ac.ir [Pharmaceutical Research Center, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of)

    2013-10-01

    Acrolein, a member of reactive α,β-unsaturated aldehydes, is a major environmental pollutant. Acrolein is also produced endogenously as a toxic by-product of lipid peroxidation. Because of high reactivity, acrolein may mediate oxidative damages to cells and tissues. It has been shown to be involved in a wide variety of pathological states including pulmonary, atherosclerosis and neurodegenerative diseases. In this study we employed proteomics approach to investigate the effects of subchronic oral exposures to 3 mg/kg of acrolein on protein expression profile in the brain of rats. Moreover effects of acrolein on malondialdehyde (MDA) levels and reduced glutathione (GSH) content were investigated. Our results revealed that treatment with acrolein changed levels of several proteins in diverse physiological process including energy metabolism, cell communication and transport, response to stimulus and metabolic process. Interestingly, several differentially over-expressed proteins, including β-synuclein, enolase and calcineurin, are known to be associated with human neurodegenerative diseases. Changes in the levels of some proteins were confirmed by Western blot. Moreover, acrolein increases the level of MDA, as a lipid peroxidation biomarker and decreased GSH concentrations, as a non-enzyme antioxidant in the brain of acrolein treated rats. These findings suggested that acrolein induces the oxidative stress and lipid peroxidation in the brain, and so that may contribute to the pathophysiology of neurological disorders. - Highlights: • Acrolein intoxication increased lipid peroxidation and deplete GSH in rat brain. • Effect of acrolein on protein levels of cerebral cortex was analyzed by 2DE-PAGE. • Levels of a number of proteins with different biological functions were increased.

  19. Time and dose effects of cigarette smoke and acrolein on protein carbonyl formation in HaCaT keratinocytes.

    Avezov, K; Reznick, A Z; Aizenbud, D

    2015-01-01

    Cigarette smoke (CS) is an important environmental source of human exposure to a highly toxic and chemically active α,β-unsaturated aldehyde: acrolein. It is capable of causing protein carbonylation and dysfunction, especially in oral tissues of smokers, constantly exposed to CS toxic constituents. The foremost damage is considered to be cumulative, but even a short exposure can be potentially harmful. The objectives of the current study were to examine the short time and dose effects of direct CS and acrolein exposure on intracellular protein carbonylation in epithelial cells. HaCaT-keratinocytes were exposed to different doses of acrolein and whole phase CS using a unique smoking simulator apparatus that mimics the exposure in smokers. The rate of intracellular protein carbonyl modification was examined 10-60 min after the exposure by Western blot. In addition, the effect of pre-incubation with a thiol scavenger N-acetylcysteine (NAC) was also assessed. We found that intracellular protein carbonyls increased as fast as 10 min after CS exposure and their concentration doubled after 20 min, with a slight elevation afterwards. Also, carbonyl levels increased gradually as CS and acrolein doses were elevated. Addition of 1 mM NAC neutralized part of the damage. We conclude that CS and acrolein intracellular protein carbonylation is dose- and time- dependent. Even a short time exposure to CS and its aldehydic constituents can be potentially harmful.

  20. A combined experimental and computational study of the catalytic dehydration of glycerol on microporous zeolites: an investigation of the reaction mechanism and acrolein selectivity.

    Lin, Xufeng; Lv, Yanhong; Qu, Yuanyuan; Zhang, Guodong; Xi, Yanyan; Phillips, David L; Liu, Chenguang

    2013-12-14

    The catalytic activity and the acrolein selectivity for liquid phase glycerol dehydration on β zeolites (HNa-β-k) were found to be dependent on the reaction temperature as well as on the amount of acid sites on the zeolites. An increase in the reaction temperature favors the acrolein selectivity. The acrolein selectivity increases with the Na(+)/H(+) ratio and the glycerol conversion decreases with it so that a maximum acrolein yield is obtained when a certain amount of acidic sites are replaced by non-active Na(+) sites. The computational results indicate that 3-hydoxylpropanal (HPA) is an important intermediate that determines the final product selectivity. The relative rates of the different reaction pathways for HAP can be affected by the amount of water molecules involved in its homogeneous reaction. Based on the reaction mechanism proposed, it was hypothesized that smaller pores reduce activity but increase selectivity to acrolein, and results of the H-MFI zeolite were consistent with this hypothesis. Our work provides important insight into the overall landscape of the reaction mechanism and can be used to help design reaction systems that have good acrolein selectivity for the liquid phase glycerol dehydration reactions.

  1. Flexible electronic-paper active-matrix displays

    Huitema, H.E.A.; Gelinck, G.H.; Lieshout, P.J.G.; Veenendaal, E. van; Touwslager, F.J.

    2006-01-01

    A 100-um-thick 320 x 240-pixel active-matrix display integrated into a functional-device prototype is presented. The active matrix is composed of alternating layers of organic materials and gold. A six-mask photolithographic process is used. An electrophoretic electronic imaging film is laminated on

  2. Molecular mechanisms of acrolein toxicity: relevance to human disease.

    Moghe, Akshata; Ghare, Smita; Lamoreau, Bryan; Mohammad, Mohammad; Barve, Shirish; McClain, Craig; Joshi-Barve, Swati

    2015-02-01

    Acrolein, a highly reactive unsaturated aldehyde, is a ubiquitous environmental pollutant and its potential as a serious environmental health threat is beginning to be recognized. Humans are exposed to acrolein per oral (food and water), respiratory (cigarette smoke, automobile exhaust, and biocide use) and dermal routes, in addition to endogenous generation (metabolism and lipid peroxidation). Acrolein has been suggested to play a role in several disease states including spinal cord injury, multiple sclerosis, Alzheimer's disease, cardiovascular disease, diabetes mellitus, and neuro-, hepato-, and nephro-toxicity. On the cellular level, acrolein exposure has diverse toxic effects, including DNA and protein adduction, oxidative stress, mitochondrial disruption, membrane damage, endoplasmic reticulum stress, and immune dysfunction. This review addresses our current understanding of each pathogenic mechanism of acrolein toxicity, with emphasis on the known and anticipated contribution to clinical disease, and potential therapies.

  3. Application of Activated Carbon Mixed Matrix Membrane for Oxygen Purification

    Tutuk Djoko Kusworo

    2010-07-01

    Full Text Available This study is performed primarily to investigate the effect of activated carbon on oxygen separation performance of polyethersulfone mixed matrix membrane. In this study, polyethersulfone (PES-activated carbon (AC mixed matrix membranes were fabricated using dry/wet technique. This study investigates the effect of polyethersulfone concentration and activated carbon loading on the performance of mixed matrix membrane in terms of permeability and selectivity of O2/N2 gas separation. The fabricated flat sheet mixed matrix membranes were characterized using permeation test, Field Emission Scanning Electron Microscopy (FESEM analysis and Differential Scanning Calorimetry (DSC. It was found that the activated carbon loading affected the gas separation performance of mixed matrix membrane. PES- 1wt% AC membrane yielded 3.75 of O2/N2 selectivity, however 5 wt% of AC can produced 5 O2/N2 selectivity

  4. Determination of molecular line parameters for acrolein (C(3)H(4)O) using infrared tunable diode laser absorption spectroscopy.

    Harward, Charles N; Thweatt, W David; Baren, Randall E; Parrish, Milton E

    2006-04-01

    Acrolein (C(3)H(4)O) molecular line parameters, including infrared (IR) absorption positions, strengths, and nitrogen broadened half-widths, must be determined since they are not included in the high resolution transmission (HITRAN) molecular absorption database of spectral lines. These parameters are required for developing a quantitative analytical method for measuring acrolein in a single puff of cigarette smoke using tunable diode laser absorption spectroscopy (TDLAS). The task is complex since acrolein has many highly overlapping infrared absorption lines in the room temperature spectrum and the cigarette smoke matrix contains thousands of compounds. This work describes the procedure for estimating the molecular line parameters for these overlapping absorption lines in the wavenumber range (958.7-958.9 cm(-1)) using quantitative reference spectra taken with the infrared lead-salt TDLAS instrument at different pressures and concentrations. The nitrogen broadened half-width for acrolein is 0.0937 cm(-1)atm(-1) and to our knowledge, is the first time it has been reported in the literature.

  5. Acrolein induction of oxidative stress and degranulation in mast cells.

    Hochman, Daniel J; Collaco, Christopher R; Brooks, Edward G

    2014-08-01

    Increases in asthma worldwide have been associated epidemiologically with expanding urban air pollution. The mechanistic relationship between airway hyper-responsiveness, inflammation, and ambient airborne triggers remains ambiguous. Acrolein, a ubiquitous aldehyde pollutant, is a product of incomplete combustion reactions. Acrolein is abundant in cigarette smoke, effluent from industrial smokestacks, diesel exhaust, and even hot oil cooking vapors. Acrolein is a potent airway irritant and can induce airway hyper-responsiveness and inflammation in the lungs of animal models. In the present study, we utilized the mast cell analog, RBL-2H3, to interrogate the responses of cells relevant to airway inflammation and allergic responses as a model for the induction of asthma-like conditions upon exposure to acrolein. We hypothesized that acrolein would induce oxidative stress and degranulation in airway mast cells. Our results indicate that acrolein at 1 ppm initiated degranulation and promoted the generation of reactive oxygen species (ROS). Introduction of antioxidants to the system significantly reduced both ROS generation and degranulation. At higher levels of exposure (above 100 ppm), RBL-2H3 cells displayed signs of severe toxicity. This experimental data indicates acrolein can induce an allergic inflammation in mast cell lines, and the initiation of degranulation was moderated by the application of antioxidants.

  6. Acrolein with an alpha, beta-unsaturated Carbonyl Group Inhibits LPS-induced Homodimerization of Toll-like Receptor 4

    Acrolein is a highly electrophilic a,ß-unsaturated aldehyde present in a number of environmental sources, especially cigarette smoke. It reacts strongly with the thiol groups of cysteine residues by Michael addition and has been reported to inhibit nuclear factor-kB (NF-kB) activation by lipopolysac...

  7. Conjugation vs hyperconjugation in molecular structure of acrolein

    Shishkina, Svitlana V.; Slabko, Anzhelika I.; Shishkin, Oleg V.

    2013-01-01

    Analysis of geometric parameters of butadiene and acrolein reveals the contradiction between the Csp2-Csp2 bond length in acrolein and classical concept of conjugation degree in the polarized molecules. In this Letter the reasons of this contradiction have been investigated. It is concluded that the Csp2-Csp2 bond length in acrolein is determined by influence of the bonding for it π-π conjugation and antibonding n → σ∗ hyperconjugation between the oxygen lone pair and the antibonding orbital of the single bond. It was shown also this bond length depends on the difference in energy of conjugative and hyperconjugative interactions.

  8. Vapour phase dehydration of glycerol to acrolein over tungstated zirconia catalysts

    Rao Ginjupalli, Srinivasa; Mugawar, Sowmya; Rajan N., Pethan; Kumar Balla, Putra; Chary Komandur, V. R.

    2014-08-01

    Tetragonal (TZ) and monoclinic (MZ) polymorphs of zirconia supports were synthesised by sol-gel method followed by variation of the calcination temperature. Tungstated (10 wt% WO3) supported on the zirconia polymorphs were prepared by impregnation method by using ammonium metatungstate precursor. The physico-chemical properties of the calcined catalysts were characterised by X-ray diffraction, UV-vis diffused reflectance spectroscopy, X-ray photoelectron spectroscopy (XPS), surface area and pore size distribution measurements to gain insight into the effect of morphology of the catalyst textural properties, and structure. The surface acidic properties have been determined by NH3 TPD method and also with FT-IR spectra of pyridine adsorption. Vapour phase dehydration of glycerol to acrolein was employed to investigate the catalytic functionalities. Glycerol conversion and acrolein selectivity was mainly dependent on the fraction of moderate acid sites with majority of them are due to Brønsted acidic sites. Monoclinic zirconia based catalysts have shown the highest activity and acrolein selectivity compared to the corresponding tetragonal zirconia catalysts.

  9. Vapour phase dehydration of glycerol to acrolein over tungstated zirconia catalysts

    Rao Ginjupalli, Srinivasa; Mugawar, Sowmya; Rajan, Pethan N.; Kumar Balla, Putra; Chary Komandur, V.R., E-mail: kvrchary@iict.res.in

    2014-08-01

    Tetragonal (TZ) and monoclinic (MZ) polymorphs of zirconia supports were synthesised by sol–gel method followed by variation of the calcination temperature. Tungstated (10 wt% WO{sub 3}) supported on the zirconia polymorphs were prepared by impregnation method by using ammonium metatungstate precursor. The physico-chemical properties of the calcined catalysts were characterised by X-ray diffraction, UV–vis diffused reflectance spectroscopy, X-ray photoelectron spectroscopy (XPS), surface area and pore size distribution measurements to gain insight into the effect of morphology of the catalyst textural properties, and structure. The surface acidic properties have been determined by NH{sub 3} TPD method and also with FT-IR spectra of pyridine adsorption. Vapour phase dehydration of glycerol to acrolein was employed to investigate the catalytic functionalities. Glycerol conversion and acrolein selectivity was mainly dependent on the fraction of moderate acid sites with majority of them are due to Brønsted acidic sites. Monoclinic zirconia based catalysts have shown the highest activity and acrolein selectivity compared to the corresponding tetragonal zirconia catalysts.

  10. Synthetic smoke with acrolein but not HCl produces pulmonary edema

    Hales, C.A.; Barkin, P.W.; Jung, W.; Trautman, E.; Lamborghini, D.; Herrig, N.; Burke, J.

    1988-03-01

    The chemical toxins in smoke and not the heat are responsible for the pulmonary edema of smoke inhalation. We developed a synthetic smoke composed of carbon particles (mean diameter of 4.3 microns) to which toxins known to be in smoke, such as HCl or acrolein, could be added one at a time. We delivered synthetic smoke to dogs for 10 min and monitored extravascular lung water (EVLW) accumulation thereafter with a double-indicator thermodilution technique. Final EVLW correlated highly with gravimetric values (r = 0.93, P less than 0.01). HCl in concentrations of 0.1-6 N when added to heated carbon (120 degrees C) and cooled to 39 degrees C produced airway damage but no pulmonary edema. Acrolein, in contrast, produced airway damage but also pulmonary edema, whereas capillary wedge pressures remained stable. Low-dose acrolein smoke (less than 200 ppm) produced edema in two of five animals with a 2- to 4-h delay. Intermediate-dose acrolein smoke (200-300 ppm) always produced edema at an average of 147 +/- 57 min after smoke, whereas high-dose acrolein (greater than 300 ppm) produced edema at 65 +/- 16 min after smoke. Thus acrolein but not HCl, when presented as a synthetic smoke, produced a delayed-onset, noncardiogenic, and peribronchiolar edema in a roughly dose-dependent fashion.

  11. Acrolein induces Hsp72 via both PKCdelta/JNK and calcium signaling pathways in human umbilical vein endothelial cells.

    Misonou, Yoshiko; Takahashi, Motoko; Park, Yong Seek; Asahi, Michio; Miyamoto, Yasuhide; Sakiyama, Haruhiko; Cheng, Xinyao; Taniguchi, Naoyuki

    2005-05-01

    Acrolein is a highly electrophilic alpha,beta-unsaturated aldehydes to which humans are exposed in a variety of environment situations and is also a product of lipid peroxidation. Increased levels of unsaturated aldehydes play an important role in the pathogenesis of a number of human diseases such as Alzheimer's disease, atherosclerosis and diabetes. A number of studies have reported that acrolein evokes downstream signaling via an elevation in cellular oxidative stress. Here, we report that low concentrations of acrolein induce Hsp72 in human umbilical vein endothelial cells (HUVEC) and that both the PKCdelta/JNK pathway and calcium pathway were involved in the induction. The findings confirm that the production of reactive oxygen species (ROS) is not directly involved in the pathway. The induction of Hsp72 was not observed in other cells such as smooth muscle cells (SMC) or COS-1 cells. The results suggest that HUVEC have a unique defense system against cell damage by acrolein in which Hsp72 is induced via activation of both the PKCd/JNK and the calcium pathway.

  12. Aggravation of brain infarction through an increase in acrolein production and a decrease in glutathione with aging.

    Uemura, Takeshi; Watanabe, Kenta; Ishibashi, Misaki; Saiki, Ryotaro; Kuni, Kyoshiro; Nishimura, Kazuhiro; Toida, Toshihiko; Kashiwagi, Keiko; Igarashi, Kazuei

    2016-04-29

    We previously reported that tissue damage during brain infarction was mainly caused by inactivation of proteins by acrolein. This time, it was tested why brain infarction increases in parallel with aging. A mouse model of photochemically induced thrombosis (PIT) was studied using 2, 6, and 12 month-old female C57BL/6 mice. The size of brain infarction in the mouse PIT model increased with aging. The volume of brain infarction in 12 month-old mice was approximately 2-fold larger than that in 2 month-old mice. The larger brain infarction in 12 month-old mice was due to an increase in acrolein based on an increase in the activity of spermine oxidase, together with a decrease in glutathione (GSH), a major acrolein-detoxifying compound in cells, based on the decrease in one of the subunits of glutathione biosynthesizing enzymes, γ-glutamylcysteine ligase modifier subunit, with aging. The results indicate that aggravation of brain infarction with aging was mainly due to the increase in acrolein production and the decrease in GSH in brain.

  13. Shunt Active and Series Active Filters-Based Power Quality Conditioner for Matrix Converter

    P. Jeno Paul

    2011-01-01

    Full Text Available This paper proposes a series active filter and shunt active filter to minimize the power quality impact present in matrix converters instead of passive filter. A matrix converter produces significant harmonics and nonstandard frequency components into load. The proposed system compensates the sag and swell problems efficiently in matrix converter. The proposed system has been tested and validated on the matrix converter using MATLAB/Simulink software. Simulated results confirm that the active power filters can maintain high performance for matrix converter.

  14. Catalytic Dehydration of Glycerol to Acrolein over a Catalyst of Pd/LaY Zeolite and Comparison with the Chemical Equilibrium

    Israel Pala Rosas

    2017-02-01

    Full Text Available Glycerol dehydration to acrolein was studied with three catalysts using zeolite-Y. This zeolite in its protonic form (HY, with La (LaY and Pd with La (Pd/LaY, was characterized by X-ray diffraction (XRD, Fourier-transform-infrared spectroscopy (FTIR with pyridine, BET, Scanning Electron Microscope (SEM–Energy-Dispersive Spectroscopy X-ray (EDS and the catalytic activity tests were carried out under H2 atmosphere. It was found that La ions exchanged in the zeolite-Y resulted in the improvement of both glycerol conversion and yield to acrolein, also a relatively constant glycerol conversion was achieved up to three hours, due to the presence of Pd on the catalyst and H2 in the feed. The comparison of the calculated and experimental yields obtained from the catalytic tests of the Pd/LaY catalyst indicates a greater activity for the reaction to acrolein than for the reaction to acetol. The calculated equilibrium yields of the dehydration reaction from glycerol to acrolein, acetol, ethanal, methanol, and water and the experimental yields of a Pd/LaY catalyst were compared. Thermodynamically, a complete conversion of glycerol can be achieved since the general system remains exothermic and promotes the path to acetol below 480 K. Above this temperature the system consumes energy and favors the production of acrolein, reaching its maximum concentration at 600 K.

  15. Cellular contractility and extracellular matrix stiffness regulate matrix metalloproteinase activity in pancreatic cancer cells.

    Haage, Amanda; Schneider, Ian C

    2014-08-01

    The pathogenesis of cancer is often driven by local invasion and metastasis. Recently, mechanical properties of the tumor microenvironment have been identified as potent regulators of invasion and metastasis, while matrix metalloproteinases (MMPs) are classically known as significant enhancers of cancer cell migration and invasion. Here we have been able to sensitively measure MMP activity changes in response to specific extracellular matrix (ECM) environments and cell contractility states. Cells of a pancreatic cancer cell line, Panc-1, up-regulate MMP activities between 3- and 10-fold with increased cell contractility. Conversely, they down-regulate MMP activities when contractility is blocked to levels seen with pan-MMP activity inhibitors. Similar, albeit attenuated, responses are seen in other pancreatic cancer cell lines, BxPC-3 and AsPC-1. In addition, MMP activity was modulated by substrate stiffness, collagen gel concentration, and the degree of collagen cross-linking, when cells were plated on collagen gels ranging from 0.5 to 5 mg/ml that span the physiological range of substrate stiffness (50-2000 Pa). Panc-1 cells showed enhanced MMP activity on stiffer substrates, whereas BxPC-3 and AsPC-1 cells showed diminished MMP activity. In addition, eliminating heparan sulfate proteoglycans using heparinase completely abrogated the mechanical induction of MMP activity. These results demonstrate the first functional link between MMP activity, contractility, and ECM stiffness and provide an explanation as to why stiffer environments result in enhanced cell migration and invasion.

  16. Google matrix of the world network of economic activities

    Kandiah, Vivek; Escaith, Hubert; Shepelyansky, Dima L.

    2015-07-01

    Using the new data from the OECD-WTO world network of economic activities we construct the Google matrix G of this directed network and perform its detailed analysis. The network contains 58 countries and 37 activity sectors for years 1995 and 2008. The construction of G, based on Markov chain transitions, treats all countries on equal democratic grounds while the contribution of activity sectors is proportional to their exchange monetary volume. The Google matrix analysis allows to obtain reliable ranking of countries and activity sectors and to determine the sensitivity of CheiRank-PageRank commercial balance of countries in respect to price variations and labor cost in various countries. We demonstrate that the developed approach takes into account multiplicity of network links with economy interactions between countries and activity sectors thus being more efficient compared to the usual export-import analysis. The spectrum and eigenstates of G are also analyzed being related to specific activity communities of countries.

  17. Polyphenol extract from Phellinus igniarius protects against acrolein toxicity in vitro and provides protection in a mouse stroke model.

    Suabjakyong, Papawee; Saiki, Ryotaro; Van Griensven, Leo J L D; Higashi, Kyohei; Nishimura, Kazuhiro; Igarashi, Kazuei; Toida, Toshihiko

    2015-01-01

    The basidiomycetous mushroom Phellinus igniarius (L.) Quel. has been used as traditional medicine in various Asian countries for many years. Although many reports exist on its anti-oxidative and anti-inflammatory activities and therapeutic effects against various diseases, our current knowledge of its effect on stroke is very limited. Stroke is a neurodegenerative disorder in which oxidative stress is a key hallmark. Following the 2005 discovery by Igarashi's group that acrolein produced from polyamines in vivo is a major cause of cell damage by oxidative stress, we now describe the effects of anti-oxidative extracts from P. igniarius on symptoms of experimentally induced stroke in mice. The toxicity of acrolein was compared with that of hydrogen peroxide in a mouse mammary carcinoma cell line (FM3A). We found that the complete inhibition of FM3A cell growth by 5 μM acrolein could be prevented by crude ethanol extract of P. igniarius at 0.5 μg/ml. Seven polyphenol compounds named 3,4-dihydroxybenzaldehyde, 4-(3,4-dihydroxyphenyl-3-buten-2one, inonoblin C, phelligridin D, inoscavin C, phelligridin C and interfungin B were identified from this ethanolic extract by LCMS and 1H NMR. Polyphenol-containing extracts of P. igniarius were then used to prevent acrolein toxicity in a mouse neuroblastoma (Neuro-2a) cell line. The results suggested that Neuro-2a cells were protected from acrolein toxicity at 2 and 5 μM by this polyphenol extract at 0.5 and 2 μg/ml, respectively. Furthermore, in mice with experimentally induced stroke, intraperitoneal treatment with P. igniarius polyphenol extract at 20 μg/kg caused a reduction of the infarction volume by 62.2% compared to untreated mice. These observations suggest that the polyphenol extract of P. igniarius could serve to prevent ischemic stroke.

  18. Synthetic tools to illuminate matrix metalloproteinase and proteasome activities

    Geurink, Paulus Petrus

    2010-01-01

    This thesis describes the design, synthesis and application of chemical tools for the activity-based protein profiling of proteases, with the main focus on matrix metalloproteinases (MMPs) and the proteasome. The use of photoaffinity labeling is described and the thesis starts with an extensive outl

  19. Experimental Investigation on Active Cooling for Ceramic Matrix Composite

    PENG Li-na; HE Guo-qiang; LIU Pei-jin

    2009-01-01

    Compared with conventional materials, the active cooling ceramic matrix composite used in ramjet or scramjet makes their structures lighter in mass and better in performance. In this paper, an active and a passive cooling refractory composite specimens are designed and tested with an experimental facility composed of multilayer smale scale cooling penel which consists of a water cooling system and a ceramic matrix composite specimen, and a gas generator used for providing lower and higher transfer rate gases to simulate the temperatures in combustion chamber of ramjst. The active cooling specimen can continuously suffer high surface temperature of 2 000K for 30s and that of 3 000 K for 9.3 s, respectively. The experiment results show that the active cooling composite structure is available for high-temperature condition in ramjet.

  20. Acrolein impairs the cholesterol transport functions of high density lipoproteins.

    Chadwick, Alexandra C; Holme, Rebecca L; Chen, Yiliang; Thomas, Michael J; Sorci-Thomas, Mary G; Silverstein, Roy L; Pritchard, Kirkwood A; Sahoo, Daisy

    2015-01-01

    High density lipoproteins (HDL) are considered athero-protective, primarily due to their role in reverse cholesterol transport, where they transport cholesterol from peripheral tissues to the liver for excretion. The current study was designed to determine the impact of HDL modification by acrolein, a highly reactive aldehyde found in high abundance in cigarette smoke, on the cholesterol transport functions of HDL. HDL was chemically-modified with acrolein and immunoblot and mass spectrometry analyses confirmed apolipoprotein crosslinking, as well as acrolein adducts on apolipoproteins A-I and A-II. The ability of acrolein-modified HDL (acro-HDL) to serve as an acceptor of free cholesterol (FC) from COS-7 cells transiently expressing SR-BI was significantly decreased. Further, in contrast to native HDL, acro-HDL promotes higher neutral lipid accumulation in murine macrophages as judged by Oil Red O staining. The ability of acro-HDL to mediate efficient selective uptake of HDL-cholesteryl esters (CE) into SR-BI-expressing cells was reduced compared to native HDL. Together, the findings from our studies suggest that acrolein modification of HDL produces a dysfunctional particle that may ultimately promote atherogenesis by impairing functions that are critical in the reverse cholesterol transport pathway.

  1. Vocal fold ion transport and mucin expression following acrolein exposure.

    Levendoski, Elizabeth Erickson; Sivasankar, M Preeti

    2014-05-01

    The vocal fold epithelium is exposed to inhaled particulates including pollutants during breathing in everyday environments. Yet, our understanding of the effects of pollutants on vocal fold epithelial function is extremely limited. The objective of this study was to investigate the effect of the pollutant acrolein on two vocal fold epithelial mechanisms: ion transport and mucin (MUC) synthesis. These mechanisms were chosen as each plays a critical role in vocal defense and in maintaining surface hydration which is necessary for optimal voice production. Healthy, native porcine vocal folds (N = 85) were excised and exposed to an acrolein or sham challenge. A 60-min acrolein, but not sham challenge significantly reduced ion transport and inhibited cyclic adenosine monophosphate-dependent, increases in ion transport. Decreases in ion transport were associated with reduced sodium absorption. Within the same timeline, no significant acrolein-induced changes in MUC gene or protein expression were observed. These results improve our understanding of the effects of acrolein on key vocal fold epithelial functions and inform the development of future investigations that seek to elucidate the impact of a wide range of pollutant exposures on vocal fold health.

  2. Ramiprilate inhibits functional matrix metalloproteinase activity in Crohn's disease fistulas

    Efsen, Eva; Saermark, Torben; Hansen, Alastair

    2011-01-01

    Increased expression of matrix metalloproteinase (MMP)-2, -3 and -9 has been demonstrated in Crohn's disease fistulas, but it is unknown whether these enzymes are biologically active and represent a therapeutic target. Therefore, we investigated the proteolytic activity of MMPs in fistula tissue...... from six controls were also included. Total functional MMP activity was measured by a high-pressure liquid chromatography (HPLC)-based, fluorogenic MMP-substrate cleavage assay, and the specific activity of MMP-2, -3 and -9 by the MMP Biotrak Activity Assay. The MMP inhibitors comprised ethylene...... activity by 72%, which is comparable to the effect of GM6001 (87%). Moreover, MMP-9 activity was completely blunted by ramiprilate. Doxycycline had no effect on MMP activity. Increased functional MMP activity, notably MMP-3 and -9, is present in Crohn's fistulas and may be inhibited by ramiprilate...

  3. Determination of Urine 3-HPMA, a Stable Acrolein Metabolite in a Rat Model of Spinal Cord Injury

    Zheng, Lingxing; Park, Jonghyuck; Walls, Michael; Tully, Melissa; Jannasch, Amber; Cooper, Bruce; Shi, Riyi

    2013-01-01

    Acrolein has been suggested to be involved in a variety of pathological conditions. The monitoring of acrolein is of significant importance in delineating the pathogenesis of various diseases. Aimed at overcoming the reactivity and volatility of acrolein, we describe a specific and stable metabolite of acrolein in urine, N-acetyl-S-3-hydroxypropylcysteine (3-HPMA), as a potential surrogate marker for acrolein quantification. Using the LC/MS/MS method, we demonstrated that 3-HPMA was significa...

  4. Matricryptins and matrikines: biologically active fragments of the extracellular matrix.

    Ricard-Blum, Sylvie; Salza, Romain

    2014-07-01

    Numerous extracellular proteins and glycosaminoglycans (GAGs) undergo limited enzymatic cleavage resulting in the release of fragments exerting biological activities, which are usually different from those of the full-length molecules. In this review, we define matrikines and matricryptins, which are bioactive fragments released from the extracellular matrix proteins, proteoglycans and GAGs and report their major biological activities. These fragments regulate a number of physiopathological processes including angiogenesis, cancer, fibrosis, inflammation, neurodegenerative diseases and wound healing. The challenges to translate these fragments from molecules biologically active in vitro and in experimental models to potential drugs are discussed in the last part of the review.

  5. Extracellular Matrix Stiffness Regulates Osteogenic Differentiation through MAPK Activation.

    Hwang, Jun-Ha; Byun, Mi Ran; Kim, A Rum; Kim, Kyung Min; Cho, Hang Jun; Lee, Yo Han; Kim, Juwon; Jeong, Mi Gyeong; Hwang, Eun Sook; Hong, Jeong-Ho

    2015-01-01

    Mesenchymal stem cell (MSC) differentiation is regulated by the extracellular matrix (ECM) through activation of intracellular signaling mediators. The stiffness of the ECM was shown to be an important regulatory factor for MSC differentiation, and transcriptional coactivator with PDZ-binding motif (TAZ) was identified as an effector protein for MSC differentiation. However, the detailed underlying mechanism regarding the role of ECM stiffness and TAZ in MSC differentiation is not yet fully understood. In this report, we showed that ECM stiffness regulates MSC fate through ERK or JNK activation. Specifically, a stiff hydrogel matrix stimulates osteogenic differentiation concomitant with increased nuclear localization of TAZ, but inhibits adipogenic differentiation. ERK and JNK activity was significantly increased in cells cultured on a stiff hydrogel. TAZ activation was induced by ERK or JNK activation on a stiff hydrogel because exposure to an ERK or JNK inhibitor significantly decreased the nuclear localization of TAZ, indicating that ECM stiffness-induced ERK or JNK activation is important for TAZ-driven osteogenic differentiation. Taken together, these results suggest that ECM stiffness regulates MSC differentiation through ERK or JNK activation.

  6. Extracellular Matrix Stiffness Regulates Osteogenic Differentiation through MAPK Activation.

    Jun-Ha Hwang

    Full Text Available Mesenchymal stem cell (MSC differentiation is regulated by the extracellular matrix (ECM through activation of intracellular signaling mediators. The stiffness of the ECM was shown to be an important regulatory factor for MSC differentiation, and transcriptional coactivator with PDZ-binding motif (TAZ was identified as an effector protein for MSC differentiation. However, the detailed underlying mechanism regarding the role of ECM stiffness and TAZ in MSC differentiation is not yet fully understood. In this report, we showed that ECM stiffness regulates MSC fate through ERK or JNK activation. Specifically, a stiff hydrogel matrix stimulates osteogenic differentiation concomitant with increased nuclear localization of TAZ, but inhibits adipogenic differentiation. ERK and JNK activity was significantly increased in cells cultured on a stiff hydrogel. TAZ activation was induced by ERK or JNK activation on a stiff hydrogel because exposure to an ERK or JNK inhibitor significantly decreased the nuclear localization of TAZ, indicating that ECM stiffness-induced ERK or JNK activation is important for TAZ-driven osteogenic differentiation. Taken together, these results suggest that ECM stiffness regulates MSC differentiation through ERK or JNK activation.

  7. Platelet activation by extracellular matrix proteins in haemostasis and thrombosis.

    Watson, Steve P

    2009-01-01

    The prevention of excessive blood loss to avoid fatal haemorrhage is a pivotal process for all organisms possessing a circulatory system. Increased circulating blood volume and pressure, as required in larger animals, make this process all the more important and challenging. It is essential to have a powerful and rapid system to detect damage and generate an effective seal, and which is also exquisitely regulated to prevent unwanted, excessive or systemic activation so as to avoid blockage of vessels. Thus, a highly specialised and efficient haemostatic system has evolved that consists of cellular (platelets) and protein (coagulation factors) components. Importantly, this is able to support haemostasis in both the low shear environment of the venous system and the high shear environment of the arterial system. Endothelial cells, lining the entire circulation system, play a crucial role in the delicate balance between activation and inhibition of the haemostatic system. An intact and healthy endothelium supports blood flow by preventing attachment of cells and proteins which is required for initiation of coagulation and platelet activation. Endothelial cells produce and release the two powerful soluble inhibitors of platelet activation, nitric oxide and prostacyclin, and express high levels of CD39 which rapidly metabolises the major platelet feedback agonist, ADP. This antithrombotic environment however can rapidly change following activation or removal of endothelial cells through injury or rupture of atherosclerotic plaques. Loss of endothelial cells exposes the subendothelial extracellular matrix which creates strong signals for activation of the haemostatic system including powerful platelet adhesion and activation. Quantitative and qualitative changes in the composition of the subendothelial extracellular matrix influence these prothrombotic characteristics with life threatening thrombotic and bleeding complications, as illustrated by formation of

  8. Ramiprilate inhibits functional matrix metalloproteinase activity in Crohn's disease fistulas

    Efsen, Eva; Saermark, Torben; Hansen, Alastair

    2011-01-01

    Increased expression of matrix metalloproteinase (MMP)-2, -3 and -9 has been demonstrated in Crohn's disease fistulas, but it is unknown whether these enzymes are biologically active and represent a therapeutic target. Therefore, we investigated the proteolytic activity of MMPs in fistula tissue...... and examined the effect of inhibitors, including clinically available drugs that beside their main action also suppress MMPs. Fistula specimens were obtained by surgical excision from 22 patients with Crohn's disease and from 10 patients with fistulas resulting from other causes. Colonic endoscopic biopsies......-diamine-tetraacetic acid (EDTA), the synthetic broad-spectrum inhibitor, GM6001, the angiotensin-converting enzyme (ACE) inhibitor, ramiprilate, and the tetracycline, doxycycline. In Crohn's disease fistulas, about 50% of the total protease activity was attributable to MMP activity. The average total MMP activity...

  9. Acrolein-mediated conduction loss is partially restored by K⁺ channel blockers.

    Yan, Rui; Page, Jessica C; Shi, Riyi

    2016-02-01

    Acrolein-mediated myelin damage is thought to be a critical mechanism leading to conduction failure following neurotrauma and neurodegenerative diseases. The exposure and activation of juxtaparanodal voltage-gated K(+) channels due to myelin damage leads to conduction block, and K(+) channel blockers have long been studied as a means for restoring axonal conduction in spinal cord injury (SCI) and multiple sclerosis (MS). In this study, we have found that 100 μM K(+) channel blockers 4-aminopyridine-3-methanol (4-AP-3-MeOH), and to a lesser degree 4-aminopyridine (4-AP), can significantly restore compound action potential (CAP) conduction in spinal cord tissue following acrolein-mediated myelin damage using a well-established ex vivo SCI model. In addition, 4-AP-3-MeOH can effectively restore CAP conduction in acrolein-damaged axons with a range of concentrations from 0.1 to 100 μM. We have also shown that while both compounds at 100 μM showed no preference of small- and large-caliber axons when restoring CAP conduction, 4-AP-3-MeOH, unlike 4-AP, is able to augment CAP amplitude while causing little change in axonal responsiveness measured in refractory periods and response to repetitive stimuli. In a prior study, we show that 4-AP-3-MeOH was able to functionally rescue mechanically injured axons. In this investigation, we conclude that 4-AP-3-MeOH is an effective K(+) channel blocker in restoring axonal conduction following both primary (physical) and secondary (chemical) insults. These findings also suggest that 4-AP-3-MeOH is a viable alternative of 4-AP for treating myelin damage and improving function following central nervous system trauma and neurodegenerative diseases.

  10. Evaluation of dementia by acrolein, amyloid-β and creatinine.

    Igarashi, Kazuei; Yoshida, Madoka; Waragai, Masaaki; Kashiwagi, Keiko

    2015-10-23

    Plasma, urine and cerebrospinal fluid (CSF) were examined for biochemical markers of dementia. Protein-conjugated acrolein (PC-Acro) and the amyloid-β (Aβ)40/42 ratio in plasma can be used to detect mild cognitive impairment (MCI) and Alzheimer's disease (AD). In plasma, PC-Acro and the Aβ40/42 ratio in MCI and AD were significantly higher relative to non-demented subjects. Furthermore, urine acrolein metabolite, 3-hydroxypropyl mercapturic acid (3-HPMA)/creatinine (Cre) and amino acid-conjugated acrolein (AC-Acro)/Cre in AD were significantly lower than MCI. It was also shown that reduced urine 3-HPMA/Cre correlated with increased plasma Aβ40/42 ratio in dementia. The Aβ40/PC-Acro ratio in CSF, together with Aβ40 and Aβ40/42 ratio, was lower in AD than MCI. Increased plasma PC-Acro and Aβ40/42 ratio and decreased urine 3-HPMA/Cre correlated with cognitive ability (MMSE). These results indicate that the measurements of acrolein derivatives together with Aβ and Cre in biologic fluids is useful to estimate severity of dementia.

  11. Determination of urine 3-HPMA, a stable acrolein metabolite in a rat model of spinal cord injury.

    Zheng, Lingxing; Park, Jonghyuck; Walls, Michael; Tully, Melissa; Jannasch, Amber; Cooper, Bruce; Shi, Riyi

    2013-08-01

    Acrolein has been suggested to be involved in a variety of pathological conditions. The monitoring of acrolein is of significant importance in delineating the pathogenesis of various diseases. Aimed at overcoming the reactivity and volatility of acrolein, we describe a specific and stable metabolite of acrolein in urine, N-acetyl-S-3-hydroxypropylcysteine (3-HPMA), as a potential surrogate marker for acrolein quantification. Using the LC/MS/MS method, we demonstrated that 3-HPMA was significantly elevated in a dose-dependent manner when acrolein was injected into rats IP or directly into the spinal cord, but not when acrolein scavengers were co-incubated with acrolein solution. A nonlinear mathematic relationship is established between acrolein injected directly into the spinal cord and a correlated dose-dependent increase of 3-HPMA, suggesting the increase of 3-HPMA becomes less apparent as the level of injected acrolein increases. The elevation of 3-HPMA was further detected in the rat spinal cord injury, a pathological condition known to be associated with elevated endogenous acrolein. This finding was further validated by concomitant confirmation of increased acrolein-lysine adducts using established dot immunoblotting techniques. The noninvasive nature of measuring 3-HPMA concentrations in urine allows for long-term monitoring of acrolein in the same animal and ultimately in human clinical studies. Due to wide spread involvement of acrolein in human health, the benefits of this study have the potential to enhance human health significantly.

  12. NBHA Reduces Acrolein-lnduced Changes in ARPE-19 Cells: Possible Involvement of TGFβ

    Vidro-Kotchan, Eileen; Yendluri, Bharat Bhushan; Le-Thai, Terrie; Tsin, Andrew

    2015-01-01

    Purpose Acrolein, a toxic, reactive aldehyde formed metabolically and environmentally, has been implicated in the damage to and dysfunction of the retinal pigment epithelium (RPE) that accompanies age-related macular degeneration (AMD). Our purpose was to investigate the potential of acrolein to influence the release of transforming growth factor beta-2 (TGFβ2) and vascular endothelial growth factor (VEGF), to assess the ability of N-benzylhydroxylamine (NBHA) to prevent the effect of acrolein on cytokine release and reduction of viable cells, and to explore the pathway by which acrolein might be causing the increase of VEGF. Materials and Methods Confluent ARPE-19 cells were treated with acrolein and/or NBHA. They were also pretreated with SIS3, a specific inhibitor of SMAD 3, and ZM39923, a JAK3 inhibitor, before being treated with acrolein. Viable cells were counted; ELISA was used to measure the TGFβ2 and/or VEGF in the conditioned media. Results Acrolein was shown to reduce the number of viable ARPE-19 cells and to upregulate the release of the proangiogenic cytokines TGFβ2 and VEGF. Co-treatment with 200 μM NBHA significantly reduced the effects of acrolein on viable cell number and TGFβ2 release. Pretreatment of the cells with SIS3 partially blocked the action of acrolein on decreased viable cell number and VEGF upregulation, suggesting that part of the effects of acrolein are mediated by the increased levels of TGFβ and its signaling. Conclusions Our results suggest that the action of acrolein on the reduction of viability and VEGF increase by ARPE-19 cells is partially mediated by TGFβ2. By reducing the effects of acrolein, NBHA and SIS3 could be potential pharmacological agents in the prevention and progression of acrolein-induced damage to the RPE that relates to AMD. PMID:21309688

  13. Crude glycerol combustion: Particulate, acrolein, and other volatile organic emissions

    Steinmetz, Scott

    2013-01-01

    Crude glycerol is an abundant by-product of biodiesel production. As volumes of this potential waste grow, there is increasing interest in developing new value added uses. One possible use, as a boiler fuel for process heating, offers added advantages of energy integration and fossil fuel substitution. However, challenges to the use of crude glycerol as a boiler fuel include its low energy density, high viscosity, and high autoignition temperature. We have previously shown that a refractory-lined, high swirl burner can overcome challenges related to flame ignition and stability. However, critical issues related to ash behavior and the possible formation of acrolein remained. The work presented here indicates that the presence of dissolved catalysts used during the esterification and transesterification processes results in extremely large amounts of inorganic species in the crude glycerol. For the fuels examined here, the result is a submicron fly ash comprised primarily of sodium carbonates, phosphates, and sulfates. These particles report to a well-developed accumulation mode (0.3-0.7 μm diameter), indicating extensive ash vaporization and particle formation via nucleation, condensation, and coagulation. Particle mass emissions were between 2 and 4 g/m3. These results indicate that glycerol containing soluble catalyst is not suitable as a boiler fuel. Fortunately, process improvements are currently addressing this issue. Additionally, acrolein is of concern due to its toxicity, and is known to be formed from the low temperature thermal decomposition of glycerol. Currently, there is no known reliable method for measuring acrolein in sources. Acrolein and emissions of other volatile organic compounds were characterized through the use of a SUMMA canister-based sampling method followed by GC-MS analysis designed for ambient measurements. Results indicate crude glycerol combustion produces relatively small amounts of acrolein (∼15 ppbv) and other volatile organic

  14. Laminated active matrix organic light-emitting devices

    Liu, Hongyu; Sun, Runguang

    2008-02-01

    Laminated active matrix organic light-emitting device (AMOLED) realizing top emission by using bottom-emitting organic light-emitting diode (OLED) structure was proposed. The multilayer structure of OLED deposited in the conventional sequence is not on the thin film transistor (TFT) backplane but on the OLED plane. The contact between the indium tin oxide (ITO) electrode of TFT backplane and metal cathode of OLED plane is implemented by using transfer electrode. The stringent pixel design for aperture ratio of the bottom-emitting AMOLED, as well as special technology for the top ITO electrode of top-emitting AMOLED, is unnecessary in the laminated AMOLED.

  15. Inhibition by acrolein of light-induced stomatal opening through inhibition of inward-rectifying potassium channels in Arabidopsis thaliana.

    Islam, Md Moshiul; Ye, Wenxiu; Matsushima, Daiki; Khokon, Md Atiqur Rahman; Munemasa, Shintaro; Nakamura, Yoshimasa; Murata, Yoshiyuki

    2015-01-01

    Acrolein is a reactive α,β-unsaturated aldehyde derived from lipid peroxides, which are produced in plants under a variety of stress. We investigated effects of acrolein on light-induced stomatal opening using Arabidopsis thaliana. Acrolein inhibited light-induced stomatal opening in a dose-dependent manner. Acrolein at 100 μM inhibited plasma membrane inward-rectifying potassium (Kin) channels in guard cells. Acrolein at 100 μM inhibited Kin channel KAT1 expressed in a heterologous system using Xenopus leaves oocytes. These results suggest that acrolein inhibits light-induced stomatal opening through inhibition of Kin channels in guard cells.

  16. Acrolein detection: potential theranostic utility in multiple sclerosis and spinal cord injury.

    Tully, Melissa; Zheng, Lingxing; Shi, Riyi

    2014-06-01

    Oxidative stress has been implicated as a major pathological process underlying CNS disease and trauma. More specifically, acrolein, an unsaturated aldehyde, produced by way of lipid peroxidation, has been shown to play a crucial role in initiating and perpetuating detrimental effects associated with multiple sclerosis and spinal cord injury. In light of these findings, quantification of acrolein levels both systemically and locally could allow for the use of acrolein as a biomarker to aid in diagnosis and guide treatment regimens. The three main approaches currently available are acrolein derivatization followed by LC/GC-MS, application of an acrolein antibody and subsequent immunoblotting, and the 3-hydroxypropylmercapturic acid-based method. Of these three strategies, the 3-hydroxypropylmercapturic acid-based method is the least invasive allowing for rapid translation of acrolein detection into a clinical setting.

  17. Development and validation of new analytical method for acrolein in air.

    Yasuhara, A; Dennis, K J; Shibamoto, T

    1989-01-01

    A new method was developed to determine vapor-phase acrolein in air samples. Air containing vapor-phase acrolein was purged into impingers filled with a dichloromethane solution of N-methylhydrazine. The resulting derivative, 1-methyl-2-pyrazoline, was analyzed by gas chromatography using a nitrogen-phosphorous detector (NPD). The detection limit was 8.9 pg 1-methyl-2-pyrazoline, equivalent to 5.9 pg acrolein. The recovery efficiencies of vapor-phase acrolein were 98.0 +/- 2.9% and 100.3 +/- 3.1% for 150 and 15 micrograms, respectively. This method was satisfactorily applied for determination of acrolein formed from various heated fats. The amounts of acrolein formed in a headspace were 109 micrograms/L from lard, 164 micrograms/L from corn oil, 5.1 micrograms/L from cotton seed oil, and 163 micrograms/L from sunflower oil.

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

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

    2012-10-01

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

  19. Kinetics and Mechanism of Protein Tyrosine Phosphatase 1B (PTP1B) Inactivation by Acrolein

    Seiner, Derrick R.; LaButti, Jason N.; Gates, Kent S.

    2007-01-01

    Human cells are exposed to the electrophilic α,β-unsaturated aldehyde acrolein from a variety of sources. Reaction of acrolein with functionally critical protein thiol residues can yield important biological consequences. Protein tyrosine phosphatases (PTPs) are an important class of cysteine-dependent enzymes whose reactivity with acrolein previously has not been well characterized. These enzymes catalyze the dephosphorylation of phosphotyrosine residues on proteins via a phosphocysteine int...

  20. Acrolein-induced oxidative stress in NAD(P)H Oxidase Subunit gp91phox knock-out mice and its modulation of NFκB and CD36.

    Yousefipour, Zivar; Zhang, Chelsea; Monfareed, Mahdieh; Walker, James; Newaz, Mohammad

    2013-11-01

    An essential component of NAD(P)H, gp91phox, maintains the functionality of the enzyme in producing oxygen radicals. NAD(P)H oxidase plays an important role in oxidative stress but its precise contribution in acrolein-induced toxicity was not explored. We examined the involvement of NAD(P)H oxidase and other oxidant system in acrolein toxicity using gp91phox knockout mice. Male gp91phox knockout (KO) mice (20-25 gm) or wild type (WT) controls were treated with acrolein (0.5 μg/kg; 1 week). Animals were sacrificed and the liver was used to determine biochemical parameters. Knockout mice generated low (1.43 ±.02 pg/μg protein) free radicals as evident in 8-Isoprostane compared with the WT mice (2.19 ± 0.1). Acrolein increased 8-Isoprostane in WT (PAcrolein increased XO in KO mice, but significantly increased it only in WT. Cycloxygenase (COX) activity was not different between WT and KO mice, although acroelin increased COX in WT. Knockout mice exhibited a significantly low (2.1 ± 0.2 μmol/mg protein) total antioxidant status (TAS) compared with the WT (3.5 ± 0.3). Acrolein reduced TAS in both WT and KO mice equally. Baseline NFκB was significantly higher in KO mice, although acrolein increased NFκB in WT but not in KO. CD36 was higher (pacrolein increased (pacrolein-induced oxidative stress. We also suggests that in the absence of NAD(P)H oxidase XO plays a definitive role together with reduced antioxidant ability to compound the toxic effects of acrolein. We propose that in absence of NAD(P)H oxidase a different signaling process may involve that utilizes CD36 besides NFκB.

  1. Dehydration of Glycerin to Acrolein Over Heteropolyacid Nano-Catalysts Supported on Silica-Alumina.

    Kang, Tae Hun; Choi, Jung Ho; Choi, Jun Seon; Song, In Kyu

    2015-10-01

    A series of H3PW12O40 nano-catalysts supported on silica-alumina (XH3PW12O40/SA (X = 10, 15, 20, 25, and 30)) with different H3PW12O40 content (X, wt%) were prepared, and they were applied to the dehydration of glycerin to acrolein. The effect of H3PW12O40 content on the physicochemical properties and catalytic activities of XH3PW12O40/SA nano-catalysts was investigated. Surface area and pore volume of XH3PW12O40/SA catalysts decreased with increasing H3PW12O40 content. Formation of H3PW12O40 aggregates was observed in the catalysts with high H3PW12O40 loading. Brønsted acidity of the catalysts showed a volcano-shaped trend with respect to H3PW12O40 content. It was revealed that yield for acrolein increased with increasing Brønsted acidity of XH3PW12O40/SA catalysts. Brønsted acidity of XH3PW12O40/SA catalysts served as a crucial factor determining the catalytic performance in the dehydration of glycerin. Among the catalysts tested, 25H3PW12O40/SA catalyst with the largest Brønsted acidity showed the best catalytic performance.

  2. Neuroprotective role of hydralazine in rat spinal cord injury-attenuation of acrolein-mediated damage.

    Park, Jonghyuck; Zheng, Lingxing; Marquis, Andrew; Walls, Michael; Duerstock, Brad; Pond, Amber; Vega-Alvarez, Sasha; Wang, He; Ouyang, Zheng; Shi, Riyi

    2014-04-01

    Acrolein, an α,β-unsaturated aldehyde and a reactive product of lipid peroxidation, has been suggested as a key factor in neural post-traumatic secondary injury in spinal cord injury (SCI), mainly based on in vitro and ex vivo evidence. Here, we demonstrate an increase of acrolein up to 300%; the elevation lasted at least 2 weeks in a rat SCI model. More importantly, hydralazine, a known acrolein scavenger can provide neuroprotection when applied systemically. Besides effectively reducing acrolein, hydralazine treatment also resulted in significant amelioration of tissue damage, motor deficits, and neuropathic pain. This effect was further supported by demonstrating the ability of hydralazine to reach spinal cord tissue at a therapeutic level following intraperitoneal application. This suggests that hydralazine is an effective neuroprotective agent not only in vitro, but in a live animal model of SCI as well. Finally, the role of acrolein in SCI was further validated by the fact that acrolein injection into the spinal cord caused significant SCI-like tissue damage and motor deficits. Taken together, available evidence strongly suggests a critical causal role of acrolein in the pathogenesis of spinal cord trauma. Since acrolein has been linked to a variety of illness and conditions, we believe that acrolein-scavenging measures have the potential to be expanded significantly ensuring a broad impact on human health.

  3. Activity-based enrichment of matrix metalloproteinases using reversible inhibitors as affinity ligands

    Freije, J.R.; Bischoff, Rainer

    2003-01-01

    Matrix metalloproteinases (MMPs) are zinc dependent metalloproteases characterized by the ability to cleave extracellular matrix and many other extracellular proteins. MMP activity is tightly regulated but disturbances in this regulation can contribute to various disease processes characterized by a

  4. A single exposure to acrolein causes arrhythmogenesis, cardiac electrical dysfunction and decreased heart rate variability in hypertensive rats

    Epidemiological studies demonstrate an association between cardiovascular morbidity, arrhythmias, and exposure to air toxicants such as acrolein. We hypothesized that a single exposure to acrolein would increase arrhythmias and cause changes in the electrocardiogram (ECG) of hype...

  5. IRIS TOXICOLOGICAL REVIEW AND SUMMARY DOCUMENTS FOR ACROLEIN (EXTERNAL REVIEW DRAFT)

    Acrolein is a colorless to yellowish flammable liquid with a disagreeable, choking odor. The principal use of acrolein is as an intermediate in the synthesis of acrylic acid, which is used to make acrylates, and of DL-methionine, an essential amino acid used as an animal feed su...

  6. UTILIZING THE PAKS METHOD FOR MEASURING ACROLEIN AND OTHER ALDEHYDES IN DEARS

    Acrolein is a hazardous air pollutant of high priority due to its high irritation potency and other potential adverse health effects. However, a reliable method is currently unavailable for measuring airborne acrolein at typical environmental levels. In the Detroit Exposure and A...

  7. Novel biological activity of ameloblastin in enamel matrix derivative

    Sachiko KURAMITSU-FUJIMOTO

    2015-02-01

    Full Text Available Objective Enamel matrix derivative (EMD is used clinically to promote periodontal tissue regeneration. However, the effects of EMD on gingival epithelial cells during regeneration of periodontal tissues are unclear. In this in vitro study, we purified ameloblastin from EMD and investigated its biological effects on epithelial cells. Material and Methods Bioactive fractions were purified from EMD by reversed-phase high-performance liquid chromatography using hydrophobic support with a C18 column. The mouse gingival epithelial cell line GE-1 and human oral squamous cell carcinoma line SCC-25 were treated with purified EMD fraction, and cell survival was assessed with a WST-1 assay. To identify the proteins in bioactive fractions of EMD, we used proteome analysis with two-dimensional gel electrophoresis followed by identification with liquid chromatography-tandem mass spectrometry (LC-MS/MS analysis. Results Purified fractions from EMD suppressed proliferation of GE-1 and SCC-25. LC-MS/MS revealed that ameloblastin in EMD is the component responsible for inhibiting epithelial cell proliferation. The inhibitory effect of ameloblastin on the proliferation of GE-1 and SCC-25 was confirmed using recombinant protein. Conclusion The inhibitory effects of EMD on epithelial cell proliferation are caused by the biological activities of ameloblastin, which suggests that ameloblastin is involved in regulating epithelial downgrowth in periodontal tissues.

  8. Monolithic Active Pixel Matrix with Binary Counters (MAMBO) ASIC

    Khalid, Farah F.; Deptuch, Grzegorz; Shenai, Alpana; Yarema, Raymond J.; /Fermilab

    2010-11-01

    Monolithic Active Matrix with Binary Counters (MAMBO) is a counting ASIC designed for detecting and measuring low energy X-rays from 6-12 keV. Each pixel contains analogue functionality implemented with a charge preamplifier, CR-RC{sup 2} shaper and a baseline restorer. It also contains a window comparator which can be trimmed by 4 bit DACs to remove systematic offsets. The hits are registered by a 12 bit ripple counter which is reconfigured as a shift register to serially output the data from the entire ASIC. Each pixel can be tested individually. Two diverse approaches have been used to prevent coupling between the detector and electronics in MAMBO III and MAMBO IV. MAMBO III is a 3D ASIC, the bottom ASIC consists of diodes which are connected to the top ASIC using {mu}-bump bonds. The detector is decoupled from the electronics by physically separating them on two tiers and using several metal layers as a shield. MAMBO IV is a monolithic structure which uses a nested well approach to isolate the detector from the electronics. The ASICs are being fabricated using the SOI 0.2 {micro}m OKI process, MAMBO III is 3D bonded at T-Micro and MAMBO IV nested well structure was developed in collaboration between OKI and Fermilab.

  9. 添加剂有机胺对丙烯选择性氧化制丙烯醛催化剂活性的影响%Effects of additive organic amine on the activity of the catalyst for selective oxidation of propene to acrolein

    郑育元; 吴粮华; 汪国军; 缪晓春; 杨斌

    2013-01-01

    The catalysts for selective oxidation of propene to acrolein were prepared by coprecipitation method.The effects of organic amine addition on the performance of the catalysts for propene selective oxidation to acrolein were investigated.The results showed that with the addition of organic amine,the activity of the catalyst was stable whereas the selectivity was enhanced greatly.The catalysts were characterized by means of scanning electron microscope,X-ray diffraction,pyridine adsorbed infrared spectrum and N2-physisorption techniques.The results showed that though the surface area of the catalyst decreased slightly,the amount of L-acid sites on the catalyst surface increased obviously,which had little influence on the catalyst activity.On the other hand,the decrease of MoO3 crystallinity and the increase of (Co0.7 Fe0.3)(MoO4) crystallinity were positive factors to the selectivity of the catalyst.Meanwhile,the decreased pore volume and the increased ratio of large pores of the catalyst were attributed to the faster removal of the products from the catalyst surface and the inhibition of the formation of deep oxides.%采用共沉淀法制备丙烯选择性氧化制丙烯醛催化剂,考察有机胺的加入对丙烯选择性氧化制丙烯醛催化性能的影响.结果表明,添加有机胺后,催化剂活性在维持不变的情况下,选择性显著提高.采用扫描电镜、X射线衍射、吡啶吸附红外光谱和N2物理吸附表征等对不同催化剂的物化性能进行表征.结果发现,添加有机胺后,催化剂比表面积略有下降,但催化剂表面的L酸性中心强度明显增加,对催化剂活性影响不大;另一方面,MoO3结晶度的下降与(Co0.7 Fe0.3)(MoO4)结晶度的上升对催化剂选择性均是积极因素.同时孔容的减小以及大孔比例增加更有利于主反应产物的脱附,能抑制深度氧化物的生成.

  10. Acrolein and chloroacetaldehyde: an examination of the cell and cell-free biomarkers of toxicity.

    MacAllister, Stephanie L; Martin-Brisac, Nicolas; Lau, Vincent; Yang, Kai; O'Brien, Peter J

    2013-02-25

    Cyclophosphamide and ifosfamide are two commonly used DNA-alkylating agents in cancer chemotherapy that undergo biotransformation to several toxic and non-toxic metabolites, including acrolein and chloroacetaldehyde (CAA). Acrolein and CAA toxicities occur by several different mechanisms, including ROS formation and protein damage (oxidation), however, these pathways of toxicity and protecting agents used to prevent them have yet to be compared and ranked in a single study. This research focused on the molecular targets of acrolein and CAA toxicities and strategies to decrease toxicities. Hepatocyte viability (cytotoxicity) was assessed using Trypan blue uptake; formation of reactive oxygen species (ROS) and endogenous H2O2 were also assessed in the hepatocyte model. In cell-free models (bovine serum albumin and hepatic microsomes), protein carbonylation was the measurement of toxicity. The present study demonstrated that acrolein was a more potent toxin than CAA for freshly isolated rat hepatocytes, bovine serum albumin and rat hepatic microsomes. Acrolein protein carbonylation was dependent on its concentration; as acrolein concentration increased, protein carbonylation increased in a linear trend, whereas, CAA deviated from the trend and did not cause protein carbonylation at lower concentrations (acrolein-treated hepatocytes. The overall effectiveness of protecting agents to prevent or suppress acrolein or CAA toxicities in cell and cell-free models were ranked in order of most effective to least effective: reducing agents (sodium borohydride, sodium bisulfite)>thiol-containing compounds (N-acetylcysteine, cysteine, glutathione, 2-mercaptoethane sulfonate [MESNA], penicillamine)>carbonyl scavengers/amines (aminoguanidine, hydralazine, hydroxylamine)>antioxidants/ROS scavengers (ascorbic acid, Trolox; only utilized in hepatocyte system). An understanding of acrolein and CAA toxicities and the ability of protecting agents to protect against toxicities may help to

  11. Collagenolytic Matrix Metalloproteinase Activities toward Peptomeric Triple-Helical Substrates.

    Stawikowski, Maciej J; Stawikowska, Roma; Fields, Gregg B

    2015-05-19

    Although collagenolytic matrix metalloproteinases (MMPs) possess common domain organizations, there are subtle differences in their processing of collagenous triple-helical substrates. In this study, we have incorporated peptoid residues into collagen model triple-helical peptides and examined MMP activities toward these peptomeric chimeras. Several different peptoid residues were incorporated into triple-helical substrates at subsites P3, P1, P1', and P10' individually or in combination, and the effects of the peptoid residues were evaluated on the activities of full-length MMP-1, MMP-8, MMP-13, and MMP-14/MT1-MMP. Most peptomers showed little discrimination between MMPs. However, a peptomer containing N-methyl Gly (sarcosine) in the P1' subsite and N-isobutyl Gly (NLeu) in the P10' subsite was hydrolyzed efficiently only by MMP-13 [nomenclature relative to the α1(I)772-786 sequence]. Cleavage site analysis showed hydrolysis at the Gly-Gln bond, indicating a shifted binding of the triple helix compared to the parent sequence. Favorable hydrolysis by MMP-13 was not due to sequence specificity or instability of the substrate triple helix but rather was based on the specific interactions of the P7' peptoid residue with the MMP-13 hemopexin-like domain. A fluorescence resonance energy transfer triple-helical peptomer was constructed and found to be readily processed by MMP-13, not cleaved by MMP-1 and MMP-8, and weakly hydrolyzed by MT1-MMP. The influence of the triple-helical structure containing peptoid residues on the interaction between MMP subsites and individual substrate residues may provide additional information about the mechanism of collagenolysis, the understanding of collagen specificity, and the design of selective MMP probes.

  12. Vapor Phase Dehydration of Glycerol to Acrolein Over SBA-15 Supported Vanadium Substituted Phosphomolybdic Acid Catalyst.

    Viswanadham, Balaga; Srikanth, Amirineni; Kumar, Vanama Pavan; Chary, Komandur V R

    2015-07-01

    Vapor phase dehydration of glycerol to acrolein was investigated over heteropolyacid (HPA) catalysts containing vanadium substituted phosphomolybdic acid (H4PMo11VO40) supported on mesoporous SBA-15. A series of HPA catalysts with HPA loadings varying from 10-50 wt% were prepared by impregnation method on SBA-15 support. The catalysts were characterized by X-ray diffraction, Raman spectroscopy, Fourier Transform infrared spectroscopy, temperature-programmed desorption of NH3, pyridine adsorbed FT-IR spectroscopy, scanning electron microscopy, pore size distribution and specific surface area measurements. The nature of acidic sites was examined by pyridine adsorbed FT-IR spectroscopy. XRD results suggest that the active phase containing HPA was highly dispersed at lower loadings on the support. FT-IR and Raman spectra results confirm that the presence of primary Keggin ion structure of HPA on the support and it was not affected during the preparation of catalysts. Pore size distribution results reveal that all the samples show unimodel pore size distribution with well depicted mesoporous structure. NH3-TPD results suggest that the acidity of catalysts increased with increase of HPA loading. The findings of acidity measurements by FT-IR spectra of pyridine adsorption reveals that the catalysts consist both the Brønsted and Lewis acidic sites and the amount of Brønsted acidic sites are increasing with HPA loading. SBA-15 supported vanadium substituted phosphomolybdic acid catalysts are found to be highly active during the dehydration reaction and exhibited 100% conversion of glycerol (10 wt% of glycerol) and the acrolein selectivity was appreciably changed with HPA active phase loading. The catalytic functionalities during glycerol dehydration are well correlated with surface acidity of the catalysts.

  13. Acrolein Microspheres Are Bonded To Large-Area Substrates

    Rembaum, Alan; Yen, Richard C. K.

    1988-01-01

    Reactive cross-linked microspheres produced under influence of ionizing radiation in aqueous solutions of unsaturated aldehydes, such as acrolein, with sodium dodecyl sulfate. Diameters of spheres depend on concentrations of ingredients. If polystyrene, polymethylmethacrylate, or polypropylene object immersed in solution during irradiation, microspheres become attached to surface. Resulting modified surface has grainy coating with reactivity similar to free microspheres. Aldehyde-substituted-functional microspheres react under mild conditions with number of organic reagents and with most proteins. Microsphere-coated macrospheres or films used to immobilize high concentrations of proteins, enzymes, hormones, viruses, cells, and large number of organic compounds. Applications include separation techniques, clinical diagnostic tests, catalytic processes, and battery separators.

  14. Scavenging of Toxic Acrolein by Resveratrol and Hesperetin and Identification of Adducts.

    Wang, Weixin; Qi, Yajing; Rocca, James R; Sarnoski, Paul J; Jia, Aiqun; Gu, Liwei

    2015-11-04

    The objective of this study was to investigate the ability of resveratrol and hesperetin to scavenge acrolein at pH 7.4 and 37 °C. About 6.4 or 5.2% of acrolein remained after reaction with resveratrol or hesperetin for 12 h at equimolar concentrations. An acrolein-resveratrol adduct and two acrolein-hesperetin adducts were isolated. Their structures were elucidated using mass and NMR spectroscopy. Acrolein reacted with resveratrol at the C-2 and C-3 positions through nucleophilic addition and formed an additional heterocyclic ring. Two similar monoacrolein-conjugated adducts were identified for hesperetin. Spectroscopic data suggested each acrolein-hesperetin adduct was a mixture of four stereoisomers due to the existence of two chiral carbon atoms. Yield of adducts was low at pH 5.4 but increased at pH 7.4 and 8.4. Higher pH also promoted the formation of diacrolein adducts. Results suggest that resveratrol and hesperetin exert health benefits in part through neutralizing toxic acrolein in vivo.

  15. 1,N(2)-propanodeoxyguanosine adduct formation in aortic DNA following inhalation of acrolein.

    Penn, A; Nath, R; Pan, J; Chen, L; Widmer, K; Henk, W; Chung, F L

    2001-03-01

    Recent reports indicate that many of the cytotoxic and health-threatening components of environmental tobacco smoke (ETS) reside in the vapor phase of the smoke. We have reported previously that inhalation of 1,3-butadiene, a prominent vapor phase component of ETS, accelerates arteriosclerotic plaque development in cockerels. In this study we asked whether inhaled acrolein, a reactive aldehyde that is also a prominent vapor-phase component of ETS, damages artery-wall DNA and accelerates plaque development. Cockerels inhaled 0, 1, or 10 ppm acrolein mixed with HEPA-filtered air for 6 hr. Half were killed immediately (day 1 group) for detection of the stable, premutagenic 1,N(2)-propanodeoxyguanosine acrolein adduct (AdG3) in aortic DNA via a (32)P-postlabeling/HPLC method, and half were killed after 10 days (day 10 group) for indirect assessment of adduct repair. In the day 1 group, acrolein-DNA adducts were 5 times higher in the 1 and 10 ppm groups than in HEPA-filtered air controls. However, in the day 10 group, adduct levels in the 1 and 10 ppm acrolein groups were reduced to the control adduct level. For the plaque studies, cockerels inhaled 1 ppm acrolein (6 hr/day, 8 weeks), mixed with the same HEPA-filtered air inhaled by controls. Plaque development was measured blind by computerized morphometry. Unlike butadiene inhalation, acrolein inhalation did not accelerate plaque development. Thus, even though repeated exposure to acrolein alone has no effect on plaque size under the exposure conditions described here, a single, brief inhalation exposure to acrolein elicits repairable DNA damage to the artery wall. These results suggest that frequent exposure to ETS may lead to persistent artery-wall DNA damage and thus provide sites on which other ETS plaque accelerants can act.

  16. CONSTRUCTION OF POLYNOMIAL MATRIX USING BLOCK COEFFICIENT MATRIX REPRESENTATION AUTO-REGRESSIVE MOVING AVERAGE MODEL FOR ACTIVELY CONTROLLED STRUCTURES

    LI Chunxiang; ZHOU Dai

    2004-01-01

    The polynomial matrix using the block coefficient matrix representation auto-regressive moving average (referred to as the PM-ARMA) model is constructed in this paper for actively controlled multi-degree-of-freedom (MDOF) structures with time-delay through equivalently transforming the preliminary state space realization into the new state space realization. The PM-ARMA model is a more general formulation with respect to the polynomial using the coefficient representation auto-regressive moving average (ARMA) model due to its capability to cope with actively controlled structures with any given structural degrees of freedom and any chosen number of sensors and actuators. (The sensors and actuators are required to maintain the identical number.) under any dimensional stationary stochastic excitation.

  17. Active Matrix Organic Light Emitting Diode (AMOLED) Environmental Test Report

    Salazar, George A.

    2013-01-01

    This report focuses on the limited environmental testing of the AMOLED display performed as an engineering evaluation by The NASA Johnson Space Center (JSC)-specifically. EMI. Thermal Vac, and radiation tests. The AMOLED display is an active-matrix Organic Light Emitting Diode (OLED) technology. The testing provided an initial understanding of the technology and its suitability for space applications. Relative to light emitting diode (LED) displays or liquid crystal displays (LCDs), AMOLED displays provide a superior viewing experience even though they are much lighter and smaller, produce higher contrast ratio and richer colors, and require less power to operate than LCDs. However, AMOLED technology has not been demonstrated in a space environment. Therefore, some risks with the technology must be addressed before they can be seriously considered for human spaceflight. The environmental tests provided preliminary performance data on the ability of the display technology to handle some of the simulated induced space/spacecraft environments that an AMOLED display will see during a spacecraft certification test program. This engineering evaluation is part of a Space Act Agreement (SM) between The NASA/JSC and Honeywell International (HI) as a collaborative effort to evaluate the potential use of AMOLED technology for future human spaceflight missions- both government-led and commercial. Under this SM, HI is responsible for doing optical performance evaluation, as well as temperature and touch screen studies. The NASA/JSC is responsible for performing environmental testing comprised of EMI, Thermal Vac, and radiation tests. Additionally, as part of the testing, limited optical data was acquired to assess performance as the display was subjected to the induced environments. The NASA will benefit from this engineering evaluation by understanding AMOLED suitability for future use in space as well as becoming a smarter buyer (or developer) of the technology. HI benefits

  18. Curved Ferroelectric Liquid Crystal Matrix Displays Driven by Field-Sequential-Color and Active-Matrix Techniques

    Fujikake, Hideo; Sato, Hiroto; Murashige, Takeshi; Fujisaki, Yoshihide; Kurita, Taiichiro; Furukawa, Tadahiro; Sato, Fumio

    This paper describes a curved field-sequential-color matrix display using fast-response ferroelectric liquid crystal. Black matrix and transparent electrode patterns were formed on a thin plastic substrate by a transfer method from a glass substrate. While a composite film of liquid crystal and micro-polymers of walls and fibers was formed between the flexible substrates by printing, laminating and curing processes of a solution of monomers and liquid crystal, the mechanical stability was enhanced by use of multi-functional monomers to form large display panels. The image pixels of the matrix panel were driven by an active matrix scheme using an external switch transistor array at a frequency of 180 Hz for intermittent three-primary-color backlight illumination. The flexible A4-paper-sized color display with 24 × 16 pixels and 60 Hz field frequency was demonstrated by illuminating it with sequential three-primary-color lights from light-emitting diodes of the backlight. Our display system is useful in various information displays because of its freedom of setting and location.

  19. Theoretical studies of acrolein hydrogenation on Au20 nanoparticle

    Li, Zhe; Chen, Zhao-Xu; He, Xiang; Kang, Guo-Jun

    2010-05-01

    Gold nanoparticles play a key role in catalytic processes. We investigated the kinetics of stepwise hydrogenation of acrolein on Au20 cluster model and compared with that on Au(110) surface. The rate-limiting step barrier of CC reduction is about 0.5 eV higher than that of CO hydrogenation on Au(110) surface. On Au20 nanoparticle, however, the energy barrier of the rate-determining step for CC hydrogenation turns out to be slightly lower than the value for the CO reduction. The selectivity difference on the two substrate models are attributed to different adsorption modes of acrolein: via the CC on Au20, compared to through both CC and CO on Au(110). The preference switch implies that the predicted selectivity of competitive hydrogenation depends on substrate model sensitively, and particles with more low-coordinated Au atoms than flat surfaces are favorable for CC hydrogenation, which is in agreement with experimental result.

  20. Adaptation to acrolein through upregulating the protection by glutathione in human bronchial epithelial cells: the materialization of the hormesis concept.

    Sthijns, Mireille M J P E; Randall, Matthew J; Bast, Aalt; Haenen, Guido R M M

    2014-04-18

    Acrolein is a thiol reactive compound present in cigarette smoke and plays a pivotal role in the deleterious effects of smoking. Acrolein causes toxicity in human bronchial epithelial cells in a dose dependent manner. GSH forms the first line of defense against acrolein-induced toxicity. At high doses of acrolein (⩾10 μM) the capacity of the cellular protection by GSH is overwhelmed and GSH is not able to quench all the acrolein, resulting in cytotoxicity. At a relatively low dose of acrolein (3 μM), no cytotoxicity is observed due to protection by GSH. Moreover we found that exposure to a low dose of acrolein protects cells against the toxic effect of a second higher dose of acrolein. The adaptation to acrolein is induced via Nrf2 mediated gene expression of γ-glutamylcysteine synthetase leading to elevated GSH levels. This upregulation of the protection by GSH demonstrates a hormetic response to acrolein. Hormesis is an adaptive or compensatory response induced by a relatively subtle challenge of homeostasis by a toxic compound. Insight into the mechanism of hormesis is mandatory for a more accurate societal regulation of toxic compounds.

  1. Matrix viscoplasticity and its shielding by active mechanics in microtissue models: experiments and mathematical modeling

    Liu, Alan S.; Wang, Hailong; Copeland, Craig R.; Chen, Christopher S.; Shenoy, Vivek B.; Reich, Daniel H.

    2016-01-01

    The biomechanical behavior of tissues under mechanical stimulation is critically important to physiological function. We report a combined experimental and modeling study of bioengineered 3D smooth muscle microtissues that reveals a previously unappreciated interaction between active cell mechanics and the viscoplastic properties of the extracellular matrix. The microtissues’ response to stretch/unstretch actuations, as probed by microcantilever force sensors, was dominated by cellular actomyosin dynamics. However, cell lysis revealed a viscoplastic response of the underlying model collagen/fibrin matrix. A model coupling Hill-type actomyosin dynamics with a plastic perfectly viscoplastic description of the matrix quantitatively accounts for the microtissue dynamics, including notably the cells’ shielding of the matrix plasticity. Stretch measurements of single cells confirmed the active cell dynamics, and were well described by a single-cell version of our model. These results reveal the need for new focus on matrix plasticity and its interactions with active cell mechanics in describing tissue dynamics. PMID:27671239

  2. Human exposure to acrolein: Time-dependence and individual variation in eye irritation.

    Claeson, Anna-Sara; Lind, Nina

    2016-07-01

    The aim of the study was to examine the time dependence on sensory irritation detection following exposure to threshold levels of acrolein, in humans. The exposures occurred in an exposure chamber and the subjects were breathing fresh air through a mask that covered the nose and mouth. All participants participated in four exposure conditions, of which three consisted of a mixture of acrolein and heptane and one of only heptane. Exposure to acrolein at a concentration half of the TLV-C lead to sensory irritation. The perceived sensory irritation resulted in both increased detectability and sensory irritation after about 6.8min of exposure in 58% of the participants. The study confirm the previously suggested LOAEL of about 0.34mg/m(3) for eye irritation due to acrolein exposure. The sensory irritation was still significant 10min after exposure. These results have implications for risk assessment and limit setting in occupational hygiene.

  3. Characterization and reactivity of 11-molybdo-1-vanadophosphoric acid catalyst supported on zirconia for dehydration of glycerol to acrolein

    Balaga Viswanadham; Amirineni Srikanth; Komandur V R Chary

    2014-03-01

    A series of vanadium-substituted phosphomolybdic acid (HPA) catalysts supported on zirconia were prepared by impregnation method with varying the HPA active phase content from 10 to 50 wt% on the support. The calcined catalysts were characterized by X-ray diffraction, Raman spectroscopy, temperatureprogrammed desorption of NH3, FT-IR spectra of pyridine adsorption and surface area measurements. XRD results suggest that the active phase of heteropolyacid is present in a highly dispersed state at lower loadings and as a crystalline phase at higher HPA loadings and these findings are well-supported by the results of FT-IR and Raman spectra. Calcination of the samples did not affect the Keggin ion structure of HPA. The ammonia TPD results suggest that acidity of the catalysts was found to increase with increase of HPA loading up to 40 wt% and decreases at higher loadings. FT-IR spectra of pyridine adsorption show that the Brønsted acidic sites increase with increase of HPA loadings up to 40 wt% catalyst. However, Lewis acid sites decrease with increase ofHPA loading. Catalytic properties were evaluated during vapour phase dehydration of glycerol to acrolein. The catalyst with 40 wt% HPA has exhibited excellent selectivity towards acrolein formation with complete conversion of glycerol at 225°C under atmospheric pressure. Catalytic performances during dehydration of glycerol are well-correlated with acidity of the catalysts.

  4. Structural Elucidation of a Carnosine-Acrolein Adduct and its Quantification in Human Urine Samples.

    Bispo, Vanderson S; de Arruda Campos, Ivan P; Di Mascio, Paolo; Medeiros, Marisa H G

    2016-01-19

    Aldehydes accumulate in inflammation, during myocardial infarction and have been associated with pain symptoms. One pathway of aldehyde detoxification is the conjugation with carnosine. A 3-methylpyridinium carnosine adduct from the reaction of carnosine and acrolein was characterized using extensive spectroscopic measurements. The adduct with urinary concentrations of 1.82 ± 0.68 nmol/mg of creatinine is one of the most abundant acrolein metabolites in urine and opens promising therapeutic strategies for carnosine.

  5. Analytical Model of Water Flow in Coal with Active Matrix

    Siemek, Jakub; Stopa, Jerzy

    2014-12-01

    This paper presents new analytical model of gas-water flow in coal seams in one dimension with emphasis on interactions between water flowing in cleats and coal matrix. Coal as a flowing system, can be viewed as a solid organic material consisting of two flow subsystems: a microporous matrix and a system of interconnected macropores and fractures. Most of gas is accumulated in the microporous matrix, where the primary flow mechanism is diffusion. Fractures and cleats existing in coal play an important role as a transportation system for macro scale flow of water and gas governed by Darcy's law. The coal matrix can imbibe water under capillary forces leading to exchange of mass between fractures and coal matrix. In this paper new partial differential equation for water saturation in fractures has been formulated, respecting mass exchange between coal matrix and fractures. Exact analytical solution has been obtained using the method of characteristics. The final solution has very simple form that may be useful for practical engineering calculations. It was observed that the rate of exchange of mass between the fractures and the coal matrix is governed by an expression which is analogous to the Newton cooling law known from theory of heat exchange, but in present case the mass transfer coefficient depends not only on coal and fluid properties but also on time and position. The constant term of mass transfer coefficient depends on relation between micro porosity and macro porosity of coal, capillary forces, and microporous structure of coal matrix. This term can be expressed theoretically or obtained experimentally. W artykule zaprezentowano nowy model matematyczny przepływu wody i gazu w jednowymiarowej warstwie węglowej z uwzględnieniem wymiany masy między systemem szczelin i matrycą węglową. Węgiel jako system przepływowy traktowany jest jako układ o podwójnej porowatości i przepuszczalności, składający się z mikroporowatej matrycy węglowej oraz z

  6. Synthesis of Acrolein from Glycerol Using FePO4 Catalyst in Liquid Phase Dehydration

    Akhmad Zainal Abidin

    2016-02-01

    Full Text Available Acrolein is currently produced using propylene from crude oil while its price and scarcity are increasing. A renewable material such as glycerol is an attractive alternative for acrolein production. It can be obtained from crude palm oil (CPO and is a byproduct of biodiesel production. Besides being able to compete economically, glycerol is an environmentally friendly material. The purpose of this study is to synthesize acrolein from glycerol using FePO4 catalyst in liquid phase dehydration. The catalyst was prepared by three different methods: hydrothermal (catalyst A, deposition at Fe/P = 1.15 (catalyst B, and deposition at Fe/P = 1.20 (catalyst C. The experimental reaction temperature was varied at 220, 240 and 260 °C under constant atmospheric pressure. The results showed that catalyst C provided the best yield (91%, followed by catalyst A (90% and catalyst B (82%. The increasing reaction temperature showed a tendency to increase the yield of acrolein, while the presence of oxygen reduced the yield of acrolein and allowed the reaction to produce more side products such as glycerol propanal, acetaldehyde, and propionate. Catalyst reuse without any regeneration resulted in a yield profile of acrolein that continued to decline.

  7. A tailored catalyst for the sustainable conversion of glycerol to acrolein: mechanistic aspect of sequential dehydration.

    Yun, Danim; Kim, Tae Yong; Park, Dae Sung; Yun, Yang Sik; Han, Jeong Woo; Yi, Jongheop

    2014-08-01

    Developing a catalyst to resolve deactivation caused from coke is a primary challenge in the dehydration of glycerol to acrolein. An open-macropore-structured and Brønsted-acidic catalyst (Marigold-like silica functionalized with sulfonic acid groups, MS-FS) was synthesized for the stable and selective production of acrolein from glycerol. A high acrolein yield of 73% was achieved and maintained for 50 h in the presence of the MS-FS catalyst. The hierarchical structure of the catalyst with macropores was found to have an important effect on the stability of the catalyst because coke polymerization and pore blocking caused by coke deposition were inhibited. In addition, the behavior of 3-hydroxypropionaldehyde (3-HPA) during the sequential dehydration was studied using density functional theory (DFT) calculations because 3-HPA conversion is one of the main causes for coke formation. We found that the easily reproducible Brønsted acid sites in MS-FS permit the selective and stable production of acrolein. This is because the reactive intermediate (3-HPA) is readily adsorbed on the regenerated acid sites, which is essential for the selective production of acrolein during the sequential dehydration. The regeneration ability of the acid sites is related not only to the selective production of acrolein but also to the retardation of catalyst deactivation by suppressing the formation of coke precursors originating from 3-HPA degradation.

  8. Acrolein stimulates the synthesis of IL-6 and C-reactive protein (CRP) in thrombosis model mice and cultured cells.

    Saiki, Ryotaro; Hayashi, Daisuke; Ikuo, Yukiko; Nishimura, Kazuhiro; Ishii, Itsuko; Kobayashi, Kaoru; Chiba, Kan; Toida, Toshihiko; Kashiwagi, Keiko; Igarashi, Kazuei

    2013-12-01

    Measurements of protein-conjugated acrolein (PC-Acro), IL-6, and C-reactive protein (CRP) in plasma were useful for identifying silent brain infarction with high sensitivity and specificity. The aim of this study was to determine whether acrolein causes increased production of IL-6 and CRP in thrombosis model mice and cultured cells. In mice with photochemically induced thrombosis, acrolein produced at the locus of infarction increased the level of IL-6 and then CRP in plasma. This was confirmed in cell culture systems - acrolein stimulated the production of IL-6 in mouse neuroblastoma Neuro-2a cells, mouse macrophage-like J774.1 cells, and human umbilical vein endothelial cells (HUVEC), and IL-6 in turn stimulated the production of CRP in human hepatocarcinoma cells. The level of IL-6 mRNA was increased by acrolein through an increase in phosphorylation of the transcription factors, c-Jun, and NF-κB p65. Furthermore, CRP stimulated IL-6 production in mouse macrophage-like J774.1 cells and HUVEC. IL-6 functioned as a protective factor against acrolein toxicity in Neuro-2a cells and HUVEC. These results show that acrolein stimulates the synthesis of IL-6 and CRP, which function as protecting factors against acrolein toxicity, and that the combined measurement of PC-Acro, IL-6, and CRP is effective for identification of silent brain infarction. The combined measurements of protein-conjugated acrolein (PC-Acro), IL-6, and C-reactive protein (CRP) in plasma were useful for identifying silent brain infarction. The aim of this study was to determine whether acrolein causes increased production of IL-6 and CRP, and indeed acrolein increased IL-6 synthesis and IL-6 in turn increased CRP synthesis. Furthermore, IL-6 decreased acrolein toxicity in several cell lines.

  9. Activity of matrix metalloproteinases during antimycobacterial therapy in mice with simulated tuberculous inflammation.

    Sumenkova, D V; Russkikh, G S; Poteryaeva, O N; Polyakov, L M; Panin, L E

    2013-05-01

    Matrix metalloproteinases are shown to be involved in the pathogenesis of tuberculosis inflammation. In the early stages of BCG-granuloma formation in mouse liver and lungs, the serum levels of matrix metalloproteinases 2 and 7 increased by 4.5 times and remained unchanged while the pathology developed. Antimycobacterial therapy with isoniazid reduced enzyme activity almost to the level of intact control. The decrease in activity of matrix metalloproteinases 2 and 7 that play the most prominent role in the development of destructive forms of tuberculosis is of great therapeutic importance.

  10. Acute systemic accumulation of acrolein in mice by inhalation at a concentration similar to that in cigarette smoke.

    Tully, Melissa; Zheng, Lingxing; Acosta, Glen; Tian, Ran; Shi, Riyi

    2014-12-01

    Cigarette smoke is an important environmental factor associated with a wide array of public health concerns. Acrolein, a component of tobacco smoke and a known toxin to various cell types, may be a key pathological factor mediating the adverse effects linked with tobacco smoke. Although acrolein is known to accumulate in the respiratory system after acute nasal exposure, it is not clear if it accumulates systemically, and less is known in the nervous system. The aim of this study was to assess the degree of acrolein accumulation in the circulation and in the spinal cord following acute acrolein inhalation in mice. Using a laboratory-fabricated inhalation chamber, we found elevated urinary 3-HPMA, an acrolein metabolite, and increased acrolein adducts in the spinal cord after weeks of nasal exposure to acrolein at a concentration similar to that in tobacco smoke. The data indicated that acrolein is absorbed into the circulatory system and some enters the nervous system. It is expected that these findings may facilitate further studies to probe the pathological role of acrolein in the nervous system resulting from smoke and other external sources.

  11. ASTM and VAMAS activities in titanium matrix composites test methods development

    Johnson, W. S.; Harmon, D. M.; Bartolotta, P. A.; Russ, S. M.

    1994-01-01

    Titanium matrix composites (TMC's) are being considered for a number of aerospace applications ranging from high performance engine components to airframe structures in areas that require high stiffness to weight ratios at temperatures up to 400 C. TMC's exhibit unique mechanical behavior due to fiber-matrix interface failures, matrix cracks bridged by fibers, thermo-viscoplastic behavior of the matrix at elevated temperatures, and the development of significant thermal residual stresses in the composite due to fabrication. Standard testing methodology must be developed to reflect the uniqueness of this type of material systems. The purpose of this paper is to review the current activities in ASTM and Versailles Project on Advanced Materials and Standards (VAMAS) that are directed toward the development of standard test methodology for titanium matrix composites.

  12. pH-Sensitive Microparticles with Matrix-Dispersed Active Agent

    Li, Wenyan (Inventor); Buhrow, Jerry W. (Inventor); Jolley, Scott T. (Inventor); Calle, Luz M. (Inventor)

    2014-01-01

    Methods to produce pH-sensitive microparticles that have an active agent dispersed in a polymer matrix have certain advantages over microcapsules with an active agent encapsulated in an interior compartment/core inside of a polymer wall. The current invention relates to pH-sensitive microparticles that have a corrosion-detecting or corrosion-inhibiting active agent or active agents dispersed within a polymer matrix of the microparticles. The pH-sensitive microparticles can be used in various coating compositions on metal objects for corrosion detecting and/or inhibiting.

  13. Immobilization of cesium in alkaline activated fly ash matrix

    Fernandez-Jimenez, A.; Macphee, D. E.; Lachowski, E. E.; Palomo, A.

    2005-11-01

    The immobilization potential of alkaline activated fly ash (AAFA) matrices for cesium has been investigated. The presence of Cs in the AAFA pastes, prepared using 8M NaOH solution as activator, showed no significant adverse effects on mechanical strength or microstructure, nor were significant quantities of Cs leached following application of the Toxic Characteristic Leaching Procedure (TCLP) and American Nuclear Society (ANS) 16.1 leaching protocols. Microstructural analysis shows Cs associated with the main reaction product in the AAFA suggesting that cesium is chemically bound rather than physically encapsulated. It is proposed that cesium is incorporated into the alkaline aluminosilicate gel, a precursor for zeolite formation.

  14. Targeting of matrix metalloproteinase activation for noninvasive detection of vulnerable atherosclerotic lesions

    Hartung, Dagmar [University of California, School of Medicine, Irvine, CA (United States); School of Medicine, Department of Radiology, Hannover (Germany); Schaefers, Michael; Kopka, Klaus [University of Muenster, Department of Nuclear Medicine, Muenster (Germany); Fujimoto, Shinichiro; Narula, Navneet; Petrov, Artiom; Narula, Jagat [University of California, School of Medicine, Irvine, CA (United States); Levkau, Bodo [University of Duisburg-Essen, Institute of Pathophysiology, Duisburg (Germany); Virmani, Renu; Kolodgie, Frank D. [Cardiovascular Pathology, Gaithersburg, MD (United States); Reutelingsperger, Chris; Hofstra, Leo [Cardiovascular Research Institute, Maastricht (Netherlands)

    2007-06-15

    Inflammation plays an important role in vulnerability of atherosclerotic plaques to rupture and hence acute coronary events. The monocyte-macrophage infiltration in plaques leads to upregulation of cytokines and metalloproteinase enzymes. Matrix metalloproteinases result in matrix dissolution and consequently expansive remodeling of the vessel. They also contribute to attenuation of fibrous cap and hence susceptibility to rupture. Assessment of metalloproteinase expression and activity should provide information about plaque instability. (orig.)

  15. Acrolein- and 4-Aminobiphenyl-DNA adducts in human bladder mucosa and tumor tissue and their mutagenicity in human urothelial cells.

    Lee, Hyun-Wook; Wang, Hsiang-Tsui; Weng, Mao-wen; Hu, Yu; Chen, Wei-sheng; Chou, David; Liu, Yan; Donin, Nicholas; Huang, William C; Lepor, Herbert; Wu, Xue-Ru; Wang, Hailin; Beland, Frederick A; Tang, Moon-shong

    2014-06-15

    Tobacco smoke (TS) is a major cause of human bladder cancer (BC). Two components in TS, 4-aminobiphenyl (4-ABP) and acrolein, which also are environmental contaminants, can cause bladder tumor in rat models. Their role in TS related BC has not been forthcoming. To establish the relationship between acrolein and 4-ABP exposure and BC, we analyzed acrolein-deoxyguanosine (dG) and 4-ABP-DNA adducts in normal human urothelial mucosa (NHUM) and bladder tumor tissues (BTT), and measured their mutagenicity in human urothelial cells. We found that the acrolein-dG levels in NHUM and BTT are 10-30 fold higher than 4-ABP-DNA adduct levels and that the acrolein-dG levels in BTT are 2 fold higher than in NHUM. Both acrolein-dG and 4-ABP-DNA adducts are mutagenic; however, the former are 5 fold more mutagenic than the latter. These two types of DNA adducts induce different mutational signatures and spectra. We found that acrolein inhibits nucleotide excision and base excision repair and induces repair protein degradation in urothelial cells. Since acrolein is abundant in TS, inhaled acrolein is excreted into urine and accumulates in the bladder and because acrolein inhibits DNA repair and acrolein-dG DNA adducts are mutagenic, we propose that acrolein is a major bladder carcinogen in TS.

  16. Active space decomposition with multiple sites: Density matrix renormalization group algorithm

    Parker, Shane M

    2014-01-01

    We extend the active space decomposition method, recently developed by us, to more than two active sites using the density matrix renormalization group algorithm. The fragment wave functions are described by complete or restricted active-space wave functions. Numerical results are shown on a benzene pentamer and a perylene diimide trimer. It is found that the truncation errors in our method decrease almost exponentially with respect to the number of renormalization states M, allowing for numerically exact calculations (to a few {\\mu}Eh or less) with M = 128 in both cases, which is in contrast to conventional ab initio density matrix renormalization group.

  17. Protective Effect of Silymarin against Acrolein-Induced Cardiotoxicity in Mice

    Elahe Taghiabadi

    2012-01-01

    Full Text Available Reactive α,β-unsaturated aldehydes such as acrolein (ACR are major components of environmental pollutants and have been implicated in the neurodegenerative and cardiac diseases. In this study, the protective effect of silymarin (SN against cardiotoxicity induced by ACR in mice was evaluated. Studies were performed on seven groups of six animals each, including vehicle-control (normal saline + 0.5% w/v methylcellulose, ACR (7.5 mg/kg/day, gavage for 3 weeks, SN (25, 50 and 100 mg/kg/day, i.p. plus ACR, vitamin E (Vit E, 100 IU/kg, i.p. plus ACR, and SN (100 mg/kg, i.p. groups. Mice received SN 7 days before ACR and daily thereafter throughout the study. Pretreatment with SN attenuated ACR-induced increased levels of malondialdehyde (MDA, serum cardiac troponin I (cTnI, and creatine kinase-MB (CK-MB, as well as histopathological changes in cardiac tissues. Moreover, SN improved glutathione (GSH content, superoxide dismutase (SOD, and catalase (CAT activities in heart of ACR-treated mice. Western blot analysis showed that SN pretreatment inhibited apoptosis provoked by ACR through decreasing Bax/Bcl-2 ratio, cytosolic cytochrome c content, and cleaved caspase-3 level in heart. In conclusion, SN may have protective effects against cardiotoxicity of ACR by reducing lipid peroxidation, renewing the activities of antioxidant enzymes, and preventing apoptosis.

  18. Conversion Matrix Analysis of GaAs HEMT Active Gilbert Cell Mixers

    Jiang, Chenhui; Johansen, Tom Keinicke; Krozer, Viktor

    2006-01-01

    In this paper, the nonlinear model of the GaAs HEMT active Gilbert cell mixer is investigated. Based on the model, the conversion gain expression of active Gilbert cell mixers is derived theoretically by using conversion matrix analysis method. The expression is verified by harmonic balance simul...... simulation with Angelov HEMT model in Agilent Advanced Design System (ADS) and by chip measurement results....

  19. Mediating the potent ROS toxicity of acrolein in neurons with silica nanoparticles and a natural product approach

    White-Schenk, Désirée.; Shi, Riyi; Leary, James F.

    2014-03-01

    Acrolein, a very reactive aldehyde, is a culprit in the biochemical cascade after primary, mechanical spinal cord injury (SCI), which leads to the destruction of tissue initially unharmed, referred to as "secondary injury". Additionally, in models of multiple sclerosis (MS) and some clinical research, acrolein levels are significantly increased. Due to its ability to make more copies of itself in the presence of tissue via lipid peroxidation, researchers believe that acrolein plays a role in the increased destruction of the central nervous system in both SCI and MS. Hydralazine, an FDAapproved hypotensive drug, has been shown to scavenge acrolein, but its side effects and short half life at the appropriate dose for acrolein scavenging must be improved for beneficial clinical translation. Therefore, a nanomedical approach has been designed using silica nanoparticles as a porous delivery vehicle hydralazine. The silica particles are formed in a one-step method that incorporates poly(ethylene) glycol (PEG), a stealth molecule, directly onto the nanoparticles. As an additional avenue for study, a natural product in green tea, epigallocatechin gallate (EGCG), has been explored for its ability to react with acrolein, disabling its reactive capabilities. Upon demonstration of attenuating acrolein, EGCG's delivery may also be improved using the nanomedical approach. The current work exposes the potential of using silica nanoparticles as a delivery vehicle and EGCG's antioxidant capabilities in B35 neuroblastoma cells exposed to acrolein. We also measure nanotoxicity to individual rat neurons using high-throughput image scanning cytometry.

  20. Airborne acrolein induces keratin-8 (Ser-73) hyperphosphorylation and intermediate filament ubiquitination in bronchiolar lung cell monolayers.

    Burcham, Philip C; Raso, Albert; Henry, Peter J

    2014-05-07

    The combustion product acrolein is a key mediator of pulmonary edema in victims of smoke inhalation injury. Since studying acrolein toxicity in conventional in vitro systems is complicated by reactivity with nucleophilic culture media constituents, we explored an exposure system which delivers airborne acrolein directly to lung cell monolayers at the air-liquid interface. Calu-3 lung adenocarcinoma cells were maintained on membrane inserts such that the basal surface was bathed in nucleophile-free media while the upper surface remained in contact with acrolein-containing air. Cells were exposed to airborne acrolein for 30 min before they were allowed to recover in fresh media, with cell sampling at defined time points to allow evaluation of toxicity and protein damage. After prior exposure to acrolein, cell ATP levels remained close to controls for 4h but decreased in an exposure-dependent manner by 24h. A loss of transepithelial electrical resistance and increased permeability to fluorescein isothiocyanate-labeled dextran preceded ATP loss. Use of antibody arrays to monitor protein expression in exposed monolayers identified strong upregulation of phospho-keratin-8 (Ser(73)) as an early consequence of acrolein exposure. These changes were accompanied by chemical damage to keratin-8 and other intermediate filament family members, while acrolein exposure also resulted in controlled ubiquitination of high mass proteins within the intermediate filament extracts. These findings confirm the usefulness of systems allowing delivery of airborne smoke constituents to lung cell monolayers during studies of the molecular basis for acute smoke intoxication injury.

  1. Acrolein inhalation causes myocardial strain delay and decreased cardiac performance as detected by high-frequency echocardiography in mice

    Acrolein, an unsaturated aldehyde found in air pollution, impairs Ca2+ flux and contraction in cardiomyocytes in vitro. To better define direct and delayed functional cardiac effects, we hypothesized that a single exposure to acrolein would modify myocardial strain and performanc...

  2. Isotope-labeling studies on the formation pathway of acrolein during heat processing of oils.

    Ewert, Alice; Granvogl, Michael; Schieberle, Peter

    2014-08-20

    Acrolein (2-propenal) is classified as a foodborne toxicant and was shown to be present in significant amounts in heated edible oils. Up to now, its formation was mainly suggested to be from the glycerol part of triacylglycerides, although a clear influence of the unsaturation of the fatty acid moiety was also obvious in previous studies. To unequivocally clarify the role of the glycerol and the fatty acid parts in acrolein formation, two series of labeled triacylglycerides were synthesized: [(13)C(3)]-triacylglycerides of stearic, oleic, linoleic, and linolenic acid and [(13)C(54)]-triacylglycerides with labeled stearic, oleic, and linoleic acid, but with unlabeled glycerol. Heating of each of the seven intermediates singly in silicon oil and measurement of the formed amounts of labeled and unlabeled acrolein clearly proved the fatty acid backbone as the key precursor structure. Enzymatically synthesized pure linoleic acid and linolenic acid hydroperoxides were shown to be the key intermediates in acrolein formation, thus allowing the discussion of a radical-induced reaction pathway leading to the formation of the aldehyde. Surprisingly, although several oils contained high amounts of acrolein after heating, deep-fried foods themselves, such as donuts or French fries, were low in the aldehyde.

  3. Acrolein as a novel therapeutic target for motor and sensor y deifcits in spinal cord injur y

    Jonghyuck Park; Breanne Muratori; Riyi Shi

    2014-01-01

    In the hours to weeks following traumatic spinal cord injuries (SCI), biochemical processes are initiated that further damage the tissue within and surrounding the initial injury site:a process termed secondary injury. Acrolein, a highly reactive unsaturated aldehyde, has been shown to play a major role in the secondary injury by contributing signiifcantly to both motor and sensory deif-cits. In particular, efforts have been made to elucidate the mechanisms of acrolein-mediated dam-age at the cellular level and the resulting paralysis and neuropathic pain. In this review, we will highlight the recent developments in the understanding of the mechanisms of acrolein in motor and sensory dysfunction in animal models of SCI. We will also discuss the therapeutic beneifts of using acrolein scavengers to attenuate acrolein-mediated neuronal damage following SCI.

  4. Enhancement of the Acrolein-Induced Production of Reactive Oxygen Species and Lung Injury by GADD34

    Yang Sun

    2015-01-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is characterized by lung destruction and inflammation. As a major compound of cigarette smoke, acrolein plays a critical role in the induction of respiratory diseases. GADD34 is known as a growth arrest and DNA damage-related gene, which can be overexpressed in adverse environmental conditions. Here we investigated the effects of GADD34 on acrolein-induced lung injury. The intranasal exposure of acrolein induced the expression of GADD34, developing the pulmonary damage with inflammation and increase of reactive oxygen species (ROS. Conversely, the integrality of pulmonary structure was preserved and the generation of ROS was reduced in GADD34-knockout mice. Acrolein-induced phosphorylation of eIF2α in GADD34-knockout epithelial cells by shRNA protected cell death by reducing misfolded protein-caused oxidative stress. These data indicate that GADD34 participates in the development of acrolein-induced lung injury.

  5. Enhancement of the acrolein-induced production of reactive oxygen species and lung injury by GADD34.

    Sun, Yang; Ito, Sachiko; Nishio, Naomi; Tanaka, Yuriko; Chen, Nana; Liu, Lintao; Isobe, Ken-ichi

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is characterized by lung destruction and inflammation. As a major compound of cigarette smoke, acrolein plays a critical role in the induction of respiratory diseases. GADD34 is known as a growth arrest and DNA damage-related gene, which can be overexpressed in adverse environmental conditions. Here we investigated the effects of GADD34 on acrolein-induced lung injury. The intranasal exposure of acrolein induced the expression of GADD34, developing the pulmonary damage with inflammation and increase of reactive oxygen species (ROS). Conversely, the integrality of pulmonary structure was preserved and the generation of ROS was reduced in GADD34-knockout mice. Acrolein-induced phosphorylation of eIF2α in GADD34-knockout epithelial cells by shRNA protected cell death by reducing misfolded protein-caused oxidative stress. These data indicate that GADD34 participates in the development of acrolein-induced lung injury.

  6. Extra-cellular matrix proteins induce matrix metalloproteinase-1 (MMP-1 activity and increase airway smooth muscle contraction in asthma.

    Natasha K Rogers

    Full Text Available Airway remodelling describes the histopathological changes leading to fixed airway obstruction in patients with asthma and includes extra-cellular matrix (ECM deposition. Matrix metalloproteinase-1 (MMP-1 is present in remodelled airways but its relationship with ECM proteins and the resulting functional consequences are unknown. We used airway smooth muscle cells (ASM and bronchial biopsies from control donors and patients with asthma to examine the regulation of MMP-1 by ECM in ASM cells and the effect of MMP-1 on ASM contraction. Collagen-I and tenascin-C induced MMP-1 protein expression, which for tenascin-C, was greater in asthma derived ASM cells. Tenascin-C induced MMP-1 expression was dependent on ERK1/2, JNK and p38 MAPK activation and attenuated by function blocking antibodies against the β1 and β3 integrin subunits. Tenascin-C and MMP-1 were not expressed in normal airways but co-localised in the ASM bundles and reticular basement membrane of patients with asthma. Further, ECM from asthma derived ASM cells stimulated MMP-1 expression to a greater degree than ECM from normal ASM. Bradykinin induced contraction of ASM cells seeded in 3D collagen gels was reduced by the MMP inhibitor ilomastat and by siRNA knockdown of MMP-1. In summary, the induction of MMP-1 in ASM cells by tenascin-C occurs in part via integrin mediated MAPK signalling. MMP-1 and tenascin-C are co-localised in the smooth muscle bundles of patients with asthma where this interaction may contribute to enhanced airway contraction. Our findings suggest that ECM changes in airway remodelling via MMP-1 could contribute to an environment promoting greater airway narrowing in response to broncho-constrictor stimuli and worsening asthma symptoms.

  7. Energy-recycling pixel for active-matrix organic light-emitting diode display

    Yang, Che-Yu; Cho, Ting-Yi; Chen, Yen-Yu; Yang, Chih-Jen; Meng, Chao-Yu; Yang, Chieh-Hung; Yang, Po-Chuan; Chang, Hsu-Yu; Hsueh, Chun-Yuan; Wu, Chung-Chih; Lee, Si-Chen

    2007-06-01

    The authors report a pixel structure for active-matrix organic light-emitting diode (OLED) displays that has a hydrogenated amorphous silicon solar cell inserted between the driving polycrystalline Si thin-film transistor and the pixel OLED. Such an active-matrix OLED pixel structure not only exhibits a reduced reflection (and thus improved contrast) compared to conventional OLEDs but also is capable of recycling both incident photon energies and internally generated OLED radiation. Such a feature of energy recycling may be of use for portable/mobile electronics, which are particularly power aware.

  8. Kinematic matrix theory and universalities in self-propellers and active swimmers

    Nourhani, Amir; Lammert, Paul E.; Borhan, Ali; Crespi, Vincent H.

    2014-06-01

    We describe an efficient and parsimonious matrix-based theory for studying the ensemble behavior of self-propellers and active swimmers, such as nanomotors or motile bacteria, that are typically studied by differential-equation-based Langevin or Fokker-Planck formalisms. The kinematic effects for elementary processes of motion are incorporated into a matrix, called the "kinematrix," from which we immediately obtain correlators and the mean and variance of angular and position variables (and thus effective diffusivity) by simple matrix algebra. The kinematrix formalism enables us recast the behaviors of a diverse range of self-propellers into a unified form, revealing universalities in their ensemble behavior in terms of new emergent time scales. Active fluctuations and hydrodynamic interactions can be expressed as an additive composition of separate self-propellers.

  9. Kinematic matrix theory and universalities in self-propellers and active swimmers.

    Nourhani, Amir; Lammert, Paul E; Borhan, Ali; Crespi, Vincent H

    2014-06-01

    We describe an efficient and parsimonious matrix-based theory for studying the ensemble behavior of self-propellers and active swimmers, such as nanomotors or motile bacteria, that are typically studied by differential-equation-based Langevin or Fokker-Planck formalisms. The kinematic effects for elementary processes of motion are incorporated into a matrix, called the "kinematrix," from which we immediately obtain correlators and the mean and variance of angular and position variables (and thus effective diffusivity) by simple matrix algebra. The kinematrix formalism enables us recast the behaviors of a diverse range of self-propellers into a unified form, revealing universalities in their ensemble behavior in terms of new emergent time scales. Active fluctuations and hydrodynamic interactions can be expressed as an additive composition of separate self-propellers.

  10. Selective oxidation of propylene to acrolein by hydrothermally synthesized bismuth molybdates

    Schuh, Kirsten; Kleist, Wolfgang; Høj, Martin

    2014-01-01

    Hydrothermal synthesis has been used as a soft chemical method to prepare bismuth molybdate catalysts for the selective oxidation of propylene to acrolein. All obtained samples displayed a plate-like morphology, but their individual aspect ratios varied with the hydrothermal synthesis conditions...... of nitric acid during hydrothermal synthesis enhanced both propylene conversion and acrolein yield, possibly due to a change in morphology. Formation of β-Bi2Mo2O9 was not observed under the applied conditions. In general, the catalytic performance of all samples decreased notably after calcination at 550...

  11. Protection of HepG2 cells against acrolein toxicity by 2-cyano-3,12-dioxooleana-1,9-dien-28-imidazolide via glutathione-mediated mechanism.

    Shah, Halley; Speen, Adam M; Saunders, Christina; Brooke, Elizabeth A S; Nallasamy, Palanisamy; Zhu, Hong; Li, Y Robert; Jia, Zhenquan

    2015-10-01

    Acrolein is an environmental toxicant, mainly found in smoke released from incomplete combustion of organic matter. Several studies showed that exposure to acrolein can lead to liver damage. The mechanisms involved in acrolein-induced hepatocellular toxicity, however, are not completely understood. This study examined the cytotoxic mechanisms of acrolein on HepG2 cells. Acrolein at pathophysiological concentrations was shown to cause apoptotic cell death and an increase in levels of protein carbonyl and thiobarbituric acid reactive acid substances. Acrolein also rapidly depleted intracellular glutathione (GSH), GSH-linked glutathione-S-transferases, and aldose reductase, three critical cellular defenses that detoxify reactive aldehydes. Results further showed that depletion of cellular GSH by acrolein preceded the loss of cell viability. To further determine the role of cellular GSH in acrolein-mediated cytotoxicity, buthionine sulfoximine (BSO) was used to inhibit cellular GSH biosynthesis. It was observed that depletion of cellular GSH by BSO led to a marked potentiation of acrolein-mediated cytotoxicity in HepG2 cells. To further assess the contribution of these events to acrolein-induced cytotoxicity, triterpenoid compound 2-cyano-3,12-dioxooleana-1,9-dien-28-imidazolide (CDDO-Im) was used for induction of GSH. Induction of GSH by CDDO-Im afforded cytoprotection against acrolein toxicity in HepG2 cells. Furthermore, BSO significantly inhibited CDDO-Im-mediated induction in cellular GSH levels and also reversed cytoprotective effects of CDDO-Im in HepG2 cells. These results suggest that GSH is a predominant mechanism underlying acrolein-induced cytotoxicity as well as CDDO-Im-mediated cytoprotection. This study may provide understanding on the molecular action of acrolein which may be important to develop novel strategies for the prevention of acrolein-mediated toxicity.

  12. A hands-on activity for teaching product-process matrix: roadmap and application

    Luciano Costa Santos

    2014-08-01

    Full Text Available The product-process matrix is a well-known framework proposed by Hayes and Wheelwright (1979 that is commonly used to identify processes types and to analyze the alignment of these processes with the products of a company. For didactic purposes, the matrix helps undergraduates beginners from Production Engineering to understand the logic of production systems, providing knowledge that will be essential for various course subjects. Considering the high level of abstraction of the concepts underlying the product-process matrix, this paper presents a way to facilitate the learning of them through the application of a hands-on activity which relies on the active learning philosophy. The proposed dynamic uses colored plastic sheets and PVC pipes as main materials, differing from the original proposal of Penlesky and Treleven (2005 . In addition to presenting an extremely simple exercise, which encourages its application in the classroom, another contribution of this paper is to define a complete roadmap for conducting the activity. This roadmap describes the assembly of fictitious products in customization and standardization scenarios for the comparison of two processes types of product-process matrix, job shop and assembly line. The activity revealed very successful after its application to two groups of Production Engineering undergraduates, confirmed with positive feedback from the students surveyed.

  13. Serum matrix metalloproteinase 3 in early rheumatoid arthritis is correlated with disease activity and radiological progression

    Posthumus, MD; Limburg, PC; Westra, J; van Leeuwen, MA; van Rijswijk, MH

    2000-01-01

    Objective. To analyze the clinical significance of serial measurements of serum matrix metalloproteinase 3 (MMP-3) levels in relation to markers of disease activity and radiological progression in early rheumatoid arthritis (RA). Methods. In a 3 year prospective study of 33 patients with early RA (s

  14. Tissue levels of active matrix metalloproteinase-2 and -9 in colorectal cancer.

    Waas, E.T.; Lomme, R.M.L.M.; Groot, J. de; Wobbes, Th.; Hendriks, T.

    2002-01-01

    The bioactivity of matrix metalloproteinases was studied in tissues from colorectal cancer patients by means of both quantitative gelatin zymography and a fluorometric activity assay. Next to paired samples of tumour tissue and distant normal mucosa (n=73), transitional tissue was analysed from a li

  15. Effect of collagen turnover and matrix metalloproteinase activity on healing of venous leg ulcers

    Meyer, F.J.; Burnand, K.G.; Abisi, S.; TeKoppele, J.M.; Els, B. van; Smith, A.

    2008-01-01

    Background: The presence of fibrous tissue in poorly healing venous leg ulcers suggests abnormal collagen metabolism. The aim was to determine whether there were differences in collagen turnover and matrix metalloproteinase (MMP) activity between ulcers that healed, those that did not heal and norma

  16. Matrix rigidity differentially regulates invadopodia activity through ROCK1 and ROCK2.

    Jerrell, Rachel J; Parekh, Aron

    2016-04-01

    ROCK activity increases due to ECM rigidity in the tumor microenvironment and promotes a malignant phenotype via actomyosin contractility. Invasive migration is facilitated by actin-rich adhesive protrusions known as invadopodia that degrade the ECM. Invadopodia activity is dependent on matrix rigidity and contractile forces suggesting that mechanical factors may regulate these subcellular structures through ROCK-dependent actomyosin contractility. However, emerging evidence indicates that the ROCK1 and ROCK2 isoforms perform different functions in cells suggesting that alternative mechanisms may potentially regulate rigidity-dependent invadopodia activity. In this study, we found that matrix rigidity drives ROCK signaling in cancer cells but that ROCK1 and ROCK2 differentially regulate invadopodia activity through separate signaling pathways via contractile (NM II) and non-contractile (LIMK) mechanisms. These data suggest that the mechanical rigidity of the tumor microenvironment may drive ROCK signaling through distinct pathways to enhance the invasive migration required for cancer progression and metastasis.

  17. Matrix metalloproteinases (MMP) and cathepsin K contribute differently to osteoclastic activities

    Delaissé, Jean-Marie; Andersen, Thomas L; Engsig, Michael T;

    2003-01-01

    is based on a model of osteoclast recruitment in primitive long bones, an assay of osteoclast invasion through collagen gel, and the effect of proteinase inhibitors/knockouts in these models. Furthermore, we mention observations indicating a role of MMPs in initiation of bone resorption. Finally, we......The best established proteolytic event of osteoclasts is bone matrix solubilization by the cysteine proteinase cathepsin K. Here, however, we draw the attention on osteoclastic activities depending on matrix metalloproteinases (MMPs). We discuss the observations supporting that MMPs contribute...

  18. Imino [4+4] cycloaddition products as exclusive and biologically relevant acrolein-amine conjugates are intermediates of 3-formyl-3,4-dehydropiperidine (FDP), an acrolein biomarker.

    Takamatsu, Masayuki; Fukase, Koichi; Kurbangalieva, Almira; Tanaka, Katsunori

    2014-11-15

    We demonstrated synthetically that the eight-membered heterocycles 2,6,9-triazabicyclo[3.3.1]nonanes and 1,5-diazacyclooctanes are the initial and exclusive products of the reaction, through an imino [4+4] cycloaddition, of biologically relevant amines with acrolein. The stabilities of the aminoacetals within the eight-membered heterocycles determined whether the product was subsequently transformed gradually into the 3-formyl-3,4-dehydropiperidine (FDP), which is widely used as an oxidative stress marker. The reactivity profiles discovered in this study suggested that some of the imino [4+4] cycloaddition products are reactive intermediates of FDP and contribute to the mechanisms underlying the oxidative stress response to acrolein.

  19. Studies on the toxicity of acetone, acrolein and carbon dioxide on stored-product insects and wheat seed.

    Pourmirza, Ali Asghar; Tajbakhsh, Mehdie

    2008-04-01

    In laboratory experiments toxicity of acetone, acrolein and carbon dioxide were investigated against 4 species of stored-product insects. In all experiments, acrolein was the most toxic compound to the tested insects. In empty-space trials, estimated LD50 values of acrolein for adults of Tribolium castaneum (Herbst) (Tenebrionidae), Rhizopertha dominica (F.) (Bostrychidae), Sitophilus oryzae L. (Curculionidae) and Oryzaephilus surinamensis L. (Silvanidae) were 7.26, 6.09, 6.37 and 5.65 microl L(-1), respectively. Penetration tests revealed that acetone and acrolein vapors could penetrate into the wheat mass and kill concealed insects in interkernel spaces. Comparison of LD50 values of acrolein between empty-space tests and penetration experiments indicated that the increase in penetration toxicity was 4.96, 4.54, 3.64 and 3.43-fold for T. castaneum, R. dominica, S. oryzae and O. surinamensis, respectively. The effect of carbon dioxide on the toxicity of acrolein and acetone was synergistic. In the hidden infestation trials, the acrolein vapors destroyed the developmental stages of S. oryzae concealed inside the wheat kernels and resulted in a complete control with concentration of 80 microl L(-1) for 24 h and subsequently observed during 8 weeks after the exposure. Wheat germination and plumule length was reduced following exposure to all doses of acrolein. Acetone and carbon dioxide were harmless to wheat seed viability. The mixture of carbon dioxide with acrolein can be considered as a potential fumigant for replacing methyl bromide or phosphine under ambient storage conditions specifically in empty-space fumigations.

  20. Lowest triplet (n, π*) electronic state of acrolein: Determination of structural parameters by cavity ringdown spectroscopy and quantum-chemical methods

    Hlavacek, Nikolaus C.; McAnally, Michael O.; Drucker, Stephen

    2013-02-01

    The cavity ringdown absorption spectrum of acrolein (propenal, CH2=CH—CH=O) was recorded near 412 nm, under bulk-gas conditions at room temperature and in a free-jet expansion. The measured spectral region includes the 0^0_0 band of the T1(n, π*) ← S0 system. We analyzed the 0^0_0 rotational contour by using the STROTA computer program [R. H. Judge et al., J. Chem. Phys. 103, 5343 (1995)], 10.1063/1.470569, which incorporates an asymmetric rotor Hamiltonian for simulating and fitting singlet-triplet spectra. We used the program to fit T1(n, π*) inertial constants to the room-temperature contour. The determined values (cm-1), with 2σ confidence intervals, are A = 1.662 ± 0.003, B = 0.1485 ± 0.0006, C = 0.1363 ± 0.0004. Linewidth analysis of the jet-cooled spectrum yielded a value of 14 ± 2 ps for the lifetime of isolated acrolein molecules in the T1(n, π*), v = 0 state. We discuss the observed lifetime in the context of previous computational work on acrolein photochemistry. The spectroscopically derived inertial constants for the T1(n, π*) state were used to benchmark a variety of computational methods. One focus was on complete active space methods, such as complete active space self-consistent field (CASSCF) and second-order perturbation theory with a CASSCF reference function (CASPT2), which are applicable to excited states. We also examined the equation-of-motion coupled-cluster and time-dependent density function theory excited-state methods, and finally unrestricted ground-state techniques, including unrestricted density functional theory and unrestricted coupled-cluster theory with single and double and perturbative triple excitations. For each of the above methods, we or others [O. S. Bokareva et al., Int. J. Quantum Chem. 108, 2719 (2008)], 10.1002/qua.21803 used a triple zeta-quality basis set to optimize the T1(n, π*) geometry of acrolein. We find that the multiconfigurational methods provide the best agreement with fitted inertial

  1. Dimerization of matrix metalloproteinase-2 (MMP-2): functional implication in MMP-2 activation.

    Koo, Bon-Hun; Kim, Yeon Hyang; Han, Jung Ho; Kim, Doo-Sik

    2012-06-29

    Matrix metalloproteinase-2 (MMP-2) functions in diverse biological processes through the degradation of extracellular and non-extracellular matrix molecules. Because of its potential for tissue damage, there are several ways to regulate MMP-2 activity, including gene expression, compartmentalization, zymogen activation, and enzyme inactivation by extracellular inhibitors. Enzyme regulation through zymogen activation is important for the regulation of MMP-2 activity. In our previous studies, we showed that thrombin directly cleaved the propeptide of MMP-2 at specific sites for enzyme activation. We also demonstrated that heparan sulfate was required for thrombin-mediated activation of pro-MMP-2 by binding to thrombin, presumably through conformational changes at the active site of the enzyme. This suggests a regulatory mechanism for thrombin-mediated activation of pro-MMP-2. In this study, we found that MMP-2 formed a reduction-sensitive homodimer in a controlled manner and that Ca(2+) ion was essential for homodimerization of MMP-2. Homodimerization was not associated with protein kinase C-mediated phosphorylation of MMP-2. MMP-2 formed a homodimer through an intermolecular disulfide bond between Cys(102) and the neighboring Cys(102). Homodimerization of MMP-2 enhanced thrombin-mediated activation of pro-MMP-2. Moreover, the MMP-2 homodimer could cleave a small peptide substrate without removal of the propeptide. Taken together, our experimental data suggest a novel regulatory mechanism for pro-MMP-2 activation that is modulated through homodimerization of MMP-2.

  2. Activation of matrix metalloproteinase-2 (MMP-2) by membrane type 1 matrix metalloproteinase through an artificial receptor for proMMP-2 generates active MMP-2.

    Nishida, Yuki; Miyamori, Hisashi; Thompson, Erik W; Takino, Takahisa; Endo, Yoshio; Sato, Hiroshi

    2008-11-01

    The suggested model for pro-matrix metalloproteinase-2 (proMMP-2) activation by membrane type 1 MMP (MT1-MMP) implicates the complex between MT1-MMP and tissue inhibitor of MMP-2 (TIMP-2) as a receptor for proMMP-2. To dissect this model and assess the pathologic significance of MMP-2 activation, an artificial receptor for proMMP-2 was created by replacing the signal sequence of TIMP-2 with cytoplasmic/transmembrane domain of type II transmembrane mosaic serine protease (MSP-T2). Unlike TIMP-2, MSP-T2 served as a receptor for proMMP-2 without inhibiting MT1-MMP, and generated TIMP-2-free active MMP-2 even at a low level of MT1-MMP. Thus, MSP-T2 did not affect direct cleavage of the substrate testican-1 by MT1-MMP, whereas TIMP-2 inhibited it even at the level that stimulates proMMP-2 processing. Expression of MSP-T2 in HT1080 cells enhanced MMP-2 activation by endogenous MT1-MMP and caused intensive hydrolysis of collagen gel. Expression of MSP-T2 in U87 glioma cells, which express a trace level of endogenous MT1-MMP, induced MMP-2 activation and enhanced cell-associated protease activity, activation of extracellular signal-regulated kinase, and metastatic ability into chick embryonic liver and lung. MT1-MMP can exert both maximum MMP-2 activation and direct cleavage of substrates with MSP-T2, which cannot be achieved with TIMP-2. These results suggest that MMP-2 activation by MT1-MMP potentially amplifies protease activity, and combination with direct cleavage of substrate causes effective tissue degradation and enhances tumor invasion and metastasis, which highlights the complex role of TIMP-2. MSP-T2 is a unique tool to analyze physiologic and pathologic roles of MMP-2 and MT1-MMP in comparison with TIMP-2.

  3. Synovial fluid matrix metalloproteinase-2 and -9 activities in dogs suffering from joint disorders.

    Murakami, Kohei; Maeda, Shingo; Yonezawa, Tomohiro; Matsuki, Naoaki

    2016-07-01

    The activity of matrix metalloproteinase (MMP)-2 and MMP-9 in synovial fluids (SF) sampled from dogs with joint disorders was investigated by gelatin zymography and densitometry. Pro-MMP-2 showed similar activity levels in dogs with idiopathic polyarthritis (IPA; n=17) or canine rheumatoid arthritis (cRA; n=4), and healthy controls (n=10). However, dogs with cranial cruciate ligament rupture (CCLR; n=5) presented significantly higher pro-MMP-2 activity than IPA and healthy dogs. Meanwhile, dogs with IPA exhibited significantly higher activity of pro- and active MMP-9 than other groups. Activity levels in pro- and active MMP-9 in cRA and CCLR dogs were not significantly different from those in healthy controls. Different patterns of MMP-2 and MMP-9 activity may reflect the differences in the underlying pathological processes.

  4. Sensory irritation to mixtures of formaldehyde, acrolein, and acetaldehyde in rats

    Cassee, F.R.; Arts, J.H.E.; Groten, J.P.; Feron, V.J.

    1996-01-01

    Sensory irritation of formaldehyde (FRM), acrolein (ACR) and acetaldehyde (ACE) as measured by the decrease in breathing frequency (DBF) was studied in male Wistar rats using nose-only exposure. Groups of four rats were exposed to each of the single compounds separately or to mixtures of FRM, ACR an

  5. Selective oxidation of propylene to acrolein by silica-supported bismuth molybdate catalysts

    Duc, Duc Truong; Ha, Hanh Nguyen; Fehrmann, Rasmus

    2011-01-01

    Silica-supported bismuth molybdate catalysts have been prepared by impregnation, structurally characterized and examined as improved catalysts for the selective oxidation of propylene to acrolein. Catalysts with a wide range of loadings (from 10 to 90 wt%) of beta bismuth molybdate (β-Bi2Mo2O9...

  6. Molecular mechanisms of acrolein-mediated myelin destruction in CNS trauma and disease.

    Shi, R; Page, J C; Tully, M

    2015-01-01

    Myelin is a critical component of the nervous system facilitating efficient propagation of electrical signals and thus communication between the central and peripheral nervous systems and the organ systems that they innervate throughout the body. In instances of neurotrauma and neurodegenerative disease, injury to myelin is a prominent pathological feature responsible for conduction deficits, and leaves axons vulnerable to damage from noxious compounds. Although the pathological mechanisms underlying myelin loss have yet to be fully characterized, oxidative stress (OS) appears to play a prominent role. Specifically, acrolein, a neurotoxic aldehyde that is both a product and an instigator of OS, has been observed in studies to elicit demyelination through calcium-independent and -dependent mechanisms and also by affecting glutamate uptake and promoting excitotoxicity. Furthermore, pharmacological scavenging of acrolein has demonstrated a neuroprotective effect in animal disease models, by conserving myelin's structural integrity and alleviating functional deficits. This evidence indicates that acrolein may be a key culprit of myelin damage while acrolein scavenging could potentially be a promising therapeutic approach for patients suffering from nervous system trauma and disease.

  7. Glycerol valorization: dehydration to acrolein over silica-supported niobia catalysts

    Shiju, N.R.; Brown, D.R.; Wilson, K.; Rothenberg, G.

    2010-01-01

    The catalytic dehydration of glycerol to acrolein is investigated over silica-supported niobia catalysts in a continuous fixed-bed gas-phase reactor. Various supported niobia catalysts are prepared and characterized using surface analysis and spectroscopic methods (XRD, UV-Vis, XPS, N2 adsorption),

  8. The First Catalytic Asymmetric Morita-Baylis-Hillman Reaction of Acrolein with Aromatic Aldehydes

    曾兴平; 刘运林; 计从斌; 周剑

    2012-01-01

    We report the first example of catalytic asymmetric Morita-Baylis-Hillman reaction of acrolein with aromatic aldehydes. The use of 10 mol% of Hatakeyama's catalyst β-isocupreidine C4, in combination with 20 mol% of 2,6-dimethoxybenzoic acid, could catalyze the reaction to give the desired products in up to 81% ee.

  9. Toxicity of formaldehyde and acrolein mixtures : in vitro studies using nasal epithelial cells

    Cassee, F.R.; Stenhuis, W.S.; Groten, J.P.; Feron, V.J.

    1996-01-01

    In vitro studies with human and rat nasal epithelial cells were carried out to investigate the combined toxicity of formaldehyde and acrolein and the role of aldehyde dehydrogenases in this process. These studies showed that the toxic effect of mixtures of aldehydes was additive. In addition, aldehy

  10. Determination of acrolein, ethanol, volatile acidity, and copper in different samples of sugarcane spirits

    José Masson

    2012-09-01

    Full Text Available Seventy-one samples of sugarcane spirits from small and average size stills produced in the northern and southern Minas Gerais (Brazil were analyzed for acrolein using HPLC (High Performance Liquid Chromatography. Ethanol and copper concentrations and volatile acidity were also determined according to methods established by the Ministry of Agriculture, Livestock and Supply (MAPA. A total of 9.85% of the samples tested showed levels of acrolein above the legal limits, while the copper concentrations of 21.00% of the samples and the volatile acidity of 8.85% of the samples were higher than the limits established by the Brazilian legislation. The concentration of acrolein varied from 0 to 21.97 mg.100 mL-1 of ethanol. However, no significant difference at 5% of significance was observed between the samples produced in the northern and southern Minas Gerais. The method used for determination of acrolein in sugarcane spirits involved the formation of a derivative with 2,4-dinitrophenylhydrazine (2,4-DNPH and subsequent analysis by HPLC.

  11. Drosophila SAF-B links the nuclear matrix, chromosomes, and transcriptional activity.

    Catalina Alfonso-Parra

    Full Text Available Induction of gene expression is correlated with alterations in nuclear organization, including proximity to other active genes, to the nuclear cortex, and to cytologically distinct domains of the nucleus. Chromosomes are tethered to the insoluble nuclear scaffold/matrix through interaction with Scaffold/Matrix Attachment Region (SAR/MAR binding proteins. Identification and characterization of proteins involved in establishing or maintaining chromosome-scaffold interactions is necessary to understand how the nucleus is organized and how dynamic changes in attachment are correlated with alterations in gene expression. We identified and characterized one such scaffold attachment factor, a Drosophila homolog of mammalian SAF-B. The large nuclei and chromosomes of Drosophila have allowed us to show that SAF-B inhabits distinct subnuclear compartments, forms weblike continua in nuclei of salivary glands, and interacts with discrete chromosomal loci in interphase nuclei. These interactions appear mediated either by DNA-protein interactions, or through RNA-protein interactions that can be altered during changes in gene expression programs. Extraction of soluble nuclear proteins and DNA leaves SAF-B intact, showing that this scaffold/matrix-attachment protein is a durable component of the nuclear matrix. Together, we have shown that SAF-B links the nuclear scaffold, chromosomes, and transcriptional activity.

  12. Communication: Active space decomposition with multiple sites: Density matrix renormalization group algorithm

    Parker, Shane M.; Shiozaki, Toru [Department of Chemistry, Northwestern University, 2145 Sheridan Rd., Evanston, Illinois 60208 (United States)

    2014-12-07

    We extend the active space decomposition method, recently developed by us, to more than two active sites using the density matrix renormalization group algorithm. The fragment wave functions are described by complete or restricted active-space wave functions. Numerical results are shown on a benzene pentamer and a perylene diimide trimer. It is found that the truncation errors in our method decrease almost exponentially with respect to the number of renormalization states M, allowing for numerically exact calculations (to a few μE{sub h} or less) with M = 128 in both cases. This rapid convergence is because the renormalization steps are used only for the interfragment electron correlation.

  13. Translesion synthesis past acrolein-derived DNA adducts by human mitochondrial DNA polymerase γ.

    Kasiviswanathan, Rajesh; Minko, Irina G; Lloyd, R Stephen; Copeland, William C

    2013-05-17

    Acrolein, a mutagenic aldehyde, is produced endogenously by lipid peroxidation and exogenously by combustion of organic materials, including tobacco products. Acrolein reacts with DNA bases forming exocyclic DNA adducts, such as γ-hydroxy-1,N(2)-propano-2'-deoxyguanosine (γ-HOPdG) and γ-hydroxy-1,N(6)-propano-2'-deoxyadenosine (γ-HOPdA). The bulky γ-HOPdG adduct blocks DNA synthesis by replicative polymerases but can be bypassed by translesion synthesis polymerases in the nucleus. Although acrolein-induced adducts are likely to be formed and persist in mitochondrial DNA, animal cell mitochondria lack specialized translesion DNA synthesis polymerases to tolerate these lesions. Thus, it is important to understand how pol γ, the sole mitochondrial DNA polymerase in human cells, acts on acrolein-adducted DNA. To address this question, we investigated the ability of pol γ to bypass the minor groove γ-HOPdG and major groove γ-HOPdA adducts using single nucleotide incorporation and primer extension analyses. The efficiency of pol γ-catalyzed bypass of γ-HOPdG was low, and surprisingly, pol γ preferred to incorporate purine nucleotides opposite the adduct. Pol γ also exhibited ∼2-fold lower rates of excision of the misincorporated purine nucleotides opposite γ-HOPdG compared with the corresponding nucleotides opposite dG. Extension of primers from the termini opposite γ-HOPdG was accomplished only following error-prone purine nucleotide incorporation. However, pol γ preferentially incorporated dT opposite the γ-HOPdA adduct and efficiently extended primers from the correctly paired terminus, indicating that γ-HOPdA is probably nonmutagenic. In summary, our data suggest that acrolein-induced exocyclic DNA lesions can be bypassed by mitochondrial DNA polymerase but, in the case of the minor groove γ-HOPdG adduct, at the cost of unprecedented high mutation rates.

  14. EFFECTS OF GENISTEIN ON INVASION AND MATRIX METALLOPROTEINASE ACTIVITIES OF HT1080 HUMAN FIBROSARCOMA CELLS

    1999-01-01

    @@ Effects of genistein on invasion and matrix metalloproteinase activities were investigated in HT1080 human sarcoma cells.Invasion of HT1080 cells through reconstituted basement membrane was inhibited when the cells were treated with 100 μ mol/L and 200 μ mol/L genistein.At the same concentrations,genistein not only suppressed latent forms of matrix metalloprotinese-2 and-9(MMP-2 and MMP-9) to convert into active forms,but also increase dramatically the tissue inhibitor of metalloproteinase(TIMP-1) mRNA contents and reverse the imbalance of MMPs and TIMPs.However,expressions of MMP-2 and MMP-9 were not significantly affected.Suppression of MMP activation and increase of TIMP-1 expression will decrease matrix degradation by MMPs,and consequently inhibit invasions of the cells.These results emphasized the existence of the imbalance between MMPs and TIMPs in tumor invasion and metastasis formation.The value of genistein as a drug for antiinvasion and anti-metastasis chemotherapy was suggested.

  15. EFFECTS OF GENISTEIN ON INVASION AND MATRIX METALLOPROTEINASE ACTIVITIES OF HT1080 HUMAN FIBROSARCOMA CELLS

    颜春洪; 韩锐

    1999-01-01

    Effects of genistein on invasion and matrix metalloproteinase activities were investigated in HT1080 human sarcoma cells, lnvasion of HTI080 cells through reconstituted basement membnme was inhibited when the cells were treated with 100μmol/L and 200μmol/L genistein; At the same concentrations,genistein not only suppressed latent forms of matrix metalloprotinese-2 and-9 (MMP-2 mad MMP-9) to convert into active forms, but also increase dramatically the tissue inhibitor of metalloproteinase (TIMP-1 ) mRNA contents and reverse the imbalance of MMPs and TIMPs. However, expressions of MMP-2 and MMP-9 were not sigrdficantly affected. Suppression of MMP activation and increase of TMP-1 expression will decrease matrix degradation by MMPs, and consequently inhibit invasions of the cells. These results emphasized the existence of the imbalance between MMPs and TIMPs in tumor invasion mad metastasis formation, The value of genistein as a drug for antiinvasion and anti-metastasis chemotherapy was suggested.

  16. Matrix stiffness modulates formation and activity of neuronal networks of controlled architectures.

    Lantoine, Joséphine; Grevesse, Thomas; Villers, Agnès; Delhaye, Geoffrey; Mestdagh, Camille; Versaevel, Marie; Mohammed, Danahe; Bruyère, Céline; Alaimo, Laura; Lacour, Stéphanie P; Ris, Laurence; Gabriele, Sylvain

    2016-05-01

    The ability to construct easily in vitro networks of primary neurons organized with imposed topologies is required for neural tissue engineering as well as for the development of neuronal interfaces with desirable characteristics. However, accumulating evidence suggests that the mechanical properties of the culture matrix can modulate important neuronal functions such as growth, extension, branching and activity. Here we designed robust and reproducible laminin-polylysine grid micropatterns on cell culture substrates that have similar biochemical properties but a 100-fold difference in Young's modulus to investigate the role of the matrix rigidity on the formation and activity of cortical neuronal networks. We found that cell bodies of primary cortical neurons gradually accumulate in circular islands, whereas axonal extensions spread on linear tracks to connect circular islands. Our findings indicate that migration of cortical neurons is enhanced on soft substrates, leading to a faster formation of neuronal networks. Furthermore, the pre-synaptic density was two times higher on stiff substrates and consistently the number of action potentials and miniature synaptic currents was enhanced on stiff substrates. Taken together, our results provide compelling evidence to indicate that matrix stiffness is a key parameter to modulate the growth dynamics, synaptic density and electrophysiological activity of cortical neuronal networks, thus providing useful information on scaffold design for neural tissue engineering.

  17. On the performance of quantum chemical methods to predict solvatochromic effects. The case of acrolein in aqueous solution

    Aidas, Kestutis; Møgelhøj, Andreas; Nilsson, Elna Johanna Kristina

    2008-01-01

    The performance of the Hartree–Fock method and the three density functionals B3LYP, PBE0, and CAM-B3LYP is compared to results based on the coupled cluster singles and doubles model in predictions of the solvatochromic effects on the vertical n¿* and ¿* electronic excitation energies of acrolein...... of acrolein in vapor phase and aqueous solution. The gas-to-aqueous solution shift of the n¿* excitation energy is well reproduced by using all density functional methods considered. However, the B3LYP and PBE0 functionals completely fail to describe the ¿* electronic transition in solution, whereas...... the recent CAM-B3LYP functional performs well also in this case. The ¿* excitation energy of acrolein in water solution is found to be very dependent on intermolecular induction and nonelectrostatic interactions. The computed excitation energies of acrolein in vacuum and solution compare well to experimental...

  18. The health- and addictive effectes due to exposure to aldehydes of cigarette smoke. Part 1; Acetaldehyde, Formaldehyde, Acrolein and Propionaldehyde

    van Andel I; Schenk E; Rambali B; Wolterink G; van de Werken G; Stevenson H; van Aerts LAGJM; Vleeming W; LEO; LGM; LOC; CRV

    2003-01-01

    In deze literatuurstudie worden de gezondheids- en mogelijke verslavende effecten van blootstelling aan aldehyden ten gevolge van het roken van sigaretten beschreven. Dit literatuuronderzoek richt zich met name op acetaldehyde, formaldehyde, acrolein, en propionaldehyde. Alle aldehyden veroorzaken

  19. Effects of acrolein and other pesticides on water quality and aquatic biota in Tule Lake National Wildlife Refuge

    US Fish and Wildlife Service, Department of the Interior — The objective of this study was to evaluate the potential impacts of acrolein and other pesticides on water quality and aquatic invertebrates and fish, with a...

  20. Acrolein and asthma attack prevalence in a representative sample of the United States adult population 2000-2009.

    B Rey deCastro

    Full Text Available BACKGROUND: Acrolein is an air toxic and highly potent respiratory irritant. There is little epidemiology available, but US EPA estimates that outdoor acrolein is responsible for about 75 percent of non-cancer respiratory health effects attributable to air toxics in the United States, based on the Agency's 2005 NATA (National-Scale Air Toxics Assessment and acrolein's comparatively potent inhalation reference concentration of 0.02 µg/m3. OBJECTIVES: Assess the association between estimated outdoor acrolein exposure and asthma attack reported by a representative cross-sectional sample of the adult United States population. METHODS: NATA 2005 chronic outdoor acrolein exposure estimates at the census tract were linked with residences oif adults (≥18 years old in the NHIS (National Health Interview Survey 2000-2009 (n = 271,348 subjects. A sample-weighted logistic regression model characterized the association between the prevalence of reporting at least one asthma attack in the 12 months prior to survey interview and quintiles of exposure to outdoor acrolein, controlling for potential confounders. RESULTS: In the highest quintile of outdoor acrolein exposure (0.05-0.46 µg/m3, there was a marginally significant increase in the asthma attack pOR (prevalence-odds ratio [95% CI]  = 1.08 [0.98∶1.19] relative to the lowest quintile. The highest quintile was also associated with a marginally significant increase in prevalence-odds (1.13 [0.98∶1.29] in a model limited to never smokers (n = 153,820. CONCLUSIONS: Chronic exposure to outdoor acrolein of 0.05-0.46 µg/m3 appears to increase the prevalence-odds of having at least one asthma attack in the previous year by 8 percent in a representative cross-sectional sample of the adult United States population.

  1. Peptide-Based Selective Inhibitors of Matrix Metalloproteinase-Mediated Activities

    Margaret W. Ndinguri

    2012-11-01

    Full Text Available The matrix metalloproteinases (MMPs exhibit a broad array of activities, some catalytic and some non-catalytic in nature. An overall lack of selectivity has rendered small molecule, active site targeted MMP inhibitors problematic in execution. Inhibitors that favor few or individual members of the MMP family often take advantage of interactions outside the enzyme active site. We presently focus on peptide-based MMP inhibitors and probes that do not incorporate conventional Zn2+ binding groups. In some cases, these inhibitors and probes function by binding only secondary binding sites (exosites, while others bind both exosites and the active site. A myriad of MMP mediated-activities beyond selective catalysis can be inhibited by peptides, particularly cell adhesion, proliferation, motility, and invasion. Selective MMP binding peptides comprise highly customizable, unique imaging agents. Areas of needed improvement for MMP targeting peptides include binding affinity and stability.

  2. Acrolein, a highly toxic aldehyde generated under oxidative stress in vivo, aggravates the mouse liver damage after acetaminophen overdose.

    Arai, Tomoya; Koyama, Ryo; Yuasa, Makoto; Kitamura, Daisuke; Mizuta, Ryushin

    2014-01-01

    Although acetaminophen-induced liver injury in mice has been extensively studied as a model of human acute drug-induced hepatitis, the mechanism of liver injury remains unclear. Liver injury is believed to be initiated by metabolic conversion of acetaminophen to the highly reactive intermediate N-acetyl p-benzoquinoneimine, and is aggravated by subsequent oxidative stress via reactive oxygen species (ROS), including hydrogen peroxide (H2O2) and the hydroxyl radical (•OH). In this study, we found that a highly toxic unsaturated aldehyde acrolein, a byproduct of oxidative stress, has a major role in acetaminophen-induced liver injury. Acetaminophen administration in mice resulted in liver damage and increased acrolein-protein adduct formation. However, both of them were decreased by treatment with N-acetyl-L-cysteine (NAC) or sodium 2-mercaptoethanesulfonate (MESNA), two known acrolein scavengers. The specificity of NAC and MESNA was confirmed in cell culture, because acrolein toxicity, but not H2O2 or •OH toxicity, was inhibited by NAC and MESNA. These results suggest that acrolein may be more strongly correlated with acetaminophen-induced liver injury than ROS, and that acrolein produced by acetaminophen-induced oxidative stress can spread from dying cells at the primary injury site, causing damage to the adjacent cells and aggravating liver injury.

  3. Acrolein enhances epigenetic modifications, FasL expression and hepatocyte toxicity induced by anti-HIV drug Zidovudine.

    Ghare, Smita S; Donde, Hridgandh; Chen, Wei-Yang; Barker, David F; Gobejishvilli, Leila; McClain, Craig J; Barve, Shirish S; Joshi-Barve, Swati

    2016-09-01

    Zidovudine (AZT) remains the mainstay of antiretroviral therapy against HIV in resource-poor countries; however, its use is frequently associated with hepatotoxicity. Not all HIV patients on AZT develop hepatotoxicity, and the determining factors are unclear. Alcohol consumption and cigarette smoking are known risk factors for HIV hepatotoxicity, and both are significant sources of acrolein, a highly reactive and toxic aldehyde. This study examines the potential hepatotoxic interactions between acrolein and AZT. Our data demonstrate that acrolein markedly enhanced AZT-induced transcriptionally permissive histone modifications (H3K9Ac and H3K9Me3) allowing the recruitment of transcription factor NF-kB and RNA polymerase II at the FasL gene promoter, resulting in FasL upregulation and apoptosis in hepatocytes. Notably, the acrolein scavenger, hydralazine prevented these promoter-associated epigenetic changes and inhibited FasL upregulation and apoptosis induced by the combination of AZT and acrolein, as well as AZT alone. Our data strongly suggest that acrolein enhancement of promoter histone modifications and FasL upregulation are major pathogenic mechanisms driving AZT-induced hepatotoxicity. Moreover, these data also indicate the therapeutic potential of hydralazine in mitigating AZT hepatotoxicity.

  4. Cooking-related PM2.5 and acrolein measured in grocery stores and comparison with other retail types.

    Chan, W R; Sidheswaran, M; Sullivan, D P; Cohn, S; Fisk, W J

    2016-06-01

    We measured particulate matter (PM), acrolein, and other indoor air contaminants in eight visits to grocery stores in California. Retail stores of other types (hardware, furniture, and apparel) were also sampled on additional visits. Based on tracer gas decay data, most stores had adequate ventilation according to minimum ventilation rate standards. Grocery stores had significantly higher concentrations of acrolein, fine and ultrafine PM, compared to other retail stores, likely attributable to cooking. Indoor concentrations of PM2.5 and acrolein exceeded health guidelines in all tested grocery stores. Acrolein emission rates to indoors in grocery stores had a mean estimate about 30 times higher than in other retail store types. About 80% of the indoor PM2.5 measured in grocery stores was emitted indoors, compared to only 20% for the other retail store types. Calculations suggest a substantial increase in outdoor air ventilation rate by a factor of three from current level is needed to reduce indoor acrolein concentrations. Alternatively, acrolein emission to indoors needs to be reduced 70% by better capturing of cooking exhaust. To maintain indoor PM2.5 below the California annual ambient standard of 12 μg/m(3) , grocery stores need to use air filters with an efficiency rating higher than the MERV 8 air filters commonly used today.

  5. Involvement of interleukin-6-regulated nitric oxide synthase in hemorrhagic cystitis and impaired bladder contractions in young rats induced by acrolein, a urinary metabolite of cyclophosphamide.

    Wang, Ching-Chia; Weng, Te-I; Wu, En-Ting; Wu, Mei-Hwan; Yang, Rong-Sen; Liu, Shing-Hwa

    2013-01-01

    Hemorrhagic cystitis is a common complication in children receiving cyclophosphamide, a chemotherapeutic alkylating agent. Acrolein is a urinary metabolite from cyclophosphamide and can induce hemorrhagic cystitis. Here, we investigated the effects and mechanisms of acrolein by intravesical instillation on urinary bladder muscle contractions and pathological alterations in rats. Acrolein instillation significantly increased the muscle contractions of rat bladder detrusor after 1 and 6 h but markedly decreased detrusor contractions after 24 h. Acrolein increased phosphorylated protein kinase C (pan-PKC) expressions in bladders after 1 and 6 h but inhibited it after 24 h. Inducible nitric oxide (NO) synthase (iNOS) protein expressions were markedly induced in bladders 24 h after acrolein treatment. Twenty-four-hour acrolein instillation increased the levels of nitrite/nitrate and interleukin-6 (IL-6) in the urinary bladder. The iNOS inhibitors significantly inhibited the acrolein-increased nitrite/nitrate levels, but not IL-6 levels. IL-6-neutralizing antibodies effectively inhibited the acrolein-increased NOx levels. The increased detrusor contractions by 1-h acrolein treatment were significantly reversed by the PKC inhibitor RO32-0432, and the decreased detrusor contractions by 24-h acrolein treatment were significantly reversed by the iNOS inhibitor and IL-6-neutralizing antibody. Both the iNOS inhibitor and IL-6-neutralizing antibody effectively reversed the increased iNOS expression, decreased PKC phosphorylation, increased bladder weight, and hemorrhagic cystitis in rats 24 h after acrolein treatment. Taken together, these results suggest that an IL-6-regulated iNOS/NO signaling pathway participates in the acrolein-triggered detrusor contraction inhibition and hemorrhagic cystitis. These findings may help us to find a new strategy to treat cyclophosphamide-induced hemorrhagic cystitis.

  6. RNase L Suppresses Androgen Receptor Signaling, Cell Migration and Matrix Metalloproteinase Activity in Prostate Cancer Cells.

    Dayal, Shubham; Zhou, Jun; Manivannan, Praveen; Siddiqui, Mohammad Adnan; Ahmad, Omaima Farid; Clark, Matthew; Awadia, Sahezeel; Garcia-Mata, Rafael; Shemshedini, Lirim; Malathi, Krishnamurthy

    2017-03-01

    The interferon antiviral pathways and prostate cancer genetics converge on a regulated endoribonuclease, RNase L. Positional cloning and linkage studies mapped Hereditary Prostate Cancer 1 (HPC1) to RNASEL. To date, there is no correlation of viral infections with prostate cancer, suggesting that RNase L may play additional roles in tumor suppression. Here, we demonstrate a role of RNase L as a suppressor of androgen receptor (AR) signaling, cell migration and matrix metalloproteinase activity. Using RNase L mutants, we show that its nucleolytic activity is dispensable for both AR signaling and migration. The most prevalent HPC1-associated mutations in RNase L, R462Q and E265X, enhance AR signaling and cell migration. RNase L negatively regulates cell migration and attachment on various extracellular matrices. We demonstrate that RNase L knockdown cells promote increased cell surface expression of integrin β1 which activates Focal Adhesion Kinase-Sarcoma (FAK-Src) pathway and Ras-related C3 botulinum toxin substrate 1-guanosine triphosphatase (Rac1-GTPase) activity to increase cell migration. Activity of matrix metalloproteinase (MMP)-2 and -9 is significantly increased in cells where RNase L levels are ablated. We show that mutations in RNase L found in HPC patients may promote prostate cancer by increasing expression of AR-responsive genes and cell motility and identify novel roles of RNase L as a prostate cancer susceptibility gene.

  7. The modulation of platelet adhesion and activation by chitosan through plasma and extracellular matrix proteins.

    Lord, Megan S; Cheng, Bill; McCarthy, Simon J; Jung, MoonSun; Whitelock, John M

    2011-10-01

    Chitosan has been shown to promote initial wound closure events to prevent blood loss. Platelet adhesion and activation are crucial early events in these processes after traumatic bleeding leading to thrombus formation. Platelet adhesion to chitosan was found to be enhanced in the presence of adsorbed plasma and extracellular matrix proteins and was found to be primarily mediated by α(IIb)β(3) integrins, while α(2)β(1) integrins were found to be involved in platelet adhesion to collagen and perlecan. Platelets were found to be activated by chitosan, as shown by an increase in the expression of α(IIb)β(3) integrins and P-selectin, while the extent of activation was modulated by the presence of proteins including perlecan and fibrinogen. Collagen-coated chitosan was found to activate platelets to the same extent as either chitosan or collagen alone. These data support the role of plasma and extracellular matrix proteins in promoting chitosan mediated platelet adhesion and activation supporting the hypothesis that chitosan promotes wound healing via these interactions.

  8. The inhibition of matrix metalloproteinase activity in chronic wounds by a polyacrylate superabsorber.

    Eming, Sabine; Smola, Hans; Hartmann, Berenike; Malchau, Gebhart; Wegner, Ronny; Krieg, Thomas; Smola-Hess, Sigrun

    2008-07-01

    Excessive matrix metalloproteinase (MMP) levels have been observed in wound fluid of impaired healing wounds. This is thought to interfere with granulation tissue formation as newly formed extracellular matrix and cytokines are degraded and the wound becomes deadlocked, unable to progress to the next healing stages. In the cleansing phase, associated with high MMP activity levels, hydroactive wound dressings containing polyacrylate superabsorber particles are particularly effective. We tested whether these particles can block MMP activity in wound fluid obtained from chronic venous leg ulcers. Polyacrylate superabsorber particles inhibited MMP activity by more than 87% in a fluorogenic peptide substrate assay. Further analysis revealed two underlying molecular mechanisms. First, experiments showed direct binding of MMPs to the particles. Secondly, polyacrylate superabsorber particles can bind Ca2+ and Zn2+ ions competing with MMPs for divalent ions required for enzymatic activity. Furthermore, we provide the first evidence in vivo that MMPs bind effectively to polyacrylate superabsorber particles within the hostile environment of chronic wounds. We conclude that polyacrylate superabsorber particles can rescue the highly proteolytic microenvironment of non-healing wounds from MMP activity so that more conductive conditions allow healing to proceed.

  9. Theoretical Studies of Active Power/angle Sub-matrix in Power Flow Jacobian for Power System Analysis

    CAO Guo-yun; ZHANG Qing; CHUNG T S; CHEN Chen

    2008-01-01

    Properties of the active power/angle sub-matrix in the power flow Jacobian for power system analysis are studied. The sub-matrix is a dominant and irreducible matrix under very general conditions of power systems, so that it is invertible. Also the necessary conditions for its singularity are given. These theoretical rsuts can be used to clarify the ambiguous understanding of the sub-matrix in current literature, and also provide the theoretical foundations for the applications based on reduced power flow Jacobian. Numerical simulation on the IEEE 118-bus power system is used to illustrate our results.

  10. Classical macrophage activation up-regulates several matrix metalloproteinases through mitogen activated protein kinases and nuclear factor-κB.

    Wei-Chun Huang

    Full Text Available Remodelling of the extracellular matrix (ECM and cell surface by matrix metalloproteinases (MMPs is an important function of monocytes and macrophages. Recent work has emphasised the diverse roles of classically and alternatively activated macrophages but the consequent regulation of MMPs and their inhibitors has not been studied comprehensively. Classical activation of macrophages derived in vitro from un-fractionated CD16(+/- or negatively-selected CD16(- macrophages up-regulated MMP-1, -3, -7, -10, -12, -14 and -25 and decreased TIMP-3 steady-state mRNA levels. Bacterial lipopolysaccharide, IL-1 and TNFα were more effective than interferonγ except for the effects on MMP-25, and TIMP-3. By contrast, alternative activation decreased MMP-2, -8 and -19 but increased MMP -11, -12, -25 and TIMP-3 steady-state mRNA levels. Up-regulation of MMPs during classical activation depended on mitogen activated protein kinases, phosphoinositide-3-kinase and inhibitor of κB kinase-2. Effects of interferonγ depended on janus kinase-2. Where investigated, similar effects were seen on protein concentrations and collagenase activity. Moreover, activity of MMP-1 and -10 co-localised with markers of classical activation in human atherosclerotic plaques in vivo. In conclusion, classical macrophage activation selectively up-regulates several MMPs in vitro and in vivo and down-regulates TIMP-3, whereas alternative activation up-regulates a distinct group of MMPs and TIMP-3. The signalling pathways defined here suggest targets for selective modulation of MMP activity.

  11. The parasite Entamoeba histolytica exploits the activities of human matrix metalloproteinases to invade colonic tissue.

    Thibeaux, Roman; Avé, Patrick; Bernier, Michèle; Morcelet, Marie; Frileux, Pascal; Guillén, Nancy; Labruyère, Elisabeth

    2014-10-07

    Intestinal invasion by the protozoan parasite Entamoeba histolytica is characterized by remodelling of the extracellular matrix (ECM). The parasite cysteine proteinase A5 (CP-A5) is thought to cooperate with human matrix metalloproteinases (MMPs) involved in ECM degradation. Here, we investigate the role CP-A5 plays in the regulation of MMPs upon mucosal invasion. We use human colon explants to determine whether CP-A5 activates human MMPs. Inhibition of the MMPs' proteolytic activities abolishes remodelling of the fibrillar collagen structure and prevents trophozoite invasion of the mucosa. In the presence of trophozoites, MMPs-1 and -3 are overexpressed and are associated with fibrillar collagen remodelling. In vitro, CP-A5 performs the catalytic cleavage needed to activate pro-MMP-3, which in turn activates pro-MMP-1. Ex vivo, incubation with recombinant CP-A5 was enough to rescue CP-A5-defective trophozoites. Our results suggest that MMP-3 and/or CP-A5 inhibitors may be of value in further studies aiming to treat intestinal amoebiasis.

  12. Nucleotide excision repair deficiency increases levels of acrolein-derived cyclic DNA adduct and sensitizes cells to apoptosis induced by docosahexaenoic acid and acrolein.

    Pan, Jishen; Sinclair, Elizabeth; Xuan, Zhuoli; Dyba, Marcin; Fu, Ying; Sen, Supti; Berry, Deborah; Creswell, Karen; Hu, Jiaxi; Roy, Rabindra; Chung, Fung-Lung

    2016-07-01

    The acrolein derived cyclic 1,N(2)-propanodeoxyguanosine adduct (Acr-dG), formed primarily from ω-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA) under oxidative conditions, while proven to be mutagenic, is potentially involved in DHA-induced apoptosis. The latter may contribute to the chemopreventive effects of DHA. Previous studies have shown that the levels of Acr-dG are correlated with apoptosis induction in HT29 cells treated with DHA. Because Acr-dG is shown to be repaired by the nucleotide excision repair (NER) pathway, to further investigate the role of Acr-dG in apoptosis, in this study, NER-deficient XPA and its isogenic NER-proficient XAN1 cells were treated with DHA. The Acr-dG levels and apoptosis were sharply increased in XPA cells, but not in XAN1 cells when treated with 125μM of DHA. Because DHA can induce formation of various DNA damage, to specifically investigate the role of Acr-dG in apoptosis induction, we treated XPA knockdown HCT116+ch3 cells with acrolein. The levels of both Acr-dG and apoptosis induction increased significantly in the XPA knockdown cells. These results clearly demonstrate that NER deficiency induces higher levels of Acr-dG in cells treated with DHA or acrolein and sensitizes cells to undergo apoptosis in a correlative manner. Collectively, these results support that Acr-dG, a ubiquitously formed mutagenic oxidative DNA adduct, plays a role in DHA-induced apoptosis and suggest that it could serve as a biomarker for the cancer preventive effects of DHA.

  13. Chromium liquid waste inertization in an inorganic alkali activated matrix: Leaching and NMR multinuclear approach

    Ponzoni, Chiara, E-mail: chiara.ponzoni@unimore.it [University of Modena and Reggio Emilia, Department of Engineering “Enzo Ferrari”, Modena (Italy); Lancellotti, Isabella; Barbieri, Luisa [University of Modena and Reggio Emilia, Department of Engineering “Enzo Ferrari”, Modena (Italy); Spinella, Alberto; Saladino, Maria Luisa [University of Palermo CGA-UniNetLab, Palermo (Italy); Martino, Delia Chillura [University of Palermo, Department STEBICEF, Palermo (Italy); Caponetti, Eugenio [University of Palermo CGA-UniNetLab, Palermo (Italy); University of Palermo, Department STEBICEF, Palermo (Italy); Armetta, Francesco [University of Palermo, Department STEBICEF, Palermo (Italy); Leonelli, Cristina [University of Modena and Reggio Emilia, Department of Engineering “Enzo Ferrari”, Modena (Italy)

    2015-04-09

    Highlights: • Inertization of chromium liquid waste in aluminosilicate matrix. • Water less inertization technique exploiting the waste water content. • Liquid waste inertization without drying step. • Long term stabilization study through leaching test. • SEM analysis and {sup 29}Si and {sup 27}Al MAS NMR in relation with long curing time. - Abstract: A class of inorganic binders, also known as geopolymers, can be obtained by alkali activation of aluminosilicate powders at room temperature. The process is affected by many parameters (curing time, curing temperature, relative humidity etc.) and leads to a resistant matrix usable for inertization of hazardous waste. In this study an industrial liquid waste containing a high amount of chromium (≈2.3 wt%) in the form of metalorganic salts is inertized into a metakaolin based geopolymer matrix. One of the innovative aspects is the exploitation of the water contained in the waste for the geopolymerization process. This avoided any drying treatment, a common step in the management of liquid hazardous waste. The evolution of the process - from the precursor dissolution to the final geopolymer matrix hardening - of different geopolymers containing a waste amount ranging from 3 to 20% wt and their capability to inertize chromium cations were studied by: i) the leaching tests, according to the EN 12,457 regulation, at different curing times (15, 28, 90 and 540 days) monitoring releases of chromium ions (Cr(III) and Cr(VI)) and the cations constituting the aluminosilicate matrix (Na, Si, Al); ii) the humidity variation for different curing times (15 and 540 days); iii) SEM characterization at different curing times (28 and 540 days); iv) the trend of the solution conductivity and pH during the leaching test; v) the characterization of the short-range ordering in terms of T−O−T bonds (where T is Al or Si) by {sup 29}Si and {sup 27}Al solid state magic-angle spinning nuclear magnetic resonance (ss MAS NMR) for

  14. Detection of acrolein and acrylonitrile with a pulsed room temperature quantum cascade laser

    Manne, J.; Jäger, W.; Tulip, J.

    2010-06-01

    We investigated the use of a pulsed, distributed feedback quantum cascade laser centered at 957 cm-1 in combination with an astigmatic Herriot cell with 250 m path length for the detection of acrolein and acrylonitrile. These molecules have been identified as hazardous air-pollutants because of their adverse health effects. The spectrometer utilizes the intra-pulse method, where a linear frequency down-chirp, that is induced when a top-hat current pulse is applied to the laser, is used for sweeping across the absorption line. Up to 450 ns long pulses were used for these measurements which resulted in a spectral window of ~2.2 cm-1. A room temperature mercury-cadmium-telluride detector was used, resulting in a completely cryogen free spectrometer. We demonstrated detection limits of ~3 ppb for acrylonitrile and ~6 ppb for acrolein with ~10 s averaging time. Laser characterization and optimization of the operational parameters for sensitivity improvement are discussed.

  15. X-ray Polarimetry with an Active-Matrix Pixel Proportional Counter

    Black, J. K.; Deines-Jones, P.; Ready, S. E.; Street, R. A.

    2003-01-01

    We report the first results from an X-ray polarimeter with a micropattern gas proportional counter using an amorphous silicon active matrix readout. With 100% polarized X-rays at 4.5 keV, we obtain a modulation factor of 0.33+/- 0.03, confirming previous reports of the high polarization sensitivity of a finely segmented pixel proportional counter. The detector described here has a geometry suitable for the focal plane of an astronomical X-ray telescope. Amorphous silicon readout technology will enable additional extensions and improvements.

  16. 1,N(2)-propanodeoxyguanosine adduct formation in aortic DNA following inhalation of acrolein.

    2001-01-01

    Recent reports indicate that many of the cytotoxic and health-threatening components of environmental tobacco smoke (ETS) reside in the vapor phase of the smoke. We have reported previously that inhalation of 1,3-butadiene, a prominent vapor phase component of ETS, accelerates arteriosclerotic plaque development in cockerels. In this study we asked whether inhaled acrolein, a reactive aldehyde that is also a prominent vapor-phase component of ETS, damages artery-wall DNA and accelerates plaqu...

  17. 丙烯醛-DNA加合物的研究进展%REVIEW:THE FORMATION AND MUTAGENESIS OF ACROLEIN-DNA ADDUCTS

    尹瑞川; 汪海林

    2011-01-01

    丙烯醛是一种活泼的a,β不饱和醛,在环境中广泛存在,香烟烟气和厨房油烟是人体丙烯醛暴露的主要环境来源.另一方面机体内丙烯醛可以通过脂质过氧化、氨基酸氧化等多种途径自发生成.进入人体后,丙烯醛和DNA发生加合生成丙烯醛-DNA加合物,目前研究最多的是丙烯醛-dG加合物,包括a-OH-PdG和γ-OH-PdG,其中γ-OH-PdG是主要dG加合物,可引起基因突变(约1%),以G→T突变为主,而次要加合物a-OH-PdG的突变概率高于γ-OH-PdG(约8%),同样以G→T突变为主,并且这些加合物与一些癌症密切相关,如吸烟相关肺癌和膀胱癌等.此外,丙烯醛可以与其它碱基发生加合,生成其它类型的DNA加合物,包括丙烯醛-dA、dC和dT加合物,其中一些加合物的结构已表征,并在体外反应中存在.%Acrolein, one of the most reactive α,β unsaturated aldehydes, is an ubiquitous environmental pollutant and is found in cigarette smoking and cooking. On the other hand, acrolein can also be endogenously released during lipid peroxidation, myeloperoxidase-mediated degradation of amino acids, and so on. Acrolein can directly react with DNA without metabolic activation. As a result several types of DNA adducts could be produced. Currently, most of studies focus on Acrolein-dG adduct, including α-OH-PdG and γ-OH-PdG. The measured amount of γ-OH-PdG is higher than α-OH-PdG in human body and it can generate about 1% gene mutation, while gene mutation frequency is 8% for α-OH-PdG. Both adducts mainly induce G→T mutation.In addition, other base adducts may also be generated in vitro, including Aerolein-dA, dC, and dT adducts.But their metabolism and genotoxicity are unknown. To unbiasedly judge the genotoxicity of acrolein, the formation, metabolism and genotoxicity of non-dG adducts should be considered.

  18. Determination of acrolein in urine by liquid chromatography and fluorescence detection of its quinoline derivative.

    al-Rawithi, S; el-Yazigi, A; Nicholls, P J

    1993-11-01

    We describe an assay for acrolein in urine, employing derivatization with m-aminophenol in the presence of ferrous sulfate solution in sulfuric acid. The derivative (7-OH quinoline; DER) and the internal standard (quinine-bisulfate; IS) were separated on a 10-micron particle, 8 mm x 10-cm C18 cartridge in conjunction with a radial compression system using a mixture of 0.05 M dibasic ammonium phosphate solution (pH 2.5):acetonitrile:methanol (92:6:2) at a flow rate of 3 mL/min as a mobile phase. The effluent was monitored fluorometrically at excitation and emission wavelengths of 360 and 495 nm, respectively. The retention times of DER and IS under these conditions were 4.3 and 26 min, respectively, and no interference in the assay from any endogenous substance or other concomitantly used drug was observed. The assay was highly linear (r > 0.994) in the range 1-20 micrograms/mL of acrolein in urine (CV at different concentrations, < or = 7.9%). This method can serve to monitor acrolein pharmacokinetics in patients.

  19. THE DIFFERENTIAL REGULATION OF CELL MOTILE ACTIVITY THROUGH MATRIX STIFFNESS AND POROSITY IN THREE DIMENSIONAL COLLAGEN MATRICES

    Miron-Mendoza, Miguel; Seemann, Joachim; Grinnell, Frederick

    2010-01-01

    In three dimensional collagen matrices, cell motile activity results in collagen translocation, cell spreading and cell migration. Cells can penetrate into the matrix as well as spread and migrate along its surface. In the current studies, we quantitatively characterize collagen translocation, cell spreading and cell migration in relationship to collagen matrix stiffness and porosity. Collagen matrices prepared with 1 to 4 mg/ml collagen exhibited matrix stiffness (storage modulus measured by oscillating rheometry) increasing from 4 to 60 Pa and matrix porosity (measured by scanning electron microscopy) decreasing from 4 to 1 μm2. Over this collagen concentration range, the consequences of cell motile activity changed markedly. As collagen concentration increased, cells no longer were able to cause translocation of collagen fibrils. Cell migration increased and cell spreading changed from dendritic to more flattened and polarized morphology depending on location of cells within or on the surface of the matrix. Collagen translocation appeared to depend primarily on matrix stiffness, whereas cell spreading and migration were less dependent on matrix stiffness and more dependent on collagen matrix porosity. PMID:20537378

  20. Anthocyanins Protect SK-N-SH Cells Against Acrolein-Induced Toxicity by Preserving the Cellular Redox State.

    Belkacemi, Abdenour; Ramassamy, Charles

    2016-01-01

    In Alzheimer's disease (AD) and in mild cognitive impairment (MCI) patients, by-products of lipid peroxidation such as acrolein accumulated in vulnerable regions of the brain. We have previously shown that acrolein is a highly reactive and neurotoxic aldehyde and its toxicity involves the alteration of several redox-sensitive pathways. Recently, protein-conjugated acrolein in cerebrospinal fluid has been proposed as a biomarker to distinguish between MCI and AD. With growing evidence of the early involvement of oxidative stress in AD etiology, one would expect that a successful therapy should prevent brain oxidative damage. In this regard, several studies have demonstrated that polyphenol-rich extracts exert beneficial effect on cognitive impairment and oxidative stress. We have recently demonstrated the efficacy of an anthocyanin formulation (MAF14001) against amyloid-β-induced oxidative stress. The aim of this study is to investigate the neuroprotective effect of MAF14001 as a mixture of anthocyanins, a particular class of polyphenols, against acrolein-induced oxidative damage in SK-N-SH neuronal cells. Our results demonstrated that MAF14001, from 5μM, was able to efficiently protect SK-N-SH cells against acrolein-induced cell death. MAF14001 was able to lower reactive oxygen species and protein carbonyl levels induced by acrolein. Moreover, MAF1401 prevented glutathione depletion and positively modulated, in the presence of acrolein, some oxidative stress-sensitive pathways including the transcription factors NF-κB and Nrf2, the proteins γ-GCS and GSK3β, and the protein adaptator p66Shc. Along with its proven protective effect against amyloid-β toxicity, these results demonstrate that MAF14001 could target multiple mechanisms and could be a promising agent for AD prevention.

  1. Collagen-binding VEGF mimetic peptide: Structure, matrix interaction, and endothelial cell activation

    Chan, Tania R.

    Long term survival of artificial tissue constructs depends greatly on proper vascularization. In nature, differentiation of endothelial cells and formation of vasculature are directed by dynamic spatio-temporal cues in the extracellular matrix that are difficult to reproduce in vitro. In this dissertation, we present a novel bifunctional peptide that mimics matrix-bound vascular endothelial growth factor (VEGF), which can be used to encode spatially controlled angiogenic signals in collagen-based scaffolds. The peptide, QKCMP, contains a collagen mimetic domain (CMP) that binds to type I collagen by a unique triple helix hybridization mechanism and a VEGF mimetic domain (QK) with pro-angiogenic activity. We demonstrate QKCMP's ability to hybridize with native and heat denatured collagens through a series of binding studies on collagen and gelatin substrates. Circular dichroism experiments show that the peptide retains the triple helical structure vital for collagen binding, and surface plasmon resonance study confirms the molecular interaction between the peptide and collagen strands. Cell culture studies demonstrate QKCMP's ability to induce endothelial cell morphogenesis and network formation as a matrix-bound factor in 2D and 3D collagen scaffolds. We also show that the peptide can be used to spatially modify collagen-based substrates to promote localized endothelial cell activation and network formation. To probe the biological events that govern these angiogenic cellular responses, we investigated the cell signaling pathways activated by collagen-bound QKCMP and determined short and long-term endothelial cell response profiles for p38, ERK1/2, and Akt signal transduction cascades. Finally, we present our efforts to translate the peptide's in vitro bioactivity to an in vivo burn injury animal model. When implanted at the wound site, QKCMP functionalized biodegradable hydrogels induce enhanced neovascularization in the granulation tissue. The results show QKCMP

  2. Photorefractive keratectomy: measuring the matrix metalloproteinase activity and chondroitin sulfate concentration in tear fluid

    Tetsuya Mutoh

    2010-09-01

    Full Text Available Tetsuya Mutoh, Masaya Nishio, Yukihiro Matsumoto, Kiyomi Arai, Makoto ChikudaDepartment of Ophthalmology, Dokkyo Medical University Koshigaya Hospital, Saitama, JapanAbstract: We herein report the case of a 20-year-old man who underwent a photorefractive keratectomy (PRK. We measured matrix metalloproteinase-9 (MMP-9 activity and chondroitin 4 sulfate and chondroitin 6 sulfate concentrations in tear fluid. Tear fluid was collected preoperatively via microcapillary tube, and was collected postoperatively on the first and fourth days, and after one week, one month, three months, and six months. Samples were formulated by dilution with 200 µL of saline. MMP-9 activity was analyzed by an enzyme immunocapture activity assay, and the concentrations of chondroitin sulfate were analyzed by enzyme-linked immunosorbent assay. No complications were observed after surgery, except for a minimal subepithelial haze. Although MMP-9 activity changed on the fourth postoperative day, the activity changed only minimally at this time. Chondroitin 4 sulfate concentrations in tear fluid increased dramatically from one week to one month, decreased transiently at three months, and increased by six months. The chondroitin 6 sulfate concentration did not normalize within one week, and decreased from one week to three months compared with the preoperative score, and was close to the preoperative score at six months. We conclude that corneal wound healing was still incomplete six months after PRK, and chondroitin 4 sulfate appears to be critical in this process.Keywords: matrix metalloproteinase, chondroitin sulfate, human tear fluid, photorefractive keratectomy, corneal wound healing

  3. Activity of Matrix Metalloproteinase in Airway Epithelial Cells of COPD Patients

    2005-01-01

    To examine the mRNA expression of matrix metalloproteinase 9 (MMP-9) and the gelatinase activity of its inhibitor, tissue inhibitor of matrix metalloproteinase 1 (TIMP-1) in the primary epithelial cells of patients with COPD, airway epithelial cells were taken from 15 COPD patients and cultured in vitro. The patients were divided into three groups, COPD group, normal smoking control group and non-smoking control group, with 5 subjects in each group, on basis of the smoking history and lung function. The semi-qualitative RT-PCR was employed to determine the mRNA levels of MMP 9 and TIMP-1 and SDS PAGE was used for the determination of the gelatinase activity of MMP-9 and TIMP-1. Our result showed that the mRNA of MMP-9 and TIMP-1 in epithelial cells of the non-smoking subjects was at a low level The mRNA of MMP 9 and TIMP-1 in COPD patients and smokers was significantly higher than that in non-smokers (P<0.05). No significant difference was found in the levels of MMP-9 and TIMP-1 in epithelial cells between the COPD patients and smokers. The MMP-9/TIMP-1 ratios in COPD patients and smokers were significantly lower than that of non-smokers (P<0.05). The gelatinase activity in the epithelial cells of both COPD patients and normal smokers was increased (P<0.05), but no difference existed in the gelatinase activity in the epithelial cells between COPD patients and normal smokers. It is concluded that the transcription of MMP-9 and TIMP-1 and the gelatinase activity of MMP-9 and MMP-2 in the epithelial cells in COPD patients were increased, which resulted in an imbalance of MMP-9/TIMP-1, thereby causing pulmonary fibrosis. These factors play important roles in the pathogenesis of COPD.

  4. Aryl hydrocarbon receptor activation impairs extracellular matrix remodeling during zebra fish fin regeneration.

    Andreasen, Eric A; Mathew, Lijoy K; Löhr, Christiane V; Hasson, Rachelle; Tanguay, Robert L

    2007-01-01

    Adult zebra fish completely regenerate their caudal (tail) fin following partial amputation. Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) inhibits this regenerative process. Proper regulation of transcription, innervation, vascularization, and extracellular matrix (ECM) composition is essential for complete fin regeneration. Previous microarray studies suggest that genes involved in ECM regulation are misexpressed following activation of the aryl hydrocarbon receptor. To investigate whether TCDD blocks regeneration by impairing ECM remodeling, male zebra fish were i.p. injected with 50 ng/g TCDD or vehicle, and caudal fins were amputated. By 3 days postamputation (dpa), the vascular network in the regenerating fin of TCDD-exposed fish was disorganized compared to vehicle-exposed animals. Furthermore, immunohistochemical staining revealed that axonal outgrowth was impacted by TCDD as early as 3 dpa. Histological analysis demonstrated that TCDD exposure leads to an accumulation of collagen at the end of the fin ray just distal to the amputation site by 3 dpa. Mature lepidotrichial-forming cells (fin ray-forming cells) were not observed in the fins of TCDD-treated fish. The capacity to metabolize ECM was also altered by TCDD exposure. Quantitative real-time PCR studies revealed that the aryl hydrocarbon pathway is active and that matrix-remodeling genes are expressed in the regenerate following TCDD exposure.

  5. The inhibitory effect of polyvinylphosphonic acid on functional matrix metalloproteinase activities in human demineralized dentin.

    Tezvergil-Mutluay, Arzu; Agee, Kelli A; Hoshika, Tomohiro; Tay, Franklin R; Pashley, David H

    2010-10-01

    This study has examined the use of polyvinylphosphonic acid (PVPA) as a potential matrix metalloproteinase (MMP) inhibitor and how brief cross-linking of demineralized dentin matrix that did not affect its mechanical properties enhanced the anti-MMP activity of PVPA. The anti-MMP potential of five PVPA concentrations (100-3000 microgml(-1)) was initially screened using a rhMMP-9 colorimetic assay. Demineralized dentin beams were treated with the same five concentrations of PVPA to collagen and then aged for 30 days in a calcium- and zinc-containing medium. The changes in modulus of elasticity, loss of dry mass and dissolution of collagen peptides were measured via three-point bending, precision weighing and hydroxyproline assay, respectively. All tested PVPA concentrations were highly effective (P<0.05) in inhibiting MMP-9. Ageing in the incubation medium did not significantly alter the modulus of elasticity of the five PVPA treatment groups. Conversely, aged dentin beams from the control group exhibited a significant decline in their modulus of elasticity (P<0.05) over time. Mass loss from the dentin beams and the corresponding increase in hydroxyproline in the medium in the five PVPA treatment groups were significantly lower than for the control (P<0.05). PVPA is a potent inhibitor of endogenous MMP activities in demineralized dentin. It may be used as an alternative to chlorhexidine to prevent collagen degradation within hybrid layers to extend the longevity of resin-dentin bonds.

  6. Gelatinase activity of matrix metalloproteinases in the cerebrospinal fluid of various patient populations.

    Valenzuela, M A; Cartier, L; Collados, L; Kettlun, A M; Araya, F; Concha, C; Flores, L; Wolf, M E; Mosnaim, A D

    1999-01-01

    We have studied the enzymatic gelatinolytic activity of matrix metalloproteinases (MMPs) present in cerebrospinal fluid (CSF) of samples obtained from 67 individuals, twenty-one nonneurological patients (considered controls) and 46 subjects with various neurological disorders e.g., vascular lesions, demyelination, inflammatory, degenerative and prion diseases. Biochemical characterization of MMPs, a family of neutral proteolytic enzymes involved in extracellular matrix modeling, included determination of substrate specificity and Ca+2 dependency, as well as the effects of protease inactivators, carboxylic and His (histidine) residue modifiers, and antibiotics. Whereas all CSF samples expressed MMP-2 (gelatinase A) activity, it corresponded in most cases (normal and pathological samples) to its latent form (proenzyme; pMMP-2). In general, inflammatory neurological diseases (especially meningitis and neurocisticercosis) were associated with the presence of a second enzyme, MMP-9 (or gelatinase B). Whereas MMP-9 was found in the CSF of every tropical spastic paraparesis patient studied, its presence in samples from individuals with vascular lesions was uncommon. Patients blood-brain barrier damage was ascertained by determining total CSF protein content using both, the conventional polyacrylamide gel electrophoresis procedure under denaturing conditions and capillary zone electrophoresis.

  7. Doxycycline blocks gastric ulcer by regulating matrix metalloproteinase-2 activity and oxidative stress

    Laishram Pradeepkumar Singh; Amartya Mishra; Debjit Saha; Snehasikta Swarnakar

    2011-01-01

    AIM: To examine the effect of doxycycline on the activity of matrix metalloproteinases (MMPs) and oxidative stress in gastric tissues of rats following gastric injury. METHODS: Gastric ulcers were generated in rats by administration of 70% ethanol, and activity of doxycycline was tested by administration 30 min prior to ethanol. Similarly, the effect of doxycycline was tested in an indomethacin-induced gastric ulcer model. The activities and expression of MMPs were examined by zymography and Western blot analysis. RESULTS: Gastric injury in rats as judged by elevated ulcer indices following exposure to ulcerogen, either indomethacin or ethanol, was reversed significantly by doxycycline. Indomethacin-induced ulcerated gastric tissues exhibited about 12-fold higher proMMP-9 activity and about 5-fold higher proMMP-3 activity as compared to control tissues. Similarly, ethanol induced about 22-fold and about 6-fold higher proMMP-9 and proMMP-3 activities, respectively, in rat gastric tissues. Both proMMP-9 and MMP-3 activities were markedly decreased by doxycycline in ulcerogen treated rat gastric tissues. In contrast, the reduced MMP-2 activity in ulcerated tissues was increased by doxycycline during ulcer prevention. On the other hand, doxycycline inhibited significantly proMMP-9, -2 and -3 activities in vitro . In addition, doxycycline reduced oxidative load in gastric tissues and scavenged H2O2 in vitro . Our results suggest a novel regulatory role of doxycycline on MMP-2 activity in addition to inhibitory action on MMP-9 and MMP-3 during prevention of gastric ulcers. CONCLUSION: This is the first demonstration of dual action of doxycycline, that is, regulation of MMP activity and reduction of oxidative stress in arresting gastric injury.

  8. Neutrophil bactericidal activity against Staphylococcus aureus adherent on biological surfaces. Surface-bound extracellular matrix proteins activate intracellular killing by oxygen-dependent and -independent mechanisms.

    Hermann, M.; Jaconi, M E; Dahlgren, C; Waldvogel, F A; Stendahl, O; Lew, D P

    1990-01-01

    The activation patterns of surface adherent neutrophils are modulated via interaction of extracellular matrix proteins with neutrophil integrins. To evaluate neutrophil bactericidal activity, Staphylococcus aureus adherent to biological surfaces were incubated with neutrophils and serum, and the survival of surface bacteria was determined. When compared to albumin-coated surfaces, the bactericidal activity of neutrophils adherent to purified human extracellular matrix was markedly enhanced (m...

  9. Activation of matrix metalloproteinases following anti-Aβ immunotherapy; implications for microhemorrhage occurrence

    Ridnour Lisa A

    2011-09-01

    Full Text Available Abstract Background Anti-Aβ immunotherapy is a promising approach to the prevention and treatment of Alzheimer's disease (AD currently in clinical trials. There is extensive evidence, both in mice and humans that a significant adverse event is the occurrence of microhemorrhages. Also, vasogenic edema was reported in phase 2 of a passive immunization clinical trial. In order to overcome these vascular adverse effects it is critical that we understand the mechanism(s by which they occur. Methods We have examined the matrix metalloproteinase (MMP protein degradation system in two previously published anti-Aβ immunotherapy studies. The first was a passive immunization study in which we examined 22 month old APPSw mice that had received anti-Aβ antibodies for 1, 2 or 3 months. The second is an active vaccination study in which we examined 16 month old APPSw/NOS2-/- mice treated with Aβ vaccination for 4 months. Results There is a significant activation of the MMP2 and MMP9 proteinase degradation systems by anti-Aβ immunotherapy, regardless of whether this is delivered through active vaccination or passive immunization. We have characterized this activation by gene expression, protein expression and zymography assessment of MMP activity. Conclusions Since the MMP2 and MMP9 systems are heavily implicated in the pathophysiology of intracerbral hemorrhage, these data may provide a potential mechanism of microhemorrhage due to immunotherapy. Increased activity of the MMP system, therefore, is likely to be a major factor in increased microhemorrhage occurrence.

  10. Intracellular matrix metalloproteinase-2 (MMP-2) regulates human platelet activation via hydrolysis of talin.

    Soslau, Gerald; Mason, Christopher; Lynch, Stephen; Benjamin, James; Ashak, Dani; Prakash, Jamunabai M; Moore, Andrew; Bagsiyao, Pamela; Albert, Trevine; Mathew, Lynn M; Jost, Monika

    2014-01-01

    Matrix metalloproteinase (MMP) activity is generally associated with normal or pathological extracellular processes such as tissue remodelling in growth and development or in tumor metastasis and angiogenesis. Platelets contain at least three MMPs, 1, 2 and 9 that have been reported to stimulate or inhibit agonist-induced platelet aggregation via extracellular signals. The non-selective Zn+2 chelating MMP inhibitor, 1,10-phenanthroline, and the serine protease inhibitor, AEBSF, were found to inhibit all tested agonist-induced platelet aggregation reactions. In vitro analysis demonstrated that 1,10-phenanthroline completely inhibited MMP-1,2,and 9 but had little to no effect on calpain activity while the converse was true with AEBSF. We now demonstrate that MMP-2 functions intracellularly to regulate agonist-induced platelet aggregations via the hydrolytic activation of talin, the presumed final activating factor of glycoprotein (GP)IIb/IIIa integrin (the inside-out signal). Once activated GPIIb/IIIa binds the dimeric fibrinogen molecule required for platelet aggregation. The active intracellular MMP-2 molecule is complexed with JAK 2/STAT 3, as demonstrated by the fact that all three proteins are co-immunoprecipitated with either anti-JAK 2, or anti-STAT 3 antibodies and by immunofluorescence studies. The MMP-2 platelet activation pathway can be synergistically inhibited with the non-selective MMP inhibitor, 1,10-phenanthroline, plus a JAK 2 inhibitor. This activation pathway is distinct from the previously reported calpain-talin activating pathway. The identification of a new central pathway for platelet aggregation presents new potential targets for drug regulation and furthers our understanding of the complexity of platelet activation mechanisms.

  11. Homogeneously embedded Pt nanoclusters on amorphous titania matrix as highly efficient visible light active photocatalyst material

    Sharma, Vipul; Kumar, Suneel; Krishnan, Venkata, E-mail: vkn@iitmandi.ac.in

    2016-08-15

    A novel and facile technique, based on colloidal synthesis route, has been utilized for the preparation of homogeneously embedded Pt nanoclusters on amorphous titania matrix. The material has been thoroughly characterized using high resolution transmission electron microscopy, energy dispersive x-ray analysis, powder x-ray diffraction, optical and Raman spectroscopic techniques to understand the morphology, structure and other physical characteristics. The photocatalytic activity of the material under visible light irradiation was demonstrated by investigations on the degradation of two organic dyes (methylene blue and rhodamine B). In comparison to other Pt−TiO{sub 2} based nanomaterials (core-shell, doped nanostructures, modified nanotubes, decorated nanospheres and binary nanocomposites), the embedded Pt nanoclusters on titania was found to be highly efficient for visible light active photocatalytic applications. The enhanced catalytic performance could be attributed to the efficient charge separation and decreased recombination of the photo generated electrons and holes at the Pt-titania interface and the availability of multiple metal-metal oxide interfaces due to homogeneous embedment of Pt nanoclusters on amorphous titania. In essence, this work illustrates that homogeneous embedment of noble metal nanoparticles/nanoclusters on semiconductor metal oxide matrices can lead to tuning of the photophysical properties of the final material and eventually enhance its photocatalytic activity. - Highlights: • Homogeneously embedded Pt nanoclusters on amorphous titania matrix has been prepared. • Facile low temperature colloidal synthesis technique has been used. • Enhanced catalytic performance could be observed. • Work can pave way for tuning photocatalytic activity of composite materials.

  12. Resveratrol as a novel agent for treatment of multiple myeloma with matrix metalloproteinase inhibitory activity

    Chun-yan SUN; Yu HU; Tao GUO; Hua-fang WANG; Xiao-ping ZHANG; Wen-juan HE; Hao TAN

    2006-01-01

    Aim: To examine the in vitro antitumor activity of resveratrol against multiple myeloma (MM) cell lines (RPMI 8226, U266, and KM3), and the mechanisms involved. Methods: The growth inhibition of resveratrol was determined by 3-(4, 5-dimethyl-2-thiazyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The effect of resveratrol on the apoptosis was investigated by combined annexin V-propidium iodide staining. The effect of resveratrol on the invasion through Matrigel matrix was detected by transwell invasion analyses. The activity of matrix metalloproteinase (MMP)-2 and -9 proteins were determined by gelatin zymography analysis. The expression of MMP-2, MMP-9, Bcl-2, Bcl-xL, XIAP and Bax protein were detected using Western blotting analysis. Results: Resveratrol inhibited proliferation of MM cells in a dose- and time-dependent manner. Incubation of MM cells with resveratrol resulted in apoptotic cell death. Resveratrol down-regulated the expression of the antiapoptotic proteins Bcl-2, Bcl-xL and XIAP and up-regulated the expression of the proapoptotic protein Bax. Furthermore, resveratrol inhibited invasion of RPMI 8226, U266, and KM3 cells with IC50 values of 64±8 μmol/L, 93±11 μmol/L, and 153±11 μmol/L, respectively. Resveratrol inhibited the constitutive expression of MMP-2 and -9 proteins of MM cells and suppressed its gelatinolytic activity. Conclusion: Resveratrol inhibits the proliferation of MM cells by inducing apoptotic cell death. Resveratrol also inhibits MM cell invasion. The inhibition of invasion may be associated with the attenuation of the enzymatic activities of MMP-2 and -9.

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

    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.

  14. Performance of Mo-V-Te-P catalysts supported on the SiC for propane selective oxidation to acrolein

    Yang Wang; Fei Ma; Shu Chen; Fang Chen; Wei Min Lu

    2011-01-01

    A series of MoTe0.15V0.1PxOn catalysts supported on the SiC were prepared by incipient wetness impregnation. The addition of P to MoTe0.15V0.1On/SiC catalysts improved the catalytic performance of selective oxidation from propane to acrolein (ACR), and the catalyst showed highest selectivity (33.7%) and yield (10.7%) when x = 0.05. The MoTe0.15Vo.1PxOn/SiC catalysts have been characterized by XRD, H2-TPR, Raman, XPS and NH3-TPD. The results indicated that a little H3PMo122O40 heteropoly acid and (VO)2P2O7 formed and M0O3 phase lessened after addition of P. The addition of P promoted the active species dispersed, increased the acidity on the surface, as well as might make the redox process easier. These significant differences improved the activity and selectivity of ACR.

  15. Inhibition of matrix metalloproteinase activity in human dentin via novel antibacterial monomer

    Li, Fang; Majd, Hessam; Weir, Michael D.; Arola, Dwayne D.; Xu, Hockin H.K.

    2015-01-01

    Objectives Dentin-composite bond failure is caused by factors including hybrid layer degradation, which in turn can be caused by hydrolysis and enzymatic degradation of the exposed collagen in the dentin. The objectives of this study were to investigate a new antibacterial monomer (dimethylaminododecyl methacrylate, DMADDM) as an inhibitor for matrix metalloproteinases (MMPs), and to determine the effects of DMADDM on both soluble recombinant human MMPs (rhMMPs) and dentin matrix-bound endogenous MMPs. Methods Inhibitory effects of DMADDM at six mass% (0.1% to 10%) on soluble rhMMP-8 and rhMMP-9 were measured using a colorimetic assay. Matrix-bound endogenous MMP activity was evaluated in demineralized human dentin. Dentin beams were divided into four groups (n = 10) and incubated in calcium- and zinc-containing media (control medium); or control medium + 0.2% chlorhexidine (CHX); 5% 12-methacryloyloxydodecylpyridinium bromide (MDPB); or 5% DMADDM. Dissolution of dentin collagen peptides was evaluated by mechanical testing in three-point flexure, loss of dentin mass, and a hydroxyproline assay. Results Use of 0.1% to 10% DMADDM exhibited a strong concentration-dependent anti-MMP effect, reaching 90% of inhibition on rhMMP-8 and rhMMP-9 at 5% DMADDM concentration. Dentin beams in medium with 5% DMADDM showed 34% decrease in elastic modulus (vs. 73% decrease for control), 3% loss of dry dentin mass (vs. 28% loss for control), and significantly less solubilized hydroxyproline when compared with control (p dentin MMPs. These results, together with previous studies showing that adhesives containing DMADDM inhibited biofilms without compromising dentin bond strength, suggest that DMADDM is promising for use in adhesives to prevent collagen degradation in hybrid layer and protect the resin-dentin bond. PMID:25595564

  16. Increasing in activity and plasma concentration of matrix metalloproteinase-9 in metastatic breast cancer patients

    Morteza Sadeghi1

    2009-01-01

    Full Text Available (Received 30 March, 2009 ; Accepted 22 July, 2009AbstractBackground and purpose: Matrix metalloproteinase are a family of proteolytic enzymes that have specific functions in digestion of cells cohesive extra cellular matrix and also, increasing metastasis behavior of acute human tumors. It has been reported that MMPs in two forms, namely proenzyme and active enzyme in biological samples. It is distinguished that among this family, (MMP-9 Matrix Metalloproteinase-9 has function in both initiation and invasion steps of breast cancer. In our previous study, we reported a correlation between C/T polymorphism at promoter region of this gene and metastasis step of breast cancer.Considering few findings regarding the relationship between the active form of this enzyme and occurrence of cancer, and also the correlation between active form and allelic genotype of persons, in this study we decided to do a parallel study on measurement of active plasma MMP-9 and its relationship with allelic genotype of breast cancer patients.Materials and methods: After analysis of data, we found that concentration of active MMP-9 has a significant difference in breast cancer patients in comparison with control group, as the concentration of active form of this enzyme was less in control group than the breast cancer patients group (0.7 ng and 1.7 ng respectively. Thus, the level of active MMP-9 showed a significant increase in persons with CT and TT genotypes in comparison with CC genotype (1.5 folds.Results: The present data suggest the concentration of active MMP-9 in breast cancer patients has significantly increased in comparison with the control group and the increased in plasma level of this enzyme is related with the existence of T allele at this gene promoter and also in progression of breast cancer in these patients. We can use the active plasma level of this enzyme or the existence of T allele as a diagnostic tool for discriminating subgroups of breast cancer

  17. The matrix-binding domain of microfibril-associated glycoprotein-1 targets active connective tissue growth factor to a fibroblast-produced extracellular matrix.

    Weinbaum, Justin S; Tranquillo, Robert T; Mecham, Robert P

    2010-11-10

    It is advantageous to use biomaterials in tissue engineering that stimulate extracellular matrix (ECM) production by the cellular component. Connective tissue growth factor (CTGF) stimulates type I collagen (COL1A1) transcription, but is functionally limited as a free molecule. Using a matrix-binding domain (MBD) from microfibril-associated glycoprotein-1, the fusion protein MBD-CTGF was targeted to the ECM and tested for COL1A1 transcriptional activation. MBD-CTGF produced by the ECM-synthesizing fibroblasts, or provided exogenously, localized to the elastic fiber ECM. MBD-CTGF, but not CTGF alone, led to a two-fold enhancement of COL1A1 expression. This study introduces a targeting technology that can be used to elevate collagen transcription in engineered tissues and thereby improve tissue mechanics.

  18. Taiwanese Native Plants Inhibit Matrix Metalloproteinase-9 Activity after Ultraviolet B Irradiation

    Yueh-Lun Lee

    2009-03-01

    Full Text Available Medicinal plants have long been used as a source of therapeutic agents. They are thought to be important anti-aging ingredients in prophylactic medicines. The aim of this study was to screen extracts from Taiwanese plant materials for phenolic contents and measure the corresponding matrix metalloproteinase-9 (MMP-9 activity. We extracted biological ingredients from eight plants native to Taiwan (Alnus formosana, Diospyros discolor, Eriobotrya deflex, Machilus japonica, Pyrrosia polydactylis, Pyrus taiwanensis, Vitis adstricta, Vitis thunbergii. Total phenolic content was measured using the Folin-Ciocalteu method. MMP-9 activities were measured by gelatin zymography. The extracted yields of plants ranged from 3.7 % to 16.9 %. The total phenolic contents ranged from 25.4 to 36.8 mg GAE/g dry material. All of these extracts (except Vitis adstricta Hance were shown to inhibit MMP-9 activity of WS-1 cell after ultraviolet B irradiation. These findings suggest that total phenolic content may influence MMP-9 activity and that some of the plants with higher phenolic content exhibited various biological activities that could serve as potent inhibitors of the ageing process in the skin. This property might be useful in the production of cosmetics.

  19. Effects of cytokines, growth factors and drugs on matrix metalloproteinases activities of osteoarthritic chondrocytes and synoviocytes

    GUAN Jian-long; HAN Xing-hai; SHI Gui-ying; YUAN Guo-hua

    2001-01-01

    Objective: To evaluate the effects of some cytokines, TGF-β1 and drugs on matrix metalloproteinases (MMPs) activities in culture medium of arthritic chondrocytes and synoviocytes. Methods: The chondrocyte and synoviocyte monolayers isolated from the cartilages and synovial fluids in 10 knee OA patients were treated with IL-1β TGF-β1, TNF-α, diclofenac acid, dexamethasone or doxycycline individually and together for 72 h. Zymography was used to determine the activities of MMP-2 and -9. Results: The chondrocyte monolayers produced MMP-2 and -9, while the synoviocytes only produced MMP-2. The MMP-9 activity was markedly enhanced by IL-1β TNF-α and diclofenac. IL-1β was the most effective stimulus, and had synergistic effect with TNF-α or diclifenac. MMP-2 activity was not affected. Doxcycline, TGF-β1 and dexamethasone could depress the activities of MMP-9 and MMP-2, and antagonize the enhancing effect of IL-1β TNF-α or diclofenac. Conclusion: IL-1β and TNF-α may play important roles degrading OA cartilage, while TGF-β1 and doxycycline may be protective factors.

  20. Optical Imaging of Matrix Metalloproteinase-7 Activity in Vivo Using a Proteolytic Nanobeacon

    Randy L. Scherer

    2008-05-01

    Full Text Available Matrix metalloproteinases (MMPs are extracellular proteolytic enzymes involved in tumor progression. We present the in vivo detection and quantitation of MMP7 activity using a specific near-infrared polymer-based proteolytic beacon, PB-M7NIR. PB-M7NIR is a pegylated polyamidoamine PAMAM-Generation 4 dendrimer core covalently coupled to a Cy5.5-labeled peptide representing a selective substrate that monitors MMP7 activity (sensor and AF750 as an internal reference to monitor relative substrate concentration (reference. In vivo imaging of tumors expressing MMP7 had a median sensor to reference ratio 2.2-fold higher than a that of a bilateral control tumor. Ex vivo imaging of intestines of multiple intestinal neoplasia (APCMin mice injected systemically with PB-M7NIR revealed a sixfold increase in the sensor to reference ratio in the adenomas of APCMin mice compared with control intestinal tissue or adenomas from MMP7-null Min mice. PB-M7NIR detected tumor sizes as small as 0.01 cm2, and the sensor to reference ratio was independent of tumor size. Histologic sectioning of xenograft tumors localized the proteolytic signal to the extracellular matrix; MMP7-overexpressing tumors displayed an approximately 300-fold enhancement in the sensor to reference ratio compared with nonexpressing tumor cells. In APCMin adenomas, the proteolytic signal colocalized with the endogenously expressed MMP7 protein, with sensor to reference ratios approximately sixfold greater than that of normal intestinal epithelium. PB-M7NIR provides a useful reagent for the in vivo and ex vivo quantitation and localization of MMP-selective proteolytic activity.

  1. Peptide from the C-terminal domain of tissue inhibitor of matrix metalloproteinases-2 (TIMP-2) inhibits membrane activation of matrix metalloproteinase-2 (MMP-2).

    Xu, Xiaoping; Mikhailova, Margarita; Chen, Zhihua; Pal, Sanjay; Robichaud, Trista K; Lafer, Eileen M; Baber, Sam; Steffensen, Bjorn

    2011-09-01

    Cellular activation of latent matrix metalloproteinase-2 (proMMP-2) requires formation of a cell membrane-associated activation complex that involves specific binding between the hemopexin domain of proMMP-2 (PEX) and the C-terminal domain of tissue inhibitor of matrix metalloproteinases-2 (C-TIMP-2). In this study, we tested the feasibility of inhibiting activation of proMMP-2 by exogenous inhibitors, which block the binding between PEX and TIMP-2. The recombinant C-TIMP-2 and synthetic peptides from C-TIMP-2 were used as inhibitors for proMMP-2 activation. Recombinant C-TIMP-2 bound specifically to both the catalytically inactive MMP-2(E404A) and the C-terminal domain of MMP-2 (PEX) in a concentration dependent manner with apparent K(d) of 3.9×10(-7)M and 1.7×10(-7)M, respectively. Moreover, C-TIMP-2 competed the binding between MMP-2(E404A) and full-length TIMP-2. Finally, activity assays showed that addition of C-TIMP-2 to HT-1080 fibrosarcoma cells inhibited proMMP-2 activation in a concentration-dependent manner. We then designed a synthetic peptide, P175L, consisting of 20 residues from the PEX-binding tail region of C-TIMP-2. P175L bound PEX and inhibited cell membrane-mediated activation of proMMP-2 in a concentration dependent manner. Deletion of the last 9 tail residues of C-TIMP-2 in P175L abrogated the inhibitory activities of the peptide showing that these residues were essential for function. Overall, these experiments have demonstrated that proMMP-2 activation can be inhibited by exogenous inhibitors which points to a potential strategy for MMP-2 specific inhibition.

  2. Performance and modeling of active metal-matrix composites manufactured by ultrasonic additive manufacturing

    Hahnlen, Ryan; Dapino, Marcelo J.

    2011-04-01

    This paper presents the development and characterization of active aluminum-matrix composites manufactured by Ultrasonic Additive Manufacturing (UAM), an emerging rapid prototyping process based on ultrasonic metal welding. The primary benefit of UAM over other metal-matrix fabrication processes is the low process temperatures, as low as 25 °C. UAM thus provides unprecedented opportunities to develop adaptive structures with seamlessly embedded smart materials and electronic components without degrading the properties that make these materials and components attractive. The objective of this research is to develop UAM composites with aluminum matrices and embedded shape memory NiTi, magnetostrictive Galfenol (FeGa), and polyvinylidene fluoride (PVDF) phases. The paper is focused on the thermally induced strain response and stiffness behavior of NiTi-Al composites, the actuation properties of FeGa-Al composites, and the embedded sensing capabilities of PVDF-Al composites. We observe up to a 10% increase over room temperature stiffness for NiTi-Al composites and a magnetomechanical response in the FeGa-Al composite up to 52.4 μɛ. The response of the PVDF-Al composite to harmonic loads is observed over a frequency range of 10 to 1000 Hz.

  3. The dimers of glyoxal and acrolein with H 2O and HF: Negative intramolecular coupling and blue-shifted C-H stretch

    Karpfen, Alfred; Kryachko, Eugene S.

    2010-04-01

    The structures and the vibrational spectra of the hydrogen-bonded complexes: glyoxal-H 2O, glyoxal-HF, acrolein-H 2O, and acrolein-HF, are investigated within the MP2/aug-cc-pVTZ computational approach. It is demonstrated that the calculated blue shifts of the C-H stretching frequencies in the glyoxal-H 2O complexes are only indirectly pertinent to hydrogen bonding to the C-H group. The comparison with the glyoxal-HF and the acrolein-HF complexes reveals that these blue shifts are a direct consequence of a negative intramolecular coupling between vicinal C dbnd O and C-H bonds in the aldehyde groups of isolated glyoxal and acrolein molecules. To support this interpretation, the halogen-bonded complexes glyoxal-BrF and acrolein-BrF are discussed.

  4. 甘油脱水制丙烯醛催化剂的研究进展%Research progress in glycerol dehydration to acrolein

    黄士学; 崔洪友; 钱绍松; 谷俊峰; 卜小蒙

    2012-01-01

    With the increasing of biodiesel production,a large volume of byproduct glycerol has led to a market surplus.Dehydration of glycerol to acrolein is considered to be an efficient and effective route to improve the economic efficiency of biodiesel production.The reaction characteristics of glycerol dehydration to acrolein under the liquid phase,gas phase and sub-/supercritical water conditions are analyzed.The emphasis is given to the catalysts for glycerol dehydration in gas phase.Effects of microstructure,acidity of the active phase and redox site on the catalytic activity,selectivity and longevity are discussed.The causes for catalyst deactivation are also involved.Moreover,the reaction mechanisms of glycerol dehydration proposed in the literature are presented and the research work in glycerol dehydration to acrolein in the future is proposed.%伴随着生物柴油的产量不断增大,大量副产的甘油导致了市场过剩。甘油脱水制取丙烯醛是提高生物柴油经济性的一条有效途径。本文结合近年来甘油脱水制丙烯醛的研究进展情况,分析了液相、气相以及超(亚)临界条件下该反应的特点,重点阐述了气相脱水催化剂的研究进展,讨论了催化剂的微观结构、活性组分的酸碱性和氧化还原位等对催化剂活性、选择性和寿命等的影响,分析了催化剂失活的原因。此外,还讨论了甘油脱水过程的反应机理,指出了今后甘油脱水制丙烯醛的研究方向。

  5. Expression and activity of matrix metalloproteinases in the uterus of bitches after spontaneous and induced abortion.

    Kanca, H; Walter, I; Miller, I; Schäfer-Somi, S; Izgur, H; Aslan, S

    2011-04-01

    Aim of this study was to determine the intrauterine activity of matrix metalloproteinases (MMP)-2 and -9 after cessation of the local effect of progesterone. For this purpose, pregnancy was terminated in 10 bitches at mid-gestation with the progesterone receptor antagonist aglepristone (10 mg/kg body weight, sc, Alizine®; Virbac, France) at two subsequent days (group IRA = induced resorption/abortion). The IRA group was divided into two subgroups (Group I, n = 5, days 25-35 of pregnancy; group II, n = 5, days 36-45). Five further bitches were introduced with beginning abortion (group SRA = spontaneous resorption/abortion). Seven healthy bitches between day 25 and 45 of gestation served as controls. After ovariohysterectomy at the end of abortion and between days 25 and 45 of gestation, respectively, the distribution and activity of collagenases were investigated by immunohistochemistry and gelatin zymography. At placental sites, MMP-2 activity in the endometrium was significantly lower in IRA groups than in the SRA group (33.7 ± 11.8% and 39.3 ± 5.4% vs 52.2 ± 10.2%, p control group (control: 21.4 ± 6.3%; p controls: 13.1 ± 2.5%; p control group in comparison to SRA and IRA groups (11.8 ± 3.2%; p control group. It is concluded that the blockade of the biological progesterone effect was associated with an increase in activity of both collagenases.

  6. Matrix metalloproteinase-9 and urokinase plasminogen activator mediate interleukin-1-induced neurotoxicity.

    Thornton, Peter; Pinteaux, Emmanuel; Allan, Stuart M; Rothwell, Nancy J

    2008-01-01

    Matrix metalloproteinases (MMPs) are endopeptidases known to mediate acute neuronal injury, but it is unclear whether these proteases are induced by the primary insult or by inflammation associated with injury. We have reported recently that interleukin-1 (IL-1) induces neurotoxicity by an astrocyte-dependent mechanism. The aim of the present study was to test the hypothesis that MMPs mediate IL-1 neurotoxicity in rat, glial-neuronal cocultures. IL-1beta induced the release of astrocytic MMP-9 in cocultures, whilst an antagonist of MMP-9 inhibited IL-1beta-induced neuronal death. Urokinase plasminogen activator (uPA) was constitutively expressed on neuronal membrane fractions, and amiloride (an antagonist of uPA) or plasminogen activator inhibitor (PAI)-1 significantly reduced IL-1beta-induced neurotoxicity. Thus, neuronal uPA contributes to IL-1 neurotoxicity, and may be responsible for activating MMP-9 released from IL-1-primed astrocytes. In summary, IL-1-induced neurotoxicity is dependent on extracellular protease activity, and these mechanisms may contribute to neuronal cell death in CNS diseases.

  7. Characterization and Synthesis of Silver Nanostructures in Rare Earth Activated GeO2-PbO Glass Matrix Using Matrix Adjustment Thermal Reduction Method

    Hj. A. A. Sidek

    2013-04-01

    Full Text Available This paper reports matrix adjustment thermal reduction method to synthesize silver nanostructures in Er3+/Yb3+ activated GeO2-PbO glass matrix. The GeO2-PbO glass, the medium of nanoparticle formation, doped with Er2O3, Yb2O3 and AgNO3 was prepared by a melt quenching method. Annealing of the glass for different times was utilized, not only due to thermally reduce Ag+ ions to Ag nanostructures, but also to influence the glassy network. This is because, the glass structural transformation temperature is near to 435 °C and heating at more than this temperature can cause some structural changes in the glass matrix. According to TEM images, samples that tolerate 450 °C annealing temperature for one hour show the formation of basil-like silver nanostructures with a mean length of 54 nm and mean diameter of 13 nm embedded in the glass matrix, whereas with annealing at 450 °C for 5 to 20 h, silver nanoparticles of about 3–4 nm mean diameter size are formed. Annealing for 30 h causes silver nanoparticles to aggregate to form larger particles due to an Oswald ripening process. Observation of the characteristic Ag-NP SPR band at 400–500 nm in the UV-visible absorption spectra confirms the existence of silver nanoparticles. The SPR band widens to longer wavelengths in one hour annealed samples, which relates to the existence of nanostructures with different size or fractal shapes. In addition, an increment in the peak of the SPR band by increasing the duration of annealing indicates the formation of more nanoparticles. Furthermore, the existence of a peak at 470 cm–1 in the FTIR spectra of annealed samples and its absence in the samples not exposed to an annealing process suggests that the glass matrix is polymerized by Pb-O chains during the 450 °C annealing process. This is the main source of different nanostructures because of the dissimilar stabilizing media. The tighter media cap the particles to form small and dense nanoparticles but a

  8. Acrolein increases macrophage atherogenicity in association with gut microbiota remodeling in atherosclerotic mice: protective role for the polyphenol-rich pomegranate juice.

    Rom, Oren; Korach-Rechtman, Hila; Hayek, Tony; Danin-Poleg, Yael; Bar, Haim; Kashi, Yechezkel; Aviram, Michael

    2016-09-30

    The unsaturated aldehyde acrolein is pro-atherogenic, and the polyphenol-rich pomegranate juice (PJ), known for its anti-oxidative/anti-atherogenic properties, inhibits macrophage foam cell formation, the hallmark feature of early atherosclerosis. This study aimed to investigate two unexplored areas of acrolein atherogenicity: macrophage lipid metabolism and the gut microbiota composition. The protective effects of PJ against acrolein atherogenicity were also evaluated. Atherosclerotic apolipoprotein E-deficient (apoE(-/-)) mice that were fed acrolein (3 mg/kg/day) for 1 month showed significant increases in serum and aortic cholesterol, triglycerides, and lipid peroxides. In peritoneal macrophages isolated from the mice and in J774A.1 cultured macrophages, acrolein exposure increased intracellular oxidative stress and stimulated cholesterol and triglyceride accumulation via enhanced rates of their biosynthesis and over-expression of key regulators of cellular lipid biosynthesis: sterol regulatory element-binding proteins (SREBPs), 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR), and diacylglycerol acyltransferase1 (DGAT1). Acrolein-fed mice demonstrated a major shift in the gut microbiota composition, including a significant phylum-level change in increased Firmicutes and decreased Bacteroidetes. At the family level, acrolein significantly increased the prevalence of Ruminococcaceae and Lachnospiraceae of which the Coprococcus genus was significantly and positively correlated with serum, aortic and macrophage lipid levels and peroxidation. The pro-atherogenic effects of acrolein on serum, aortas, macrophages, and the gut microbiota were substantially abolished by PJ. In conclusion, these findings provide novel mechanisms by which acrolein increases macrophage lipid accumulation and alters the gut microbiota composition in association with enhanced atherogenesis. Moreover, PJ was found as an effective strategy against acrolein atherogenicity.

  9. NMR investigation of acrolein stability in hydroalcoholic solution as a foundation for the valid HS-SPME/GC–MS quantification of the unsaturated aldehyde in beverages

    Kächele, Martin [Chemisches und Veterinäruntersuchungsamt (CVUA) Karlsruhe, Weissenburger Strasse 3, D-76187 Karlsruhe (Germany); Hochschule Mannheim, Paul-Wittsack-Strasse 10, D-68163 Mannheim (Germany); Monakhova, Yulia B. [Chemisches und Veterinäruntersuchungsamt (CVUA) Karlsruhe, Weissenburger Strasse 3, D-76187 Karlsruhe (Germany); Bruker Biospin GmbH, Silbersteifen, 76287 Rheinstetten (Germany); Department of Chemistry, Saratov State University, Astrakhanskaya Street 83, 410012 Saratov (Russian Federation); Kuballa, Thomas [Chemisches und Veterinäruntersuchungsamt (CVUA) Karlsruhe, Weissenburger Strasse 3, D-76187 Karlsruhe (Germany); Lachenmeier, Dirk W., E-mail: lachenmeier@web.de [Chemisches und Veterinäruntersuchungsamt (CVUA) Karlsruhe, Weissenburger Strasse 3, D-76187 Karlsruhe (Germany); Ministry of Rural Affairs and Consumer Protection, Kernerplatz 10, 70182 Stuttgart (Germany)

    2014-04-01

    Highlights: • Acrolein in hydroalcoholic solution degrades to 1,3,3-propanetriol and 3-hydroxypropionaldehyde. • Hydroquinone (0.2%) at pH 3.0 stabilizes acrolein solutions. • Quantitative HS-SPME/GC–MS determination of acrolein in alcoholic beverages was developed (LOD 14 μg L⁻¹. • 6 of 117 samples had acrolein levels above the WHO threshold (1500 μg L⁻¹). Abstract: Acrolein (propenal) is found in many foods and beverages and may pose a health hazard due to its cytotoxicity. Considerable knowledge gaps regarding human exposure to acrolein exist, and there is a lack of reliable analytical methods. Hydroalcoholic dilutions prepared for calibration purposes from pure acrolein show considerable degradation of the compound and nuclear magnetic resonance (NMR) spectroscopy showed that 1,3,3-propanetriol and 3-hydroxypropionaldehyde are formed. The degradation can be prevented by addition of hydroquinone as stabilizer to the calibration solutions, which then show linear concentration-response behaviour required for quantitative analysis. The stabilized calibration solutions were used for quantitative headspace solid-phase microextraction/gas chromatography–mass spectrometry (HS-SPME/GC–MS) determination of acrolein in alcoholic beverages with a detection limit of 14 μg L⁻¹. Of 117 tested alcoholic beverages, 64 were tested positive with the highest incidence in grape marc spirits and whiskey (100%, mean 252 μg L⁻¹), followed by fruit spirits (86%, mean 591 μg/L⁻¹), tequila (86%, mean 404 μg L⁻¹), Asian spirits (43%, mean 54 μg L⁻¹) and wine (9%, mean 0.7 μg L⁻¹). Acrolein could not be detected in beer, vodka, absinthe and bottled water. Six of the fruit and grape marc spirits had acrolein levels above the World Health Organization (WHO) provisional tolerable concentration of 1.5 mg L⁻¹.

  10. A Possible Role of Acrolein in Diabetic Retinopathy: Involvement of a VEGF/TGFβ Signaling Pathway of the Retinal Pigment Epithelium in Hyperglycemia

    Grigsby, Jeffery; Betts, Brandi; Vidro-Kotchan, Eileen; Culbert, Richard; Tsin, Andrew

    2015-01-01

    Purpose Acrolein has been implicated in retinal pigment epithelium (RPE) cell death, and has been associated with diabetic retinopathy. Our purpose was to investigate the potential effect of high glucose in influencing acrolein-mediated RPE cytokine production and cell death. We investigated the influence of the acrolein effect on ARPE-19 cells in high glucose conditions and quantified the release of transforming growth factor β (TGFβ1 and 2) and vascular endothelial growth factor (VEGF). We assessed the ability of N-benzylhydroxylamine(NBHA) as well as TGFβ pathway inhibitors SIS3 and SB431542 to prevent this effect of acrolein on ARPE-19 cells. Materials and methods Confluent ARPE-19 cells were treated with acrolein and/or NBHA in both 5.5 and 18.8 mM glucose conditions. Cells were also pretreated with SIS3, a specific inhibitor of the SMAD3 pathway, and SB431542, a specific inhibitor of TGFβ signaling pathway, before treating them with acrolein. Viable cells were counted and ELISAs were performed to measure the cytokines TGFβ1 and 2, and VEGF released into the conditioned media. Results In ARPE-19 cells exposed to acrolein and hyperglycemia there was reduced cell viability and an increase in the cell media of VEGF, TGFβ1, and TGFβ2, which was reversed by NBHA. Acrolein/hyperglycemia-induced cell viability reduction and cytokine overproduction was also reduced by TGFβ pathway blockade. Conclusions We conclude that the effect of acrolein on the reduction of viability and VEGF increase by ARPE-19 cells in hyperglycemic media is conducted through the TGFβ signaling pathway. Our results suggest that benefits of sequestering acrolein by NBHA and the blockage of the TGFβ pathway by SB431542 and SIS3 offer suggestions as to potential useful pharmacological drug candidates for the prevention of diabetes-induced complications in the eye. PMID:22906079

  11. Quantum Monte Carlo calculations of electronic excitation energies: the case of the singlet $n \\to \\pi^*$ (CO) transition in acrolein

    Toulouse, Julien; Reinhardt, Peter; Hoggan, Philip E; Umrigar, C J

    2010-01-01

    We report state-of-the-art quantum Monte Carlo calculations of the singlet $n \\to \\pi^*$ (CO) vertical excitation energy in the acrolein molecule, extending the recent study of Bouab\\c{c}a {\\it et al.} [J. Chem. Phys. {\\bf 130}, 114107 (2009)]. We investigate the effect of using a Slater basis set instead of a Gaussian basis set, and of using state-average versus state-specific complete-active-space (CAS) wave functions, with or without reoptimization of the coefficients of the configuration state functions (CSFs) and of the orbitals in variational Monte Carlo (VMC). It is found that, with the Slater basis set used here, both state-average and state-specific CAS(6,5) wave functions give an accurate excitation energy in diffusion Monte Carlo (DMC), with or without reoptimization of the CSF and orbital coefficients in the presence of the Jastrow factor. In contrast, the CAS(2,2) wave functions require reoptimization of the CSF and orbital coefficients to give a good DMC excitation energy. Our best estimates of ...

  12. Novel Digital Driving Method Using Dual Scan for Active Matrix Organic Light-Emitting Diode Displays

    Jung, Myoung Hoon; Choi, Inho; Chung, Hoon-Ju; Kim, Ohyun

    2008-11-01

    A new digital driving method has been developed for low-temperature polycrystalline silicon, transistor-driven, active-matrix organic light-emitting diode (AM-OLED) displays by time-ratio gray-scale expression. This driving method effectively increases the emission ratio and the number of subfields by inserting another subfield set into nondisplay periods in the conventional digital driving method. By employing the proposed modified gravity center coding, this method can be used to effectively compensate for dynamic false contour noise. The operation and performance were verified by current measurement and image simulation. The simulation results using eight test images show that the proposed approach improves the average peak signal-to-noise ratio by 2.61 dB, and the emission ratio by 20.5%, compared with the conventional digital driving method.

  13. Driving technology for improving motion quality of active-matrix organic light-emitting diode display

    Kim, Jongbin; Kim, Minkoo; Kim, Jong-Man; Kim, Seung-Ryeol; Lee, Seung-Woo

    2014-09-01

    This paper reports transient response characteristics of active-matrix organic light emitting diode (AMOLED) displays for mobile applications. This work reports that the rising responses look like saw-tooth waveform and are not always faster than those of liquid crystal displays. Thus, a driving technology is proposed to improve the rising transient responses of AMOLED based on the overdrive (OD) technology. We modified the OD technology by combining it with a dithering method because the conventional OD method cannot successfully enhance all the rising responses. Our method can improve all the transitions of AMOLED without modifying the conventional gamma architecture of drivers. A new artifact is found when OD is applied to certain transitions. We propose an optimum OD selection method to mitigate the artifact. The implementation results show the proposed technology can successfully improve motion quality of scrolling texts as well as moving pictures in AMOLED displays.

  14. Voltage Drop Compensation Method for Active Matrix Organic Light Emitting Diode Displays

    Choi, Sang-moo; Ryu, Do-hyung; Kim, Keum-nam; Choi, Jae-beom; Kim, Byung-hee; Berkeley, Brian

    2011-03-01

    In this paper, the conventional voltage drop compensation methods are reviewed and the novel design and driving scheme, the advanced power de-coupled (aPDC) driving method, is proposed to effectively compensate the voltage IR drop of active matrix light emitting diode (AMOLED) displays. The advanced PDC driving scheme can be applied to general AMOLED pixel circuits that have been developed with only minor modification or without requiring modification in pixel circuit. A 14-in. AMOLED panel with the aPDC driving scheme was fabricated. Long range uniformity (LRU) of the 14-in. AMOLED panel was improved from 43% without the aPDC driving scheme, to over 87% at the same brightness by using the scheme and the layout complexity of the panel with new design scheme is less than that of the panel with the conventional design scheme.

  15. Low-Voltage, Low-Power, Organic Light-Emitting Transistors for Active Matrix Displays

    McCarthy, M. A.; Liu, B.; Donoghue, E. P.; Kravchenko, I.; Kim, D. Y.; So, F.; Rinzler, A. G.

    2011-04-01

    Intrinsic nonuniformity in the polycrystalline-silicon backplane transistors of active matrix organic light-emitting diode displays severely limits display size. Organic semiconductors might provide an alternative, but their mobility remains too low to be useful in the conventional thin-film transistor design. Here we demonstrate an organic channel light-emitting transistor operating at low voltage, with low power dissipation, and high aperture ratio, in the three primary colors. The high level of performance is enabled by a single-wall carbon nanotube network source electrode that permits integration of the drive transistor and the light emitter into an efficient single stacked device. The performance demonstrated is comparable to that of polycrystalline-silicon backplane transistor-driven display pixels.

  16. Inhibitory Effects of Polygoni Multiflori Caulis Extracts on Matrix Metalloproteinase Activities

    LIU Jun-song; YANG Jin-gang; HONG Yuan; JIN Feng-hai; WANG Ming-cui; ZHAO Shu-hua; FANG Xue-xun

    2009-01-01

    Matrix metalloproteinases(MMPs) play an essential role in development and tissue remodeling of living organisms.However,the overexpression of MMPs has lead to a series of diseases,such as cancer,arthritis,and atherosclerosis;and inhibition of MMPs may have therapeutic benefits.The discovery of MMP inhibitors from herbal has become a prospective event.We showed that the extract of Polygoni multiflori caulis from ethy1 acetate or water(ethy1 acetate extract and water extract) can inhibit the activities of MMPs 9,14,and 16 in a dose-dependent manner and n-buty1 alcohol extract of it can also inhibit these MMPs.Furthermore,we found that n-buty1 alcohol extract and water extract of it influence the cell viability.These discoveries may contribute to the development of MMP inhibitors for the therapy of a variety of pathological conditions.

  17. MONOLITHIC ACTIVE PIXEL MATRIX WITH BINARY COUNTERS IN AN SOI PROCESS.

    DUPTUCH,G.; YAREMA, R.

    2007-06-07

    The design of a Prototype monolithic active pixel matrix, designed in a 0.15 {micro}m CMOS SOI Process, is presented. The process allowed connection between the electronics and the silicon volume under the layer of buried oxide (BOX). The small size vias traversing through the BOX and implantation of small p-type islands in the n-type bulk result in a monolithic imager. During the acquisition time, all pixels register individual radiation events incrementing the counters. The counting rate is up to 1 MHz per pixel. The contents of counters are shifted out during the readout phase. The designed prototype is an array of 64 x 64 pixels and the pixel size is 26 x 26 {micro}m{sup 2}.

  18. Cartilage oligomeric matrix protein in patients with juvenile idiopathic arthritis: relation to growth and disease activity

    Bjørnhart, Birgitte; Juul, Anders; Nielsen, Susan;

    2009-01-01

    : 87 patients with JIA entered the study, including oligoarticular JIA (n = 34), enthesitis-related arthritis (n = 8), polyarticular rheumatoid factor (RF)-positive JIA (n = 2), polyarticular RF-negative JIA (n = 27), systemic JIA (n = 6), and undifferentiated JIA (n = 10). Plasma levels of COMP were......OBJECTIVE: Cartilage oligomeric matrix protein (COMP) has been identified as a prognostic marker of progressive joint destruction in rheumatoid arthritis. In this population based study we evaluated associations between plasma concentrations of COMP, disease activity, and growth velocity...... in patients with recent-onset juvenile idiopathic arthritis (JIA). COMP levels in JIA and healthy children were compared with those in healthy adults. Plasma levels of insulin-like growth factor I (IGF-1), which has been associated with COMP expression and growth velocity, were studied in parallel. METHODS...

  19. Monolithic ionizing particle detector based on active matrix of functionally integrated structures

    Murashev, V.N. [National University of Science and Technology “MISIS” (Russian Federation); Legotin, S.A., E-mail: serlego@mail.ru [National University of Science and Technology “MISIS” (Russian Federation); Karmanov, D.E. [Lomonosov Moscow State University, Skobeltsyn Institute of Nuclear Physics (MSU SINP) (Russian Federation); Baryshnikov, F.M.; Didenko, S.I. [National University of Science and Technology “MISIS” (Russian Federation)

    2014-02-15

    Highlights: • A new type of monolithic silicon position detector is presented. • An operating principle, design and technology of the detector are described. • Calculated estimations of the detecting efficiency are carried out. • Experimental results of alpha-particle and electron detection are shown. -- Abstract: An operating principle, design and technology of a new type of the monolithic silicon position detector (MSPD) for registration of ionizing particles and photons are described. The detector represents a specialized monolithic silicon VLSI that contains a two-dimensional detecting matrix of active functionally integrated bipolar structures and peripheral electronic circuitry for signal amplification and processing. This paper presents experimental results of α-particles and electrons detection with position accuracy and operation speed better than 12.5 μm and 1 ns, respectively. The given estimations show the capabilities of this detector and its advantages in comparison with analogs.

  20. Colorimetric characterization models based on colorimetric characteristics evaluation for active matrix organic light emitting diode panels.

    Gong, Rui; Xu, Haisong; Tong, Qingfen

    2012-10-20

    The colorimetric characterization of active matrix organic light emitting diode (AMOLED) panels suffers from their poor channel independence. Based on the colorimetric characteristics evaluation of channel independence and chromaticity constancy, an accurate colorimetric characterization method, namely, the polynomial compensation model (PC model) considering channel interactions was proposed for AMOLED panels. In this model, polynomial expressions are employed to calculate the relationship between the prediction errors of XYZ tristimulus values and the digital inputs to compensate the XYZ prediction errors of the conventional piecewise linear interpolation assuming the variable chromaticity coordinates (PLVC) model. The experimental results indicated that the proposed PC model outperformed other typical characterization models for the two tested AMOLED smart-phone displays and for the professional liquid crystal display monitor as well.

  1. Matrix metalloproteinase 13 mediates nitric oxide activation of endothelial cell migration

    López-Rivera, Esther; Lizarbe, Tania R.; Martínez-Moreno, Mónica; López-Novoa, José Miguel; Rodríguez-Barbero, Alicia; Rodrigo, José; Fernández, Ana Patricia; Álvarez-Barrientos, Alberto; Lamas, Santiago; Zaragoza, Carlos

    2005-01-01

    To explore the mechanisms by which NO elicits endothelial cell (EC) migration we used murine and bovine aortic ECs in an in vitro wound-healing model. We found that exogenous or endogenous NO stimulated EC migration. Moreover, migration was significantly delayed in ECs derived from endothelial NO synthase-deficient mice compared with WT murine aortic EC. To assess the contribution of matrix metalloproteinase (MMP)-13 to NO-mediated EC migration, we used RNA interference to silence MMP-13 expression in ECs. Migration was delayed in cells in which MMP-13 was silenced. In untreated cells MMP-13 was localized to caveolae, forming a complex with caveolin-1. Stimulation with NO disrupted this complex and significantly increased extracellular MMP-13 abundance, leading to collagen breakdown. Our findings show that MMP-13 is an important effector of NO-activated endothelial migration. PMID:15728377

  2. Coordinate regulation of fibronectin matrix assembly by the plasminogen activator system and vitronectin in human osteosarcoma cells

    McKeown-Longo Paula J

    2006-03-01

    Full Text Available Abstract Background Plasminogen activators are known to play a key role in the remodeling of bone matrix which occurs during tumor progression, bone metastasis and bone growth. Dysfunctional remodeling of bone matrix gives rise to the osteoblastic and osteolytic lesions seen in association with metastatic cancers. The molecular mechanisms responsible for the development of these lesions are not well understood. Studies were undertaken to address the role of the plasminogen activator system in the regulation of fibronectin matrix assembly in the osteoblast-like cell line, MG-63. Results Treatment of MG-63 cells with P25, a peptide ligand for uPAR, resulted in an increase in assembly of fibronectin matrix which was associated with an increase in the number of activated β1 integrins on the cell surface. Overexpression of uPAR in MG-63 cells increased the effect of P25 on fibronectin matrix assembly and β1 integrin activation. P25 had no effect on uPAR null fibroblasts, confirming a role for uPAR in this process. The addition of plasminogen activator inhibitor Type I (PAI-1 to cells increased the P25-induced fibronectin polymerization, as well as the number of activated integrins. This positive regulation of PAI-1 on fibronectin assembly was independent of PAI-1's anti-proteinase activity, but acted through PAI-1 binding to the somatomedin B domain of vitronectin. Conclusion These results indicate that vitronectin modulates fibronectin matrix assembly in osteosarcoma cells through a novel mechanism involving cross-talk through the plasminogen activator system.

  3. Matrix metalloproteinases 2 and 9 and MMP9/NGAL complex activity in women with PCOS.

    Ranjbaran, Javad; Farimani, Marzieh; Tavilani, Heidar; Ghorbani, Marzieh; Karimi, Jamshid; Poormonsefi, Faranak; Khodadadi, Iraj

    2016-04-01

    It is believed that matrix metalloproteinases (MMPs) play important roles in follicular development and pathogenesis of polycystic ovary syndrome (PCOS). However, conflicting results are available about the alteration of MMP2 and MMP9 concentrations or activities in PCOS. In fact, there is no study entirely investigating both concentration and activity of these MMPs and serum levels of their tissue inhibitors TIMP2 and TIMP1, as well as lipocalin-bound form of MMP9 (MMP9/NGAL). Therefore, the thoroughness of previous studies is questionable. This study was conducted to determine circulatory concentration of MMP2, MMP9, MMP9/NGAL complex, TIMP1 and TIMP2 as well as gelatinase activities of MMP2, MMP9 and MMP9/NGAL complex in women with PCOS and controls. Mean age and BMI as well as serum levels of total cholesterol, triacylglycerol, HDL-C, LDL-C, fasting blood sugar (FBS), insulin, estradiol and sex hormone-binding globulin did not differ between groups, whereas a marked decrease in FSH and significant increases in LH, LH/FSH ratio, testosterone and free androgen index were observed. Women with PCOS and controls showed closed concentrations of MMP2, MMP9, MMP9/NGAL, TIMP1 and TIMP2. Gelatinase activity of MMP9 was found significantly higher in PCOS than in controls (64.53±15.32 vs 44.61±18.95 respectively) while patients and healthy subjects showed similar activities of MMP2 and MMP9/NGAL complex. Additionally, PCOS patients showed a higher MMP9/TIMP1 ratio compared with control women. Direct correlations were also observed between circulatory MMP9 level and the concentration and activity of MMP9/NGAL complex. In conclusion, based on the results of present study, we believe that MMP9 may be involved in the pathogenesis of PCOS.

  4. Environmental and biological determination of acrolein using new cold fiber solid phase microextraction with gas chromatography mass spectrometry.

    Dias, Cláudia M; Menezes, Helvécio C; Cardeal, Zenilda L

    2017-04-01

    Acrolein is a pollutant released daily to the indoor environment from different sources. The present study reports the development of a simple and sensitive cold fiber solid phase microextraction sampling method for the determination of acrolein in exhaled air and indoor air by gas chromatography mass spectrometry. O-(2,3,4,5,6-pentafluorobenzyl) hydroxylamine was used as derivatizing agent supported on a 65-μm polydimethylsiloxane-divinylbenzene SPME fiber. An acrolein permeation tube at 326.25 ng min(-1) rate was used to generate gaseous standards. The method shows good results for main validation parameters. The limits of detection and quantification were 2.88 and 5.08 μg m(-3), respectively, for indoor analysis; and 2.40 and 3.79 μg m(-3), respectively, for exhaled air analysis. The precision showed standard deviation ranges from 6.00 to 8.00% for intra-assay analyses and from 8.00 to 10.00% for inter-assay analyses. After optimizing the conditions, analyses of real samples were performed on indoor environments contaminated by cigarette smoke, or heated oil, including pastry shops, restaurants, churros stands, and closed parking cars located in the city of Belo Horizonte, Brazil. Acrolein breaths of exposed people were also determined. A good Pearson correlation coefficient (r = 0.901) was observed between the concentration of acrolein in indoor air and exhaled air, allowing to propose acrolein breath as environmental exposure biomarker. Graphical Abstract Cold fiber solid phase microextraction gas chromatography/mass spectrometry.

  5. Tissue sensitivity of the rat upper and lower extrapulmonary airways to the inhaled electrophilic air pollutants diacetyl and acrolein.

    Cichocki, Joseph A; Smith, Gregory J; Morris, John B

    2014-11-01

    The target site for inhaled vapor-induced injury often differs in mouth-breathing humans compared with nose-breathing rats, thus complicating the use of rat inhalation toxicity data for assessment of human risk. We sought to examine sensitivity of respiratory/transitional nasal (RTM) and tracheobronchial (TBM) mucosa to two electrophilic irritant vapors: diacetyl and acrolein. Computational fluid dynamic physiologically based pharmacokinetic modeling was coupled with biomarker assessment to establish delivered dose-response relationships in RTM and TBM in male F344 rats following 6 h exposure to diacetyl or acrolein. Biomarkers included glutathione status, proinflammatory and antioxidant gene mRNA levels, and nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Modeling revealed that 0.0094-0.1653 μg acrolein/min-cm(2) and 3.9-21.6 μg diacetyl/min-cm(2) were deposited into RTM/TBM. Results indicate RTM and TBM were generally of similar sensitivity to diacetyl and acrolein. For instance, both tissues displayed induction of antioxidant and proinflammatory genes, and nuclear accumulation of Nrf2 after electrophile exposure. Hierarchical cellular response patterns were similar in RTM and TBM but differed between vapors. Specifically, diacetyl exposure induced proinflammatory and antioxidant genes concomitantly at low exposure levels, whereas acrolein induced antioxidant genes at much lower exposure levels than that required to induce proinflammatory genes. Generally, diacetyl was less potent than acrolein, as measured by maximal induction of transcripts. In conclusion, the upper and lower extrapulmonary airways are of similar sensitivity to inhaled electrophilic vapors. Dosimetrically based extrapolation of nasal responses in nose-breathing rodents may provide an approach to predict risk to the lower airways of humans during mouth-breathing.

  6. Determination of acrolein in serum by high-performance liquid chromatography with fluorescence detection after pre-column fluorogenic derivatization using 1,2-diamino-4,5-dimethoxybenzene.

    Imazato, Takahiro; Kanematsu, Mariko; Kishikawa, Naoya; Ohyama, Kaname; Hino, Takako; Ueki, Yukitaka; Maehata, Eisuke; Kuroda, Naotaka

    2015-09-01

    Acrolein is a major unsaturated aldehyde that is generated during the lipid peroxidation process. The measurement of acrolein in biological samples should be useful to estimate the degree of lipid peroxidation and to evaluate the effect of hazardous properties of acrolein on human health. In this study, a highly sensitive and selective high-performance liquid chromatography with fluorescence detection method was developed for the determination of acrolein in human serum. The proposed method involves the pre-column fluorogenic derivatization of acrolein with 1,2-diamino-4,5-dimethoxybenzene (DDB) as a reagent. The fluorescent derivative of acrolein could be detected clearly without any interfering reagent blank peaks because DDB does not have intrinsic fluorescence itself, and the detection limit was 10 nM (signal-to-noise ratio = 3). The proposed method could selectively detect acrolein in human serum with a simple protein precipitation treatment.

  7. Neutrophil bactericidal activity against Staphylococcus aureus adherent on biological surfaces. Surface-bound extracellular matrix proteins activate intracellular killing by oxygen-dependent and -independent mechanisms.

    Hermann, M; Jaconi, M E; Dahlgren, C; Waldvogel, F A; Stendahl, O; Lew, D P

    1990-09-01

    The activation patterns of surface adherent neutrophils are modulated via interaction of extracellular matrix proteins with neutrophil integrins. To evaluate neutrophil bactericidal activity, Staphylococcus aureus adherent to biological surfaces were incubated with neutrophils and serum, and the survival of surface bacteria was determined. When compared to albumin-coated surfaces, the bactericidal activity of neutrophils adherent to purified human extracellular matrix was markedly enhanced (mean survival: 34.2% +/- 9.0% of albumin, P less than 0.0001) despite similar efficient ingestion of extracellular bacteria. Enhancement of killing was observed when surfaces were coated with purified constituents of extracellular matrix, i.e., fibronectin, fibrinogen, laminin, vitronectin, or type IV collagen. In addition to matrix proteins, the tetrapeptide RGDS (the sequence recognized by integrins) crosslinked to surface bound albumin was also active (survival: 74.5% +/- 5.5% of albumin, P less than 0.02), and fibronectin-increased killing was inhibited by soluble RGDS. Chemiluminescence measurements and experiments with CGD neutrophils revealed that both oxygen-dependent and -independent bactericidal mechanisms are involved. In conclusion, matrix proteins enhance intracellular bactericidal activity of adherent neutrophils, presumably by integrin recognition of RGDS-containing ligands. These results indicate a role for extracellular matrix proteins in the enhancement of the host defense against pyogenic infections.

  8. High-resolution synchrotron infrared spectroscopy of acrolein: The vibrational levels between 700 and 820 cm-1

    McKellar, A. R. W.; Billinghurst, B. E.

    2015-09-01

    The weak combination bands ν12 + ν18 and ν17 + ν18 of trans-acrolein in the 700-760 cm-1 region are observed at high resolution (facility. A detailed rotational analysis of the 121181 and 171181 upper states is made which includes the nearby perturbing states 185, 132181, and 131183. Taking the results of this 5-state fit, together with earlier results on lower lying vibrations, we now have experimental characterization for all 15 excited vibrational states of acrolein lying below 820 cm-1.

  9. Effective VTeO/SBA-15 Catalyst Prepared by Precursor Method for the Selective Oxidation of Propane to Acrolein

    FENG Mao-ying; HUANG Chuan-jing; WENG Wei-zheng; WAN Hui-lin; XU Qin; ZHOU Zhao-hui

    2008-01-01

    Precursor decomposition was used for the preparation of VTeO/SBA-15 catalyst for the selective oxidation of propane to acrolein.The catalyst shows a better performance compared with those prepared by conventional impregnant method.A yield of 9.3% of acrolein was achieved with 2% V Ioadings at 500℃.XRD,N2-adsorption,H2-TPR,Py-IR and XPS measurements were used to unclose the relationship between the structure and performance of the catalyst.

  10. The role of valvular endothelial cell paracrine signaling and matrix elasticity on valvular interstitial cell activation.

    Gould, Sarah T; Matherly, Emily E; Smith, Jennifer N; Heistad, Donald D; Anseth, Kristi S

    2014-04-01

    The effects of valvular endothelial cell (VlvEC) paracrine signaling on VIC phenotype and nodule formation were tested using a co-culture platform with physiologically relevant matrix elasticities and diffusion distance. 100 μm thin poly(ethylene glycol) (PEG) hydrogels of 3-27 kPa Young's moduli were fabricated in transwell inserts. VICs were cultured on the gels, as VIC phenotype is known to change significantly within this range, while VlvECs lined the underside of the membrane. Co-culture with VlvECs significantly reduced VIC activation to the myofibroblast phenotype on all gels with the largest percent decrease on the 3 kPa gels (~70%), while stiffer gels resulted in approximately 20-30% decrease. Additionally, VlvECs significantly reduced αSMA protein expression (~2 fold lower) on both 3 and 27 kPa gels, as well as the number (~2 fold lower) of nodules formed on the 27 kPa gels. Effects of VlvECs were prevented when nitric oxide (NO) release was inhibited with l-NAME, suggesting that VlvEC produced NO inhibits VIC activation. Withdrawal of l-NAME after 3, 5, and 7 days with restoration of VlvEC NO production for 2 additional days led to a partial reversal of VIC activation (~25% decrease). A potential mechanism by which VlvEC produced NO reduced VIC activation was studied by inhibiting initial and mid-stage cGMP pathway molecules. Inhibition of soluble guanylyl cyclase (sGC) with ODQ or protein kinase G (PKG) with RBrcGMP or stimulation of Rho kinase (ROCK) with LPA, abolished VlvEC effects on VIC activation. This work contributes substantially to the understanding of the valve endothelium's role in preventing VIC functions associated with aortic valve stenosis initiation and progression.

  11. Gas phase dehydration of glycerol to acrolein catalyzed by zirconium phosphate%磷酸锆催化甘油气相脱水制备丙烯醛

    干慧媚; 赵秀阁; 宋宝宁; 郭立; 张然; 陈晨; 陈吉忠; 朱闻闻; 侯震山

    2014-01-01

    Zirconium phosphates were prepared by precipitation, hydrothermal synthesis, and impregnation methods and were characterized by X-ray diffraction, thermogravimetric analysis, nitrogen adsorp-tion, Fourier transform infrared spectroscopy, and Hammett indicators. The different preparation methods have crucial effects on the texture and surface acidity of the zirconium phosphates. The zirconium phosphates were employed as catalysts for the gas phase dehydration of glycerol under mild reaction conditions. The zirconium phosphates from the precipitation method afforded the highest activity with the complete conversion of glycerol, 81% selectivity to acrolein, and no obvi-ous deactivation over 24 h. Surface acidic sites played an important role in the activity, selectivity to acrolein, and life of catalysts.%以沉淀法、水热合成法和浸渍法制备了磷酸锆催化剂,通过X射线衍射、热重分析、氮气物理吸附、红外光谱和Hammett指示剂法对催化剂进行了表征,并将该催化剂用于甘油气相脱水反应。研究表明,由沉淀法得到的磷酸锆经过400°C焙烧后能达到最佳催化活性,在温和条件下,甘油可完全转化,丙烯醛选择性为81%,反应24 h内催化剂失活不明显。不同方法制备的磷酸锆其结构和表面酸性显著不同,催化剂表面酸性对催化剂活性、丙烯醛选择性和催化剂的寿命均有较大影响。

  12. Induction of matrix metalloproteinase-9 and -2 activity in mouse blastocyst by fibronectin-integrin interaction

    2000-01-01

    Fibronectin, a major extracellular matrix, plays an important role in embryo implantation by mediating embryo adhesion and outgrowth. In this work, mouse blastocysts produced pro-matrix metalloproteinase-9, pro-matrix metalloproteinase-2 and 64 ku matrix metalloproteinase-2 when they were co-cultured with fibronectin. In contrast, mouse blastocysts did not produce these proteinases without fibronectin. Focal adhesion kinase is a fundamental molecule of integrin signaling pathway and its antisense oligodeoxynucleiotide inhibited blastocyst matrix metalloproteinases expression induced by fibronectin. The results indicated that fibronectin triggered matrix metalloproteinase-9 and -2 expression in mouse blastocyst through its integrin receptors and subsequent signaling pathway, which enhanced the synchronization of blastocyst invasiveness and uterine receptivity and ensured the accuracy of events relative to implantation in timing and spatiality.

  13. Glycerol Dehydration to Acrolein Catalyzed by ZSM‐5 Zeolite in Supercritical Carbon Dioxide Medium

    Zou, Bin; Ren, Shoujie

    2016-01-01

    Abstract Supercritical carbon dioxide (SC‐CO2) has been used for the first time as a reaction medium for the dehydration of glycerol to acrolein catalyzed by a solid acid. Unprecedented catalyst stability over 528 hours of time‐on‐stream was achieved and the rate of coke deposition on the zeolite catalyst was the lowest among extensive previous studies, showing potential for industrial application. Coking pathways in SC‐CO2 were also elucidated for future development. The results have potential implications for other dehydration reactions catalyzed by solid acids. PMID:27796088

  14. Augmented expression of urokinase plasminogen activator and extracellular matrix proteins associates with multiple myeloma progression.

    Khan, Rehan; Gupta, Nidhi; Kumar, Raman; Sharma, Manoj; Kumar, Lalit; Sharma, Alpana

    2014-06-01

    Multiple myeloma (MM) represents a B cell malignancy, characterized by a monoclonal proliferation of malignant plasma cells. Interactions between tumor cells and extracellular matrix (ECM) are of importance for tumor invasion and metastasis. Protein levels of urokinase plasminogen activator (uPA) and fibulin 1, nidogen and laminin in plasma and serum respectively and mRNA levels of these molecules in peripheral blood mononuclear cells were determined in 80 subjects by using ELISA and quantitative PCR and data was analyzed with severity of disease. Pearson correlation was determined to observe interrelationship between different molecules. A statistical significant increase for ECM proteins (laminin, nidogen and fibulin 1) and uPA at circulatory level as well as at mRNA level was observed compared to healthy controls. The levels of these molecules in serum might be utilized as a marker of active disease. Significant positive correlation of all ECM proteins with uPA was found and data also correlates with severity of disease. Strong association found between ECM proteins and uPA in this study supports that there might be interplay between these molecules which can be targeted. This study on these molecules may help to gain insight into processes of growth, spread, and clinical behavior of MM.

  15. Captopril and lisinopril only inhibit matrix metalloproteinase-2 (MMP-2) activity at millimolar concentrations.

    Kuntze, Luciana B; Antonio, Raquel C; Izidoro-Toledo, Tatiane C; Meschiari, Cesar A; Tanus-Santos, Jose E; Gerlach, Raquel F

    2014-03-01

    Matrix metalloproteinase-2 (MMP-2) shares structural similarities with the angiotensin-converting enzyme (ACE). ACE inhibitors have been described to inhibit MMP-2, but this inhibitory potential was not shown using a highly purified MMP-2. This study aimed to investigate the inhibitory potential of captopril and lisinopril regarding MMP-2 activity. The first objective was to test the potential of captopril to change the pH of the buffer solution. The second objective was to test the direct inhibitory effect of captopril and lisinopril on plasma MMP-2 and on recombinant human MMP-2 (rhMMP-2). The in vitro activity assays included gelatin zymography and a fluorimetric assay. Captopril solubilization significantly decreased the pH of the 50 mM Tris buffer solution at the following concentrations: 2 mM (p MMP-2 and rhMMP-2 showed that inhibition only happened at captopril concentrations ≥ 4 and 1 mM, respectively (p MMP-2 (p MMP-2 are 3 orders of magnitude higher than those present in vivo after drug administration. We also discuss possible pitfalls for gelatinase inhibitory assays (besides the obvious pH problem already cited). In conclusion, this study's data show that captopril and lisinopril did not inhibit MMP-2 directly at the concentrations reached in vivo.

  16. Dynamic changes in myocardial matrix metalloproteinase activity in mice with viral myocarditis

    MENG Xiao-hui 孟晓慧; SONG Guo-jie 宋国杰; WANG Yi 汪翼; ZHUANG Jian-xin 庄建新; HAN Xiu-zhen 韩秀珍; CHEN Yao 陈瑶; JIN You-peng 靳有鹏; WANG Yu-lin 王玉林; YU Yong-hui 于永慧; James P. Spires

    2004-01-01

    Background Matrix metalloproteinases (MMPs) are the major regulators of collagen degradation involved in the pathogenesis of several diseases of the heart. The purpose of this study was to investigate the dynamic changes in myocardial MMP activity in mice with viral myocarditis (VM), the relationship between MMP activity and both cardiac function and the quantity of myocardial collagen, and the role MMPs playing in the pathological lesions of VM.Methods Sixty-five six-week-old male DBA/2 mice were divided into two groups. Mice in the infected group (n=50) were inoculated intraperitoneally with 0.14 ml of Coxsackievirus B3 (CVB3, Nancy strain). Control mice (n=15) were inoculated intraperitoneally with 0.14 ml of Eagle's medium. Eight infected mice and three control mice were sacrificed on each of days 3, 7, 10, 21 and 30 after inoculation. MMP activity was measured on an SDS-PAGE substrate gel embedded with type Ⅰ gelatin (zymography). Echocardiographic studies were performed under anesthesia with 3% chloralhydrate administered intraperitoneally (0.01 ml/g-0.015 ml/g). Cardiac systolic function indices, such as peak velocity of the aorta (Vp), flow velocity integral of the aorta (Vi), ejection fraction (EF), and fractional shortening (FS) were determined by echocardiography. Histological cross sections of the hearts were stained with hematoxylin-eosin and myocardial histopathological scores were determined under an optical microscope. The amount of myocardial collagen was measured by means of hydroxyproline quantification. Results In virus-infected mice, both MMP-2 and MMP-9 activities were significantly higher than in control mice, reaching a peak on day 10 (P0.05). However, the amount of myocardial collagen in infected mice at the recovery stage (on days 21 and 30) was significantly greater than those of the control mice. MMP-2 and MMP-9 activities positively correlated with myocardial histopathological scores (r=0.801,0.821, P<0.01) and negatively correlated

  17. Janus-faced Acrolein prevents allergy but accelerates tumor growth by promoting immunoregulatory Foxp3+ cells: Mouse model for passive respiratory exposure

    Roth-Walter, Franziska; Bergmayr, Cornelia; Meitz, Sarah; Buchleitner, Stefan; Stremnitzer, Caroline; Fazekas, Judit; Moskovskich, Anna; Müller, Mario A.; Roth, Georg A.; Manzano-Szalai, Krisztina; Dvorak, Zdenek; Neunkirchner, Alina; Jensen-Jarolim, Erika

    2017-01-01

    Acrolein, a highly reactive unsaturated aldehyde, is generated in large amounts during smoking and is best known for its genotoxic capacity. Here, we aimed to assess whether acrolein at concentrations relevant for smokers may also exert immunomodulatory effects that could be relevant in allergy or cancer. In a BALB/c allergy model repeated nasal exposure to acrolein abrogated allergen-specific antibody and cytokine formation, and led to a relative accumulation of regulatory T cells in the lungs. Only the acrolein-treated mice were protected from bronchial hyperreactivity as well as from anaphylactic reactions upon challenge with the specific allergen. Moreover, grafted D2F2 tumor cells grew faster and intratumoral Foxp3+ cell accumulation was observed in these mice compared to sham-treated controls. Results from reporter cell lines suggested that acrolein acts via the aryl-hydrocarbon receptor which could be inhibited by resveratrol and 3′-methoxy-4′-nitroflavone Acrolein- stimulation of human PBMCs increased Foxp3+ expression by T cells which could be antagonized by resveratrol. Our mouse and human data thus revealed that acrolein exerts systemic immunosuppression by promoting Foxp3+ regulatory cells. This provides a novel explanation why smokers have a lower allergy, but higher cancer risk. PMID:28332605

  18. Atmospheric-Pressure Cold Plasmas Used to Embed Bioactive Compounds in Matrix Material for Active Packaging of Fruits and Vegetables

    Fernandez, Sulmer; Pedrow, Patrick; Powers, Joseph; Pitts, Marvin

    2009-10-01

    Active thin film packaging is a technology with the potential to provide consumers with new fruit and vegetable products-if the film can be applied without deactivating bioactive compounds.Atmospheric pressure cold plasma (APCP) processing can be used to activate monomer with concomitant deposition of an organic plasma polymerized matrix material and to immobilize a bioactive compound all at or below room temperature.Aims of this work include: 1) immobilize an antimicrobial in the matrix; 2) determine if the antimicrobial retains its functionality and 3) optimize the reactor design.The plasma zone will be obtained by increasing the voltage on an electrode structure until the electric field in the feed material (argon + monomer) yields electron avalanches. Results will be described using Red Delicious apples.Prospective matrix precursors are vanillin and cinnamic acid.A prospective bioactive compound is benzoic acid.

  19. Increasing extracellular matrix collagen level and MMP activity induces cyst development in polycystic kidney disease

    Liu Bin

    2012-09-01

    Full Text Available Abstract Background Polycystic Kidney Disease (PKD kidneys exhibit increased extracellular matrix (ECM collagen expression and metalloproteinases (MMPs activity. We investigated the role of these increases on cystic disease progression in PKD kidneys. Methods We examined the role of type I collagen (collagen I and membrane bound type 1 MMP (MT1-MMP on cyst development using both in vitro 3 dimensional (3D collagen gel culture and in vivo PCK rat model of PKD. Results We found that collagen concentration is critical in controlling the morphogenesis of MDCK cells cultured in 3D gels. MDCK cells did not form 3D structures at collagen I concentrations lower than 1 mg/ml but began forming tubules when the concentration reaches 1 mg/ml. Significantly, these cells began to form cyst when collagen I concentration reached to 1.2 mg/ml, and the ratios of cyst to tubule structures increased as the collagen I concentration increased. These cells exclusively formed cyst structures at a collagen I concentration of 1.8 mg/ml or higher. Overexpression of MT1-MMP in MDCK cells significantly induced cyst growth in 3D collagen gel culture. Conversely, inhibition of MMPs activity with doxycycline, a FDA approved pan-MMPs inhibitor, dramatically slowed cyst growth. More importantly, the treatment of PCK rats with doxycycline significantly decreased renal tubule cell proliferation and markedly inhibited the cystic disease progression. Conclusions Our data suggest that increased collagen expression and MMP activity in PKD kidneys may induce cyst formation and expansion. Our findings also suggest that MMPs may serve as a therapeutic target for the treatment of human PKD.

  20. Development of an integrated system for activity-based profiling of matrix metallo-proteases

    Freije, Jan Robert

    2006-01-01

    Matrix metallo-proteases constitute a family of extracellular zinc-dependent endopeptidases that are involved in degradation of extracellular matrix (ECM) components and other bioactive non-ECM molecules. A plethora of studies have implicated important roles for MMPs in many diseases (including canc

  1. Production of active lysozyme films by matrix assisted pulsed laser evaporation at 355 nm

    Purice, Andreea; Schou, Jørgen; Kingshott, P.;

    2007-01-01

    Thin lysozyme films have been produced in a dry environment by MAPLE (matrix assisted pulsed laser evaporation) from a water ice matrix irradiated by laser light at 355 nm above the absorption threshold of the protein. A significant part of the lysozyme molecules are transferred to the film without...

  2. Probing matrix and tumor mechanics with in situ calibrated optical trap based active microrheology

    Staunton, Jack Rory; Vieira, Wilfred; Tanner, Kandice; Tissue Morphodynamics Unit Team

    Aberrant extracellular matrix deposition and vascularization, concomitant with proliferation and phenotypic changes undergone by cancer cells, alter mechanical properties in the tumor microenvironment during cancer progression. Tumor mechanics conversely influence progression, and the identification of physical biomarkers promise improved diagnostic and prognostic power. Optical trap based active microrheology enables measurement of forces up to 0.5 mm within a sample, allowing interrogation of in vitro biomaterials, ex vivo tissue sections, and small organisms in vivo. We fabricated collagen I hydrogels exhibiting distinct structural properties by tuning polymerization temperature Tp, and measured their shear storage and loss moduli at frequencies 1-15k Hz at multiple amplitudes. Lower Tp gels, with larger pore size but thicker, longer fibers, were stiffer than higher Tp gels; decreasing strain increased loss moduli and decreased storage moduli at low frequencies. We subcutanously injected probes with metastatic murine melanoma cells into mice. The excised tumors displayed storage and loss moduli 40 Pa and 10 Pa at 1 Hz, increasing to 500 Pa and 1 kPa at 15 kHz, respectively.

  3. Organic thin-film transistor arrays for active-matrix organic light emitting diode

    Lee, Sangyun; Moon, Hyunsik; Kim, Do H.; Koo, Bon-Won; Jeong, Eun-Jeong; Lee, Bang-Lin; Kim, Joo-Young; Lee, Eunkyung; Hahn, Kook-Min; Han, Jeong-Seok; Park, Jung-Il; Seon, Jong-Baek; Kim, Jung-Woo; Chun, Young-Tea; Kim, Sangyeol; Kang, Sung K.

    2007-09-01

    We developed an active matrix organic light-emitting diodes (AMOLEDs) on a glass using two organic thin-film transistors (OTFTs) and a capacitor in a pixel. OTFTs switching-arrays with 64 scan lines and 64 (RGB) data lines were designed and fabricated to drive OLED arrays. In this study, OTFT devices have bottom contact structures with an ink-jet printed polymer semiconductor and an organic insulator as a gate dielectric. The width and length of the switching OTFT is 500μm and 10μm, respectively and the driving OTFT has 900μm channel width with the same channel length. The characteristics of the OTFTs were examined using test cells around display area. On/off ratio, mobility, on-current of switching OTFT and on-current of driving OTFT were 10 6, 0.1 cm2/V-sec, order of 8μA and over 70 μA respectively. These properties were enough to drive the AMOLEDs over 60 Hz frame rate. AMOLEDs composed of the OTFT switching arrays and OLEDs made by deposition of small molecule materials were fabricated and driven to make moving images, successfully.

  4. Active matrix organic light emitting diode (OLED)-XL life test results

    Fellowes, David A.; Wood, Michael V.; Hastings, Arthur R., Jr.; Ghosh, Amalkumar P.; Prache, Olivier

    2008-04-01

    OLED displays have been known to exhibit high levels of performance with regards to contrast, response time, uniformity, and viewing angle, but a lifetime improvement has been perceived to be essential for broadening the applications of OLED's in the military and in the commercial market. As a result of this need, the US Army and eMagin Corporation established a Cooperative Research and Development Agreement (CRADA) to improve the lifetime of OLED displays. In 2006, eMagin Corporation developed long-life OLED-XL devices for use in their AMOLED microdisplays for head-worn applications, and RDECOM CERDEC NVESD ran life tests on these displays, finding over 200% lifetime improvement for the XL devices over the standard displays. Early results were published at the 2007 SPIE Defense and Security Symposium. Further life testing of XL and standard devices at ambient conditions and at high temperatures will be presented this year along with a recap of previous data. This should result in a better understanding of the applicability of AMOLEDs in military and commercial head mounted systems: where good fits are made, and where further development might be needed. This is a continuation of the paper "Life test results of OLED-XL long-life devices for use in active matrix organic light emitting diode (AMOLED) displays for head mounted applications" presented at SPIE DSS in 2007.

  5. Stretchable active-matrix organic light-emitting diode display using printable elastic conductors

    Sekitani, Tsuyoshi; Nakajima, Hiroyoshi; Maeda, Hiroki; Fukushima, Takanori; Aida, Takuzo; Hata, Kenji; Someya, Takao

    2009-06-01

    Stretchability will significantly expand the applications scope of electronics, particularly for large-area electronic displays, sensors and actuators. Unlike for conventional devices, stretchable electronics can cover arbitrary surfaces and movable parts. However, a large hurdle is the manufacture of large-area highly stretchable electrical wirings with high conductivity. Here, we describe the manufacture of printable elastic conductors comprising single-walled carbon nanotubes (SWNTs) uniformly dispersed in a fluorinated rubber. Using an ionic liquid and jet-milling, we produce long and fine SWNT bundles that can form well-developed conducting networks in the rubber. Conductivity of more than 100Scm-1 and stretchability of more than 100% are obtained. Making full use of this extraordinary conductivity, we constructed a rubber-like stretchable active-matrix display comprising integrated printed elastic conductors, organic transistors and organic light-emitting diodes. The display could be stretched by 30-50% and spread over a hemisphere without any mechanical or electrical damage.

  6. Separated Carbon Nanotube Macroelectronics for Active Matrix Organic Light-Emitting Diode Displays

    Fu, Yue; Zhang, Jialu; Wang, Chuan; Chen, Pochiang; Zhou, Chongwu

    2012-02-01

    Active matrix organic light-emitting diode (AMOLED) display holds great potential for the next generation visual technologies due to its high light efficiency, flexibility, lightweight, and low-temperature processing. However, suitable thin-film transistors (TFTs) are required to realize the advantages of AMOLED. Pre-separated, semiconducting enriched carbon nanotubes are excellent candidates for this purpose because of their excellent mobility, high percentage of semiconducting nanotubes, and room-temperature processing compatibility. Here we report, for the first time, the demonstration of AMOLED displays driven by separated nanotube thin-film transistors (SN-TFTs) including key technology components such as large-scale high-yield fabrication of devices with superior performance, carbon nanotube film density optimization, bilayer gate dielectric for improved substrate adhesion to the deposited nanotube film, and the demonstration of monolithically integrated AMOLED display elements with 500 pixels driven by 1000 SN-TFTs. Our approach can serve as the critical foundation for future nanotube-based thin-film display electronics.

  7. Piezoelectric properties of the new generation active matrix hybrid (micro-nano) composites

    Parali, Levent; Şabikoğlu, İsrafil; Kurbanov, Mirza A.

    2014-11-01

    A hybrid piezoelectric composite structure is obtained by addition of nano-sized BaTiO3, SiO2 to the micro-sized PZT and polymers composition. Although the PZT material itself has excellent piezoelectric properties, PZT-based composite variety is limited. Piezoelectric properties of PZT materials can be varied with an acceptor or a donor added to the material. In addition, varieties of PZT-based sensors can be increased with doping polymers which have physical-mechanical, electrophysical, thermophysical and photoelectrical properties. The active matrix hybrid structure occurs when bringing together the unique piezoelectric properties of micro-sized PZT with electron trapping properties of nano-sized insulators (BaTiO3 or SiO2), and their piezoelectric, mechanic and electromechanic properties significantly change. In this study, the relationship between the piezoelectric constant and the coupling factor values of microstructure (PZT-PVDF) and the hybrid structure (PZT-PVDF-BaTiO3) composite are compared. The d33 value and the coupling factor of the hybrid structure have shown an average of 54 and 62% increase according to microstructure composite, respectively. In addition, the d33 value and the coupling factor of the hybrid structure (PZT-HDPE-SiO2) have exhibited about 68 and 52% increase according to microstructure composite (PZT-HDPE), respectively.

  8. An asynchronous, pipelined, electronic acquisition system for Active Matrix Flat-Panel Imagers (AMFPIs)

    Huang, W.; Antonuk, L.E. E-mail: antonuk@umich.edu; Berry, J.; Maolinbay, M.; Martelli, C.; Mody, P.; Nassif, S.; Yeakey, M

    1999-07-11

    The development of a full-custom electronic acquisition system designed for readout of large-area active matrix flat-panel imaging arrays is reported. The arrays, which comprise two-dimensional matrices of pixels utilizing amorphous silicon thin-film transistors, are themselves under development for a wide variety of X-ray imaging applications. The acquisition system was specifically designed to facilitate detailed, quantitative investigations of the properties of these novel imaging arrays and contains significant enhancements compared to a previously developed acquisition system. These enhancements include pipelined preamplifier circuits to allow faster readout speed, expanded addressing capabilities allowing a maximum of 4096 array data lines, and on-board summing of image frames. The values of many acquisition system parameters, including timings and voltages, may be specified and downloaded from a host computer. Once acquisition is enabled, the system operates asynchronously of its host computer. The system allows image capture in both radiographic mode (corresponding to the capture of individual X-ray images), and fluoroscopic mode (corresponding to the capture of a continual series of X-ray images). A detailed description of the system architecture and the underlying motivations for the design is reported in this paper. (author)

  9. Matrix Effects on the Stability and Antioxidant Activity of Red Cabbage Anthocyanins under Simulated Gastrointestinal Digestion

    Anna Podsędek

    2014-01-01

    Full Text Available Red cabbage is, among different vegetables, one of the major sources of anthocyanins. In the present study an in vitro digestion method has been used to assay the influence of the physiological conditions in the stomach and small intestine, as well as faecal microflora on anthocyanins stability in red cabbage and anthocyanin-rich extract. The recovery of anthocyanins during in vitro gastrointestinal digestion was strongly influenced by food matrix. The results showed that other constituents present in cabbage enhanced the stability of anthocyanins during the digestion. The amount of anthocyanins (HPLC method and antioxidant capacity (ABTS and FRAP assays strongly decreased after pancreatic-bile digestion in both matrices but total phenolics content (Folin-Ciocalteu assay in these digestions was higher than in initial samples. Incubation with human faecal microflora caused further decline in anthocyanins content. The results obtained suggest that intact anthocyanins in gastric and products of their decomposition in small and large intestine may be mainly responsible for the antioxidant activity and other physiological effects after consumption of red cabbage.

  10. Sensitive detection of acrolein and acrylonitrile with a pulsed quantum-cascade laser

    Manne, J.; Lim, A.; Tulip, J.; Jäger, W.

    2012-05-01

    We report on spectroscopic measurements of acrolein and acrylonitrile at atmospheric pressure using a pulsed distributed feedback quantum-cascade laser in combination with intra- and inter-pulse techniques and compare the results. The measurements were done in the frequency region around 957 cm-1. In the inter-pulse technique, the laser is excited with short current pulses (5-10 ns), and the pulse amplitude is modulated with an external current ramp resulting in a ˜2.3 cm-1 frequency scan. In the intra-pulse technique, a linear frequency down-chirp during the pulse is used for sweeping across the absorption line. Long current pulses up to 500 ns were used for these measurements which resulted in a spectral window of ˜2.2 cm-1 during the down-chirp. These comparatively wide spectral windows facilitated the measurements of the relatively broad absorption lines (˜1 cm-1) of acrolein and acrylonitrile. The use of a room-temperature mercury-cadmium-telluride detector resulted in a completely cryogen-free spectrometer. We demonstrate ppb level detection limits within a data acquisition time of ˜10 s with these methodologies.

  11. Influenza A infection attenuates relaxation responses of mouse tracheal smooth muscle evoked by acrolein.

    Cheah, Esther Y; Mann, Tracy S; Burcham, Philip C; Henry, Peter J

    2015-02-15

    The airway epithelium is an important source of relaxant mediators, and damage to the epithelium caused by respiratory tract viruses may contribute to airway hyperreactivity. The aim of this study was to determine whether influenza A-induced epithelial damage would modulate relaxation responses evoked by acrolein, a toxic and prevalent component of smoke. Male BALB/c mice were inoculated intranasally with influenza A/PR-8/34 (VIRUS-infected) or allantoic fluid (SHAM-infected). On day 4 post-inoculation, isometric tension recording studies were conducted on carbachol pre-contracted tracheal segments isolated from VIRUS and SHAM mice. Relaxant responses to acrolein (30 μM) were markedly smaller in VIRUS segments compared to SHAM segments (2 ± 1% relaxation vs. 28 ± 5%, n=14, pacrolein and SP were reduced in VIRUS segments (>35% reduction, n=6, pacrolein were profoundly diminished in tracheal segments isolated from influenza A-infected mice. The mechanism through which influenza A infection attenuates this response appears to involve reduced production of PGE2 in response to SP due to epithelial cell loss, and may provide insight into the airway hyperreactivity observed with influenza A infection.

  12. The health- and addictive effectes due to exposure to aldehydes of cigarette smoke. Part 1; Acetaldehyde, Formaldehyde, Acrolein and Propionaldehyde

    Andel I van; Schenk E; Rambali B; Wolterink G; Werken G van de; Stevenson H; Aerts LAGJM van; Vleeming W; LEO; LGM; LOC; CRV

    2003-01-01

    In the desk study presented here, health effects and possible addictive effects of aldehyde exposure due to cigarette smoking are discussed. In the light of currently available literature the health effects of exposure to acetaldehyde, formaldehyde, acrolein and propionaldehyde were assessed. All al

  13. Simultaneous exposure to concentrated ambient particles and acrolein causes cardiac effects mediated by parasympathetic modulation in mice

    This study shows that exposure to CAPs and acrolein causes an increase in HRV that is mediated by the parasympathetic nervous system. Numerous studies show that short-term air pollution exposure modulates heart rate variability (HRV), which is an indicator of autonomic influence...

  14. Changes in the nasal epithelium of rats exposed by inhalation to mixtures of formaldehyde, acetaldehyde, and acrolein

    Cassee, F.R.; Groten, J.P.; Feron, V.J.

    1996-01-01

    Formaldehyde, acetaldehyde, and acrolein are well-known upper respiratory tract irritants and occur simultaneously as pollutants in many indoor and outdoor environments. The upper respiratory tract, and especially the nose, is the prime target for inhaled aldehydes. To study possible additive or int

  15. The adsorption of acrolein on a Pt (1 1 1): A study of chemical bonding and electronic structure

    Pirillo, S.; López-Corral, I.; Germán, E.; Juan, A.

    2012-12-01

    The adsorption of acrolein on a Pt (1 1 1) surface was studied using ab-initio and semiempirical calculations. Geometry optimization and densities of states (DOS) curves were carried out using the Vienna Ab-initio Simulation Package (VASP) code. We started our study with the preferential geometries corresponding to the different acrolein/Pt (1 1 1) adsorption modes previously reported. Then, we examined the evolution of the chemical bonding in these geometries, using the crystal orbital overlap population (COOP) and overlap population (OP) analysis of selected pairs of atoms. We analyzed the acrolein intramolecular bonds, Pt (1 1 1) superficial bonds and new moleculesbnd surface formed bonds after adsorption. We found that Ptsbnd Pt bonds interacting with the molecule and acrolein Cdbnd O and Cdbnd C bonds are weakened after adsorption; this last bond is significantly linked to the surface. The obtained Csbnd Pt and Osbnd Pt OP values suggest that the most stable adsorption modes are η3-cis and η4-trans, while the η1-trans is the less favored configuration. We also found that C pz orbital and Pt pz and d orbitals participate strongly in the adsorption process.

  16. Acrolein Causes TRPA1-Mediated Sensory Irritation and Indirect Potentiation of TRPV1-Mediated Pulmonary Chemoreflex Response

    We previously demonstrated that acute exposure to acrolein causes immediate sensory irritation, with rapid decrease in heart rate (HR) and increase in inspiratory time (Ti), and potentiation of pulmonary chemoreflex response 24hrs later; of these effects only the latter is mediat...

  17. Direct sp(3)C-H acroleination of N-aryl-tetrahydroisoquinolines by merging photoredox catalysis with nucleophilic catalysis.

    Feng, Zhu-Jia; Xuan, Jun; Xia, Xu-Dong; Ding, Wei; Guo, Wei; Chen, Jia-Rong; Zou, You-Quan; Lu, Liang-Qiu; Xiao, Wen-Jing

    2014-04-07

    Sequence catalysis merging photoredox catalysis (PC) and nucleophilic catalysis (NC) has been realized for the direct sp(3) C-H acroleination of N-aryl-tetrahydroisoquinoline (THIQ). The reaction was performed under very mild conditions and afforded products in 50-91% yields. A catalytic asymmetric variant was proved to be successful with moderate enantioselectivities (up to 83 : 17 er).

  18. Detection of Colorectal Adenomas Using a Bioactivatable Probe Specific for Matrix Metalloproteinase Activity

    Margie L. Clapper

    2011-08-01

    Full Text Available A significant proportion of colorectal adenomas, in particular those that lack an elevated growth component, continue to escape detection during endoscopic surveillance. Elevation of the activity of matrix metalloproteinases (MMPs, a large family of zinc endopeptidases, in adenomas serves as a biomarker of early tumorigenesis. The goal of this study was to assess the feasibility of using a newly developed near-infrared bioactivatable probe (MMPSense 680 that reports the activity of a broad array of MMP isoforms to detect early colorectal adenomas. Adenomatous polyposis coli (Apc+/Min-FCCC mice that spontaneously develop multiple colorectal adenomas were injected with MMPSense 680, and the colons were imaged in an IVIS Spectrum system ex vivo. Image analyses were correlated with histopathologic findings for all regions of interest (ROIs. The biochemical basis of fluorescent signal was investigated by immunohistochemical staining of MMP-7 and -9. A strong correlation (Kendall = 0.80 was observed between a positive signal and the presence of pathologically confirmed colonic adenomas; 92.9% of the 350 ROIs evaluated were classified correctly. The correlation between two independent observers was 0.87. MMP-7 expression was localized to epithelial cells of adenomas and microadenomas, whereas staining of MMP-9 was found in infiltrating polymorphonuclear leukocytes within the adenomas. MMPSense 680 identifies colorectal adenomas, both polypoid and nonpolypoid, in Apc+/Min-FCCC mice with high specificity. Use of this fluorescent probe in combination with colonoscopy could aid in preventing colorectal neoplasias by providing new opportunities for early detection and therapeutic intervention.

  19. Cytotoxicity of Thirdhand Smoke and Identification of Acrolein as a Volatile Thirdhand Smoke Chemical That Inhibits Cell Proliferation.

    Bahl, Vasundhra; Weng, Nikki J-H; Schick, Suzaynn F; Sleiman, Mohamad; Whitehead, Jacklyn; Ibarra, Allison; Talbot, Prue

    2016-03-01

    Thirdhand smoke (THS) is a mixture of chemicals that remain on indoor surfaces after smoking has ceased. These chemicals can be inhaled, ingested, or absorbed dermally, and thus could impact human health. We evaluated the cytotoxicity and mode of action of fresh and aged THS, the toxicity of volatile organic chemicals (VOCs) in THS, and the molecular targets of acrolein, a VOC in THS. Experiments were done using mouse neural stem cells (mNSC), human pulmonary fibroblasts (hPF), and lung A549 epithelial cells. THS-exposed cotton cloth was extracted in Dulbecco's Eagle Medium and caused cytotoxicity in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. THS extracts induced blebbing, immotility, vacuolization, cell fragmentation, severing of microfilaments and depolymerization of microtubules in mNSC. Cytotoxicity was inversely related to headspace volume in the extraction container and was lost upon aging, suggesting that VOCs in THS were cytotoxic. Phenol, 2',5'-dimethyl furan and acrolein were identified as the most cytotoxic VOCs in THS, and in combination, their cytotoxicity increased. Acrolein inhibited proliferation of mNSC and hPF and altered expression of cell cycle regulatory genes. Twenty-four hours of treatment with acrolein decreased expression of transcription factor Dp-1, a factor needed for the G1 to S transition in the cell cycle. At 48 h, WEE1 expression increased, while ANACP1 expression decreased consistent with blocking entry into and completion of the M phase of the cell cycle. This study identified acrolein as a highly cytotoxic VOC in THS which killed cells at high doses and inhibited cell proliferation at low doses.

  20. α,β-Unsaturated aldehyde pollutant acrolein suppresses cardiomyocyte contractile function: Role of TRPV1 and oxidative stress.

    Wu, Zhenbiao; He, Emily Y; Scott, Glenda I; Ren, Jun

    2015-01-01

    Air pollution is associated with an increased prevalence of heart disease and is known to trigger a proinflammatory response via stimulation of transient receptor potential vanilloid cation channels (TRPV1, also known as the capsaicin receptor). This study was designed to examine the effect of acrolein, an essential α,β-unsaturated aldehyde pollutant, on myocardial contractile function and the underlying mechanism involved with a focus on TRPV1 and oxidative stress. Cardiomyocyte mechanical and intracellular Ca(2+) properties were evaluated using an IonOptix MyoCam® system including peak shortening (PS), maximal velocity of shortening/relengthening (± dL/dt), time-to-PS (TPS), time-to-90% relengthening (TR90 ), fura-2 fluorescence intensity (FFI) and intracellular Ca(2+) decay. Changes in apoptosis and TRPV1 were evaluated using Western blot analysis. The degree of oxidative stress was assessed using the ratio between reduced and oxidized glutathione. Results obtained revealed that exposure of cardiomyocytes to acrolein acutely compromised contractile and intracellular Ca(2+) properties including depressed PS, ± dL/dt and ΔFFI, as well as prolonged TR90 and intracellular Ca(2+) decay. In addition, acrolein exposure upregulated TRPV1 associated with an increase in both apoptosis and oxidative stress. However, the acrolein-induced cardiomyocyte contractile and intracellular Ca(2+) anomalies, as well as apoptosis (as evidenced by Bcl-2, Bax, FasL, Caspase-3 and -8), were negated by the reactive oxygen species (ROS) scavenger glutathione or the TRPV1 antagonist capsazepine. Collectively these data suggest that the α,β-unsaturated aldehyde pollutant acrolein may play a role in the pathogenesis and sequelae of air pollution-induced heart disease via a TRPV1- and oxidative stress-dependent mechanism.

  1. A study on leaching behaviour of cement blocks used as matrix for fixation of Cs activity along with ferric

    Pushpa Muthiah; K S Seshadri; P K Sinha; K B Lal

    2007-10-01

    Study on the cementation of the regenerated activity (from spent resin using ferric as regenerant) containing ferric in cement matrix showed that compressive strength and leaching behaviour are better when the ferric strength was < 5 N. The diffusion coefficient of Cs from the cement matrix was found to be in the range 2.4 × 10-5 cm2/day and 5.9 × 10-5 cm2/day with ferric solutions of strength in the range 0.5–3 N. When bentonite and vermiculite were included in the cement matrix, the diffusion coefficient of Cs was found to be in the range 6.2 × 10-7 cm2/day to 1.26 × 10-5 cm2/day with ferric strength in the same range.

  2. Systemic Metabolic Impairment and Lung Injury Following Acrolein Inhalation

    A single ozone exposure causes pulmonary injury and systemic metabolic alterations through neuronal and hypothalamus pituitary adrenal axis activation. Metabolically impaired Goto Kakizaki (GK) rats with non-obese type-2 diabetes are more sensitive to ozone induced changes than h...

  3. Countering beam divergence effects with focused segmented scintillators for high DQE megavoltage active matrix imagers

    Liu, Langechuan; Antonuk, Larry E.; Zhao, Qihua; El-Mohri, Youcef; Jiang, Hao

    2012-08-01

    The imaging performance of active matrix flat-panel imagers designed for megavoltage imaging (MV AMFPIs) is severely constrained by relatively low x-ray detection efficiency, which leads to a detective quantum efficiency (DQE) of only ∼1%. Previous theoretical and empirical studies by our group have demonstrated the potential for addressing this constraint through the utilization of thick, two-dimensional, segmented scintillators with optically isolated crystals. However, this strategy is constrained by the degradation of high-frequency DQE resulting from spatial resolution loss at locations away from the central beam axis due to oblique incidence of radiation. To address this challenge, segmented scintillators constructed so that the crystals are individually focused toward the radiation source are proposed and theoretically investigated. The study was performed using Monte Carlo simulations of radiation transport to examine the modulation transfer function and DQE of focused segmented scintillators with thicknesses ranging from 5 to 60 mm. The results demonstrate that, independent of scintillator thickness, the introduction of focusing largely restores spatial resolution and DQE performance otherwise lost in thick, unfocused segmented scintillators. For the case of a 60 mm thick BGO scintillator and at a location 20 cm off the central beam axis, use of focusing improves DQE by up to a factor of ∼130 at non-zero spatial frequencies. The results also indicate relatively robust tolerance of such scintillators to positional displacements, of up to 10 cm in the source-to-detector direction and 2 cm in the lateral direction, from their optimal focusing position, which could potentially enhance practical clinical use of focused segmented scintillators in MV AMFPIs.

  4. Identification of collagen binding domain residues that govern catalytic activities of matrix metalloproteinase-2 (MMP-2).

    Mikhailova, Margarita; Xu, Xiaoping; Robichaud, Trista K; Pal, Sanjay; Fields, Gregg B; Steffensen, Bjorn

    2012-01-01

    An innovative approach to enhance the selectivity of matrix metalloproteinase (MMP) inhibitors comprises targeting these inhibitors to catalytically required substrate binding sites (exosites) that are located outside the catalytic cleft. In MMP-2, positioning of collagen substrate molecules occurs via a unique fibronectin-like domain (CBD) that contains three distinct modular collagen binding sites. To characterize the contributions of these exosites to gelatinolysis by MMP-2, seven MMP-2 variants were generated with single, or concurrent double and triple alanine substitutions in the three fibronectin type II modules of the CBD. Circular dichroism spectroscopy verified that recombinant MMP-2 wild-type (WT) and variants had the same fold. Moreover, the MMP-2 WT and variants had the same activity on a short FRET peptide substrate that is hydrolyzed independently of CBD binding. Among single-point variants, substitution in the module 3 binding site had greatest impact on the affinity of MMP-2 for gelatin. Simultaneous substitutions in two or three CBD modules further reduced gelatin binding. The rates of gelatinolysis of MMP-2 variants were reduced by 20-40% following single-point substitutions, by 60-75% after double-point modifications, and by >90% for triple-point variants. Intriguingly, the three CBD modules contributed differentially to cleavage of dissociated α-1(I) and α-2(I) collagen chains. Importantly, kinetic analyses (k(cat)/K(m)) revealed that catalysis of a triple-helical FRET peptide substrate by MMP-2 relied primarily on the module 3 binding site. Thus, we have identified three collagen binding site residues that are essential for gelatinolysis and constitute promising targets for selective inhibition of MMP-2.

  5. Exogenous l-arginine reduces matrix metalloproteinase-2 and -9 activities and oxidative stress in patients with hypertension

    Garcia, Vinicius P; Rocha, Helena N M; Silva, Gustavo M;

    2016-01-01

    AIMS: Increased matrix metalloproteinases activity and reduced nitric oxide (NO) bioavailability contributes to development of hypertension and this may be associated with a defective l-arginine-NO pathway. Exogenous l-arginine improves endothelial function to prevent the onset of cardiovascular ...... between groups during the saline infusion (P>0.05). SIGNIFICANCE: Exogenous l-arginine diminished metalloproteinase-2 and -9 activities and MMP-9/TIMP-1 ratio along with restoring the oxidative stress balance in patients with hypertension.......AIMS: Increased matrix metalloproteinases activity and reduced nitric oxide (NO) bioavailability contributes to development of hypertension and this may be associated with a defective l-arginine-NO pathway. Exogenous l-arginine improves endothelial function to prevent the onset of cardiovascular...

  6. Flax Fiber Hydrophobic Extract Inhibits Human Skin Cells Inflammation and Causes Remodeling of Extracellular Matrix and Wound Closure Activation

    Monika Styrczewska

    2015-01-01

    Full Text Available Inflammation is the basis of many diseases, with chronic wounds amongst them, limiting cell proliferation and tissue regeneration. Our previous preclinical study of flax fiber applied as a wound dressing and analysis of its components impact on the fibroblast transcriptome suggested flax fiber hydrophobic extract use as an anti-inflammatory and wound healing preparation. The extract contains cannabidiol (CBD, phytosterols, and unsaturated fatty acids, showing great promise in wound healing. In in vitro proliferation and wound closure tests the extract activated cell migration and proliferation. The activity of matrix metalloproteinases in skin cells was increased, suggesting activation of extracellular components remodeling. The expression of cytokines was diminished by the extract in a cannabidiol-dependent manner, but β-sitosterol can act synergistically with CBD in inflammation inhibition. Extracellular matrix related genes were also analyzed, considering their importance in further stages of wound healing. The extract activated skin cell matrix remodeling, but the changes were only partially cannabidiol- and β-sitosterol-dependent. The possible role of fatty acids also present in the extract is suggested. The study shows the hydrophobic flax fiber components as wound healing activators, with anti-inflammatory cannabidiol acting in synergy with sterols, and migration and proliferation promoting agents, some of which still require experimental identification.

  7. Flax Fiber Hydrophobic Extract Inhibits Human Skin Cells Inflammation and Causes Remodeling of Extracellular Matrix and Wound Closure Activation.

    Styrczewska, Monika; Kostyn, Anna; Kulma, Anna; Majkowska-Skrobek, Grazyna; Augustyniak, Daria; Prescha, Anna; Czuj, Tadeusz; Szopa, Jan

    2015-01-01

    Inflammation is the basis of many diseases, with chronic wounds amongst them, limiting cell proliferation and tissue regeneration. Our previous preclinical study of flax fiber applied as a wound dressing and analysis of its components impact on the fibroblast transcriptome suggested flax fiber hydrophobic extract use as an anti-inflammatory and wound healing preparation. The extract contains cannabidiol (CBD), phytosterols, and unsaturated fatty acids, showing great promise in wound healing. In in vitro proliferation and wound closure tests the extract activated cell migration and proliferation. The activity of matrix metalloproteinases in skin cells was increased, suggesting activation of extracellular components remodeling. The expression of cytokines was diminished by the extract in a cannabidiol-dependent manner, but β-sitosterol can act synergistically with CBD in inflammation inhibition. Extracellular matrix related genes were also analyzed, considering their importance in further stages of wound healing. The extract activated skin cell matrix remodeling, but the changes were only partially cannabidiol- and β-sitosterol-dependent. The possible role of fatty acids also present in the extract is suggested. The study shows the hydrophobic flax fiber components as wound healing activators, with anti-inflammatory cannabidiol acting in synergy with sterols, and migration and proliferation promoting agents, some of which still require experimental identification.

  8. Transient receptor potential cation channel A1 (TRPA1) mediates changes in heart rate variability following a single exposure to acrolein in mice

    The data show that a single exposure to acrolein causes autonomic imbalance in mice through the TRPA1 sensor and subsequent cardiac dysfunction. Human and animal studies have shown that short-term air pollution exposure causes...

  9. Food matrix and processing influence on carotenoid bioaccessibility and lipophilic antioxidant activity of fruit juice-based beverages.

    Rodríguez-Roque, María Janeth; de Ancos, Begoña; Sánchez-Vega, Rogelio; Sánchez-Moreno, Concepción; Cano, M Pilar; Elez-Martínez, Pedro; Martín-Belloso, Olga

    2016-01-01

    The biological activity of carotenoids depends on their bioaccessibility and solubilization in the gastrointestinal tract. These compounds are poorly dispersed in the aqueous media of the digestive tract due to their lipophilic nature. Thus, it is important to analyze the extent to which some factors, such as the food matrix and food processing, may improve their bioaccessibility. Beverages formulated with a blend of fruit juices and water (WB), milk (MB) or soymilk (SB) were treated by high-intensity pulsed electric fields (HIPEF) (35 kV cm(-1) with 4 μs bipolar pulses at 200 Hz for 1800 μs), high-pressure processing (HPP) (400 MPa at 40 °C for 5 min) or thermal treatment (TT) (90 °C for 1 min) in order to evaluate the influence of food matrix and processing on the bioaccessibility of carotenoids and on the lipophilic antioxidant activity (LAA). The bioaccessibility of these compounds diminished after applying any treatment (HIPEF, HPP and TT), with the exception of cis-violaxanthin + neoxanthin, which increased by 79% in HIPEF and HPP beverages. The lowest carotenoid bioaccessibility was always obtained in TT beverages (losses up to 63%). MB was the best food matrix for improving the bioaccessibility of carotenoids, as well as the LAA. The results demonstrate that treatment and food matrix modulated the bioaccessibility of carotenoids as well as the lipophilic antioxidant potential of beverages. Additionally, HIPEF and HPP could be considered as promising technologies to obtain highly nutritional and functional beverages.

  10. Effects of Acrolein on Apoptosis of H9c2 Cardiacmyocytes with Hypoxia/Reoxygenation Injury%丙烯醛对缺氧复氧H9c2心肌细胞损伤的影响及机制初探

    邵庆瑞; 杜丹; 何阳; 吴晓华; 黄文; 邢志华

    2012-01-01

    Objective To determine the cytotoxic effects of acrolein on hypoxia/ reoxygenation (H/R) injury in H9c2 cardiacmyocytes and investigate the intracellular signaling pathways. Methods Hypoxia/reoxygenation (H/R) injury model was established with H9c2 cells. The H9c2 cells were divided into four groups, the control group, acrolein group (ACR), H/R group, acrolein+ H/R group (ACR+ H/R). H9cZ cells pretreated with or without acrolein (10 μmol/L) for 30 min were exposed to 2 h hypoxia and 16 h reoxygenation. The effect of acrolein on the cellular viability and apoptosis of H9c2 cells was measured by MTT assay, DAPI stainning and flow cytometry (FCM) respectively. The expression of apotosis-related proteins (cytochrome c, caspase 9 and caspase 3) in the H9c2 cells was detected by Western blot. Results Compared with mere H/R treatment, the decrease in cell viability and increase in the number of apoptotic cells in H9c2 cells subjected to H/R were significantly exacerbated in the presence of acrolein (P<0. 05). The liberation of cytochrome c from mitochondria to cytosol, the cleavages of the initiator caspase 9 and the effector caspase 3 have been observed after pretreatment with acrolein followed by H/ R in H9c2 cells. Conclusion Acrolein could aggravate H/R injury and that this effect may be related, in part, to the modification of proteins involved the release of cytochrome c from mitochondria to cytosol and activation of caspases cascade reaction.%目的 研究丙烯醛对缺氧复氧H9c2心肌细胞损伤的影响,并探讨其促凋亡作用机理.方法 建立H9c2心肌细胞缺氧复氧(H/R)损伤模型,分为正常对照组、丙烯醛组(ACR)、缺氧复氧组(H/R)、丙烯醛+缺氧复氧组(ACR+H/R).用10μmol/L丙烯醛预处理H9c2心肌细胞30mmin后2h缺氧16h复氧,采用MTT法检测细胞存活率,4’,6-二脒基-2苯基吲哚(DAPI)荧光染色检测细胞核凋亡的形态学改变,流式细胞术检测细胞凋

  11. DFT-Based Explanation of the Effect of Simple Anionic Ligands on the Regioselectivity of the Heck Arylation of Acrolein Acetals

    Henriksen, Signe Teuber; Tanner, David Ackland; Cacchi, Sandro

    2009-01-01

    The Heck arylation of acrolein acetal has been studied computationally and compared to the corresponding reaction with allyl ethers. The reaction can be controlled to give either cinnamaldehydes or arylpropanoic esters by addition of different coordinating anions, acetate, or chloride. The comput......The Heck arylation of acrolein acetal has been studied computationally and compared to the corresponding reaction with allyl ethers. The reaction can be controlled to give either cinnamaldehydes or arylpropanoic esters by addition of different coordinating anions, acetate, or chloride...

  12. NMR investigation of acrolein stability in hydroalcoholic solution as a foundation for the valid HS-SPME/GC-MS quantification of the unsaturated aldehyde in beverages.

    Kächele, Martin; Monakhova, Yulia B; Kuballa, Thomas; Lachenmeier, Dirk W

    2014-04-11

    Acrolein (propenal) is found in many foods and beverages and may pose a health hazard due to its cytotoxicity. Considerable knowledge gaps regarding human exposure to acrolein exist, and there is a lack of reliable analytical methods. Hydroalcoholic dilutions prepared for calibration purposes from pure acrolein show considerable degradation of the compound and nuclear magnetic resonance (NMR) spectroscopy showed that 1,3,3-propanetriol and 3-hydroxypropionaldehyde are formed. The degradation can be prevented by addition of hydroquinone as stabilizer to the calibration solutions, which then show linear concentration-response behaviour required for quantitative analysis. The stabilized calibration solutions were used for quantitative headspace solid-phase microextraction/gas chromatography-mass spectrometry (HS-SPME/GC-MS) determination of acrolein in alcoholic beverages with a detection limit of 14 μg L(-1). Of 117 tested alcoholic beverages, 64 were tested positive with the highest incidence in grape marc spirits and whiskey (100%, mean 252 μg L(-1)), followed by fruit spirits (86%, mean 591 μg/L(-1)), tequila (86%, mean 404 μg L(-1)), Asian spirits (43%, mean 54 μg L(-1)) and wine (9%, mean 0.7 μg L(-1)). Acrolein could not be detected in beer, vodka, absinthe and bottled water. Six of the fruit and grape marc spirits had acrolein levels above the World Health Organization (WHO) provisional tolerable concentration of 1.5 mg L(-1).

  13. Acrolein, A Reactive Product of Lipid Peroxidation, Induces Oxidative Modification of Cytochrome c

    Kang, Jung Hoon [Cheongju Univ., Cheongju (Korea, Republic of)

    2013-11-15

    Acrolein (ACR) is a well-known carbonyl toxin produced by lipid peroxidation of polyunsaturated fatty acids, which is involved in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). In Alzheimer's brain, ACR was found to be elevated in hippocampus and temporal cortex where oxidative stress is high. In this study, we evaluated oxidative modification of cytochrome c occurring after incubation with ACR. When cytochrome c was incubated with ACR, protein aggregation increased in a dose-dependent manner. The formation of carbonyl compounds and the release of iron were obtained in ACR-treated cytochrome c. Reactive oxygen species scavengers and iron specific chelator inhibited the ACR-mediated cytochrome c modification and carbonyl compound formation. Our data demonstrate that oxidative damage of cytochrome c by ACR might induce disruption of cyotochrome c structure and iron mishandling as a contributing factor to the pathology of AD.

  14. Explicit solvent model for spectral shift of acrolein and simulation with molecular dynamics

    ZHU Quan; LIU Jifeng; FU Kexiang; HAN Keli; LI Xiangyuan

    2006-01-01

    By introducing the concept of spring energy of permanent dipole and taking the conformations of solvent molecules into account, the formulas of electrostatic solvation energy in equilibrium and nonequilibrium are derived from the explicit solvent scheme, with the spatial distribution of the discrete permanent charges and induced dipoles of the solvent molecules involved. The energy change of solute due to the variation of wave function from the case of vacuum to that in solution is estimated by treating the solvent effect as external field in the iteration cycles of the self-consistent field. The expression for spectral shift is deduced and applied to the processes of light absorption and emission in solution. According to the new formulations, the averaged solvent electrostatic potential/molecular dynamics program is modified and adopted to investigate the equilibrium solvation energy of water molecule and spectral shift of acrolein.

  15. CCR5 delta32, matrix metalloproteinase-9 and disease activity in multiple sclerosis

    Sellebjerg, Finn; Madsen, Hans O; Jensen, Claus V

    2000-01-01

    Chemokines and matrix metalloproteinases (MMPs) appear to be crucial in leukocyte recruitment to the central nervous system in multiple sclerosis (MS). CCR5 delta32, a truncated allele of the CC chemokine receptor CCR5 gene encoding a non-functional receptor, did not confer protection from MS. CCR5...

  16. Electronic excitations in a dielectric continuum solvent with quantum Monte Carlo: Acrolein in water

    Floris, Franca Maria; Filippi, Claudia; Amovilli, Claudio

    2014-01-01

    We investigate here the vertical n → π* and π → π* transitions of s-trans-acrolein in aqueous solution by means of a polarizable continuum model (PCM) we have developed for the treatment of the solute at the quantum Monte Carlo (QMC) level of the theory. We employ the QMC approach which allows us to work with highly correlated electronic wave functions for both the solute ground and excited states and, to study the vertical transitions in the solvent, adopt the commonly used scheme of considering fast and slow dielectric polarization. To perform calculations in a non-equilibrium solvation regime for the solute excited state, we add a correction to the global dielectric polarization charge density, obtained self consistently with the solute ground-state wave function by assuming a linear-response scheme. For the solvent polarization in the field of the solute in the ground state, we use the static dielectric constant while, for the electronic dielectric polarization, we employ the solvent refractive index evaluated at the same frequency of the photon absorbed by the solute for the transition. This choice is shown to be better than adopting the most commonly used value of refractive index measured in the region of visible radiation. Our QMC calculations show that, for standard cavities, the solvatochromic shifts obtained with the PCM are underestimated, even though of the correct sign, for both transitions of acrolein in water. Only by reducing the size of the cavity to values where more than one electron is escaped to the solvent region, we regain the experimental shift for the n → π* case and also improve considerably the shift for the π → π* transition.

  17. Electronic excitations in a dielectric continuum solvent with quantum Monte Carlo: Acrolein in water

    Floris, Franca Maria, E-mail: floris@dcci.unipi.it; Amovilli, Claudio [Dipartimento di Chimica e Chimica Industriale, Università di Pisa, Via Risorgimento 35, 56126 Pisa (Italy); Filippi, Claudia [MESA Institute for Nanotechnology, University of Twente, P.O. Box 217, 7500 AE Enschede (Netherlands)

    2014-01-21

    We investigate here the vertical n → π{sup *} and π → π{sup *} transitions of s-trans-acrolein in aqueous solution by means of a polarizable continuum model (PCM) we have developed for the treatment of the solute at the quantum Monte Carlo (QMC) level of the theory. We employ the QMC approach which allows us to work with highly correlated electronic wave functions for both the solute ground and excited states and, to study the vertical transitions in the solvent, adopt the commonly used scheme of considering fast and slow dielectric polarization. To perform calculations in a non-equilibrium solvation regime for the solute excited state, we add a correction to the global dielectric polarization charge density, obtained self consistently with the solute ground-state wave function by assuming a linear-response scheme. For the solvent polarization in the field of the solute in the ground state, we use the static dielectric constant while, for the electronic dielectric polarization, we employ the solvent refractive index evaluated at the same frequency of the photon absorbed by the solute for the transition. This choice is shown to be better than adopting the most commonly used value of refractive index measured in the region of visible radiation. Our QMC calculations show that, for standard cavities, the solvatochromic shifts obtained with the PCM are underestimated, even though of the correct sign, for both transitions of acrolein in water. Only by reducing the size of the cavity to values where more than one electron is escaped to the solvent region, we regain the experimental shift for the n → π{sup *} case and also improve considerably the shift for the π → π{sup *} transition.

  18. A new kinetic model based on the remote control mechanism to fit experimental data in the selective oxidation of propene into acrolein on biphasic catalysts

    Abdeldayem, H.M.; Ruiz, P.; Delmon, B. [Unite de Catalyse et Chimie des Materiaux Divises, Universite Catholique de Louvain, Louvain-La-Neuve (Belgium); Thyrion, F.C. [Unite des Procedes Faculte des Sciences Appliquees, Universite Catholique de Louvain, Louvain-La-Neuve (Belgium)

    1998-12-31

    A new kinetic model for a more accurate and detailed fitting of the experimental data is proposed. The model is based on the remote control mechanism (RCM). The RCM assumes that some oxides (called `donors`) are able to activate molecular oxygen transforming it to very active mobile species (spillover oxygen (O{sub OS})). O{sub OS} migrates onto the surface of the other oxide (called `acceptor`) where it creates and/or regenerates the active sites during the reaction. The model contains tow terms, one considering the creation of selective sites and the other the catalytic reaction at each site. The model has been tested in the selective oxidation of propene into acrolein (T=380, 400, 420 C; oxygen and propene partial pressures between 38 and 152 Torr). Catalysts were prepared as pure MoO{sub 3} (acceptor) and their mechanical mixtures with {alpha}-Sb{sub 2}O{sub 4} (donor) in different proportions. The presence of {alpha}-Sb{sub 2}O{sub 4} changes the reaction order, the activation energy of the reaction and the number of active sites of MoO{sub 3} produced by oxygen spillover. These changes are consistent with a modification in the degree of irrigation of the surface by oxygen spillover. The fitting of the model to experimental results shows that the number of sites created by O{sub SO} increases with the amount of {alpha}-Sb{sub 2}O{sub 4}. (orig.)

  19. Aryl Hydrocarbon Receptor Activation by TCDD Modulates Expression of Extracellular Matrix Remodeling Genes during Experimental Liver Fibrosis

    Lamb, Cheri L.; Cholico, Giovan N.; Perkins, Daniel E.; Fewkes, Michael T.; Oxford, Julia Thom; Lujan, Trevor J.; Morrill, Erica E.

    2016-01-01

    The aryl hydrocarbon receptor (AhR) is a soluble, ligand-activated transcription factor that mediates the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Increasing evidence implicates the AhR in regulating extracellular matrix (ECM) homeostasis. We recently reported that TCDD increased necroinflammation and myofibroblast activation during liver injury elicited by carbon tetrachloride (CCl4). However, TCDD did not increase collagen deposition or exacerbate fibrosis in CCl4-treated mice, which raises the possibility that TCDD may enhance ECM turnover. The goal of this study was to determine how TCDD impacts ECM remodeling gene expression in the liver. Male C57BL/6 mice were treated for 8 weeks with 0.5 mL/kg CCl4, and TCDD (20 μg/kg) was administered during the last two weeks. Results indicate that TCDD increased mRNA levels of procollagen types I, III, IV, and VI and the collagen processing molecules HSP47 and lysyl oxidase. TCDD also increased gelatinase activity and mRNA levels of matrix metalloproteinase- (MMP-) 3, MMP-8, MMP-9, and MMP-13. Furthermore, TCDD modulated expression of genes in the plasminogen activator/plasmin system, which regulates MMP activation, and it also increased TIMP1 gene expression. These findings support the notion that AhR activation by TCDD dysregulates ECM remodeling gene expression and may facilitate ECM metabolism despite increased liver injury. PMID:27672655

  20. Relationship between activation volume and polymer matrix effects on photochromic performance: bridging molecular parameter to macroscale effect.

    Shima, Kentaro; Mutoh, Katsuya; Kobayashi, Yoichi; Abe, Jiro

    2015-02-19

    Photochromic compounds have attracted attention as ophthalmic lenses because of their reversible color modulation upon irradiation with light. However, the efficiency of the photochromism is strongly affected by their surrounding because of the structural changes concomitant with the photochromism, which causes the decrease in the photochromic performance in the polymer matrix. Therefore, the clarification of the degree of the structural changes is necessary to apply to the ophthalmic lenses. Bridged imidazole dimers are one of the fast photoswitch molecules possessing high photochromic quantum yield and durability. Although the enhancement of the photochromic properties of bridged imidazole dimers has been vigorously studied, the quantitative information about the structural changes has not been revealed in detail. In this study, we investigated the pressure effects on the photochromic properties of bridged imidazole dimers. The activation volume for the thermal back-reaction of the photogenerated biradical species becomes an effective measure to predict the degree of the structural change during the photochromic reaction. We revealed that the smaller activation volume is suitable for keeping the efficient photochromic reaction in the polymer matrix because the photochromic reaction is not affected by the surroundings. These fundamental insights into the molecular dynamics provide valuable information to develop fast photochromic compounds that are suitable for the use in the polymer matrix and pressure sensitive photochromic materials.

  1. Sol-gel coatings as active barriers to protect ceramic reinforcement in aluminum matrix composites

    Rams, J.; Urena, A.; Campo, M. [Departamento de Tecnologia Quimica, Ambiental y de los Materiales, ESCET, Universidad Rey Juan Carlos C/ Tulipan s/nMostoles 28933 Madrid (Spain)

    2004-02-01

    Silica obtained through a sol-gel process is used as a coating for ceramic reinforcements (SiC) in aluminium matrix composite materials. The interaction between molten aluminium and the coated particles during material casting can be controlled by means of the thermal treatment given to the coating. Wettability is increased because the coating reacts with molten aluminium, and the formation of the degrading aluminium carbide is inhibited. (Abstract Copyright [2004], Wiley Periodicals, Inc.)

  2. Carbon Nanotube Active-Matrix Backplanes for Conformal Electronics and Sensors

    2011-11-03

    can be potentially combined with inkjet printing of metal contacts to achieve lithography-free fabrication of low-cost flexible and stretchable...report a promising approach for fabricating large-scale flexible and stretchable electronics using a semiconductor-enriched carbon nanotube solution...Matrix Backplanes for Conformal Electronics and Sensors Report Title ABSTRACT In this paper, we report a promising approach for fabricating large

  3. Biochemical and toxicological evaluation of nano-heparins in cell functional properties, proteasome activation and expression of key matrix molecules.

    Piperigkou, Zoi; Karamanou, Konstantina; Afratis, Nikolaos A; Bouris, Panagiotis; Gialeli, Chrysostomi; Belmiro, Celso L R; Pavão, Mauro S G; Vynios, Dimitrios H; Tsatsakis, Aristidis M

    2016-01-05

    The glycosaminoglycan heparin and its derivatives act strongly on blood coagulation, controlling the activity of serine protease inhibitors in plasma. Nonetheless, there is accumulating evidence highlighting different anticancer activities of these molecules in numerous types of cancer. Nano-heparins may have great biological significance since they can inhibit cell proliferation and invasion as well as inhibiting proteasome activation. Moreover, they can cause alterations in the expression of major modulators of the tumor microenvironment, regulating cancer cell behavior. In the present study, we evaluated the effects of two nano-heparin formulations: one isolated from porcine intestine and the other from the sea squirt Styela plicata, on a breast cancer cell model. We determined whether these nano-heparins are able to affect cell proliferation, apoptosis and invasion, as well as proteasome activity and the expression of extracellular matrix molecules. Specifically, we observed that nano-Styela compared to nano-Mammalian analogue has higher inhibitory role on cell proliferation, invasion and proteasome activity. Moreover, nano-Styela regulates cell apoptosis, expression of inflammatory molecules, such as IL-6 and IL-8 and reduces the expression levels of extracellular matrix macromolecules, such as the proteolytic enzymes MT1-MMP, uPA and the cell surface proteoglycans syndecan-1 and -2, but not on syndecan-4. The observations reported in the present article indicate that nano-heparins and especially ascidian heparin are effective agents for heparin-induced effects in critical cancer cell functions, providing an important possibility in pharmacological targeting.

  4. How, with whom and when: an overview of CD147-mediated regulatory networks influencing matrix metalloproteinase activity.

    Grass, G Daniel; Toole, Bryan P

    2015-11-24

    Matrix metalloproteinases (MMPs) comprise a family of 23 zinc-dependent enzymes involved in various pathologic and physiologic processes. In cancer, MMPs contribute to processes from tumour initiation to establishment of distant metastases. Complex signalling and protein transport networks regulate MMP synthesis, cell surface presentation and release. Earlier attempts to disrupt MMP activity in patients have proven to be intolerable and with underwhelming clinical efficacy; thus targeting ancillary proteins that regulate MMP activity may be a useful therapeutic approach. Extracellular matrix metalloproteinase inducer (EMMPRIN) was originally characterized as a factor present on lung cancer cells, which stimulated collagenase (MMP-1) production in fibroblasts. Subsequent studies demonstrated that EMMPRIN was identical with several other protein factors, including basigin (Bsg), all of which are now commonly termed CD147. CD147 modulates the synthesis and activity of soluble and membrane-bound [membrane-type MMPs (MT-MMPs)] in various contexts via homophilic/heterophilic cell interactions, vesicular shedding or cell-autonomous processes. CD147 also participates in inflammation, nutrient and drug transporter activity, microbial pathology and developmental processes. Despite the hundreds of manuscripts demonstrating CD147-mediated MMP regulation, the molecular underpinnings governing this process have not been fully elucidated. The present review summarizes our present knowledge of the complex regulatory systems influencing CD147 biology and provides a framework to understand how CD147 may influence MMP activity.

  5. One-step synthesis of bismuth molybdate catalysts via flame spray pyrolysis for the selective oxidation of propylene to acrolein

    Schuh, K.; Kleist, W.; Høj, Martin

    2014-01-01

    Flame spray pyrolysis (FSP) of Bi(III)-and Mo(VI)-2-ethylhexanoate dissolved in xylene resulted in various nanocrystalline bismuth molybdate phases depending on the Bi/Mo ratio. Besides alpha-Bi2Mo3O12 and gamma-Bi2MoO6, FSP gave direct access to the metastable beta-Bi2Mo2O9 phase with high surfa...... to acrolein at temperatures relevant for industrial applications (360 degrees C)....

  6. Supplemental Immobilization of Hanford Low-Activity Waste: Cast Stone Augmented Formulation Matrix Tests

    Cozzi, A. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Crawford, C. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Fox, K. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Hansen, E. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Roberts, K. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2015-07-20

    More than 56 million gallons of radioactive and hazardous waste are stored in 177 underground storage tanks at the U.S. Department of Energy’s (DOE’s) Hanford Site in Washington State. The HLW will be vitrified in the HLW facility for ultimate disposal at an offsite federal repository. A portion (~35%) of the LAW will be vitrified in the LAW vitrification facility for disposal onsite at the Integrated Disposal Facility (IDF). The pretreatment and HLW vitrification facilities will have the capacity to treat and immobilize all of the wastes destined for those facilities. However, a second facility will be needed for the expected volume of LAW requiring immobilization. Cast Stone, a cementitious waste form, is being considered to provide the required additional LAW immobilization capacity. The Cast Stone waste form must be acceptable for disposal in the IDF. The Cast Stone waste form and immobilization process must be tested to demonstrate that the final Cast Stone waste form can comply with the waste acceptance criteria for the disposal facility and that the immobilization processes can be controlled to consistently provide an acceptable waste form product. A testing program was developed in fiscal year (FY) 2012 describing in detail the work needed to develop and qualify Cast Stone as a waste form for the solidification of Hanford LAW. A statistically designed test matrix was used to evaluate the effects of key parameters on the properties of the Cast Stone as it is initially prepared and after curing. For the processing properties, the water-to-dry-blend mix ratio was the most significant parameter in affecting the range of values observed for each property. The single shell tank (SST) Blend simulant also showed differences in measured properties compared to the other three simulants tested. A review of the testing matrix and results indicated that an additional set of tests would be beneficial to improve the understanding of the impacts noted in the Screening

  7. 环磷酰胺代谢产物丙烯醛对未成熟睾丸支持细胞骨架的影响及机制研究%Effect of acrolein on cytoskeleton of Sertoli cells

    刘丰; 李旭良; 林涛; 何大维; 魏光辉; 刘俊宏

    2011-01-01

    Objective To investigate the mechanism and the effect of Acrolein on cytoskeleton of Sertoli cells. Methods We isolated and identified Sertoli cells from 8-day-old SD rats' testes. The experimental groups were treated with Acrolein, The control group were treated with phosphate buffered solution. After 12 hours, the treated cells were dyed with DHE to assay the distribution of superoxide anion, and the ultrastructure of the Sertoli cells was examined with transmission electron microscope, F-actin was stained with fluorescent antibody, and the expression of ERK and p38 in Sertoli cells were assayed by Western blot. Results The photodensity of superoxide anion, the expression of ERK and p38 were increased in the experimental groups. After treatment with Acrolein, the ultrastructure of the Sertoli cells was changed, manisfested as chondriosome swelling; chromatin clumping, condensed endochylema; split nuclei and vacuolization. All of these changes were followed by a F-actin accumulation, marginalization and regionalization. Conclusions Acrolein, the main toxic metabolite of cyclophosphamide, damages the cytoskeleton of immature Sertoli cells through oxidization stress, which might activate the MAPK signaling pathway mainly by increasing the expressions of ERK and p38.%目的 探讨环磷酰胺(cyclophosphamide,CP)代谢产物丙烯醛(acrolein,ACR)对未成熟睾丸Sertoli细胞骨架的损伤及其机制.方法 建立新生SD大鼠Sertoli细胞原代培养模型,实验组给予100 μmol/L浓度的ACR溶液,对照组给予PBS溶液,12 h后分别用超氧化物阴离子荧光探针染色观察Sertoli细胞内超氧化阴离子的变化,透射电子显微镜观察ACR对细胞超微结构的影响,免疫荧光染色观察细胞骨架中F-actin的分布变化,Western blot方法测定ERK和p38的表达水平.结果 ①ACR能增强sertoli细胞内活性氧的水平;②ACR处理后,实验组细胞线粒体发生了肿胀,染色质发生了凝集,出现胞质浓缩、核溢

  8. Evaluation of N-acetylcysteine and methylprednisolone as therapies for oxygen and acrolein-induced lung damage

    Critchley, J.A.J.H. (Univ. of Edinburgh (England)); Beeley, J.M.; Clark, R.J.; Buchanan, J.D. (Royal Naval Hospital Hoslar, Gosport (England)); Summerfield, M.; Bell, S. (Admiralty Research Establishment, Alverstoke (England)); Spurlock, M.S.; Edginton, J.A.G. (Chemical Defence Establishment, Porton Down (England))

    1990-04-01

    Reactive oxidizing species are implicated in the etiology of a range of inhalational pulmonary injuries. Consequently, various free radical scavengers have been tested as potential prophylactic agents. The sulfydryl compound, N-acetylcysteine (NAC) is the only such compound clinically available for use in realistic dosages, and it is well established as an effective antidote for the hepatic and renal toxicity of paracetamol. Another approach in pulmonary injury prophylaxis is methylprednisolone therapy. The authors evaluated NAC and methylprednisolone in two rats models of inhalation injury: 40-hr exposure to >97% oxygen at 1.1 bar and 15-min exposure to acrolein vapor (210 ppm). The increases in lung wet/dry weight ratios, seen with both oxygen and acrolein toxicity were reduced with both treatments. However, with oxygen, NAC therapy was associated with considerably increased mortality and histological changes. Furthermore, IP NAC administration resulted in large volumes of ascitic fluid. With acrolein, IV, NAC had no significant effect on mortality or pulmonary histological damage. Methylprednisolone had no beneficial effects on either the mortality or histological damage observed in either toxicity model. They caution against the ad hoc use of NAC in the management of inhalational pulmonary injury.

  9. Research Advances in Biomarkers of Acrolein Exposure%丙烯醛生物标志物研究进展

    侯宏卫; 熊巍; 张小涛; 范多清; 者为; 唐纲岭; 胡清源

    2011-01-01

    丙烯醛是普遍存在于环境中的有机污染物,同时也是卷烟烟气中重要有害成分,长时间暴露可诱发多种疾病。研究丙烯醛对人体的暴露水平可为有效控制环境中的丙烯醛污染提供基础数据,揭示其对人体健康的早期影响。该文对丙烯醛的体内代谢途径、主要的生物标志物、检测方法等进行综述,并展望其在烟气接触人群和普通人群生物监测中的应用。%Acrolein is a ubiquitous organic pollutant in the environment, but also an important harmful component in cigarette smoke. Long-term exposure can induce many kinds of diseases in human. Researches on human acrolein exposure levels and risk evaluation for the effective control of pollution in the environment can provide the basic data, and revealed the early effects on human health. In the present paper, the metabolism of acrolein, the major biomarkers and test methods were reviewed, and the application of them in biomonitoring was discussed also.

  10. New Insights in the Pathogenesis of Multiple Sclerosis—Role of Acrolein in Neuronal and Myelin Damage

    Riyi Shi

    2013-10-01

    Full Text Available Multiple sclerosis (MS is an autoimmune disease of the central nervous system (CNS characterized by an inappropriate inflammatory reaction resulting in widespread myelin injury along white matter tracts. Neurological impairment as a result of the disease can be attributed to immune-mediated injury to myelin, axons and mitochondria, but the molecular mechanisms underlying the neuropathy remain incompletely understood. Incomplete mechanistic knowledge hinders the development of therapies capable of alleviating symptoms and slowing disease progression in the long-term. Recently, oxidative stress has been implicated as a key component of neural tissue damage prompting investigation of reactive oxygen species (ROS scavengers as a potential therapeutic option. Despite the establishment of oxidative stress as a crucial process in MS development and progression, ROS scavengers have had limited success in animal studies which has prompted pursuit of an alternative target capable of curtailing oxidative stress. Acrolein, a toxic β-unsaturated aldehyde capable of initiating and perpetuating oxidative stress, has been suggested as a viable point of intervention to guide the development of new treatments. Sequestering acrolein using an FDA-approved compound, hydralazine, offers neuroprotection resulting in dampened symptom severity and slowed disease progression in experimental autoimmune encephalomyelitis (EAE mice. These results provide promise for therapeutic development, indicating the possible utility of neutralizing acrolein to preserve and improve neurological function in MS patients.

  11. 丙烯醛生产工艺技术进展%Progress in the Production Process Technology of Acrolein

    徐燏

    2014-01-01

    Acrolein, also known as allyl aldehyde, is an important organic chemical raw materials with wide range of uses. At present, it is mainly used for the preparation of animal feed additive methionine. There are many method of synthesizing acrolein, some of them are not industrialized due to the raw materials do not have the extensive to get easily and with poor economy, and some synthesis methods with cheap and readily available raw materials have no catalysts with better performance resulting in its selectivity and yield are not high. Currently air oxidation of propylene is the main method to produce acrolein.%丙烯醛又称烯丙醛,是一种用途广泛的重要有机化工原料。目前主要用于动物饲料添加剂蛋氨酸的制备。合成丙烯醛的方法较多,有些因原料不具有广泛易得经济性较差,原料廉价易得的合成方法因没有性能较好的催化剂致使其选择性、收率不高等原因而未工业化。目前丙烯空气氧化法生产丙烯醛是主要方法。

  12. Modulation of Active Site Electronic Structure by the Protein Matrix to Control [NiFe] Hydrogenase Reactivity

    Smith, Dayle MA; Raugei, Simone; Squier, Thomas C.

    2014-09-30

    Control of the reactivity of the nickel center of the [NiFe] hydrogenase and other metalloproteins commonly involves outer coordination sphere ligands that act to modify the geometry and physical properties of the active site metal centers. We carried out a combined set of classical molecular dynamics and quantum/classical mechanics calculations to provide quantitative estimates of how dynamic fluctuations of the active site within the protein matrix modulate the electronic structure at the catalytic center. Specifically we focused on the dynamics of the inner and outer coordination spheres of the cysteinate-bound Ni–Fe cluster in the catalytically active Ni-C state. There are correlated movements of the cysteinate ligands and the surrounding hydrogen-bonding network, which modulate the electron affinity at the active site and the proton affinity of a terminal cysteinate. On the basis of these findings, we hypothesize a coupling between protein dynamics and electron and proton transfer reactions critical to dihydrogen production.

  13. Evaluation of matrix metalloproteinase and cysteine cathepsin activity in dentin hybrid layer by gelatin zymography

    Sekar Mahalaxmi

    2016-01-01

    Conclusion: Etch and rinse adhesive activated MMPs and CCs within the hybrid layer that remained active till 7th day and no gelatinolytic activity was found on 21st day and MMPs are more active compared to CCs and MMP-2.

  14. Sunlight activated lanthanide complex for luminescent solar collector applications: effect of waveguide matrix

    Shahi, Praveen Kumar; Singh, Priyam; Bahadur Rai, Shyam

    2017-02-01

    The performance of Eu(DBM)3Phen complex (EDP) dispersed in PMMA poly-(methyl methacrylate) polymer matrix, as simple planner luminescent solar collectors (LSCs) is demonstrated using spectroscopic and photovoltaic (PV) measurements. The organic ligands absorb ultra-violet-blue (UV-blue) radiation (220–450 nm) very efficiently and transfer its energy to the Eu3+ ion, which gives an intense red emission even in sunlight exposure. The excellent optical properties of EDP in PMMA permit its coating on the front surface of c-Si solar cell (10  ×  10 cm2) for PV measurements. The PV characterizations reveal the improvement in the short circuit current density (J sc) of PV cell and maximum improvement is found to be 4.6% for 2.5 wt% EDP concentration in PMMA matrix. The efficiency of solar cell increases from 17.22% to 18.33% for bare and 2.5% EDP in PMMA. At a higher concentration of EDP, the thin film starts losing its transparency and hence PV efficiency decreases. These results illustrate that a EDP complex combined with a PV cell could work as a prototype of a new generation solar cell.

  15. Recent progress in glycerol dehydration to acrolein%甘油选择性脱水制备丙烯醛研究进展

    陈维苗; 丁云杰; 宁丽丽; 龚磊峰; 吕元

    2009-01-01

    生物柴油以其环保性和可再生性而被公认为是可替代石化柴油的新型能源,其迅猛发展将导致其副产物甘油的大量过剩,因此,开发和深度利用甘油,使其成为新一代从生物质到化学品的转化平台成为近期研究热点,其中,甘油脱水制丙烯醛是重要途径.综述了实现该过程的催化剂体系研究进展,探讨了催化剂结构和反应条件对甘油脱水反应性能的影响,分析了甘油脱水的反应路径,以期对开发高性能催化体系和合理工艺提供参考.由于匀相催化剂存在活性低、操作条件苛刻和设备腐蚀等缺点,开发的重点集中在固体酸催化剂上,虽然活性较高,但易失活,稳定性差.仍需进一步提高催化剂性能,同时结合反应器和工艺的设计和选择,综合考量.%The rapidly rising production of biodiesel from vegetable oils will lead to a drastic surplus of by-product glycerol in chemical markets. The utilization of large amount of glycerol is the driving force of developing new processes. As a sustainable alternative, acrolein can be produced by the dehydration of glycerol. Recent progress in catalyst systems for glycerol dehydration to acrolein was reviewed. The effects of catalyst properties and reaction conditions on glycerol dehydration performance were discussed, as well as its reaction networks. Due to severe operation conditions and corrosion, the researches were focused on the heterogeneous solid acid catalysts. The catalysts had higher activity, but lower stability. The future study should concentrate on further improvement of the catalyst performances, especially sta-bility, and optimization of reaction conditions and selection of proper reactor.

  16. Low Power, Red, Green and Blue Carbon Nanotube Enabled Vertical Organic Light Emitting Transistors for Active Matrix OLED Displays

    McCarthy, M. A. [University of Florida, Gainesville; Liu, B. [University of Florida, Gainesville; Donoghue, E. P. [University of Florida, Gainesville; Kravchenko, Ivan I [ORNL; Kim, D. Y. [University of Florida, Gainesville; So, Franky [University of Florida, Gainesville; Rinzler, A. G. [University of Florida, Gainesville

    2011-01-01

    Organic semiconductors are potential alternatives to polycrystalline silicon as the semiconductor used in the backplane of active matrix organic light emitting diode displays. Demonstrated here is a light-emitting transistor with an organic channel, operating with low power dissipation at low voltage, and high aperture ratio, in three colors: red, green and blue. The single-wall carbon nanotube network source electrode is responsible for the high level of performance demonstrated. A major benefit enabled by this architecture is the integration of the drive transistor, storage capacitor and light emitter into a single device. Performance comparable to commercialized polycrystalline-silicon TFT driven OLEDs is demonstrated.

  17. Solution-Processed Organic Thin-Film Transistor Array for Active-Matrix Organic Light-Emitting Diode

    Harada, Chihiro; Hata, Takuya; Chuman, Takashi; Ishizuka, Shinichi; Yoshizawa, Atsushi

    2013-05-01

    We developed a 3-in. organic thin-film transistor (OTFT) array with an ink-jetted organic semiconductor. All layers except electrodes were fabricated by solution processes. The OTFT performed well without hysteresis, and the field-effect mobility in the saturation region was 0.45 cm2 V-1 s-1, the threshold voltage was 3.3 V, and the on/off current ratio was more than 106. We demonstrated a 3-in. active-matrix organic light-emitting diode (AMOLED) display driven by the OTFT array. The display could provide clear moving images. The peak luminance of the display was 170 cd/m2.

  18. Enhanced Pixel-Driving Circuits for Active-Matrix Organic-Light-Emitting Diode Displays with Large Sizes

    Yu, Sang Ho; Choi, Sung Wook; Shin, Hong Jae; Kwack, Kae Dal; Kim, Tae Whan

    2005-03-01

    Enhanced pixel-driving circuits for active-matrix organic-light-emitting diode (AM-OLED) displays with large sizes and highly uniform brightnesses were designed for system on panel. The driving method used the pre-charge functions of the data for a highly uniform brightness during a short time to program the current. The currents of the designed pixel-driving circuits were not significantly affected by variations in the threshold voltages, or by the mobilities of the driving thin-film transistors. These results indicate that the proposed pixel-driving circuits hold promise for potential applications in AM-OLED displays with large sizes and highly uniform brightnesses.

  19. Environmental Topology and Water Availability Modulates the Catalytic Activity of β-Galactosidase Entrapped in a Nanosporous Silicate Matrix

    M. Ines Burgos; Manuel I. Velasco; Acosta, Rodolfo H.; María A. Perillo

    2016-01-01

    In the present work we studied the catalytic activity of E. coli β-Gal confined in a nanoporous silicate matrix (Eβ-Gal) at different times after the beginning of the sol-gel polymerization process. Enzyme kinetic experiments with two substrates (ONPG and PNPG) that differed in the rate-limiting steps of the reaction mechanism for their β-Gal-catalyzed hydrolysis, measurements of transverse relaxation times (T 2 ) of water protons through 1H-NMR, and scanning electron microscopy analysis of t...

  20. Novel inhibitors of urokinase-type plasminogen activator and matrix metalloproteinase expression in metastatic cancer cell lines.

    Cakarovski, Kristina; Leung, Jenny Y; Restall, Christina; Carin-Carlson, Anna; Yang, Eunice; Perlmutter, Patrick; Anderson, Robin; Medcalf, Robert; Dear, Anthony E

    2004-07-01

    The plasminogen-activating (PA) and matrix metalloproteinase (MMP) enzyme systems are implicated in proteolytic turnover of the extracellular matrix (ECM) associated with biologic processes including wound healing, inflammation and angiogenesis. Aberrant expression of components of the PA and MMP enzyme systems occurs in the pathogenesis of metastatic cancer. Oxamflatin (Ox), a novel hydroxamic acid derivative, inhibits u-PA mRNA expression and proteolytic activity while simultaneously upregulating the expression of the natural inhibitor of u-PA, plasminogen activator inhibitor type 2 (PAI-2) in metastatic cancer cells. We have characterized the effects of Ox and a novel derivative, Metacept-1 (MCT-1), on PA and MMP-mediated proteolysis and invasion in several metastatic tumor lines. Both compounds are able to inhibit u-PA-, MMP-2- and MMP-9-mediated gene expression at low micromolar concentrations as well as u-PA- and MMP-mediated proteolysis as assessed by zymography, with MCT-1 being the more effective of the 2 agents in some assays. Cellular invasion assays correlate with gene expression and zymography experiments identifying both Ox and MCT-1 as able to inhibit invasion of metastatic cancer cell lines through matrigel at nanomolar concentrations, with MCT-1 more effective than Ox in 2 of the 3 cancer cell lines assessed.

  1. AMP-Activated Protein Kinase Alleviates Extracellular Matrix Accumulation in High Glucose-Induced Renal Fibroblasts through mTOR Signaling Pathway

    Xia Luo

    2015-01-01

    Full Text Available Background/Aims: Extracellular matrix accumulation contributes significantly to the pathogenesis of diabetic nephropathy. Although AMP-activated protein kinase (AMPK has been found to inhibit extracellular matrix synthesis by experiments in vivo and vitro, its role in alleviating the deposition of extracellular matrix in renal interstitial fibroblasts has not been well defined. Methods: Currently, we conducted this study to investigate the effects of AMPK on high glucose-induced extracellular matrix synthesis and involved intracellular signaling pathway by using western blot in the kidney fibroblast cell line (NRK-49f. Results: Collagen IV protein levels were significantly increased by high glucose in a time-dependent manner. This was associated with a decrease in Thr72 phosphorylation of AMPK and an increase in phosphorylation of mTOR on Ser2448. High glucose-induced extracellular matrix accumulation and mTOR activation were significantly inhibited by the co-treatment of rAAV-AMPKα1312 (encoding constitutively active AMPKα1 whereas activated by r-AAV-AMPKα1D157A (encoding dominant negative AMPKα1. In cultured renal fibroblasts, overexpression of AMPKα1D157A upregulated mTOR signaling and matrix synthesis, which were ameliorated by co-treatment with the inhibitor of mTOR, rapamycin. Conclusion: Collectively, these findings indicate that AMPK exerts renoprotective effects by inhibiting the accumulation of extracellular matrix through mTOR signaling pathway.

  2. Effect of lipid matrix and cytoskeleton proteins on Ca2+-activated K+ channels in erythrocytes of alcoholic and II type diabetes mellitus patients.

    Prokop'eva, V D; Petrova, I V; Sitozhevskii, A V; Kremeno, S V; Koryukin, V I; Baskakov, M B; Bokhan, N A; Novitskii, V V

    2002-10-01

    We studied the effect of changes in erythrocyte volume and irreversible thermal denaturation of cytoskeleton proteins and lipid matrix on activity of Ca(2+)-activated K+ channels in erythrocytes of alcoholic and patients with II type diabetes mellitus. Changes in Ca(2+)-dependent potassium permeability of erythrocyte membrane in alcoholic patients and patients with II type diabetes mellitus are related to modification of cytoskeleton, rather than to changes in lipid matrix.

  3. Mueller-matrix ellipsometry studies of optically active structures in scarab beetles

    Järrendahl, K.; Landin, J.; Arwin, H.

    2010-06-01

    The complexity of multilayers, photonic crystals, metamaterials and other artificial materials has promoted the use of spectroscopic, variable angle, generalized and Mueller-matrix ellipsometry. Naturally occurring structures may show even higher complexity than artificial structures but with a more narrow range of constituent materials. Fascinating reflection properties result from intricate photonic structures in, for instance, the wing scales and cuticles of insects. Currently there is a large interest to explore such functional supramolecular architectures for exploitation in nanotechnology. In this study, Mueller-matrix spectroscopic ellipsometry is applied in the spectral range of 250 to 1000 nm to investigate optical response and structures of the cuticle of Scarab beetles of the Cetoniinae subfamily. The cuticle of Cetonia aurata (the rose chafer, la cétoine dorée) is green with a metallic appearance and reflects left-handed circular/elliptically polarized light. It has been suggested that the polarization of this metallic gloss is caused by a helical structure in the chitinous cuticle. We find that the polarization effect is limited to the narrow spectral range 470-550 nm whereas for shorter or longer wavelengths the reflection properties are similar to those from a near-dielectric material. Model calculations and parameterization of the nanostructure employing a heliocoidal structure are discussed. As a comparison the polarization effects from light reflected from two other beetles will be presented. Coptomia laevis has a similar appearance as Cetonia aurata but has very different polarization properties. The golden Plusiotis argentiola has very interesting properties showing both left and right-handed polarization depending on incidence angle and wavelength.

  4. Mueller-matrix ellipsometry studies of optically active structures in scarab beetles

    Arwin H.

    2010-06-01

    Full Text Available The complexity of multilayers, photonic crystals, metamaterials and other artificial materials has promoted the use of spectroscopic, variable angle, generalized and Mueller-matrix ellipsometry. Naturally occurring structures may show even higher complexity than artificial structures but with a more narrow range of constituent materials. Fascinating reflection properties result from intricate photonic structures in, for instance, the wing scales and cuticles of insects. Currently there is a large interest to explore such functional supramolecular architectures for exploitation in nanotechnology. In this study, Mueller-matrix spectroscopic ellipsometry is applied in the spectral range of 250 to 1000 nm to investigate optical response and structures of the cuticle of Scarab beetles of the Cetoniinae subfamily. The cuticle of Cetonia aurata (the rose chafer, la cétoine dorée is green with a metallic appearance and reflects left-handed circular/elliptically polarized light. It has been suggested that the polarization of this metallic gloss is caused by a helical structure in the chitinous cuticle. We find that the polarization effect is limited to the narrow spectral range 470-550 nm whereas for shorter or longer wavelengths the reflection properties are similar to those from a near-dielectric material. Model calculations and parameterization of the nanostructure employing a heliocoidal structure are discussed. As a comparison the polarization effects from light reflected from two other beetles will be presented. Coptomia laevis has a similar appearance as Cetonia aurata but has very different polarization properties. The golden Plusiotis argentiola has very interesting properties showing both left and right-handed polarization depending on incidence angle and wavelength.

  5. The urokinase plasminogen activator receptor-associated protein/endo180 is coexpressed with its interaction partners urokinase plasminogen activator receptor and matrix metalloprotease-13 during osteogenesis

    Engelholm, L H; Nielsen, B S; Netzel-Arnett, S;

    2001-01-01

    The urokinase plasminogen activator receptor-associated protein/Endo180 (uPARAP/Endo180) is a newly discovered member of the macrophage mannose receptor family that was reported to interact with ligand-bound urokinase plasminogen activator receptor (uPAR), matrix metalloprotease-13 (MMP-13), and ......, uPARAP/Endo180 expression was detected only in a mesenchymal condensation of the midbrain and in the developing lungs. The data suggest a function of this novel protease receptor in bone development, possibly mediated through its interactions with uPAR, MMP-13, or collagen V....

  6. Factor H-related protein 5 interacts with pentraxin 3 and the extracellular matrix and modulates complement activation.

    Csincsi, Ádám I; Kopp, Anne; Zöldi, Miklós; Bánlaki, Zsófia; Uzonyi, Barbara; Hebecker, Mario; Caesar, Joseph J E; Pickering, Matthew C; Daigo, Kenji; Hamakubo, Takao; Lea, Susan M; Goicoechea de Jorge, Elena; Józsi, Mihály

    2015-05-15

    The physiological roles of the factor H (FH)-related proteins are controversial and poorly understood. Based on genetic studies, FH-related protein 5 (CFHR5) is implicated in glomerular diseases, such as atypical hemolytic uremic syndrome, dense deposit disease, and CFHR5 nephropathy. CFHR5 was also identified in glomerular immune deposits at the protein level. For CFHR5, weak complement regulatory activity and competition for C3b binding with the plasma complement inhibitor FH have been reported, but its function remains elusive. In this study, we identify pentraxin 3 (PTX3) as a novel ligand of CFHR5. Binding of native CFHR5 to PTX3 was detected in human plasma and the interaction was characterized using recombinant proteins. The binding of PTX3 to CFHR5 is of ∼2-fold higher affinity compared with that of FH. CFHR5 dose-dependently inhibited FH binding to PTX3 and also to the monomeric, denatured form of the short pentraxin C-reactive protein. Binding of PTX3 to CFHR5 resulted in increased C1q binding. Additionally, CFHR5 bound to extracellular matrix in vitro in a dose-dependent manner and competed with FH for binding. Altogether, CFHR5 reduced FH binding and its cofactor activity on pentraxins and the extracellular matrix, while at the same time allowed for enhanced C1q binding. Furthermore, CFHR5 allowed formation of the alternative pathway C3 convertase and supported complement activation. Thus, CFHR5 may locally enhance complement activation via interference with the complement-inhibiting function of FH, by enhancement of C1q binding, and by activating complement, thereby contributing to glomerular disease.

  7. Expression and characterization of common carp (Cyprinus carpio) matrix metalloproteinase-2 and its activity against type I collagen.

    Wang, Ci; Zhan, Chun-Lan; Cai, Qiu-Feng; Du, Cui-Hong; Liu, Guang-Ming; Su, Wen-Jin; Cao, Min-Jie

    2014-05-10

    Matrix metalloproteinases (MMPs) play essential roles in the metabolism of animal collagen while few reports are available for MMPs in aquatic animals. In this study, we report the complete sequence of matrix metalloproteinase-2 (MMP-2) gene from common carp (Cyprinus carpio) skeletal muscle. The full-length cDNA of MMP-2 was 2792bp which contains an open reading frame of 1974bp, corresponding to a protein of 657 amino acid residues. Based on the structural feature of MMP-2, the gene of the catalytic domain containing 351 amino acid residues was cloned and expressed in Escherichia coli. SDS-PAGE showed that the truncated recombinant MMP-2 (trMMP-2) with molecular mass of approximately 38kDa was in the form of inclusion body. The trMMP-2 was further purified by immobilized metal ion affinity chromatography. After renaturation, similar to native MMP-2, the trMMP-2 exhibited high hydrolyzing activity toward gelatin as appeared on gelatin zymography and optimal activity was at pH 8.0 and 40°C. The activity of the trMMP-2 was completely suppressed by metalloproteinase inhibitors, including EDTA, EGTA and 1,10-phenanthroline while other proteinase inhibitors did not show any inhibitory effect. Divalent metal ion Ca(2+) was necessary for the gelatinolytic activity, suggesting it is a calcium-dependent metalloproteinase. Moreover, the trMMP-2 effectively hydrolyzed native type I collagen at 37°C and even at 4°C, implying its potential application value as a collagenase for preparation of biologically active oligopeptides.

  8. A Decision Matrix Approach to Evaluating the Impacts of Land-Use Activities Undertaken to Mitigate Climate Change

    Kueppers, L.M.; Harte, J.; Smith, M.E. [Department of Environmental Science, Policy and Management, University of California Berkeley, 151 Hilgard Hall, Berkeley, CA 94720 (United States); Baer, P. [Energy and Resources Group, University of California Berkeley, 310 Barrows Hall, Berkeley, CA 94720 (United States); Haya, B.; Koteen, L.E. [Energy and Resources Group, University of California Berkeley, 310 Barrows Hall, Berkeley, CA 94720 (United States)

    2004-07-01

    Land-use activities that affect the global balance of greenhouse gases have been a topic of intense discussion during ongoing climate change treaty negotiations. Policy mechanisms that reward countries for implementing climatically beneficial land-use practices have been included in the Bonn and Marrakech agreements on implementation of the Kyoto Protocol. However some still fear that land-use projects focused narrowly on carbon gain will result in socioeconomic and environmental harm, and thus conflict with the explicit sustainable development objectives of the agreement. We propose a policy tool, in the form of a multi-attribute decision matrix, which can be used to evaluate potential and completed land-use projects for their climate, environmental and socioeconomic impacts simultaneously. Project evaluation using this tool makes tradeoffs explicit and allows identification of projects with multiple co-benefits for promotion ahead of others. Combined with appropriate public participation, accounting, and verification policies, a land-use activity decision matrix can help ensure that progressive land management practices are an effective part of the solution to global climate change.

  9. Approach to In- Situ Producing Reinforcing Phase Within an Active-Transient Liquid Phase Bond Seam for Aluminum Matrix Composite

    Zhang, Guifeng; Liao, Xianjin; Chen, Bo; Zhang, Linjie; Zhang, Jianxun

    2015-06-01

    To optimize the braze composition design route for aluminum matrix composite, the feasibility of in situ producing reinforcing phase within the transient liquid phase bond seam matrix, by adding active melting point increaser (MPI, e.g., Ti) together with general melting point depressant (MPD, e.g., Cu) into the interlayer, was demonstrated. For SiC p /A356 composite, by comparing the wettability, joint microstructure, joint shear strength, and fracture path for the developed Al-19Cu-1Ti, Al-19Cu, Al-33Cu-1Ti, Al-33Cu (wt pct), and commercial Cu foils as interlayer, the feasibility of in situ producing reinforcing phase within the bond seam by adding Ti was demonstrated. Especially for Al-19Cu-1Ti active braze, small and dispersed ternary aluminide of Al-Si-Ti phase was obtained within the bond seam as in situ reinforcement, leading to a favorable fracture path within SiC p /A356, not along the initial interface or within the bond seam. For the formation mechanism of the in situ reinforcing phase of MPI-containing intermetallic compound within the bond seam, a model of repeating concentration-precipitation-termination-engulfment during isothermal solidification is proposed.

  10. Tumor necrosis factor-alpha induced expression of matrix metalloproteinase-9 through p21-activated Kinase-1

    Garner Warren

    2009-03-01

    Full Text Available Abstract Background Expressed in embryonic development, matrix metalloprotein-9 (MMP-9 is absent in most of developed adult tissues, but recurs in inflammation during tissue injury, wound healing, tumor formation and metastasis. Expression of MMP-9 is tightly controlled by extracellular cues including pro-inflammatory cytokines and extracellular matrix (ECM. While the pathologic functions of MMP-9 are evident, the intracellular signaling pathways to control its expression are not fully understood. In this study we investigated mechanism of cytokine induced MMP-9 with particular emphasis on the role of p21-activated-kinase-1 (PAK1 and the down stream signaling. Results In response to TNF-alpha or IL-1alpha, PAK1 was promptly activated, as characterized by a sequential phosphorylation, initiated at threonine-212 followed by at threonine-423 in the activation loop of the kinase, in human skin keratinocytes, dermal fibroblasts, and rat hepatic stellate cells. Ectopic expression of PAK1 variants, but not p38 MAP kinase, impaired the TNF-alpha-induced MMP-9 expression, while other MMPs such as MMP-2, -3 and -14 were not affected. Activation of Jun N-terminal kinase (JNK and NF-kappaB has been demonstrated to be essential for MMP-9 expression. Expression of inactive PAK1 variants impaired JNK but not NF-kappaB activation, which consequently suppressed the 5'-promoter activities of the MMP-9 gene. After the cytokine-induced phosphorylation, both ectopically expressed and endogenous PAK1 proteins were promptly accumulated even in the condition of suppressing protein synthesis, suggesting the PAK1 protein is stabilized upon TNF-alpha stimulation. Stabilization of PAK1 protein by TNF-alpha treatment is independent of the kinase catalytic activity and p21 GTPase binding capacities. In contrast to epithelial cells, mesenchymal cells require 3-dimensional type-I collagen in response to TNF-alpha to massively express MMP-9. The collagen effect is mediated, in

  11. Hydrogen sulfide inhibits high glucose-induced matrix protein synthesis by activating AMP-activated protein kinase in renal epithelial cells.

    Lee, Hak Joo; Mariappan, Meenalakshmi M; Feliers, Denis; Cavaglieri, Rita C; Sataranatarajan, Kavithalakshmi; Abboud, Hanna E; Choudhury, Goutam Ghosh; Kasinath, Balakuntalam S

    2012-02-10

    Hydrogen sulfide, a signaling gas, affects several cell functions. We hypothesized that hydrogen sulfide modulates high glucose (30 mm) stimulation of matrix protein synthesis in glomerular epithelial cells. High glucose stimulation of global protein synthesis, cellular hypertrophy, and matrix laminin and type IV collagen content was inhibited by sodium hydrosulfide (NaHS), an H(2)S donor. High glucose activation of mammalian target of rapamycin (mTOR) complex 1 (mTORC1), shown by phosphorylation of p70S6 kinase and 4E-BP1, was inhibited by NaHS. High glucose stimulated mTORC1 to promote key events in the initiation and elongation phases of mRNA translation: binding of eIF4A to eIF4G, reduction in PDCD4 expression and inhibition of its binding to eIF4A, eEF2 kinase phosphorylation, and dephosphorylation of eEF2; these events were inhibited by NaHS. The role of AMP-activated protein kinase (AMPK), an inhibitor of protein synthesis, was examined. NaHS dose-dependently stimulated AMPK phosphorylation and restored AMPK phosphorylation reduced by high glucose. Compound C, an AMPK inhibitor, abolished NaHS modulation of high glucose effect on events in mRNA translation as well as global and matrix protein synthesis. NaHS induction of AMPK phosphorylation was inhibited by siRNA for calmodulin kinase kinase β, but not LKB1, upstream kinases for AMPK; STO-609, a calmodulin kinase kinase β inhibitor, had the same effect. Renal cortical content of cystathionine β-synthase and cystathionine γ-lyase, hydrogen sulfide-generating enzymes, was significantly reduced in mice with type 1 diabetes or type 2 diabetes, coinciding with renal hypertrophy and matrix accumulation. Hydrogen sulfide is a newly identified modulator of protein synthesis in the kidney, and reduction in its generation may contribute to kidney injury in diabetes.

  12. Mesoporous siliconiobium phosphate as a pure Brønsted acid catalyst with excellent performance for the dehydration of glycerol to acrolein.

    Choi, Youngbo; Park, Dae Sung; Yun, Hyeong Jin; Baek, Jayeon; Yun, Danim; Yi, Jongheop

    2012-12-01

    The development of solid acid catalysts that contain a high density of Brønsted acid sites with suitable acidity, as well as a long lifetime, is one of great challenges for the efficient dehydration of glycerol to acrolein. Herein, we report on a mesoporous siliconiobium phosphate (NbPSi-0.5) composite, which is a promising solid Brønsted acid that is a potential candidate for such a high-performance catalyst. A variety of characterization results confirm that NbPSi-0.5 contains nearly pure Brønsted acid sites and has well-defined large mesopores. In addition, NbPSi-0.5 contains a similar amount of acid sites and exhibits weaker acidity than that of the highly acidic niobium phosphate and HZSM-5 zeolite. NbPSi-0.5 is quite stable and has a high activity for the dehydration of glycerol. The stability of NbPSi-0.5 is about three times higher than that of the reported catalyst. The significantly enhanced catalytic performance of NbPSi-0.5 can be attributed to 1) nearly pure Brønsted acidity, which suppresses side reactions that lead to coke formation; 2) a significant reduction of pore blocking due to the mesopores; and 3) a decrease in the amount and oxidation temperature of coke.

  13. Activation of Toll-like Receptor-2 by Endogenous Matrix Metalloproteinase-2 Modulates Dendritic-Cell-Mediated Inflammatory Responses

    Emmanuelle Godefroy

    2014-12-01

    Full Text Available Matrix metalloproteinase-2 (MMP-2 is involved in several physiological mechanisms, including wound healing and tumor progression. We show that MMP-2 directly stimulates dendritic cells (DCs to both upregulate OX40L on the cell surface and secrete inflammatory cytokines. The mechanism underlying DC activation includes physical association with Toll-like receptor-2 (TLR2, leading to NF-κB activation, OX40L upregulation on DCs, and ensuing TH2 differentiation. Significantly, MMP-2 polarizes T cells toward type 2 responses in vivo, in a TLR2-dependent manner. MMP-2-dependent type 2 polarization may represent a key immune regulatory mechanism for protection against a broad array of disorders, such as inflammatory, infectious, and autoimmune diseases, which can be hijacked by tumors to evade immunity.

  14. A matrix-focused structure-activity and binding site flexibility study of quinolinol inhibitors of botulinum neurotoxin serotype A.

    Harrell, William A; Vieira, Rebecca C; Ensel, Susan M; Montgomery, Vicki; Guernieri, Rebecca; Eccard, Vanessa S; Campbell, Yvette; Roxas-Duncan, Virginia; Cardellina, John H; Webb, Robert P; Smith, Leonard A

    2017-02-01

    Our initial discovery of 8-hydroxyquinoline inhibitors of BoNT/A and separation/testing of enantiomers of one of the more active leads indicated considerable flexibility in the binding site. We designed a limited study to investigate this flexibility and probe structure-activity relationships; utilizing the Betti reaction, a 36 compound matrix of quinolinol BoNT/A LC inhibitors was developed using three 8-hydroxyquinolines, three heteroaromatic amines, and four substituted benzaldehydes. This study has revealed some of the most effective quinolinol-based BoNT/A inhibitors to date, with 7 compounds displaying IC50 values ⩽1μM and 11 effective at ⩽2μM in an ex vivo assay.

  15. Activation of Toll-like receptor-2 by endogenous matrix metalloproteinase-2 modulates dendritic cell-mediated inflammatory responses

    Godefroy, Emmanuelle; Gallois, Anne; Idoyaga, Juliana; Merad, Miriam; Tung, Navpreet; Monu, Ngozi; Saenger, Yvonne; Fu, Yichun; Nair, Rajesh; Pulendran, Bali; Jotereau, Francine; Trombetta, Sergio; Bhardwaj, Nina

    2015-01-01

    SUMMARY Matrix metalloproteinase-2 (MMP-2) is involved in several physiological mechanisms, including wound healing and tumor progression. We show that MMP-2 directly stimulates dendritic cells (DCs) to both up-regulate OX40L on the cell surface and secrete inflammatory cytokines. The mechanism underlying DC activation includes physical association with Toll-like receptor-2 (TLR2), leading to NF-κB activation, OX40L up-regulation on DCs and ensuing TH2 differentiation. Significantly, MMP-2 polarizes T cells towards type-2 responses in vivo, in a TLR2-dependent manner. MMP-2-dependent type-2 polarization may represent a key immune regulatory mechanism to protect against a broad array of disorders, such as inflammatory, infectious and autoimmune diseases, which can be hijacked by tumors to evade immunity. PMID:25466255

  16. Activation of toll-like receptor-2 by endogenous matrix metalloproteinase-2 modulates dendritic-cell-mediated inflammatory responses.

    Godefroy, Emmanuelle; Gallois, Anne; Idoyaga, Juliana; Merad, Miriam; Tung, Navpreet; Monu, Ngozi; Saenger, Yvonne; Fu, Yichun; Ravindran, Rajesh; Pulendran, Bali; Jotereau, Francine; Trombetta, Sergio; Bhardwaj, Nina

    2014-12-11

    Matrix metalloproteinase-2 (MMP-2) is involved in several physiological mechanisms, including wound healing and tumor progression. We show that MMP-2 directly stimulates dendritic cells (DCs) to both upregulate OX40L on the cell surface and secrete inflammatory cytokines. The mechanism underlying DC activation includes physical association with Toll-like receptor-2 (TLR2), leading to NF-κB activation, OX40L upregulation on DCs, and ensuing TH2 differentiation. Significantly, MMP-2 polarizes T cells toward type 2 responses in vivo, in a TLR2-dependent manner. MMP-2-dependent type 2 polarization may represent a key immune regulatory mechanism for protection against a broad array of disorders, such as inflammatory, infectious, and autoimmune diseases, which can be hijacked by tumors to evade immunity.

  17. Influenza matrix protein 2 alters CFTR expression and function through its ion channel activity.

    Londino, James D; Lazrak, Ahmed; Jurkuvenaite, Asta; Collawn, James F; Noah, James W; Matalon, Sadis

    2013-05-01

    The human cystic fibrosis transmembrane conductance regulator (CFTR) is a cyclic AMP-activated chloride (Cl(-)) channel in the lung epithelium that helps regulate the thickness and composition of the lung epithelial lining fluid. We investigated whether influenza M2 protein, a pH-activated proton (H(+)) channel that traffics to the plasma membrane of infected cells, altered CFTR expression and function. M2 decreased CFTR activity in 1) Xenopus oocytes injected with human CFTR, 2) epithelial cells (HEK-293) stably transfected with CFTR, and 3) human bronchial epithelial cells (16HBE14o-) expressing native CFTR. This inhibition was partially reversed by an inhibitor of the ubiquitin-activating enzyme E1. Next we investigated whether the M2 inhibition of CFTR activity was due to an increase of secretory organelle pH by M2. Incubation of Xenopus oocytes expressing CFTR with ammonium chloride or concanamycin A, two agents that alkalinize the secretory pathway, inhibited CFTR activity in a dose-dependent manner. Treatment of M2- and CFTR-expressing oocytes with the M2 ion channel inhibitor amantadine prevented the loss in CFTR expression and activity; in addition, M2 mutants, lacking the ability to transport H(+), did not alter CFTR activity in Xenopus oocytes and HEK cells. Expression of an M2 mutant retained in the endoplasmic reticulum also failed to alter CFTR activity. In summary, our data show that M2 decreases CFTR activity by increasing secretory organelle pH, which targets CFTR for destruction by the ubiquitin system. Alteration of CFTR activity has important consequences for fluid regulation and may potentially modify the immune response to viral infection.

  18. In Vivo Molecular Imaging of Cathepsin and Matrix Metalloproteinase Activity Discriminates between Arthritic and Osteoarthritic Processes in Mice

    Eline A. Vermeij

    2014-01-01

    Full Text Available Rheumatoid arthritis (RA and osteoarthritis (OA are serologically and clinically distinctive, but at the local level, both diseases have many molecular pathways in common. In vivo molecular imaging can unravel the local pathologic processes involved in both diseases. In this study, we investigated matrix metalloproteinase (MMP and cathepsin activity during cartilage destruction, in an RA and an OA mouse model, using biophotonic imaging of substrate-based probes. Mice with collagen-induced arthritis (CIA or destabilization of the medial meniscus (DMM were imaged using near-infrared fluorescent probes, activated by several cathepsins or MMPs. Fluorescence signal intensity was compared to synovial gene expression, histology, and cartilage staining of a neoepitope of aggrecan cleaved by MMPs with the amino acids DIPEN. Increased cathepsin and MMP activity was seen during CIA, whereas the DMM model only showed increased MMP activity. DIPEN expression was seen only during CIA. A possible explanation can be differences in gene expressions; MMP3 and -13, known to produce DIPEN neoepitopes, were upregulated in the CIA model, whereas MMP12, known to be involved in elastin degradation and chemokine inhibition, was upregulated in the DMM model. Thus, molecular imaging showed no cathepsin activity at the time of cartilage damage in the DMM model, whereas both cathepsins and MMPs are active in the CIA model during disease progression.

  19. Biotransformation of acrolein in rat: excretion of mercapturic acids after inhalation and intraperitoneal injection.

    Linhart, I; Frantík, E; Vodicková, L; Vosmanská, M; Smejkal, J; Mitera, J

    1996-01-01

    Biotransformation of acrolein (ACR) was studied in vivo in the rat following inhalation and ip administration. The major and minor urinary metabolites were 3-hydroxypropylmercapturic acid (HPMA) and 2-carboxyethylmercapturic acid (CEMA), respectively. Male Wistar rats were exposed to ACR, 23, 42, 77 and 126 mg/m3, for 1 hr. The sum of mercapturic acids HPMA and CEMA excreted within 24 hr after the exposure amounted to 0.87 +/- 0.12, 1.34 +/- 0.5, 2.81 +/- 1.15, and 7.13 +/- 1.56 mumol/kg, i.e., 10.9 +/- 1.5, 13.3 +/- 5.0, 16.7 +/- 6.9, and 21.5 +/- 4.8% of the estimated absorbed dose, respectively. The dose estimate was based on reported values of minute respiratory volume and respiratory tract retention and was corrected for the ACR-induced changes in minute respiratory volume. In the relevant dose range (8.9 to 35.7 mumol/kg) the portion of mercapturic acids excreted was nearly constant for ip exposed rats. The sum of HPMA and CEMA amounted to 29.1 +/- 6.5% of the dose. These results indicate that the deficiency in rat lung metabolism of ACR to acrylic acid previously observed is not compensated by the other detoxication pathway in vivo, mercapturic acid formation. The health hazard arising from inhalation of ACR is likely to be higher than that from other routes of exposure.

  20. Ornithine decarboxylase, mitogen-activated protein kinase and matrix metalloproteinase-2 expressions in human colon tumors

    Takahiro Nemoto; Shunichiro Kubota; Hideyuki Ishida; Nobuo Murata; Daijo Hashimoto

    2005-01-01

    AIM: To investigate the expressions of omithine decarboxylase (ODC), MMP-2, and Erk, and their relationship in human colon tumors.METHODS: ODC activity, MMP-2 expression, and mitogenactivated protein (MAP) kinase activity (Erk phosphorylation) were determined in 58 surgically removed human colon tumors and their adjacent normal tissues, using [1-14C]-ornithine as a substrate, ELISA assay, and Western blotting, respectively.RESULTS: ODC activity, MMP-2 expression, and Erk phosphorylation were significantly elevated in colon tumors, compared to those in adjacent normal tissues. A significant correlation was observed between ODC activities and MMP-2 levels.CONCLUSION: This is the first report showing a significant correlation between ODC activities and MMP-2 levels in human colon tumors. As MMP-2 is involved in cancer invasion and metastasis, and colon cancer overexpresses ODC, suppression of ODC expression may be a rational approach to treat colon cancer which overexpresses ODC.

  1. Acute eccentric resistance exercise decreases matrix metalloproteinase activity in obese elderly women.

    Nascimento, Dahan da Cunha; Navalta, James Wilfred; Durigan, João Luiz Quagliotti; Marqueti, Rita de Cassia; Tibana, Ramires Alsamir; Luiz Franco, Octavio; de Almeida, Jesser Alves; Camarço, Nathalia Ferreira; Neto, Ivo Vieira de Sousa; Prestes, Jonato

    2016-03-01

    The association of ageing with obesity commits elderly women and has been correlated with multiple degenerative processes, which could be occasioned by an enhancing in levels of matrix metalloproteinase-2 and metalloproteinase-9 (MMPs) as well by an cytokine unbalance that included an enhancing on interleukin-6 (IL-6). Furthermore, other factors could be also related to degenerative process, as they could be reduced by eccentric resistance exercise (ERE), which seems particularly important to initiate resistance training in obese older adults. In this view, this study aims to determinate the effects of an acute ERE session on serum MMP-2, MMP-9 and IL-6 in elderly obese women. Ten elderly obese women participated in this study and completed a 10 repetitions maximum test (10 RM) utilizing leg extension exercise. Subjects then completed an acute ERE session consisting of seven sets of 10 repetitions at 110% of 10 RM with a rest of 3 min between sets. Blood samples were collected before, immediately after, 3, 24 and 48 h following the ERE session. Zymograms were utilized to measure the MMP-2 and MMP-9 enzymes from all individuals. Moreover, IL-6 concentration was also determinated. After ERE session, MMP-2 and MMP-9 decreased, remaining significantly below baseline values after 48 h (Pelderly obese women, possibly indicating a transient protection against the low grade inflammation present in this specific population.

  2. Matrix suites applying when making the commercial-company-activity-andfinancial-risks-express-diagnostics

    Valentina Petrovn Neganova

    2011-09-01

    Full Text Available This paper describes an original technique and peculiarities of its use for the express diagnostics of a company and analysis of financial risks. The feature of this technique is potential Russian reality accountance of optimizational transformations of statements in order to minimize taxation and refract the information field of a business system for the apperception. It is based on the conceptual principle of studies of the University of Ghent, according to which, these three cycles affect stability of the companies to the important risk - the risk of bankruptcy. It is noted that the use of matrix analysis can become an additional powerful tool for solving the conceptual verification problem of financial permanence of business systems operation in the marketplace because it allows to determine the internal nature of the underlying processes that occur within an atomic business system and to make every effort to minimize potential and actual manifestations of instability of the external and internal environment of the business system. This method satisfies the multiple set of conditions-equations: apperceptive, asymptotic and simplificational functions that form the basis of calculations for model creation. The technique can be applied by commercial banks in the analysis of the elements of their loan portfolio. Application of this technique allows analyzing the performance of a commercial company in the features of Russian life with minimal iterations.

  3. Matrix Producing Cells in Chronic Kidney Disease: Origin, Regulation, and Activation.

    Kramann, Rafael; Dirocco, Derek P; Maarouf, Omar H; Humphreys, Benjamin D

    2013-12-01

    Chronic injury to the kidney causes kidney fibrosis with irreversible loss of functional renal parenchyma and leads to the clinical syndromes of chronic kidney disease (CKD) and end-stage renal disease (ESRD). Regardless of the type of initial injury, kidney disease progression follows the same pathophysiologic processes characterized by interstitial fibrosis, capillary rarefaction and tubular atrophy. Myofibroblasts play a pivotal role in fibrosis by driving excessive extracellular matrix (ECM) deposition. Targeting these cells in order to prevent the progression of CKD is a promising therapeutic strategy, however, the cellular source of these cells is still controversial. In recent years, a growing amount of evidence points to resident mesenchymal cells such as pericytes and perivascular fibroblasts, which form extensive networks around the renal vasculature, as major contributors to the pool of myofibroblasts in renal fibrogenesis. Identifying the cellular origin of myofibroblasts and the key regulatory pathways that drive myofibroblast proliferation and transdifferentiation as well as capillary rarefaction is the first step to developing novel anti-fibrotic therapeutics to slow or even reverse CKD progression and ultimately reduce the prevalence of ESRD. This review will summarize recent findings concerning the cellular source of myofibroblasts and highlight recent discoveries concerning the key regulatory signaling pathways that drive their expansion and progression in CKD.

  4. Acrolein-Induced Oxidative Stress and Cell Death Exhibiting Features of Apoptosis in the Yeast Saccharomyces cerevisiae Deficient in SOD1.

    Kwolek-Mirek, Magdalena; Zadrąg-Tęcza, Renata; Bednarska, Sabina; Bartosz, Grzegorz

    2015-04-01

    The yeast Saccharomyces cerevisiae is a useful eukaryotic model to study the toxicity of acrolein, an important environmental toxin and endogenous product of lipid peroxidation. The study was aimed at elucidation of the cytotoxic effect of acrolein on the yeast deficient in SOD1, Cu, Zn-superoxide dismutase which is hypersensitive to aldehydes. Acrolein generated within the cell from its precursor allyl alcohol caused growth arrest and cell death of the yeast cells. The growth inhibition involved an increase in production of reactive oxygen species and high level of protein carbonylation. DNA condensation and fragmentation, exposition of phosphatidylserine at the cell surface as well as decreased dynamic of actin microfilaments and mitochondria disintegration point to the induction of apoptotic-type cell death besides necrotic cell death.

  5. Plasma matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 as biomarkers of ulcerative colitis activity

    Alicja Wiercinska-Drapalo; Jerzy Jaroszewicz; Robert Flisiak; Danuta Prokopowicz

    2003-01-01

    AIM: Overexpression of mucosal metalloproteinases (MMP)has been demonstrated recently in inflammatory boweldisease. Their activity can be counterbalanced by the tissueinhibitor of metalloproteinases (TIMP). The aim of this studywas to evaluate the effect of ulcerative colitis (UC) on MMP-1 and TTMP-1 plasma concentrations, as two possiblebiomarkers of the disease activity.METHODS: MMP-1 and TIMP-1 plasma concentrations weremeasured with an enzyme immunoassay in 16 patients withendoscopically confirmed active UC.RESULTS: Plasma concentrations of both MMP-11 (13.7±0.2ng/ml) and TIMP-L (799±140 ng/ml) were significantlyelevated in UC patients in comparison to healthy controls(11.9±0.9 ng/ml and 220±7 ng/ml respectively). There wasno correlation between TIMP-1 and MMP-1 concentrations(r=-0.02). TIMP-1 levels revealed significant positivecorrelations with scored endoscopic degree of mucosai injury,disease activity index and clinical activity index values aswell as C-reactive protein concentration. There was nocorrelation between MMP-1 and laboratory, clinical orendoscopic indices of the disease activity.CONCLUSION: These results confirm the role of both MMP-1 and TIMP-1 in the pathogenesis of ulcerative colitis.However only TIMP-1 can be useful as a biomarker of thedisease activity, demonstrating association with clinical andendoscopic pictures.

  6. A SUBCHRONIC INHALATION STUDY OF FISCHER 344 RATS EXPOSED TO 0, 0.4, 1.4 OR 4.0 PPM ACROLEIN.

    KUTZMAN,R.S.

    1981-10-01

    Fischer 344 rats were exposed to 0.0, 0.4, 1.4, or 4.0 ppm acrolein for 62 days. The major objective of the study was to relate the results of a series of pulmonary function tests to biochemical and pathological alterations observed in the lung. Cytological and reproductive potential endpoints were also assessed after acrolein exposure. Rats were exposed to acrolein for 6 hours/day, 5 days/week for 62 days. Mortality was observed only in the 4.0 ppm chamber where 32 of 57 exposed males died; however, none of the 8 exposed females died. Most of the mortality occurred within the first 10 exposure days. Histologic examination indicated that the animals died of acute bronchopneumonia. The surviving males and females exposed to 4.0 ppm acrolein gained weight at a significantly slower rate than control animals. The growth of both sexes in the 0.4 and 1.4 ppm groups was similar to that of their respective controls. Histopathologic examination of animals after 62 days of exposure revealed bronchiolar epithelial necrosis and sloughing, bronchiolar edema with macrophages, and focal pulmonary edema in the 4.0 ppm group. These lesions were, in some cases, associated with edema of the trachea and peribronchial lymph nodes, and acute rhinitis which indicated an upper respiratory tract effect of acrolein. Of particular interest was the variability of response between rats in the 4.0 ppm group, some not affected at all while others were moderately affected. Intragroup variability in toxicity was also apparent in the 1.4 ppm exposure group where only 3 of 31 animals examined had lesions directly related to acrolein exposure. Extra respiratory organs appeared unaffected.

  7. Use of In Vivo and In Vitro Data to Derive a Chronic Reference Value for Crotonaldehyde Based on Relative Potency to Acrolein.

    Grant, Roberta L; Jenkins, Allison F

    2015-01-01

    The Texas Commission on Environmental Quality (TCEQ) conducted a chronic inhalation noncancer toxicity assessment for crotonaldehyde (CRO). Since there were limited toxicity data for CRO, a reference value (ReV) was derived using a relative potency factor (RPF) approach with acrolein as the index chemical. Both CRO and acrolein are α,β-unsaturated carbonyls and share common steps in their mode of action (MOA). Only studies that investigated the effects of CRO and acrolein in the same study were used to calculate a CRO:acrolein RPF. In vivo findings measuring both 50% respiratory depression in rats and two species of mice and subcutaneous 50% lethality in rats and mice were used to calculate an RPF of 3 (rounded to one significant figure). In vitro data were useful to compare the MOA of CRO and acrolein and to support the RPF determined using in vivo data. In vitro cell culture studies investigating cytotoxicity in normal human lung fibroblast cultures using the propidium iodide cytotoxicity assay and in mouse lymphocyte cultures using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay were used to calculate an in vitro RPF of 3, which supports the in vivo RPF. The chronic ReV for acrolein of 1.2 ppb derived by TCEQ was multiplied by the RPF of 3 to calculate the ReV for CRO of 3.6 ppb (10 μg/m(3)). The ReV for CRO was developed to protect the general public from adverse health effects from chronic exposure to CRO in ambient air.

  8. Calculation of activity coefficients for components in ternary Ti alloys and intermetallics as matrix of composites

    朱艳; 杨延清; 孙军

    2004-01-01

    Based on Kohler's ternary solution model and Miedema's model for calculating the formation heat of binary solution, the integral equation was established for calculating the activity coefficients in ternary alloys and intermetallics. The activity coefficients for components in alloy Ti-5Al-2.5Sn, Ti-6Al-4V and intermetallics TiAl, Ti3 Al and Ti2 AlNb were calculated with the equations. The calculated data coincide well with the experimental ones found in literatures. According to the calculated activity coefficients and activities, it can be predicted that the interfacial reaction in SiC/Ti3 Al composite is more severe than that in composites SiC/Ti2 AlNb and SiC/TiAl.

  9. Spontaneous and cytokine induced expression and activity of matrix metalloproteinases in human colonic epithelium

    Pedersen, G; Saermark, T; Kirkegaard, T;

    2009-01-01

    for MMP cleavage. HT-29 and DLD-1 expressed several MMPs and levels of MMP-3, -10 and -13 mRNA expression were increased significantly by tumour necrosis factor (TNF)-alpha exposure. Transcripts of MMP-1, -3, -7, -9, -10 and -12 were detected in CECs and all, except MMP12, at significantly increased...... levels in cells from inflamed IBD mucosa. MMP-2 and -8 mRNA were expressed inconsistently and MMP-11, -13 and -14 mRNA undetectable. Proteolytic MMP activity was detected in CEC supernatants and the level was increased significantly in inflamed IBD epithelium. The enzyme activity was inhibited strongly...... by a specific MMP inhibitor (GM 6001). A significant TNF-alpha-mediated increase in MMP enzyme activity was also detected in HT-29 cells in vitro. In conclusion, the expression of several MMPs as well as the level of functional MMPactivity is increased in CEC from patients with active IBD. The results suggest...

  10. Tetracycline and Glutathione Inhibit Matrix Metalloproteinase Activity: An In Vitro Study Using Culture Supernatants of L929 and Dalton Lymphoma Cell Lines

    Gajanan Kendre

    2013-01-01

    Full Text Available Tetracycline and glutathione inhibited the protease activities of matrix metalloproteinase-2 and matrix metalloproteinase-9 expressed by mouse fibrosarcoma cells (L929 and Dalton lymphoma cells, respectively. The inhibitory activity of the tetracycline may be due to its ability to chelate metal ions such as calcium and zinc. Gelatin-zymography technique was used to demonstrate the inhibitory activity of both tetracycline and glutathione. The intensity of the bands corresponding to metalloproteinase activity in zymography gel was reduced in the presence of 50–100 μg/mL of tetracycline. The presence of 10–100 μg/mL of tetracycline in the medium increased the adherence of L929 cancer cells. These results clearly indicate the antimetastatic property of tetracycline. Reduced glutathione, a compound which is produced endogenously by the cells to maintain the redox status, was shown to inhibit the matrix metalloproteinase activity (in vitro. Therefore, it is assumed that decreased glutathione levels in synovial fluids or plasma might increase the activity of MMP. Reduced glutathione at 100 μg/mL inhibited the metalloproteinase activity in gelatin-zymographic gel. As both tetracycline and glutathione exhibited an inhibitory effect on matrix metalloproteinase activity, it was of great interest to check their clinical effects on various MMP associated pathological conditions such as cancer metastasis and arthritis. Here we report that tetracycline and reduced glutathione inhibited the activity of MMP2 completely and activity of MMP9 partly.

  11. Regulation of Matrix Metalloproteinase-2 Activity by COX-2-PGE2-pAKT Axis Promotes Angiogenesis in Endometriosis

    Ray, Amlan K.; DasMahapatra, Pramathes; Swarnakar, Snehasikta

    2016-01-01

    Endometriosis is characterized by the ectopic development of the endometrium which relies on angiogenesis. Although studies have identified the involvement of different matrix metalloproteinases (MMPs) in endometriosis, no study has yet investigated the role of MMP-2 in endometriosis-associated angiogenesis. The present study aims to understand the regulation of MMP-2 activity in endothelial cells and on angiogenesis during progression of ovarian endometriosis. Histological and biochemical data showed increased expressions of vascular endothelial growth factor (VEGF), VEGF receptor-2, cycloxygenase (COX)-2, von Willebrand factor along with angiogenesis during endometriosis progression. Women with endometriosis showed decreased MMP-2 activity in eutopic endometrium as compared to women without endometriosis. However, ectopic ovarian endometrioma showed significantly elevated MMP-2 activity with disease severity. In addition, increased MT1MMP and decreased tissue inhibitors of metalloproteinases (TIMP)-2 expressions were found in the late stages of endometriosis indicating more MMP-2 activation with disease progression. In vitro study using human endothelial cells showed that prostaglandin E2 (PGE2) significantly increased MMP-2 activity as well as tube formation. Inhibition of COX-2 and/or phosphorylated AKT suppressed MMP-2 activity and endothelial tube formation suggesting involvement of PGE2 in regulation of MMP-2 activity during angiogenesis. Moreover, specific inhibition of MMP-2 by chemical inhibitor significantly reduced cellular migration, invasion and tube formation. In ovo assay showed decreased angiogenic branching upon MMP-2 inhibition. Furthermore, a significant reduction of lesion numbers was observed upon inhibition of MMP-2 and COX-2 in mouse model of endometriosis. In conclusion, our study establishes the involvement of MMP-2 activity via COX-2-PGE2-pAKT axis in promoting angiogenesis during endometriosis progression. PMID:27695098

  12. Matrix Vesicle Enzyme Activity and Phospholipid Content in Endosteal Bone Following Implantation of Osseointegrating and Non-Osseointegrating Implant Materials.

    1991-11-01

    matrix vesicles (Schwartz et al., 1990a; Boyan et al., 1988; Peress et al., 1974) and is intimately associated with mineral formation as the principle...directly related to the process of primary mineral formation in tissues adjacent to osseointegrating and non- integrating materials. Of particular...Evans, L. 1981. Mechanisms of mineral formation by matrix vesicles. In: Matrix Vesicles, Proc. 3rd Int. Conf. Matrix Vesicles. Ascenci, A., Bonucci, D

  13. 3-Phosphoinositide-dependent Protein Kinase-1 (PDK1 promotes invasion and activation of matrix metalloproteinases

    Zeng Xiao

    2006-03-01

    Full Text Available Abstract Background Metastasis is a major cause of morbidity and mortality in breast cancer with tumor cell invasion playing a crucial role in the metastatic process. PDK1 is a key molecule that couples PI3K to cell proliferation and survival signals in response to growth factor receptor activation, and is oncogenic when expressed in mouse mammary epithelial cells. We now present evidence showing that PDK1-expressing cells exhibit enhanced anchorage-dependent and -independent cell growth and are highly invasive when grown on Matrigel. These properties correlate with induction of MMP-2 activity, increased MT1-MMP expression and a unique gene expression profile. Methods Invasion assays in Matrigel, MMP-2 zymogram analysis, gene microarray analysis and mammary isografts were used to characterize the invasive and proliferative function of cells expressing PDK1. Tissue microarray analysis of human breast cancers was used to measure PDK1 expression in invasive tumors by IHC. Results Enhanced invasion on Matrigel in PDK1-expressing cells was accompanied by increased MMP-2 activity resulting from stabilization against proteasomal degradation. Increased MMP-2 activity was accompanied by elevated levels of MT1-MMP, which is involved in generating active MMP-2. Gene microarray analysis identified increased expression of the ECM-associated genes decorin and type I procollagen, whose gene products are substrates of MT1-MMP. Mammary fat pad isografts of PDK1-expressing cells produced invasive adenocarcinomas. Tissue microarray analysis of human invasive breast cancer indicated that PDK1pSer241 was strongly expressed in 90% of samples. Conclusion These results indicate that PDK1 serves as an important effector of mammary epithelial cell growth and invasion in the transformed phenotype. PDK1 mediates its effect in part by MT1-MMP induction, which in turn activates MMP-2 and modulates the ECM proteins decorin and collagen. The presence of increased PDK1

  14. Effects of Switching to Electronic Cigarettes with and without Concurrent Smoking on Exposure to Nicotine, Carbon Monoxide, and Acrolein.

    McRobbie, Hayden; Phillips, Anna; Goniewicz, Maciej L; Smith, Katie Myers; Knight-West, Oliver; Przulj, Dunja; Hajek, Peter

    2015-09-01

    Concern has been raised about the presence of toxicants in electronic cigarette (EC) aerosol, particularly carbonyl compounds (e.g., acrolein) that can be produced by heating glycerol and glycols used in e-liquids. We investigated exposure to carbon monoxide (CO), nicotine (by measuring cotinine in urine), and to acrolein (by measuring its primary metabolite, S-(3-hydroxypropyl)mercapturic acid (3-HPMA) in urine) before and after 4 weeks of EC (green smoke, a "cig-a-like" EC, labeled 2.4% nicotine by volume) use, in 40 smokers. Thirty-three participants were using EC at 4 weeks after quitting, 16 (48%) were abstinent (CO-validated) from smoking during the previous week (EC only users), and 17 (52%) were "dual users." A significant reduction in CO was observed in EC-only users [-12 ppm, 95% confidence interval (CI), -16 to -7, 80% decrease) and dual users (-12 ppm, 95%CI, -19 to -6, 52% decrease). Cotinine levels also declined, but to a lesser extent (EC-only users: -184 ng/mg creatinine; 95% CI, -733 to -365, 17% decrease; and dual users: -976 ng/mg creatinine; 95%CI, -1,682 to -270, 44% decrease). Mean 3-HPMA levels had decreased at 4 weeks by 1,280 ng/mg creatinine (95%CI, -1,699 to -861, 79% decrease) in EC-only users and by 1,474 ng/mg creatinine (95%CI, -2,101 to -847, 60% decrease) in dual users. In dual users, EC use significantly reduced exposure to CO and acrolein because of a reduction in smoke intake. EC may reduce harm even in smokers who continue to smoke, but long-term follow-up studies are needed to confirm this.

  15. Performance evaluation of nonnegative matrix factorization algorithms to estimate task-related neuronal activities from fMRI data.

    Ding, Xiaoyu; Lee, Jong-Hwan; Lee, Seong-Whan

    2013-04-01

    Nonnegative matrix factorization (NMF) is a blind source separation (BSS) algorithm which is based on the distinct constraint of nonnegativity of the estimated parameters as well as on the measured data. In this study, according to the potential feasibility of NMF for fMRI data, the four most popular NMF algorithms, corresponding to the following two types of (1) least-squares based update [i.e., alternating least-squares NMF (ALSNMF) and projected gradient descent NMF] and (2) multiplicative update (i.e., NMF based on Euclidean distance and NMF based on divergence cost function), were investigated by using them to estimate task-related neuronal activities. These algorithms were applied firstly to individual data from a single subject and, subsequently, to group data sets from multiple subjects. On the single-subject level, although all four algorithms detected task-related activation from simulated data, the performance of multiplicative update NMFs was significantly deteriorated when evaluated using visuomotor task fMRI data, for which they failed in estimating any task-related neuronal activities. In group-level analysis on both simulated data and real fMRI data, ALSNMF outperformed the other three algorithms. The presented findings may suggest that ALSNMF appears to be the most promising option among the tested NMF algorithms to extract task-related neuronal activities from fMRI data.

  16. α-Solanine inhibits human melanoma cell migration and invasion by reducing matrix metalloproteinase-2/9 activities.

    Lu, Ming-Kun; Shih, Yuan-Wei; Chang Chien, Tzu-Tsung; Fang, Li-Heng; Huang, Hsiang-Ching; Chen, Pin-Shern

    2010-01-01

    α-Solanine, a naturally occurring steroidal glycoalkaloid in potato sprouts, was found to possess anti-carcinogenic properties, such as inhibiting proliferation and inducing apoptosis of tumor cells. However, the effect of α-solanine on cancer metastasis remains unclear. In the present study, we examined the effect of α-solanine on metastasis in vitro. Data demonstrated that α-solanine inhibited proliferation of human melanoma cell line A2058 in a dose-dependent manner. When treated with non-toxic doses of α-solanine, cell migration and invasion were markedly suppressed. Furthermore, α-solanine reduced the activity of matrix metalloproteinase-2 (MMP-2) and MMP-9, which are involved in the migration and invasion of cancer cells. Our biochemical assays indicated that α-solanine potently suppressed the phosphorylation of c-Jun N-terminal kinase (JNK), phosphatidylinositide-3 kinase (PI3K) and Akt, while it did not affect phosphorylation of extracellular signal regulating kinase (ERK). In addition, α-solanine significantly decreased the nuclear level of nuclear factor kappa B (NF-κB), suggesting that α-solanine inhibited NF-κB activity. Taken together, the results suggested that α-solanine inhibited migration and invasion of A2058 cells by reducing MMP-2/9 activities. It also inhibited JNK and PI3K/Akt signaling pathways as well as NF-κB activity. These findings reveal new therapeutic potential for α-solanine in anti-metastatic therapy.

  17. AMPK Activation by Metformin Suppresses Abnormal Extracellular Matrix Remodeling in Adipose Tissue and Ameliorates Insulin Resistance in Obesity.

    Luo, Ting; Nocon, Allison; Fry, Jessica; Sherban, Alex; Rui, Xianliang; Jiang, Bingbing; Xu, X Julia; Han, Jingyan; Yan, Yun; Yang, Qin; Li, Qifu; Zang, Mengwei

    2016-08-01

    Fibrosis is emerging as a hallmark of metabolically dysregulated white adipose tissue (WAT) in obesity. Although adipose tissue fibrosis impairs adipocyte plasticity, little is known about how aberrant extracellular matrix (ECM) remodeling of WAT is initiated during the development of obesity. Here we show that treatment with the antidiabetic drug metformin inhibits excessive ECM deposition in WAT of ob/ob mice and mice with diet-induced obesity, as evidenced by decreased collagen deposition surrounding adipocytes and expression of fibrotic genes including the collagen cross-linking regulator LOX Inhibition of interstitial fibrosis by metformin is likely attributable to the activation of AMPK and the suppression of transforming growth factor-β1 (TGF-β1)/Smad3 signaling, leading to enhanced systemic insulin sensitivity. The ability of metformin to repress TGF-β1-induced fibrogenesis is abolished by the dominant negative AMPK in primary cells from the stromal vascular fraction. TGF-β1-induced insulin resistance is suppressed by AMPK agonists and the constitutively active AMPK in 3T3L1 adipocytes. In omental fat depots of obese humans, interstitial fibrosis is also associated with AMPK inactivation, TGF-β1/Smad3 induction, aberrant ECM production, myofibroblast activation, and adipocyte apoptosis. Collectively, integrated AMPK activation and TGF-β1/Smad3 inhibition may provide a potential therapeutic approach to maintain ECM flexibility and combat chronically uncontrolled adipose tissue expansion in obesity.

  18. Density matrix renormalization group (DMRG) method as a common tool for large active-space CASSCF/CASPT2 calculations

    Nakatani, Naoki; Guo, Sheng

    2017-03-01

    This paper describes an interface between the density matrix renormalization group (DMRG) method and the complete active-space self-consistent field (CASSCF) method and its analytical gradient, as well as an extension to the second-order perturbation theory (CASPT2) method. This interfacing allows large active-space multi-reference computations to be easily performed. The interface and its extension are both implemented in terms of reduced density matrices (RDMs) which can be efficiently computed via the DMRG sweep algorithm. We also present benchmark results showing that, in practice, the DMRG-CASSCF calculations scale with active-space size in a polynomial manner in the case of quasi-1D systems. Geometry optimization of a binuclear iron-sulfur cluster using the DMRG-CASSCF analytical gradient is demonstrated, indicating that the inclusion of the valence p-orbitals of sulfur and double-shell d-orbitals of iron lead to non-negligible changes in the geometry compared to the results of small active-space calculations. With the exception of the selection of M values, many computational settings in these practical DMRG calculations have been tuned and black-boxed in our interface, and so the resulting DMRG-CASSCF and DMRG-CASPT2 calculations are now available to novice users as a common tool to compute strongly correlated electronic wavefunctions.

  19. Increased expression and activation of gelatinolytic matrix metalloproteinases is associated with the progression and recurrence of human cervical cancer.

    Sheu, Bor-Ching; Lien, Huang-Chun; Ho, Hong-Nerng; Lin, Ho-Hsiung; Chow, Song-Nan; Huang, Su-Cheng; Hsu, Su-Ming

    2003-10-01

    Cancer-derived matrix metalloproteinases (MMPs) are proposed to be essential for tumor stromal invasion and subsequent metastasis. To explore the role of MMPs in cancer progression, we examined the expression of various MMPs and tissue inhibitors of MMPs in precancerous and cancerous lesions of the uterine cervix. Immunohistochemical studies demonstrated that MMP-2 and MMP-9 were expressed in >90% of squamous cell carcinomas (SCC) and 83-100% of high-grade squamous intraepithelial lesions (HSIL), but were less frequently expressed in low-grade squamous intraepithelial lesions and normal squamous epithelium (13%). MMP-1, MMP-14, and MMP-15 were detected in 55-81% of SCC cases, and MMP-1 was detected in 39% of HSIL. The tissue inhibitors of MMPs were weakly expressed in SCC (10-61%). By direct analysis of enzyme activities in microdissected specimens, we found that the gelatinolytic activity of MMP-9 was significantly higher in HSIL and SCC than in normal cervix (P < 0.01). The levels of active-form MMP-2 increased progressively from HSIL to SCC of stage I and more advanced stages (P < 0.01). The gelatinolytic activity of MMP-9 and active-form MMP-2 in SCC were strongly correlated with lymphovascular permeation and subsequent lymph node metastasis (P < 0.02). Moreover, the gelatinolytic activity and immunoreactive percentage of both MMP-2 and MMP-9 were significantly higher in SCC cases who had a recurrence than in those who remained free of disease (P < 0.001). Thus, our data demonstrate progressively up-regulated expression of MMP-2 and MMP-9 with SCC progression, and significant associations among their gelatinolytic activity and stage, nodal metastasis, and recurrence.

  20. Theoretical Study on Regioselectivity of the Diels-Alder Reaction between 1,8-Dichloroanthracene and Acrolein

    Mujeeb A. Sultan

    2016-09-01

    Full Text Available A theoretical study of the regioselectivity of the Diels-Alder reaction between 1,8-dichloroanthracene and acrolein is performed using DFT at the B3LYP/6-31G(d,p level of theory. The FMO analysis, global and local reactivity indices confirmed the reported experimental results. Potential energy surface analysis showed that the cycloadditions (CAs favor the formation of the anti product. These results are in good agreement with the reported results obtained experimentally where the anti is the major product.

  1. Embedded Touch Sensing Circuit Using Mutual Capacitance for Active-Matrix Organic Light-Emitting Diode Display

    Park, Young-Ju; Seok, Su-Jeong; Park, Sang-Ho; Kim, Ohyun

    2011-03-01

    We propose and simulate an embedded touch sensing circuit for active-matrix organic light-emitting diode (AMOLED) displays. The circuit consists of three thin-film transistors (TFTs), one fixed capacitor, and one variable capacitor. AMOLED displays do not have a variable capacitance characteristic, so we realized a variable capacitor to detect touches in the sensing pixel by exploiting the change in the mutual capacitance between two electrodes that is caused by touch. When a dielectric substance approaches two electrodes, the electric field is shunted so that the mutual capacitance decreases. We use the existing TFT process to form the variable capacitor, so no additional process is needed. We use advanced solid-phase-crystallization TFTs because of their stability and uniformity. The proposed circuit detects multi-touch points by a scanning process.

  2. Time-Domain Quaternary-Weighted Pulse Width Modulation Driving Method for Active Matrix Organic Light-Emitting Diode Displays

    Park, Hyun-Sang; Kuk, Seung-Hee; Han, Min-Koo

    2008-03-01

    We proposed a new digital driving method and its pixel structure for active matrix organic light-emitting diode (AMOLED) displays employing time-domain quaternary-weighted pulse width modulation. In the new digital driving method, the luminance of AMOLED displays is accurately determined by averaging photon flux to the desired level over a frame period. The proposed pixel was verified by spice simulation and the output linearity between the grayscale and the OLED current was successfully achieved. In the proposed digital driving pixel, the timing margin was increased and the effect on luminance of AMOLED displays by the troublesome variation of the thin-film transistors (TFTs) was suppressed without additional compensation schemes.

  3. A New Low Temperature Polycrystalline Silicon Thin Film Transistor Pixel Circuit for Active Matrix Organic Light Emitting Diode

    Fan, Ching-Lin; Lin, Yi-Yan; Chang, Jyu-Yu; Sun, Bo-Jhang; Liu, Yan-Wei

    2010-06-01

    This study presents one novel compensation pixel design and driving method for active matrix organic light-emitting diode (AMOLED) displays that use low-temperature polycrystalline silicon thin-film transistors (LTPS-TFTs) with a voltage feed-back method and the simulation results are proposed and verified by SPICE simulator. The measurement and simulation of LTPS TFT characteristics demonstrate the good fitting result. The proposed circuit consists of four TFTs and two capacitors with an additional signal line. The error rates of OLED anode voltage variation are below 0.3% under the threshold voltage deviation of driving TFT (ΔVTH = ±0.33 V). The simulation results show that the pixel design can improve the display image non-uniformity by compensating the threshold voltage deviation of driving TFT and the degradation of OLED threshold voltage at the same time.

  4. A signal processing approach for enhanced Acoustic Emission data analysis in high activity systems: Application to organic matrix composites

    Kharrat, M.; Ramasso, E.; Placet, V.; Boubakar, M. L.

    2016-03-01

    Structural elements made of Organic Matrix Composites (OMC) under complex loading may suffer from high Acoustic Emission (AE) activity caused by the emergence of different emission sources at high rates with high noise level, which finally engender continuous emissions. The detection of hits in this situation becomes a challenge particularly during fatigue tests. This work suggests an approach based on the Discrete Wavelet Transform (DWT) denoising applied on signal segments. A particular attention is paid to the adjustment of the denoising parameters based on pencil lead breaks and their influence on the quality of the denoised AE signals. The validation of the proposed approach is performed on a ring-shaped Carbon Fiber Reinforced Plastics (CFRP) under in-service-like conditions involving continuous emissions with superimposed damage-related transients. It is demonstrated that errors in hit detection are greatly reduced leading to a better identification of the natural damage scenario based on AE signals.

  5. Effects of Diosgenin on Myometrial Matrix Metalloproteinase-2 and -9 Activity and Expression in Ovariectomized Rats

    Chi-Chen Chang, Tang-Ching Kuan, Yao-Yuan Hsieh, Ying-Jui Ho, Yu-Ling Sun, Chih-Sheng Lin

    2011-01-01

    Full Text Available Diosgenin, a traditional Yam extraction, has been used in hormone replacement for menopausal women. We aimed to investigate the influences of diosgenin administration upon the MMP-2 and -9 activity and expression and reproductive hormones of ovariectomized (OVX rats, a model of menopausal status. Seven-week old female Wistar rats with bilateral OVX or sham operation (controls were divided and administered different dosages of diosgenin (0, 10, 50, or 100 mg/kg/day for 8 weeks. Serum was then sampled for progesterone (P4 and estradiol (E2 assay and uterine horns harvested. Myometrial MMP-2 and -9 activity and expression were surveyed and myometrial collagen expression was also assayed. The results show higher body weight in OVX rats across the 8 weeks post surgery and no significant differences were noted among OVX or Sham rats with diosgenin supplements. There were lower P4 and E2 concentrations in OVX rats compared to Sham rats, and higher P4 concentration of Sham rats post diosgenin supplement. MMP-2 and -9 mRNA expression and activity was lower in OVX rats, although higher MMP-2 and lower MMP-9 activity/mRNA expression was observed in OVX rats post diosgenin supplementation. Collagen mRNA expression was higher in OVX rats compared to Sham controls, and diosgenin administration decreased collagen mRNA expression in OVX rats. In conclusion, diosgenin is associated with gelatinase expression and collagen metabolism in OVX rats. Diosgenin administration can partially reverse the effects of OVX upon MMP functions and hormone status. Adequate diosgenin supplement might modulate myometrial gelatinase expression and collagen metabolism in menopausal subjects.

  6. Scaffold/matrix-attached regions: structural properties creating transcriptionally active loci.

    Bode, J; Schlake, T; Ríos-Ramírez, M; Mielke, C; Stengert, M; Kay, V; Klehr-Wirth, D

    1995-01-01

    The expression characteristics of the human interferon-beta gene, as part of a long stretch of genomic DNA, led to the discovery of the putative domain bordering elements. The chromatin structure of these elements and their surroundings was determined during the process of gene activation and correlated with their postulated functions. It is shown that these "scaffold-attached regions" (S/MAR elements) have some characteristics in common with and others distinct from enhancers with which they cooperate in various ways. Our model of S/MAR function will focus on their properties of mediating topological changes within the respective domain.

  7. Relative contribution of matrix metalloprotease and cysteine protease activities to cytokine-stimulated articular cartilage degradation

    Sondergaard, B C; Henriksen, K; Wulf, H

    2006-01-01

    explants were stimulated with oncostatin M (OSM) 10 ng/ml and tumor necrosis factor-alpha (TNF-alpha) 20 ng/ml in the presence or absence of the broad-spectrum MMP inhibitor GM6001 and the cysteine protease inhibitor, E64. Cartilage degradation was evaluated in the conditioned medium by glycosaminoglycans...... in vivo in CK null mice. CONCLUSION: Inhibition of MMP activity reduced both proteoglycan loss and type II collagen degradation. In contrast, inhibition of cysteine proteases resulted in an increase rather than a decrease in MMP derived fragments of collagen type II degradation, CTX-II, suggesting altered...

  8. Detection of acrolein-derived cyclic DNA adducts in human cells by monoclonal antibodies.

    Pan, Jishen; Awoyemi, Bisola; Xuan, Zhuoli; Vohra, Priya; Wang, Hsiang-Tsui; Dyba, Marcin; Greenspan, Emily; Fu, Ying; Creswell, Karen; Zhang, Lihua; Berry, Deborah; Tang, Moon-Shong; Chung, Fung-Lung

    2012-12-17

    Acrolein (Acr) is a ubiquitous environmental pollutant found in cigarette smoke and automobile exhaust. It can also be produced endogenously by oxidation of polyunsaturated fatty acids. The Acr-derived 1,N(2)-propanodeoxyguanosine (Acr-dG) adducts in DNA are mutagenic lesions that are potentially involved in human cancers. In this study, monoclonal antibodies were raised against Acr-dG adducts and characterized using ELISA. They showed strong reactivity and specificity toward Acr-dG, weaker reactivity toward crotonaldehyde- and trans-4-hydroxy-2-nonenal-derived 1,N(2)-propanodeoxyguanosines, and weak or no reactivity toward 1,N(6)-ethenodeoxyadenosine and 8-oxo-deoxyguanosine. Using these antibodies, we developed assays to detect Acr-dG in vivo: first, a simple and quick FACS-based assay for detecting these adducts directly in cells; second, a highly sensitive direct ELISA assay for measuring Acr-dG in cells and tissues using only 1 μg of DNA without DNA digestion and sample enrichment; and third, a competitive ELISA for better quantitative measurement of Acr-dG levels in DNA samples. The assays were validated using Acr-treated HT29 cell DNA samples or calf thymus DNA, and the results were confirmed by LC-MS/MS-MRM. An immunohistochemical assay was also developed to detect and visualize Acr-dG in HT29 cells as well as in human oral cells. These antibody-based methods provide useful tools for the studies of Acr-dG as a cancer biomarker and of the molecular mechanisms by which cells respond to Acr-dG as a ubiquitous DNA lesion.

  9. Human ovarian neoplasm cell CD147 stimulates production and activation of matrix metalloproteinases in co-cultures with mouse fibroblasts

    YANG Hong; ZOU Wei; XIN Xiao-yan

    2005-01-01

    Objective: To investigate the expression of CD147 on human ovarian neoplasm cell lines and its influence on production and activation of matrix metallproteinases(MMPs). Methods: The expression of CD147 on different human ovarian neoplasm cell lines was studied by western blotting. Co-culture was carried out to investigate the stimulative effect of the positive expression CD147 cell HO-8910 on the production of MMPs of fibroblast cell in vitro. Zymography and immune blotting were used to study the production and activity of positive MMPs, at the time, to explore the relation between CD147 and MMPs. Results: CD147 was positively presented in 2 ovarian neoplasm cell lines(HO-8910,3-AO), but in SKOV3, TC-1,NIN3T3 cell was negative. MMP-2 and MMP-9 were detected by HO-8910 cell line, mouse fibroblast cell and co-culture cells; but the expression in co-culture cell is obviously higher than individual cultures of each type alone.CD147 stimulated MMPs in dose-dependent manner. Conclusion: CD147 causes increased production and activation of MMP-2, MMP-9.CD147 is probably a indirect marker of some ovarian cancer cells with invasion and metastasis.

  10. Minocycline Attenuates Neonatal Germinal-Matrix-Hemorrhage-Induced Neuroinflammation and Brain Edema by Activating Cannabinoid Receptor 2.

    Tang, Jun; Chen, Qianwei; Guo, Jing; Yang, Liming; Tao, Yihao; Li, Lin; Miao, Hongping; Feng, Hua; Chen, Zhi; Zhu, Gang

    2016-04-01

    Germinal matrix hemorrhage (GMH) is the most common neurological disease of premature newborns leading to detrimental neurological sequelae. Minocycline has been reported to play a key role in neurological inflammatory diseases by controlling some mechanisms that involve cannabinoid receptor 2 (CB2R). The current study investigated whether minocycline reduces neuroinflammation and protects the brain from injury in a rat model of collagenase-induced GMH by regulating CB2R activity. To test this hypothesis, the effects of minocycline and a CB2R antagonist (AM630) were evaluated in male rat pups that were post-natal day 7 (P7) after GMH. We found that minocycline can lead to increased CB2R mRNA expression and protein expression in microglia. Minocycline significantly reduced GMH-induced brain edema, microglial activation, and lateral ventricular volume. Additionally, minocycline enhanced cortical thickness after injury. All of these neuroprotective effects of minocycline were prevented by AM630. A cannabinoid CB2 agonist (JWH133) was used to strengthen the hypothesis, which showed the identical neuroprotective effects of minocycline. Our study demonstrates, for the first time, that minocycline attenuates neuroinflammation and brain injury in a rat model of GMH, and activation of CBR2 was partially involved in these processes.

  11. Anti-photoaging activity and inhibition of matrix metalloproteinase (MMP) by marine red alga, Corallina pilulifera methanol extract

    Ryu, BoMi; Qian, Zhong-Ji; Kim, Moon-Moo; Nam, Ki Wan; Kim, Se-Kwon

    2009-02-01

    Matrix metalloproteinases (MMPs), a key component in photoaging of the skin due to exposure to ultraviolet A, appear to be increased by UV-irradiation-associated generation of reactive oxygen species (ROS). In this study, the alga Corallina pilulifera methanol (CPM) extract has been shown to exert a potent antioxidant activity and protective effect on UVA-induced oxidative stress of human dermal fibroblast (HDF) cell. Antioxidant evaluated by various antioxidant assays. These include reducing power, total antioxidant, DPPH radical scavenging, hydroxyl radical scavenging and protective effect on DNA damage caused by hydroxyl radicals generated. Further, the ROS level was detected using a fluorescence probe, 2',7'-dichlorofluorescein diacetate (DCFH-DA), which could be converted to highly fluorescent dichlorofluorescein (DCF) with the presence of intracellular ROS on HT-1080 cells. Those various antioxidant activities were compared to standard antioxidants such as α-tocopherol. In addition, the in vitro activities of MMP-2 and MMP-9 in HDF cell were inhibited by C. pilulifera methanol extract dose dependently by using gelatin zymography method. The results obtained in the present study suggested that the C. pilulifera methanol extract may be a potential source of natural anti-photoaging.

  12. Anti-photoaging activity and inhibition of matrix metalloproteinase (MMP) by marine red alga, Corallina pilulifera methanol extract

    Ryu, Bo Mi [Department of Chemistry, Pukyoung National University, Busan 608-737 (Korea, Republic of); Qian Zhongji [Marine Bioprocess Research Center, Pukyong National University, Busan 608-737 (Korea, Republic of); Kim, Moon-Moo [Department of Chemistry, Dong-Eui University, Busan 614-714 (Korea, Republic of); Nam, Ki Wan [Department of Marine Biology, Pukyong National University, Busan 608-737 (Korea, Republic of); Kim, Se-Kwon [Department of Chemistry, Pukyoung National University, Busan 608-737 (Korea, Republic of); Marine Bioprocess Research Center, Pukyong National University, Busan 608-737 (Korea, Republic of)], E-mail: sknkim@pknu.ac.kr

    2009-02-15

    Matrix metalloproteinases (MMPs), a key component in photoaging of the skin due to exposure to ultraviolet A, appear to be increased by UV-irradiation-associated generation of reactive oxygen species (ROS). In this study, the alga Corallina pilulifera methanol (CPM) extract has been shown to exert a potent antioxidant activity and protective effect on UVA-induced oxidative stress of human dermal fibroblast (HDF) cell. Antioxidant evaluated by various antioxidant assays. These include reducing power, total antioxidant, DPPH radical scavenging, hydroxyl radical scavenging and protective effect on DNA damage caused by hydroxyl radicals generated. Further, the ROS level was detected using a fluorescence probe, 2',7'-dichlorofluorescein diacetate (DCFH-DA), which could be converted to highly fluorescent dichlorofluorescein (DCF) with the presence of intracellular ROS on HT-1080 cells. Those various antioxidant activities were compared to standard antioxidants such as {alpha}-tocopherol. In addition, the in vitro activities of MMP-2 and MMP-9 in HDF cell were inhibited by C. pilulifera methanol extract dose dependently by using gelatin zymography method. The results obtained in the present study suggested that the C. pilulifera methanol extract may be a potential source of natural anti-photoaging.

  13. Porous poly(DL-lactic acid) matrix film with antimicrobial activities for wound dressing application.

    Chitrattha, Sasiprapa; Phaechamud, Thawatchai

    2016-01-01

    Poly(lactic acid) (PLA) is polymeric biomaterial that has been used for wound dressing due to its biodegradability and biocompatibility. However, PLA has some limitations including poor toughness, low degradation rate and high hydrophobicity. The aim of this study is to develop an antibiotic drug-loaded PLA porous film as wound dressing with antibacterial activity. PLA porous film was fabricated by temperature change technique using solvent casting method. Polyethylene glycol (PEG) 400 was added for improving the pore interconnectivity of film. Gentamicin sulfate (GS) or metronidazole (MZ) was incorporated into PLA porous films. PLA containing PEG 400 exhibited the more amorphous form than plain PLA film and contained 55.31 ± 2.85% porosity and 20 μm of the pore size which significantly improved the water vapor transmission rate, oxygen transmission rate, degradation rate and percentage of drug release, respectively. Drug-loaded porous films efficiently inhibited the bacteria growth. GS-loaded film inhibited Staphylococcus aureus, Proteus mirabilis, Pseudomonas aeruginosa, whereas MZ-loaded film inhibited Bacteroides fragilis and the sustainable antibacterial activity was attained for 7 days.

  14. Effects of Toluene, Acrolein and Vinyl Chloride on Motor Activity of Drosophila Melanogaster

    The data generated by current high-throughput assays for chemical toxicity require information to link effects at molecular targets to adverse outcomes in whole animals. In addition, more efficient methods for testing volatile chemicals are needed. Here we begin to address these ...

  15. Increased release and activity of matrix metalloproteinase-9 in patients with mandibuloacral dysplasia type A, a rare premature ageing syndrome.

    Lombardi, F; Fasciglione, G F; D'Apice, M R; Vielle, A; D'Adamo, M; Sbraccia, P; Marini, S; Borgiani, P; Coletta, M; Novelli, G

    2008-10-01

    Mandibuloacral dysplasia type A (MADA; OMIM 248370), a rare disorder caused by mutation in the LMNA gene, is characterized by post-natal growth retardation, craniofacial and skeletal anomalies (mandibular and clavicular hypoplasia, acroosteolysis, delayed closure of cranial sutures, low bone mass and joint contractures), cutaneous changes and partial lipodystrophy. Little is known about the molecular mechanisms by which LMNA mutations produce bone alterations. An altered bone extracellular matrix (ECM) remodelling could play a pivotal role in this disorder and influence part of the typical bone phenotype observed in patients. Therefore, we have focused our investigation on matrix metalloproteinases (MMPs), which are degradative enzymes involved in ECM degradation and ECM remodelling, thus likely contributing to the altered bone mineral density and bone metabolism values seen in five MADA patients. We evaluated the serum levels of several MMPs involved in bone development, remodelling and homeostasis, such as MMP-9, -2, -3, -8 and -13, and found that only the 82 kDa active enzyme forms of MMP-9 are significantly higher in MADA sera compared with healthy controls (n = 16). The serum level of MMP-3 was instead lower in all patients. No significant differences were observed between controls and MADA patients for the serum levels of MMP-2, -8 and -13 and of tissue inhibitor of metalloproteinase 2, a natural inhibitor of MMP-9. Similarly, normal serum levels of tumour necrosis factor alpha (TNF-alpha), interleukin (IL)-6 and IL-1beta were detected. These data suggest a possible involvement of MMP-9 in MADA disease, underlying the potential use in diagnosis and therapy.

  16. A Reduction-Based Sensor for Acrolein Conjugates with the Inexpensive Nitrobenzene as an Alternative to Monoclonal Antibody

    Takamatsu, Masayuki; Fukase, Koichi; Oka, Ritsuko; Kitazume, Shinobu; Taniguchi, Naoyuki; Tanaka, Katsunori

    2016-01-01

    Acrolein, a highly toxic α, β–unsaturated aldehyde, has been a longstanding key biomarker associated with a range of disorders related to oxidative stresses. One of the most promising methods for detecting acrolein involves the use of antibodies that can recognize the acrolein–lysine conjugate, 3-formyl-3, 4-dehydropiperidines (FDP), within oxidatively stressed cells and tissues from various disease states. We have uncovered here that FDP could reduce nitroarenes in high yields at 100 °C in the presence of excess CaCl2 as a Lewis acid promoter. This unique transformation allowed for the development of a de novo method for detecting levels of FDPs generated from proteins in urine or blood serum samples. Thus we successfully converted a non-fluorescent and inexpensive 4-nitrophthalonitrile probe to the corresponding fluorescent aniline, thereby constituting the concept of fluorescent switching. Its sensitivity level (0.84 nmol/mL) is more than that of ELISA assays (3.13 nmol/mL) and is already equally reliable and reproducible at this early stage of development. More importantly, this method is cost effective and simple to operate, requiring only mixing of samples with a kit solution. Our method thus possesses potential as a future alternative to the more costly and operatively encumbered conventional antibody-based methods. PMID:27782170

  17. Comparative analysis of the vibrational structure of the absorption spectra of acrolein in the excited ( S 1) electronic state

    Koroleva, L. A.; Tyulin, V. I.; Matveev, V. K.; Pentin, Yu. A.

    2012-04-01

    The assignments of absorption bands of the vibrational structure of the UV spectrum are compared with the assignments of bands obtained by the CRDS method in a supersonic jet from the time of laser radiation damping for the trans isomer of acrolein in the excited ( S 1) electronic state. The ν00 trans = 25861 cm-1 values and fundamental frequencies, including torsional vibration frequency, obtained by the two methods were found to coincide in the excited electronic state ( S 1) for this isomer. The assignments of several absorption bands of the vibrational structure of the spectrum obtained by the CRDS method were changed. Changes in the assignment of (0-v') transition bands of the torsional vibration of the trans isomer in the Deslandres table from the ν00 trans trans origin allowed the table to be extended to high quantum numbers v'. The torsional vibration frequencies up to v' = 5 were found to be close to the frequencies found by analyzing the vibrational structure of the UV spectrum and calculated quantum-mechanically. The coincidence of the barrier to internal rotation (the cis-trans transition) in the one-dimensional model with that calculated quantum-mechanically using the two-dimensional model corresponds to a planar structure of the acrolein molecule in the excited ( S 1) electronic state.

  18. High throughput liquid chromatography-tandem mass spectrometry assay for mercapturic acids of acrolein and crotonaldehyde in cigarette smokers' urine.

    Carmella, Steven G; Chen, Menglan; Zarth, Adam; Hecht, Stephen S

    2013-09-15

    3-Hydroxypropylmercapturic acid (3-HPMA) and 3-hydroxy-1-methylpropylmercapturic acid (HMPMA) are urinary metabolites of the toxicants acrolein and crotonaldehyde, respectively. Virtually all human urine samples contain these metabolites, resulting from the action of glutathione-S-transferases on acrolein and crotonaldehyde, which are lipid peroxidation products, environmental and dietary contaminants, and constituents of cigarette smoke. We have developed a high throughput liquid chromatography-tandem mass spectrometry method for quantitative analysis of 3-HPMA and HMPMA in large numbers of small urine samples, as would be required in molecular epidemiology and clinical studies relating levels of these metabolites to cancer risk. Solid-phase extraction on mixed mode reverse phase-anion exchange 96-well plates provided sufficient purification for LC-MS/MS analysis, which was performed by auto-injection using a 96-well format, and resulted in clean, readily interpretable chromatograms, with detection limits of 4.5pmol/mL urine for 3-HPMA and 3.5pmol/mL urine for HMPMA. Accuracy was 92% for 3-HPMA and 97% for HMPMA while inter-day precision was 9.1% (coefficient of variation) for 3-HPMA and 11.0% for HMPMA. The method was applied to more than 2600 urine samples from smokers; mean levels of 3-HPMA and HMPMA were 4800±5358 (S.D.)pmol/mL and 3302±3341pmol/mL, respectively.

  19. Approximate inclusion of triple excitations in combined coupled cluster/molecular mechanics: Calculations of electronic excitation energies in solution for acrolein, water, formamide, and n-methylacetamide

    Sneskov, Kristian; Gras, Eduard Matito; Kongsted, Jacob

    2010-01-01

    as being applicable for averaging over many solvent configurations derived from, for example, molecular simulations. We test the proposed model using as a benchmark the two lowest-lying valence singlet excitations (n → π* and π → π*) of acrolein, formamide, and N-methylacetamide in aqueous solution as well...

  20. Mercapturic Acids Derived from the Toxicants Acrolein and Crotonaldehyde in the Urine of Cigarette Smokers from Five Ethnic Groups with Differing Risks for Lung Cancer.

    Park, Sungshim L; Carmella, Steven G; Chen, Menglan; Patel, Yesha; Stram, Daniel O; Haiman, Christopher A; Le Marchand, Loic; Hecht, Stephen S

    2015-01-01

    The Multiethnic Cohort epidemiology study has clearly demonstrated that, compared to Whites and for the same number of cigarettes smoked, African Americans and Native Hawaiians have a higher risk for lung cancer whereas Latinos and Japanese Americans have a lower risk. Acrolein and crotonaldehyde are two important constituents of cigarette smoke which have well documented toxic effects and could play a role in lung cancer etiology. Their urinary metabolites 3-hydroxypropylmercapturic acid (3-HPMA) and 3-hydroxy-1-methylpropylmercapturic acid (HMPMA), respectively, are validated biomarkers of acrolein and crotonaldehyde exposure. We quantified levels of 3-HPMA and HMPMA in the urine of more than 2200 smokers from these five ethnic groups, and also carried out a genome wide association study using blood samples from these subjects. After adjusting for age, sex, creatinine, and total nicotine equivalents, geometric mean levels of 3-HPMA and HMPMA were significantly different in the five groups (P acrolein and crotonaldehyde may be involved in lung cancer etiology, and that their divergent levels may partially explain the differing risks of Native Hawaiian and Latino smokers. No strong signals were associated with 3-HPMA in the genome wide association study, suggesting that formation of the glutathione conjugate of acrolein is mainly non-enzymatic, while the top significant association with HMPMA was located on chromosome 12 near the TBX3 gene, but its relationship to HMPMA excretion is not clear.

  1. Breathing patterns of awake rats exposed to acrolein and perfluorisobutylene determined with an integrated system of nose-only exposure and online analyzed multiple monitoring of breathing

    Bergers, W.W.A.; Beyersbergen Van Henegouwen, A.G.; Hammer, A.H.; Bruijnzeel, P.L.B.

    1996-01-01

    Studies on changes in breathing patterns of rats due to exposure to acrolein and the Leflon pyrolysis product perfluorisobutylene (PFIB) were performed to evaluate a new developed integrated system of nose- only exposure and multiple monitoring of breathing of up to eight rats. Measurements of breat

  2. 丙烯醛路线制备3-甲基吡啶研究进展%Advances in Preparation of 3 -Methylpyridine from Acrolein

    王开明; 王展旭

    2011-01-01

    Summarized the research advances in preparation of 3 -methylpyridine from acrolein. Formaldehyde, acetaldehyde, propionaldehyde or acetone and acrolein can synthesize 3 -methylpyridine with ammonia and catalysts. Property of catalysts and separation and purification of products have been did immense amounts of concrete research. It was suggested that the acrolein route played an important role in increasing selectivity of 3 -methylpyridine and the key problem was how to solve the self- aggregation of acrolein.%综述了以丙烯醛为原料制备3-甲基吡啶的研究进展。有氨和催化剂存在的条件下,甲醛、乙醛、丙醛或丙酮均可以和丙烯醛发生反应生成3-甲基吡啶。研究人员对催化剂的性能和产物的分离提纯做了大量的实验。本文认为采用丙烯醛路线对于提高反应选择性具有重要作用,指出该路线的关键问题是解决其自身聚合问题。

  3. Acrolein Exposure Blocks Down-Regulation of Cytokines and IgE Antibody in a Mucosal Tolerance Model but does not Alter Phenotypic Markers of Allergic Lung Disease

    Acrolein (ACR) is a highly reactive upper airway toxicant that humans are exposed in a variety of environmental situations. Here we examined the effect of ACR exposure on development of immune tolerance in mice. To induce tolerance, female BALB/C mice were intranasally inoculate...

  4. Matrix metalloproteinase-1 inhibitory activities of Morinda citrifolia seed extract and its constituents in UVA-irradiated human dermal fibroblasts.

    Masuda, Megumi; Murata, Kazuya; Naruto, Shunsuke; Uwaya, Akemi; Isami, Fumiyuki; Matsuda, Hideaki

    2012-01-01

    The objective of this study was to examine whether a 50% ethanolic extract (MCS-ext) of the seeds of Morinda citrifolia (noni) and its constituents have matrix metalloproteinase-1 (MMP-1) inhibitory activity in UVA-irradiated normal human dermal fibroblasts (NHDFs). The MCS-ext (10 μg/mL) inhibited MMP-1 secretion from UVA-irradiated NHDFs, without cytotoxic effects, at 48 h after UV exposure. The ethyl acetate-soluble fraction of MCS-ext was the most potent inhibitor of MMP-1 secretion. Among the constituents of the fraction, a lignan, 3,3'-bisdemethylpinoresinol (1), inhibited the MMP-1 secretion at a concentration of 0.3 μM without cytotoxic effects. Furthermore, 1 (0.3 μM) reduced the level of intracellular MMP-1 expression. Other constituents, namely americanin A (2), quercetin (3) and ursolic acid (4), were inactive. To elucidate inhibition mechanisms of MMP-1 expression and secretion, the effect of 1 on mitogen-activated protein kinases (MAPKs) phosphorylation was examined. Western blot analysis revealed that 1 (0.3 μM) reduced the phosphorylations of p38 and c-Jun-N-terminal kinase (JNK). These results suggested that 1 suppresses intracellular MMP-1 expression, and consequent secretion from UVA-irradiated NHDFs, by down-regulation of MAPKs phosphorylation.

  5. Environmental Topology and Water Availability Modulates the Catalytic Activity of β-Galactosidase Entrapped in a Nanosporous Silicate Matrix.

    Burgos, M Ines; Velasco, Manuel I; Acosta, Rodolfo H; Perillo, María A

    2016-11-04

    In the present work we studied the catalytic activity of E. coli β-Gal confined in a nanoporous silicate matrix (Eβ-Gal) at different times after the beginning of the sol-gel polymerization process. Enzyme kinetic experiments with two substrates (ONPG and PNPG) that differed in the rate-limiting steps of the reaction mechanism for their β-Gal-catalyzed hydrolysis, measurements of transverse relaxation times (T2) of water protons through (1)H-NMR, and scanning electron microscopy analysis of the gel nanostructure, were performed. In conjunction, results provided evidence that water availability is crucial for the modulation observed in the catalytic activity of β-Gal as long as water participate in the rate limiting step of the reaction (only with ONPG). In this case, a biphasic rate vs. substrate concentration was obtained exhibiting one phase with catalytic rate constant (kcA), similar to that observed in solution, and another phase with a higher and aging-dependent catalytic rate constant (kcB). More structured water populations (lower T2) correlates with higher catalytic rate constants (kcB). The T2-kcB negative correlation observed along the aging of gels within the 15-days period assayed reinforces the coupling between water structure and the hydrolysis catalysis inside gels.

  6. Inhibiting Invasion into Human Bladder Carcinoma 5637 Cells with Diallyl Trisulfide by Inhibiting Matrix Metalloproteinase Activities and Tightening Tight Junctions

    Yung Hyun Choi

    2013-10-01

    Full Text Available Diallyl trisulfide (DATS, an organosulfur compound in garlic, possesses pronounced anti-cancer potential. However, the anti-invasive mechanism of this compound in human bladder carcinoma is not fully understood. In this study, we evaluated the anti-invasive effects of DATS on a human bladder carcinoma (5637 cell line and investigated the underlying mechanism. The results indicated that DATS suppressed migration and invasion of 5637 cells by reducing the activities and expression of matrix metalloproteinase (MMP-2 and MMP-9 at both the protein and mRNA levels. DATS treatment up-regulated expression of tissue inhibitor of metalloproteinase (TIMP-1 and TIMP-2 in 5637 cells. The inhibitory effects of DATS on invasiveness were associated with an increase in transepithelial electrical resistance and repression of the levels of claudin family members. Although further studies are needed, our data demonstrate that DATS exhibits anti-invasive effects in 5637 cells by down-regulating the activity of tight junctions and MMPs. DATS may have future utility in clinical applications for treating bladder cancer.

  7. Discoidin Domain Receptor 2 Mediates Collagen-Induced Activation of Membrane-Type 1 Matrix Metalloproteinase in Human Fibroblasts.

    Majkowska, Iwona; Shitomi, Yasuyuki; Ito, Noriko; Gray, Nathanael S; Itoh, Yoshifumi

    2017-03-07

    Membrane-Type 1 Matrix Metalloproteinase (MT1-MMP) is a membrane-bound MMP that is highly expressed in cells with invading capacity including fibroblasts and invasive cancer cell. A potential physiological stimulus for MT1-MMP expression is fibrillar collagen, and it has been shown that it upregulates both MT1-MMP gene and functions in various cell types. However, the mechanisms of collagen-mediated MT1-MMP activation is not clearly understood. In this study we identified discoidin domain receptor 2 (DDR2) as a crucial receptor that mediates this process in human fibroblasts. Knocking down DDR2, but not β1 integrin subunit, a common subunit for all collagen-binding integrins, inhibited collagen-induced activation of proMMP-2 and upregulation of MT1-MMP at the gene and protein level. Interestingly DDR2 knockdown or pharmacological inhibition of DDR2 also inhibited MT1-MMP-dependent cellular degradation of collagen film, suggesting that cell surface collagen degradation by MT1-MMP involves DDR2-mediated collagen signalling. This DDR2-mediated mechanism is only present in non-transformed mesenchymal cells, as collagen-induced MT1-MMP activation in HT1080 fibrosarcoma cells and MT1-MMP function in MDA-MB231 breast cancer cells were not affected by DDR kinase inhibition. DDR2 activation was found to be noticeably more effective when cells were stimulated by collagen without non-helical telopeptides region compared to intact collagen fibrils. Those data suggest that DDR2 is a microenvironmental sensor that regulates fibroblasts migration in collagen-rich environment.

  8. 丙烯醛诱导大鼠脉络膜新生血管的形成%The formation of rats’ choroidal neovascularization induced by acrolein

    王观峰; 邹秀兰; 李东豪; 王琛; 李文立; 皮荣标

    2016-01-01

    目的::探讨丙烯醛( AC)诱导大鼠脉络膜新生血管( CNV)的形成。方法:选取远交群大鼠( SD)12只,随机将大鼠分为三组,即空白组,AC诱导4wk组和AC诱导8wk组,其中空白对照组每日200μL新鲜自来水灌胃,实验组为200μL AC溶液(2.5 mg/kg/d)每日灌胃,分为诱导4wk组和8wk组,取材后视网膜组织石蜡包埋,切片及HE染色。结果:空白对照组及AC诱导4 wk组均见RPE-Bruch膜连续性完整,未见明显异常;AC 诱导8 wk 组发现 RPE-Bruch膜连续性缺失,脉络膜新生血管长入视网膜神经上皮层内。结论:长期使用AC可以诱导大鼠脉络膜新生血管形成。%AlM:To investigate the formation of rats′ choroidal neovascularization ( CNV) induced by acrolein.METHODS:Twelve Sprague-Dawley rats were randomly divided into three groups. Acrolein 200μL (2. 5 mg/kg/d) was poured into the rats′stomach for 4wk as acrolein 4wk and for 8wk as acrolein 8wk group. The same volume of fresh water was also done to the rats as the control group. Remove all eye balls and embed into paraffin with HE staining.RESLUTS:The RPE-Bruch membrane was intact with no obvious abnormality in the control group and acrolein 4wk group. Lost in the continuity of RPE and the movement of choroidal neovascularization were found in the acrolein 8wk.CONCLUSlON:The long time use of acrolein can induce the formation of choroial neovascularization in rats.

  9. Adsorption of acrolein, propanal, and allyl alcohol on Pd(111): a combined infrared reflection-absorption spectroscopy and temperature programmed desorption study.

    Dostert, Karl-Heinz; O'Brien, Casey P; Mirabella, Francesca; Ivars-Barceló, Francisco; Schauermann, Swetlana

    2016-05-18

    Atomistic-level understanding of the interaction of α,β-unsaturated aldehydes and their derivatives with late transition metals is of fundamental importance for the rational design of new catalytic materials with the desired selectivity towards C[double bond, length as m-dash]C vs. C[double bond, length as m-dash]O bond partial hydrogenation. In this study, we investigate the interaction of acrolein, and its partial hydrogenation products propanal and allyl alcohol, with Pd(111) as a prototypical system. A combination of infrared reflection-absorption spectroscopy (IRAS) and temperature programmed desorption (TPD) experiments was applied under well-defined ultrahigh vacuum (UHV) conditions to obtain detailed information on the adsorption geometries of acrolein, propanal, and allyl alcohol as a function of coverage. We compare the IR spectra obtained for multilayer coverages, reflecting the molecular structure of unperturbed molecules, with the spectra acquired for sub-monolayer coverages, at which the chemical bonds of the molecules are strongly distorted. Coverage-dependent IR spectra of acrolein on Pd(111) point to the strong changes in the adsorption geometry with increasing acrolein coverage. Acrolein adsorbs with the C[double bond, length as m-dash]C and C[double bond, length as m-dash]O bonds lying parallel to the surface in the low coverage regime and changes its geometry to a more upright orientation with increasing coverage. TPD studies indicate decomposition of the species adsorbed in the sub-monolayer regime upon heating. Similar strong coverage dependence of the IR spectra were found for propanal and allyl alcohol. For all investigated molecules a detailed assignment of vibrational bands is reported.

  10. Neovibsanin B increases extracellular matrix proteins in optic nerve head cells via activation of Smad signalling pathway.

    Wang, Zhen; Xu, Wei; Rong, Ao; Lin, Yan; Qiu, Xu-Ling; Qu, Shen; Lan, Xian-Hai

    2015-01-01

    The present study demonstrates the effect of neovibsanin B on the synthesis and deposition of ECM proteins and the signalling pathways used in optic nerve head (ONH) astrocytes and lamina cribrosa (LC) cells. For investigation of the signalling pathway used by neovibsanin B, ONH cells were treated with neovibsanin B. Western blot and immunostaining analyses were used to examine the phosphorylation of proteins involved in Smad and non-Smad signalling pathway. The results revealed that ONH cells on treatment with neovibsanin B showed enhanced synthesis of extracellular matrix (ECM) proteins. Neovibsanin B induced phosphorylation of canonical signalling proteins, Smad2/3. However phosphorylation of non-canonical signalling proteins, extracellular signal-regulated kinases, p38, and c-Jun N-terminal kinases (JNK) 1/2 remained unaffected. There was also increase in co-localization of pSmad2/3 with Co-Smad4 in the nucleus of ONH astrocytes and LC cells indicating activation of the canonical Smad signalling pathway. Treatment of ONH cells with SIS3, inhibitor of Smad3 phosphorylation reversed the neovibsanin B stimulated ECM expression as well as activation of canonical pathway signalling molecules. In addition, inhibition of Smad2 or Smad3 using small interfering RNA (siRNA) also suppressed neovibsanin B stimulated ECM protein synthesis in ONH astrocytes and LC cells. Thus neovibsanin B utilizes the canonical Smad signalling pathway to stimulate ECM synthesis in human ONH cells. The neovibsanin B induced ECM synthesis and activation of the canonical Smad signalling pathway may be due to its effect on transforming growth factor-β2 (TGF-β2). However, further studies are under process to understand the mechanism.

  11. Interleukin-1{beta} regulates cell proliferation and activity of extracellular matrix remodelling enzymes in cultured primary pig heart cells

    Zitta, Karina; Brandt, Berenice [Department of Anesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel (Germany); Wuensch, Annegret [Institute of Molecular Animal Breeding and Biotechnology, Ludwig Maximilians University, Munich (Germany); Meybohm, Patrick; Bein, Berthold; Steinfath, Markus; Scholz, Jens [Department of Anesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel (Germany); Albrecht, Martin, E-mail: Albrecht@anaesthesie.uni-kiel.de [Department of Anesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel (Germany)

    2010-09-03

    Research highlights: {yields} Levels of IL-1{beta} are increased in the pig myocardium after infarction. {yields} Cultured pig heart cells possess IL-1 receptors. {yields} IL-1{beta} increases cell proliferation of pig heart cells in-vitro. {yields} IL-1{beta} increases MMP-2 and MMP-9 activity in pig heart cells in-vitro. {yields} IL-1{beta} may be important for tissue remodelling events after myocardial infarction. -- Abstract: After myocardial infarction, elevated levels of interleukins (ILs) are found within the myocardial tissue and IL-1{beta} is considered to play a major role in tissue remodelling events throughout the body. In the study presented, we have established a cell culture model of primary pig heart cells to evaluate the effects of different concentrations of IL-1{beta} on cell proliferation as well as expression and activity of enzymes typically involved in tissue remodelling. Primary pig heart cell cultures were derived from three different animals and stimulated with recombinant pig IL-1{beta}. RNA expression was detected by RT-PCR, protein levels were evaluated by Western blotting, activity of matrix metalloproteinases (MMPs) was quantified by gelatine zymography and cell proliferation was measured using colorimetric MTS assays. Pig heart cells express receptors for IL-1 and application of IL-1{beta} resulted in a dose-dependent increase of cell proliferation (P < 0.05 vs. control; 100 ng/ml; 24 h). Gene expression of caspase-3 was increased by IL-1{beta} (P < 0.05 vs. control; 100 ng/ml; 3 h), and pro-caspase-3 but not active caspase was detected in lysates of pig heart cells by Western blotting. MMP-2 gene expression as well as enzymatic activities of MMP-2 and MMP-9 were increased by IL-1{beta} (P < 0.05 vs. control; 100 ng/ml; 3 h for gene expression, 48 and 72 h for enzymatic activities of MMP-2 and MMP-9, respectively). Our in vitro data suggest that IL-1{beta} plays a major role in the events of tissue remodelling in the heart. Combined

  12. Red Grape Skin Polyphenols Blunt Matrix Metalloproteinase-2 and -9 Activity and Expression in Cell Models of Vascular Inflammation: Protective Role in Degenerative and Inflammatory Diseases

    Nadia Calabriso

    2016-08-01

    Full Text Available Matrix metalloproteinases (MMPs are endopeptidases responsible for the hydrolysis of various components of extracellular matrix. MMPs, namely gelatinases MMP-2 and MMP-9, contribute to the progression of chronic and degenerative diseases. Since gelatinases’ activity and expression are regulated by oxidative stress, we sought to evaluate whether supplementation with polyphenol-rich red grape skin extracts modulated the matrix-degrading capacity in cell models of vascular inflammation. Human endothelial and monocytic cells were incubated with increasing concentrations (0.5–25 μg/mL of Negroamaro and Primitivo red grape skin polyphenolic extracts (NSPE and PSPE, respectively or their specific components (0.5–25 μmol/L, before stimulation with inflammatory challenge. NSPE and PSPE inhibited, in a concentration-dependent manner, endothelial invasion as well as the MMP-9 and MMP-2 release in stimulated endothelial cells, and MMP-9 production in inflamed monocytes, without affecting tissue inhibitor of metalloproteinases (TIMP-1 and TIMP-2. The matrix degrading inhibitory capacity was the same for both NSPE and PSPE, despite their different polyphenolic profiles. Among the main polyphenols of grape skin extracts, trans-resveratrol, trans-piceid, kaempferol and quercetin exhibited the most significant inhibitory effects on matrix-degrading enzyme activities. Our findings appreciate the grape skins as rich source of polyphenols able to prevent the dysregulation of vascular remodelling affecting degenerative and inflammatory diseases.

  13. A flexible organic active matrix circuit fabricated using novel organic thin film transistors and organic light-emitting diodes

    Gutiérrez-Heredia, Gerardo

    2010-10-04

    We present an active matrix circuit fabricated on plastic (polyethylene naphthalene, PEN) and glass substrates using organic thin film transistors and organic capacitors to control organic light-emitting diodes (OLEDs). The basic circuit is fabricated using two pentacene-based transistors and a capacitor using a novel aluminum oxide/parylene stack (Al2O3/ parylene) as the dielectric for both the transistor and the capacitor. We report that our circuit can deliver up to 15 μA to each OLED pixel. To achieve 200 cd m-2 of brightness a 10 μA current is needed; therefore, our approach can initially deliver 1.5× the required current to drive a single pixel. In contrast to parylene-only devices, the Al2O 3/parylene stack does not fail after stressing at a field of 1.7 MV cm-1 for >10 000 s, whereas \\'parylene only\\' devices show breakdown at approximately 1000 s. Details of the integration scheme are presented. © 2010 IOP Publishing Ltd.

  14. A High-Performance Current-Mode Source Driver IC for Mobile Active Matrix Organic Light Emitting Diode Displays

    Jeong, Il-Hun; Kwon, Oh-Kyong

    2008-03-01

    In this paper, we describe two types of 8-bit current-mode driver ICs with a small area and good performance for applications high accuracy current-mode digital-to-analog converters (DACs), and improved channel-to-channel uniformity for active matrix organic light-emitting diode (AMOLED) displays. One uses the proposed current steering DAC (type A), which is an improved architecture of a binary-weighted DAC, and the other uses a DAC that is a combination of a thermometer-decoded of the DAC and a binary-weighted type. The measured results show that the peak integral nonlinearity (INL) is within ±0.5 the least significant bit (LSB), the peak differential nonlinearity (DNL) is within ±0.5 LSB, and the nonuniformity of output current among channels and chips is within ±0.5 LSB. The size of the driver IC is 15,820 ×1,500 µm2 and the total power consumption of the current-mode driver IC is less than 9 mW when the display has full-white pattern with a luminance of 150 cd/m2. The chip area and power consumption with the proposed current DAC are reduced by 26 and 10%, respectively, compared with those of conventional driver ICs with a fully binary-weighted DAC.

  15. A flexible organic active matrix circuit fabricated using novel organic thin film transistors and organic light-emitting diodes

    Gutiérrez-Heredia, G.; González, L. A.; Alshareef, H. N.; Gnade, B. E.; Quevedo-López, M.

    2010-11-01

    We present an active matrix circuit fabricated on plastic (polyethylene naphthalene, PEN) and glass substrates using organic thin film transistors and organic capacitors to control organic light-emitting diodes (OLEDs). The basic circuit is fabricated using two pentacene-based transistors and a capacitor using a novel aluminum oxide/parylene stack (Al2O3/parylene) as the dielectric for both the transistor and the capacitor. We report that our circuit can deliver up to 15 µA to each OLED pixel. To achieve 200 cd m-2 of brightness a 10 µA current is needed; therefore, our approach can initially deliver 1.5× the required current to drive a single pixel. In contrast to parylene-only devices, the Al2O3/parylene stack does not fail after stressing at a field of 1.7 MV cm-1 for >10 000 s, whereas 'parylene only' devices show breakdown at approximately 1000 s. Details of the integration scheme are presented.

  16. Investigation of Pattern-Induced Brightness Non-uniformity in Active-Matrix Organic Light-Emitting Diode Displays

    Kim, Kyoung-Bo; Park, Hye-Hyang; Kwon, Ohseob; Kim, Moojin; Lee, Ki-Yong; Park, Yongwoo; Choi, JongHyun; Yu, CheolHo; Kim, Hye-Dong; Kim, Sung Chul; Chung, Ho-Kyoon

    2008-01-01

    We recently improved the brightness non-uniformity in active-matrix organic light-emitting diode (AMOLED) regarding non-uniform laser energy distribution by applying a “shot mixing” technique in sequential lateral solidification (SLS) method. Although the new SLS technique was employed, another brightness non-uniformity that appeared as oblique lines on AMOLED panels became a crucial issue. In this work, we attempted to investigate the origins of the non-uniformity. Our systematic analysis on the oblique lines revealed that the line type non-uniformity was attributed to both the SLS process and the thin-film transistor (TFT) fabrication processes. In particular, we found that such oblique patterns might be related to moiré patterns that appear when primary grain boundaries aligned in a repetitive pattern is placed over other repetitive TFT patterns such as metal lines. We adopted a method to diminish the moiré pattern type non-uniformity by applying top emission TFT structure.

  17. Structural Characterization of Sputtered Silicon Thin Films after Rapid Thermal Annealing for Active-Matrix Organic Light Emitting Diode

    Mugiraneza, Jean de Dieu; Miyahira, Tomoyuki; Sakamoto, Akinori; Chen, Yi; Okada, Tatsuya; Noguchi, Takashi; Itoh, Taketsugu

    2010-12-01

    The microcrystalline phase obtained by adopting a two-step rapid thermal annealing (RTA) process for rf-sputtered silicon films deposited on thermally durable glass was characterized. The optical properties, surface morphology, and internal stress of the annealed Si films are investigated. As the thermally durable glass substrate allows heating of the deposited films at high temperatures, micro-polycrystalline silicon (micro-poly-Si) films of uniform grain size with a smooth surface and a low internal stress could be obtained after annealing at 750 °C. The thermal stress in the Si films was 100 times lower than that found in the films deposited on conventional glass. Uniform grains with an average grain size of 30 nm were observed by transmission electron microscopy (TEM) in the films annealed at 800 °C. These micro-poly-Si films have potential application for fabrication of uniform and reliable thin film transistors (TFTs) for large scale active-matrix organic light emitting diode (AMOLED) displays.

  18. 3.4-Inch Quarter High Definition Flexible Active Matrix Organic Light Emitting Display with Oxide Thin Film Transistor

    Hatano, Kaoru; Chida, Akihiro; Okano, Tatsuya; Sugisawa, Nozomu; Inoue, Tatsunori; Seo, Satoshi; Suzuki, Kunihiko; Oikawa, Yoshiaki; Miyake, Hiroyuki; Koyama, Jun; Yamazaki, Shunpei; Eguchi, Shingo; Katayama, Masahiro; Sakakura, Masayuki

    2011-03-01

    In this paper, we report a 3.4-in. flexible active matrix organic light emitting display (AMOLED) display with remarkably high definition (quarter high definition: QHD) in which oxide thin film transistors (TFTs) are used. We have developed a transfer technology in which a TFT array formed on a glass substrate is separated from the substrate by physical force and then attached to a flexible plastic substrate. Unlike a normal process in which a TFT array is directly fabricated on a thin plastic substrate, our transfer technology permits a high integration of high performance TFTs, such as low-temperature polycrystalline silicon TFTs (LTPS TFTs) and oxide TFTs, on a plastic substrate, because a flat, rigid, and thermally-stable glass substrate can be used in the TFT fabrication process in our transfer technology. As a result, this technology realized an oxide TFT array for an AMOLED on a plastic substrate. Furthermore, in order to achieve a high-definition AMOLED, color filters were incorporated in the TFT array and a white organic light-emitting diode (OLED) was combined. One of the features of this device is that the whole body of the device can be bent freely because a source driver and a gate driver can be integrated on the substrate due to the high mobility of an oxide TFT. This feature means “true” flexibility.

  19. An Antifungal Combination Matrix Identifies a Rich Pool of Adjuvant Molecules that Enhance Drug Activity against Diverse Fungal Pathogens

    Nicole Robbins

    2015-11-01

    Full Text Available There is an urgent need to identify new treatments for fungal infections. By combining sub-lethal concentrations of the known antifungals fluconazole, caspofungin, amphotericin B, terbinafine, benomyl, and cyprodinil with ∼3,600 compounds in diverse fungal species, we generated a deep reservoir of chemical-chemical interactions termed the Antifungal Combinations Matrix (ACM. Follow-up susceptibility testing against a fluconazole-resistant isolate of C. albicans unveiled ACM combinations capable of potentiating fluconazole in this clinical strain. We used chemical genetics to elucidate the mode of action of the antimycobacterial drug clofazimine, a compound with unreported antifungal activity that synergized with several antifungals. Clofazimine induces a cell membrane stress for which the Pkc1 signaling pathway is required for tolerance. Additional tests against additional fungal pathogens, including Aspergillus fumigatus, highlighted that clofazimine exhibits efficacy as a combination agent against multiple fungi. Thus, the ACM is a rich reservoir of chemical combinations with therapeutic potential against diverse fungal pathogens.

  20. Image quality affected by diffraction of aperture structure arrangement in transparent active-matrix organic light-emitting diode displays.

    Tsai, Yu-Hsiang; Huang, Mao-Hsiu; Jeng, Wei-de; Huang, Ting-Wei; Lo, Kuo-Lung; Ou-Yang, Mang

    2015-10-01

    Transparent display is one of the main technologies in next-generation displays, especially for augmented reality applications. An aperture structure is attached on each display pixel to partition them into transparent and black regions. However, diffraction blurs caused by the aperture structure typically degrade the transparent image when the light from a background object passes through finite aperture window. In this paper, the diffraction effect of an active-matrix organic light-emitting diode display (AMOLED) is studied. Several aperture structures have been proposed and implemented. Based on theoretical analysis and simulation, the appropriate aperture structure will effectively reduce the blur. The analysis data are also consistent with the experimental results. Compared with the various transparent aperture structure on AMOLED, diffraction width (zero energy position of diffraction pattern) of the optimize aperture structure can be reduced 63% and 31% in the x and y directions in CASE 3. Associated with a lenticular lens on the aperture structure, the improvement could reach to 77% and 54% of diffraction width in the x and y directions. Modulation transfer function and practical images are provided to evaluate the improvement of image blurs.

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

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

    2016-01-01

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

  2. Effect of transparent film desiccant on the lifetime of top-emitting active matrix organic light emitting diodes

    Lee, Byoung Duk; Cho, Yoon-Hyung; Kim, Won-Jong; Oh, Min Ho; Lee, Jong Hyuk; Zang, Dong Sik

    2007-03-01

    The effects of a transparent film desiccant on the lifetime of top-emitting active matrix organic light emitting diodes (AMOLEDs) were investigated. The transparent film desiccants were prepared by mixing solutions dispersed with calcium oxide powders and ultraviolet-curable resins. As the solid content in the solutions increased from 15to30wt%, the average particle size increased from 107to240nm, whereas the transmittance of the films decreased from 98% to 80% in the visible range. The devices encapsulated with the transparent film desiccants which contained 20wt% CaO exhibited no dark spots and 97% of the initial luminance, even after being stored for over 500h at 70°C and 90% relative humidity. Also, the operational lifetime of these devices was 1850h, ten times longer than that of a device without desiccant. These results confirmed that the transparent film desiccants, which absorbed the moisture that penetrated into the devices, could be applied to the encapsulation of top-emitting AMOLEDs.

  3. Optimal Topology and Experimental Evaluation of Piezoelectric Materials for Actively Shunted General Electric Polymer Matrix Fiber Composite Blades

    Choi, Benjamin B.; Duffy, Kirsten; Kauffman, Jeffrey L.; Kray, Nicholas

    2012-01-01

    NASA Glenn Research Center, in collaboration with GE Aviation, has begun the development of a smart adaptive structure system with piezoelectric (PE) transducers to improve composite fan blade damping at resonances. Traditional resonant damping approaches may not be realistic for rotating frame applications such as engine blades. The limited space in which the blades reside in the engine makes it impossible to accommodate the circuit size required to implement passive resonant damping. Thus, a novel digital shunt scheme has been developed to replace the conventional electric passive shunt circuits. The digital shunt dissipates strain energy through the load resistor on a power amplifier. General Electric (GE) designed and fabricated a variety of polymer matrix fiber composite (PMFC) test specimens. Investigating the optimal topology of PE sensors and actuators for each test specimen has revealed the best PE transducer location for each target mode. Also a variety of flexible patches, which can conform to the blade surface, have been tested to identify the best performing PE patch. The active damping control achieved significant performance at target modes. This work has been highlighted by successful spin testing up to 5000 rpm of subscale GEnx composite blades in Glenn s Dynamic Spin Rig.

  4. Extracellular matrix biomarker, fibulin-1, is closely related to NT-proBNP and soluble urokinase plasminogen activator receptor in patients with aortic valve stenosis (the SEAS study)

    Kruger, Ruan; Rasmussen, Lars M; Argraves, William S;

    2014-01-01

    BACKGROUND: Fibulin-1, a circulating extracellular matrix glycoprotein, has been associated with arterial disease and elevated N-terminal prohormone B-type natriuretic peptide (NT-proBNP) in diabetes. Soluble urokinase plasminogen activator receptor (suPAR), a marker of inflammation, has been ass...

  5. GALNT3, a gene associated with hyperphosphatemic familial tumoral calcinosis, is transcriptionally regulated by extracellular phosphate and modulates matrix metalloproteinase activity

    2008-01-01

    GALNT3, a gene associated with Hyperphosphatemic Familial Tumoral Calcinosis, is transcriptionally regulated by extracellular phosphate and modulates matrix metalloproteinase activity correspondence: Corresponding author. Laboratory of Molecular Dermatology Department of Dermatology Rambam Medical Center POB 9602, Haifa 31096, Israel. Tel.: +972 4 8541919; fax: +972 4 8542951. (Sprecher, Eli) (Sprecher, Eli) Labo...

  6. Pesticide-Exposure Matrix

    The "Pesticide-exposure Matrix" was developed to help epidemiologists and other researchers identify the active ingredients to which people were likely exposed when their homes and gardens were treated for pests in past years.

  7. In vivo imaging of matrix metalloprotease 12 and matrix metalloprotease 13 activities in the mouse model of collagen-induced arthritis

    Lim, Ngee Han; Meinjohanns, Ernst; Bou-Gharios, George;

    2014-01-01

    from a peptide phosphinic inhibitor library. Selectivity of the probes was demonstrated in vitro using MMP-1, MMP-2, MMP-3, MMP-12, and MMP-13. In vivo activation of the probe was tested in the zymosan-induced mouse model of inflammation and probe specificity was evaluated by the metalloprotease...

  8. Computational Approaches to the Determination of the Molecular Geometry of Acrolein in its T_1(n,π*) State

    McAnally, Michael O.; Hlavacek, Nikolaus C.; Drucker, Stephen

    2012-06-01

    The spectroscopically derived inertial constants for acrolein (propenal) in its T_1(n,π*) state were used to test predictions from a variety of computational methods. One focus was on multiconfigurational methods, such as CASSCF and CASPT2, that are applicable to excited states. We also examined excited-state methods that utilize single reference configurations, including EOM-EE-CCSD and TD-PBE0. Finally, we applied unrestricted ground-state techniques, such as UCCSD(T) and the more economical UPBE0 method, to the T_1(n,π*) excited state under the constraint of C_s symmetry. The unrestricted ground-state methods are applicable because at a planar geometry, the T_1(n,π*) state of acrolein is the lowest-energy state of its spin multiplicity. Each of the above methods was used with a triple zeta quality basis set to optimize the T_1(n,π*) geometry. This procedure resulted in the following sets of inertial constants: Inertial constants (cm-1) of acrolein in its T_1(n,π*) state Method A B C Method A B C CASPT2(6,5) 1.667 0.1491 0.1368 UCCSD(T)^b 1.668 0.1480 0.1360 CASSCF(6,5) 1.667 0.1491 0.1369 UPBE0 1.699 0.1487 0.1367 EOM-EE-CCSD 1.675 0.1507 0.1383 TD-PBE0 1.719 0.1493 0.1374 Experiment^a 1.662 0.1485 0.1363 The two multiconfigurational methods produce the same inertial constants, and those constants agree closely with experiment. However the sets of computed bond lengths differ significantly for the two methods. In the CASSCF calculation, the lengthening of the C=O and C=C bonds and the shortening of the C--C bond are more pronounced than in CASPT2. O. S. Bokareva et al., Int. J. Quant. Chem. {108}, 2719 (2008).

  9. Acrolein-induced cell apoptosis in adult mice cardiomyocytes%丙烯醛致成年小鼠心肌细胞凋亡的作用

    王丽娟; 胡健; 齐国先

    2007-01-01

    目的 丙烯醛是一种具有高反应性的不饱和脂肪醛,它是丙烯胺的代谢产物,在体内外对各种细胞具有毒性作用.本研究探讨丙烯醛对成年小鼠心肌细胞氧自由基及钙浓度的影响及细胞凋亡的作用.方法 采用改良langendorff方法分离成年小鼠心肌细胞.分别应用DCF及Fura-2 AM测定细胞内氧自由基水平及钙离子钙浓度,WST法测定心肌细胞存活率,观察凋亡DNA片段及细胞凋亡的形态变化.结果 应用1 μmol/L丙烯醛可明显增加心肌细胞内氧自由基水平及钙离子浓度,分别达到用药前的12倍及2倍.而且,丙烯醛引起心肌细胞损伤是一种剂量依赖性的,应用25,50及100 μmol/L丙烯醛治疗的心肌细胞存活率明显低于对照组(P<0.01).丙烯醛处理心肌细胞后,可观察到DNA断裂片段及典型的凋亡细胞形态变化.结论 丙烯醛可引起成年小鼠心肌细胞的凋亡,其作用可能是由于细胞内氧自由及钙浓度的增加.%Purpose To investigate the responsiveness of intracellular oxygen free radical and calcium on acrolein exposure and acrolein-induced cardiomyocytes apoptosis. Methods The viable adult mice cardiac myocytes were isolated by modified langendorff methods. We have examined the intracellular oxygen free radical and calcium concentration using DCF and Fura-2 AM, and the cardiomyocytes viability with WST assay. Are evaluated the DNA ladder pattern and cell apoptotic morphology on the adult mice cardiomyocytes that are exposed to acrolein. Results Our results show that acrolein can increase markedly the intracellular oxygen free radical and calcium concentration, that reach 12 fold and twofold respectively compared to the resting value when the cells were exposed to 1 μmol/L of acrolein. Moreover, the injury induced by acrolein in cardiac myocytes is concentration-dependent. The cardiomyocytes viability treated with 25, 50, 100 μmol/L of acrolein respectively were significantly lower

  10. Osteoblast response (initial adhesion and alkaline phosphatase activity following exposure to a barrier membrane/enamel matrix derivative combination

    Thangakumaran S

    2009-01-01

    Full Text Available Background and Objective: The enamel matrix derivative (EMD has been used in combination with barrier membranes to optimize regeneration in vertical osseous defects. However, the osteoblast response when exposed to the EMD/barrier membrane combination has not yet been evaluated. The osteoblast behavior when exposed to a combination of regenerative materials must be evaluated to fully understand their effect on bone regeneration. Therefore, the present study was undertaken to estimate the initial adhesion and alkaline phosphatase (ALP activity of an osteoblast cell line (SaOS-2 when exposed to four commercially available resorbable membranes and determine if the addition of EMD had any modulatory effect on osteoblast behavior. Materials and Methods: 5 x 104 SaOS-2 cells between passages 7-10 were cultured in two 24-well culture plates. Plate A was used for the adhesion assay and Plate B was used for the ALP assay. A MTT (3-[4, 5-dimethylthiazolyl-2]-2, 5-diphenyltetrazolium bromide assay was done after 24 hours to determine the adhesion of the osteoblastic cells to four barrier membranes: 1 a non cross-linked porcine Type I and III collagen membrane (BG, 2 a weakly cross-linked Type I collagen membrane (HG, 3 a glutaraldehyde cross-linked bovine Type I collagen (BM, and 4 a resorbable polymer membrane (CP. Osteoblast differentiation was studied using an ALP assay with p-nitro phenyl phosphate as the substrate at 24 hours, 72 hours, and 1 week. A total of 50 µg/ml of EMD dissolved in 10 mM acetic acid was added into each well and the entire experimental protocol outlined above was repeated. Results: The osteoblast adhesion to collagen barriers showed a statistically insignificant reduction following the addition of EMD. Adhesion to the polymer barrier, although significantly lower when compared with collagen barriers, was unaffected by the addition of EMD. ALP activity after 1 week among the various groups was as follows: EMD alone (75.59±2

  11. One-step synthesis of bismuth molybdate catalysts via flame spray pyrolysis for the selective oxidation of propylene to acrolein.

    Schuh, K; Kleist, W; Høj, M; Trouillet, V; Jensen, A D; Grunwaldt, J-D

    2014-12-18

    Flame spray pyrolysis (FSP) of Bi(III)- and Mo(VI)-2-ethylhexanoate dissolved in xylene resulted in various nanocrystalline bismuth molybdate phases depending on the Bi/Mo ratio. Besides α-Bi2Mo3O12 and γ-Bi2MoO6, FSP gave direct access to the metastable β-Bi2Mo2O9 phase with high surface area (19 m(2) g(-1)). This phase is normally only obtained at high calcination temperatures (>560 °C) resulting in lower surface areas. The β-phase was stable up to 400 °C and showed superior catalytic performance compared to α- and γ-phases in selective oxidation of propylene to acrolein at temperatures relevant for industrial applications (360 °C).

  12. High-resolution synchrotron infrared spectroscopy of acrolein: The vibrational levels between 850 and 1020 cm-1

    McKellar, A. R. W.; Billinghurst, B. E.; Xu, Li-Hong; Lees, R. M.

    2015-11-01

    Using spectra obtained at the Canadian Light Source synchrotron radiation facility, a previously unobserved out-of-plane vibration of trans-acrolein (propenal) is reliably assigned for the first time. Its origin is at 1002.01 cm-1, which is about 20 cm-1 higher than usually quoted in the past. This mode is thus labelled as v14, leaving the label v15 for the known vibration at 992.66 cm-1. Weak combination bands 171182 ← 182, 171131 ← 131, 121182 ← 181, and 171182 ← 181 are studied for the first time, and assignments in the known v11, v16, and v15 fundamental bands are also extended. The seven excited vibrations involved in these bands are analyzed, together with five more unobserved vibrations in the same region (850-1020 cm-1), in a large 12-state simultaneous fit which accounts for most of the many observed perturbations in the spectra.

  13. Occurrence of matrix-bound phosphine in polar ornithogenic tundra ecosystems: effects of alkaline phosphatase activity and environmental variables.

    Zhu, Renbin; Ma, Dawei; Ding, Wei; Bai, Bo; Liu, Yashu; Sun, Jianjun

    2011-09-01

    Phosphine (PH(3)), a reduced phosphorus compound, is a highly toxic and reactive atmospheric trace gas. In this study, a total of ten ornithogenic soil/sediment profiles were collected from tundra ecosystems of east Antarctica and Arctic, and matrix-bound phosphine (MBP), the phosphorus fractions and alkaline phosphatase activity (APA) were analyzed. High MBP concentrations were found in these profiles with the range from 39.59 ng kg(-1) dw to 11.77 μg kg(-1) dw. MBP showed a consistent vertical distribution pattern in almost all the soil profiles, and its concentrations increased at soil surface layers and then decreased with depths. MBP levels in the ornithogenic soils were two to three orders of magnitude lower than those in ornithogenic sediments. The yield of PH(3) as a fraction of total P in all the profiles ranged from 10(-5) to 10(-9) mgPH(3) mg(-1)P with higher mean PH(3) yield in the ornithogenic sediments. The ornithogenic soils showed high concentrations of total phosphorus (TP), organic phosphorus (OP), inorganic phosphorus (IP) and metal elements (Cu, Zn, Mn, Fe, Al and Ca) but low MBP levels, vice versa for the ornithogenic sediments. No correlation had been obtained between MBP concentrations and IP, OP and TP. There existed an exponential correlation (r=0.67, psoil/sediment moisture. MBP concentrations showed a significant positive correlation with APA (r=0.668, psoils/sediments. Our results indicated that MBP is an important gaseous link in the phosphorus biogeochemical cycles of ornithogenic tundra ecosystems in Antarctica and Arctic.

  14. Piwil2 modulates the proliferation and metastasis of colon cancer via regulation of matrix metallopeptidase 9 transcriptional activity.

    Li, Dawei; Sun, Xing; Yan, Dongwang; Huang, Jianfeng; Luo, Qiongzhen; Tang, Huamei; Peng, Zhihai

    2012-10-01

    Piwi-like protein 2 (Piwil2) has recently emerged as a putative oncogene which is amplified in several human malignancies. However, the role of Piwil2 in colon cancer remains poorly understood. The aim of this study was to investigate the clinical and pathological significance of Piwil2, and the possible role in the proliferation and metastasis of colon cancer. Primary colon cancer paired with adjacent normal colon tissue and lymph node metastasis (LNM) lesions in 66 patients' tissue microarrays (TMA) were used to determine the expression of Piwil2. Knocked down Piwil2 expression in SW620 and SW480 colon cancer cell lines was performed to evaluate the role of Piwil2 in cell proliferation, invasion, metastasis in vitro and tumorigenicity in vivo. The possible roles of Piwil2 in the regulation of a 2 kb matrix metallopeptidase 9 (MMP9) promoter fragment and on the regulation of apoptotic pathways were evaluated by using a luciferase reporter construct and Western blots, respectively. Significantly higher expression levels of Piwil2 were observed in primary colon cancer tissue and in LNM in comparison with normal colon mucosa. Piwil2 expression significantly correlated with more aggressive clinical and pathological parameters with poorer five-year metastasis-free survival and overall survival. Piwil2 silencing significantly reduced cancer cell proliferation, colony formation ability and increased apoptosis in vitro and inhibited tumor growth in vivo. Piwil2 knockdown also attenuated migration and invasion of colon cancer cells via modulation of MMP9 transcriptional activities. Our results indicate that Piwil2 moderates the proliferation and metastasis potential of colon cancer.

  15. The theoretical study of passive and active optical devices via planewave based transfer (scattering) matrix method and other approaches

    Zhuo, Ye [Iowa State Univ., Ames, IA (United States)

    2011-01-01

    In this thesis, we theoretically study the electromagnetic wave propagation in several passive and active optical components and devices including 2-D photonic crystals, straight and curved waveguides, organic light emitting diodes (OLEDs), and etc. Several optical designs are also presented like organic photovoltaic (OPV) cells and solar concentrators. The first part of the thesis focuses on theoretical investigation. First, the plane-wave-based transfer (scattering) matrix method (TMM) is briefly described with a short review of photonic crystals and other numerical methods to study them (Chapter 1 and 2). Next TMM, the numerical method itself is investigated in details and developed in advance to deal with more complex optical systems. In chapter 3, TMM is extended in curvilinear coordinates to study curved nanoribbon waveguides. The problem of a curved structure is transformed into an equivalent one of a straight structure with spatially dependent tensors of dielectric constant and magnetic permeability. In chapter 4, a new set of localized basis orbitals are introduced to locally represent electromagnetic field in photonic crystals as alternative to planewave basis. The second part of the thesis focuses on the design of optical devices. First, two examples of TMM applications are given. The first example is the design of metal grating structures as replacements of ITO to enhance the optical absorption in OPV cells (chapter 6). The second one is the design of the same structure as above to enhance the light extraction of OLEDs (chapter 7). Next, two design examples by ray tracing method are given, including applying a microlens array to enhance the light extraction of OLEDs (chapter 5) and an all-angle wide-wavelength design of solar concentrator (chapter 8). In summary, this dissertation has extended TMM which makes it capable of treating complex optical systems. Several optical designs by TMM and ray tracing method are also given as a full complement of this

  16. Visible-light driven photocatalytic activity of β-indium sulfide (In2S3) quantum dots embedded in Nafion matrix

    Sumi, R.; Warrier, Anita R.; Vijayan, C.

    2014-03-01

    We report on the visible-light-driven photocatalytic activity of highly stable β-indium sulfide (In2S3) quantum dots embedded in Nafion matrix. β-indium sulfide (In2S3) quantum dots (6-10 nm) embedded in Nafion matrix with strong quantum confinement were synthesized by a simple chemical route. The UV-Vis absorption spectrum shows a large blue shift (˜1 eV) which can be controlled by the reaction temperature and time. Strong broadband photoluminescence is observed in the blue, green and red regions of the emission spectrum with variation in particle size and stoichiometry of the quantum dots. Photocatalytic activity measurements show that these hybrid membranes synthesized with equimolar precursors of In and S show paramount photocatalytic activity under visible-light irradiation, with the degradation of Rhodamine-6G dyes up to 95% within 90 min. The photocatalytic membranes are tested for reusable and stable operation.

  17. Flavonol-enriched fraction from Vaccinium macrocarpon fruit inhibits matrix metalloproteinase-2, matrix metalloproteinase-9 and urokinase-type plasminogen activator expression in human prostate cancer cells in vitro

    James MacPhee

    2014-11-01

    Full Text Available Background: Prostate cancer, amongst other cancer types has a genetic and environmental component, which can contribute to prostate cancer development and progression. Vaccinum macrocarpon (American cranberry is a botanical that contains several phytochemicals which have been suggested to play a role in preventing cardiovascular disease, cancer, and urinary tract infections as well as in the maintenance of oral health. Context and purpose of this study: This investigation evaluated the effects of a flavonolenriched fraction (FL from the American cranberry (Vaccinium macrocarpon containing quercetin and myricetin glycosides on matrix metalloproteinase (MMP and urokinase-type plasminogen activator (uPA activities and their associated regulatory proteins in DU145 human prostate cancer cells in vitro. Results: A flavonol-enriched fraction (FL was prepared from Vaccinium macrocarpon berries and the effect of this fraction on prostate cancer cell behaviour was assessed using biochemical and molecular approaches including cytotoxicity assays and Western blot analysis to determine protein expression. Cranberry FL decreased cellular viability of DU145 cells at a concentration of 25 ug/ml by 20% after 6 hours of treatment. Further investigations determined that associated with this cytotoxicity, cranberry FL decreases matrix metalloproteinase (MMP ( specifically MMP-2 and MMP-9 activity and urokinase plasminogen activator (uPA activity through effects on specific temporal MMP regulators and uPA regulators and by affecting either the phosphorylation status and/or expression of specific MAP kinase, PI-3 kinase, NF-kB and AP-1 pathway associated proteins. Conclusion: This study demonstrates, for the first time, the ability of Vaccinium macrocarpon flavonols to modulate cellular pathways associated with migration, invasion, and proliferation, suggesting that cranberry (Vaccinium macrocarpon is a viable candidate for further research as a natural product that

  18. Matrix calculus

    Bodewig, E

    1959-01-01

    Matrix Calculus, Second Revised and Enlarged Edition focuses on systematic calculation with the building blocks of a matrix and rows and columns, shunning the use of individual elements. The publication first offers information on vectors, matrices, further applications, measures of the magnitude of a matrix, and forms. The text then examines eigenvalues and exact solutions, including the characteristic equation, eigenrows, extremum properties of the eigenvalues, bounds for the eigenvalues, elementary divisors, and bounds for the determinant. The text ponders on approximate solutions, as well

  19. Structure and stability of acrolein and allyl alcohol networks on Ag(111) from density functional theory based calculations with dispersion corrections

    Ferullo, Ricardo M.; Branda, Maria Marta; Illas, Francesc

    2013-11-01

    The interaction of acrolein and allyl alcohol with the Ag(111) surface has been studied by means of periodic density functional theory based calculations including explicitly dispersion terms. Different coverage values have been explored going from isolated adsorbed molecules to isolated dimers, interacting dimers or ordered overlayers. The inclusion of the dispersion terms largely affects the calculated values of the adsorption energy and also the distance between adsorbed molecule and the metallic surface but much less the adsorbate-adsorbate interactions. Owing to the large dipole moment of acrolein, the present calculations predict that at high coverage this molecule forms a stable extensive two-dimensional network on the surface, caused by the alignment of the adsorbate dipoles. For the case of allyl alcohol, dimers and complex networks exhibit similar stability.

  20. Mechanism of repair of acrolein- and malondialdehyde-derived exocyclic guanine adducts by the α-ketoglutarate/Fe(II) dioxygenase AlkB.

    Singh, Vipender; Fedeles, Bogdan I; Li, Deyu; Delaney, James C; Kozekov, Ivan D; Kozekova, Albena; Marnett, Lawrence J; Rizzo, Carmelo J; Essigmann, John M

    2014-09-15

    The structurally related exocyclic guanine adducts α-hydroxypropano-dG (α-OH-PdG), γ-hydroxypropano-dG (γ-OH-PdG), and M1dG are formed when DNA is exposed to the reactive aldehydes acrolein and malondialdehyde (MDA). These lesions are believed to form the basis for the observed cytotoxicity and mutagenicity of acrolein and MDA. In an effort to understand the enzymatic pathways and chemical mechanisms that are involved in the repair of acrolein- and MDA-induced DNA damage, we investigated the ability of the DNA repair enzyme AlkB, an α-ketoglutarate/Fe(II) dependent dioxygenase, to process α-OH-PdG, γ-OH-PdG, and M1dG in both single- and double-stranded DNA contexts. By monitoring the repair reactions using quadrupole time-of-flight (Q-TOF) mass spectrometry, it was established that AlkB can oxidatively dealkylate γ-OH-PdG most efficiently, followed by M1dG and α-OH-PdG. The AlkB repair mechanism involved multiple intermediates and complex, overlapping repair pathways. For example, the three exocyclic guanine adducts were shown to be in equilibrium with open-ring aldehydic forms, which were trapped using (pentafluorobenzyl)hydroxylamine (PFBHA) or NaBH4. AlkB repaired the trapped open-ring form of γ-OH-PdG but not the trapped open-ring of α-OH-PdG. Taken together, this study provides a detailed mechanism by which three-carbon bridge exocyclic guanine adducts can be processed by AlkB and suggests an important role for the AlkB family of dioxygenases in protecting against the deleterious biological consequences of acrolein and MDA.

  1. HPLC-MS Determination of Acrolein and Acetone Generated from 13C3 -Labeled Glycerol Added to Cigarette Tobacco Using Two Machine-Smoking Regimes

    Yip SH

    2014-12-01

    Full Text Available The extent of blend glycerol degradation in a burning cigarette to form acrolein and acetone has been quantitatively determined by the addition of glycerol-13C3 to three styles of a leading commercial cigarette brand. Multiple Cambridge pads soaked with a solution of 2,4-dinitrophenylhydrazine (DNPH were employed to trap hydrazone derivatives of low molecular weight carbonyl compounds in both mainstream and sidestream smoke. High performance liquid chromatography coupled with negative ion mass spectrometry was used to isolate DNPH derivatives of the volatile carbonyl products of combustion and to ascertain their concentration. Acrolein, acetone, and propionaldehyde were the principal compounds of interest. The DNPH derivatives of acrolein-13C3 and acetone-13C3 were independently synthesized, and they served as external standards for absolute quantitation. The cost of fully labeled propionaldehyde precluded its use in this study. The brand styles selected for study represent the cigarette design features that are most prevalent in the U.S. market today and afford a representative range of standardized “tar” yields (14, 10, and 5 mg/cig, respectively by the Cambridge Filter Method. The brand styles studied are part of a commercial cigarette brand family that does not contain additives to the tobacco blend, including glycerol. Mainstream smoke was generated by an automated smoking machine employing the standard Cambridge Filter Smoking Regime and a more intense regime requiring larger, more frequent puffs and 100% vent blocking that is specified for regulatory purposes by the Canadian federal government. The research indicated that only a small fraction of added glycerol (~0.25%-0.30%, w/w was converted to the two compounds of interest, with the larger portion generally observed in sidestream smoke. Less than 0.1% of the added glycerol was converted to acrolein in mainstream smoke for all cigarette designs and smoking regimes studied.

  2. Mercapturic Acids Derived from the Toxicants Acrolein and Crotonaldehyde in the Urine of Cigarette Smokers from Five Ethnic Groups with Differing Risks for Lung Cancer.

    Sungshim L Park

    Full Text Available The Multiethnic Cohort epidemiology study has clearly demonstrated that, compared to Whites and for the same number of cigarettes smoked, African Americans and Native Hawaiians have a higher risk for lung cancer whereas Latinos and Japanese Americans have a lower risk. Acrolein and crotonaldehyde are two important constituents of cigarette smoke which have well documented toxic effects and could play a role in lung cancer etiology. Their urinary metabolites 3-hydroxypropylmercapturic acid (3-HPMA and 3-hydroxy-1-methylpropylmercapturic acid (HMPMA, respectively, are validated biomarkers of acrolein and crotonaldehyde exposure. We quantified levels of 3-HPMA and HMPMA in the urine of more than 2200 smokers from these five ethnic groups, and also carried out a genome wide association study using blood samples from these subjects. After adjusting for age, sex, creatinine, and total nicotine equivalents, geometric mean levels of 3-HPMA and HMPMA were significantly different in the five groups (P < 0.0001. Native Hawaiians had the highest and Latinos the lowest geometric mean levels of both 3-HPMA and HMPMA. Levels of 3-HPMA and HMPMA were 3787 and 2759 pmol/ml urine, respectively, in Native Hawaiians and 1720 and 2210 pmol/ml urine in Latinos. These results suggest that acrolein and crotonaldehyde may be involved in lung cancer etiology, and that their divergent levels may partially explain the differing risks of Native Hawaiian and Latino smokers. No strong signals were associated with 3-HPMA in the genome wide association study, suggesting that formation of the glutathione conjugate of acrolein is mainly non-enzymatic, while the top significant association with HMPMA was located on chromosome 12 near the TBX3 gene, but its relationship to HMPMA excretion is not clear.

  3. Activities of cardiac tissue matrix metalloproteinases 2 and 9 are reduced by remote ischemic preconditioning in cardiosurgical patients with cardiopulmonary bypass

    Zitta, Karina; Meybohm, Patrick; Bein, Berthold; Gruenewald, Matthias; Lauer, Fabian; Steinfath, Markus; Cremer, Jochen; Zacharowski, Kai; Albrecht, Martin

    2014-01-01

    BACKGROUND: Transient episodes of ischemia in a remote organ or tissue (remote ischemic preconditioning, RIPC) can attenuate myocardial injury. Myocardial damage is associated with tissue remodeling and the matrix metalloproteinases 2 and 9 (MMP-2/9) are crucially involved in these events. Here we investigated the effects of RIPC on the activities of heart tissue MMP-2/9 and their correlation with serum concentrations of cardiac troponin T (cTnT), a marker for myocardial damage. METHODS: I...

  4. Capillary-induced Homogenization of Matrix in Paper: A Powerful Approach for the Quantification of Active Pharmaceutical Ingredients Using Mass Spectrometry Imaging

    de Menezes, Maico; de Oliveira, Diogo Noin; Catharino, Rodrigo Ramos

    2016-07-01

    Herein we present a novel approach for the quantification of active pharmaceutical ingredients (APIs) using mass spectrometry imaging. This strategy uses a filter paper previously “eluted” with a MALDI matrix solution as a support for analyte application. Samples are submitted to mass spectrometry imaging (MSI) and quantification through characteristic fingerprints is ultimately performed. Results for the content of rosuvastatin from a known formulation are comparable to those obtained with a validated HPLC method.

  5. Induction of tissue inhibitor of matrix metalloproteinase-2 by cholesterol depletion leads to the conversion of proMMP-2 into active MMP-2 in human dermal fibroblasts.

    Kim, Sangmin; Oh, Jang-Hee; Lee, Youngae; Lee, Jeongyoon; Cho, Kwang Hyun; Chung, Jin Ho

    2010-01-31

    Cholesterol is one of major components of cell membrane and plays a role in vesicular trafficking and cellular signaling. We investigated the effects of cholesterol on matrix metalloproteinase-2 (MMP-2) activation in human dermal fibroblasts. We found that tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) expression and active form MMP-2 (64 kD) were dose-dependently increased by methyl-beta-cyclodextrin (MbetaCD), a cholesterol depletion agent. In contrast, cholesterol depletion-induced TIMP-2 expression and MMP-2 activation were suppressed by cholesterol repletion. Then we investigated the regulatory mechanism of TIMP-2 expression by cholesterol depletion. We found that the phosphorylation of JNK as well as ERK was significantly increased by cholesterol depletion. Moreover, cholesterol depletion-induced TIMP-2 expression and MMP-2 activation was significantly decreased by MEK inhibitor U0126, and JNK inhibitor SP600125, respectively. While a low dose of recombinant TIMP-2 (100 ng/ml) increased the level of active MMP-2 (64 kD), the high dose of TIMP-2 (>or=200 ng/ml) decreased the level of active MMP-2 (64 kD). Taken together, we suggest that the induction of TIMP-2 by cholesterol depletion leads to the conversion of proMMP-2 (72 kD) into active MMP-2 (64 kD) in human dermal fibroblasts.

  6. Characterization of silica particles prepared via urease-catalyzed urea hydrolysis and activity of urease in sol-gel silica matrix

    Kato, Katsuya, E-mail: katsuya-kato@aist.go.jp [National Institute of Advanced Industrial Science and Technology (AIST), 2266-98 Anagahora, Shimoshidami, Moriyama-ku, Nagoya 463-8560 (Japan); Nishida, Masakazu [National Institute of Advanced Industrial Science and Technology (AIST), 2266-98 Anagahora, Shimoshidami, Moriyama-ku, Nagoya 463-8560 (Japan); Ito, Kimiyasu; Tomita, Masahiro [Division of Chemistry for Materials, Graduate School of Engineering, Mie University, 1577 Kurimamachiya-cho, Tsu, Mie 514-8570 (Japan)

    2012-12-01

    Highlights: Black-Right-Pointing-Pointer Silica precipitation occurred via urease-catalytic reactions. Black-Right-Pointing-Pointer Higher urease activity for silica synthesis enables mesostructure of silica-urease composites. Black-Right-Pointing-Pointer Urease encapsulating in silica matrix retained high activity. - Abstract: Urease templated precipitation of silica synthesized by sol-gel chemistry produces a composite material allowing high urease activity. This study investigates the structural properties of the composite material that allow for the retention of the urease hydrolysis activity. Scanning (SEM) and transmission (TEM) electron microscopy reveal that the composite has a mesoporous structure composed of closely packed spherical structures {approx}20-50 nm in diameter. Brunauer-Emmett-Teller (BET) analysis revealed that the surface area and pore volume of the composite prepared under the conditions of 50 mM urea and 25 Degree-Sign C is relatively high (324 m{sup 2}/g and 1.0 cm{sup 3}/g). These values are equivalent to those of usual mesoporous silica materials synthesized from the self-assembly of triblock copolymers as organic templates. In addition, after encapsulating in a sol-gel silica matrix, urease retained high activity ({approx}90% of the activity compared with native urease). Our results suggest a new method for synthesizing mesoporous silica materials with highly tunable pore sizes and shapes under mild conditions.

  7. FGF receptor-4 (FGFR4) polymorphism acts as an activity switch of a membrane type 1 matrix metalloproteinase - FGFR4 complex

    Sugiyama, N.; Varjosalo, M.; Meller, P.; Lohi, J; Chan, K.M.; Zhou, Z.; Alitalo, K; Taipale, J; Keski-Oja, J.; Lehti, K

    2010-01-01

    Tumor cells use membrane type 1 matrix metalloproteinase (MT1-MMP) for invasion and metastasis. However, the signaling mechanisms that underlie MT1-MMP regulation in cancer have remained unclear. Using a systematic gain-of-function kinome screen for MT1-MMP activity, we have here identified kinases that significantly enhance MT1-MMP activity in tumor cells. In particular, we discovered an MT1-MMP/FGF receptor-4 (FGFR4) membrane complex that either stimulates or suppresses MT1-MMP and FGFR4 ac...

  8. Biomimetic aggrecan reduces cartilage extracellular matrix from degradation and lowers catabolic activity in ex vivo and in vivo models.

    Sharma, Shaili; Lee, Aeju; Choi, Kuiwon; Kim, Kwangmeyung; Youn, Inchan; Trippel, Stephen B; Panitch, Alyssa

    2013-09-01

    Aggrecan, a major macromolecule in cartilage, protects the extracellular matrix (ECM) from degradation during the progression of osteoarthritis (OA). However, aggrecan itself is also susceptible to proteolytic cleavage. Here, the use of a biomimetic proteoglycan (mAGC) is presented, which functionally mimics aggrecan but lacks the known cleavage sites, protecting the molecule from proteolytic degradation. The objective of this study is to test the efficacy of this molecule in ex vivo (human OA synovial fluid) and in vivo (Sprague-Dawley rats) osteoarthritic models. These results indicate that mAGC's may protect articular cartilage against the loss of key ECM components, and lower catabolic protein and gene expression in both models. This suppression of matrix degradation has the potential to provide a healthy environment for tissue repair.

  9. Matrix Thermalization

    Craps, Ben; Nguyen, Kévin

    2016-01-01

    Matrix quantum mechanics offers an attractive environment for discussing gravitational holography, in which both sides of the holographic duality are well-defined. Similarly to higher-dimensional implementations of holography, collapsing shell solutions in the gravitational bulk correspond in this setting to thermalization processes in the dual quantum mechanical theory. We construct an explicit, fully nonlinear supergravity solution describing a generic collapsing dilaton shell, specify the holographic renormalization prescriptions necessary for computing the relevant boundary observables, and apply them to evaluating thermalizing two-point correlation functions in the dual matrix theory.

  10. Matrine inhibits IL-1β-induced expression of matrix metalloproteinases by suppressing the activation of MAPK and NF-κB in human chondrocytes in vitro.

    Lu, Shijin; Xiao, Xungang; Cheng, Minghua

    2015-01-01

    Interleukin (IL)-1β plays an important role in promoting osteoarthritis (OA) lesions by inducing chondrocytes to secrete matrix metalloproteinases (MMPs), which degrade the extracellular matrix and facilitate chondrocyte apoptosis. Matrine was shown to exert anti-inflammatory effects. However, the role of matrine in OA is still unclear. Therefore, in this study, we investigated the effects of matrine on the expression of MMPs in IL-1β-treated human chondrocytes and the underlying mechanism. The cell viability of chondrocytes was detected by MTT assay. The cell apoptosis of chondrocytes was measured by flow cytometric analysis. The protein production of MMPs was determined by ELISA. The protein expression of phosphorylation of mitogen-activated protein kinases (MAPKs) and the inhibitor of kappaB alpha (IκBα) was determined by Western blot. Matrine significantly inhibited the IL-1β-induced apoptosis in chondrocytes. It also significantly inhibited the IL-1β-induced release of MMP-3 and MMP-13, and increased the production of TIMP-1. Furthermore, matrine inhibits the phosphorylation of p-38, extracellular regulated kinase (ERK), c-Jun-N-terminal kinase (JNK) and IκBα degradation induced by IL-1β in chondrocytes. Taken together, our results show that matrine inhibits IL-1β-induced expression of matrix metalloproteinases by suppressing the activation of MAPK and NF-κB in human chondrocytes in vitro. Therefore,-matrine may be beneficial in the treatment of OA.

  11. Gel structure has an impact on pericellular and extracellular matrix deposition, which subsequently alters metabolic activities in chondrocyte-laden PEG hydrogels.

    Nicodemus, G D; Skaalure, S C; Bryant, S J

    2011-02-01

    While designing poly(ethylene glycol) hydrogels with high moduli suitable for in situ placement is attractive for cartilage regeneration, the impact of a tighter crosslinked structure on the organization and deposition of the matrix is not fully understood. The objectives of this study were to characterize the composition and spatial organization of new matrix as a function of gel crosslinking and study its impact on chondrocytes in terms of anabolic and catabolic gene expression and catabolic activity. Bovine articular chondrocytes were encapsulated in hydrogels with three crosslinking densities (compressive moduli 60, 320 and 590 kPa) and cultured for 25 days. Glycosaminoglycan production increased with culture time and was greatest in the gels with lowest crosslinking. Collagens II and VI, aggrecan, link protein and decorin were localized to pericellular regions in all gels, but their presence decreased with increasing gel crosslinking. Collagen II and aggrecan expression were initially up-regulated in gels with higher crosslinking, but increased similarly up to day 15. Matrix metalloproteinase (MMP)-1 and MMP-13 expression were elevated (∼25-fold) in gels with higher crosslinking throughout the study, while MMP-3 was unaffected by gel crosslinking. The presence of aggrecan and collagen degradation products confirmed MMP activity. These findings indicate that chondrocytes synthesized the major cartilage components within PEG hydrogels, however, gel structure had a significant impact on the composition and spatial organization of the new tissue and on how chondrocytes responded to their environment, particularly with respect to their catabolic expression.

  12. Metal Ion-dependent Heavy Chain Transfer Activity of TSG-6 Mediates Assembly of the Cumulus-Oocyte Matrix.

    Briggs, David C; Birchenough, Holly L; Ali, Tariq; Rugg, Marilyn S; Waltho, Jon P; Ievoli, Elena; Jowitt, Thomas A; Enghild, Jan J; Richter, Ralf P; Salustri, Antonietta; Milner, Caroline M; Day, Anthony J

    2015-11-27

    The matrix polysaccharide hyaluronan (HA) has a critical role in the expansion of the cumulus cell-oocyte complex (COC), a process that is necessary for ovulation and fertilization in most mammals. Hyaluronan is organized into a cross-linked network by the cooperative action of three proteins, inter-α-inhibitor (IαI), pentraxin-3, and TNF-stimulated gene-6 (TSG-6), driving the expansion of the COC and providing the cumulus matrix with its required viscoelastic properties. Although it is known that matrix stabilization involves the TSG-6-mediated transfer of IαI heavy chains (HCs) onto hyaluronan (to form covalent HC·HA complexes that are cross-linked by pentraxin-3) and that this occurs via the formation of covalent HC·TSG-6 intermediates, the underlying molecular mechanisms are not well understood. Here, we have determined the tertiary structure of the CUB module from human TSG-6, identifying a calcium ion-binding site and chelating glutamic acid residue that mediate the formation of HC·TSG-6. This occurs via an initial metal ion-dependent, non-covalent, interaction between TSG-6 and HCs that also requires the presence of an HC-associated magnesium ion. In addition, we have found that the well characterized hyaluronan-binding site in the TSG-6 Link module is not used for recognition during transfer of HCs onto HA. Analysis of TSG-6 mutants (with impaired transferase and/or hyaluronan-binding functions) revealed that although the TSG-6-mediated formation of HC·HA complexes is essential for the expansion of mouse COCs in vitro, the hyaluronan-binding function of TSG-6 does not play a major role in the stabilization of the murine cumulus matrix.

  13. Inhibitory Effects of Isorhamnetin on the Invasion of Human Breast Carcinoma Cells by Downregulating the Expression and Activity of Matrix Metalloproteinase-2/9.

    Li, Chenglin; Yang, Dan; Zhao, Yuanwei; Qiu, Yu; Cao, Xin; Yu, Yanyan; Guo, Hao; Gu, Xiaoke; Yin, Xiaoxing

    2015-01-01

    Matrix metalloproteinases (MMPs) play an active role in facilitating the invasion of cancer cells with excessive extracellular matrix (ECM) degradation. In the present study, we investigated the antiinvasive effects of isorhamnetin, a naturally occurring flavonoid, on MDA-MB-231 human breast carcinoma cells. The results indicated that isorhamnetin significantly inhibited the adhesion, migration, and invasion of the cells in vitro. Moreover, isorhamnetin suppressed the activity and expression of MMP-2 and MMP-9, which were determined by gelatin zymography, real-time PCR, and Western blot analysis, respectively. Besides, isorhamnetin had little effect on the secretion of urokinase plasminogen activator. Further elucidation of the mechanism revealed that isorhamnetin exerted an inhibitory effect on the phosphorylation of p38 and STAT3, although it had no effect on ERK1/2 and JNK. Taken together, these data demonstrated that isorhamnetin could significantly inhibit the invasion of MDA-MB-231 cells by downregulating the expression and activity of MMP-2 and MMP-9, which was potentially associated with the suppression of p38 MAPK and STAT3. Therefore, the findings provide new evidence for the anti-cancer activity of isorhamnetin.

  14. Matrix metaloproteinases activity during the evolution of hypoxic-ischemic brain damage in the immature rat. The effect of 1-methylnicotinamide (MNA).

    Dragun, P; Makarewicz, D; Wójcik, L; Ziemka-Nałecz, M; Słomka, M; Zalewska, T

    2008-09-01

    Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that degrade the extracellular matrix and carry out key functions during brain development. Apart from a physiological role, excessive activation of MMPs in brain tissue has been postulated to represent a pathway for cell death arising from ischemia. To evaluate the possible involvement of MMPs in the perinatal brain asphyxia, we exposed 7-day-old rats to hypoxia-ischemia (HI). Unilateral HI was administered by ligation of the common carotid artery followed by hypoxia (7.4% O2/92.6% N2) for 65 minutes. This insult is known to produce brain damage confined to the cerebral hemisphere ipsilateral to the arterial occlusion in > 90% of animals. HI resulted in a significant elevation of MMP-2 and MMP-9 activity in the ipsilateral forebrain. The maximum activation was found at 48 hours and 7-14 days after the insult. These results suggest that early and late induction of MMPs may play a role in neuronal death as well as in repair processes. The treatment of animals subjected to HI with 1-methylnicotinamide (MNA), the anti-inflammatory agent, led to the inhibition of MMP-9 in an acute phase of ischemic damage and to the activation of MMP-2 in the later stages after injury. The timing of MMPs modulation by MNA may indicate its possible therapeutic implications.

  15. Highly selective and stable CsPW/Nb2O5 catalysts for dehydration of glycerol to acrolein%高选择性和稳定性的CsPW/Nb2O5催化剂用于甘油脱水制备丙烯醛

    刘蓉; 王铁峰; 刘畅; 金涌

    2013-01-01

    Acrolein production by gas-phase dehydration of glycerol at 300 °C, catalyzed by a Cs+-substituted Keggin-type phosphotungstate, Cs2.5H0.5PW12O40 (CsPW), supported on Nb2O5 was investigated. The catalysts were characterized using N2 adsorption-desorption, X-ray diffraction, Fourier-transform infrared and Raman spectroscopies, and NH3 temperature-programmed desorption. It was demon-strated that Lewis acid sites were responsible for byproduct formation, and that Brönsted acid sites of medium strength were the active sites for acrolein production by glycerol dehydration. The acid-ity of the supported CsPW was affected by the calcination temperature and CsPW loading. The CsPW was well dispersed on Nb2O5 at loadings£20 wt%, and the strong acid sites of bulk CsPW were converted to selective medium acid sites. The CsPW catalyst with 20%of CsPW loading cal-cined at 500 °C gave 96%of glycerol conversion and 80%of acrolein selectivity, and there was no significant deactivation in 10 h. The catalyst with a 20%decrease in activity was regenerated by simple coke burning with air at 500 °C.%以磷钨酸铯盐Cs2.5H0.5PW12O40(CsPW)为活性组分,负载到Nb2O5载体上,并用于甘油脱水制备丙烯醛的反应中.通过调节焙烧温度(400-700°C)以及活性组分负载量(5-60 wt%),对催化剂酸性进行调节. CsPW负载量为20 wt%,500°C焙烧的CsPW/Nb2O5催化剂性能最佳,甘油转化率为96%,丙烯醛选择性为80%,反应10 h内没有失活现象,并且该催化剂具有良好的热稳定性,可通过烧炭进行再生.

  16. [Autoradiographic investigations on postnatal proliferative activity of the telencephalic and diencephalic matrix-zones in the axolotl (Ambystoma mexicanum), with special references to the olfactory organ (author's transl)].

    Richter, W; Kranz, D

    1981-01-01

    The localization and proliferative activity of the matrix-zones has been investigated in the telencephalon and in the diencephalon of 21 axolotls (Ambystoma mexicanum) by means of autoradiographs, after injection of tritiated thymidine at different stages of the postnatal life. There are no previous detailed autoradiographical reports on postnatal brain development in the axolotl. Matrix-zones (i.e. ventricular and subventricular zone) exist in the dorsal part and in the ventral part of the telencephalon, we have found these also in the diencephalon in the wall of the preoptic recessus and ventrally of the habenula. The quantitative part of this study indicates high values of the labeling-index in the early postnatal stages. Then, the labeling-index decreases, but also in 3 years old specimens labeled cells were observed in the matrix-zones of the telencephalon; therefore a few of proliferative capacity remains in the central nervous system of adult axolotls. Labeled cells were also found in the olfactory organ of early postnatal and adult axolotls; these are neuroblasts which have relevance for the regeneration of the forebrain.

  17. The relative roles of collagen adhesive receptor DDR2 activation and matrix stiffness on the downregulation of focal adhesion kinase in vascular smooth muscle cells.

    Bhadriraju, Kiran; Chung, Koo-Hyun; Spurlin, Tighe A; Haynes, Ross J; Elliott, John T; Plant, Anne L

    2009-12-01

    Cells within tissues derive mechanical anchorage and specific molecular signals from the insoluble extracellular matrix (ECM) that surrounds them. Understanding the role of different cues that extracellular matrices provide cells is critical for controlling and predicting cell response to scaffolding materials. Using an engineered extracellular matrix of Type I collagen we examined how the stiffness, supramolecular structure, and glycosylation of collagen matrices influence the protein levels of cellular FAK and the activation of myosin II. Our results show that (1) cellular FAK is downregulated on collagen fibrils, but not on a non-fibrillar monolayer of collagen, (2) the downregulation of FAK is independent of the stiffness of the collagen fibrils, and (3) FAK levels are correlated with levels of tyrosine phosphorylation of the collagen adhesion receptor DDR2. Further, siRNA depletion of DDR2 blocks FAK downregulation. Our results suggest that the collagen receptor DDR2 is involved in the regulation of FAK levels in vSMC adhered to Type I collagen matrices, and that regulation of FAK levels in these cells appears to be independent of matrix stiffness.

  18. Thermal activated energy transfer between luminescent states of Mn2+-doped ZnTe nanoparticles embedded in a glass matrix.

    Dantas, Noelio O; Silva, Alessandra S; Freitas Neto, Ernesto S; Lourenço, Sidney A

    2012-03-14

    Zn(1-x)Mn(x)Te nanocrystals (NCs), at various concentrations x, were successfully grown in a host glass matrix by the fusion method after appropriate annealing. Growth of these NCs was evidenced by optical absorption (OA), X-Ray Diffraction (XRD), magnetic force microscopy (MFM) and photoluminescence (PL) measurements. From the room temperature OA spectra, it was possible to observe the formation of two well defined, different sized groups of NCs, one attributed to quantum dots (QDs) and the other to bulk-like nanocrystals (NCs). XRD results have confirmed that the cubic zincblend structure of nanoparticles is not altered by the substitutional incorporation of Mn(2+) ions into the ZnTe NCs. MFM images supported the OA spectra results and thus provided additional confirmation of the formation of Zn(1-x)Mn(x)Te magnetic nanoparticles in the host glass matrix. The two groups of NCs were also observed in the PL spectra as well as deep defects attributed to the presence of oxygen centers in the electronic structure of the Zn(1-x)Mn(x)Te NCs. Strong agreement between the fitting model, based on rate equation, and experimental PL intensity data at different temperatures demonstrates that this model adequately describes the energy transfer processes between the NCs and the defects of the Zn(1-x)Mn(x)Te system at different temperatures.

  19. Concerns regarding 24-h sampling for formaldehyde, acetaldehyde, and acrolein using 2,4-dinitrophenylhydrazine (DNPH)-coated solid sorbents

    Herrington, Jason S.; Hays, Michael D.

    2012-08-01

    There is high demand for accurate and reliable airborne carbonyl measurement methods due to the human and environmental health impacts of carbonyls and their effects on atmospheric chemistry. Standardized 2,4-dinitrophenylhydrazine (DNPH)-based sampling methods are frequently applied for measuring gaseous carbonyls in the atmospheric environment. However, there are multiple short-comings associated with these methods that detract from an accurate understanding of carbonyl-related exposure, health effects, and atmospheric chemistry. The purpose of this brief technical communication is to highlight these method challenges and their influence on national ambient monitoring networks, and to provide a logical path forward for accurate carbonyl measurement. This manuscript focuses on three specific carbonyl compounds of high toxicological interest—formaldehyde, acetaldehyde, and acrolein. Further method testing and development, the revision of standardized methods, and the plausibility of introducing novel technology for these carbonyls are considered elements of the path forward. The consolidation of this information is important because it seems clear that carbonyl data produced utilizing DNPH-based methods are being reported without acknowledgment of the method short-comings or how to best address them.

  20. Vibrationally specific photoionization cross sections of acrolein leading to the Χ{sup ~}A{sup '} ionic state

    López-Domínguez, Jesús A.; Lucchese, Robert R., E-mail: lucchese@mail.chem.tamu.edu [Department of Chemistry, Texas A and M University, College Station, Texas 77843-3255 (United States); Fulfer, K. D.; Hardy, David; Poliakoff, E. D. [Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana 70803 (United States); Aguilar, A. A. [Advanced Light Source, Lawrence Berkeley National Laboratory, University of California, Berkeley, California 94720 (United States)

    2014-09-07

    The vibrational branching ratios in the photoionization of acrolein for ionization leading to the Χ{sup ~}A{sup '} ion state were studied. Computed logarithmic derivatives of the cross section and the corresponding experimental data derived from measured vibrational branching ratios for several normal modes (ν{sub 9}, ν{sub 10}, ν{sub 11}, and ν{sub 12}) were found to be in relatively good agreement, particularly for the lower half of the 11–100 eV photon energy range considered. Two shape resonances have been found near photon energies of 15.5 and 23 eV in the photoionization cross section and have been demonstrated to originate from the partial cross section of the A{sup ′} scattering symmetry. The wave functions computed at the resonance complex energies are delocalized over the whole molecule. By looking at the dependence of the cross section on the different normal mode displacements together with the wave function at the resonant energy, a qualitative explanation is given for the change of the cross sections with respect to changing geometry.

  1. Vibrationally specific photoionization cross sections of acrolein leading to the tilde{X} {}^2 A^' } ionic state

    López-Domínguez, Jesús A.; Lucchese, Robert R.; Fulfer, K. D.; Hardy, David; Poliakoff, E. D.; Aguilar, A. A.

    2014-09-01

    The vibrational branching ratios in the photoionization of acrolein for ionization leading to the tilde{X} {}^2 A^' } ion state were studied. Computed logarithmic derivatives of the cross section and the corresponding experimental data derived from measured vibrational branching ratios for several normal modes (ν9, ν10, ν11, and ν12) were found to be in relatively good agreement, particularly for the lower half of the 11-100 eV photon energy range considered. Two shape resonances have been found near photon energies of 15.5 and 23 eV in the photoionization cross section and have been demonstrated to originate from the partial cross section of the A' scattering symmetry. The wave functions computed at the resonance complex energies are delocalized over the whole molecule. By looking at the dependence of the cross section on the different normal mode displacements together with the wave function at the resonant energy, a qualitative explanation is given for the change of the cross sections with respect to changing geometry.

  2. Matrix inequalities

    Zhan, Xingzhi

    2002-01-01

    The main purpose of this monograph is to report on recent developments in the field of matrix inequalities, with emphasis on useful techniques and ingenious ideas. Among other results this book contains the affirmative solutions of eight conjectures. Many theorems unify or sharpen previous inequalities. The author's aim is to streamline the ideas in the literature. The book can be read by research workers, graduate students and advanced undergraduates.

  3. Advance in commercial acrylic acid catalysts Ⅰ.Acrolein catalysts%工业丙烯酸催化剂研究进展Ⅰ.丙烯醛催化剂

    汪劲松; 张剑; 苏东风

    2013-01-01

    The core of two-steps oxidation method of propene to acrolein and acrylic acid is the catalyst.The research trend of the main acrolein catalyst patentee at home and abroad was tracked.The research progress in acrolein catalyst focused by commercial production was reviewed,and its development prospects were also outlined.%催化剂是丙烯两步气相催化氧化法生产丙烯醛和丙烯酸的核心.跟踪了国内外主要丙烯醛催化剂专利商的研究动向,对工业生产关注的丙烯醛催化剂的研究进展进行综述,并展望丙烯醛催化剂的发展前景.

  4. Threshold-Voltage-Shift Compensation and Suppression Method Using Hydrogenated Amorphous Silicon Thin-Film Transistors for Large Active Matrix Organic Light-Emitting Diode Displays

    Oh, Kyonghwan; Kwon, Oh-Kyong

    2012-03-01

    A threshold-voltage-shift compensation and suppression method for active matrix organic light-emitting diode (AMOLED) displays fabricated using a hydrogenated amorphous silicon thin-film transistor (TFT) backplane is proposed. The proposed method compensates for the threshold voltage variation of TFTs due to different threshold voltage shifts during emission time and extends the lifetime of the AMOLED panel. Measurement results show that the error range of emission current is from -1.1 to +1.7% when the threshold voltage of TFTs varies from 1.2 to 3.0 V.

  5. Preliminary evidence for a matrix metalloproteinase-2 (MMP-2)-dependent shedding of soluble CD40 ligand (sCD40L) from activated platelets.

    Reinboldt, Stephan; Wenzel, Folker; Rauch, Bernhard H; Hohlfeld, Thomas; Grandoch, Maria; Fischer, Jens W; Weber, Artur-Aron

    2009-09-01

    Platelets are the major source of soluble CD40 ligand (sCD40L) in the blood. It has been demonstrated that CD40L is cleaved from the surface of activated platelets to release sCD40L. However, the enzyme involved in sCD40L shedding has not been identified yet. Using a panel of pharmacological inhibitors of serine, cysteine, aspartate, or metalloproteinases, preliminary evidence is presented for the hypothesis that matrix metalloproteinase-2 (MMP-2) might be the protease, primarily responsible for CD40L cleavage from platelet surface.

  6. High Glucose-Induced Oxidative Stress Mediates Apoptosis and Extracellular Matrix Metabolic Imbalances Possibly via p38 MAPK Activation in Rat Nucleus Pulposus Cells

    Xiaofei Cheng

    2016-01-01

    Full Text Available Objectives. To investigate whether high glucose-induced oxidative stress is implicated in apoptosis of rat nucleus pulposus cells (NPCs and abnormal expression of critical genes involved in the metabolic balance of extracellular matrix (ECM. Methods. NPCs were cultured with various concentrations of glucose to detect cell viability and apoptosis. Cells cultured with high glucose (25 mM were untreated or pretreated with N-acetylcysteine or a p38 MAPK inhibitor SB 202190. Reactive oxygen species (ROS production was evaluated. Activation of p38 MAPK was measured by Western blot. The expression of ECM metabolism-related genes, including type II collagen, aggrecan, SRY-related high-mobility-group box 9 (Sox-9, matrix metalloproteinase 3 (MMP-3, and tissue inhibitor of metalloproteinase 1 (TIMP-1, was analyzed by semiquantitative RT-PCR. Results. High glucose reduced viability of NPCs and induced apoptosis. High glucose resulted in increased ROS generation and p38 MAPK activation. In addition, it negatively regulated the expression of type II collagen, aggrecan, Sox-9, and TIMP-1 and positively regulated MMP-3 expression. These results were changed by pretreatment with N-acetylcysteine or SB 202190. Conclusions. High glucose might promote apoptosis of NPCs, trigger ECM catabolic pathways, and inhibit its anabolic activities, possibly through a p38 MAPK-dependent oxidative stress mechanism.

  7. Anti-elastase, anti-tyrosinase and matrix metalloproteinase-1 inhibitory activity of earthworm extracts as potential new anti-aging agent

    Nurhazirah Azmi; Puziah Hashim; Dzulkifly M Hashim; Normala Halimoon; Nik Muhamad Nik Majid

    2014-01-01

    Objective: To examine whether earthworms of Eisenia fetida, Lumbricus rubellus and Eudrilus eugeniae extracts have elastase, tyrosinase and matrix metalloproteinase-1 (MMP-1) inhibitory activity.Methods:activity and compared with the positive controls. It was also evaluated for whitening and anti-wrinkle capacity.Results:The earthworms extract was screened for elastase, tyrosinase and MMP-1 inhibitory and excellent MMP-1 inhibition compared to N-Isobutyl-N-(4-methoxyphenylsulfonyl)-glycylhydroxamic acid.Conclusions:Earthworms extract showed effective inhibition of tyrosinase, elastase and MMP-1 The extract showed significantly (P<0.05) good elastase and tyrosinase inhibition activities. Therefore, this experiment further rationalizes the traditional use of this worm extracts which may be useful as an anti-wrinkle agent.

  8. Decreased expression of the plasminogen activator inhibitor type 1 is involved in degradation of extracellular matrix surrounding cervical cancer stem cells.

    Sato, Masakazu; Kawana, Kei; Adachi, Katsuyuki; Fujimoto, Asaha; Yoshida, Mitsuyo; Nakamura, Hiroe; Nishida, Haruka; Inoue, Tomoko; Taguchi, Ayumi; Takahashi, Juri; Kojima, Satoko; Yamashita, Aki; Tomio, Kensuke; Nagamatsu, Takeshi; Wada-Hiraike, Osamu; Oda, Katsutoshi; Osuga, Yutaka; Fujii, Tomoyuki

    2016-02-01

    The plasminogen activator (PA) system consists of plasminogen activator inhibitor type 1 (PAI-1), urokinase-type plasminogen activator and its receptor (uPA and uPAR). PAI-1 inhibits the activation of uPA (which converts plasminogen to plasmin), and is involved in cancer invasion and metastasis, by remodeling the extracellular matrix (ECM) through regulating plasmin. Cancer stem cells (CSCs) are a small subset of cells within tumors, and are thought to be involved in tumor recurrence and metastasis. Considering these facts, we investigated the relationship between PAI-1 and cervical CSCs. We used ALDH1 as a marker of cervical CSCs. First, we demonstrated that culturing ALDH1-high cells and ALDH-low cells on collagen IV-coted plates increased their expression of active PAI-1 (ELISA), and these increases were suggested to be at mRNA expression levels (RT-qPCR). Secondly, we demonstrated PAI-1 was indeed involved in the ECM maintenance. With gelatin zymography assays, we found that ALDH1-high cells and ALDH-low cells expressed pro-matrix metalloproteinase-2 (pro-MMP-2) irrespective of their coatings. With gelatinase/collagenase assay kit, we confirmed that collagenase activity was increased when ALDH1-low cells were exposed to TM5275, a small molecule inhibitor of PAI-1. Putting the data together, we hypothesized that cancer cells adhered to basal membrane secrete abundant PAI-1, on the other hand, cancer cells (especially CSCs rather than non-CSCs) distant from basal membrane secrete less PAI-1, which makes the ECM surrounding CSCs more susceptible to degradation. Our study could be an explanation of conflicting reports, where some researchers found negative impacts of PAI-1 expression on clinical outcomes and others not, by considering the concept of CSCs.

  9. Global Matrix 2.0: Report Card Grades on the Physical Activity of Children and Youth Comparing 38 Countries

    Tremblay, Mark S.; Barnes, Joel; Gonzales, Silvia;

    2016-01-01

    , understand underlying determinants, conceive innovative solutions, and mitigate the global childhood inactivity crisis. The paradox of higher physical activity and lower sedentary behavior in countries reporting poorer infrastructure, and lower physical activity and higher sedentary behavior in countries...

  10. Global Matrix 2.0: Report Card Grades on the Physical Activity of Children and Youth Comparing 38 Countries

    Tremblay, Mark S.; Barnes, Joel; Gonzales, Silvia

    2016-01-01

    Participation, Active Play, Active Transportation, Sedentary Behavior, Family and Peers, School, Community and the Built Environment, and Government Strategies and Investments), and all Report Cards were generated through a harmonized development process and a standardized grading framework (from A = excellent......, understand underlying determinants, conceive innovative solutions, and mitigate the global childhood inactivity crisis. The paradox of higher physical activity and lower sedentary behavior in countries reporting poorer infrastructure, and lower physical activity and higher sedentary behavior in countries...

  11. Global Matrix 2.0 : Report Card Grades on the Physical Activity of Children and Youth Comparing 38 Countries

    Tremblay, Mark S; Barnes, Joel D; González, Silvia A; Katzmarzyk, Peter T; Onywera, Vincent O; Reilly, John J; Tomkinson, Grant R; Takken, T

    2016-01-01

    The Active Healthy Kids Global Alliance organized the concurrent preparation of Report Cards on the physical activity of children and youth in 38 countries from 6 continents (representing 60% of the world's population). Nine common indicators were used (Overall Physical Activity, Organized Sport Par

  12. In-situ growth of antimony sulfide in carbon nanoparticle matrix: Enhanced electrocatalytic activity as counter electrode in dye-sensitized solar cells

    Sun, Panpan; Zhang, Ming; Ai, Changzhi; Wu, Zhixin; Lu, Shuang; Zhang, Xintong; Huang, Niu; Sun, Yihua; Sun, Xiaohua

    2016-07-01

    Considering the undesirable electrocatalytic activity toward I-/I3- redox system of prinstine antimony sulfide (Sb2S3) fabricated with the existing conditions, a mesoporous carbon nanoparticle film (CNP) is introduced here for in-situ growth of Sb2S3 to construct a Sb2S3@CNP hybrid catalyst. Based on a Sb-thiourea precursor solution, in-situ growth of Sb2S3 can be achieved via solution deposition (denoted as Sb2S3@CNP-S) as well as atmospheric pressure thermal evaporation (denoted as Sb2S3@CNP-T) in CNP matrix. Structural characterizations indicate that Sb2S3 particles have well dispersed in the pores of CNP matrix. Because of the introduction of porous and conductive CNP matrix to support Sb2S3, the hybrid catalyst exhibits lower charge transfer resistance at the catalyst/electrolyte interface and higher electrocatalytic activity. When used as counter electrode (CE) for dye-sensitized solar cells (DSSCs), devices using Sb2S3@CNP hybrid catalyst as CE produce fill factor of 67.6% and 66.3%, which is significantly higher than that using pristine Sb2S3 fabricated in our previous work (52.8%). Finally, the corresponding power conversion efficiencies reach 6.69% (Sb2S3@CNP-S) and 6.24% (Sb2S3@CNP-T), respectively, which are comparable to that using Pt CE measured under the same conditions (6.74%).

  13. TNF-α Up-regulates Matrix Metalloproteinase-9 Expression and Activity in Alveolar Macrophages from Patients with Chronic Obstructive Pulmonary Disease

    2006-01-01

    To study the effects of tumor necrosis factor (TNF)-α on matrix metalloproteinase (MMP)-9 expression and activity in alveolar macrophages (AM) and to investigate the role of NF-κB in the induction, AM were collected from bronchoalveolar lavage fluid (BALF) of healthy subjects and patients with chronic obstructive pulmonary disease (COPD). MMP-9 expression and activity were detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), Western blotting and zymography. NF-κB activity was detected by electrophoretic mobility shift assay (EMSA). MMP-9 expression and activity induced by TNF-α in AM from healthy subjects or patients with COPD were significantly increased in a dose-dependent manner (P<0.05). NF-κB activity induced by TNF-α was significantly increased in AM from patients with COPD, and pyrrolidine dithiocarbamate (PDTC) and N-acetyl-L-cysteine (NAC) significantly inhibited the activation of NF-κB induced by TNF-α (P<0.05). The presents study suggested that the expression and activity of MMP-9 from AM can be induced by TNF-α, and TNF-α/NF-κB signal pathway may play an important role in the induction.

  14. The use of a diode matrix in commissioning activities for electron energies {>=}9 MeV: A feasibility study

    Casanova Borca, Valeria; Pasquino, Massimo; Ozzello, Franca; Tofani, Santi [S. C. Fisica Sanitaria, Azienda Sanitaria ASL TO 4, Via Di Vittorio 1, 10015 Ivrea, Torino (Italy)

    2009-04-15

    The contribution of a commercially available diode matrix (MapCHECK trade mark sign , provided by Sun Nuclear, Melbourne, FL) for the commissioning procedures of the voxel based Monte Carlo (VMC++) algorithm for electron beams of MasterPlan treatment planning system was investigated. The attention is mainly focused on the calculation in homogeneous and heterogeneous phantoms. With this aim, following a data set similar to that proposed by Electron Collaborative Working Group (ECWG), the dose profiles and two-dimensional (2D) dose distributions measured by the diode matrix were compared with the calculated ones using the gamma analysis method with acceptance criteria for the dose difference and the distance to agreement equal to 4% and 4 mm, respectively. The average and standard deviation of the percentage of points satisfying the constraint {gamma}{<=}1 are 98.3{+-}4.1% and 99.3{+-}1.7% for the 9 and 12 MeV electron beam, respectively, showing that the accuracy of MasterPlan electron beam algorithm is good for simple two-dimensional geometries as well as for more complicated three-dimensional ones. The results are in agreement with those reported in literature by Cygler et al. [''Evaluation of the first commercial Monte Carlo dose calculation engine for electron beam treatment planning,'' Med. Phys. 31, 142-153 (2004)]. In addition, the authors have also analyzed the response of the 2D array in terms of dose profiles at different depths, comparing the results with those obtained in water phantom using an electron diode. The results show that in the low gradient regions there were no deviations larger than the criteria of acceptability set by Van Dyk et al. [''Commissioning and quality assurance of treatment planning computers,'' Int. J. Radiat. Oncol. Biol. Phys. 26, 261-273 (1993)]; in the high gradient region, the maximum deviations are less than 2 mm with most of the values less than 1 mm. The present article shows that

  15. The use of a diode matrix in commissioning activities for electron energies > or = 9 MeV: a feasibility study.

    Borca, Valeria Casanova; Pasquino, Massimo; Ozzello, Franca; Tofani, Santi

    2009-04-01

    The contribution of a commercially available diode matrix (MapCHECK, provided by Sun Nuclear, Melbourne, FL) for the commissioning procedures of the voxel based Monte Carlo (VMC++) algorithm for electron beams of MasterPlan treatment planning system was investigated. The attention is mainly focused on the calculation in homogeneous and heterogeneous phantoms. With this aim, following a data set similar to that proposed by Electron Collaborative Working Group (ECWG), the dose profiles and two-dimensional (2D) dose distributions measured by the diode matrix were compared with the calculated ones using the gamma analysis method with acceptance criteria for the dose difference and the distance to agreement equal to 4% and 4 mm, respectively. The average and standard deviation of the percentage of points satisfying the constraint gamma < or = 1 are 98.3 +/- 4.1% and 99.3 +/- 1.7% for the 9 and 12 MeV electron beam, respectively, showing that the accuracy of MasterPlan electron beam algorithm is good for simple two-dimensional geometries as well as for more complicated three-dimensional ones. The results are in agreement with those reported in literature by Cygler et al. ["Evaluation of the first commercial Monte Carlo dose calculation engine for electron beam treatment planning," Med. Phys. 31, 142-153 (2004)]. In addition, the authors have also analyzed the response of the 2D array in terms of dose profiles at different depths, comparing the results with those obtained in water phantom using an electron diode. The results show that in the low gradient regions there were no deviations larger than the criteria of acceptability set by Van Dyk et al. ["Commissioning and quality assurance of treatment planning computers," Int. J. Radiat. Oncol. Biol. Phys. 26, 261-273 (1993)]; in the high gradient region, the maximum deviations are less than 2 mm with most of the values less than 1 mm. The present article shows that MapCHECK can play a useful role in the commissioning of

  16. Matrix analysis

    Bhatia, Rajendra

    1997-01-01

    A good part of matrix theory is functional analytic in spirit. This statement can be turned around. There are many problems in operator theory, where most of the complexities and subtleties are present in the finite-dimensional case. My purpose in writing this book is to present a systematic treatment of methods that are useful in the study of such problems. This book is intended for use as a text for upper division and gradu­ ate courses. Courses based on parts of the material have been given by me at the Indian Statistical Institute and at the University of Toronto (in collaboration with Chandler Davis). The book should also be useful as a reference for research workers in linear algebra, operator theory, mathe­ matical physics and numerical analysis. A possible subtitle of this book could be Matrix Inequalities. A reader who works through the book should expect to become proficient in the art of deriving such inequalities. Other authors have compared this art to that of cutting diamonds. One first has to...

  17. How cysteine reacts with citral: an unexpected reaction of beta,beta-disubstituted acroleins with cysteine leading to hexahydro-1,4-thiazepines.

    Starkenmann, Christian; Brauchli, Robert; Maurer, Bruno

    2005-11-16

    The reaction of beta,beta-disubstituted acroleins [3-methyl-2-butenal (1), 3-methyl-2-hexenal (2), and citral (3)] with cysteine gave 1:2 adducts of a novel structural type, namely hexahydro-1,4-thiazepines. To the best of our knowledge, the spontaneous formation of a seven-membered heterocycle from the addition of cysteine to alpha,beta-unsaturated aldehydes is unprecedented. The adduct 6 obtained from citral, under acidic conditions, reacted further to give the new bicyclic compound 8.

  18. Cavity Ringdown Absorption Spectrum of the T_1(n,π*) ← S_0 Transition of Acrolein: Analysis of the 0^0_0 Band Rotational Contour

    Hlavacek, Nikolaus C.; McAnally, Michael O.; Drucker, Stephen

    2012-06-01

    Acrolein (propenal, CH_2=CH---CH=O) is the simplest conjugated enal molecule and serves as a prototype for investigating the photochemical properties of larger enals and enones. Acrolein has a coplanar arrangement of heavy atoms in its ground electronic state. Much of the photochemistry is mediated by the T_1(π,π*) state, which has a CH_2--twisted equilibrium structure. In solution, the T_1(π,π*) state is typically accessed via intersystem crossing from an intially prepared planar S_1(n,π*) state. An intermediate in this photophysical transformation is the lowest ^3 (n,π*) state, a planar species with adiabatic excitation energy below S_1 and above T_1(π,π*). The present work focuses on this ^3 (n,π*) intermediate state; it is designated T_1(n,π*) as the lowest-energy triplet state of acrolein having a planar equilibrium structure. The T_1(n,π*) ← S_0 band system, with origin near 412 nm, was first recorded in the 1970s at medium (0.5 cm-1) resolution using a long-path absorption cell. Here we report the cavity ringdown spectrum of the 0^0_0 band, recorded using a pulsed dye laser with 0.1 cm-1 spectral bandwidth. The spectrum was measured under both bulk-gas (room-temperature) and jet-cooled conditions. The band contour in each spectrum was analyzed by using a computer program developed for simulating and fitting the rotational structure of singlet-triplet transitions. The assignment of several resolved sub-band heads in the room-temperature spectrum permitted approximate fitting of the inertial constants for the T_1(n,π*) state. The determined values (cm-1) are A=1.662, B=0.1485, C=0.1363. For the parameters A and (B+C)/2, estimated uncertainties of ± 0.003 cm-1 and ± 0.0004 cm-1, respectively, correspond to a range of values that produce qualitatively satisfactory global agreement with the observed room-temperature contour. The fitted inertial constants were used to simulate the rotational contour of the 0^0_0 band under jet-cooled conditions

  19. (60)Co in cast steel matrix: A European interlaboratory comparison for the characterisation of new activity standards for calibration of gamma-ray spectrometers in metallurgy.

    Tzika, Faidra; Burda, Oleksiy; Hult, Mikael; Arnold, Dirk; Marroyo, Belén Caro; Dryák, Pavel; Fazio, Aldo; Ferreux, Laurent; García-Toraño, Eduardo; Javornik, Andrej; Klemola, Seppo; Luca, Aurelian; Moser, Hannah; Nečemer, Marijan; Peyrés, Virginia; Reis, Mario; Silva, Lidia; Šolc, Jaroslav; Svec, Anton; Tyminski, Zbigniew; Vodenik, Branko; Wätjen, Uwe

    2016-08-01

    Two series of activity standards of (60)Co in cast steel matrix, developed for the calibration of gamma-ray spectrometry systems in the metallurgical sector, were characterised using a European interlaboratory comparison among twelve National Metrology Institutes and one international organisation. The first standard, consisting of 14 disc shaped samples, was cast from steel contaminated during production ("originally"), and the second, consisting of 15 similar discs, from artificially-contaminated ("spiked") steel. The reference activity concentrations of (60)Co in the cast steel standards were (1.077±0.019) Bqg(-1) on 1 January 2013 12h00 UT and (1.483±0.022) Bqg(-1) on 1 June 2013 12h00 UT, respectively.

  20. Influence of Polyphenol Extract from Evening Primrose (Oenothera Paradoxa Seeds on Proliferation of Caco-2 Cells and on Expression, Synthesis and Activity of Matrix Metalloproteinases and Their Inhibitors

    Szewczyk Karolina

    2014-09-01

    Full Text Available Evening primrose (Oenothera paradoxa Hudziok seeds are a rich source of not only a valuable oil containing an essential fatty acid - ᵧ-linolenic acid (GLA - but also polyphenols which can be obtained from the biomass remaining after oil pressing. The aim of our studies was to evaluate the influence of a polyphenol extract from defatted seeds of evening primrose on human colorectal adenocarcinoma Caco-2 cell proliferation and matrix metalloproteinases (MMPs synthesis and activity. To assess the effect of evening primrose extract on Caco-2 cell proliferation, crystal violet staining and sulforhodamine B (SRB assays were used whereas mRNA expression and activity of MMPs were evaluated by RT-PCR and gelatin zymography.

  1. Identification of Proteins with Potential Osteogenic Activity Present in the Water-Soluble Matrix Proteins from Crassostrea gigas Nacre Using a Proteomic Approach

    Daniel V. Oliveira

    2012-01-01

    Full Text Available Nacre, when implanted in vivo in bones of dogs, sheep, mice, and humans, induces a biological response that includes integration and osteogenic activity on the host tissue that seems to be activated by a set of proteins present in the nacre water-soluble matrix (WSM. We describe here an experimental approach that can accurately identify the proteins present in the WSM of shell mollusk nacre. Four proteins (three gigasin-2 isoforms and a cystatin A2 were for the first time identified in WSM of Crassostrea gigas nacre using 2DE and LC-MS/MS for protein identification. These proteins are thought to be involved in bone remodeling processes and could be responsible for the biocompatibility shown between bone and nacre grafts. These results represent a contribution to the study of shell biomineralization process and opens new perspectives for the development of new nacre biomaterials for orthopedic applications.

  2. Non-zero $\\theta_{13}$ with Unbroken $\\mu-\\tau$ Symmetry of the Active Neutrino Mass Matrix in the Presence of a Light Sterile Neutrino

    Borah, Debasish

    2016-01-01

    We revisit the possibility of generating non-zero reactor mixing angle in a scenario where there is a sterile neutrino at the eV scale apart from the usual three sub-eV scale active neutrinos. We show that the $3\\times3$ active neutrino mass matrix can possess a $\\mu-\\tau$ symmetry and can still be consistent with non-zero value of the reactor mixing angle $\\theta_{13}$, provided the symmetry is broken in the sterile neutrino sector. We first propose a simple $A_4$ realisation of such a scenario and then numerically evaluate the complete $3+1$ neutrino parameter space that allows such a possibility. We also discuss the possible implications at neutrinoless double beta decay $(0\

  3. Phosphodiesterase inhibition mediates matrix metalloproteinase activity and the level of collagen degradation fragments in a liver fibrosis ex vivo rat model

    Veidal Sanne Skovgård

    2012-12-01

    Full Text Available Abstract Background Accumulation of extracellular matrix (ECM and increased matrix metalloproteinase (MMP activity are hallmarks of liver fibrosis. The aim of the present study was to develop a model of liver fibrosis combining ex vivo tissue culture of livers from CCl4 treated animals with an ELISA detecting a fragment of type III collagen generated in vitro by MMP-9 (C3M, known to be associated with liver fibrosis and to investigate cAMP modulation of MMP activity and liver tissue turnover in this model. Findings In vivo: Rats were treated for 8 weeks with CCl4/Intralipid. Liver slices were cultured for 48 hours. Levels of C3M were determined in the supernatants of slices cultured without treatment, treated with GM6001 (positive control or treated with IBMX (phosphodiesterase inhibitor. Enzymatic activity of MMP-2 and MMP-9 were studied by gelatin zymography. Ex vivo: The levels of serum C3M increased 77% in the CCl4-treated rats at week 8 (p 4-treated animals had highly increased MMP-9, but not MMP-2 activity, compared to slices derived from control animals. Conclusions We have combined an ex vivo model of liver fibrosis with measurement of a biochemical marker of collagen degradation in the condition medium. This technology may be used to evaluate the molecular process leading to structural fibrotic changes, as collagen species are the predominant structural part of fibrosis. These data suggest that modulation of cAMP may play a role in regulation of collagen degradation associated with liver fibrosis.

  4. Calcium alginate gels as stem cell matrix-making paracrine stem cell activity available for enhanced healing after surgery.

    Andreas Schmitt

    Full Text Available Regeneration after surgery can be improved by the administration of anabolic growth factors. However, to locally maintain these factors at the site of regeneration is problematic. The aim of this study was to develop a matrix system containing human mesenchymal stem cells (MSCs which can be applied to the surgical site and allows the secretion of endogenous healing factors from the cells. Calcium alginate gels were prepared by a combination of internal and external gelation. The gelling behaviour, mechanical stability, surface adhesive properties and injectability of the gels were investigated. The permeability of the gels for growth factors was analysed using bovine serum albumin and lysozyme as model proteins. Human MSCs were isolated, cultivated and seeded into the alginate gels. Cell viability was determined by AlamarBlue assay and fluorescence microscopy. The release of human VEGF and bFGF from the cells was determined using an enzyme-linked immunoassay. Gels with sufficient mechanical properties were prepared which remained injectable through a syringe and solidified in a sufficient time frame after application. Surface adhesion was improved by the addition of polyethylene glycol 300,000 and hyaluronic acid. Humans MSCs remained viable for the duration of 6 weeks within the gels. Human VEGF and bFGF was found in quantifiable concentrations in cell culture supernatants of gels loaded with MSCs and incubated for a period of 6 weeks. This work shows that calcium alginate gels can function as immobilization matrices for human MSCs.

  5. A composite demineralized bone matrix--self assembling peptide scaffold for enhancing cell and growth factor activity in bone marrow.

    Hou, Tianyong; Li, Zhiqiang; Luo, Fei; Xie, Zhao; Wu, Xuehui; Xing, Junchao; Dong, Shiwu; Xu, Jianzhong

    2014-07-01

    The need for suitable bone grafts is high; however, there are limitations to all current graft sources, such as limited availability, the invasive harvest procedure, insufficient osteoinductive properties, poor biocompatibility, ethical problems, and degradation properties. The lack of osteoinductive properties is a common problem. As an allogenic bone graft, demineralized bone matrix (DBM) can overcome issues such as limited sources and comorbidities caused by invasive harvest; however, DBM is not sufficiently osteoinductive. Bone marrow has been known to magnify osteoinductive components for bone reconstruction because it contains osteogenic cells and factors. Mesenchymal stem cells (MSCs) derived from bone marrow are the gold standard for cell seeding in tissue-engineered biomaterials for bone repair, and these cells have demonstrated beneficial effects. However, the associated high cost and the complicated procedures limit the use of tissue-engineered bone constructs. To easily enrich more osteogenic cells and factors to DBM by selective cell retention technology, DBM is modified by a nanoscale self-assembling peptide (SAP) to form a composite DBM/SAP scaffold. By decreasing the pore size and increasing the charge interaction, DBM/SAP scaffolds possess a much higher enriching yield for osteogenic cells and factors compared with DBM alone scaffolds. At the same time, SAP can build a cellular microenvironment for cell adhesion, proliferation, and differentiation that promotes bone reconstruction. As a result, a suitable bone graft fabricated by DBM/SAP scaffolds and bone marrow represents a new strategy and product for bone transplantation in the clinic.

  6. Calcium alginate gels as stem cell matrix-making paracrine stem cell activity available for enhanced healing after surgery.

    Schmitt, Andreas; Rödel, Philipp; Anamur, Cihad; Seeliger, Claudine; Imhoff, Andreas B; Herbst, Elmar; Vogt, Stephan; van Griensven, Martijn; Winter, Gerhard; Engert, Julia

    2015-01-01

    Regeneration after surgery can be improved by the administration of anabolic growth factors. However, to locally maintain these factors at the site of regeneration is problematic. The aim of this study was to develop a matrix system containing human mesenchymal stem cells (MSCs) which can be applied to the surgical site and allows the secretion of endogenous healing factors from the cells. Calcium alginate gels were prepared by a combination of internal and external gelation. The gelling behaviour, mechanical stability, surface adhesive properties and injectability of the gels were investigated. The permeability of the gels for growth factors was analysed using bovine serum albumin and lysozyme as model proteins. Human MSCs were isolated, cultivated and seeded into the alginate gels. Cell viability was determined by AlamarBlue assay and fluorescence microscopy. The release of human VEGF and bFGF from the cells was determined using an enzyme-linked immunoassay. Gels with sufficient mechanical properties were prepared which remained injectable through a syringe and solidified in a sufficient time frame after application. Surface adhesion was improved by the addition of polyethylene glycol 300,000 and hyaluronic acid. Humans MSCs remained viable for the duration of 6 weeks within the gels. Human VEGF and bFGF was found in quantifiable concentrations in cell culture supernatants of gels loaded with MSCs and incubated for a period of 6 weeks. This work shows that calcium alginate gels can function as immobilization matrices for human MSCs.

  7. Modulation of 3D Fibrin Matrix Stiffness by Intrinsic Fibrinogen–Thrombin Compositions and by Extrinsic Cellular Activity

    Duong, Haison; Wu, Benjamin

    2009-01-01

    Fibrin is a substance formed through catalytic conversion of coagulation constituents: fibrinogen and thrombin. The kinetics of the two constituents determines the structural properties of the fibrin architecture. We have shown previously that changing the fibrinogen and thrombin concentrations in the final three-dimensional (3D) fibrin matrix influenced cell proliferation and differentiation. In this study, we further examined the effect of changing fibrinogen and thrombin concentrations in the absence or presence of fibroblasts on the structural modulus or stiffness of 3D fibrin matrices. We have prepared fibroblast-free and fibroblast-embedded 3D fibrin matrices of different fibrinogen and thrombin formulations, and tested the stiffness of these constructs using standard mechanical testing assays. Results showed that there was a corresponding increase in stiffness with increasing thrombin and fibrinogen concentrations; the increase was more notable with fibrinogen and to a lesser degree with thrombin. The effect of fibroblasts on the stiffness of the fibrin construct was also examined. We have observed a small increase in the stiffness of the fibroblast-incorporated fibrin construct as they proliferated and exhibited spreading morphology. To our knowledge, this is the first comprehensive report detailing the relationship between fibrinogen and thrombin concentrations, cell proliferation, and stiffness in 3D fibrin matrices. The data obtained may lead to optimally design suitable bioscaffolds where we can control both cell proliferation and structural integrity for a variety of tissue engineering applications. PMID:19309239

  8. Combinatorial Screening Identifies Novel Promiscuous Matrix Metalloproteinase Activities that Lead to Inhibition of the Therapeutic Target IL-13

    Urbach, Carole; Gordon, Nathaniel C; Strickland, Ian; Lowne, David; Joberty-Candotti, Cathy; May, Richard; Herath, Athula; Hijnen, DirkJan; Thijs, Judith L; Bruijnzeel-Koomen, Carla A; Minter, Ralph R; Hollfelder, Florian; Jermutus, Lutz

    2015-01-01

    The practical realization of disease modulation by catalytic degradation of a therapeutic target protein suffers from the difficulty to identify candidate proteases, or to engineer their specificity. We identified 23 measurable, specific, and new protease activities using combinatorial screening of

  9. An Inter-Laboratory Comparison for the Urinary Acrolein Biomarker 3-Hydroxypropyl-Mercapturic Acid (3-HPMA

    Scherer Gerhard

    2017-01-01

    Full Text Available An inter-laboratory comparison study on the acrolein biomarker of exposure 3-hydroxypropyl-mercapturic acid (3-HPMA with 12 laboratories from 7 globally distributed countries was performed. The laboratories received coded triplicates of 4 spiked and lyophilized urine samples (LU, 12 samples as well as 5 authentic urine pool samples (PU, 15 samples covering the 3-HPMA concentration range from background (non-smoking to heavy smoking levels for analysis by using their own (in-house analytical method. All laboratories applied liquid chromatography with tandem mass spectrometry (LC-MS/MS, with most of them (10 of 12 using solid phase extraction (SPE as sample work-up procedure. The intra-laboratory variation (indicating repeatability was determined by calculating the standard deviation (sr and the coefficient of variation (CVr of the triplicates, whereas the inter-laboratory variation (indicating reproducibility was determined by calculating the standard deviation between laboratories (sR and the corresponding coefficient of variation (CVR. After removal of outlier samples or laboratories, the mean CVr values for LU and PU test samples ranged from 2.1–3.6% (mean: 2.8% and 2.4–3.7% (mean: 3.3%, respectively, indicating good repeatability for the determination of 3-HPMA in both sample types. CVR for LU and PU test samples ranged from 9.1–31.9% (mean: 18.8% and 13.9–27.0% (mean: 18.5%, respectively, indicating limited reproducibility in 3-HPMA analysis for both sample types. Re-calculation of the PU results by applying an embedded calibration (EC, derived from the reported peak areas for the LU test samples, somewhat improved the CVR values (range: 9.6–28.8%, mean: 16.7%.

  10. Matrix pentagons

    Belitsky, A V

    2016-01-01

    The Operator Product Expansion for null polygonal Wilson loop in planar maximally supersymmetric Yang-Mills theory runs systematically in terms of multiparticle pentagon transitions which encode the physics of excitations propagating on the color flux tube ending on the sides of the four-dimensional contour. Their dynamics was unravelled in the past several years and culminated in a complete description of pentagons as an exact function of the 't Hooft coupling. In this paper we provide a solution for the last building block in this program, the SU(4) matrix structure arising from internal symmetry indices of scalars and fermions. This is achieved by a recursive solution of the Mirror and Watson equations obeyed by the so-called singlet pentagons and fixing the form of the twisted component in their tensor decomposition. The non-singlet, or charged, pentagons are deduced from these by a limiting procedure.

  11. Inhibitory effects of kaempferol on the invasion of human breast carcinoma cells by downregulating the expression and activity of matrix metalloproteinase-9.

    Li, Chenglin; Zhao, Yuanwei; Yang, Dan; Yu, Yanyan; Guo, Hao; Zhao, Ziming; Zhang, Bei; Yin, Xiaoxing

    2015-02-01

    Matrix metalloproteinases (MMPs) have been regarded as major critical molecules assisting tumor cells during metastasis, for excessive ECM (ECM) degradation, and cancer cell invasion. In the present study, in vitro and in vivo assays were employed to examine the inhibitory effects of kaempferol, a natural polyphenol of flavonoid family, on tumor metastasis. Data showed that kaempferol could inhibit adhesion, migration, and invasion of MDA-MB-231 human breast carcinoma cells. Moreover, kaempferol led to the reduced activity and expression of MMP-2 and MMP-9, which were detected by gelatin zymography, real-time PCR, and western blot analysis, respectively. Further elucidation of the mechanism revealed that kaempferol treatment inhibited the activation of transcription factor activator protein-1 (AP-1) and MAPK signaling pathway. Moreover, kaempferol repressed phorbol-12-myristate-13-acetate (PMA)-induced MMP-9 expression and activity through suppressing the translocation of protein kinase Cδ (PKCδ) and MAPK signaling pathway. Our results also indicated that kaempferol could block the lung metastasis of B16F10 murine melanoma cells as well as the expression of MMP-9 in vivo. Taken together, these results demonstrated that kaempferol could inhibit cancer cell invasion through blocking the PKCδ/MAPK/AP-1 cascade and subsequent MMP-9 expression and its activity. Therefore, kaempferol might act as a therapeutic potential candidate for cancer metastasis.

  12. Fisetin regulates TPA-induced breast cell invasion by suppressing matrix metalloproteinase-9 activation via the PKC/ROS/MAPK pathways.

    Noh, Eun-Mi; Park, Yeon-Ju; Kim, Jeong-Mi; Kim, Mi-Seong; Kim, Ha-Rim; Song, Hyun-Kyung; Hong, On-Yu; So, Hong-Seob; Yang, Sei-Hoon; Kim, Jong-Suk; Park, Samg Hyun; Youn, Hyun-Jo; You, Yong-Ouk; Choi, Ki-Bang; Kwon, Kang-Beom; Lee, Young-Rae

    2015-10-05

    Invasion and metastasis are among the main causes of death in patients with malignant tumors. Fisetin (3,3',4',7-tetrahydroxyflavone), a natural flavonoid found in the smoke tree (Cotinus coggygria), is known to have antimetastatic effects on prostate and lung cancers; however, the effect of fisetin on breast cancer metastasis is unknown. The aim of this study was to determine the anti-invasive activity of fisetin in human breast cancer cells. Matrix metalloproteinase (MMP)-9 is a major component facilitating the invasion of many cancer tumor cell types, and thus the inhibitory effect of fisetin on MMP-9 expression in 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated human breast cancer cells was investigated in this study. Fisetin significantly attenuated TPA-induced cell invasion in MCF-7 human breast cancer cells, and was found to inhibit the activation of the PKCα/ROS/ERK1/2 and p38 MAPK signaling pathways. This effect was furthermore associated with reduced NF-κB activation, suggesting that the anti-invasive effect of fisetin on MCF-7 cells may result from inhibited TPA activation of NF-κB and reduced TPA activation of PKCα/ROS/ERK1/2 and p38 MAPK signals, ultimately leading to the downregulation of MMP-9 expression. Our findings indicate the role of fisetin in MCF-7 cell invasion, and clarify the underlying molecular mechanisms of this role, suggesting fisetin as a potential chemopreventive agent for breast cancer metastasis.

  13. Caffeic Acid Phenethyl Ester Inhibits Oral Cancer Cell Metastasis by Regulating Matrix Metalloproteinase-2 and the Mitogen-Activated Protein Kinase Pathway

    Chih-Yu Peng

    2012-01-01

    Full Text Available Caffeic acid phenethyl ester (CAPE, an active component extracted from honeybee hives, exhibits anti-inflammatory and anticancer activities. However, the molecular mechanism by which CAPE affects oral cancer cell metastasis has yet to be elucidated. In this study, we investigated the potential mechanisms underlying the effects of CAPE on the invasive ability of SCC-9 oral cancer cells. Results showed that CAPE attenuated SCC-9 cell migration and invasion at noncytotoxic concentrations (0 μM to 40 μM. Western blot and gelatin zymography analysis findings further indicated that CAPE downregulated matrix metalloproteinase-2 (MMP-2 protein expression and inhibited its enzymatic activity. CAPE exerted its inhibitory effects on MMP-2 expression and activity by upregulating tissue inhibitor of metalloproteinase-2 (TIMP-2 and potently decreased migration by reducing focal adhesion kinase (FAK phosphorylation and the activation of its downstream signaling molecules p38/MAPK and JNK. These data indicate that CAPE could potentially be used as a chemoagent to prevent oral cancer metastasis.

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

    Franco, Gilson C.N. [Department of Immunology, Forsyth Institute, Cambridge, MA (United States); Department of Pharmacology, FOP/UNICAMP, Piracicaba, SP (Brazil); Kajiya, Mikihito [Department of Immunology, Forsyth Institute, Cambridge, MA (United States); Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA (United States); Nakanishi, Tadashi [Department of Immunology, Forsyth Institute, Cambridge, MA (United States); Ohta, Kouji [Department of Immunology, Forsyth Institute, Cambridge, MA (United States); Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA (United States); Rosalen, Pedro L.; Groppo, Francisco C. [Department of Pharmacology, FOP/UNICAMP, Piracicaba, SP (Brazil); Ernst, Cory W.O.; Boyesen, Janie L. [Department of Immunology, Forsyth Institute, Cambridge, MA (United States); Bartlett, John D.; Stashenko, Philip [Department of Cytokine Biology, Forsyth Institute, Cambridge, MA (United States); Taubman, Martin A. [Department of Immunology, Forsyth Institute, Cambridge, MA (United States); Kawai, Toshihisa, E-mail: tkawai@forsyth.org [Department of Immunology, Forsyth Institute, Cambridge, MA (United States); Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA (United States)

    2011-06-10

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

  15. Curcumin alleviates matrix metalloproteinase-3 and -9 activities during eradication of Helicobacter pylori infection in cultured cells and mice.

    Parag Kundu

    Full Text Available Current therapy-regimens against Helicobacter pylori (Hp infections have considerable failure rates and adverse side effects that urge the quest for an effective alternative therapy. We have shown that curcumin is capable of eradicating Hp-infection in mice. Here we examine the mechanism by which curcumin protects Hp infection in cultured cells and mice. Since, MMP-3 and -9 are inflammatory molecules associated to the pathogenesis of Hp-infection, we investigated the role of curcumin on inflammatory MMPs as well as proinflammatory molecules. Curcumin dose dependently suppressed MMP-3 and -9 expression in Hp infected human gastric epithelial (AGS cells. Consistently, Hp-eradication by curcumin-therapy involved significant downregulation of MMP-3 and -9 activities and expression in both cytotoxic associated gene (cag(+ve and cag(-ve Hp-infected mouse gastric tissues. Moreover, we demonstrate that the conventional triple therapy (TT alleviated MMP-3 and -9 activities less efficiently than curcumin and curcumin's action on MMPs was linked to decreased pro-inflammatory molecules and activator protein-1 activation in Hp-infected gastric tissues. Although both curcumin and TT were associated with MMP-3 and -9 downregulation during Hp-eradication, but unlike TT, curcumin enhanced peroxisome proliferator-activated receptor-γ and inhibitor of kappa B-α. These data indicate that curcumin-mediated healing of Hp-infection involves regulation of MMP-3 and -9 activities.

  16. Beta-adrenoceptor Activation by Norepinephrine Enhances Lipopolysaccharide-induced Matrix Metalloproteinase-9 Expression Through the ERK/JNK-c-Fos Pathway in Human THP-1 Cells

    Yin, Xiang; Zhou, Linli; Han, Fei; Han, Jie; Zhang, Yuanyuan; Sun, Zewei; Zhao, Wenting; Wang, Zhen

    2017-01-01

    Aim: Atherosclerosis is a chronic inflammatory disease, which leads to thrombosis and acute coronary syndrome. Matrix metalloproteinase-9 (MMP-9) is involved in the stability of the extracellular matrix (ECM) and atherosclerosis plaque. Until now, it is established that lipopolysaccharide (LPS) and norepinephrine (NE) are associated with the pathological process of atherosclerosis. However, the combined effect of LPS and NE on MMP-9 is unclear. We investigated the combined effect of LPS and NE on MMP-9 expression in human monocytes and the mechanism involved in the process. Methods: THP-1 cells were cultured and treated with LPS and/or NE. MMP-9 and TIMP-1 gene and protein expression were detected by real time PCR and ELISA, respectively. MMP-9 activity was detected by gelatin zymography. Adrenoceptor antagonists and MAPKs inhibitors were used to clarify the mechanism. Pathway-related proteins were detected by Western blot. Results: We found that NE enhances LPS-induced MMP-9 and TIMP-1 expression as well as MMP-9 activity in THP-1 cells. This effect is reversed by the beta (β)-adrenoceptor antagonist propranolol, extracellular signal-regulated kinases (ERK) inhibitor U0126, and c-Jun N-terminal kinase (JNK) inhibitor SP600125. NE enhances LPS-induced ERK/JNK phosphorylation. NE up-regulates LPS-induced c-Fos expression, which is counteracted by propranolol, U0126, and SP600125. Furthermore, c-Fos silence reverses the effect of NE on MMP-9 activity. Conclusions: Our results suggest that NE enhances LPS-induced MMP-9 expression through β-adrenergic receptor and downstream ERK/JNK-c-Fos pathway. This study may help us to understand the combined effect and mechanism of NE/LPS on MMP-9 expression. PMID:27237101

  17. Tumor necrosis factor-α and receptor activator of nuclear factor-κB ligand augment human macrophage foam-cell destruction of extracellular matrix through protease-mediated processes

    Skjøt-Arkil, Helene; Barascuk, Natasha; Larsen, Lise;

    2012-01-01

    component of extracellular matrix (ECM) in plaques, and to establish whether the pro-inflammatory molecules, tumor necrosis factor (TNF)-alpha, and receptor activator of nuclear factor-κB ligand (RANK-L) increase this degradation. CD14+ monocytes isolated from peripheral blood were differentiated......% and 72%, respectively. This is, to our knowledge, the first data describing a simple in vitro system in which macrophage foam cells degradation of matrix proteins can be monitored. This degradation can be enhanced by cytokines since TNF-alpha and RANK-L significantly increased the matrix degradation...

  18. Controlled formation of reactive Fe particles dispersed in a carbon matrix active for the oxidation of aqueous contaminants with H₂O₂.

    Tristão, Juliana Cristina; de Mendonça, Fernanda Gomes; Lago, Rochel Montero; Ardisson, José Domingos

    2015-01-01

    In this work, reactive iron nanoparticles dispersed in a carbon matrix were produced by the controlled thermal decomposition of Fe(3+) ions in sucrose. During the sucrose decomposition, the Fe(3+) ions are reduced to form iron nanometric cores dispersed in a porous carbonaceous matrix. The materials were prepared with iron contents of 1, 4, and 8 wt.% and heated at 400, 600, and 800 °C. Analyses by X-ray diffraction, Mössbauer spectroscopy, magnetization measurements, Raman spectroscopy, termogravimetric analyses, BET surface area, scanning, and transmission electron microscopy showed that at 400 °C, the materials are composed essentially of Fe3O4 particles, while treatments at higher temperatures, i.e., 600 and 800 °C, produced phases such as Fe(0) and Fe3C. The composites were tested for the oxidation of methylene blue with H2O2 by a Fenton-type reaction and also H2O2 decomposition, showing better performance for the material containing 8 % of iron heated at 400 and 600 °C. These results are discussed in terms of Fe(2+) surface species in the Fe3O4 nanoparticles active for the Fenton reaction.

  19. Recovery of active anti TNF-α ScFv through matrix-assisted refolding of bacterial inclusion bodies using CIM monolithic support.

    Sushma, Krishnan; Bilgimol, Chuvappumkal Joseph; Vijayalakshmi, Mookambeswaran A; Satheeshkumar, Padikara Kutty

    2012-04-01

    Anti TNF-α molecules are important as therapeutic agents for many of the autoimmune diseases in chronic stage. Here we report the expression and purification of a recombinant single chain variable fragment (ScFv) specific to TNF-α from inclusion bodies. In contrast to the conventional on column refolding using the soft gel supports, an efficient methodology using monolithic matrix has been employed. Nickel (II) coupled to convective interaction media (CIM) support was utilized for this purpose with 6M guanidine hydrochloride (GuHCl) as the chaotropic agent. The protein purified after solubilization and refolding proved to be biologically active with an IC₅₀ value of 15 μg. To the best of our knowledge, this is the first report showing the application of methacrylate based chromatographic supports for matrix-assisted refolding and purification of Escherichia coli inclusion bodies. The results are promising to elaborate the methodology further to exploit the potential positive features of monoliths in protein refolding science.

  20. Acute morphine activates satellite glial cells and up-regulates IL-1β in dorsal root ganglia in mice via matrix metalloprotease-9

    Berta Temugin

    2012-03-01

    Full Text Available Abstract Background Activation of spinal cord glial cells such as microglia and astrocytes has been shown to regulate chronic opioid-induced antinociceptive tolerance and hyperalgesia, due to spinal up-regulation of the proinflammatory cytokines such as interleukin-1 beta (IL-1β. Matrix metalloprotease-9 (MMP-9 has been implicated in IL-1β activation in neuropathic pain. However, it is unclear whether acute opioid treatment can activate glial cells in the peripheral nervous system. We examined acute morphine-induced activation of satellite glial cells (SGCs and up-regulation of IL-1β in dorsal root ganglia (DRGs, and further investigated the involvement of MMP-9 in these opioid-induced peripheral changes. Results Subcutaneous morphine injection (10 mg/kg induced robust peripheral glial responses, as evidenced by increased GFAP expression in DRGs but not in spinal cords. The acute morphine-induced GFAP expression is transient, peaking at 2 h and declining after 3 h. Acute morphine treatment also increased IL-1β immunoreactivity in SGCs and IL-1β activation in DRGs. MMP-9 and GFAP are expressed in DRG neurons and SGCs, respectively. Confocal analysis revealed a close proximity of MMP-9 and GFAP immunostaining. Importantly, morphine-induced DRG up-regulation of GFAP expression and IL-1β activation was abolished after Mmp9 deletion or naloxone pre-treatment. Finally, intrathecal injections of IL-1β-selective siRNA not only reduced DRG IL-1β expression but also prolonged acute morphine-induced analgesia. Conclusions Acute morphine induces opioid receptors- and MMP-9-dependent up-regulation of GFAP expression and IL-1β activation in SGCs of DRGs. MMP-9 could mask and shorten morphine analgesia via peripheral neuron-glial interactions. Targeting peripheral glial activation might prolong acute opioid analgesia.

  1. Inhibitory effect of Chinese green tea on cigarette smoke-induced up-regulation of airway neutrophil elastase and matrix metalloproteinase-12 via antioxidant activity.

    Chan, Ka Ho; Chan, Stanley Chi Hang; Yeung, Sze Chun; Man, Ricky Ying Keung; Ip, Mary Sau Man; Mak, Judith Choi Wo

    2012-09-01

    Our recent study has indicated that Chinese green tea (Lung Chen), in which epigallocatechin-3-gallate (EGCG) accounts for 60% of catechins, protected cigarette smoke-induced lung injury. We now hypothesized that Lung Chen tea may also have potential effect on lung oxidative stress and proteases/anti-proteases in a smoking rat model. Sprague-Dawley rats were exposed to either sham air (SA) or 4% cigarette smoke (CS) plus 2% Lung Chen tea or water by oral gavage. Serine proteases, matrix metalloproteinases (MMPs) and their respective endogenous inhibitors were determined in bronchoalveolar lavage (BAL) and lung tissues by gelatin/casein zymography and biochemical assays. Green tea consumption significantly decreased CS-induced elevation of lung lipid peroxidation marker, malondialdehyde (MDA), and CS-induced up-regulation of neutrophil elastase (NE) concentration and activity along with that of α(1)-antitrypsin (α(1)-AT) and secretory leukoproteinase inhibitor (SLPI) in BAL and lung. In parallel, significant elevation of MMP-12 activity was found in BAL and lung of the CS-exposed group, which returned to the levels of SA-exposed group after green tea consumption but not CS-induced reduction of tissue inhibitor of metalloproteinase (TIMP)-1 activity, which was not reversed by green tea consumption. Taken together, our data supported the presence of local oxidative stress and protease/anti-protease imbalance in the airways after CS exposure, which might be alleviated by green tea consumption through its biological antioxidant activity.

  2. Hydrogenation of the alpha,beta-Unsaturated Aldehydes Acrolein, Crotonaldehyde, and Prenal over Pt Single Crystals: A Kinetic and Sum-Frequency Generation Vibrational Spectroscopy Study

    Kliewer, C.J.; Somorjai, G.A.

    2008-11-26

    Sum-frequency generation vibrational spectroscopy (SFG-VS) and kinetic measurements using gas chromatography have been used to study the surface reaction intermediates during the hydrogenation of three {alpha},{beta}-unsaturated aldehydes, acrolein, crotonaldehyde, and prenal, over Pt(111) at Torr pressures (1 Torr aldehyde, 100 Torr hydrogen) in the temperature range of 295K to 415K. SFG-VS data showed that acrolein has mixed adsorption species of {eta}{sub 2}-di-{sigma}(CC)-trans, {eta}{sub 2}-di-{sigma}(CC)-cis as well as highly coordinated {eta}{sub 3} or {eta}{sub 4} species. Crotonaldehyde adsorbed to Pt(111) as {eta}{sub 2} surface intermediates. SFG-VS during prenal hydrogenation also suggested the presence of the {eta}{sub 2} adsorption species, and became more highly coordinated as the temperature was raised to 415K, in agreement with its enhanced C=O hydrogenation. The effect of catalyst surface structure was clarified by carrying out the hydrogenation of crotonaldehyde over both Pt(111) and Pt(100) single crystals while acquiring the SFG-VS spectra in situ. Both the kinetics and SFG-VS showed little structure sensitivity. Pt(100) generated more decarbonylation 'cracking' product while Pt(111) had a higher selectivity for the formation of the desired unsaturated alcohol, crotylalcohol.

  3. 甘油制备丙烯醛的最新研究进展%Research progress in glycerol dehydration to acrolein

    吴梁鹏; 周舟宇; 李新军

    2012-01-01

    Glycerol can be transformed into the desirable and higher valuable chemicals via various technical routes,among which glycerol dehydration to acrolein is an important one. This paper summarizes the research progress achieved in catalyst system,and also discusses the possible pathway and the catalytic mechanism for glycerol dehydration to acrolein. In addition,the current main problems in the technical route are analyzed,and the application prospect is also forecasted.%甘油可以通过各种工艺转化为具有高附加值的化工品,其中选择性催化脱水制备丙烯醛是一个重要的利用途径.在综述甘油制备丙烯醛催化剂体系最新研究进展的基础上,分析了该反应体系的反应历程和催化反应机理,讨论了目前该工艺过程中存在的问题,并对其应用前景进行了展望.

  4. Hydrogenation of the alpha,beta-unsaturated aldehydes acrolein, crotonaldehyde, and prenal over Pt single crystals: a kinetic and sum-frequency generation vibrational spectroscopy study.

    Kliewer, Christopher J; Bieri, Marco; Somorjai, Gabor A

    2009-07-29

    Sum-frequency generation vibrational spectroscopy (SFG-VS) and kinetic measurements using gas chromatography have been used to study the surface reaction intermediates during the hydrogenation of three alpha,beta-unsaturated aldehydes, acrolein, crotonaldehyde, and prenal, over Pt(111) at Torr pressures (1 Torr of aldehyde, 100 Torr of hydrogen) in the temperature range of 295-415 K. SFG-VS data showed that acrolein has mixed adsorption species of eta(2)-di-sigma(CC)-trans, eta(2)-di-sigma(CC)-cis as well as highly coordinated eta(3) or eta(4) species. Crotonaldehyde adsorbed to Pt(111) as eta(2) surface intermediates. SFG-VS during prenal hydrogenation also suggested the presence of the eta(2) adsorption species and became more highly coordinated as the temperature was raised to 415 K, in agreement with its enhanced C=O hydrogenation. The effect of catalyst surface structure was clarified by carrying out the hydrogenation of crotonaldehyde over both Pt(111) and Pt(100) single crystals while acquiring the SFG-VS spectra in situ. Both the kinetics and SFG-VS showed little structure sensitivity. Pt(100) generated more decarbonylation "cracking" product while Pt(111) had a higher selectivity for the formation of the desired unsaturated alcohol, crotyl alcohol.

  5. Effect of the activation of a clay-base paper industry by-product on cement matrix behaviour

    García, R.

    2008-12-01

    Full Text Available The present study addresses variations in the calcination temperature (600-750 ºC and kiln time (two to five hours applied to activate coated paper waste and their effect on the rheological, physical and mechanical behaviour of cement matrices containing these active additions.The results obtained showed that the conditions under which kaolinite was activated had a direct effect on the subsequent behaviour of the calcined products. At activating temperatures of over 700 ºC, pozzolanic activity and mechanical strength were observed to be lower, setting time shorter and the mortar less workable.El presente trabajo de investigación aborda la influencia de las condiciones de activación (600-750 ºC y 2-5 horas de permanencia en el horno de los lodos de papel procedente de la fabricación de papel estucado en el comportamiento reológico, físico y mecánico de las matrices de cementos elaboradas con este tipo de adiciones activas.Los resultados obtenidos muestran una influencia directa entre las condiciones de activación de la caolinita y el comportamiento posterior de los productos calcinados. Así, en condiciones de activación superiores a 700 ºC se observa una menor actividad puzolánica, tiempo de fraguado más corto, disminución de la trabajabilidad de los morteros mezcla y resistencia mecánica más baja.

  6. Mangiferin exerts antitumor activity in breast cancer cells by regulating matrix metalloproteinases, epithelial to mesenchymal transition, and β-catenin signaling pathway

    Li, Hongzhong; Huang, Jing; Yang, Bing; Xiang, Tingxiu; Yin, Xuedong; Peng, Weiyan; Cheng, Wei [Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Wan, Jingyuan; Luo, Fuling [Department of Pharmacology, Chongqing Medical University, Chongqing (China); Li, Hongyuan [Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Ren, Guosheng, E-mail: rgs726@163.com [Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China)

    2013-10-01

    Although mangiferin which is a naturally occurring glucosylxanthone has exhibited promising anticancer activities, the detailed molecular mechanism of mangiferin on cancers still remains enigmatic. In this study, the anticancer activity of mangiferin was evaluated in breast cancer cell line-based in vitro and in vivo models. We showed that mangiferin treatment resulted in decreased cell viability and suppression of metastatic potential in breast cancer cells. Further mechanistic investigation revealed that mangiferin induced decreased matrix metalloproteinase (MMP)-7 and -9, and reversal of epithelial–mesenchymal transition (EMT). Moreover, it was demonstrated that mangiferin significantly inhibited the activation of β-catenin pathway. Subsequent experiments showed that inhibiting β-catenin pathway might play a central role in mangiferin-induced anticancer activity through modulation of MMP-7 and -9, and EMT. Consistent with these findings in vitro, the antitumor potential was also verified in mangiferin-treated MDA-MB-231 xenograft mice where significantly decreased tumor volume, weight and proliferation, and increased apoptosis were obtained, with lower expression of MMP-7 and -9, vimentin and active β-catenin, and higher expression of E-cadherin. Taken together, our study suggests that mangiferin might be used as an effective chemopreventive agent against breast cancer. - Highlights: • Mangiferin inhibits growth and metastatic potential in breast cancer cells. • Mangiferin down-regulates MMP-7 and -9 in breast cancer cells. • Mangiferin induces the reversal of EMT in metastatic breast cancer cells. • Mangiferin inhibits the activation of β-catenin pathway in breast cancer cells. • Inhibiting β-catenin is responsible for the antitumor activity of mangiferin.

  7. Salvianolic Acid B Down-regulates Matrix Metalloproteinase-9 Activity and Expression in Tumor Necrosis Factor-α-induced Human Coronary Artery Endothelial Cells

    Le Ma; Yun-Qian Guan; Zhong-Dong Du

    2015-01-01

    Background:Salvianolic acid B (Sal B) is a bioactive water-soluble compound of Salviae miltiorrhizae,a traditional herbal medicine that has been used clinically tor the treatment of cardiovascular diseases.This study sought to evaluate the effect of Sal B on matrix metalloproteinase-9 (MMP-9) and on the underlying mechanisms in tumor necrosis factor-α (TNF-α)-activated human coronary artery endothelial cells (HCAECs),a cell model of Kawasaki disease.Methods:HCAECs were pretreated with 1 l0 μmol/L of Sal B,and then stimulated by TNF-α at different time points.The protein expression and activity of MMP-9 were determined by Western blot assay and gelatin zymogram assay,respectively.Nuclear factor-κB (NF-κB) activation was detected with immunofluorescence,electrophoretic mobility shift assay,and Western blot assay.Protein expression levels of mitogen-activated protein kinase (c-Jun N-terminal kinase [JNK],extra-cellular signal-regulated kinase [ERK],and p38) were determined by Western blot assay.Results:After HCAECs were exposed to TNF-α,1-10 μtmol/L Sal B significantly inhibited TNF-α-induced MMP-9 expression and activity.Furthermore,Sal B significantly decreased IκBα phosphorylation and p65 nuclear translocation in HCAECs stimulated with TNF-α for 30 min.In addition,Sal B decreased the phosphorylation of JNK and ERK1/2 proteins in cells treated with TNF-α for 10 min.Conclusions:The data suggested that Sal B suppressed TNF-α-induced MMP-9 expression and activity by blocking the activation of NF-κB,JNK,and ERK1/2 signaling pathways.

  8. Amorphous In-Ga-Zn-O Thin Film Transistor Current-Scaling Pixel Electrode Circuit for Active-Matrix Organic Light-Emitting Displays

    Chen, Charlene; Abe, Katsumi; Fung, Tze-Ching; Kumomi, Hideya; Kanicki, Jerzy

    2009-03-01

    In this paper, we analyze application of amorphous In-Ga-Zn-O thin film transistors (a-InGaZnO TFTs) to current-scaling pixel electrode circuit that could be used for 3-in. quarter video graphics array (QVGA) full color active-matrix organic light-emitting displays (AM-OLEDs). Simulation results, based on a-InGaZnO TFT and OLED experimental data, show that both device sizes and operational voltages can be reduced when compare to the same circuit using hydrogenated amorphous silicon (a-Si:H) TFTs. Moreover, the a-InGaZnO TFT pixel circuit can compensate for the drive TFT threshold voltage variation (ΔVT) within acceptable operating error range.

  9. Driving Method for Compensating Reliability Problem of Hydrogenated Amorphous Silicon Thin Film Transistors and Image Sticking Phenomenon in Active Matrix Organic Light-Emitting Diode Displays

    Shin, Min-Seok; Jo, Yun-Rae; Kwon, Oh-Kyong

    2011-03-01

    In this paper, we propose a driving method for compensating the electrical instability of hydrogenated amorphous silicon (a-Si:H) thin film transistors (TFTs) and the luminance degradation of organic light-emitting diode (OLED) devices for large active matrix OLED (AMOLED) displays. The proposed driving method senses the electrical characteristics of a-Si:H TFTs and OLEDs using current integrators and compensates them by an external compensation method. Threshold voltage shift is controlled a using negative bias voltage. After applying the proposed driving method, the measured error of the maximum emission current ranges from -1.23 to +1.59 least significant bit (LSB) of a 10-bit gray scale under the threshold voltage shift ranging from -0.16 to 0.17 V.

  10. Driving Method Compensating for the Hysteresis of Polycrystalline Silicon Thin-Film Transistors for Active-Matrix Organic Light-Emitting Diode Displays

    Jung, Myoung-Hoon; Kim, Ohyun; Kim, Byeong-Koo; Chung, Hoon-Ju

    2009-05-01

    A new driving method for active-matrix organic light-emitting diode displays is proposed and evaluated. The pixel structure of the proposed driving method is composed of three thin-film transistors (TFTs) and one capacitor. It inserts black data into display images to reset driving TFTs for the purpose of maintaining constant electrical characteristics of driving TFTs. The proposed driving scheme is less sensitive to the hysteresis of low-temperature polycrystalline silicon (LTPS) TFTs than the conventional pixel structure with two TFTs and one capacitor, and this scheme can virtually eliminate the recoverable residual image that occurs owing to the hysteresis characteristics of LTPS TFTs. In the proposed driving scheme, black data are inserted into displayed images so that the motion image quality is improved.

  11. Transparent Pixel Circuit with Threshold Voltage Compensation Using ZnO Thin-Film Transistors for Active-Matrix Organic Light Emitting Diode Displays

    Yang, Ik-Seok; Kwon, Oh-Kyong

    2009-03-01

    A transparent pixel circuit with a threshold voltage compensating scheme using ZnO thin-film transistors (TFTs) for active-matrix organic light emitting diode (AMOLED) displays is proposed. This circuit consists of five n-type ZnO TFTs and two capacitors and can compensate for the threshold voltage variation of ZnO TFTs in real time. From simulation results, the maximum deviation of the emission current of the pixel circuit with a threshold voltage variation of ±1 V is determined to be less than 10 nA. From measurement results, it is verified that the maximum deviation of measured emission currents with measurement position in a glass substrate is less than 15 nA in a higher current range, and the deviation of emission current with time is less than 3%.

  12. New Driving Scheme to Improve Hysteresis Characteristics of Organic Thin Film Transistor-Driven Active-Matrix Organic Light Emitting Diode Display

    Yamamoto, Toshihiro; Nakajima, Yoshiki; Takei, Tatsuya; Fujisaki, Yoshihide; Fukagawa, Hirohiko; Suzuki, Mitsunori; Motomura, Genichi; Sato, Hiroto; Tokito, Shizuo; Fujikake, Hideo

    2011-02-01

    A new driving scheme for an active-matrix organic light emitting diode (AMOLED) display was developed to prevent the picture quality degradation caused by the hysteresis characteristics of organic t